bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene mutations in members of the PI3K/Akt signalling pathway are related to immune thrombocytopenia pathogenesis
Authors: Sun Rui-Jie , Liu Shu-yan , Zhang Xiao-mei , Zhu Jing-jing , Yuan Dai , Shan Ning-ning 
Published: November 2020

AbstractPurposeImmune thrombocytopenic (ITP) is an autoimmune bleeding disease with genetic susceptibility. In this research, we conducted an in-depth genomic analysis of a cohort of patients and elucidated the molecular features associated with the pathogenesis of ITP.MethodHigh-molecular-weight genomic DNA was extracted from freshly frozen bone marrow blood mononuclear cells (BMBMCs) from 20 active ITP patients. Next, the samples were subjected to molecular genetic analysis by whole-exome sequencing (WES), and the results were confirmed by Sanger sequencing. The signalling pathways and cellular processes associated with the mutated genes were identified with gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.ResultsThe results of this study revealed 3,998 missense mutations involving 2,269 genes in more than 10 individuals. Some unique genetic variants, including phosphatase and tensin homologue (PTEN), insulin receptor (INSR) and coagulation factor C homology (COCH) variants, were the most associated with the pathogenesis of ITP. Functional analysis revealed that these gene mutations mainly affected the phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt) signalling pathways (signal transduction) and platelet activation (immune system).ConclusionsOur findings demonstrate the functional connections between these gene variants and ITP. Although the underlying mechanisms and the impact of these genetic variants remain to be revealed through further investigation, the application of next-generation sequencing in ITP in this paper is valuable for revealing the genetic mechanisms of ITP.SummaryImmune thrombocytopenic (ITP) is an autoimmune bleeding disease with genetic susceptibility. DNA mutation profile of ITP patient bone marrow samples (n=20) were investigated by using next-generation sequencing (NGS), and then confirmed by sanger sequencing method. Our results showed PTEN, INSR and COCH were mutated in all ITP patients. Functional analysis revealed these mutation genes mainly participate PI3K/Akt signaling pathways and platelet activation. These results suggest that genetic alterations might be involved in the pathogenesis of ITP.
Mouse eradication is required to prevent local extinction of an endangered seabird on an oceanic island
Authors: Jones Christopher W. , Risi Michelle M. , Osborne Alexis M. , Ryan Peter G. , Oppel Steffen 
Published: November 2020

AbstractPetrels (Procellariidae) are a highly diverse family of seabirds, many of which are globally threatened due to the impact of invasive species on breeding populations. While predation by invasive cats and rats has led to the extinction of petrel populations, the impact of invasive house miceMus musculusis slower and less well documented. However, mice impact small burrow-nesting species such as MacGillivray’s prionPachyptila macgillivrayi,a species classified as endangered because it has been extirpated on islands in the Indian Ocean by introduced rodents. We use historic abundance data and demographic monitoring data from 2014 to 2020 to predict the population trajectory of MacGillivray’s prion on Gough Island with and without a mouse eradication using a stochastic integrated population model. Given very low annual breeding success (0.01 fledglings per breeding pair in ‘poor’ years (83%) or 0.38 in ‘good’ years (17%), n = 320 nests over 6 years) mainly due to mouse predation, our model predicted that the population collapsed from ~3.5 million pairs in 1956 to an estimated 175,000 pairs in 2020 despite reasonably high adult survival probability(ϕ= 0.901). Based on these parameters, the population is predicted to decline at a rate of 9% per year over the next 36 years without a mouse eradication, with a 31% probability that by 2057 the MacGillivray’ prion population would become extremely vulnerable to extinction. Our models predict population stability (λ = 1.01) and a lower extinction risk (<10%) if mouse eradication on Gough Island restores annual breeding success to 0.519, which is in line with that of closely-related species on predator-free islands. This study demonstrates the devastating impacts that introduced house mice can have on small burrowing petrels and highlights the urgency to eradicate invasive mammals from oceanic islands.
Streptococcus pneumoniaeserotypes carried by young children and their association with Acute Otitis Media during the period 2016 – 2019
Authors: Ekinci Esra , Desmet Stefanie , Van Heirstraeten Liesbet , Mertens Colette , Wouters Ine , Beutels Philippe , Verhaegen Jan , Malhotra-Kumar Surbhi , Theeten Heidi ,   NPcarriage group
Published: November 2020

AbstractBackgroundStreptococcus pneumoniae(Sp) is a major cause of acute otitis media (AOM). Pneumococcal conjugate vaccine (PCV) programs have altered pneumococcal serotype epidemiology in disease and carriage. To establish the clinical picture of AOM in young children exposed to the PCV program in Belgium and the Sp strains they carry, a cross-sectional study started in 2016.Material/methodsIn three collection periods from February 2016 to May 2018, nasopharyngeal swabs and background characteristics were collected from children aged 6-30 months either presenting at their physician with AOM (AOM-group) or healthy and attending day care (DCC-group). Sp was detected, quantified, and characterized using both conventional culture and qPCR. Clinical signs of AOM episodes and treatment were registered by the physicians.ResultsAmong 3264 collected samples, overall pneumococcal carriage and density were similar in AOM (79.2% and 0.50 ×106copies/μl) and DCC (77.5% and 0.42 ×106copies/μl). Non-vaccine serotypes were most frequent: 23B (AOM: 12.3%; DCC: 17.4%), 11A (AOM: 7.5%; DCC: 7.4%) and 15B (AOM: 7.5%; DCC: 7.1%). Serotypes 3, 6C, 7B, 9N, 12F, 17F and 29 were more frequent in AOM than in DCC, whereas 23A and 23B frequencies were lower. Antibiotic susceptibility of Sp strains was similar in both groups . No predictors of AOM severity were identified, and 77.3% received an antibiotic prescription.ConclusionYoung children with AOM did not carry Sp more frequently or at higher load than healthy children in day care, but some ST were more frequent in AOM and are not included in the currently used vaccines.
Combined polygenic risk scores of different psychiatric traits predict general and specific psychopathology in childhood
Authors: Neumann Alexander , Jolicoeur-Martineau Alexia , Szekely Eszter , Sallis Hannah M. , O’Donnel Kieran , Greenwood Celia M.T. , Levitan Robert , Meaney Michael J. , Wazana Ashley , Evans Jonathan , Tiemeier Henning 
Published: November 2020

ABSTRACTBackgroundPolygenic risk scores (PRSs) operationalize genetic propensity towards a particular mental disorder and hold promise as early predictors of psychopathology, but before a PRS can be used clinically, explanatory power must be increased and the specificity for a psychiatric domain established. To enable early detection it is crucial to study these psychometric properties in childhood. We examined whether PRSs associate more with general or with specific psychopathology in school-aged children. Additionally, we tested whether psychiatric PRSs can be combined into a multi-PRS score for improved performance.MethodsWe computed 16 PRSs based on GWASs of psychiatric phenotypes, but also neuroticism and cognitive ability, in mostly adult populations. Study participants were 9247 school-aged children from three population-based cohorts of the DREAM-BIG consortium: ALSPAC (UK), The Generation R Study (Netherlands) and MAVAN (Canada). We associated each PRS with general and specific psychopathology factors, derived from a bifactor model based on self-, parental-, teacher-, and observer reports. After fitting each PRS in separate models, we also tested a multi-PRS model, in which all PRSs are entered simultaneously as predictors of the general psychopathology factor.ResultsSeven PRSs were associated with the general psychopathology factor after multiple testing adjustment, two with specific externalizing and five with specific internalizing psychopathology. PRSs predicted general psychopathology independently of each other, with the exception of depression and depressive symptom PRSs. Most PRSs associated with a specific psychopathology domain, were also associated with general child psychopathology.ConclusionsThe results suggest that PRSs based on current GWASs of psychiatric phenotypes tend to be associated with general psychopathology, or both general and specific psychiatric domains, but not with one specific psychopathology domain only. Furthermore, PRSs can be combined to improve predictive ability. PRS users should therefore be conscious of non-specificity and consider using multiple PRSs simultaneously, when predicting psychiatric disorders.
Biochemical and Biophysical Characterization of the dsDNA packaging motor from theLactococcus lactisbacteriophage asccphi28
Authors: Reyes-Aldrete Emilio , Dill Erik A. , Bussetta Cecile , Szymanski Michal R. , Diemer Geoffrey , Maindola Priyank , White Mark A. , Bujalowski Wlodzimierz M. , Choi Kyung H. , Morais Marc C. 
Published: November 2020

AbstractDouble-stranded DNA viruses package their genomes into pre-assembled protein procapsids. This process is driven by macromolecular motors that transiently assemble at a unique vertex of the procapsid and utilize homomeric ring ATPases to couple genome encapsidation to ATP hydrolysis. Here we describe biochemical and biophysical characterization of the packaging ATPase from Lactococcus lactis phage asccφ28. Size-exclusion chromatography, analytical ultracentrifugation, small angle x-ray scattering, and negative stain TEM indicate that the ~45 kDa protein formed a 443 kDa cylindrical assembly with a maximum dimension of ~155 Å and radius of gyration of ~54 Å. Together with the dimensions of the crystallographic asymmetric unit from preliminary X-ray diffraction experiments, these results indicate that gp11 forms a decameric D5-symmetric complex consisting of two pentameric rings related by 2-fold symmetry. Additional kinetic analysis shows that recombinantly expressed gp11 has ATPase activity comparable to that of functional ATPase rings assembled on procapsids in other genome packaging systems. Hence, gp11 forms rings in solution that likely reflect the fully assembled ATPases in active virus-bound motor complexes. Whereas ATPase functionality in other dsDNA phage packaging systems requires assembly on viral capsids, the ability to form functional rings in solution imparts gp11 with significant advantages for high resolution structural studies and rigorous biophysical/biochemical analysis.
Dissection of barrier dysfunction in organoid-derived human intestinal epithelia induced byGiardia duodenalis
Authors: Kraft Martin , Holthaus David , Krug Susanne M. , Holland Gudrun , Schulzke Joerg-Dieter , Aebischer Toni , Klotz Christian 
Published: November 2020

AbstractBackground and aimsThe protozoaGiardia duodenalisis a major cause of gastrointestinal illness worldwide, but underlying pathophysiological mechanisms remain obscure, partly due to the absence of adequate cellular models. We aimed to overcome these limitations and to recapitulate the authentic series of events in the primary human duodenal tissue by using the human organoid system.MethodsWe established a compartmentalized cellular transwell system with electrophysiological and barrier properties akin to duodenal mucosa and dissected the events leading toG. duodenalis-induced barrier breakdown by functional analysis of transcriptional, electrophysiological and tight junction components.ResultsOrganoid-derived cell layers of different donors showed a time- and parasite load-dependent leak flux indicated by collapse of epithelial barrier uponG. duodenalisinfection. Transcriptomic analysis suggested major expression changes in genes contributing to ion transport and tight junction structure. SLC12A2/NKCC1- and CFTR-dependent chloride secretion was reduced early after infection, while changes in the tight junction composition, localization and structural organization occurred later as revealed by immunofluorescence analysis and freeze fracture electron microscopy.ConclusionData suggest a previously unknown sequence of events culminating in intestinal barrier dysfunction uponG. duodenalisinfection ignited by alterations of cellular ion transport followed by breakdown of the tight junctional complex and loss of epithelial integrity. The newly established organoid-derived model to studyG. duodenalisinfection will help enable further molecular dissection of the disease mechanism and, thus, can help to find new options treating disease and infection, in particular relevant for chronic cases of giardiasis.
UniBind: maps of high-confidence direct TF-DNA interactions across nine species
Authors: Puig Rafael Riudavets , Boddie Paul , Khan Aziz , Castro-Mondragon Jaime Abraham , Mathelier Anthony 
Published: November 2020

ABSTRACTTranscription factors (TFs) bind specifically to TF binding sites (TFBSs) at cis-regulatory regions to control transcription. Hence, it is critical to locate these TF-DNA interactions to understand transcriptional regulation. The availability of datasets generated by chromatin immunoprecipitation followed by sequencing (ChIP-seq) empowers our efforts to predict the specific locations of TFBSs with greater confidence than previously possible by fusing computational and experimental approaches. In this work, we processed ~10,000 public ChIP-seq datasets from nine species to provide high-quality TFBS predictions. After quality control, it culminated with the prediction of ~56 million TFBSs with experimental and computational evidence for direct TF-DNA interactions for 644 TFs in >1,000 cell lines and tissues. These TFBSs were used to predict >198,000 cis-regulatory modules representing clusters of binding events in the corresponding genomes. The high-quality of the TFBSs was reinforced by their evolutionary conservation, enrichment at active cis-regulatory regions, and capacity to predict combinatorial binding of TFs. Further, we confirmed that the cell type and tissue specificity of enhancer activity was correlated with the number of TFs with binding sites predicted in these regions. All the data is provided to the community through the UniBind database that can be accessed through its web-interface (https://unibind.uio.no/), a dedicated RESTful API, and as genomic tracks. Finally, we provide an enrichment tool, available as a web-service and an R package, for users to find TFs with enriched TFBSs in a set of provided genomic regions. UniBind is the first resource of its kind, providing the largest collection of high-confidence direct TF-DNA interactions in nine species.
The proteomic landscape of resting and activated CD4+ T cells reveal insights into cell differentiation and function
Authors: Subbannayya Yashwanth , Haug Markus , Pinto Sneha M. , Mohanty Varshasnata , Meås Hany Zakaria , Flo Trude Helen , Prasad T.S. Keshava , Kandasamy Richard K. 
Published: November 2020

AbstractCD4+ T cells (T helper cells) are cytokine-producing adaptive immune cells that activate or regulate the responses of various immune cells. The activation and functional status of CD4+ T cells is important for adequate responses to pathogen infections but has also been associated with auto-immune disorders and survival in several cancers. In the current study, we carried out a label-free high-resolution FTMS-based proteomic profiling of resting and T cell receptor-activated (72h) primary human CD4+ T cells from peripheral blood of healthy donors as well as SUP-T1 cells. We identified 5,237 proteins, of which significant alterations in the levels of 1,119 proteins were observed between resting and activated CD4+ T cells. We confirmed several known T-cell activation-related processes such as IL-2 response, metabolic and signaling changes, cell cycle induction, differentiation into effector cells among others. Several stimulatory/inhibitory immune checkpoint markers were altered considerably between resting and activated CD4+ T cells. Network analysis identified several known regulatory hubs of CD4+ T cell activation, including IFNG, IRF1, FOXP3, AURKA, and novel hubs such as RIOK2. Comparison of primary CD4+ T cell proteomic profiles with human lymphoblastic cell lines revealed a substantial overlap, while comparison with mouse CD+ T cell data suggested interspecies proteomic differences.
HIV-induced membraneless organelles orchestrate post-nuclear entry steps
Authors: Scoca Viviana , Morin Renaud , Collard Maxence , Tinevez Jean-Yves , Di Nunzio Francesca 
Published: November 2020

AbstractHIV integration occurs in chromatin sites that favor the release of high levels of viral progeny, alternatively the virus is also able to discreetly coexist with the host. The viral infection perturbs the cellular environment inducing the remodeling of the nuclear landscape. Indeed, HIV-1 triggers the nuclear clustering of the host factor CPSF6, but the underlying mechanism is poorly understood. Our data indicate that HIV usurps a recently discovered biological phenomenon, called liquid-liquid phase separation (LLPS), to hijack the host cell. We observed CPSF6 clusters as part of HIV-induced membraneless organelles (HIV-1 MLOs) in macrophages, which are one of the main HIV target cells. We describe that HIV-1 MLOs follow phase separation rules and represent functional biomolecular condensates. We highlight HIV-1 MLOs as hubs of nuclear reverse transcription, while the double stranded viral DNA, once formed, rapidly migrates outside these structures. Transcription-competent proviruses localize outside, but near HIV-1 MLOs, in LEDGF-abundant regions, known to be active chromatin sites. Therefore, HIV-1 MLOs orchestrate viral events prior to the integration step and create a favorable environment for the viral replication. This study uncovers single functional host-viral complexes in their nuclear landscape, which is markedly restructured by HIV-1.
New Measures of Visual Scanning Efficiency and Cognitive Effort
Authors: Lv Zezhong , Xu Qing , Schoeffmann Klaus , Parkinson Simon 
Published: November 2020

AbstractVisual scanning plays an important role in sampling visual information from the surrounding environments for a lot of everyday sensorimotor tasks, such as walking and car driving. In this paper, we consider the problem of visual scanning mechanism underpinning sensorimotor tasks in3Ddynamic environments. We exploit the use of eye tracking data as a behaviometric, for indicating the visuo-motor behavioral measures in the context of virtual driving. A new metric of visual scanning efficiency (VSE), which is defined as a mathematical divergence between a fixation distribution and a distribution of optical flows induced by fixations, is proposed by making use of a widely-known information theoretic tool, namely the square root ofJensen-Shannon divergence. Based on the proposed efficiency metric, a cognitive effort measure (CEM) is developed by using the concept of quantity of information. Psychophysical eye tracking studies, in virtual reality based driving, are conducted to reveal that the new metric of visual scanning efficiency can be employed very well as a proxy evaluation for driving performance. In addition, the effectiveness of the proposed cognitive effort measure is demonstrated by a strong correlation between this measure and pupil size change. These results suggest that the exploitation of eye tracking data provides an effective behaviometric for sensorimotor activity.
Training with audio and video games improves audiospatial performance in a “cocktail-party” task: A controlled intervention study in young adults
Authors: Schuchert Jonathan Barend , Lewald Jörg 
Published: November 2020

AbstractComputer game playing has been suggested to be an effective training to enhance perceptual and cognitive abilities. Focusing on potential improvements in auditory selective spatial attention induced by computer gaming, we compared a passive waiting-control group with two gaming groups, playing either a first-person audio-only action game requiring spatial attention and sound localization or a platform side-scroller video game without audiospatial components, which has been shown to improve cognitive performance in previous studies. Prior to and immediately after game training for 1 month for at least 30 min per day (total training time ≥15 h), healthy young adults were tested in an audiospatial task simulating a “cocktail-party” situation with multiple speakers at different positions. The proportion of correct target localizations was significantly increased after audio and video gaming compared with the control group. However, there were no significant differences between gaming groups, with similarly strong effects of action audio game and non-action video game trainings on auditory selective spatial attention. Thus, it seems as if successful training of “cocktail-party” listening can be induced not only by modality-specific near-transfer learning within the audiospatial domain, but also by far transfer of trained cognitive skills across sensory modalities, which may enhance domain-general processes supporting selective attention.
A large panel of chicken cells are invadedin vivobySalmonellaTyphimurium even when depleted of all known invasion factors
Authors: Roche S. M. , Holbert S. , Le Vern Y. , Rossignol C. , Rossignol A. , Velge P. , Virlogeux-Payant I. 
Published: November 2020

AbstractPoultry are the main source of human infection bySalmonella. As infected poultry are asymptomatic, the identification of infected poultry farms is difficult. Controlling animal infections is thus of primary importance. As cell tropism is known to govern disease, our aim was therefore to identify the infected host-cell types in chicks and the role of the three known invasion factors in this process (T3SS-1, Rck and PagN). Chicks were inoculated with wild-type or isogenic fluorescentSalmonellaTyphimurium mutants via the intraperitoneal route. Our results show that liver, spleen, gall bladder and aortic vessels could befociof infection and that phagocytic and non-phagocytic cells, including immune, epithelial and endothelial cells, are invadedin vivoin each organ. Moreover, a mutant defective for the T3SS-1, Rck and PagN remained able to colonize organs as the wild-type strain and invaded non-phagocytic cells in each organ studied. As the infection of gall bladder was not really described in chicks, invasion of gall bladder cells was confirmed by immunohistochemistry and infection was shown to last several weeks after inoculation of chicks. All together, these findings provide new insights into the dynamics ofSalmonellaspreadin vivoin chicks at the organ and cellular levels.