bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative analysis of neutrophil and monocyte epigenomes
Authors: Rico Daniel , Martens Joost HA , Downes Kate , Carrillo-de-Santa-Pau Enrique , Pancaldi Vera , Breschi Alessandra , Richardson David , Heath Simon , Saeed Sadia , Frontini Mattia , Chen Lu , Watt Stephen , Müller Fabian , Clarke Laura , Kerstens Hindrik HD , Wilder Steven P , Palumbo Emilio , Djebali Sarah , Raineri Emanuele , Merkel Angelika , Esteve-Codina Anna , Sultan Marc , van Bommel Alena , Gut Marta , Yaspo Marie-Laure , Rubio Miriam , Fernandez José María , Attwood Anthony , de la Torre Victor , Royo Romina , Fragkogianni Stamatina , Gelpí Josep Lluis , Torrents David , Iotchkova Valentina , Logie Colin , Aghajanirefah Ali , Singh Abhishek A , Janssen-Megens Eva M , Berentsen Kim , Erber Wendy , Rendon Augusto , Kostadima Myrto , Loos Remco , van der Ent Martijn A , Kaan Anita , Sharifi Nilofar , Paul Dirk S , Ifrim Daniela C , Quintin Jessica , Love Michael I. , Pisano David G , Burden Frances , Foad Nicola , Farrow Samantha , Zerbino Daniel R , Dunham Ian , Kuijpers Tacow , Lehrach Hans , Lengauer Thomas , Bertone Paul , Netea Mihai G , Vingron Martin , Beck Stephan , Flicek Paul , Gut Ivo , Ouwehand Willem H , Bock Christoph , Soranzo Nicole , Guigo Rodericw , Valencia Alfonso , Stunnenberg Hendrik G 
Published: December 2017

ABSTRACTNeutrophils and monocytes provide a first line of defense against infections as part of the innate immune system. Here we report the integrated analysis of transcriptomic and epigenetic landscapes for circulating monocytes and neutrophils with the aim to enable downstream interpretation and functional validation of key regulatory elements in health and disease. We collected RNA-seq data, ChIP-seq of six histone modifications and of DNA methylation by bisulfite sequencing at base pair resolution from up to 6 individuals per cell type. Chromatin segmentation analyses suggested that monocytes have a higher number of cell-specific enhancer regions (4-fold) compared to neutrophils. This highly plastic epigenome is likely indicative of the greater differentiation potential of monocytes into macrophages, dendritic cells and osteoclasts. In contrast, most of the neutrophil-specific features tend to be characterized by repressed chromatin, reflective of their status as terminally differentiated cells. Enhancers were the regions where most of differences in DNA methylation between cells were observed, with monocyte-specific enhancers being generally hypomethylated. Monocytes show a substantially higher gene expression levels than neutrophils, in line with epigenomic analysis revealing that gene more active elements in monocytes. Our analyses suggest that the overexpression of c-Myc in monocytes and its binding to monocyte-specific enhancers could be an important contributor to these differences. Altogether, our study provides a comprehensive epigenetic chart of chromatin states in primary human neutrophils and monocytes, thus providing a valuable resource for studying the regulation of the human innate immune system.
Going through the motions: incorporating movement analyses into disease research
Authors: Dougherty Eric R. , Seidel Dana P. , Carlson Colin J. , Spiegel Orr , Getz Wayne M. 
Published: December 2017

AbstractThough epidemiology dates back to the 1700s, most mathematical representations of epidemics still use transmission rates averaged at the population scale, especially for wildlife diseases. In simplifying the contact process, we ignore the heterogeneities in host movements that complicate the real world, and overlook their impact on spatiotemporal patterns of disease burden. Movement ecology offers a set of tools that help unpack the transmission process, letting researchers more accurately model how animals within a population interact and spread pathogens. Analytical techniques from this growing field can also help expose the reverse process: how infection impacts movement behaviors, and therefore other ecological processes like feeding, reproduction, and dispersal. Here, we synthesize the contributions of movement ecology in disease research, with a particular focus on studies that have successfully used movement-based methods to quantify individual heterogeneity in exposure and transmission risk. Throughout, we highlight the rapid growth of both disease and movement ecology, and comment on promising but unexplored avenues for research at their overlap. Ultimately, we suggest, including movement empowers ecologists to pose new questions expanding our understanding of host-pathogen dynamics, and improving our predictive capacity for wildlife and even human diseases.
AYbRAH: a curated ortholog database for yeasts and fungi spanning 600 million years of evolution
Authors: Correia Kevin , Yu Shi M. , Mahadevan Radhakrishnan 
Published: December 2017

ABSTRACTBudding yeasts inhabit a range of environments by exploiting various metabolic traits. The genetic bases for these traits are mostly unknown, preventing their addition or removal in a chassis organism for metabolic engineering. To help understand the molecular evolution of these traits in yeasts, we created Analyzing Yeasts by Reconstructing Ancestry of Homologs (AYbRAH), an open-source database of predicted and manually curated ortholog groups for 33 diverse fungi and yeasts in Dikarya, spanning 600 million years of evolution. OrthoMCL and OrthoDB were used to cluster protein sequence into ortholog and homolog groups, respectively; MAFFT and PhyML were used to reconstruct the phylogeny of all homolog groups. Ortholog assignments for enzymes and small metabolite transporters were compared to their phylogenetic reconstruction, and curated to resolve any discrepancies. Information on homolog and ortholog groups can be viewed in the AYbRAH web portal (https://kcorreia.github.io/aybrah/) to review ortholog groups, predictions for mitochondrial localization and transmembrane domains, literature references, and phylogenetic reconstructions. Ortholog groups in AYbRAH were compared to HOGENOM, KEGG Orthology, OMA, eggNOG, and PANTHER. PANTHER and OMA had the most congruent ortholog groups with AYbRAH, while the other phylogenomic databases had greater amounts of under-clustering, over-clustering, or no ortholog annotations for proteins. Future plans are discussed for AYbRAH, and recommendations are made for other research communities seeking to create curated ortholog databases.
The individual functional connectome is unique and stable over months to years
Authors: Horien Corey , Shen Xilin , Scheinost Dustin , Constable R. Todd 
Published: December 2017

AbstractFunctional connectomes computed from fMRI provide a means to characterize individual differences in the patterns of BOLD synchronization across regions of the entire brain. Using four resting-state fMRI datasets with a wide range of ages, we show that individual differences of the functional connectome are stable across three months to three years. Medial frontal and frontoparietal networks appear to be both unique and stable, resulting in high ID rates, as did a combination of these two networks. We conduct analyses demonstrating that these results are not driven by head motion. We also show that the edges demonstrating the most individualized features tend to connect nodes in the frontal and parietal cortices, while edges contributing the least tend to connect cross-hemispheric homologs. Our results demonstrate that the functional connectome is stable across years and is not an idiosyncratic aspect of a specific dataset, but rather reflects stable individual differences in the functional connectivity of the brain.Research highlightsWhole-brain functional connectivity profiles obtained from four resting-state fMRI datasets are unique and stable across 3 months-3 years in adolescents, young adults, and older adultsMedial frontal and frontoparietal networks tended to be both unique and stableIndividual edges in the frontal and parietal cortices tended to be most discriminative of individual subjects
Active site alanine substitutions can convert deubiquitinating enzymes into avid ubiquitin-binding domains
Authors: Morrow Marie , Morgan Michael , Clerici Marcello , Growkova Katerina , Yan Ming , Komander David , Simicek Michal , Sixma Titia , Wolberger Cynthia 
Published: December 2017

ABSTRACTA common strategy for studying the biological role of deubiquitinating enzymes (DUBs) in different pathways is to study the effects of replacing the wild type DUB with a catalytically inactive mutant in cells. We report here that a commonly studied DUB mutation, in which the catalytic cysteine is replaced with alanine, can dramatically increase the affinity of some DUBs for ubiquitin. Overexpression of these tight-binding mutants thus has the potential to sequester cellular pools of monoubiquitin and ubiquitin chains. As a result, cells expressing these mutants may display unpredictable dominant negative physiological effects that are not related to loss of DUB activity. The structure of the SAGA DUB module bound to free ubiquitin reveals the structural basis for the 30-fold higher affinity of Ubp8C146A for ubiquitin. We show that an alternative option, substituting the active site cysteine with arginine, can inactivate DUBs while also decreasing the affinity for ubiquitin.
Hydrogen production bySulfurospirillumspp. enables syntrophic interactions of Epsilonproteobacteria
Authors: Kruse Stefan , Goris Tobias , Westermann Martin , Adrian Lorenz , Diekert Gabriele 
Published: December 2017

AbstractHydrogen-producing bacteria are of environmental and biotechnological importance in anoxic environments, since hydrogen is an important electron donor for prokaryotes and of interest as an alternative energy source. Epsilonproteobacteria, inhabiting ecologically, clinically or biotechnologically relevant environments, are currently considered to be hydrogen-oxidizing bacteria exclusively. Here, we report hydrogen production for a genus of free-living Epsilonproteobacteria,Sulfurospirillumspp. inhabiting sediments, wastewater plants, bioelectrodes, oil reservoirs, contaminated areas, or marine habitats. The amount of hydrogen production was largely different in two subgroups ofSulfurospirillumspp., represented byS. cavoleiandS. multivorans. The former is shown to be the more potent hydrogen producer and excretes acetate as sole organic acid, while the latter exhibited a more flexible fermentation, producing additionally lactate and succinate. The observed hydrogen production could be assigned to a group 4 hydrogenase similar to Hydrogenase 4 (Hyf) inE. coli. We propose thatSulfurospirillumspp. produce molecular hydrogen with electrons derived from pyruvate oxidation by pyruvate:ferredoxin oxidoreductase and reduced ferredoxin. This hypothesis is supported by comparative proteome data, in which both PFOR and ferredoxin as well as hydrogenase 4 are up-regulated. A co-culture experiment withS. multivoransandMethanococcus voltaecultivated with lactate as sole substrate shows a syntrophic interaction between both organisms, since the former cannot grow fermentatively on lactate alone and the latter relies on hydrogen as electron donor. This opens up new perspectives on microbial communities, since Epsilonproteobacteria could play a yet unrecognized role as hydrogen producers in anoxic microbial communities.
Visualizing genome synteny with xmatchview
Authors: Warren René L. 
Published: December 2017

AbstractIn genomics research, the visual representation of DNA sequences is of prime importance. When displayed with additional information, or tracks, showing the position of annotated genes, alignments of sequence of interest, etc., these displays facilitate our understanding of genome and gene structure, and become powerful tools to assess the relationship between various sequence data. They can be used for troubleshooting sequence assemblies, in-depth sequence analysis, and eventually find their way in publications and oral presentations as they often translate complex and abundant data succinctly, with esthetically pleasing images. Here, I introduce xmatchview and xmatchview-conifer, two python applications for comparing genomes visually and assessing their synteny. Availability: https://github.com/warrenlr/xmatchview
Does force-field adaptation induce after-effects on space representation?
Authors: Michel Carine , Bonnetain Lucie , White Olivier 
Published: December 2017

AbstractPrism adaptation is a well-known model to study sensorimotor adaptive processes. It has been shown that following prism exposure, after-effects are not only restricted to the sensorimotor level but extend as well into spatial cognition. The main purpose of the present study was to investigate in healthy individuals whether expansion to spatial cognition is restricted to adaptive processes peculiar to prism adaptation or whether it occurs as well following other forms of adaptive process such as adaptation to a novel dynamic environment during pointing movements. Representational after-effects were assessed by the perceptual line bisection task before and after adaptation to a leftward or a rightward force field. The main results showed that adaptation developed at sensorimotor level but did not produce after-effects in space representation. However appropriate analysis showed that the slower a participant de-adapt to a rightward dynamic perturbation, the stronger the influence on the perceptual midline judgment during the late phase of the bisection task. The discussion highlights the commonalities between prism and dynamic adaptation on the effects on space representation.
Cell-type specific parallel circuits in the bed nucleus of the stria terminalis and the central nucleus of the amygdala of the mouse
Authors: Ye Jiahao , Veinante Pierre 
Published: December 2017

AbstractThe central extended amygdala (EAc) is a forebrain macrosystem which has been widely implicated in fear, anxiety and pain. Its two key structures, the lateral bed nucleus of the stria terminalis (STL) and the central nucleus of amygdala (CeA), share similar mesoscale connectivity. However, it is not known whether they also share similar cell-specific neuronal circuits. We addressed this question using tract-tracing and immunofluorescence to reveal the connectivity of two neuronal populations expressing either protein kinase C delta (PKCδ) or somatostatin (SOM). PKCδ and SOM are expressed predominantly in the dorsal part of STL (STLD) and in the lateral/capsular parts of CeA (CeL/C). We found that, in both STLD and CeL/C, PKCδ+ cells are the main recipient of extra-EAc inputs from the external lateral part of the parabrachial nucleus (LPBE), while SOM+ cells are the sources of long-range projections to extra-EAc targets, including LPBE and periaqueductal gray. PKCδ+ cells can also integrate inputs from posterior basolateral nucleus of amygdala or insular cortex. Within EAc, PKCδ+, but not SOM+ neurons, serve as the major source of projections to the ventral part of STL and to the medial part of CeA. However, both cell types mediate interconnections between STLD and CeL/C. These results unveil the pivotal positions of PKCδ and SOM neurons in organizing parallel cell-specific neuronal circuits of CeA and STL, which further support the idea of EAc as a structural and functional macrostructure.
Aberrant cerebellar-default-mode functional connectivity underlying auditory verbal hallucinations in schizophrenia revealed by multi-voxel pattern analysis of resting-state functional connectivity MRI data
Authors: Itahashi Takashi , Mimura Masaru , Hasegawa Sayaka , Tani Masayuki , Kato Nobumasa , Hashimoto Ryu-ichiro 
Published: December 2017

AbstractPast neuroimaging studies have reported that aberrant functional connectivity (FC) underlying auditory verbal hallucinations (AVHs) in schizophrenia is highly distributed over multiple functional networks. There is thus a need for exploratory approaches without limiting analysis to particular seed regions or functional networks, to identify FC alterations underlying AVH. We applied a multi-voxel pattern analysis (MVPA) of FC together with a series of post-hoc FC analyses to resting-state fMRI data acquired from 25 patients with schizophrenia and 25 matched healthy controls. First, the MVPA revealed multiple clusters exhibiting altered FC patterns in schizophrenia. Subsequent multiple linear regression analysis using scores of these clusters identified that FC alteration in the right cerebellum crus I was significantly associated with the severity of AVH. Furthermore, post-hoc FC analysis with the right crus I as a seed revealed significant FC alterations with regions distributed across multiple functional networks, including speech, default-mode, thalamus, and cerebellum. Subsequent linear regression analyses further demonstrated that, among these regions, only reduced FC in the left precuneus was significantly associated with the severity of AVH. Our unbiased exploratory analysis of FC data revealed a novel evidence for the crucial role of FC between cerebellar and default-mode networks in AVH. (198 words)
Modulatory upregulation of an insulin peptide gene by different pathogens in C. elegans
Authors: Lee Song-Hua , Omi Shizue , Thakur Nishant , Taffoni Clara , Belougne Jérôme , Engelmann Ilka , Ewbank Jonathan J. , Pujol Nathalie 
Published: December 2017

ABSTRACTWhen an animal is infected, its innate immune response needs to be tightly regulated across tissues and coordinated with other aspects of organismal physiology. Previous studies with Caenorhabditis elegans have demonstrated that insulin-like peptide genes are differentially expressed in response to different pathogens. They represent prime candidates for conveying signals between tissues upon infection. Here, we focused on one such gene, ins-11 and its potential role in mediating cross-tissue regulation of innate immune genes. While diverse bacterial intestinal infections can trigger the up-regulation of ins-11 in the intestine, we show that epidermal infection with the fungus Drechmeria coniospora triggers an upregulation of ins-11 in the epidermis. Using the Shigella virulence factor OpsF, a MAP kinase inhibitor, we found that in both cases, ins-11 expression is controlled cell autonomously by p38 MAPK, but via distinct transcription factors, STA-2/STAT in the epidermis and HLH-30/TFEB in the intestine. We established that ins-11, and the insulin signaling pathway more generally, are not involved in the regulation of antimicrobial peptide gene expression in the epidermis. The up-regulation of ins-11 in the epidermis does, however, affect intestinal gene expression in a complex manner, and has a deleterious effect on longevity. These results support a model in which insulin signaling, via ins-11, contributes to the coordination of the organismal response to infection, influencing the allocation of resources in an infected animal.
Late cortical tracking of ignored speech facilitates neural selectivity in acoustically challenging conditions
Authors: Fiedler Lorenz , Wöstmann Malte , Herbst Sophie K. , Obleser Jonas 
Published: December 2017

AbstractListening requires selective neural processing of the incoming sound mixture, which in humans is borne out by a surprisingly clean representation of attended-only speech in auditory cortex. How this neural selectivity is achieved even at negative signal-to-noise ratios (SNR) remains unclear. We show that, under such conditions, a late cortical representation (i.e., neural tracking) of the ignored acoustic signal is key to successful separation of attended and distracting talkers (i.e., neural selectivity). We recorded and modelled the electroencephalographic response of 18 participants who attended to one of two simultaneously presented stories, while the SNR between the two talkers varied dynamically. The neural tracking showed an increasing early-to-late attention-biased selectivity. Importantly, acoustically dominant ignored talkers were tracked neurally by late involvement of fronto-parietal regions, which contributed to enhanced neural selectivity. This neural selectivity by way of representing the ignored talker poses a mechanistic neural account of attention under real-life acoustic conditions.
DeepSimulator: a deep simulator for Nanopore sequencing
Authors: Li Yu , Han Renmin , Bi Chongwei , Li Mo , Wang Sheng , Gao Xin 
Published: December 2017

ABSTRACTMotivationOxford Nanopore sequencing is a rapidly developed sequencing technology in recent years. To keep pace with the explosion of the downstream data analytical tools, a versatile Nanopore sequencing simulator is needed to complement the experimental data as well as to benchmark those newly developed tools. However, all the currently available simulators are based on simple statistics of the produced reads, which have difficulty in capturing the complex nature of the Nanopore sequencing procedure, the main task of which is the generation of raw electrical current signals.ResultsHere we propose a deep learning based simulator, DeepSimulator, to mimic the entire pipeline of Nanopore sequencing. Starting from a given reference genome or assembled contigs, we simulate the electrical current signals by a context-dependent deep learning model, followed by a base-calling procedure to yield simulated reads. This workflow mimics the sequencing procedure more naturally. The thorough experiments performed across four species show that the signals generated by our context-dependent model are more similar to the experimentally obtained signals than the ones generated by the official context-independent pore model. In terms of the simulated reads, we provide a parameter interface to users so that they can obtain the reads with different accuracies ranging from 83% to 97%. The reads generated by the default parameter have almost the same properties as the real data. Two case studies demonstrate the application of DeepSimulator to benefit the development of tools in de novo assembly and in low coverage SNP detection.AvailabilityThe software can be accessed freely at: https://github.com/lykaust15/deep_simulator.
Hepatic NF-kB-inducing Kinase (NIK) Suppresses Liver Regeneration in Chronic Liver Disease
Authors: Xiong Yi , Torsoni Adriana Souza , Wu Feihua , Shen Hong , Liu Yan , Canet Mark J , Shah M. Yatrik , Omary M. Bishr , Liu Yong , Rui Liangyou 
Published: December 2017

SummaryHepatocyte replication maintains liver homeostasis and integrity. It is impaired in chronic liver disease, promoting disease progression. Herein, we have identified NF-kB-inducing kinase (NIK) as an unrecognized suppressor of hepatocyte replication. Hepatic NIK was aberrantly activated in chronic liver disease. Hepatocyte-specific deletion of NIK or its downstream mediator IKKα substantially accelerated hepatocyte proliferation and liver regeneration following partial hepatectomy. Mechanistically, NIK and IKKα suppressed the mitogenic JAK2/STAT3 pathway, thereby inhibiting hepatocyte cell cycle progression. Remarkably, inactivation of hepatic NIK largely reversed suppression of the hepatic JAK2/STAT3 pathway, hepatocyte replication, and liver regeneration induced by either chronic liver injury or metabolic stress. Our data suggest that hepatic NIK acts as a rheostat for liver regeneration to restrain liver overgrowth. Pathologic activation of hepatic NIK blocks hepatocyte replication, likely contributing to liver disease progression.