bluuebunny/crossref_metadata_2025_split huggingface dataset:
The application of community ecology theory to co-infections in wildlife hosts
Authors: Ramsay Chloe , Rohr Jason R. 
Published: April 2020

AbstractPriority effect theory, a foundational concept from community ecology, states that the order and timing of species arrival during species assembly can affect species composition. Although this theory has been applied to co-infecting parasite species, it has almost always been with a single time lag between co-infecting parasites. Thus, how the timing of parasite species arrival affects co-infections and disease remains poorly understood. To address this gap in the literature, we exposed post-metamorphic Cuban tree frogs (Osteopilus septentrionalis) to Ranavirus, the fungusBatrachochytrium dendrobatidis(Bd), a nematodeAplectana hamatospicula, or pairs of these parasites either simultaneously or sequentially at a range of time lags and quantified load of the secondary parasite and host growth, survival and parasite tolerance. Prior exposure to Bd orA. hamatospiculasignificantly increased viral loads relative to hosts singly infected with Ranavirus, whereasA. hamatospiculaloads in hosts were higher when co-exposed to Bd than when co-exposed to Ranavirus. There was a significant positive relationship between time since Ranavirus infection and Bd load, and prior exposure toA. hamatospiculadecreased Bd loads compared to simultaneous co-infection with these parasites. Infections with Bd and Ranavirus either singly or in co-infections decreased host growth and survival. This research reveals that time lags between co-infections can affect parasite loads, in line with priority effects theory. As co-infections in the field are unlikely to be simultaneous, an understanding of when co-infections are impacted by time lags between parasite exposures may play a major role in controlling problematic co-infections.
Adaptive rescheduling of error monitoring in multitasking
Authors: Steinhauser Robert , Steinhauser Marco 
Published: April 2020

AbstractThe concurrent execution of temporally overlapping tasks leads to considerable interference between the subtasks. This also impairs control processes associated with the detection of performance errors. In the present study, we investigated how the human brain adapts to this interference between task representations in such multitasking scenarios. In Experiment 1, participants worked on a dual-tasking paradigm with partially overlapping execution of two tasks (T1 and T2), while we recorded error-related scalp potentials. The error positivity (Pe), a correlate of higher-level error evaluation, was reduced after T1 errors but occurred after a correct T2-response instead. MVPA-based and regression-based single-trial analysis revealed that the immediate Pe and deferred Pe are negatively correlated, suggesting a trial-wise trade-off between immediate and postponed error processing. Experiment 2 confirmed this finding and additionally showed that this result is not due to credit-assignment errors in which a T1 error is falsely attributed to T2. For the first time reporting a Pe that is temporally detached from its eliciting error event by a considerable amount of time, this study illustrates how reliable error detection in dual-tasking is maintained by a mechanism that adaptively schedules error processing, thus demonstrating a remarkable flexibility of the human brain when adapting to multitasking situations.Significance StatementMultitasking situations are associated with impaired performance, as the brain needs to allocate resources to more than one task at a time. This also makes it more difficult to detect one’s own performance errors in such complex scenarios. In two experiments, we recorded error-related electroencephalographic (EEG) activity and found that the commonly assumed fixed temporal succession of control processes in error monitoring can be strategically interrupted. Individual processes of error detection can be temporally rescheduled to after completion of competing tasks. This reduces interference between the neural task representations and supports a more efficient execution of concurrent tasks in multitasking.
Breakage of the Oligomeric CaMKII Hub by the Regulatory Segment of the Kinase
Authors: Karandur Deepti , Bhattacharyya Moitrayee , Xia Beryl , Lee Young Kwang , Muratcioglu Serena , McAffee Darren , McSpadden Ethan D. , Qiu Baiyu , Groves Jay , Williams Evan , Kuriyan John 
Published: April 2020

AbstractCa2+/calmodulin dependent protein kinase II (CaMKII) is a dodecameric or tetradecameric enzyme with crucial roles in neuronal signaling and cardiac function. Activation of CaMKII is reported to trigger the exchange of subunits between holoenzymes, which can increase spread of the active state. Using mass spectrometry, we now show that peptides derived from the sequence of the CaMKII-α regulatory segment can bind to the CaMKII-α hub assembly and break it into smaller oligomers. Molecular dynamics simulations show that the regulatory segments can dock spontaneously at the interface between hub subunits, trapping large fluctuations in hub structure. Single-molecule fluorescence intensity analysis of human CaMKII-α isolated from mammalian cells shows that activation of CaMKII-α results in the destabilization of the holoenzyme. Our results show how the release of the regulatory segment by activation and phosphorylation could allow it to destabilize the hub, producing smaller CaMKII assemblies that can reassemble to form new holoenzymes.
Efficient chromatin accessibility mappingin situby nucleosome-tethered tagmentation
Authors: Henikoff Steven , Henikoff Jorja G. , Kaya-Okur Hatice S. , Ahmad Kami 
Published: April 2020

AbstractChromatin accessibility mapping is a powerful approach to identify potential regulatory elements. A popular example is ATAC-seq, whereby Tn5 transposase inserts sequencing adapters into accessible DNA (‘tagmentation’). CUT&Tag is a tagmentation-based epigenomic profiling method in which antibody tethering of Tn5 to a chromatin epitope of interest profiles specific chromatin features in small samples and single cells. Here we show that by simply modifying the tagmentation conditions for histone H3K4me2 or H3K4me3 CUT&Tag, antibody-tethered tagmentation of accessible DNA sites is redirected to produce chromatin accessibility maps that are indistinguishable from the best ATAC-seq maps. Thus, chromatin accessibility maps can be produced in parallel with CUT&Tag maps of other epitopes with all steps from nuclei to amplified sequencing-ready libraries performed in single PCR tubes in the laboratory or on a home workbench. As H3K4 methylation is produced by transcription at promoters and enhancers, our method identifies transcription-coupled accessible regulatory sites.
Auditory features modelling reveals sound envelope representation in striate cortex
Authors: Martinelli Alice , Handjaras Giacomo , Betta Monica , Leo Andrea , Cecchetti Luca , Pietrini Pietro , Ricciardi Emiliano , Bottari Davide 
Published: April 2020

SummaryThe striate cortex is no longer considered exclusively visual in its function. Proofs that its activity is modulated by acoustic inputs have accrued. By employing category-based and feature modeling approaches, here we characterized V1 activity (in absence of retinal input) during the processing of natural and synthetically derived sounds. First, we showed that distinct sound categories could be dissociated by the analysis of V1 multivoxel response patterns. Hence, we assessed whether a hallmark of sound neural representations is mapped in V1. In each sound category, we modeled sound envelopes and assessed whether these were represented at the single-voxel level in the striate cortex and, as a control, in the temporal cortex. The hierarchical organization of sound categories allowed to exert control over dimensions that could spuriously lead to sound envelope V1 mapping. Variations of sound amplitude over time were successfully decoded in V1 regardless of the category class. Results confirm that the human striate cortex receives acoustic category-based input and demonstrate that V1 is a genuine locus of sound envelope representation.
Maintenance of variation in virulence and reproduction in populations of an agricultural plant pathogen
Authors: Dutta Anik , Croll Daniel , McDonald Bruce A. , Barrett Luke G. 
Published: April 2020

AbstractGenetic diversity within pathogen populations is critically important for predicting pathogen evolution, disease outcomes and prevalence. However, we lack a good understanding of the processes maintaining genetic variation and constraints on pathogen life-history evolution. Here, we analyzed interactions between 12 wheat host genotypes and 145 strains ofZymoseptoria triticifrom five global populations to investigate the evolution and maintenance of variation in pathogen virulence and reproduction. We found a strong positive correlation between virulence and reproduction, with substantial variation in both traits maintained within each pathogen population. On average, highly virulent isolates exhibited higher fecundity, which might increase transmission potential in agricultural fields planted to homogeneous hosts at a high density. We further showed that pathogen strains with a narrow host range (i.e. specialists) for fecundity were on average less virulent, and those with a broader host range (i.e. generalists) for virulence were on average less fecund on a given specific host. These trade-offs costs associated with host specialization might constrain the directional evolution of virulence and fecundity. We conclude that selection favoring pathogen strains that are virulent across diverse hosts, coupled with selection that maximizes fecundity on specific hosts, may explain the maintenance of these pathogenicity traits within and among pathogen populations.
In situreprogramming of gut bacteria by oral delivery
Authors: Hsu Bryan B. , Plant Isaac N. , Lyon Lorena , Anastassacos Frances M. , Way Jeffrey C. , Silver Pamela A. 
Published: April 2020

AbstractAbundant links between the gut microbiota and human health indicate that the modification of bacterial function could be a powerful therapeutic strategy. The inaccessibility of the gut and inter-connections between gut bacteria and the host make it difficult to precisely target bacterial functions without disrupting the microbiota and/or host physiology. Herein we describe a multidisciplinary approach to modulate the expression of a specific bacterial gene within the gut by oral administration. We first demonstrate that an engineered temperate phage λ expressing a programmable dCas9 represses a targetedE. coligene in the mammalian gut. To facilitate phage administration while minimizing disruption to host processes, we develop an aqueous-based encapsulation formulation with a microbiota-based release mechanism and show that it facilitates the oral delivery of phagein vivo. Finally we combine these technologies and show that bacterial gene expression in the mammalian gut can be precisely modifiedin situwith a single oral dose.
UNCURL-App: Interactive database-driven analysis of scRNA-Seq data
Authors: Zhang Yue , Mao Shunfu , Mukherjee Sumit , Kannan Sreeram , Seelig Georg 
Published: April 2020

AbstractMotivationAnalysis of single cell RNA sequencing (scRNA-seq) datasets is a complex and time-consuming process, requiring both biological knowledge and technical skill. With the rapid growth in scRNA-seq datasets, there is a need to simplify and systematize this process.ResultsWe introduce UNCURL-App, an online GUI-based interactive tool which integrates the scRNA-seq analysis pipeline with prior knowledge. UNCURL-App introduces two key innovations: First, cell type databases are integrated directly with the rest of the analysis process, allowing the user to identify potential cell types or pathways directly from the data. Second, tools for interactive re-analysis allow the user to create, merge, or delete clusters. In addition, UNCURL-App integrates multiple stages of the data analysis pipeline into a single interface, including dimensionality reduction, clustering, differential expression, and cell type identification.AvailabilityThe web tool is available athttps://uncurl.cs.washington.edu/. Source code is available athttps://github.com/yjzhang/uncurl_appContactgseelig@uw.edu
Structure-based design of hepatitis C virus E2 glycoprotein improves serum binding and cross-neutralization
Authors: Pierce Brian G. , Keck Zhen-Yong , Wang Ruixue , Lau Patrick , Garagusi Kyle , Elkholy Khadija , Toth Eric A. , Urbanowicz Richard A. , Guest Johnathan D. , Agnihotri Pragati , Kerzic Melissa C. , Marin Alexander , Andrianov Alexander K. , Ball Jonathan K. , Mariuzza Roy A. , Fuerst Thomas R. , Foung Steven K.H. 
Published: April 2020

AbstractAn effective vaccine for hepatitis C virus (HCV) is a major unmet need, and it requires an antigen that elicits immune responses to key conserved epitopes. Based on structures of antibodies targeting HCV envelope glycoprotein E2, we designed immunogens to modulate the structure and dynamics of E2 and favor induction of bNAbs in the context of a vaccine. These designs include a point mutation in a key conserved antigenic site to stabilize its conformation, as well as redesigns of an immunogenic region to add a new N-glycosylation site and mask it from antibody binding. Designs were experimentally characterized for binding to a panel of human monoclonal antibodies (HMAbs) and the coreceptor CD81 to confirm preservation of epitope structure and preferred antigenicity profile. Selected E2 designs were tested for immunogenicity in mice, with and without hypervariable region 1, which is an immunogenic region associated with viral escape. One of these designs showed improvement in polyclonal immune serum binding to HCV pseudoparticles and neutralization of isolates associated with antibody resistance. These results indicate that antigen optimization through structure-based design of the envelope glycoproteins is a promising route to an effective vaccine for HCV.
Neuropsychiatric copy number variants exert shared effects on human brain structure
Authors: Modenato Claudia , Kumar Kuldeep , Moreau Clara , Martin-Brevet Sandra , Huguet Guillaume , Schramm Catherine , Martineau Jean-Louis , Martin Charles-Olivier , Younis Nadine , Tamer Petra , Douard Elise , Thébault-Dagher Fanny , Côté V. , Charlebois A.R. , Deguire F. , Maillard Anne M. , Rodriguez-Herreros Borja , Pain Aurèlie , Richetin Sonia ,   16p11.2 European Consortium,   Simons Variation in Individuals Project (VIP) Consortium, Kushan Leila , Melie-Garcia Lester , Silva Ana I. , van den Bree Marianne B.M. , Linden David E.J. , Owen Michael J. , Hall Jeremy , Lippé Sarah , Chakravarty Mallar , Bzdok Danilo , Bearden Carrie E. , Draganski Bogdan , Jacquemont Sébastien 
Published: April 2020

AbstractBackgroundCopy Number Variants (CNVs) associated with autism and schizophrenia have large effects on brain anatomy. Yet, neuroimaging studies have been conducted one mutation at a time. We hypothesize that neuropsychiatric CNVs may exert general effects on brain morphometry because they confer risk for overlapping psychiatric conditions.MethodsWe analyzed T1-weighted MRIs and characterized shared patterns on brain anatomy across 8 neuropsychiatric CNVs. Clinically ascertained samples included 1q21.1 (n=48), 16p11.2 (n=156), or 22q11.2 (n=96) and 331 non-carriers. Non-clinically ascertained samples from the UK Biobank included 1q21.1 (n=19), 16p11.2 (n=8), 22q11.2 (n=9), 15q11.2 (n=148) and 965 non-carriers. Canonical correlation analysis (CCA) and univariate models were used to interrogate brain morphometry changes across 8 CNVs.ResultsEight CNVs affect regional brain volumes along two main gene-morphometry dimensions identified by CCA. While fronto-temporal regions contributed to dimension 1, dimension 2 was driven by subcortical, parietal and occipital regions. Consistently, voxel-wise whole-brain analyses identified the same regions involved in patterns of alteration present across the 4 deletions and duplications. These neuroanatomical patterns are similar to those observed in cross-psychiatric disorder meta-analyses. Deletions and duplications at all 4 loci show mirror effects at either the global and/or the regional level.ConclusionNeuropsychiatric CNVs share neuroanatomical signatures characterized by a parsimonious set of brain dimensions. The latter may underlie the risk conferred by CNVs for a similar spectrum of neuropsychiatric conditions.
Analysis of the COVID-19 epidemic in french overseas department Mayotte based on a modified deterministic and stochastic SEIR model
Authors: Manou-Abi Solym Mawaki , Balicchi Julien 
Published: April 2020

AbstractIn order to anticipate a future trends in the development of the novel coronavirus COVID-19 epidemic started early at march 13, in the french overseas department Mayotte, we consider in this paper a modified deterministic and stochastic epidemic model. The model divides the total population into several possible states or compartment: susceptible (S), exposed (E) infected and being under an incubation period, infected (I) being infectious, simple or mild removed RM, severe removed (including hospitalized) RS and death cases (D). The adding of the two new compartment RM and RS are driven by data which together replace the original R compartment in the classical SEIR model.We first fit the constant transmission rate parameter to the epidemic data in Mayotte during an early exponential growth phase using an algorithm with a package of the software R and based on a Maximum Likewood estimator. This allows us to predict the epidemic without any control in order to understand how the control measure and public policies designed are having the desired impact of controlling the epidemic. To do this, we introduce a temporally varying decreasing transmission rate parameter with a control or quarantine parameter q. Then we pointed out some values of q to maintain control which is critical in Mayotte given the fragility of its health infrastructure and the significant fraction of the population without access to water.
Areas of global importance for terrestrial biodiversity, carbon, and water
Authors: Jung Martin , Arnell Andy , de Lamo Xavier , García-Rangel Shaenandhoa , Lewis Matthew , Mark Jennifer , Merow Cory , Miles Lera , Ondo Ian , Pironon Samuel , Ravilious Corinna , Rivers Malin , Schepashenko Dmitry , Tallowin Oliver , van Soesbergen Arnout , Govaerts Rafaël , Boyle Bradley L. , Enquist Brian J. , Feng Xiao , Gallagher Rachael V. , Maitner Brian , Meiri Shai , Mulligan Mark , Ofer Gali , Hanson Jeffrey O. , Jetz Walter , Di Marco Moreno , McGowan Jennifer , Rinnan D. Scott , Sachs Jeffrey D. , Lesiv Myroslava , Adams Vanessa , Andrew Samuel C. , Burger Joseph R. , Hannah Lee , Marquet Pablo A. , McCarthy James K. , Morueta-Holme Naia , Newman Erica A. , Park Daniel S. , Roehrdanz Patrick R. , Svenning Jens-Christian , Violle Cyrille , Wieringa Jan J. , Wynne Graham , Fritz Steffen , Strassburg Bernardo B.N. , Obersteiner Michael , Kapos Valerie , Burgess Neil , Schmidt-Traub Guido , Visconti Piero 
Published: April 2020

Summary paragraphTo meet the ambitious objectives of biodiversity and climate conventions, countries and the international community require clarity on how these objectives can be operationalized spatially, and multiple targets be pursued concurrently1. To support governments and political conventions, spatial guidance is needed to identify which areas should be managed for conservation to generate the greatest synergies between biodiversity and nature’s contribution to people (NCP). Here we present results from a joint optimization that maximizes improvements in species conservation status, carbon retention and water provisioning and rank terrestrial conservation priorities globally. We found that, selecting the top-ranked 30% (respectively 50%) of areas would conserve 62.4% (86.8%) of the estimated total carbon stock and 67.8% (90.7%) of all clean water provisioning, in addition to improving the conservation status for 69.7% (83.8%) of all species considered. If priority was given to biodiversity only, managing 30% of optimally located land area for conservation may be sufficient to improve the conservation status of 86.3% of plant and vertebrate species on Earth. Our results provide a global baseline on where land could be managed for conservation. We discuss how such a spatial prioritisation framework can support the implementation of the biodiversity and climate conventions.
BRD4 Interacts with GATA4 to Govern Mitochondrial Homeostasis in Adult Cardiomyocytes
Authors: Padmanabhan Arun , Alexanian Michael , Linares-Saldana Ricardo , González-Terán Bárbara , Andreoletti Gaia , Huang Yu , Connolly Andrew J. , Kim Wonho , Hsu Austin , Duan Qiming , Winchester Sarah A. B. , Haldar Saptarsi M. , Jain Rajan , Srivastava Deepak 
Published: April 2020

AbstractGene regulatory networks control tissue plasticity during basal homeostasis and disease in a cell-type specific manner. Ubiquitously expressed chromatin regulators modulate these networks, yet the mechanisms governing how tissue-specificity of their function is achieved are poorly understood. BRD4, a member of the BET (Bromo- and Extra-Terminal domain) family of ubiquitously expressed acetyl-lysine reader proteins, plays a pivotal role as a coactivator of enhancer signaling across diverse tissue types in both health and disease, and has been implicated as a pharmacologic target in heart failure. However, the cell-specific role of BRD4 in adult cardiomyocytes remains unknown. Here, we show that cardiomyocyte-specific deletion of BRD4 in adult mice leads to acute deterioration of cardiac contractile function with mutant animals demonstrating a transcriptomic signature enriched for decreased expression of genes critical for mitochondrial energy production. Genome-wide occupancy data show that BRD4 enriches at many downregulated genes and preferentially co-localizes with GATA4, a lineage determining cardiac transcription factor not previously implicated in regulation of adult cardiac metabolism. Co-immunoprecipitation assays demonstrate that BRD4 and GATA4 form a complex in a bromodomain-independent manner, revealing a new interaction partner for BRD4 that has functional consequences for target transactivation and may allow for locus and tissue specificity. These results highlight a novel role for a BRD4-GATA4 module in cooperative regulation of a cardiomyocyte specific gene program governing bioenergetic homeostasis in the adult heart.
Modelling the spatial-temporal distributions and associated determining factors of a keystone pelagic fish
Authors: Andrews Samantha , Leroux Shawn J. , Fortin Marie-Josée 
Published: April 2020

AbstractMobile pelagic species habitat is structured around dynamic oceanographic and ecological processes which operate and interact horizontally and vertically throughout the water column and change over time. However, pelagic species movements and distributions are often poorly understood. We use the Maxent species distribution model to assess how changes in the relative importance of modelled oceanographic (e.g., temperature) and climatic variables (e.g., the North Atlantic Oscillation) over 17-years affect the monthly average horizontal and vertical distribution of a keystone pelagic forage species, Atlantic Canadian capelin (Mallotus villosus). We show the range and distribution of capelin occurrence probabilities vary across horizontal and vertical axes over time, with binary presence/absence predictions indicating capelin occupy between 0.72% (April) and 3.45% (November) of the total modelled space. Furthermore, our analysis reveals that the importance of modelled oceanographic variables, such as temperature, vary between months (44% permutation importance in August to 2% in May). By capturing the spatial dynamics of capelin over horizontal, vertical, and temporal axes, our analysis builds on work that improves our understanding and predictive modelling ability of pelagic species distributions under current and future conditions for pro-active ecosystem-based management.