bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissociable Neural Systems Support the Learning and Transfer of Hierarchical Control Structure
Authors: Eichenbaum Adam , Scimeca Jason M. , D’Esposito Mark 
Published: January 2020

AbstractHumans can draw insight from previous experiences in order to quickly adapt to novel environments that share a common underlying structure. Here we combine functional imaging and computational modeling to identify the neural systems that support the discovery and transfer of hierarchical task structure. Human subjects completed multiple blocks of a reinforcement learning task that contained a global hierarchical structure governing stimulus-response action mapping. First, behavioral and computational evidence showed that humans successfully discover and transfer the hierarchical rule structure embedded within the task. Next, analysis of fMRI BOLD data revealed activity across a frontal-parietal network that was specifically associated with the discovery of this embedded structure. Finally, activity throughout a cingulo-opercular network and in caudal frontal cortex supported the transfer and implementation of this discovered structure. Together, these results reveal a division of labor in which dissociable neural systems support the learning and transfer of abstract control structures.
Two pectate lyases fromCaldicellulosiruptor besciiwith the same CALG domain had distinct properties on plant biomass degradation
Authors: Hamouda Hamed I. , Ali Nasir , Su Hang , Feng Jie , Lu Ming , Li Fu-Li 
Published: January 2020

AbstractPectin deconstruction is the initial step in breaking the recalcitrance of plant biomass by using selected microorganisms that carry pectinolytic enzymes. Pectate lyases that cleave α-1,4-galacturonosidic linkage of pectin are widely used in industries, such as paper making and fruit softening. However, reports on pectate lyases with high thermostability are few. Two pectate lyases (CbPL3 andCbPL9) from a thermophilic bacteriumCaldicellulosiruptor besciiwere investigated. Although these two enzymes belonged to different families of polysaccharide lyase, both were Ca2+-dependent. Similar biochemical properties were shown under optimized conditions 80 °C–85 °C and pH 8–9. However, the degradation products on pectin and polygalacturonic acids (pGA) were different, revealing the distinct mode of action. A concanavalin A-like lectin/glucanase (CALG) domain, located in theN-terminus of twoCbPLs, shares 100% amino acid identity. CALG-truncated mutant ofCbPL9 showed lower activities than the wild-type, whereas theCbPL3 with CALG knock-out portion was reported with enhanced activities, thereby revealing the different roles of CALG in twoCbPLs. I-TASSER predicted that the CALG in twoCbPLs is structurally close to the family 66 carbohydrate binding module (CBM66). Furthermore, substrate-binding assay indicated that the catalytic domains in twoCbPLs had strong affinities on pectate-related substrates, but CALG showed weak interaction with a number of lignocellulosic carbohydrates, except sodium carboxymethyl cellulose and sodium alginate. Finally, scanning electron microscope analysis and total reducing sugar assay showed that the two enzymes could improve the saccharification of switchgrass. The twoCbPLs are impressive sources for degradation of plant biomass.ImportanceThermophilic proteins could be implemented in diverse industrial applications. We sought to characterize two pectate lyases,CbPL3 andCbPL9, from a thermophilic bacteriumCaldicellulosiruptor bescii. The two enzymes had high optimum temperature, low optimum pH, and good thermostability at evaluated temperature. A family-66 carbohydrate binding module (CBM66) was identified in twoCbPLs with sharing 100% amino acid identity. Deletion of CBM66 obviously decreased the activity ofCbPL9, but increase the activity and thermostability ofCbPL3, suggesting the different roles of CBM66 in two enzymes. Moreover, the degradation products by twoCbPLs were different. These results revealed these enzymes could represent a potential pectate lyase for applications in paper and textile industries.
Most of Staphylococcus aureus and Pseudomonas aeruginosa co-infecting isolates coexist, a condition that may impact clinical outcomes in Cystic Fibrosis patients
Authors: Briaud Paul , Bastien Sylvère , Camus Laura , Boyadjian Marie , Reix Philippe , Mainguy Catherine , Vandenesch François , Doléans-Jordheim Anne , Moreau Karen 
Published: January 2020

AbstractStaphylococcus aureus (SA) is the major colonizer of the lung of cystic fibrosis (CF) patient during childhood and adolescence. As patient aged, the prevalence of SA decreases and Pseudomonas aeruginosa (PA) becomes the major pathogen infecting adult lungs. Nonetheless, SA remains significant and patients harbouring both SA and PA are frequently found in worldwide cohort. Impact of coinfection remains controversial. Furthermore, co-infecting isolates may compete or coexist. The aim of this study was to analyse if co-infection and coexistence of SA and PA could lead to worse clinical outcomes. The clinical and bacteriological data of 212 Lyon CF patients were collected retrospectively, and patients were ranked into three groups, SA only (n=112), PA only (n=48) or SA plus PA (n=52). In addition, SA and PA isolates from co-infecting patients were tested in vitro to define their interaction profile. Sixty five percent (n=34) of SA/PA pairs coexist. Using univariate and multivariate analysis, we confirm that SA patients have a clinical condition less severe than others, and PA induce a poor outcome independently of the presence of SA. FEV1 is lower in patients infected by competition strain pairs than in those infected by coexisting strain pairs compared to SA mono-infection. Coexistence between SA and PA may be an important step in the natural history of lung bacterial colonization within CF patients.
Assessing Knowledge, Attitudes, and Practices towards Causal Directed Acyclic Graphs: a qualitative research project
Authors: Barnard-Mayers Ruby , Childs Ellen , Corlin Laura , Caniglia Ellen C , Fox Matthew P , Donnelly John P. , Murray Eleanor J 
Published: January 2020

AbstractBackgroundCausal graphs provide a key tool for optimizing the validity of causal effect estimates. Although a large literature exists on the mathematical theory underlying the use of causal graphs, less literature exists to aid applied researchers in understanding how best to develop and use causal graphs in their research projects.MethodsWe sought to understand why researchers do or do not regularly use DAGs by surveying practicing epidemiologists and medical researchers on their knowledge, level of interest, attitudes, and practices towards the use of causal graphs in applied epidemiology and health research. We used Twitter and the Society for Epidemiologic Research to disseminate the survey.ResultsOverall, a majority of participants reported being comfortable with using causal graphs and reported using them ‘sometimes’, ‘often’, or ‘always’ in their research. Having received training appeared to improve comprehension of the assumptions displayed in causal graphs. Many of the respondents who did not use causal graphs reported lack of knowledge as a barrier to using DAGs in their research.ConclusionCausal graphs are of interest to epidemiologists and medical researchers, but there are several barriers to their uptake. Additional training and clearer guidance are needed. In addition, methodological developments regarding visualization of effect measure modification and interaction on causal graphs is needed.
Dynamic longitudinal behavior in animals exposed to chronic social defeat stress
Authors: Wendelmuth M. , Willam M. , Todorov H. , Radyushkin K. , Gerber S. , Schweiger S. 
Published: January 2020

AbstractChronic social defeat (CSD) can lead to impairments in social interaction and other behaviors that are supposed to model features of major depressive disorder (MDD). Not all animals subjected to CSD, however, develop these impairments, and maintained social interaction in some animals is widely used as a model for resilience to stress-induced mental dysfunctions. So far, animals have mainly been studied shortly (24 hours and 7 days) after CSD exposure and longitudinal development of behavioral phenotypes in individual animals has been mostly neglected. We have analyzed social interaction and novel object recognition behavior of stressed mice at different time points after CSD and have found very dynamic courses of behavior of individual animals. Instead of the two groups, resilient or susceptible, that are found at early time points our data suggest four groups with (i, ii) animals behaving resilient or susceptible at early and late time points, respectively (iii) animals that start susceptible and recover with time or (iv) animals that are resilient at early time points but develop vulnerability later on.
Complement C5a impairs phagosomal maturation in the neutrophil through phosphoproteomic remodelling
Authors: Wood Alexander J.T. , Vassallo Arlette M. , Ruchaud-Sparagano Marie-Hélène , Scott Jonathan , Zinnato Carmelo , Gonzalez-Tejedo Carmen , Kishore Kamal , D’Santos Clive S. , Simpson A. John , Menon David K. , Summers Charlotte , Chilvers Edwin R. , Okkenhaug Klaus , Morris Andrew Conway 
Published: January 2020

AbstractCritical illness is accompanied by the release of large amounts of the anaphylotoxin, C5a. C5a suppresses antimicrobial functions of neutrophils which is associated with adverse outcomes. The signalling pathways that mediate C5a-induced neutrophil dysfunction are incompletely understood. Healthy donor neutrophils exposed to purified C5a demonstrated a prolonged defect (7 hours) in phagocytosis ofStaphylococcus aureus. Phosphoproteomic profiling of 2712 phosphoproteins identified persistent C5a signalling and selective impairment of phagosomal protein phosphorylation on exposure toS. aureus.Notable proteins included early endosomal marker ZFYVE16 and V-ATPase proton channel component ATPV1G1. A novel assay of phagosomal acidification demonstrated C5a-induced impairment of phagosomal acidification which was recapitulated in neutrophils from critically ill patients. Examination of the C5a-impaired protein phosphorylation indicated a role for the phosphatidylinositol 3-kinase VPS34 in phagosomal maturation. Inhibition of VPS34 impaired neutrophil phagosomal acidification and killing ofS. aureus. This study provides a phosphoproteomic assessment of human neutrophil signalling in response toS. aureusand its disruption by C5a, identifying a defect in phagosomal maturation and new mechanisms of immune failure in critical illness.
Accelerated EM Connectome Reconstruction using 3D Visualization and Segmentation Graphs
Authors: Hubbard Philip M. , Berg Stuart , Zhao Ting , Olbris Donald J. , Umayam Lowell , Maitin-Shepard Jeremy , Januszewski Michal , Katz William T. , Neace Erika R. , Plaza Stephen M. 
Published: January 2020

AbstractRecent advances in automatic image segmentation and synapse prediction in electron microscopy (EM) datasets of the brain enable more efficient reconstruction of neural connectivity. In these datasets, a single neuron can span thousands of images containing complex tree-like arbors with thousands of synapses. While image segmentation algorithms excel within narrow fields of views, the algorithms sometimes struggle to correctly segment large neurons, which require large context given their size and complexity. Conversely, humans are comparatively good at reasoning with large objects. In this paper, we introduce several semi-automated strategies that combine 3D visualization and machine guidance to accelerate connectome reconstruction. In particular, we introduce a strategy to quickly correct a segmentation through merging andcleaving, or splitting a segment along supervoxel boundaries, with both operations driven by affinity scores in the underlying segmentation. We deploy these algorithms as streamlined workflows in a tool calledNeu3and demonstrate superior performance compared to prior work, thus enabling efficient reconstruction of much larger datasets. The insights into proofreading from our work clarify the trade-offs to consider when tuning the parameters of image segmentation algorithms.
Identification of a novel population of peripheral sensory neuron that regulates blood pressure
Authors: Morelli Chiara , Castaldi Laura , Brown Sam J. , Streich Lina L. , Websdale Alexander , Taberner Francisco J. , Cerreti Blanka , Barenghi Alessandro , Blum Kevin M. , Sawitzke Julie , Frank Tessa , Steffens Laura , Doleschall Balint , Serrao Joana , Lechner Stefan G. , Prevedel Robert , Heppenstall Paul A. 
Published: January 2020

SummaryThe vasculature is innervated by a network of peripheral afferents that sense and regulate blood flow. Here, we describe a system of non-peptidergic sensory neurons with cell bodies in the spinal ganglia that regulate vascular tone in the distal arteries. We identify a population of mechanosensitive neurons marked by TrkC and Tyrosine hydroxylase in the dorsal root ganglia that project to blood vessels. Local stimulation of these neurons decreases vessel diameter and blood flow, while systemic activation increases systolic blood pressure and heart rate variability via the sympathetic nervous system. Chemogenetic inactivation or ablation of the neurons provokes variability in local blood flow leading to a reduction in systolic blood pressure, increased heart rate variability and ultimately lethality within 48 hours. Thus, TrkC/Tyrosine hydroxylase positive sensory neurons form part of a sensory feedback mechanism that maintains cardiovascular homeostasis through the autonomic nervous system.
Radula diversification promotes ecomorph divergence in an adaptive radiation of freshwater snails
Authors: Hilgers Leon , Hartmann Stefanie , Pfaender Jobst , Lentge-Maaß Nora , von Rintelen Thomas , Hofreiter Michael 
Published: January 2020

AbstractAdaptive diversification of complex traits plays a pivotal role for the evolution of organismal diversity. However, the underlying molecular mechanisms remain largely elusive. In the freshwater snail genusTylomelania,adaptive radiations were likely promoted by trophic specialization via diversification of their key foraging organ, the radula. To investigate the molecular basis of radula diversification and its contribution to lineage divergence, we use pooled tissue-specific transcriptomes of two sympatricTylomelania sarasinorumecomorphs. We show that divergence in both gene expression and coding sequences is stronger between radula transcriptomes compared to mantle and foot transcriptomes. These findings support the hypothesis that diversifying selection on the radula is driving speciation inTylomelaniaradiations. We also identify several candidate genes for radula divergence. Putative homologs of some candidates (hh,arx,gbb) also contributed to trophic specialization in cichlids and Darwin’s finches, indicating that some molecular pathways may be especially prone to adaptive diversification.
Grassland irrigation and fertilisation alter vegetation height and vegetation within temperature and negatively affect orthopteran populations
Authors: Humbert Jean-Yves , Delley Sarah , Arlettaz Raphaël 
Published: January 2020

AbstractEuropean mountain meadows are hosting an exceptionally rich biodiversity. While they have long been exposed to land abandonment, they are nowadays additionally threatened by agriculture intensification through aerial irrigation and slurry application. The consequences of this intensification on arthropods are not well documented and studies are needed to fulfil this knowledge gap. Six experimental management treatments combining a full factorial design and a gradual level of fertilisation and irrigation were implemented in 2010 in twelve different montane and subalpine Swiss meadows. In 2013, orthopterans were sampled to assess the influence of the management practices on their population. In addition changes in vegetation height and temperature induced by intensification were recorded in order to better appraise underlying mechanisms. Intensification had a negative impact on Caelifera (grasshoppers); with decreases of up to 70% in densities and 50% in species richness in the most intensively managed treatment plots. In parallel intensification induced an increase in mean vegetation height and a cooling of up to 4.2 °C (10 cm aboveground) within most intensively managed plots. These microhabitat and microclimate changes are likely to have affected Caelifera development, in particular thermophilous species. In contrast, Ensifera (bush crickets) densities and species richness did not respond to the management treatments. The use of irrigation (without fertilisation) had limited impacts on orthopterans and microclimate. In conclusion, orthopterans, in particular Caelifera, are relatively sensitive to grassland intensification and to conserve the full community, mountain agricultural systems need to maintain extensively managed meadows.
Supraphysiological protection from replication stress does not extend mammalian lifespan
Authors: Albers Eliene , Avram Alexandra , Sbroggio Mauro , Fernandez-Capetillo Oscar , Lopez-Contreras Andres J 
Published: January 2020

AbstractReplication Stress (RS) is a type of DNA damage generated at the replication fork, characterized by single-stranded DNA (ssDNA) accumulation, and which can be caused by a variety of factors. Previous studies have reported elevated RS levels in aged cells. In addition, mouse models with a deficient RS response show accelerated aging. However, the relevance of endogenous or physiological RS, compared to other sources of genomic instability, for the normal onset of aging is unknown. We have performed long term survival studies of transgenic mice with extra copies of theChk1and/orRrm2genes, which we previously showed extend the lifespan of a progeroid ATR-hypomorphic model suffering from high levels of RS. In contrast to their effect in the context of progeria, the lifespan ofChk1, Rrm2andChk1/Rrm2transgenic mice was similar to WT littermates in physiological settings. Most mice studied died due to tumors -mainly lymphomas-irrespective of their genetic background. Interestingly, a slightly higher percentage of transgenic mice developed tumors compared to WT mice. Our results indicate that supraphysiological protection from RS does not extend lifespan, indicating that RS may not be a relevant source of genomic instability on the onset of “normal” aging.
ATX expression from GFAP+cells is essential for embryonic development
Authors: Sevastou Ioanna , Ninou Ioanna , Aidinis Vassilis 
Published: January 2020

AbstractAutotaxin (ATX) is secreted by various type of cells in health and disease and catalyzes the extracellular production of lysophosphatidic acid (LPA). In turn, LPA is a bioactive lysophospholipid promoting a wide array of cellular functions through its multiple G-protein coupled receptors, differentially expressed in almost all cell types. ATX expression has been shown necessary for embryonic development and has been suggested to participate in the pathogenesis of different chronic inflammatory diseases and cancer. Deregulated ATX and LPA levels have been reported in multiple sclerosis (MS) and its experimental model, experimental autoimmune encephalomyelitis (EAE). ATX genetic deletion from macrophages and microglia (CD11b+cells) attenuated the severity of EAE, thus proposing a pathogenic role for the ATX/LPA axis in MS/EAE. In this report, increased ATX staining was localized to glial fibrillary acidic protein positive (GFAP+) cells, mostly astrocytes, in spinal cord sections from EAE mice at the peak of the disease. However, genetic deletion of ATX from GFAP+cells resulted in embryonic lethality, suggesting a major role for ΑΤΧ expression from GFAP+cells in embryonic development, that urges further dissection. Moreover, the re-expression of ATX from GFAP+ cells during the pathogenesis of EAE, reinforces the concept that ATX/LPA is a developmental program aberrantly reactivated upon chronic inflammation.
A computational model to unravel the function of amyloid-βpeptide in contact with a phospholipid membrane
Authors: Quoc Huy Pham Dinh , Krupa Pawel , Nguyen Hoang Linh , La Penna Giovanni , Li Mai Suan 
Published: January 2020

AbstractThe normal synapse activity involves the release of copper and other divalent cations in the synaptic region. These ions have a strong impact on the membrane properties, especially when the membrane has charged groups, like it is the case of synapse. In this work we use an atomistic computational model of dimyristoyl-phosphatidylcholine (DMPC) membrane bilayer. We perturb this model with a simple model of divalent cation (Mg2+), and with a single amyloid-β(Aβ) peptide of 42 residues, both with and without a single Cu2+ion bound to the N-terminus. In agreement with experimental results reported in the literature, the model confirms that divalent cations locally destabilize the DMPC membrane bilayer, and, for the first time, that the monomeric form of Aβhelps in avoiding the interactions between divalent cations and DMPC, preventing significant effects on the DMPC bilayer properties. These results are discussed in the frame of a protective role of diluted Aβpeptide floating in the synaptic region.Author summaryWe modelled the behavior of a Mg2+divalent cation, with the size of Zn2+and Cu2+, in contact with a phosphatidyl lipid bilayer. We also modelled the monomeric amyloid-βpeptide 1-42, both free and Cu-loaded, the latter mimicking the final step of the binding between the peptide and the divalent cation. On the basis of the simulation results, we propose that the peptide hinders the strong interactions between the divalent cation and the membrane.
Genome-wide co-expression distributions as a metric to prioritize genes of functional importance
Authors: Alexandre Pâmela A. , Hudson Nicholas J. , Lehnert Sigrid A. , Fortes Marina R.S. , Naval-Sánchez Marina , Nguyen Loan T. , Porto-Neto Laercio R. , Reverter Antonio 
Published: January 2020

AbstractGenome-wide gene expression is routinely used as a tool to gain a systems-level understanding of complex, biological processes. Numerical approaches that have been used to highlight influential genes include abundance, differential expression, differential variation, network connectivity and differential connectivity. Network connectivity tends to be built on a small subset of extremely high co-expression signals that are deemed significant, but this overlooks the vast majority of pairwise signals. Here, we aimed to assess a complementary strategy, namely whether the entire shape of the distribution of genome-wide co-expression values contains a meaningful biological signal that has hitherto remained hidden from view. We have developed a computational pipeline to assign one of 8 distributions (including normal, skewed, bimodal, kurtotic, inverted) to every gene. We then used a hypergeometric enrichment process to determine if particular genes (regulators versus non-regulators) and properties (differentially expressed or not) tend to be associated with particular distributions greater than would be expected by chance. Examination of several distinct data sets spanning 4 species indicates that there is indeed an additional biological signal present in the genome-wide distribution of co-expression values which would be overlooked by currently adopted approaches.Author summaryHigh-throughput technologies, such as RNA-Seq, enables access to a vast amount of data. Here, we describe a new approach to interrogate these data and extract further information to help researchers to understand complex phenotypes. Our method is based on gene-level co-expression distributions which were compared to eight possible template shapes to group genes with similar behaviours. The method was tested using five different datasets and the consistency of the results indicate it can be used as a complementary strategy to analyse transcriptomic data.