bluuebunny/crossref_metadata_2025_split huggingface dataset:
Helicobacter pyloriand Epstein-Barr virus coinfection stimulates the aggressiveness in gastric cancer through the regulation of gankyrin
Authors: Kashyap Dharmendra , Baral Budhadev , Varshney Nidhi , Singh Anil Kumar , Jha Hem Chandra 
Published: November 2020

AbstractPersistent coinfection ofHelicobacter pylori (H. pylori)and Epstein-Barr virus (EBV) promotes aggressive gastric carcinoma. The molecular mechanisms underlying the aggressiveness inH. pyloriand EBV coinfected gastric cancer is not well characterized. In the current study, we investigated the molecular mechanism involved in the cooperation ofH. pyloriand EBV-driven proliferation of gastric epithelial cells. Results showed that the coinfections are significantly more advantageous to the pathogens to create a microenvironment that favors the higher pathogen-associated gene expression. The EBV latent genes EBNA1 and EBNA3C are highly overexpressed in the coinfections compared to individual EBV infection at different time points (12 and 24 hrs). TheH. pylori-associated genes 16s rRNA, CagA, and BabA has also been highly overexpressed in coinfections compared toH. pylorialone. Gankyrin is a small protein of 25 KDa involved in multiple biological and physiological processes. The upregulation of gankyrin modulates the various cell signaling pathways, leading to oncogenesis. The gankyrin shows a similar expression pattern as EBNA3C at both transcript and protein levels, suggesting a possible correlation. Further EBV andH. pyloricreate microenvironments that induce cell transformation and oncogenesis by dysregulation of the cell-cycle regulator, GC marker, cell migration, DNA response, and antiapoptotic genes in infected gastric epithelial cells by enhancing the expression of gankyrin. Our study provides new insights into the molecular mechanism where the interplay between two oncogenic agents (H. pyloriand EBV) leads to the enhanced carcinogenic activity of gastric epithelial cells through overexpression of oncoprotein gankyrin.ImportanceIn the present study, we have evaluated the synergistic effect of EBV andH. pyloriinfection on gastric epithelial cells in various coinfection models. These coinfection models depict the first exposures of gastric epithelial cells with EBV and then theH. pylori.While other coinfection models narrated the first exposures ofH. pylorifollowed by the infection of EBV. This led to an enhanced oncogenic phenotype in gastric epithelial cells. We determined the coinfection of EBV andH. pylorienhanced the expression of oncogenic protein gankyrin. The interplay between EBV andH. pyloripromotes the oncogenic properties of AGS cells through the newly discovered oncoprotein gankyrin. EBV andH. pylorimediated upregulation of gankyrin further dysregulates various cancer-associated hallmarks of genes such as cell-migratory, gastric cancer marker, tumor suppressor, DNA damage response, and proapoptotic genes.
Bacterial inhibition of CD8+T-cells mediated cell death promotes neuroinvasion and within-host persistence
Authors: Maudet Claire , Kheloufi Marouane , Levallois Sylvain , Gaillard Julien , Huang Lei , Gaultier Charlotte , Tsai Yu-Huan , Disson Olivier , Lecuit Marc 
Published: November 2020

AbstractCentral nervous system infections are amongst the most severe1,2, yet the mechanisms by which pathogens access the brain remain poorly understood. The model microorganismListeria monocytogenes (Lm)is a major foodborne pathogen that causes neurolisteriosis, one of the deadliest central nervous system infections3,4. While immunosuppression is a well-established host risk factor for neurolisteriosis3,5, little is known regarding the bacterial factors underlyingLmneuroinvasion. We have developed a clinically-relevant experimental model of neurolisteriosis, using hypervirulent neuroinvasive strains6inoculated in a humanized mouse model of infection7, and we show that the bacterial protein InlB protects infected monocytes from CD8+T-cells Fas-mediated cell death, in a c-Met/PI3-kinase/FLIP-dependent manner. This blockade of anti-Lmspecific cellular immune response lengthens infected monocytes lifespan, favoringLmtransfer from infected monocytes to the brain. The intracellular niche created by InlB-mediated cell-autonomous immunosuppression also promotesLmfecal shedding, accounting for its selection as aLmcore virulence gene. Here, we have uncovered an unanticipated specific mechanism by which a bacterial pathogen confers to the cells it infects an increased lifespan by rendering them resistant to cell-mediated immunity. This promotesLmwithin-host persistence and dissemination to the central nervous system, and transmission.
Protein Cargo Assessment through Residue Alterations
Authors: Arslan Ahmed 
Published: November 2020

AbstractMotivationThe transport of proteins plays a crucial role in the cellular phenotype. Changes in the protein targeting sequence can result in missing protein delivery to the right destination and at the right time, and can disrupt various cellular pathways. Given the importance of single residue change(s) in the protein targeting sequence we developed a missing computational method.ResultsBy taking into account various protein features like conservation, protein modifications, charge, isoelectric effect and biochemical properties of peptides, the method,TransSite, assess the impact of mutations on the protein transportation. We applied this method to big human (cancer proteins) and nonhuman data, and discovered, in both cases, several phenotype related proteins harbour recurring mutations in their targeting sequences.Availabilityhttps://github.com/AhmedArslan/TransSiteContactaarslan@staford.eduSupplementary informationSupplementary data are available at#online.
Intranasal oxytocin drives coordinated social approach
Authors: Monari Patrick K. , Rieger Nathaniel S. , Schefelker Juliette , Marler Catherine A. 
Published: November 2020

AbstractCoordinated responses to challenge are essential to survival for bonded monogamous animals and may depend on behavioral compatibility. Oxytocin (OT) context-dependently regulates social affiliation and vocal communication, but its role in pair members’ decision to jointly respond to challenge is unclear. To test for OT effects, California mouse females received an intranasal dose of OT (IN-OT) or saline after bonding with males either matched or in their approach response to an aggressive vocal challenge. Pair mates were re-tested jointly for approach response, time spent together, and vocalizations. Females and males converged in their approach after pairing, but mismatched pairs with females given a single dose of IN-OT displayed a greater convergence that resulted from behavioral changes by both pair members. Unpaired females given IN-OT did not change their approach, indicating a social partner was necessary for effects to emerge. Moreover, IN-OT increased time spent approaching together, suggesting behavioral coordination beyond a further increase in bonding. This OT-induced increase in joint approach was associated with a decrease in the proportion of sustained vocalizations, a type of vocalization that can be associated with intra-pair conflict. Our results expand OT’s effects on behavioral coordination and underscore the importance of emergent social context.
Temporal dynamics of animacy categorization in the brain of patients with mild cognitive impairment
Authors: Karimi Hamed , Marefat Haniye , Khanbagi Mahdiyeh , Kalafatis Chris , Modarres Hadi , Vahabi Zahra , Khaligh-Razavi Seyed-Mahdi 
Published: November 2020

AbstractElectroencephalography (EEG) has been commonly used to measure brain alterations in Alzheimer’s Disease (AD). However, reported changes are limited to those obtained from using univariate measures, including activation level and frequency bands. To look beyond the activation level, we used multivariate pattern analysis (MVPA) to extract patterns of information from EEG responses to images in an animacy categorization task. Comparing healthy controls (HC) with patients with mild cognitive impairment (MCI), we found that the neural speed of animacy information processing is decreased in MCI patients. Moreover, we found critical time-points during which the representational pattern of animacy for MCI patients was significantly discriminable from that of HC, while the activation level remained unchanged. Together, these results suggest that the speed and pattern of animacy information processing provide clinically useful information as a potential biomarker for detecting early changes in MCI and AD patients.
Type I interferons promote germinal centers through B cell intrinsic signaling and dendritic cell dependent Th1 and Tfh cell lineages
Authors: Dahlgren Madelene W. , Plumb Adam W. , Niss Kristoffer , Lahl Katharina , Brunak Søren , Johansson-Lindbom Bengt 
Published: November 2020

AbstractType I interferons (IFNs) play an essential role in antiviral immunity, correlate with severity of systemic autoimmune disease, and are likely to represent a key component of mRNA vaccine-adjuvanticity. Relevant to all, type I IFNs can enhance germinal center (GC) B cell responses but underlying signaling pathways are incompletely understood due to pleiotropic effects in multiple cell types. Here, we demonstrate that a succinct type I IFN response promotes GC formation and associated IgG subclass distribution primarily through signaling in cDCs and B cells. Type I IFN signaling in cDCs, distinct from cDC1, stimulates development of separable Tfh and Th1 cell subsets. However, Th cell-derived IFN-γ induces T-bet expression and IgG2c isotype switching prior to this bifurcation and has no evident effects once GCs andbona fideTfh cells developed. This pathway acts in synergy with early B cell-intrinsic type I IFN signaling, which reinforces T-bet expression in B cells and leads to a selective amplification of the IgG2c+GC B cell response. Despite the strong Th1 polarizing effect of type I IFNs, the Tfh cell subset develops into IL-4 producing cells that control the overall magnitude of the GCs and promote generation of IgG1+GC B cells. Thus, type I IFNs act on B cells and cDCs to drive GC formation and to coordinate IgG subclass distribution through parallel Th1 and Tfh cell-dependent pathways.
Cellulosic wall thickenings restrict cell expansion to shape the 3D puzzle sclereids of the walnut shell
Authors: Antreich Sebastian J. , Xiao Nannan , Huss Jessica C. , Gierlinger Notburga 
Published: November 2020

AbstractWalnut (Juglans regia) kernels are protected by a tough shell consisting of polylobate sclereids that interlock into a 3D puzzle. The shape transformations from isodiametric to lobed cells is well documented for 2D pavement cells, but not for 3D puzzle sclereids. Here, we tackle the morphogenesis of these cells by using a combination of different imaging techniques. Serial face-microtomy enabled us to reconstruct tissue growth of whole walnut fruits in 3D and serial block face-scanning electron microscopy exposed cell shapes and their transformation in 3D during shell tissue development. In combination with Raman and fluorescence microscopy we revealed multiple loops of cellulosic thickenings in cell walls, acting as stiff restrictions during cell expansion and leading to the lobed cell shape. Our findings contribute to a better understanding of the 3D shape transformation of polylobate sclereids and the role of pectin and cellulose within this process.
Scalable pooled CRISPR screens with single-cell chromatin accessibility profiling
Authors: Liscovitch-Brauer Noa , Montalbano Antonino , Deng Jiale , Méndez-Mancilla Alejandro , Wessels Hans-Hermann , Moss Nicholas G. , Kung Chia-Yu , Sookdeo Akash , Guo Xinyi , Geller Evan , Jaini Suma , Smibert Peter , Sanjana Neville E. 
Published: November 2020

AbstractPooled CRISPR screens have been used to identify genes responsible for specific phenotypes and diseases, and, more recently, to connect genetic perturbations with multi-dimensional gene expression profiles. Here, we describe a method to link genome-wide chromatin accessibility to genetic perturbations in single cells. This scalable, cost-effective method combines pooled CRISPR perturbations with a single-cell combinatorial indexing assay for transposase-accessible chromatin (CRISPR-sciATAC). Using a human and mouse species-mixing experiment, we show that CRISPR-sciATAC separates single cells with a low doublet rate. Then, in human myelogenous leukemia cells, we apply CRISPR-sciATAC to target 21 chromatin-related genes that are frequently mutated in cancer and 84 subunits and cofactors of chromatin remodeling complexes, generating chromatin accessibility data for ~30,000 single cells. Using this large-scale atlas, we correlate loss of specific chromatin remodelers with changes in accessibility — globally and at the binding sites of individual transcription factors. For example, we show that loss of the H3K27 methyltransferase EZH2 leads to increased accessibility at heterochromatic regions involved in embryonic development and triggers expression of multiple genes in theHOXAandHOXDclusters. At a subset of regulatory sites, we also analyze dynamic changes in nucleosome spacing upon loss of chromatin remodelers. CRISPR-sciATAC is a high-throughput, low-cost single-cell method that can be applied broadly to study the role of genetic perturbations on chromatin in normal and disease states.
STATegra: Multi-omics data integration - A conceptual scheme and a bioinformatics pipeline
Authors: Planell Nuria , Lagani Vincenzo , Sebastian-Leon Patricia , van der Kloet Frans , Ewing Ewoud , Karathanasis Nestoras , Urdangarin Arantxa , Arozarena Imanol , Jagodic Maja , Tsamardinos Ioannis , Tarazona Sonia , Conesa Ana , Tegner Jesper , Gomez-Cabrero David 
Published: November 2020

AbstractTechnologies for profiling samples using different omics platforms have been at the forefront since the human genome project. Large-scale multi-omics data hold the promise of deciphering different regulatory layers. Yet, while there is a myriad of bioinformatics tools, each multi-omics analysis appears to start from scratch with an arbitrary decision over which tools to use and how to combine them. It is therefore an unmet need to conceptualize how to integrate such data and to implement and validate pipelines in different cases. We have designed a conceptual framework (STATegra), aiming it to be as generic as possible for multi-omics analysis, combining machine learning component analysis, non-parametric data combination and a multi-omics exploratory analysis in a step-wise manner. While in several studies we have previously combined those integrative tools, here we provide a systematic description of the STATegra framework and its validation using two TCGA case studies. For both, the Glioblastoma and the Skin Cutaneous Melanoma cases, we demonstrate an enhanced capacity to identify features in comparison to single-omics analysis. Such an integrative multi-omics analysis framework for the identification of features and components facilitates the discovery of new biology. Finally, we provide several options for applying the STATegra framework when parametric assumptions are fulfilled, and for the case when not all the samples are profiled for all omics. The STATegra framework is built using several tools, which are being integrated step-by-step as OpenSource in the STATegRa Bioconductor packagehttps://bioconductor.org/packages/release/bioc/html/STATegra.html.
Environmental DNA sampling provides new management strategies for vernal pool branchiopods in California
Authors: Kieran Shannon Rose , Hull Joshua , Finger Amanda 
Published: November 2020

ABSTRACTCalifornia’s vernal pools are declining ecosystems that support valuable native plant and animal diversity. Vernal pool branchiopods are particularly at risk from vernal pool habitat loss and conservation efforts have targeted their long-term protection through the establishment of preserves and conservation banks. These conservation strategies require repeated, perpetual monitoring of preserved habitat, which is currently carried out through dip-net surveys and visual identification of specimens. Dip-netting may be destructive and frequently requires some sacrifice of protected species. Environmental DNA offers a new, modern method to monitor many protected freshwater organisms. We designed qPCR-based species-specific assays for four of California’s vernal pool branchiopods: The Vernal Pool Fairy ShrimpBranchinecta lynchi(BRLY), the Midvalley Fairy ShrimpBranchinecta mesovallensis(BRME), and the Conservancy Fairy ShrimpBranchinecta conservatio(BRCO), and the Vernal Pool Tadpole ShrimpLepidurus packardi(LEPA). We tested these assays using eDNA sampling protocols alongside traditional dip-net surveys to assess their viability as an alternative method to monitor vernal pool branchiopods. Based on occupancy modeling, each of our assays achieved a 95% or higher detection rate when using optimized sampling protocols.
A putativeermgene is present inΔermB Clostridioides difficileisolates showing high levels of resistance to clindamycin
Authors: Ramírez-Hernández Viviana , Ramírez-Vargas Gabriel 
Published: November 2020

AbstractClostridioidesdifficile has become the leading cause of hospital-acquired diarrhea. Clindamycin is a member of the macrolide-lincosamide-streptogramin B family of protein synthesis inhibitors. Been the ribosomal methylation the most widespread mechanism of resistance to these antibiotics inC difficile ermgenes usually produce high levels of resistance to these drugs. In this short report we present evidence about the presence of an unreported putativeermgene inC difficileisolates that despite of presenting a ΔermBgenotype maintain high levels of clindamycin resistance.
Co-existence of prediction and error signals in electrophysiological responses to natural speech
Authors: Broderick Michael P. , Lalor Edmund C. 
Published: November 2020

AbstractPrior knowledge facilitates perception and allows us to interpret our sensory environment. However, the neural mechanisms underlying this process remain unclear. Theories of predictive coding propose that feedback connections between cortical levels carry predictions about upcoming sensory events whereas feedforward connections carry the error between the prediction and the sensory input. Although predictive coding has gained much ground as a viable mechanism for perception, in the context spoken language comprehension it lacks empirical support using more naturalistic stimuli. In this study, we investigated theories of predictive coding using continuous, everyday speech. EEG recordings from human participants listening to an audiobook were analysed using a 2-stage regression framework. This tested the effect of top-down linguistic information, estimated using computational language models, on the bottom-up encoding of acoustic and phonetic speech features. Our results show enhanced encoding of both semantic predictions and surprising words, based on preceding context. This suggests that signals pertaining to prediction and error units can be observed in the same electrophysiological responses to natural speech. In addition, temporal analysis of these signals reveals support for theories of predictive coding that propose that perception is first biased towards what is expected followed by what is informative.Significance StatementOver the past two decades, predictive coding has grown in popularity as an explanatory mechanism for perception. However, there has been lack of empirical support for this theory in research studying natural speech comprehension. We address this issue by developing an analysis framework that tests the effects of top-down linguistic information on the auditory encoding of continuous speech. Our results provide evidence for the co-existence of prediction and error signals and support theories of predictive coding using more naturalistic stimuli.
Whole genome sequence analysis of Shigella from Malawi identifies fluoroquinolone resistance
Authors: Stenhouse George E. , Jere Khuzwayo C. , Peno Chikondi , Bengtsson Rebecca J. , Chinyama End , Mandolo Jonathan , Cain Amy K. , Iturriza-Gómara Miren , Bar-Zeev Naor , Cunliffe Nigel A. , Cornick Jennifer , Baker Kate S. 
Published: November 2020

AbstractIncreasing antimicrobial resistance and limited alternative treatments led to fluoroquinolone resistant Shigella strain inclusion on the WHO global priority pathogens list. In this study we characterised multiple Shigella isolates from Malawi with whole genome sequence analysis, identifying the acquirable fluoroquinolone resistance determinant qnrS1.
Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion
Authors: Slováková Jana , Sikora Mateusz , Caballero-Mancebo Silvia , Krens S.F. Gabriel , Kaufmann Walter A. , Huljev Karla , Heisenberg Carl-Philipp 
Published: November 2020

AbstractTension of the actomyosin cell cortex plays a key role in determining cell-cell contact growth and size. The level of cortical tension outside of the cell-cell contact, when pulling at the contact edge, scales with the total size to which a cell-cell contact can grow1,2. Here we show in zebrafish primary germ layer progenitor cells that this monotonic relationship only applies to a narrow range of cortical tension increase, and that above a critical threshold, contact size inversely scales with cortical tension. This switch from cortical tension increasing to decreasing progenitor cell-cell contact size is caused by cortical tension promoting E-cadherin anchoring to the actomyosin cytoskeleton, thereby increasing clustering and stability of E-cadherin at the contact. Once tension-mediated E-cadherin stabilization at the contact exceeds a critical threshold level, the rate by which the contact expands in response to pulling forces from the cortex sharply drops, leading to smaller contacts at physiologically relevant timescales of contact formation. Thus, the activity of cortical tension in expanding cell-cell contact size is limited by tension stabilizing E-cadherin-actin complexes at the contact.
2019 Association of Biomolecular Resource Facilities Multi-Laboratory Data-Independent Acquisition Study
Authors: Neely Benjamin A. , Stemmer Paul M. , Searle Brian C. , Herring Laura E. , Martin LeRoy , Midha Mukul K. , Phinney Brett S. , Shan Baozhen , Palmblad Magnus , Wang Yan , Jagtap Pratik D. , Kirkpatrick Joanna 
Published: November 2020

AbstractDespite the advantages of fewer missing values by collecting fragment ion data on all analytes in the sample, as well as the potential for deeper coverage, the adoption of data-independent acquisition (DIA) in core facility settings has been slow. The Association of Biomolecular Resource Facilities conducted a large interlaboratory study to evaluate DIA performance in laboratories with various instrumentation. Participants were supplied with generic methods and a uniform set of test samples. The resulting 49 DIA datasets act as benchmarks and have utility in education and tool development. The sample set consisted of a tryptic HeLa digest spiked with high or low levels of four exogenous proteins. Data are available in MassIVE MSV000086479. Additionally, we demonstrate how the data can be analysed by focusing on two datasets using different library approaches and show the utility of select summary statistics. These data can be used by DIA newcomers, software developers, or DIA experts evaluating performance with different platforms, acquisition settings and skill levels.