bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic comorbidity between major depression and cardio-metabolic disease, stratified by age at onset of major depression
Authors: Hagenaars SP , Coleman JRI , Choi S , Gaspar H , Adams MJ , Howard D , Hodgson K , Traylor M , Air TM , Andlauer TFM , Arolt V , Baune BT , Binder EB , Blackwood DHR , Boomsma DI , Campbell A , Cearns M , Czamara D , Dannlowski U , Domschke K , de Geus EJC , Hamilton SP , Hayward C , Hickie I , Hottenga JJ , Ising M , Jones I , Jones LA , Kutalik Z , Lucae S , Martin NG , Milaneschi Y , Mueller-Myhsok B , Owen MJ , Padmanabhan S , Penninx BWJH , Pistis G , Porteous DJ , Preisig M , Ripke S , Shyn SI , Sullivan PF , Whitfield J , Wray NR ,   Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium,   MEGASTROKE consortium, McIntosh AM , Deary IJ , Breen G , Lewis CM 
Published: May 2019

AbstractIntroductionIt’s imperative to understand the specific and shared aetiologies of major depression and cardio-metabolic disease, as both traits are frequently comorbid and each represents a major burden to society. This study examined whether there is a genetic association between major depression and cardio-metabolic traits and if this association is stratified by age at onset for major depression.MethodsPolygenic risk scores analysis and linkage disequilibrium score regression was performed to examine whether differences in shared genetic aetiology exist between depression case control status (N cases = 40,940, N controls = 67,532), earlier (N = 15,844), and later onset depression (N = 15,800) with body mass index, coronary artery disease, stroke, and type 2 diabetes in eleven data sets from the Psychiatric Genomics Consortium, Generation Scotland, and UK Biobank.ResultsAll cardio-metabolic polygenic risk scores were associated with depression status. Significant genetic correlations were found between depression and body mass index, coronary artery disease, and type 2 diabetes. Higher polygenic risk for body mass index, coronary artery disease and type 2 diabetes was associated with both early and later onset depression, while higher polygenic risk for stroke was associated with later onset depression only. Significant genetic correlations were found between body mass index and later onset depression, and between coronary artery disease and both early and late onset depression.ConclusionsThe phenotypic associations between major depression and cardio-metabolic traits may partly reflect their overlapping genetic aetiology irrespective of the age depression first presents.
Bayesian model discrimination for partially-observed epidemic models
Authors: Walker James N. , Black Andrew J. , Ross Joshua V. 
Published: May 2019

AbstractAn efficient method for Bayesian model selection is presented for a broad class of continuous-time Markov chain models and is subsequently applied to two important problems in epidemiology. The first problem is to identify the shape of the infectious period distribution; the second problem is to determine whether individuals display symptoms before, at the same time, or after they become infectious. In both cases we show that the correct model can be identified, in the majority of cases, from symptom onset data generated from multiple outbreaks in small populations. The method works by evaluating the likelihood using a particle filter that incorporates a novel importance sampling algorithm designed for partially-observed continuous-time Markov chains. This is combined with another importance sampling method to unbiasedly estimate the model evidence. These come with estimates of precision, which allow for stopping criterion to be employed. Our method is general and can be applied to a wide range of model selection problems in biological and epidemiological systems with intractable likelihood functions.
Species-specific InDel markers for authentication of the Korean herbsZanthoxylum schinifoliumandZanthoxylum piperitum
Authors: Kim Yonguk , Shin Jawon , Cho Seung-Sik , Hwang Yong-Pil , Choi Chulyung 
Published: May 2019

AbstractObjectiveZanthoxylum schinifoliumandZanthoxylum piperitumare the sources of the well-known traditional Korean herbal medicines “sancho” (prickly ash) and “chopi” (Korean pepper), respectively. Sancho and chopi are often indiscriminately mixed due to the similar appearance of the herbal materials when used as spices and herbal medicines. Moreover, commercial sancho and chopi products often contain adulterants, which could compromise drug efficacy and safety.MethodsIn this study, we developed hypervariable InDel markers to distinguish between sancho and chopi products by comparing the complete chloroplast genome sequences of fourZanthoxylumspecies deposited in NCBI GenBank.ResultsComparative analyses of the nucleotide diversity (Pi) of theseZanthoxylumgenomes revealed four hypervariable divergent sites (trnH-psbA, psbZ-trnG, trnfM-rps14, andtrnF-ndhK) withPi> 0.025 among 520 windows. Of these four regions, including two genic and two intergenic regions, onlypsbZ-trnGyielded accurate PCR amplification results between commercial sancho and chopi products from the Korean herbal medicine market. We therefore selectedpsbZ-trnG, an InDel-variable locus with high discriminatory powers, as a candidate DNA barcode locus.ConclusionThis InDel marker could be used as a valuable, simple, and efficient tool for identifying these medicinal herbs, thereby increasing the safety of these spices and herbal materials in the commercial market.
PfCERLI1, a conserved rhoptry associated protein essential for invasion byPlasmodium falciparummerozoites
Authors: Liffner Benjamin , Frölich Sonja , Heinemann Gary K. , Liu Boyin , Dixon Matthew W. A. , Gilberger Tim-Wolf , Wilson Danny W. 
Published: May 2019

AbstractThe disease-causing blood stage of thePlasmodium falciparumlifecycle begins with invasion of human erythrocytes by merozoites. Many vaccine candidates with key roles in binding to the erythrocyte surface and entry are secreted from the large bulb-like rhoptry organelles at the apical tip of the merozoite. Here we identify an essential role for the conserved proteinP. falciparumCytosolicallyExposedRhoptryLeafletInteracting protein 1 (PfCERLI1) in rhoptry function. We show that PfCERLI1 localises to the cytosolic face of the rhoptry bulb membrane and knockdown of PfCERLI1 inhibits merozoite invasion. While schizogony and merozoite organelle biogenesis appear normal, biochemical techniques and semi-quantitative super-resolution microscopy show that PfCERLI1 knockdown prevents secretion of key rhoptry antigens that coordinate merozoite invasion. PfCERLI1 is the first rhoptry associated protein identified to have a direct role in function of this essential malaria invasion organelle which has broader implications for understanding apicomplexan invasion biology.
End-to-end assessment of fecal bacteriome analysis: from sample processing to DNA sequencing and bioinformatics results
Authors: Christoff Ana Paula , Cruz Giuliano Netto Flores , Sereia Aline Fernanda Rodrigues , EikoYamanaka Laís , Silveira Paola Paz , Oliveira Luiz Felipe Valter 
Published: May 2019

AbstractIntestinal microbiome, comprising the whole microbiota, their genes and genomes living in the human gut have significant roles in promoting health or disease status. As many studies showed so far, identifying the bacterial components of the microbiome can reveal important biomarkers to help in the disease comprehension to a further adequate treatment. However, the human nature is quite variable considering the genetic components associated with life styles, directly reflecting on the gut microbiome. Thus, it is extremely important to know the populational microbiome background in order to draw conclusions regarding the health and disease conditions. Also, methodological best practices and knowledge about the methods being used are essential for the results quality and applicability with clinical relevance. In this way, we standardized the sample collection and processing methods used for the Probiome assay, a test developed to identify the Brazilian bacteriome from stool samples. EncodeTools Metabarcode pipeline of analysis was developed to obtain the best result from the samples. This pipeline uses the information of amplicon single variants (ASVs) in 100% identical oligotype clusters, and performs a de novo taxonomical assignment based on similarity for unknown sequences. To better comprehend the results obtained in Probiome assays, is essential to know the intestinal bacteriome diversity of Brazilians. Thus, we applied the standardized methods herein developed and began characterizing our populational data to allow a better understanding of the Brazilian bacteriome profiles and how they can be related to other microbiome studies.
Action representation in the mouse parieto-frontal network
Authors: Tombaz Tuce , Dunn Benjamin A. , Hovde Karoline , Cubero Ryan J. , Mimica Bartul , Mamidanna Pranav , Roudi Yasser , Whitlock Jonathan R. 
Published: May 2019

AbstractThe posterior parietal cortex (PPC), along with anatomically linked frontal areas, form a cortical network which mediates several functions that support goal-directed behavior, including sensorimotor transformations and decision making. In primates, this network also links performed and observed actions via mirror neurons, which fire both when an individual performs an action and when they observe the same action performed by a conspecific. Mirror neurons are thought to be important for social learning and imitation, but it is not known whether mirror-like neurons occur in similar networks in other species that can learn socially, such as rodents. We therefore imaged Ca2+ responses in large neural ensembles in PPC and secondary motor cortex (M2) while mice performed and observed several actions in pellet reaching and wheel running tasks. In all animals, we found spatially overlapping neural ensembles in PPC and M2 that robustly encoded a variety of naturalistic behaviors, and that subsets of cells could stably encode multiple actions. However, neural responses to the same set of observed actions were absent in both brain areas, and across animals. Statistical modeling analyses also showed that performed actions, especially those that were task-specific, outperformed observed actions in predicting neural responses. Overall, these findings show that performed and observed actions do not drive the same cells in the parieto-frontal network in mice, and suggest that sensorimotor mirroring in the mammalian cortex may have evolved more recently, and only in certain species.
Functional Analysis of Enzyme Families Using Residue-Residue Coevolution Similarity Networks
Authors: Atallah Christian , Skelton David James , Charnock Simon J. , Wipat Anil 
Published: May 2019

AbstractMotivationResidue-residue coevolution has been used to elucidate structural information of enzymes. Networks of coevolution patterns have also been analyzed to discover residues important for the function of individual enzymes. In this work, we take advantage of the functional importance of coevolving residues to perform network-based clustering of subsets of enzyme families based on similarities of their coevolution patterns, or “Coevolution Similarity Networks”. The power of these networks in the functional analysis of sets of enzymes is explored in detail, using Sequence Similarity Networks as a benchmark.ResultsA novel method to produce protein-protein networks showing the similarity between proteins based on the matches in the patterns of their intra-residue residue coevolution is described. The properties of these co-evolution similarity networks (CSNs) was then explored, especially in comparison to widely used sequence similarity networks (SSNs). We focused on the predictive power of CSNs and SSNs for the annotation of enzyme substrate specificity in the form of Enzyme Commission (EC) numbers using a label propagation approach. A method for systematically defining the threshold necessary to produce the optimally predictive CSNs and SSNs is described. Our data shows that, for the two protein families we analyse, CSNs show higher predictive power for the reannotation of substrate specificity for previously annotated enzymes retrieved from Swissprot. A topological analysis of both CSNs and SSNs revealed core similarities in the structure, topology and annotation distribution but also reveals a subset of nodes and edges that are unique to each network type, highlighting their complementarity. Overall, we propose CSNs as a new method for analysing the function enzyme families that complements, and offers advantages to, other network based methods for protein family analysis.AvailabilitySource code available on request.
Improved Statistical Efficiency of Simultaneous Multi-Slice fMRI by Reconstruction with Spatially Adaptive Temporal Smoothing
Authors: Chiew Mark , Miller Karla L. 
Published: May 2019

AbstractWe introduce an approach to reconstruction of simultaneous multi-slice (SMS)-fMRI data that improves statistical efficiency. The method incorporates regularization to adjust temporal smoothness in a spatially varying, encoding-dependent manner, reducing the g-factor noise amplification per temporal degree of freedom. This results in a net improvement in tSNR and GLM efficiency, where the efficiency gain can be derived analytically as a function of the encoding and reconstruction parameters. Residual slice leakage and aliasing is limited when fMRI signal energy is dominated by low frequencies. Analytical predictions, simulated and experimental results demonstrate a marked improvement in statistical efficiency in the temporally regularized reconstructions compared to conventional slice-GRAPPA reconstructions, particularly in central brain regions. Furthermore, experimental results confirm that residual slice leakage and aliasing errors are not noticeably increased compared to slice-GRAPPA reconstruction. This approach to temporally regularized image reconstruction in SMS-fMRI improves statistical power, and allows for explicit choice of reconstruction parameters by directly assessing their impact on noise variance per degree of freedom.
Modulation of the primary auditory thalamus when recognising speech in noise
Authors: Mihai Paul Glad , Tschentscher Nadja , von Kriegstein Katharina 
Published: May 2019

AbstractRecognising speech in background noise is a strenuous daily activity, yet most humans can master it. A mechanistic explanation of how the human brain deals with such sensory uncertainty is the Bayesian Brain Hypothesis. In this view, the brain uses a dynamic generative model to simulate the most likely trajectory of the speech signal. Such simulation account can explain why there is a task-dependent modulation of sensory pathway structures (i.e., the sensory thalami) for recognition tasks that require tracking of fast-varying stimulus properties (i.e., speech) in contrast to relatively constant stimulus properties (e.g., speaker identity) despite the same stimulus input. Here we test the specific hypothesis that this task-dependent modulation for speech recognition increases in parallel with the sensory uncertainty in the speech signal. In accordance with this hypothesis, we show—by using ultra-high-resolution functional magnetic resonance imaging in human participants—that the task-dependent modulation of the left primary sensory thalamus (ventral medial geniculate body, vMGB) for speech is particularly strong when recognizing speech in noisy listening conditions in contrast to situations where the speech signal is clear. Exploratory analyses showed that this finding was specific to the left vMGB; it was not present in the midbrain structure of the auditory pathway (left inferior colliculus, IC). The results imply that speech in noise recognition is supported by modifications at the level of the subcortical sensory pathway providing driving input to the auditory cortex.
Developmentally-orchestrated mitochondrial processes prime the selection against harmful mtDNA mutations
Authors: Chen Zhe , Wang Zong-Heng , Zhang Guofeng , Bleck Christopher K. E. , Chung Dillon J. , Madison Grey , Lindberg Eric , Combs Christian , Balaban Robert S. , Xu Hong 
Published: May 2019

AbstractAlthough mitochondrial DNA (mtDNA) is prone to mutation and not all conventional DNA repair systems operate in mitochondria, deleterious mutations are exceedingly rare. How the transmission of detrimental mtDNA mutations is restricted through the maternal lineage is debated. Here, we useDrosophilato dissect the mechanisms of mtDNA selective inheritance and understand their molecular underpinnings. Our observations support a purifying selection at the organelle level based on a series of developmentally-orchestrated mitochondrial processes. We demonstrate that mitochondrial fission, together with the lack of mtDNA replication in early germarium, effectively segregates mtDNA into individual organelles. After mtDNA segregation, mtDNA transcription begins, which leads to the activation of respiration in each organelle. The expression of mtDNA-encoded genes allows the functional manifestation of different mitochondrial genotypes in heteroplasmic cells, and hence functions as a stress test for each individual genome and sets the stage for the replication competition. We also show that the Balbiani body has a minor role in mtDNA selective inheritance by supplying healthy mitochondria to the pole plasm. The two selection mechanisms may act synergistically to secure the transmission of functional mtDNA throughDrosophilaoogenesis.
Accurate and Efficient Gene Function Prediction using a Multi-Bacterial Network
Authors: Law Jeffrey , Kale Shiv , Murali T. M. 
Published: May 2019

AbstractMotivationNearly 40% of the genes in sequenced genomes have no experimentally- or computationally-derived functional annotations. To fill this gap, we seek to develop methods for network-based gene function prediction that can integrate heterogeneous data for multiple species with experimentally-based functional annotations and systematically transfer them to newly-sequenced organisms on a genomewide scale. However, the large size of such networks pose a challenge for the scalability of current methods.ResultsWe develop a label propagation algorithm called FastSinkSource. By formally bounding its the rate of progress, we decrease the running time by a factor of 100 without sacrificing accuracy. We systematically evaluate many approaches to construct multi-species bacterial networks and apply FastSinkSource and other state-of-the-art methods to these networks. We find that the most accurate and efficient approach is to pre-compute annotation scores for species with experimental annotations, and then to transfer them to other organisms. In this manner, FastSinkSource runs in under three minutes for 200 bacterial species.Availability and ImplementationPython implementations of each algorithm and all data used in this research are available at http://bioinformatics.cs.vt.edu/~jeffl/supplements/2020-fastsinksource.Contactmurali@cs.vt.eduSupplementary InformationA supplementary file is available at bioRxiv online.
Selective modulation of the glucocorticoid receptor with CORT108297 during chronic adolescent stress evokes sex-specific effects in adulthood
Authors: Cotella Evelin , Morano Rachel , Wulsin Aynara , Martelle Susan , Lemen Paige , Fitzgerald Maureen , Packard Benjamin A. , Moloney Rachel , Herman James 
Published: May 2019

AbstractAdolescent animals are vulnerable to the effects of stress on brain development. We hypothesized that long-term effects of adolescent chronic stress are mediated by glucocorticoid receptor (GR) signaling. We used a specific GR modulator (CORT108297) to pharmacologically disrupt GR signaling in adolescent rats during exposure chronic variable stress (CVS). Male and female rats received 30mg/kg of drug concomitantly with a 2-week CVS protocol starting at PND46. Emotional reactivity (open field) and coping behaviors (forced swim test (FST)) were then tested in adulthood, 5 weeks after the end of the CVS protocol. Blood samples were collected two days before FST and serial samples after the onset of the swim test to determine baseline and stress response levels of HPA hormones respectively.Our results support differential behavioral, physiological and stress circuit reactivity to adolescent chronic stress exposure in males vs. females, with variable involvement of GR signaling. In response to adolescent stress, males had heightened reactivity to novelty and exhibited marked reduction in neuronal excitation following swim stress in adulthood, whereas females developed a passive coping strategy and enhanced HPA axis stress reactivity. Only the latter effect was attenuated by treatment with the GR modulator C108297. Our data suggest that adolescent stress differentially affects emotional behavior and circuit development in females, and that GR plays a role in driving some but not all sequelae of adolescent stress.
Information Theoretic Feature Selection Methods for Single Cell RNA-Sequencing
Authors: Varma Umang , Colacino Justin , Gilbert Anna 
Published: May 2019

AbstractSingle cell RNA-sequencing (scRNA-seq) technologies have generated an expansive amount of new biological information, revealing new cellular populations and hierarchical relationships. A number of technologies complementary to scRNA-seq rely on the selection of a smaller number of marker genes (or features) to accurately differentiate cell types within a complex mixture of cells. In this paper, we benchmark differential expression methods against information-theoretic feature selection methods to evaluate the ability of these algorithms to identify small and efficient sets of genes that are informative about cell types. Unlike differential methods, that are strictly binary and univariate, information-theoretic methods can be used as any combination of binary or multiclass and univariate or multivariate. We show for some datasets, information theoretic methods can reveal genes that are both distinct from those selected by traditional algorithms and that are as informative, if not more, of the class labels. We also present detailed and principled theoretical analyses of these algorithms. All information theoretic methods in this paper are implemented in our PicturedRocks Python package that is compatible with the widely used scanpy package.