bluuebunny/crossref_metadata_2025_split huggingface dataset:
A neural network model for the orbitofrontal cortex and task space acquisition during reinforcement learning
Authors: Zhang Zhewei , Cheng Zhenbo , Lin Zhongqiao , Nie Chechang , Yang Tianming 
Published: March 2017

AbstractReinforcement learning has been widely used in explaining animal behavior. In reinforcement learning, the agent learns the value of the states in the task, collectively constituting the task state space, and use the knowledge to choose actions and acquire desired outcomes. It has been proposed that the orbitofrontal cortex (OFC) encodes the task state space during reinforcement learning. However, it is not well understood how the OFC acquires and stores task state information. Here, we propose a neural network model based on reservoir computing. Reservoir networks exhibit heterogeneous and dynamic activity patterns that are suitable to encode task states. The information can be extracted by a linear readout trained with reinforcement learning. We demonstrate how the network acquires and stores the task structures. The network exhibits reinforcement learning behavior and its aspects resemble experimental findings of the OFC. Our study provides a theoretical explanation of how the OFC may contribute to reinforcement learning and a new approach to understanding the neural mechanism underlying reinforcement learning.
Cysteine proteases of human hookwormNecator Americanus as virulencefactors and implications for drug design with anti-heparin and heparin analogs: A bioinformatics study
Authors: Banerjee Arpita , Widmer Kevin , Caffrey Conor R , Abagyan Ruben A. 
Published: March 2017

AbstractHuman hookwormNecator Americanus (NA)causes iron deficiency anemia, as the parasite ingests blood from the gastrointestinal tract of its human host. This bioinformatics-based study focuses on eight of the cathepsin B-like cysteine proteases (CPs) of the worm to explore their pathogenic potential. CP1 - CP6, which harbored the active site cysteine residue for enzymatic activity, were relevantly observed to have N-terminal signal peptide for extracellular localization. The secretory CPs could be releasing indigenous worm heparin at the host-pathogen interface for anticoagulation purposes. CP2 and CP3 showed a novel hemoglobinase motif that could be a prerequisite for hemoglobin degradation. CP1 and CP6 shared similar enzymatic-pocket features with cathepsin B and cruzain that cleave high molecular weight kininogen for blood-thinning activity. CP1, CP2, CP3, CP5 and CP6 were predicted to bind heparin, at their C terminal domain, like human cathepsin B and cruzain non-covalently bind heparin to enhance their activity.NACPs’ action in concert with heparin, have implications for anti-heparin and heparin analog design against hookworm infection.
Autonomous bird sound recording outperforms direct human observation: Synthesis and new evidence
Authors: Darras Kevin , Batáry Péter , Furnas Brett , Fitriawan Irfan , Mulyani Yeni , Tscharntke Teja 
Published: March 2017

Abstract1)Autonomous sound recording techniques have gained considerable traction in the last decade, but the question still remains whether they can replace human observation surveys to sample some animal taxa. Especially bird survey methods have been tested using classical point counts and autonomous sound recording techniques.2)We review the latest information by comparing both survey methods' standardization, verifiability, sampling completeness, data types, compatibility, and practicality by means of a systematic review and a meta-analysis of alpha and gamma species richness levels sampled by both methods across 20 separate studies.3)Although sound recording surveys have hitherto not enjoyed the most effective setups, they yield very similar results in terms of alpha and gamma species richness. We also reveal the crucial importance of the microphone (high signal-to-noise ratio) as the sensor that replaces human senses.4)We discuss key differences between both methods, while richness estimates are closely related and 81% of all species were detected by both methods. Sound recording techniques provide a more powerful and promising tool to monitor birds in a standardized, verifiable, and exhaustive way against the golden standard of point counts. Advantages include the capability of sampling continuously through day or season and of difficult-to-reach regions in an autonomous way, avoidance of observer bias and human disturbance effects and higher detection probability of rare species due to extensive recordings.
Flipping between Polycomb repressed and active transcriptional states introduces noise in gene expression
Authors: Kar Gozde , Kim Jong Kyoung , Kolodziejczyk Aleksandra A. , Natarajan Kedar Nath , Triglia Elena Torlai , Mifsud Borbala , Elderkin Sarah , Marioni John C. , Pombo Ana , Teichmann Sarah A. 
Published: March 2017

AbstractPolycomb repressive complexes (PRCs) are important histone modifiers, which silence gene expression, yet there exists a subset of PRC-bound genes actively transcribed by RNA polymerase II (RNAPII). It is likely that the role of PRC is to dampen expression of these PRC-active genes. However, it is unclear how this flipping between chromatin states alters the kinetics of transcriptional burst size and frequency relative to genes with exclusively activating marks. To investigate this, we integrate histone modifications and RNAPII states derived from bulk ChIP-seq data with single-cell RNA-sequencing data. We find that PRC-active genes have a greater cell-to-cell variation in expression than active genes with the same mean expression levels, and validate these results by knockout experiments. We also show that PRC-active genes are clustered on chromosomes in both two and three dimensions, and interactions with active enhancers promote a stabilization of gene expression noise. These findings provide new insights into how chromatin regulation modulates stochastic gene expression and transcriptional bursting, with implications for regulation of pluripotency and development.
Early candidate biomarkers found from urine of astrocytoma rat before changes in MRI
Authors: Ni Yanying , Zhang Fanshuang , An Manxia , Yin Wei , Gao Youhe 
Published: March 2017

AbstractAstrocytoma is the most common aggressive glioma and its early diagnosis remains difficult. Biomarkers are changes associated with the disease. Urine, which is not regulated by homeostatic mechanisms, accumulates changes and therefore is a better source for biomarker discovery. In this study, C6 cells were injected into Wistar rats brain as astrocytoma model. Urine samples were collected at day 2, day 6, day 10 and day 13 after injection, and the urinary proteomes were analyzed. On the 10th day, lesions appeared in magnetic resonance imaging. On the 13th day, clinical symptoms started. But differential urinary proteins were changed with the development of the astrocytoma, and can provide clues even on the 2nd and 6th day. Twenty-seven differential proteins with human orthologs had been reported to associate with astrocytoma. Thirty-nine proteins were verified in four more rats as candidate biomarkers of astrocytoma using multiple-reaction monitoring. A panel of differential urinary proteins may provide early biomarkers for diagnose of astrocytoma.
Comprehensive pathway analyses of schizophrenia risk loci point to dysfunctional postsynaptic signaling
Authors: Schijven Dick , Kofink Daniel , Tragante Vinicius , Verkerke Marloes , Pulit Sara L. , Kahn René S. , Veldink Jan H. , Vinkers Christiaan H. , Boks Marco P. , Luykx Jurjen J. 
Published: March 2017

AbstractLarge-scale genome-wide association studies (GWAS) have implicated many low-penetrance loci in schizophrenia. However, its pathological mechanisms are poorly understood, which in turn hampers the development of novel pharmacological treatments. Pathway and gene set analyses carry the potential to generate hypotheses about disease mechanisms and have provided biological context to genome-wide data of schizophrenia. We aimed to examine which biological processes are likely candidates to underlie schizophrenia by integrating novel and powerful pathway analysis tools using data from the largest Psychiatric Genomics Consortium schizophrenia GWAS (N = 79 845) and the most recent 2018 schizophrenia GWAS (N = 105 318). By applying a primary unbiased analysis (Multi-marker Analysis of GenoMic Annotation; MAGMA) to weigh the role of biological processes from the MSigDB database, we identified enrichment of common variants in synaptic plasticity and neuron differentiation gene sets. We supported these findings using MAGMA, Meta-Analysis Gene-set Enrichment of variaNT Associations (MAGENTA) and Interval Enrichment Analysis (INRICH) on detailed synaptic signaling pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and found enrichment in mainly the dopaminergic and cholinergic synapses. Moreover, shared genes involved in these neurotransmitter systems had a large contribution to the observed enrichment, protein products of top genes in these pathways showed more direct and indirect interactions than expected by chance, and expression profiles of these genes were largely similar among brain tissues. In conclusion, we provide strong and consistent genetics and protein-interaction informed evidence for the role of postsynaptic signaling processes in schizophrenia, opening avenues for future translational and psychopharmacological studies.
Demographic compensation does not rescue populations at a trailing range edge
Authors: Sheth Seema Nayan , Angert Amy Lauren 
Published: March 2017

ABSTRACTAs climate change shifts species' climatic envelopes across the landscape, equilibrium between geographic ranges and niches is likely diminishing due to time lags in demography and dispersal. If a species' range and niche are out of equilibrium, then population performance should decrease from cool, “leading” range edges, where populations are expanding into recently ameliorated habitats, to warm, “trailing” range edges, where populations are contracting from newly unsuitable areas. Population contraction signals that compensatory changes in vital rates are insufficient to buffer population growth from deteriorating environments. Life history theory predicts tradeoffs between fast development, high reproduction, and short longevity at low latitudes and slow development, less frequent but multiple bouts of reproduction, and long lifespan at high latitudes. If demographic compensation is driven by life history evolution, compensatory negative correlations in vital rates may be associated with this fast-slow continuum. An outstanding question is whether range limits and range contractions reflect inadequate compensatory life history shifts along environmental gradients, causing population growth rates to fall below replacement levels at range edges. We surveyed demography of 32 populations of the scarlet monkeyflower (Erythranthe cardinalis) spanning 11° latitude in western North America and used integral projection models to infer population dynamics and assess demographic compensation. Population growth rates decreased from north to south, consistent with leading-trailing dynamics. Southern populations are declining due to reduced survival, growth, and recruitment, despite compensatory increases in reproduction and faster life history characteristics, suggesting that demographic compensation will not rescue populations at the trailing range edge.SIGNIFICANCE STATEMENTWhile climate change is causing poleward shifts in many species' geographic distributions, some species' ranges have remained stable, particularly at low-latitude limits. One explanation for why some species' ranges have not shifted is demographic compensation, whereby declines in some demographic processes are offset by increases in others, potentially buffering populations from extinction. However, we have limited understanding of whether demographic compensation can prevent collapse of populations facing climate change. We examined the demography of natural populations of a perennial herb spanning a broad latitudinal gradient. Despite increases in reproduction, low-latitude populations declined due to diminished survival, growth, and recruitment. Thus, demographic compensation may not be sufficient to rescue low-latitude, warm-edge populations from extinction.
Force-dependent binding of vinculin to α-catenin regulates cell-cell contacts stability and collective cell behavior
Authors: Seddiki Rima , Sankara Narayana Gautham Hari Narayana , Strale Pierre-Olivier , Balcioglu Hayri Emrah , Peyret Grégoire , Yao Mingxi , Le Anh Phuong , Teck Lim Chwee , Yan Jie , Ladoux Benoit , Mège René-Marc 
Published: March 2017

AbstractThe shaping of a multicellular body and repair of adult tissues require fine-tuning of cell adhesion, cell mechanics and intercellular transmission of mechanical load.Adherensjunctions (AJs) are the major intercellular junctions by which cells sense and exert mechanical force on each other. However, how AJs adapt to mechanical stress and how this adaptation contributes to cell-cell cohesion and eventually to tissue-scale dynamics and mechanics remains largely unknown. Here, by analyzing the tension-dependent recruitment of vinculin, α-catenin and F-actin as a function of stiffness, as well as the dynamics of GFP-tagged wild-type and mutated α-catenins, altered for their binding capability to vinculin, we demonstrate that the force-dependent binding of vinculin stabilizes α-catenin and is responsible for AJ adaptation to force. Challenging cadherin complexes mechanical coupling with magnetic tweezers, and cell-cell cohesion during collective cell movements, further highlight that tension-dependent adaptation of AJs regulates cell-cell contact dynamics and coordinated collective cell migration. Altogether, these data demonstrate that the force-dependent α-catenin/vinculin interaction, manipulated here by mutagenesis and mechanical control, is a core regulator of AJ mechanics and long-range cell-cell interactions.Summary statementCombining cell biology and biomechanical analysis, we show here that the coupling between cadherin complexes and actin trough tension-dependent α-catenin/vinculin association is regulating AJ stability and dynamics as well as tissue-scale mechanics.
Genome-wide analysis in UK Biobank identifies four loci associated with mood instability and genetic correlation with major depressive disorder, anxiety disorder and schizophrenia
Authors: Ward Joey , Strawbridge Rona J. , Bailey Mark E. S. , Graham Nicholas , Amy Ferguson , Lyall Donald M. , DClinPsy Breda Cullen , Pidgeon Laura M. , Cavanagh Jonathan , Mackay Daniel F. , Pell Jill P. , O’Donovan Michael , Escott-Price Valentina , Smith Daniel J. 
Published: March 2017

AbstractMood instability is a core clinical feature of affective and psychotic disorders. In keeping with the Research Domain Criteria (RDoC) approach, it may be a useful construct for identifying biology that cuts across psychiatric categories. We aimed to investigate the biological validity of a simple measure of mood instability and evaluate its genetic relationship with several psychiatric disorders, including major depressive disorder (MDD), bipolar disorder (BD), schizophrenia, attention deficit hyperactivity disorder (ADHD), anxiety disorder and post-traumatic stress disorder (PTSD). We conducted a genome-wide association study (GWAS) of mood instability in 53,525 cases and 60,443 controls from UK Biobank, identifying four independently-associated loci (on chromosomes eight, nine, 14 and 18), and a common single nucleotide polymorphism (SNP)-based heritability estimate of approximately 8%. We found a strong genetic correlation between mood instability and MDD (rg=0.60, SE=0.07, p=8.95 × 10−17) and a small but significant genetic correlation with both schizophrenia (rg=0.11, SE=0.04, p=0.01) and anxiety disorders (rg=0.28, SE=0.14, p=0.04), although no genetic correlation with BD, ADHD or PTSD. Several genes at the associated loci may have a role in mood instability, including theDCC netrin 1 receptor (DCC) gene,eukaryotic translation initiation factor 2B subunit beta (eIF2B2),placental growth factor (PGF), andprotein tyrosine phosphatase, receptor type D (PTPRD). Strengths of this study include the very large sample size, but our measure of mood instability may be limited by the use of a single question. Overall, this work suggests a polygenic basis for mood instability. This simple measure can be obtained in very large samples; our findings suggest that doing so may offer the opportunity to illuminate the fundamental biology of mood regulation.
A theta rhythm in macaque visual cortex and its attentional modulation
Authors: Spyropoulos Georgios , Bosman Conrado A. , Fries Pascal 
Published: March 2017

AbstractTheta rhythms govern rodent sniffing and whisking, and human language processing. Human psychophysics suggests a role for theta also in visual attention. Yet, little is known about theta in visual areas and its attentional modulation. We used electrocorticography (ECoG) to record local field potentials (LFPs) simultaneously from areas V1, V2, V4 and TEO of two macaque monkeys performing a selective visual attention task. We found a ≈4 Hz theta rhythm within both the V1-V2 and the V4-TEO region, and theta synchronization between them, with a predominantly feedforward directed influence. ECoG coverage of large parts of these regions revealed a surprising spatial correspondence between theta and visually induced gamma. Furthermore, gamma power was modulated with theta phase. Selective attention to the respective visual stimulus strongly reduced these theta-rhythmic processes, leading to an unusually strong attention effect for V1. Microsaccades (MSs) were partly locked to theta. Yet, neuronal theta rhythms tended to be even more pronounced for epochs devoid of MSs. Thus, we find an MS-independent theta rhythm specific to visually driven parts of V1-V2, which rhythmically modulates local gamma and entrains V4-TEO, and which is strongly reduced by attention. We propose that the less theta-rhythmic and thereby more continuous processing of the attended stimulus serves the exploitation of this behaviorally most relevant information. The theta-rhythmic and thereby intermittent processing of the unattended stimulus likely reflects the ecologically important exploration of less relevant sources of information.
Complex coding and regulatory polymorphisms in a restriction factor determine the susceptibility ofDrosophilato viral infection
Authors: Cao Chuan , Cogni Rodrigo , Barbier Vincent , Jiggins Francis M. 
Published: March 2017

AbstractIt is common to find that major-effect genes are an important cause of variation in susceptibility to infection. Here we have characterised natural variation in a gene calledpastrelthat explains over half of the genetic variance in susceptibility to the virus DCV in populations ofDrosophila melanogaster. We found extensive allelic heterogeneity, with a sample of seven alleles ofpastrelfrom around the world conferring four phenotypically distinct levels of resistance. By modifying candidate SNPs in transgenic flies, we show that the largest effect is caused by an amino acid polymorphism that arose when an ancestral threonine was mutated to alanine, greatly increasing resistance to DCV. Overexpression of the ancestral susceptible allele provides strong protection against DCV, indicating that this mutation acted to improve an existing restriction factor. Thepastrellocus also contains complex structural variation andcis-regulatory polymorphisms altering gene expression. We find that higher expression ofpastrelis associated with increased survival after DCV infection. To understand why this variation is maintained in populations, we investigated genetic variation surrounding the amino acid variant that is causing flies to be resistant. We found no evidence of natural selection causing either recent changes in allele frequency or geographical variation in frequency, suggesting that this is an old polymorphism that has been maintained at a stable frequency. Overall, our data demonstrate how complex genetic variation at a single locus can control susceptibility to a virulent natural pathogen.
Validation of a novel molecular host response assay to diagnose infection in hospitalized patients admitted to the ICU with acute respiratory failure
Authors: Koster-Brouwer Maria E. , Verboom Diana M. , Scicluna Brendon P. , van de Groep Kirsten , Frencken Jos F. , Janssen Davy , Schuurman Rob , Schultz Marcus J. , Poll Tom van der , Bonten Marc J.M. , Cremer Olaf L. ,   on behalf of the MARS consortium
Published: March 2017

AbstractPurposeThe discrimination between infectious and non-infectious causes of acute respiratory failure (ARF) in hospitalized patients admitted to the intensive care unit (ICU) is difficult. Using a novel diagnostic test measuring the expression of four RNA biomarkers in blood (SeptiCyte LAB) we aimed to distinguish between infection and inflammation in this setting.MethodsWe enrolled hospitalized patients with ARF requiring prompt intubation in the ICU from 2011 to 2013. We excluded patients having an established infection diagnosis or an evidently non-infectious reason for intubation. Blood samples were collected upon ICU admission. Test results were categorized into four probability bands (with higher bands indicating a higher probability of infection) and compared with the plausibility of infection as rated by post-hoc assessment using predefined definitions.ResultsOf 467 included patients, 373 (80%) were treated for a suspected infection at admission. Plausibility of infection was classified as ruled-out, undetermined, or confirmed in 41 (11%), 135 (36%), and 197 (53%) of these, respectively. Overall, the pre-test probability of infection was 42%. Test results correlated with the plausibility of infection (Spearman’s rho 0.332; p<0.001). After exclusion of undetermined cases, positive predictive values were 29%, 54%, and 76% for probability bands 2, 3, and 4, respectively, whereas the negative predictive value for band 1 was 76%. However, SeptiCyte LAB did not outperform CRP when comparing diagnostic discrimination (AUC 0.731; 95%CI 0.677-0.786 vs. 0.727; 95%CI 0.666-0.788).ConclusionIn a setting of hospitalized patients admitted to the ICU with ARF, the diagnostic value of SeptiCyte LAB seems limited.
Balance between mutually exclusive traits shifted by variants of a yeast transcription factor
Authors: Dorrity Michael W. , Cuperus Josh T. , Carlisle Jolie A. , Fields Stanley , Queitsch Christine 
Published: March 2017

AbstractInSaccharomyces cerevisiae, the decision to mate or invade relies on environmental cues that converge on a shared transcription factor, Ste12. Specificity toward invasion occurs via Ste12 binding cooperatively with the co-factor Tec1. Here, we characterize thein vitrobinding preferences of Ste12 to identify a defined spacing and orientation of dimeric sites, one that is common in pheromone-regulated genes. We find that single amino acid changes in the DNA-binding domain of Ste12 can shift the preference of yeast toward either mating or invasion. These mutations define two distinct regions of this domain, suggesting alternative modes of DNA binding for each trait. Some exceptional Ste12 mutants promote hyperinvasion in a Tec1-independent manner; these fail to bind cooperative sites with Tec1 and bind to unusual dimeric Ste12 sites that contain one highly degenerate half site. We propose a model for how activation of invasion genes could have evolved with Ste12 alone.