bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nicotinamide restricts neural precursor proliferation to enhance catecholaminergic neuronal subtype differentiation from mouse embryonic stem cells
Authors: Griffin Síle M. , Pickard Mark R. , Hawkins Clive P. , Williams Adrian C. , Fricker Rosemary A. 
Published: May 2020

AbstractEmerging evidence indicates that a strong relationship exists between brain regenerative therapies and nutrition. Early life nutrition plays an important role during embryonic brain development, and there are clear consequences to an imbalance in nutritional factors on both the production and survival of mature neuronal populations and the infant’s risk of diseases in later life. Our research and that of others suggest that vitamins play a fundamental role in the formation of neurons and their survival. There is a growing body of evidence that nicotinamide, the water-soluble amide form of vitamin B3, is implicated in the conversion of pluripotent stem cells to clinically relevant cells for regenerative therapies. This study investigated the ability of nicotinamide to promote the development of mature catecholaminergic neuronal populations (associated with Parkinson’s disease) from mouse embryonic stem cells, as well as investigating the underlying mechanisms of nicotinamide’s action.Nicotinamide selectively enhanced the production of tyrosine hydroxylase-expressing neurons and serotonergic neurons from mouse embryonic stem cell cultures (Sox1GFP knock-in 46C cell line). A 5-Ethynyl-2’-deoxyuridine (EdU) assay ascertained that nicotinamide, when added in the initial phase, reduced cell proliferation. Nicotinamide drove tyrosine hydroxylase-expressing neuron differentiation as effectively as an established cocktail of signalling factors, reducing the proliferation of neural progenitors and accelerating neuronal maturation, neurite outgrowth and neurotransmitter expression.These novel findings show that nicotinamide enhanced and enriched catecholaminergic differentiation and inhibited cell proliferation by directing cell cycle arrest in mouse embryonic stem cell cultures, thus driving a critical neural proliferation-to-differentiation switch from neural progenitors to neurons. Further research into the role of vitamin metabolites in embryogenesis will significantly advance cell-based regenerative medicine, and help realize their role as crucial developmental signalling molecules in brain development.
Rethinking GPS Navigation: Creating Cognitive Maps Through Auditory Clues
Authors: Clemenson Gregory D. , Maselli Antonella , Fiannaca Alex , Miller Amos , Gonzalez-Franco Mar 
Published: May 2020

AbstractGPS navigation is commonplace in everyday life. While it has the capacity to make our lives easier, it is often used to automate functions that were once exclusively performed by our brain. Staying mentally active is key to healthy brain aging. Therefore, is GPS navigation causing more harm than good? Here we demonstrate that traditional turn-by-turn navigation promotes passive spatial navigation and ultimately, poor spatial learning of the surrounding environment. We propose an alternative form of GPS navigation based on sensory augmentation, that has the potential to fundamentally alter the way we navigate with GPS. By implementing a 3D spatial audio system similar to an auditory compass, users are directed towards their destination without explicit directions. Rather than being led passively through verbal directions, users are encouraged to take an active role in their own spatial navigation, leading to more accurate cognitive maps of space. Technology will always play a significant role in everyday life; however, it is important that we actively engage with the world around us. By simply rethinking the way we interact with GPS navigation, we can engage users in their own spatial navigation, leading to a better spatial understanding of the explored environment.
Pattern Separation Contributes to Categorical Face Perception
Authors: Baker Stevenson , Youm Ariana , Levy Yarden , Moscovitch Morris , Rosenbaum R. Shayna 
Published: May 2020

AbstractTraditionally considered a memory structure, the hippocampus has been shown to contribute to non-memory functions, from perception to language. Recent evidence suggests that the ability to differentiate highly confusable faces could involve pattern separation, a mnemonic process mediated by the hippocampal dentate gyrus (DG). Hippocampal involvement, however, may depend on existing face memories. To investigate these possibilities, we tested BL, a rare individual with bilateral lesions selective to the DG, and healthy controls. Both were administered morphed images of famous and nonfamous faces in a categorical perception (CP) identification and discrimination experiment. All participants exhibited nonlinear identification of famous faces with a midpoint category boundary. Controls identified newly learned nonfamous faces with lesser fidelity, while BL showed a notable shift in category boundary. When discriminating face pairs, controls showed typical CP effects of better between-category than within-category discrimination — but only for famous faces. BL showed extreme within-category “compression,” reflecting his tendency to pattern complete following suboptimal pattern separation. We provide the first evidence that pattern separation contributes to CP of faces.
Cell fate coordinates mechano-osmotic forces in intestinal crypt morphogenesis
Authors: Yang Qiutan , Xue Shi-Lei , Chan Chii Jou , Rempfler Markus , Vischi Dario , Gutierrez Francisca Mauer , Hiiragi Takashi , Hannezo Edouard , Liberali Prisca 
Published: May 2020

AbstractIntestinal organoids derived from single cells undergo complex crypt-villus patterning and morphogenesis. However, the nature and coordination of the underlying forces remains poorly characterized. Through light-sheet microscopy and mechanical perturbations, we demonstrate that organoid crypt formation coincides with stark lumen volume reduction, which works synergistically with actomyosin-generated crypt apical and villus basal tension to drive morphogenesis. We analyse these mechanical features in a quantitative 3D biophysical model and detect a critical point in actomyosin tensions, above which crypt becomes robust to volume changes. Finally, via single-cell RNA sequencing and pharmacological perturbations, we show that enterocyte-specific expressed sodium/glucose cotransporter modulates lumen volume reduction via promoting cell swelling. Altogether, our study reveals how cell fate-specific changes in osmotic and actomyosin forces coordinate robust organoid morphogenesis.One Sentence SummaryEmergence of region-specific cell fates drive actomyosin patterns and luminal osmotic changes in organoid development
Epigraph Hemagglutinin Vaccine Induces Broad Cross-reactive Immunity Against Swine H3 Influenza Virus
Authors: Bullard Brianna L. , Corder Brigette N. , Korber Bette , Weaver Eric A. 
Published: May 2020

AbstractSwine influenza virus (SIV) is a significant burden on the pork industry and threat to human health due to its zoonotic potential. Here, we utilized epigraph, a computational algorithm, to design a universal swine H3 (swH3) influenza vaccine. The epigraph hemagglutinin proteins were delivered using an Adenovirus type 5 vector and compared to a wild type hemagglutinin and the commercial inactivated vaccine, FluSure. In mice, epigraph vaccination led to significant cross-reactive antibody and T-cell responses against a diverse panel of swH3 isolates. Epigraph vaccination also reduced weight loss and lung viral titers in mice after challenge with three divergent swH3 viruses. Vaccination studies in swine, the target species for this vaccine, showed stronger levels of cross-reactive antibodies and T-cell responses after immunization with epigraph vaccine compared to the wild type and FluSure vaccines. In both murine and swine models, epigraph vaccination showed superior cross-reactive immunity that should be further investigated as a universal swH3 vaccine.
ACE2 interaction networks in COVID-19: a physiological framework for prediction of outcome in patients with cardiovascular risk factors
Authors: Wicik Zofia , Eyileten Ceren , Jakubik Daniel , Simões Sérgio N , Martins David C , Pavão Rodrigo , Siller-Matula Jolanta M. , Postula Marek 
Published: May 2020

Abstract(1)BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019; COVID-19) is associated with adverse outcomes in patients with cardiovascular disease (CVD). The aim of the study was to characterize the interaction between SARS-CoV-2 and Angiotensin-Converting Enzyme 2 (ACE2) functional networks with a focus on CVD.;(2)MethodsUsing the network medicine approach and publicly available datasets, we investigated ACE2 tissue expression and described ACE2 interaction networks which could be affected by SARS-CoV-2 infection in the heart, lungs and nervous system. We compared them with changes in ACE-2 networks following SARS-CoV-2 infection by analyzing public data of stem cell-derived cardiomyocytes (hiPSC-CMs). This analysis was performed using the NERI algorithm, which integrates protein-protein interaction with co-expression networks. We also performed miRNA-target predictions to identify which ones regulate ACE2-related networks and could play a role in the COVID19 outcome. Finally, we performed enrichment analysis for identifying the main COVID-19 risk groups.(3)ResultsWe found similar ACE2 expression confidence levels in respiratory and cardiovascular systems, supporting that heart tissue is a potential target of SARS-CoV-2. Analysis of ACE2 interaction networks in infected hiPSC-CMs identified multiple hub genes with corrupted signalling which can be responsible for cardiovascular symptoms. The most affected genes were EGFR, FN1, TP53, HSP90AA1, and APP, while the most affected interactions were associated with MAST2 and CALM1. Enrichment analysis revealed multiple diseases associated with the interaction networks of ACE2, especially cancerous diseases, obesity, hypertensive disease, Alzheimer’s disease, non-insulin-dependent diabetes mellitus, and congestive heart failure. Among affected ACE2-network components connected with SARS-Cov-2 interactome, we identified AGT, CAT, DPP4, CCL2, TFRC and CAV1, associated with cardiovascular risk factors. We described for the first time miRNAs which were common regulators of ACE2 networks and virus-related proteins in all analyzed datasets. The top miRNAs were miR-27a-3p, miR-26b-5p, miR-10b-5p, miR-302c-5p, hsa-miR-587, hsa-miR-1305, hsa-miR-200b-3p, hsa-miR-124-3p, and hsa-miR-16-5p.;(4)ConclusionOur study provides a complete mechanistic framework for investigating the ACE2 network which was validated by expression data. This framework predicted risk groups, including the established ones, thus providing reliable novel information regarding the complexity of signalling pathways affected by SARS-CoV-2. It also identified miR which could be used in personalized diagnosis in COVID-19.
Single cell analysis of the cellular heterogeneity and interactions in the injured mouse spinal cord
Authors: Milich Lindsay M , Choi James , Ryan Christine , Yahn Stephanie L , Tsoulfas Pantelis , Lee Jae K 
Published: May 2020

AbstractThe wound healing process that occurs after spinal cord injury is critical for maintaining tissue homeostasis and limiting tissue damage, but eventually results in a scar-like environment that is not conducive to regeneration and repair. A better understanding of this dichotomy is critical to developing effective therapeutics that target the appropriate pathobiology, but a major challenge has been the large cellular heterogeneity that results in immensely complex cellular interactions. In this study, we used single cell RNA sequencing to assess virtually all cell types that comprise the mouse spinal cord injury site. In addition to discovering novel subpopulations, we used expression values of receptor-ligand pairs to identify signaling pathways that potentially drive specific cellular interactions during angiogenesis, gliosis, and fibrosis. Our dataset is a valuable resource that provides novel mechanistic insight into the pathobiology of not only spinal cord injury, but also other traumatic disorders of the CNS.
Huge and variable diversity of episymbiotic CPR bacteria and DPANN archaea in groundwater ecosystems
Authors: He Christine , Keren Ray , Whittaker Michael , Farag Ibrahim F. , Doudna Jennifer , Cate Jamie H. D. , Banfield Jillian 
Published: May 2020

AbstractCandidate Phyla Radiation (CPR) bacteria and DPANN archaea are uncultivated, small-celled symbionts often detected in groundwater. However, variations in CPR/DPANN organism abundance, distribution, taxonomic diversity, and degree/nature of host association with groundwater chemistry remain understudied. Here, we performed genome-resolved metagenomic characterization of one agriculturally-impacted and seven pristine groundwater microbial communities in California, recovering 746 dereplicated CPR and DPANN genomes. Our finding of up to 31% CPR bacteria and 4% DPANN archaea in the pristine sites, which serve as local sources of drinking water, may hold health relevance, given growing awareness of the presence of CPR/DPANN organisms in human microbiomes and their association with disease. There is little species-level genome overlap across groundwater sites, indicating that CPR and DPANN communities are highly differentiated according to host populations and physicochemical conditions. Cryo-TEM imaging and genomic analyses indicate that CPR growth may be stimulated by attachment to the surface of host cells, and identified CPR and DPANN lineages with particularly prevalent and/or resilient host cell attachment. These results establish the huge but site-specific diversity of CPR bacteria and DPANN archaea coexisting with diverse hosts in groundwater aquifers, and raise important questions about potential impacts on human health.
Kidney single-cell atlas reveals myeloid heterogeneity in progression and regression of kidney disease
Authors: Conway Bryan R , O’Sullivan Eoin D , Cairns Carolynn , O’Sullivan James , Simpson Daniel J. , Salzano Angela , Connor Katie , Ding Peng , Humphries Duncan , Stewart Kevin , Teenan Oliver , Henderson Neil C , Benezech Cecile , Ramachandran Prakash , Ferenbach David , Hughes Jeremy , Chandra Tamir , Denby Laura 
Published: May 2020

AbstractThe kidney has a limited capacity to repair following injury, however, the endogenous reparative pathways are not well understood. Here we employ integrated droplet- and plate-based scRNA-seq in the murine reversible unilateral ureteric obstruction model to dissect the transcriptomic landscape at the single cell level during renal injury and resolution of fibrosis. We generate a comprehensive catalogue of the changes induced during injury and repair, revealing significant myeloid cell heterogeneity, which would not have been identifiable by conventional flow cytometry. We identify new markers for the myeloid populations within the kidney as well as identification of novel subsets including anArg1+monocyte population specific to early injury and aMmp12+macrophage subset exclusive to repair. Finally, using paired blood exchange to track circulating immune cells, we confirm that monocytes are recruited to the kidney early after injury and are the source ofCcr2+macrophages that accumulate in late injury. Our data demonstrate the utility of complementary technologies to identify novel myeloid subtypes that may represent therapeutic targets to inhibit progression or promote regression of kidney disease.
Rapid diffusion of large TatA complexes detected using single particle tracking microscopy
Authors: Varadarajan Aravindan , Oswald Felix , Lill Holger , Peterman Erwin J.G. , Bollen Yves J. M. 
Published: May 2020

AbstractThe twin-arginine translocation (Tat) system transports folded proteins across the cytoplasmic membrane of most bacteria and archaea. TatA, which contains a single membrane-spanning helix, is believed to be responsible for the actual translocation. According to the prevalent model, multiple TatA subunits form a transient protein-conducting pore, which disassembles after each translocation event. An alternative model exists, in which TatA proteins locally weaken the lipid bilayer to translocate folded proteins. Here, we imaged eGFP-fused TatA expressed from the genome in liveE. colicells. Images showed TatA occuring both in highly mobile monomers or small oligomers and in large, stable complexes that do not dissociate. Single-particle tracking revealed that large TatA complexes switch between fast and slow diffusion. The fast diffusion is too fast for a transmembrane protein complex consisting of multiple TatA monomers. In line with recent data on rhomboid proteases, we propose that TatA complexes switch between a slowly diffusing transmembrane conformation and a rapidly diffusing membrane-disrupting state that enables folded proteins to cross the membrane, in accordance with the membrane-weakening model.
Growth factor receptor signaling inhibition prevents SARS-CoV-2 replication
Authors: Klann Kevin , Bojkova Denisa , Tascher Georg , Ciesek Sandra , Münch Christian , Cinatl Jindrich 
Published: May 2020

SummarySARS-CoV-2 infections are rapidly spreading around the globe. The rapid development of therapies is of major importance. However, our lack of understanding of the molecular processes and host cell signaling events underlying SARS-CoV-2 infection hinder therapy development. We employed a SARS-CoV-2 infection system in permissible human cells to study signaling changes by phospho-proteomics. We identified viral protein phosphorylation and defined phosphorylation-driven host cell signaling changes upon infection. Growth factor receptor (GFR) signaling and downstream pathways were activated. Drug-protein network analyses revealed GFR signaling as key pathway targetable by approved drugs. Inhibition of GFR downstream signaling by five compounds prevented SARS-CoV-2 replication in cells, assessed by cytopathic effect, viral dsRNA production, and viral RNA release into the supernatant. This study describes host cell signaling events upon SARS-CoV-2 infection and reveals GFR signaling as central pathway essential for SARS-CoV-2 replication. It provides with novel strategies for COVID-19 treatment.
DNN-Assisted Statistical Analysis of a Model of Local Cortical Circuits
Authors: Zhang Yaoyu , Young Lai-Sang 
Published: May 2020

AbstractThis paper is about the use of Deep Neural Networks (DNN) to assist in the statistical analysis of a network of a few hundred integrate-and-fire neurons intended to model local circuits in the cerebral cortex. Using training data produced by direct numerical simulations, our first task was to discover, with the aid of a DNN, the mapping that yields model response for each set of parameters and input values. After evaluating the performance of the DNN surrogate both in the accuracy of its outputs and in its performance in parameter tuning, we analyzed the outputs of the well-trained DNN to gain insight into local circuits as basic cortical computational units. Because the DNN surrogate computed with vastly higher speeds than actual simulations of the neuronal network, we were able to sample large sets of parameters and input values to produce a broad statistical picture of input-output relations. One of the aims of this paper is to demonstrate that statistical analyses of this kind can provide general theoretical information on model behavior as well as suggest cortical mechanisms. Among our results are the following: Through a derivative analysis of model responses we identified a certain dichotomy in the behavior of I-neurons, leading to a characterization of high gain states which in turn offered insight into mechanisms for surround suppression. A second-derivative analysis revealed limitations of models of integrate-and-fire neurons, namely their inability to replicate the nonlinearities in gain curves observed in real neurons.Author summaryLocal circuits are basic computational units of the cerebral cortex, and statistical analysis of detailed models of such circuits will shed light on cortical computation. Because analytical tools are either overly simplistic or not applicable, systematic numerical exploration of high-dimensional parameter space is not feasible and simulation-based arguments are seldom more than heuristic, we propose in this paper a data-driven DNN-assisted approach that falls into the general framework of surrogate-based modeling. We consider as a test case a network of integrate-and-fire neurons intended to model local circuits in cortex. With the help of an accurate yet extremely efficient DNN surrogate, we reveal the statistics of model response, providing a detailed picture of model behavior. The information obtained is both general and of a fundamental nature, with direct application to neuroscience. Our results suggest that the methodology proposed can be scaled up to larger and more complex neuronal models.
Potential mechanisms of action of celastrol against rheumatoid arthritis: transcriptomic and proteomic analysis
Authors: Song Xinqiang , Dai Erqin , Zhang Yu , Du Hongtao , Wang Lei , Yang Ningning 
Published: May 2020

AbstractBackgroundThe natural triterpene celastrol exhibits potential anti-inflammatory activity in inflammatory diseases such as rheumatoid arthritis (RA).MethodsHere we explored through what proteins and processes celastrol may act in activated fibroblast-like synoviocytes (FLS) from RA patients. Differential expression of genes and proteins after celastrol treatment of FLS was examined using RNA sequencing, label-free relatively quantitative proteomics and molecular docking.ResultsExpression of 26,565 genes and 3,372 proteins was analyzed. Celastrol was associated with significant changes in genes that respond to oxidative stress and oxygen levels, as well as genes that stabilize or synthesize components of the extracellular matrix.ConclusionsThese results identify several potential mechanisms through which celastrol may inhibit inflammation in RA.