bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Metagenomic Meta-Analysis Reveals Functional Signatures of Health and Disease in the Human Gut Microbiome
Authors: Armour Courtney , Nayfach Stephen , Pollard Katherine , Sharpton Thomas 
Published: March 2018

ABSTRACTWhile recent research indicates that human health depends, in part, upon the symbiotic relationship between gut microbes and their host, the specific interactions between host and microbe that define health are poorly resolved. Metagenomic clinical studies clarify this definition by revealing gut microbial taxa and functions that stratify healthy and diseased individuals. However, the typical single-disease focus of microbiome studies limits insight into which microbiome features robustly associate with health, indicate general deviations from health, or predict specific diseases. Additionally, the focus on taxonomy may limit our understanding of how the microbiome relates to health given observations that different taxonomic members can fulfill similar functional roles. To improve our understanding of the association between the gut microbiome and health, we integrated about 2,000 gut metagenomes obtained from eight clinical studies in a statistical meta-analysis. We identify characteristics of the gut microbiome that associate generally with disease, including functional alpha-diversity, beta-diversity, and beta-dispersion. Moreover, we resolve microbiome modules that stratify diseased individuals from controls in a manner independent of study-specific effects. Many of the differentially abundant functions overlap multiple diseases suggesting a role in host health, while others are specific to a single disease and may associate with disease-specific etiologies. Our results clarify potential microbiome-mediated mechanisms of disease and reveal features of the microbiome that may be useful for the development of microbiome-based diagnostics. Ultimately, our study clarifies the definition of a healthy microbiome and how perturbations to it associate with disease.
Genomic analysis ofAcinetobacter baumanniiprophages reveals remarkable diversity and suggests profound impact on bacterial virulence and fitness
Authors: Costa Ana Rita , Monteiro Rodrigo , Azeredo Joana 
Published: March 2018

AbstractThe recent nomination by the World Health Organization ofAcinetobacter baumanniias the number one priority pathogen for the development of new antibiotics is a direct consequence of its fast evolution of pathogenicity, and in particular of multidrug resistance. While the development of new antibiotics is critical, understanding the mechanisms behind the crescent bacterial pathogenicity is equally relevant. Often, resistance and other bacterial virulence elements are contained on highly mobile pieces of DNA that can easily spread to other bacteria. Prophages are one of the mediators of this form of gene transfer, and have been frequently found in bacterial genomes, often offering advantageous features to the host. Here we question the contribution of prophages for the evolution ofA. baumanniipathogenicity. We found prophages to be notably diverse and widely disseminated inA. baumanniigenomes. Also remarkably,A. baumanniiprophages encode for multiple putative virulence factors that may be implicated in the bacterium’s capacity to colonize host niches, evade the host immune system, subsist in unfavorable environments, and tolerate antibiotics. Overall our results point towards a significant contribution of prophages for the dissemination and evolution of pathogenicity inA. baumannii, and highlight their clinical relevance.
SISS-Geo: Leveraging Citizen Science to Monitor Wildlife Health Risks in Brazil
Authors: Chame Marcia , Barbosa Helio J. C. , Gadelha Luiz M. R. , Augusto Douglas A. , Krempser Eduardo , Abdalla Livia 
Published: March 2018

AbstractThe well-being of wildlife health involves many challenges, such as monitoring the movement of pathogens; expanding health surveillance beyond humans; collecting data and extracting information to identify and predict risks; integrating specialists from different areas to handle data, species and distinct social and environmental contexts; and, the commitment to bringing relevant information to society. In Brazil, there is still the difficulty of building a mechanism that is not impaired by its large territorial extension and its poorly integrated sectoral policies. The Brazilian Wildlife Health Information System, SISS-Geo, is a platform for collaborative monitoring that intends to overcome the challenges in wildlife health. It aims integration and participation of various segments of society, encompassing: the registration of occurrences by citizen scientists; the reliable diagnosis of pathogens from the laboratory and expert networks; and computational and mathematical challenges in analytical and predictive systems, knowledge extraction, data integration and visualization, and geographic information systems. It has been successfully applied to support decision-making on recent wildlife health events, such as a Yellow Fever epizooty.
Mitotic progression, arrest, exit or death is determined by centromere integrity and independent of de novo transcription
Authors: Novais-Cruz Marco , Abad Maria Alba , van Ijcken Wilfred F.J. , Galjart Niels , Jeyaprakash A. Arockia , Maiato Helder , Ferrás Cristina 
Published: March 2018

AbstractRecent studies have challenged the prevailing dogma that transcription is repressed during mitosis. Transcription was also proposed to sustain the spindle assembly checkpoint (SAC) for several hours in response to unattached kinetochores. Here we used live-cell imaging of human cells in culture, combined with RNA-seq and qPCR, to investigate the requirement for de novo transcription during mitosis. Under conditions of persistently unattached kinetochores, transcription inhibition with actinomycin D, or treatment with other DNA-intercalating drugs, delocalized the chromosomal passenger complex (CPC) protein Aurora B from centromeres, compromising SAC robustness and cell fate. However, we were unable to detect significant changes in transcript levels. Moreover, inhibition of transcription independently of DNA intercalation had no effect on SAC response, mitotic progression, exit or death. Mechanistically, we show that DNA intercalating agents reduce the interaction of the CPC with nucleosomes. Thus, the capacity of human cells to progress, sustain, exit or die in mitosis relies on centromere integrity, rather than de novo transcription.
Rhizosphere bacterial community composition depends on plant diversity legacy in soil and plant species identity
Authors: Schmid Marc W. , Hahl Terhi , van Moorsel Sofia J. , Wagg Cameron , De Deyn Gerlinde B. , Schmid Bernhard 
Published: March 2018

AbstractSoil microbes are known to be involved in a number of essential ecosystem processes such as nutrient cycling, plant productivity and the maintenance of plant species diversity. However, how plant species diversity and identity affect soil microbial diversity and community composition is largely unknown. We tested whether, over the course of 11 years, distinct soil bacterial communities developed under plant monocultures and mixtures, and if over this timeframe plants with a monoculture or mixture history changed in the microbial communities they associated with. For eight species, we grew offspring of plants that had been grown for 11 years in the same monocultures or mixtures (monoculture- or mixture-type plants) in pots inoculated with microbes extracted from the monoculture and mixture soils. After five months of growth in the glasshouse, we collected rhizosphere soil from each plant and used 16S-rRNA gene sequencing to determine the community composition and diversity of the bacterial communities. Microbial community structure in the plant rhizosphere was primarily determined by soil legacy (monoculture vs. mixture soil) and by plant species identity, but not by plant legacy (monoculture- vs. mixture-type plants). In seven out of the eight plant species bacterial abundance was larger when inoculated with microbes from mixture soil. We conclude that plant diversity can strongly affect belowground community composition and diversity, feeding back to the assemblage of rhizosphere microbial communities in newly establishing plants. Thereby our work demonstrates that concerns for plant biodiversity loss are also concerns for soil biodiversity loss.
Efficiently inferring the demographic history of many populations with allele count data
Authors: Kamm John A. , Terhorst Jonathan , Durbin Richard , Song Yun S. 
Published: March 2018

AbstractThe sample frequency spectrum (SFS), or histogram of allele counts, is an important summary statistic in evolutionary biology, and is often used to infer the history of population size changes, migrations, and other demographic events affecting a set of populations. The expected multipopulation SFS under a given demographic model can be efficiently computed when the populations in the model are related by a tree, scaling to hundreds of populations. Admixture, back-migration, and introgression are common natural processes that violate the assumption of a tree-like population history, however, and until now the expected SFS could be computed for only a handful of populations when the demographic history is not a tree. In this article, we present a new method for efficiently computing the expected SFS and linear functionals of it, for demographies described by general directed acyclic graphs. This method can scale to more populations than previously possible for complex demographic histories including admixture. We apply our method to an 8-population SFS to estimate the timing and strength of a proposed “basal Eurasian” admixture event in human history. We implement and release our method in a new open-source software packagemomi2.
DNA metabarcoding from sample fixative as a quick and voucher preserving biodiversity assessment method
Authors: Alida Zizka Vera Marie , Leese Florian , Peinert Bianca , Geiger Matthias Felix 
Published: March 2018

AbstractMetabarcoding is a powerful tool for biodiversity assessment and has become increasingly popular in recent years. Although its reliability and applicability have been proven in numerous scientific studies, metabarcoding still suffers from some drawbacks. One is the usually mandatory destruction of specimens before DNA extraction, which is problematic because it does not allow a later taxonomic evaluation of the results. Additionally, metabarcoding often implements a time-consuming step, where specimens need to be separated from substrate or sorted in different size classes. A non-destructive protocol, excluding any sorting step, where the extraction of DNA is conducted from a samples fixative (ethanol) could serve as an alternative. We test an innovative protocol, where the sample preserving ethanol is filtered and DNA extracted from the filter for subsequent DNA metabarcoding. We first tested the general functionality of this approach on 15 mock communities comprising one individual of eight different macroinvertebrate taxa each and tried to increase DNA yield through different treatments (ultrasonic irradiation, shaking, freezing). Application of the method was successful for most of the samples and taxa, but showed weaknesses in detecting mollusc taxa. In a second step, the community composition detected in DNA from ethanol was compared to conventional bulk sample metabarcoding of complex environmental samples. We found that especially taxa with pronounced exoskeleton or shells (Coleoptera, Isopoda) and small taxa (Trombidiformes) were underrepresented in ethanol samples regarding taxa diversity and read numbers. However, read numbers of Diptera (mainly chironomids) and Haplotaxida were higher in ethanol derived DNA samples, which might indicate the detection of stomach content, which would be an additional advantage of this approach. Concerning EPT (Ephemeroptera, Plecoptera, Trichoptera) taxa which are decisive for the determination of ecological statuses, both methods had 46 OTUs in common with 4 unique to the ethanol samples and 10 to the bulk samples. Results indicate that fixative-based metabarcoding is a non-destructive, time-saving alternative for biodiversity assessments focussing on taxa used for ecological status determination. For a comprehensive picture on total biodiversity, the method might however not be sufficient and conventional bulk sample metabarcoding should be applied.
Non-productive Binding Modes as a Prominent Feature of Aβ1-40Fiber Elongation: Insights from Molecular Dynamics Simulation
Authors: Kar Rajiv K , Brender Jeffrey R , Ghosh Anirban , Bhunia Anirban 
Published: March 2018

Abstract:Amyloid formation has been implicated in a number of neurodegenerative diseases. The elongation of amyloid fibers is thermodynamically strongly favorable but kinetic traps exist where the incoming monomer binds in an incompatible conformation that blocks further elongation. Unfortunately, this process is difficult to follow experimentally at the atomic level. It is also too complex to simulate in full detail and thus so far has been explored either through coarse-grained simulations, which may miss many important interactions, or full atomic simulations in which the incoming peptide is constrained to be near the ideal fiber geometry. Here we use an alternate approach starting from a docked complex in which the monomer is from an experimental NMR structure of one of the major conformations in the unbound ensemble, a largely unstructured peptide with the central hydrophobic region in a 310helix. A 1000 ns full atomic simulation in explicit solvent shows the formation of a metastable intermediate by sequential, concerted movements of both the fiber and monomer. A Markov state model shows the unfolded monomer is trapped at the end of the fiber in a set of interconverting anti-parallel β-hairpin conformations. The simulation here may serve as a model for the binding of other non-β-sheet conformations to amyloid fibers.
Complex haplotypes of metabolizingGSTM1gene deletion harbors signatures of a selective sweep in East Asian populations
Authors: Saitou M. , Satta Y. , Gokcumen O. 
Published: March 2018

ABSTRACTThe deletion of the metabolizing Glutathione S-transferase Mu 1 (GSTM1) gene was previously associated with multiple cancers, metabolic and autoimmune disorders, as well as drug response. It is unusually common, with allele frequency reaching up to 75% in some human populations. Such high allele frequency of a derived allele with apparent impact on an otherwise conserved gene is a rare phenomenon. To investigate the evolutionary history of this locus, we analyzed 310 genomes using population genetics tools. Our analysis revealed a surprising lack of linkage disequilibrium between the deletion and the flanking single nucleotide variants in this locus, indicating gene conversion events. Tests that measure extended homozygosity and rapid change in allele frequency identified signatures of an incomplete soft-sweep in the locus. Using empirical approaches, we identified theTanukihaplogroup, which carries theGSTM1deletion and is found in approximately 70% of East Asian chromosomes. This haplogroup has rapidly increased its frequency in East Asian populations, contributing to a high population differentiation among continental human populations. We showed that extended homozygosity and population differentiation for this haplogroup is incompatible with simulated neutral expectations in East Asian populations. In parallel, we revealed that theTanukihaplogroup is significantly associated with the expression levels of otherGSTMgenes. Collectively, our results suggest that theTanukihaplogroup has likely undergone a soft sweep in East Asia with multiple functional consequences. Our study provides the necessary framework for further studies to elucidate the evolutionary reasons that maintain disease-susceptibility variants in theGSTM1locus.Lay summaryHere, we describe the evolutionary forces that shape the variation in a genomic region, which has been associated with bladder cancer, metabolic and autoimmune disorders and response to different drugs. Our results reveal a new genetic type common in Asian populations that may have important evolutionary and biomedical implications.
Mavacamten stabilizes the auto-inhibited state of two-headed cardiac myosin
Authors: Rohde John A. , Thomas David D. , Muretta Joseph M. 
Published: March 2018

AbstractWe used transient biochemical and structural kinetics to elucidate the molecular mechanism of mavacamten, an allosteric cardiac myosin inhibitor and prospective treatment for hypertrophic cardiomyopathy. We find that mavacamten stabilizes an auto-inhibited state of two-headed cardiac myosin, not found in the isolated S1 myosin motor fragment. We determined this by measuring cardiac myosin actin-activated and actin-independent ATPase and single ATP turnover kinetics. A two-headed myosin fragment exhibits distinct auto-inhibited ATP turnover kinetics compared to a single-headed fragment. Mavacamten enhanced this auto-inhibition. It also enhanced auto-inhibition of ADP release. Furthermore, actin changes the structure of the auto-inhibited state by forcing myosin lever-arm rotation. Mavacamten slows this rotation in two-headed myosin but does not prevent it. We conclude that cardiac myosin is regulated in solution by an interaction between its two heads and propose that mavacamten stabilizes this state.Significance StatementSmall-molecule allosteric effectors designed to target and modulate striated and smooth myosin isoforms for the treatment of disease show promise in preclinical and clinical trials. Beta-cardiac myosin is an especially important target, as heart disease remains a primary cause of death in the U.S. One prevalent type of heart disease is hypertrophic cardiomyopathy (HCM), which is hypothesized to result from dysregulated force generation by cardiac myosin. Mavacamten is a potent cardiac myosin ATPase activity inhibitor that improves cardiac output in HCM animal models. Our results show that mavacamten selectively stabilizes a two-head dependent, auto-inhibited state of cardiac myosin in solution. The kinetics and energetics of this state are consistent with the auto-inhibited super-relaxed state, previously only observed in intact sarcomeres.
Early identity recognition of familiar faces is not dependent on holistic processing
Authors: Mohr Sarah , Wang Anxu , Engell Andrew D. 
Published: March 2018

AbstractIt is widely accepted that holistic processing is critical for early face recognition, but recent work has suggested a larger role for feature-based processing. The earliest step in familiar face recognition is thought to be matching a perceptual representation of a familiar face to a stored representation of that face, which is thought to be indexed by the N250r event-related potential (ERP). In the current face priming studies, we investigated whether this perceptual representation can be effectively activated by feature-based processing. In the first experiment, prime images were familiar whole faces, isolated eyes, or isolated mouths. Whole faces and isolated eyes, but not isolated mouths, effectively modulated the N250r. In the second experiment, prime images were familiar whole faces presented either upright or inverted. Inverted face primes were no less effective than upright face primes in modulating the N250r. Together, the results of these studies indicate that activation of the earliest face recognition processes is not dependent on holistic processing of a typically configured face. Rather, feature-based processing can effectively activate the perceptual memory of a familiar face. However, not all features are effective primes as we found eyes, but not mouths, were effective in activating early face recognition.HighlightsHolistic processing is not necessary for early identity recognition of familiar faces.Inverted faces and isolated features can effectively activate the perceptual memory of a familiar face.This effectiveness was observed for eyes, but not mouths.
Reproductive interference hampers species coexistence despite conspecific sperm precedence
Authors: Iritani Ryosuke , Noriyuki Suzuki 
Published: March 2018

AbstractNegative interspecific mating interactions, known as reproductive interference, can hamper species coexistence in a local patch and promote niche partitioning or geographical segregation of closely related species. Conspecific sperm precedence (CSP), which occurs when females that have mated with both conspecific and heterospecific males preferentially use conspecific sperm for fertilization, might contribute to species coexistence by mitigating the costs of interspecific mating and hybridization. We examined whether two closely related species exhibiting CSP can coexist in a local environment in the presence of reproductive interference. First, using a behaviourally explicit mathematical model, we demonstrated that two species characterized by negative mating interactions are unlikely to coexist because the costs of reproductive interference, such as loss of mating opportunity with conspecific partners, are inevitably incurred when individuals of both species are present. Second, we experimentally demonstrated differences in mating activity and preference in twoHarmonialadybird species known to exhibit CSP. According to the developed mathematical model of reproductive interference, these behavioural differences should lead to local extinction ofH. yedoensisbecause of reproductive interference byH. axyridis. This prediction is consistent with field observations thatH. axyridisuses various food sources and habitats whereasH. yedoensisis confined to a less preferred prey item and a pine tree habitat. Finally, by a comparative approach, we showed that niche partitioning or parapatric distribution, but not sympatric coexistence in the same habitat, is maintained between species with CSP belonging to a wide range of taxa, including vertebrates and invertebrates living in aquatic or terrestrial environments. Taken together, these results lead us to conclude that reproductive interference generally destabilizes local coexistence even in closely related species that exhibit CSP.
Cell type-specific interchromosomal interactions as a mechanism for transcriptional diversity
Authors: Horta A. , Monahan K. , Bashkirova E. , Lomvardas S. 
Published: March 2018

AbstractThe eukaryotic genome is partitioned into topologically associated domains (TADs) that assemble into compartments of shared chromatin valance. This architecture is influenced by the physical constraints imposed by the DNA polymer, which restricts DNA interactions predominantly to genomic segments from the same chromosome. Here, we report a dramatic divergence from this pattern of nuclear organization that occurs during the differentiation and specification of mouse olfactory sensory neurons (OSNs). In situ HiC on FAC-sorted OSNs shows that olfactory receptor (OR) genes from numerous chromosomes make frequent, extensive, and highly specific interchromosomal contacts that strengthen with differentiation. Moreover, in terminally differentiated OSNs, >30 intergenic enhancers generate a multi-chromosomal hub that associates only with the single active OR from a pool of ∼1400 genes. Our data reveal that interchromosomal interactions can form with remarkable stereotypy between like neurons, generating a regulatory landscape for stochastic, monogenic, and monoallelic gene expression.