bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heat stress reveals high molecular mass proteasomes inArabidopsis thalianasuspension cells cultures
Authors: Aristizábal Daniel , Rivas Viridiana , Cassab Gladys , Lledías Fernando 
Published: December 2018

AbstractBecause of their sessile nature, plants have evolved complex and robust mechanisms to respond to adverse environments. Stress conditions trigger an increase in protein turnover and degradation. Proteasomes are essential to the cell for removing, in a highly regulated manner, partially denatured or oxidized proteins thus minimizing their cytotoxicity. We observed that suspension cells ofArabidopsis thalianatreated with high temperature (37 °C) directed the assembly of high molecular mass proteasomes. The removal of a 75% of the original ubiquitin conjugates and the maintenance of protein carbonyls at basal levels correlated with a specific proteasome profiles. The profiles obtained by the separation of different proteasomes populations by Blue-Native Polyacrylamide Gel Electrophoresis and western blot analysis suggest that synthesis, assembly, and heavy ubiquitination of 20S (CP) subunits are promoted by heat stress.
3DeFDR: Identifying cell type-specific looping interactions with empirical false discovery rate guided thresholding
Authors: Fernandez Lindsey , Gilgenast Thomas G. , Phillips-Cremins Jennifer E. 
Published: December 2018

AbstractThe mammalian genome is connected into tens of thousands of long-range looping interactions critically linked to spatiotemporal gene expression regulation. An important unanswered question is to what extent looping interactions change across developmental models, genetic perturbations, drug treatments, and disease states. Although methods exist for calling loops in single biological conditions, there is a severe shortage of computational tools for rigorous assessment of cell type-specific looping interactions across multiple biological conditions. Here we present 3DeFDR, a simple and effective statistical tool for classifying dynamic looping interactions across biological conditions from Chromosome-Conformation-Capture-Carbon-Copy (5C) data. 3DeFDR parses chromatin contacts into invariant and cell type-specific classes by thresholding on differences in modeled interaction strength signal across two or three cellular states. Thresholds are iteratively adjusted based on a target empirical false discovery rate computed between real and simulated 5C maps. 3DeFDR enables the sensitive detection of high-confidence looping interactions and markedly reduces false positives when benchmarked against a classic analysis of variance (ANOVA) test, our newly formulated parametric likelihood ratio test (3DLRT), and the leading Hi-C differential interaction caller diffHic. 3DeFDR also sensitively and specifically calls loops in Mb-scale genomic regions parsed from Hi-C data. Our work provides a statistical framework and an open-source coding library for identifying dynamic long-range looping interactions in high-resolution 5C data from multiple cellular conditions.
Medial prefrontal cortex activity reflects ordinal retrieval modes and hippocampal activity reflects temporal context retrieval modes
Authors: Reeders Puck C. , Hamm Amanda G. , Allen Timothy A. , Mattfeld Aaron T. 
Published: December 2018

ABSTRACTRemembering sequences of events defines episodic memory, but retrieval can be driven by both ordinality and temporal contexts. Whether these modes of retrieval operate at the same time or not remains unclear. Theoretically, medial prefrontal cortex (mPFC) confers ordinality, while the hippocampus (HC) associates events in gradually changing temporal contexts. Here, we looked for evidence of each with BOLD fMRI in a sequence task that taxes both retrieval modes. To test ordinal modes, items were transferred between sequences but retained their position (e.g., AB3). Ordinal modes activated mPFC, but not HC. To test temporal contexts, we examined items that skipped ahead across lag distances (e.g., ABD). HC, but not mPFC, tracked temporal contexts. There was a mPFC and HC by retrieval mode interaction. These current results suggest that the mPFC and HC are concurrently engaged in different retrieval modes in support of remembering when an event occurred.Significance StatementMemory for sequences of events is a defining aspect of everyday episodic memory allowing our brain to separate unique experiences that otherwise have overlapping sensory and spatial content. Sequence memory is impaired in typical aging and in disorders such as Alzheimer’s disease. The results of the current study provide new evidence that two retrieval modes concurrently arise during sequence memory, and they have distinct neural correlates. The medial prefrontal cortex contributes to an ordinal retrieval mode, while at the same time, the hippocampus contributes a gradually-changing temporal context mode of retrieval. These data shed new light on why typical episodic memory requires both the medial prefrontal cortex and the hippocampus, and suggests a functional dissociation between the medial prefrontal cortex and hippocampus across these modes of retrieval.
Neurocomputational underpinnings of expected surprise
Authors: Lecaignard Françoise , Bertrand Olivier , Caclin Anne , Mattout Jérémie 
Published: December 2018

AbstractPredictive coding accounts of brain functions profoundly influence current approaches to perceptual synthesis. However, a fundamental paradox has emerged, that may be very relevant for understanding hallucinations, psychosis or cognitive inflexibility. This paradox is that in some situations surprise or prediction error related responses can decrease when predicted and yet, they can increase when we know they are predictable. This paradox is resolved by recognizing that brain responses reflect precision weighted prediction error. This then presses us to disambiguate the contributions of precision and prediction error in electrophysiology. We report, for the first time, an experimental paradigm that may be able to meet this challenge. We examined brain responses to unexpected and expected surprising sounds, assuming that the latter yield a smaller prediction error but much more amplified by a larger precision weight. Importantly, addressing this modulation requires the modelling of trial-by-trial variations of brain responses, that we reconstructed within a fronto-temporal network by combining EEG and MEG. Our results reveal an adaptive learning of surprise with larger integration of past (relevant) information in the context of expected surprises. Within the auditory hierarchy, this adaptation was found tied down to specific connections and reveals in particular and crucially precision encoding through neuronal excitability. Strikingly, these fine processes are automated as sound sequences were unattended. These findings directly speak to applications in psychiatry, where it has been suggested that a specifically impaired precision weighting is at the heart of several conditions such as schizophrenia and autism.
Non-CG methylation and multiple epigenetic layers associate child abuse with immune and small GTPase dysregulation
Authors: Lutz Pierre-Eric , Chay Marc-Aurèle , Pacis Alain , Chen Gary G , Aouabed Zahia , Maffioletti Elisabetta , Théroux Jean-François , Grenier Jean-Christophe , Yang Jennie , Aguirre Maria , Ernst Carl , Redensek Adriana , van Kempen Léon C. , Yalcin Ipek , Kwan Tony , Mechawar Naguib , Pastinen Tomi , Turecki Gustavo 
Published: December 2018

AbstractEarly-life adversity (ELA) is a major predictor of psychopathology, and is thought to increase lifetime risk by epigenetically regulating the genome. Here, focusing on the lateral amygdala, a major brain site for emotional homeostasis, we described molecular cross-talk among multiple epigenetic mechanisms, including 6 histone marks, DNA methylation and the transcriptome, in subjects with a history of ELA and controls. We first uncovered, in the healthy brain, previously unknown interactions among epigenetic layers, in particular related to non-CG methylation in the CAC context. We then showed that ELA associates with methylomic changes that are as frequent in the CAC as in the canonical CG context, while these two forms of plasticity occur in sharply distinct genomic regions, features, and chromatin states. Combining these multiple data indicated that immune-related and small GTPase signaling pathways are most consistently impaired in the amygdala of ELA individuals. Overall, this work provides new insights into epigenetic brain regulation as a function of early-life experience.
Linking Demyelination to Compound Action Potential Dispersion with a Spike-Diffuse-Spike Approach
Authors: Naud Richard , Longtin André 
Published: December 2018

AbstractTo establish and exploit novel biomarkers of demyelinating diseases requires a mechanistic understanding of axonal propagation. Here, we present a novel computational framework called the stochastic spike-diffuse-spike (SSDS) model for assessing the effects of demyelination on axonal transmission. It models transmission through nodal and internodal compartments with two types of operations: a stochastic integrate-and-fire operation captures nodal excitability and a linear filtering operation describes internodal propagation. The effects of demyelinated segments on the probability of transmission, transmission delay and spike time jitter are explored. We argue that demyelination induced impedance mismatch prevents propagation mostly when the action potential leaves a demyelinated region, not when it enters a demyelinated region. In addition, we model sodium channel remodeling as a homeostatic control of nodal excitability. We find that the effects of mild demyelination on transmission probability and delay can be largely counterbalanced by an increase in excitability at the nodes surrounding the demyelination. The spike timing jitter, however, reflects the level of demyelination whether excitability is fixed or is allowed to change in compensation. This jitter can accumulate over long axons and leads to a broadening of the compound action potential, linking microscopic defects to a mesoscopic observable. Our findings articulate why action potential jitter and compound action potential dispersion can serve as potential markers of weak and sporadic demyelination.
Evolution of sperm competition: Natural variation and genetic determinants ofCaenorhabditis eleganssperm size
Authors: Gimond Clotilde , Vielle Anne , Silva-Soares Nuno , Zdraljevic Stefan , McGrath Patrick T. , Andersen Erik C. , Braendle Christian 
Published: December 2018

ABSTRACTSperm morphology is critical for sperm competition and thus for reproductive fitness. In the male-hermaphrodite nematodeCaenorhabditis elegans, sperm size is a key feature of sperm competitive ability. Yet despite extensive research, the molecular mechanisms regulatingC. eleganssperm size and the genetic basis underlying its natural variation remain unknown. Examining 97 genetically distinctC. elegansstrains, we observe significant heritable variation in male sperm size but genome-wide association mapping did not yield any QTL (Quantitative Trait Loci). While we confirm larger male sperm to consistently outcompete smaller hermaphrodite sperm, we find natural variation in male sperm size to poorly predict male fertility and competitive ability. In addition, although hermaphrodite sperm size also shows significant natural variation, male and hermaphrodite sperm size do not correlate, implying a sex-specific genetic regulation of sperm size. To elucidate the molecular basis of intraspecific sperm size variation, we focused on recently diverged laboratory strains, which evolved extreme sperm size differences. Using mutants and quantitative complementation tests, we demonstrate that variation in the genenurf-1– previously shown to underlie the evolution of improved hermaphrodite reproduction – also explains the evolution of reduced male sperm size. This result illustrates how adaptive changes inC. eleganshermaphrodite function can cause the deterioration of a male-specific fitness trait due to a sexually antagonistic variant, representing an example of intralocus sexual conflict with resolution at the molecular level. Our results further provide first insights into the genetic determinants ofC. eleganssperm size, pointing at an involvement of the NURF chromatin remodelling complex.
Different molecular signatures in lung cancer types from integrative bioinformatic analyses of RNASeq data
Authors: Lucchetta Marta , Piedade Isabelle da , Mounir Mohamed , Vabistsevits Marina , Terkelsen Thilde , Papaleo Elena 
Published: December 2018

AbstractBackgroundGenomic initiatives such as The Cancer Genome Atlas (TCGA) project contain data on profiling of thousands of tumors with different-omics approaches, providing a valuable source of information which may be used to decipher cancer signaling and related alterations. Managing and analyzing data from large-scale projects such as TCGA is a demanding task. Indeed, it is difficult to dissect the high complexity hidden in genomic data and to adequately account for tumor heterogeneity.ResultsIn this study, we used a robust statistical framework along with the integration of diverse bioinformatic tools to analyze next-generation sequencing data from more than 1000 patient samples from two different lung cancer subtypes, i.e., the lung adenocarcinoma (LUAD) and the squamous cell carcinoma (LUSC). In particular, we used RNA-Seq gene expression data to identify both co-expression modules and differentially expressed genes to accurately discriminate between LUAD and LUSC. Moreover, we identified a group of genes which could act as specific oncogenes or tumor suppressor genes in one of the two lung cancer types, as well as two dual role genes. Our results have also been cross-validated against other transcriptomics data of lung cancer patients.ConclusionsOur integrative approach allowed to identify two key features: a substantial up-regulation of genes involved in O-glycosylation of mucins in LUAD, and a compromised immune response in LUSC. The immune-profile associated with LUSC is linked to the activation of three specific oncogenic pathways which promote the evasion of antitumor immune response, providing new future directions for the design of target therapies.
Analysis of small RNA silencing in Zymoseptoria tritici – wheat interactions
Authors: Kettles Graeme J. , Hofinger Bernhard J. , Hu Pingsha , Bayon Carlos , Rudd Jason J. , Balmer Dirk , Courbot Mikael , Hammond-Kosack Kim E. , Scalliet Gabriel , Kanyuka Kostya 
Published: December 2018

AbstractCross-kingdom small RNA (sRNA) silencing has recently emerged as a mechanism facilitating fungal colonization and disease development. Here we characterized RNAi pathways in Zymoseptoria tritici, a major fungal pathogen of wheat, and assessed their contribution to pathogenesis. Computational analysis of fungal sRNA and host mRNA sequencing datasets was used to define the global sRNA populations in Z. tritici and predict their mRNA targets in wheat. 389 in planta-induced sRNA loci were identified. sRNAs generated from some of these loci were predicted to target wheat mRNAs including those potentially involved in pathogen defense. However, molecular approaches failed to validate targeting of selected wheat mRNAs by fungal sRNAs. Mutant strains of Z. tritici carrying deletions of genes encoding key components of RNAi such as Dicer-like (DCL) and Argounate (AGO) proteins were generated, and virulence bioassays suggested that these are dispensable for full infection of wheat. Nonetheless, our results did suggest the existence of non-canonical DCL-independent pathway(s) for sRNA biogenesis in Z. tritici. dsRNA targeting essential fungal genes applied in vitro or generated from an RNA virus vector in planta in a procedure known as HIGS (Host-Induced Gene Silencing) was ineffective in preventing Z. tritici growth or disease. We also demonstrated that Z. tritici is incapable of dsRNA uptake. Collectively, our data suggest that RNAi approaches for gene function analyses in this fungal species and potentially also as a control measure may not be as effective as has been demonstrated for some other plant pathogenic fungi.
A novel rationale for targeting FXI: Insights from the hemostatic miRNA targetome for emerging anticoagulant strategies
Authors: Nourse Jamie , Danckwardt Sven 
Published: December 2018

AbstractTherapeutic targeting of blood coagulation is a challenging task as it interferes with the delicate balance of pro- and anticoagulant activities. Anticoagulants are employed in millions of thrombophilic patients worldwide each year. The treatment and prevention of venous thromboembolism has changed drastically with the replacement of traditional anticoagulant vitamin K antagonists by direct oral anticoagulants (DOACs), which selectively target coagulation factors Xa or IIa. However for a growing population with comorbidities satisfying therapeutic options are still lacking and the quest for novel therapeutics continues. Recently targeting factors XI or XII have emerged as new therapeutic strategies. As these factors play important roles in thrombosis, nevertheless are practically functionally dispensable for hemostasis, they may potentially overcome the functional obstacle of treating or preventing thrombosis without affecting hemostasis. Based on the recent elucidation of the hemostatic miRNA targetome, we introduce and discuss a hitherto unrecognized rationale for the therapeutic targeting of factor XI. This is based on mimicking endogenous factor XI expression control by therapeutic delivery of miRNA mimics. We discuss the functional difference between various gene targeting approaches, and propose the hemostatic system to represent an ideal model for assessment of the efficacy and safety of such therapeutic components, ushering in a novel therapeutic era with broad applicability.
iCn3D, a Web-based 3D Viewer for Sharing 1D/2D/3D Representations of Biomolecular Structures
Authors: Wang Jiyao , Youkharibache Philippe , Zhang Dachuan , Lanczycki Christopher J. , Geer Renata C. , Madej Thomas , Phan Lon , Ward Minghong , Lu Shennan , Marchler Gabriele H. , Wang Yanli , Bryant Stephen H. , Geer Lewis Y. , Marchler-Bauer Aron 
Published: December 2018

AbstractSummaryiCn3D (I-see-in-3D) is a web-based 3D molecular structure viewer focusing on the interactive structural analysis. It can simultaneously show 3D structure, 2D molecular contacts, and 1D protein and nucleotide sequences through an integrated sequence/annotation browser. Pre-defined and arbitrary molecular features can be selected in any of the 1D/2D/3D windows as sets of residues and these selections are synchronized dynamically in all displays. Biological annotations such as protein domains, single nucleotide variations, etc. can be shown as tracks in the 1D sequence/annotation browser. These customized displays can be shared with colleagues or publishers via a simple URL. iCn3D can display structure-structure alignment obtained from NCBI’s VAST+ service. It can also display the alignment of a sequence with a structure as identified by BLAST, and thus relate 3D structure to a large fraction of all known proteins. iCn3D can also display electron density maps or electron microscopy (EM) density maps, and export files for 3D printing. The following example URL exemplifies some of the 1D/2D/3D representations: https://www.ncbi.nlm.nih.gov/Structure/icn3d/full.html?mmdbid=1TUP&showanno=1&show2d=1&showsets=1.Availability and implementationiCn3D is freely available to the public. Its source code is available at https://github.com/ncbi/icn3d.Supplementary informationUser instructions are available at Bioinformatics online
Drivers of human gut microbial community assembly: Coadaptation, determinism and stochasticity
Authors: Oliphant Kaitlyn , Parreira Valeria R. , Cochrane Kyla , Allen-Vercoe Emma 
Published: December 2018

AbstractMicrobial community assembly is a complex process shaped by multiple factors, including habitat filtering, species assortment and stochasticity. Understanding the relative importance of these drivers would enable scientists to design strategies initiating a desired reassembly for e.g., remediating low diversity ecosystems. Here, we aimed to examine if a human fecal-derived defined microbial community cultured in bioreactors assembled deterministically or stochastically, by completing replicate experiments under two growth medium conditions characteristic of either high fiber or high protein diets. Then, we recreated this defined microbial community by matching different strains of the same species sourced from distinct human donors, in order to elucidate whether coadaptation of strains within a host influenced community dynamics. Each defined microbial ecosystem was evaluated for composition using marker gene sequencing, and for behaviour using 1H-NMR based metabonomics. We found that stochasticity had the largest influence on the species structure when substrate concentrations varied, whereas habitat filtering greatly impacted the metabonomic output. Evidence of coadaptation was elucidated from comparisons of the two communities; we found that the artificial community tended to exclude saccharolytic Firmicutes species and was enriched for metabolic intermediates, such as Stickland fermentation products, suggesting overall that polysaccharide utilization by Firmicutes is dependent on cooperation.
Non-covalently-associated peptides are observed during liquid chromatography-mass spectrometry and affect crosslink analyses
Authors: Giese Sven H. , Belsom Adam , Sinn Ludwig , Fischer Lutz , Rappsilber Juri 
Published: December 2018

AbstractCrosslinking mass spectrometry draws structural information from covalently-linked peptide pairs. When these links do not match to previous structural models, they may indicate changes in protein conformation. Unfortunately, such links can also be the result of experimental error or artefacts. Here, we describe the observation of non-covalently-associated peptides during liquid chromatography-mass spectrometry analysis, which can easily be misidentified as crosslinked. Strikingly, they often mismatch to the protein structure. Non-covalently-associated peptides presumably form during ionization and can be distinguished from crosslinked peptides by observing co-elution of the corresponding linear peptides in MS1, as well as the presence of the individual (intact) peptide fragments in MS2 spectra. To suppress non-covalent peptide formations increasingly disruptive ionization settings can be used, such as in-source fragmentation.