bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR-223 represents a biomarker in acute and chronic liver injury
Authors: Schueller Florian , Roy Sanchari , Loosen Sven Heiko , Alder Jan , Koppe Christiane , Schneider Anne Theres , Wandrer Franziska , Bantel Heike , Vucur Mihael , Mi Qing-Sheng , Trautwein Christian , Luedde Tom , Roderburg Christoph 
Published: June 2017

Background: Dysregulation of miRNAs has been described in tissue and serum from patients with acute and chronic liver diseases. However, only little information on the role of miR-223 in the pathophysiology of acute liver failure (ALF) and liver cirrhosis is available.
Methods: We analysed cell and tissue specific expression levels as well as serum concentrations of miR-223 in mouse models of acute (hepatic ischaemia and reperfusion, single CCl4 injection) and chronic (repetitive CCl4 injection, bile duct ligation (BDL)) liver diseases. Results were validated in patients and correlated with clinical data. The specific hepatic role of miR-223 was analysed by using miR-223−/− mice in these models.
Results: miR-223 expression was significantly dysregulated in livers from mice after induction of acute liver injury and liver fibrosis as well as in liver samples from patients with ALF or liver cirrhosis. In acute and chronic models, hepatic miR-223 up-regulation was restricted to hepatocytes and correlated with degree of liver injury and hepatic cell death. Moreover, elevated miR-223 expression was reflected by significantly higher serum levels of miR-223 during acute liver injury. However, functional in vitro and in vivo experiments revealed no differences in the degree of liver cell death and liver fibrosis as miR-223−/− mice behaved identical with wild-type (wt) mice in all tested models.
Conclusion: miR-223 represents a promising diagnostic marker in a panel of serum markers of liver injury. Together with previously published data, our results highlight that the role of miR-223 in the pathophysiology of the liver is complex and needs further analysis.
Cervical Spine Deformity—Part 2: Management Algorithm and Anterior Techniques
Authors: Tan Lee A. , Riew K. Daniel , Traynelis Vincent C. 
Published: June 2017

Abstract
A sound operative plan based on solid understanding of the pathology and biomechanics is the most important part of cervical deformity correction. Many different surgical options exist for operative management of cervical spine deformities. However, selecting the correct approach that ensures the optimal clinical outcome can be challenging and often controversial. In Part 2 of this three-part review series, we discuss the pre-operative planning, management algorithm, and anterior surgical techniques for cervical deformity correction.
Mitochondrial genome ofPlasmodium vivax/simiumdetected in an endemic region for malaria in the Atlantic Forest of Espírito Santo state, Brazil: do mosquitoes, simians and humans harbor the same parasite?
Authors: Buery JC , Rodrigues PT , Natal L , Salla LC , Loss AC , Vicente CR , Rezende HR , Duarte AMCR , Fux B , Malafronte RS , Falqueto A , Cerutti C. 
Published: June 2017

AbstractBackgroundThe transmission of malaria in the extra-Amazonian regions of Brazil, although interrupted in the 1960s, has persisted to the present time in some areas of dense Atlantic Forest, with reports of cases characterized by particular transmission cycles and clinical presentations. Bromeliad-malaria, as it is named, is particularly frequent in the state of Espírito Santo, withPlasmodium vivaxbeing the parasite commonly recognized as the etiologic agent of human infections. With regard to the spatial and temporal distances between cases reported in this region, the transmission cycle does not fit the traditional malaria cycle. The existence of a zoonosis, with infected simians participating in the epidemiology, is therefore hypothesized. In the present study, zoonotic transmission of bromeliad-malaria in Espírito Santo is investigated, based on the complete mitochondrial genome of DNA extracted from isolates ofPlasmodiumspecies which had infected humans, a simian from the genusAllouata, andAnophelesmosquitoes.Plasmodium vivax/simiumwas identified in the samples by both nested-PCR and real-time PCR. After amplification, the mitochondrial genome was completely sequenced and compared in a haplotype network, including all sequences ofP. vivax/simiummitochondrial genomes sampled from humans and simians from all regions in Brazil.ResultsThe haplotype network demonstrates that humans and simians from the Atlantic Forest share the same haplotype, but some isolates from humans are not identical to the simian isolate. In addition, the plasmodial DNA extracted from mosquitoes revealed sequences different from those obtained from simians, but similar to two isolates from humans.ConclusionsThese findings reinforce the hypothesis that in the Atlantic Forest, and especially in the state with the highest frequency of bromeliad-malaria in Brazil, the same parasite species is shared by humans and simians, at least in part. The difference between the sequences of mosquitoes and simians raises two hypotheses: (1) two distinct transmission cycles for human malaria exist in the study area, one of them involving simians and the other exclusive to human hosts, or (2) there is only one transmission cycle involving humans and simians, but the identification of variations among simians was not possible due to a lack of other samples.
Genome-wide analysis reveals distinct genetic mechanisms of diet-dependent lifespan and healthspan inD. melanogaster
Authors: Wilson Kenneth A. , Nelson Christopher S. , Beck Jennifer N. , Brem Rachel B. , Kapahi Pankaj 
Published: June 2017

ABSTRACTDietary restriction (DR) robustly extends lifespan and delays age-related diseases across species. An underlying assumption in aging research has been that DR mimetics extend both lifespan and healthspan jointly, though this has not been rigorously tested in different genetic backgrounds. Furthermore, nutrient response genes important for lifespan or healthspan extension remain underexplored, especially in natural populations. To address these gaps, we utilized over 150 DGRP strains to measure nutrient-dependent changes in lifespan and age-related climbing ability to measure healthspan. DR extended lifespan and delayed decline in climbing ability on average, but there was no evidence of correlation between these traits across individual strains. Through GWAS, we then identified and validatedjugheadandFerredoxinas determinants of diet-dependent lifespan, andDaedalusfor diet-dependent physical activity. Modulating these genes produced independent effects on lifespan and climbing ability, further suggesting that these age-related traits are likely to be regulated through distinct genetic mechanisms.
Structure and misfolding of the flexible tripartite coiled coil domain of glaucoma-associated myocilin
Authors: Hill Shannon E. , Nguyen Elaine , Donegan Rebecca K. , Hazel Anthony , Gumbart James C. , Lieberman Raquel L. 
Published: June 2017

SummaryGlaucoma-associated myocilin is a member of the olfactomedins, a protein family broadly involved in neuronal development and human disease. Molecular studies of the myocilin N-terminal coiled coil demonstrate a unique tripartite architecture: a disulfide-linked, parallel dimer-of-dimers Y-shaped molecule, with distinct tetramer and dimer regions. The structure of the C-terminal 7-heptad dimer elucidates an unexpected repeat pattern involving electrostatic inter-strand stabilization. Molecular dynamics simulations reveal an alternate conformation in which the terminal inter-strand disulfide bond limits the extent of unfolding and results in a kinked configuration. Taken together, full-length myocilin is also branched, with two pairs of C-terminal olfactomedin domains. Selected variants within the N-terminal region alter the apparent quaternary structure of myocilin but do so without compromising stability or causing aggregation. In addition to increasing our structural knowledge of extracellular coiled coils for protein design and biomedically important olfactomedins, this work broadens the scope of protein misfolding in the pathogenesis of myocilin-associated glaucoma.HighlightsGlaucoma-causing extracellular protein associated with amyloid forming propensityStructural studies confirm tripartite parallel dimer-of-dimers coiled coilLeucine zipper exhibits non-canonical heptad repeat pattern with disulfide capGlaucoma-associated variants in tetramer alter structure but not stabilityeTOC blurbHill et al describe the structure of the coiled-coil region of myocilin, the extracellular olfactomedin family member closely associated with the ocular disorder glaucoma. Myocilin’s coiled coil adopts a unique Y-shaped parallel dimer-of-timers employing an unusual heptad repeat pattern. Selected disease variants alter quaternary structure.
RNA interference pathways display high rates of adaptive protein evolution across multiple invertebrates
Authors: Palmer William H. , Hadfield Jarrod , Obbard Darren J. 
Published: June 2017

AbstractConflict between organisms can lead to reciprocal adaptation that manifests itself as an increased evolutionary rate in the genes mediating the conflict. This adaptive signature has been observed in RNA interference (RNAi) pathway genes involved in the suppression of viruses and transposable elements inDrosophila melanogaster, suggesting that a subset ofDrosophilaRNAi genes may be locked into an arms race with these parasites. However, it is not known whether rapid evolution of RNAi genes is a general phenomenon across invertebrates, or which RNAi genes generally evolve adaptively. Here we use population genomic data from eight invertebrate species to infer rates of adaptive sequence evolution, and to test for past and ongoing selective sweeps in RNAi genes. We assess rates of adaptive protein evolution across species by using a formal meta-analytic framework to combine data across species, and by implementing a multispecies generalised linear mixed model of mutation counts. In all species, we find that RNAi genes display a greater rate of adaptive protein substitution than other genes, and that this is primarily mediated by positive selection acting on the subset of genes that are most likely to defend against viruses and transposable elements. In contrast, evidence for recent selective sweeps is broadly spread across functional classes of RNAi genes and differs substantially among species. Finally, we identify genes that exhibit elevated adaptive evolution across the analysed insect species combined, perhaps due to concurrent parasite-mediated arms races.
A Deep Learning Approach to Estimate Collagenous Tissue Nonlinear Anisotropic Stress-Strain Responses from Microscopy Images
Authors: Liang Liang , Liu Minliang , Sun Wei 
Published: June 2017

ABSTRACTBiological collagenous tissues comprised of networks of collagen fibers are suitable for a broad spectrum of medical applications owing to their attractive mechanical properties. In this study, we developed a noninvasive approach to estimate collagenous tissue elastic properties directly from microscopy images using Machine Learning (ML) techniques. Glutaraldehyde-treated bovine pericardium (GLBP) tissue, widely used in the fabrication of bioprosthetic heart valves and vascular patches, was chosen as a representative collagenous tissue. A Deep Learning model was designed and trained to process second harmonic generation (SHG) images of collagen networks in GLBP tissue samples, and directly predict the tissue elastic mechanical properties. The trained model is capable of identifying the overall tissue stiffness with a classification accuracy of 84%, and predicting the nonlinear anisotropic stress-strain curves with average regression errors of 0.021 and 0.031. Thus, this study demonstrates the feasibility and great potential of using the Deep Learning approach for fast and noninvasive assessment of collagenous tissue elastic properties from microstructural images.
Intestinal epithelial and intraepithelial T cell crosstalk mediates a dynamic response to infection
Authors: Hoytema van Konijnenburg David P. , Reis Bernardo S. , Pedicord Virginia , Farache Julia , Victora Gabriel D. , Mucida Daniel 
Published: June 2017

SummaryIntestinal intraepithelial lymphocytes (IELs) are located at the critical interface between the intestinal lumen, which is chronically exposed to food and microbes, and the core of the body. Using high-resolution microscopy techniques and intersectional genetic tools, we investigated the nature of IEL responses to luminal microbes. We observed that TCRγδ IELs exhibit distinct location and movement patterns in the epithelial compartment that were microbiota-dependent and quickly altered upon enteric infections. These infection-induced changes included increased inter-epithelial cell (EC) scanning, anti-microbial gene expression and glycolysis. Direct modulation of glycolysis was sufficient to change γδ IEL behavior and susceptibility to early pathogen invasion. Both γδ IEL behavioral and metabolic changes were dependent on EC pathogen sensing. Our results uncover a coordinated EC–IEL response to enteric infections that modulates lymphocyte energy utilization and dynamics and supports maintenance of the intestinal epithelial barrier.
Estimates of introgression as a function of pairwise distances
Authors: Pfeifer Bastian , Kapan Durrell D 
Published: June 2017

AbstractBackgroundResearch over the last 10 years highlights the increasing importance of hybridization between species as a major force structuring the evolution of genomes and potentially providing raw material for adaptation by natural and/or sexual selection. Fueled by research in a few model systems where phenotypic hybrids are easily identified, research into hybridization and introgression (the flow of genes between species) has exploded with the advent of whole-genome sequencing and emerging methods to detect the signature of hybridization at the whole-genome or chromosome level. Amongst these are a general class of methods that utilize patterns of single-nucleotide polymorphisms (SNPs) across a tree as markers of hybridization. These methods have been applied to a variety of genomic systems ranging from butterflies to Neanderthal’s to detect introgression, however, when employed at a fine genomic scale these methods do not perform well to quantify introgression in small sample windows.ResultsWe introduce a novel method to detect introgression by combining two widely used statistics: pairwise nucleotide diversitydxyand Patterson’sD. The resulting statistic, theBasic distance fraction(Bdf), accounts for genetic distance across possible topologies and is designed to simultaneously detect and quantify introgression. We also relate our new method to the recently publishedfdand incorporate these statistics into the powerful genomics R-package PopGenome, freely available on GitHub (pievos101/PopGenome). The supplemental material contains a wide range of simulation studies and a detailed manual how to perform the statistics within the PopGenome framework.ConclusionWe present a new distance based statisticBdfthat avoids the pitfalls of Patterson’sDwhen applied to small genomic regions and accurately quantifies the fraction of introgression (f) for a wide range of simulation scenarios.
Spatiotemporal relationships defining the adaptive gating of the bacterial mechanosensitive channel MscS
Authors: Çetiner Uğur , Sukharev Sergei 
Published: June 2017

AbstractAdaptive desensitization and inactivation are common properties of most ion channels and receptors. The mechanosensitive channel of small conductance MscS, which serves as a low-threshold osmolyte release valve in most bacteria, is unusual because it slowly inactivates not from the open, but from the resting state under moderate tensions. The manifestation of this mechanism is the channel’s ability to discriminate the rate of tension application, i.e., to ignore slow tension ramps but fully respond to abruptly applied stimuli. In this work, we present a reconstruction of the landscape for tension-dependent MscS transitions based on patch current kinetics recorded under specially designed pressure protocols. The data are analyzed with a three-state continuous time Markov model of gating, where the tension-dependent transition rates are governed by Arrhenius-type relations. The analysis provides assignments to the intrinsic opening, closing, inactivation, and recovery rates as well as their tension dependencies. These parameters, which define the spatial (areal) distances between the energy wells and the positions of barriers, describe the tension-dependent distribution of the channel population between the three states and quantitatively predict the experimentally observed dynamic pulse and ramp responses. Our solution also provides an analytic expression for the area of the inactivated state in terms of two experimentally accessible parameters: the tension at which inactivation probability is maximized, γ*, and the midpoint tension for activation, γ0.5. The analysis initially performed onEscherichia coliMscS shows its applicability to the previously uncharacterized MscS homolog fromPseudomonas aeruginosa. MscS inactivation minimizes metabolic losses during osmotic permeability response and thus contributes to the environmental fitness of bacteria.
Multivariate Heteroscedasticity Models for Functional Brain Connectivity
Authors: Seiler Christof , Holmes Susan 
Published: June 2017

ABSTRACTFunctional brain connectivity is the co-occurrence of brain activity in different areas during resting and while doing tasks. The data of interest are multivariate timeseries measured simultaneously across brain parcels using resting-state fMRI (rfMRI). We analyze functional connectivity using two heteroscedasticity models. Our first model is low-dimensional and scales linearly in the number of brain parcels. Our second model scales quadratically. We apply both models to data from the Human Connectome Project (HCP) comparing connectivity between short and conventional sleepers. We find stronger functional connectivity in short than conventional sleepers in brain areas consistent with previous findings. This might be due to subjects falling asleep in the scanner. Consequently, we recommend the inclusion of average sleep duration as a covariate to remove unwanted variation in rfMRI studies. A power analysis using the HCP data shows that a sample size of 40 detects 50% of the connectivity at a false discovery rate of 20%. We provide implementations using R and the probabilistic programming language Stan.
Electronic Health Record and Genome-wide Genetic Data in Generation Scotland Participants
Authors: Kerr Shona M. , Campbell Archie , Marten Jonathan , Vitart Veronique , McIntosh Andrew , Porteous David J. , Hayward Caroline 
Published: June 2017

AbstractThis paper provides the first detailed demonstration of the research value of the Electronic Health Record (EHR) linked to research data in Generation Scotland Scottish Family Health Study (GS:SFHS) participants, together with how to access this data. The structured, coded variables in the routine biochemistry, prescribing and morbidity records in particular represent highly valuable phenotypic data for a genomics research resource. Access to a wealth of other specialized datasets including cancer, mental health and maternity inpatient information is also possible through the same straightforward and transparent application process. The Electronic Health Record linked dataset is a key component of GS:SFHS, a biobank conceived in 1999 for the purpose of studying the genetics of health areas of current and projected public health importance. Over 24,000 adults were recruited from 2006 to 2011, with broad and enduring written informed consent for biomedical research. Consent was obtained from 23,603 participants for GS:SFHS study data to be linked to their Scottish National Health Service (NHS) records, using their Community Health Index (CHI) number. This identifying number is used for NHS Scotland procedures (registrations, attendances, samples, prescribing and investigations) and allows healthcare records for individuals to be linked across time and location. Here, we describe the NHS EHR dataset on the sub-cohort of 20,032 GS:SFHS participants with consent and mechanism for record linkage plus extensive genetic data. Together with existing study phenotypes, including family history and environmental exposures such as smoking, the EHR is a rich resource of real world data that can be used in research to characterise the health trajectory of participants, available at low cost and a high degree of timeliness, matched to DNA, urine and serum samples and genome-wide genetic information.
Patterns of conservation and diversification in the fungal polarization network
Authors: Diepeveen Eveline T. , Pourquié Valérie , Gehrmann Thies , Abeel Thomas , Laan Liedewij 
Published: June 2017

AbstractThe combined actions of proteins in networks underlie all fundamental cellular functions. Deeper insights into the dynamics of network composition across species and their functional consequences are crucial to fully understand protein network evolution. Large-scale comparative studies with high phylogenetic resolution are now feasible through the recent rise in available genomic datasets of both modelandnon-model species. Here we focus on the polarity network, which is universally essential for cell proliferation and studied in great detail in the model organism,Saccharomyces cerevisiae. We examine 34 proteins, directly related to cell polarization, across 200 fungal strains/species to determine evolution of the composition of the network and patterns of conservation and diversification.We observe strong protein conservation for a group of 16 core proteins: 95% of all strains/species possess at least 75% of these proteins, albeit in varying compositions. We find high levels of variation in prevalence and sequence identity in the remaining 18 proteins, resulting in distinct lineage-specific compositions of the network in the majority of strains/species. We test if the observed diversification in network composition correlates with potential underlying factors and find that lineage, lifestyle, and genetic distance co-vary with network size. Yeast, filamentous and basal unicellular fungi form distinctive groups based on these analyses, with substantial differences to their polarization network. Our study shows that evolution of the fungal polarization network is highly dynamic, even between closely related species, and that functional conservation is achieved by varying structural conservation of the fungal polarization proteins.Data DepositionSequence alignments used are available upon request.