bluuebunny/crossref_metadata_2025_split huggingface dataset:
Commonalities in alpha and beta neural desynchronizations during prediction in language comprehension and production
Authors: Gastaldon Simone , Arcara Giorgio , Navarrete Eduardo , Peressotti Francesca 
Published: May 2020

AbstractThe present study investigates whether predictions during language comprehension are generated by engaging the production system. We recorded EEG from participants performing both a comprehension and a production task in two separate blocks. Participants listened to high and low constraint incomplete sentences and were asked either to name a picture to complete it (production) or to simply listen to the final word (comprehension). We found that in a silent gap before the final stimulus, predictable stimuli elicited alpha (8-10 Hz) and beta (13-30 Hz) desynchronization in both tasks. Source estimation highlighted not only the involvement of the left-lateralized language network, but also of temporo-parietal areas in the right hemisphere. Furthermore, correlations between the desynchronizations in comprehension and production showed spatiotemporal commonalities in language-relevant areas in the left hemisphere, especially in the temporal, lateral inferior and dorsal frontal, and inferior parietal corteces. As proposed by prediction-by-production models, our results show that comprehenders engage the production system while predicting upcoming words.
Statistics of nascent and mature RNA fluctuations in a stochastic model of transcriptional initiation, elongation, pausing, and termination
Authors: Filatova Tatiana , Popovic Nikola , Grima Ramon 
Published: May 2020

AbstractRecent advances in fluorescence microscopy have made it possible to measure the fluctuations of nascent (actively transcribed) RNA. These closely reflect transcription kinetics, as opposed to conventional measurements of mature (cellular) RNA, whose kinetics is affected by additional processes downstream of transcription. Here, we formulate a stochastic model which describes promoter switching, initiation, elongation, premature detachment, pausing, and termination while being analytically tractable. By computational binning of the gene into smaller segments, we derive exact closed-form expressions for the mean and variance of nascent RNA fluctuations in each of these segments, as well as for the total nascent RNA on a gene. We also derive exact expressions for the first two moments of mature RNA fluctuations, and approximate distributions for total numbers of nascent and mature RNA. Our results, which are verified by stochastic simulation, uncover the explicit dependence of the statistics of both types of RNA on transcriptional parameters and potentially provide a means to estimate parameter values from experimental data.
Dose-dependent and disease-modifying effects of striatal infusion of cholesterol in Huntington’s disease
Authors: Birolini Giulia , Valenza Marta , Di Paolo Eleonora , Vezzoli Elena , Talpo Francesca , Maniezzi Claudia , Caccia Claudio , Leoni Valerio , Bocchi Vittoria D. , Conforti Paola , Sogne Elisa , Petricca Lara , Cariulo Cristina , Verani Margherita , Caricasole Andrea , Falqui Andrea , Biella Gerardo , Cattaneo Elena 
Published: May 2020

AbstractA variety of pathophysiological mechanisms are implicated in Huntington’s disease (HD). Among them, reduced cholesterol biosynthesis has been detected in the HD mouse brain from pre-symptomatic stages, leading to diminished cholesterol synthesis, particularly in the striatum. In addition, systemic injection of cholesterol-loaded brain-permeable nanoparticles ameliorates synaptic and cognitive function in a transgenic mouse model of HD. To identify an appropriate treatment regimen and gain mechanistic insights into the beneficial activity of exogenous cholesterol in the HD brain, we employed osmotic mini-pumps to infuse three escalating doses of cholesterol directly into the striatum of HD mice in a continuous and rate-controlled manner. All tested doses prevented cognitive decline, while amelioration of disease-related motor defects was dose-dependent. In parallel, we found morphological and functional recovery of synaptic transmission involving both excitatory and inhibitory synapses of striatal medium spiny neurons. The treatment also enhanced endogenous cholesterol biosynthesis and clearance of mutant Huntingtin aggregates. These results indicate that cholesterol infusion to the striatum can exert a dose-dependent, disease-modifying effect and may be therapeutically relevant in HD.
Quantitative measurement of activity of JAK-STAT signaling pathways in blood samples and immune cells to predict innate and adaptive cellular immune response to viral infection and accelerate vaccine development
Authors: Bouwman Wilbert , Verhaegh Wim , Holtzer Laurent , van de Stolpe Anja 
Published: May 2020

AbstractThe host immune response determines the clinical course of a viral infection, for example in case of COVID-19 infection. The effectiveness of vaccination also depends on the induced immune response. Currently there is no method to measure the cellular immune response in blood samples. The functional activity of cells of innate and adaptive immune system is determined by coordinated activity of signaling pathways, especially the JAK-STAT pathways. Using a previously described approach we developed mRNA-based tests to measure activity of these signaling pathways, and show that they can be used to measure in a quantitative manner the cellular innate and adaptive immune response to a viral infection or vaccine in whole blood, PBMC, and specific immune cell type samples. Pathway activity level and range in healthy individuals was established, enabling interpretation of a pathway activity score on a patient sample without the need for a reference sample. Evidence is presented that the pathway activity analysis may also be useful for in vitro vaccine development and assessment of vaccine immunogenicity. Other envisioned applications lie in development of immunomodulatory drugs and drug response prediction and monitoring. Tests are expected to be of value in the COVID-19 crisis. In addition to the described Affymetrix microarray-based pathway tests for measuring host immune response, qPCR-based versions are in development; the latter can in principle be performed within three hours in routine hospital labs.
Anaplerotic pathways inHalomonas elongata: the role of the sodium gradient
Authors: Hobmeier Karina , Goëss Marie C. , Sehr Christiana , Kunte Hans Jörg , Kremling Andreas , Pflüger-Grau Katharina , Marin-Sanguino Alberto 
Published: May 2020

AbstractSalt tolerance in theγ-proteobacteriumHalomonas elongatais linked to its ability to produce the compatible solute ectoine. The metabolism of ectoine production is of great interest since it can shed light on the biochemical basis of halotolerance as well as pave the way for the improvement of the biotechnological production of such compatible solute. The ectoine production pathway uses oxaloacetate as a precursor, thereby connecting ectoine production to the anaplerotic reactions that refill carbon into the TCA cycle. This places a high demand on these reactions and creates the need to regulate them not only in response to growth but also in response to extracellular salt concentration. In this work we combine modeling and experiments to analyze how these different needs shape the anaplerotic reactions inH. elongata. First, the stoichiometric and thermodynamic factors that condition the flux distributions are analyzed, then the optimal patterns of operation for oxaloacetate production are calculated. Finally, the phenotype of two deletion mutants lacking potentially relevant anaplerotic enzymes: Phosphoenolpyruvate carboxylase (Ppc) and Oxaloacetate decarboxylase (Oad) is experimentally characterized. The results show that the anaplerotic reactions inH. elongataare indeed subject to different evolutionary pressures than those of other gram-negative bacteria. Ectoine producing halophiles must meet a higher metabolic demand for oxaloacetate and the reliance of many marine bacteria on the Entner-Doudoroff pathway compromises the anaplerotic efficiency of Ppc, which is usually one of the main enzymes fulfilling this role. The anaplerotic flux inH. elongatais contributed not only by Ppc but also by Oad, an enzyme that has not yet been shown to play this rolein vivo. Ppc is necessary forH. elongatato grow normally at low salt concentrations but it is not required to achieve near maximal growth rates as long as there is a steep sodium gradient. On the other hand, the lack of Oad presents serious difficulties to grow at high salt concentrations. This points to a shared role of these two enzymes in guaranteeing the supply of OAA for biosynthetic reactions.
Transcription Co-Factor LBH Is Necessary for Maintenance of Stereocilia Bundles and Survival of Cochlear Hair Cells
Authors: Liu Huizhan , Giffen Kimberlee P. , M’Hamed Grati , Morrill Seth W. , Li Yi , Liu Xuezhong , Briegel Karoline J. , He David Z. 
Published: May 2020

AbstractHearing loss affects ~10% of adults worldwide and is irreversible. Most sensorineural hearing loss is caused by progressive loss of mechanosensitive hair cells (HCs) in the cochlea of the inner ear. The molecular mechanisms underlying HC maintenance and loss are largely unknown. Our previous cell-specific transcriptome analysis showed that Limb-Bud-and-Heart (LBH), a transcription co-factor implicated in development, is abundantly expressed in outer hair cells (OHCs). We usedLbh-null mice to identify its role. Surprisingly,Lbhdeletion did not affect differentiation and early development of HCs, as nascent HCs inLbhknockout mice had normal looking stereocilia bundles. Whole-cell recording showed that the stereocilia bundle was mechanosensitive and OHCs exhibited the characteristic electromotility. However,Lbh-null mice displayed progressive hearing loss, with stereocilia bundle degeneration and OHC loss as early as postnatal day 12. Cell-specific RNA-seq and bioinformatic analyses identifiedSpp1, Six2, Gps2, Ercc6, Snx6as well asPlscr1, Rarb, Per2, GmnnandMap3k5among the top five transcription factors up- or down-regulated inLbh-null OHCs. Furthermore, this analysis showed significant gene enrichment of biological processes related to transcriptional regulation, cell cycle, DNA damage/repair and autophagy. In addition, Wnt and Notch pathway-related genes were found to be dysregulated inLbh-deficient OHCs. We speculate that LBH may promote maintenance of HCs and stereocilia bundles by regulating Notch and Wnt signaling activity. Our study implicates, for the first time, loss of LBH function in progressive hearing loss, and demonstrates a critical requirement of LBH in promoting HC survival.
NDI: A platform-independent data interface and database for neuroscience physiology and imaging experiments
Authors: García Murillo Daniel , Rogovin Ora , Zhao Yixin , Chen Shufei , Wang Ziqi , Keeley Zoey C. , Shin Daniel I. , Suárez Casanova Victor M. , Zhu Yannan , Martin Lisandro , Papaemmanouil Olga , Hooser Stephen D. Van 
Published: May 2020

AbstractCollaboration in neuroscience is impeded by the difficulty of sharing primary data, results, and software across labs. Here we introduce Neuroscience Data Interface (NDI), a platform-independent standard that allows an analyst to use and create software that functions independently from the format of the raw data or the manner in which the data is organized into files. The interface is rooted in a simple vocabulary that describes common apparatus and storage devices used in neuroscience experiments. Results of analyses – and analyses of analyses – are stored as documents in a scalable, queryable database that stores the relationships and history among the experiment elements and documents. The interface allows the development of an application ecosystem where applications can focus on calculation rather than data format or organization. This tool can be used by individual labs to exchange and analyze data, and it can serve to curate neuroscience data for searchable archives.
Immunoinformatic identification of B cell and T cell epitopes in the SARS-CoV-2 proteome
Authors: Crooke Stephen N. , Ovsyannikova Inna G. , Kennedy Richard B. , Poland Gregory A. 
Published: May 2020

AbstractA novel coronavirus (SARS-CoV-2) emerged from China in late 2019 and rapidly spread across the globe, infecting millions of people and generating societal disruption on a level not seen since the 1918 influenza pandemic. A safe and effective vaccine is desperately needed to prevent the continued spread of SARS-CoV-2; yet, rational vaccine design efforts are currently hampered by the lack of knowledge regarding viral epitopes targeted during an immune response, and the need for more in-depth knowledge on betacoronavirus immunology. To that end, we developed a computational workflow using a series of open-source algorithms and webtools to analyze the proteome of SARS-CoV-2 and identify putative T cell and B cell epitopes. Using increasingly stringent selection criteria to select peptides with significant HLA promiscuity and predicted antigenicity, we identified 41 potential T cell epitopes (5 HLA class I, 36 HLA class II) and 6 potential B cell epitopes, respectively. Docking analysis and binding predictions demonstrated enrichment for peptide binding to HLA-B (class I) and HLA-DRB1 (class II) molecules. Overlays of predicted B cell epitopes with the structure of the viral spike (S) glycoprotein revealed that 4 of 6 epitopes were located in the receptor-binding domain of the S protein. To our knowledge, this is the first study to comprehensively analyze all 10 (structural, non-structural and accessory) proteins from SARS-CoV-2 using predictive algorithms to identify potential targets for vaccine development.Significance StatementThe novel coronavirus SARS-CoV-2 recently emerged from China, rapidly spreading and ushering in a global pandemic. Despite intensive research efforts, our knowledge of SARS-CoV-2 immunology and the proteins targeted by the immune response remains relatively limited, making it difficult to rationally design candidate vaccines. We employed a suite of bioinformatic tools, computational algorithms, and structural modeling to comprehensively analyze the entire SARS-CoV-2 proteome for potential T cell and B cell epitopes. Utilizing a set of stringent selection criteria to filter peptide epitopes, we identified 41 T cell epitopes (5 HLA class I, 36 HLA class II) and 6 B cell epitopes that could serve as promising targets for peptide-based vaccine development against this emerging global pathogen.
Human DICER helicase domain recruits PKR and modulates its antiviral activity
Authors: Montavon Thomas C. , Baldaccini Morgane , Lefèvre Mathieu , Girardi Erika , Chane-Woon-Ming Béatrice , Messmer Mélanie , Hammann Philippe , Chicher Johana , Pfeffer Sébastien 
Published: May 2020

AbstractThe antiviral innate immune response mainly involves type I interferon (IFN) in mammalian cells. The contribution of the RNA silencing machinery remains to be established, but several recent studies indicate that the ribonuclease DICER can generate viral siRNAs in specific conditions. It has also been proposed that type I IFN and RNA silencing could be mutually exclusive antiviral responses. In order to decipher the implication of DICER during infection of human cells with alphaviruses such as the Sindbis virus and Semliki forest virus, we determined its interactome by proteomics analysis. We show that DICER specifically interacts with several double-stranded RNA binding proteins and RNA helicases during viral infection. In particular, proteins such as DHX9, ADAR-1 and the protein kinase RNA-activated (PKR) are enriched with DICER in virus-infected cells. We demonstrate that the helicase domain of DICER is essential for this interaction and that its deletion confers antiviral properties to DICER in an RNAi-independent, PKR-dependent, manner.Author summaryWhile RNAi has been recognized as an efficient antiviral defense system in organisms such as plants and insects, its physiological importance in mammals remains to be determined. DICER is an enzyme involved in cleaving long double-stranded RNAs and is essential for RNAi induction. Using mass spectrometry analysis, we determined its interactome in human cells and showed that RNA binding proteins such as PKR are specifically enriched upon infection with the Sindbis virus or the Semliki forest virus. We determined that the N terminal helicase domain of the DICER protein acts as a platform to recruit these factors during infection and that its deletion confers an antiviral activity to DICER.
On the automatic annotation of gene functions using observational data and phylogenetic trees
Authors: Vega Yon George G. , Thomas Duncan C. , Morrison John , Mi Huaiyu , Thomas Paul D. , Marjoram Paul 
Published: May 2020

AbstractMotivationGene function annotation is important for a variety of downstream analyses of genetic data. Yet experimental characterization of function remains costly and slow, making computational prediction an important endeavor. In this paper we use a probabilistic evolutionary model built upon phylogenetic trees and experimental Gene Ontology functional annotations that allows automated prediction of function for unannotated genes.ResultsWe have developed a computationally efficient model of evolution of gene annotations using phylogenies based on a Bayesian framework using Markov Chain Monte Carlo for parameter estimation. Unlike previous approaches, our method is able to estimate parameters over many different phylogenetic trees and functions. The resulting parameters agree with biological intuition, such as the increased probability of function change following gene duplication. The method performs well on leave-one-out validation, and we further validated some of the predictions in the experimental scientific literature.AvailabilityOur method has been implemented as an R package and it is available online athttps://github.com/USCBiostats/aphylo. Code needed to reproduce the tables and figures can be found inhttps://github.com/USCbiostats/aphylo-simulations.Author summaryUnderstanding the individual role that genes play in life is a key issue in biomedical-sciences. While information regarding gene functions is continuously growing, the number of genes with unknown biological purpose is yet greater. Because of this, scientists have dedicated much of their time to build and design tools that automatically infer gene functions. In this paper, we present yet another attempt to do such. While very simple, our model of gene-function evolution has some key features that have the potential to generate an impact in the field: (a) compared to other methods, ours is highly-scalable, which means that it is possible to simultaneously analyze hundreds of what are known as gene-families, compromising thousands of genes, (b) supports our biological intuition as our model’s data-driven results coherently agree with what theory dictates regarding how gene-functions evolved, (c) notwithstanding its simplicity, the model’s prediction accuracy is comparable to other more complex alternatives, and (d) perhaps most importantly, it can be used to both support new annotations and to suggest areas in which existing annotations show inconsistencies that may indicate errors or controversies.
Homogeneity among glyphosate-resistantAmaranthus palmeriin geographically distant locations
Authors: Molin William T. , Patterson Eric L. , Saski Christopher A. 
Published: May 2020

AbstractSince the initial report of glyphosate-resistant (GR)Amaranthus palmeri(S) Wats. in 2006, resistant populations have been reported in 28 states. The mechanism of resistance is amplification of a 399-kb extrachromosomal circular DNA, called theEPSPSreplicon, and is unique to glyphosate-resistant plants. The replicon contains a single copy of the 10-kb 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene which causes the concomitant increased expression of EPSP synthase, the target enzyme of glyphosate. It is not known whether the resistance by this amplification mechanism evolved once and then spread across the country or evolved independently in several locations. To compare genomic representation and variation across theEPSPSreplicon, whole genome shotgun sequencing (WGS) and mapping of sequences from both GR and susceptible (GS) biotypes to the replicon consensus sequence was performed. Sampling of GR biotypes from AZ, KS, GA, MD and DE and GS biotypes from AZ, KS and GA revealed complete contiguity and deep representation with sequences from GR plants, but lack of homogeneity and contiguity with breaks in coverage were observed with sequences from GS biotypes. The high sequence conservation among GR biotypes with very few polymorphisms which were widely distributed across the USA further supports the hypothesis that glyphosate resistance most likely originated from a single population. We show that the replicon from different populations was unique to GR plants and had similar levels of amplification.
A Cross-Sectional Study of Prevalence and Spatial Patterns of Major Limb Loss in the Acholi Sub-Region of Uganda
Authors: Atim Pamela , Loum Constantine S. , Okello Tom R. , Magada Samuel M. , Yagos Walter Onen , Abelle Peter , Moro Emmanuel B. , Huck Jonathan J. , Redmond Anthony , Nirmalan Mahesh 
Published: May 2020

AbstractBACKGROUNDThere is a widely reported preponderance of major limb loss in Northern Uganda, which is believed to have been caused in large part by prolonged civil war. Access to rehabilitation facilities is extremely limited, and there has never been a study to understand how many people have major limb loss, nor how many of them have had access to medical or rehabilitative services.AIMThe first prevalence study of disability and major limb loss in the region, and evaluated spatial patterns of cases of MLL.DESIGNCross-sectional survey.SETTINGThis research was undertaken in a community setting (at subjects’ homes).POPULATION7,864 randomly selected households throughout the Acholi Sub-Region of Northern Uganda.METHODSThis study comprised two questionnaires, the first to be completed by the head of every sampled household (n=7,864), and the second by any member of the household with major limb loss (n=181). Household locations were examined for spatial autocorrelation using Moran’sIstatistic. The χ2goodness of fit statistic was used to profile those with major limb loss in comparison with the underlying population.RESULTSWe conservatively estimate that there are c.10,117 people with major limb loss in the region who require long-term rehabilitation services (c.0.5% of the population), and c.150,512 people with disabilities other than MLL (c.8.2% of the population). People with major limb loss are spread throughout the region (as opposed to clustered in specific locations) and are disproportionately male, older and less well educated than the general population.CONCLUSIONThis research demonstrates, for the first time, the extent of the inadequacy of long-term rehabilitation services for those with major limb-loss in the study area. We provide new insight into the reasons that people are not accessing medical and rehabilitative services, and propose a way forward through the successful demonstration of an ‘outreach clinic’ model.CLINICAL REHABILITATION IMPACTThe discovery of the spatial pattern of those with major limb loss, alongside the demonstration of the clinical outreach model, provides a compelling argument for the need of more such services and associated policy frameworks in remote and rural regions in the Global South.TIDIER ChecklistWe confirm that this manuscript conforms to theSTROBE Checklist for Cross-Sectional Studies