bluuebunny/crossref_metadata_2025_split huggingface dataset:
Home and work-related injuries in Makwanpur district, Nepal: a household survey
Authors: Pant Puspa Raj , Deave Toity , Banstola Amrit , Bhatta Sumiksha , Joshi Elisha , Adhikari Dhruba , Manandhar Sunil , Joshi Sunil Kumar , Mytton Julie 
Published: September 2020

AbstractObjectiveThis paper describes the epidemiology of home- and work-related injuries, their mechanisms, inequalities and costs associated with these injuries.MethodsA household survey was undertaken in three palikas (administrative areas) of Makwanpur district between April-June, 2019. Data were collected electronically on non-fatal injuries that occurred in the previous three months and fatal injuries that occurred in the previous five years.Findings17,593 individuals were surveyed from 3,327 households. The injury rate was 8.0/1000 population for home injuries and 6.4/1000 for work-related injuries; 61.0% of home injuries were among females and 69.9% of work-related injuries among males. Forty-eight percent of all home injuries were due to falls (28 males (50.9%) and 40 females (46.5%)); burn/scalds were higher among females 15 (10.5%). Cuts and piercings accounted for 40% of all work-related injuries and 36.3% were falls. Injury incidence varied by ethnic group: home injuries were highest in Brahmin (12/1000) and work-related injuries highest in Rai groups (21.0 per 1000). The total mean cost of work-related injury was US$143.3 (SD 276.7), higher than for home injuries (US$130.4, SD 347.6). The number of home (n = 74, 64.9%) and work-related (n = 67, 77.9%) injuries were higher in families below the poverty line (<US$1.9) than families in the next income bracket (US$1.9–3.2)(home: n = 22, 19.3%; work: n = 11, 12.8%).ConclusionsHome and occupational fall injuries are common. The inequalities in injury identified in our study by rurality, age, sex, income level and ethnic group can help target injury prevention interventions for vulnerable groups.What is already known on the subjectLimited epidemiological data are available in Nepal about the location of injury, activity taking place when injury occurred and the costs of injuryThere is limited information about the distribution of injuries by ethnicity and income groups.What this study addsPeople from rural areas experience more injuries than people living in urban or city areasManual workers sustain more work-related injuries than those in other occupationsCertain ethnic groups have higher rates of injuries than other ethnic groupsPeople with lower income experience more injuries than people with higher incomesInjury costs are high in relation to average per capita income.
Maximizing and evaluating the impact of test-trace-isolate programs
Authors: Grantz Kyra H. , Lee Elizabeth C. , McGowan Lucy D’Agostino , Lee Kyu Han , Metcalf C. Jessica E. , Gurley Emily S. , Lessler Justin 
Published: September 2020

AbstractSeptember 2, 2020BackgroundTest-trace-isolate programs are an essential part of COVID-19 control that offer a more targeted approach than many other non-pharmaceutical interventions. Effective use of such programs requires methods to estimate their current and anticipated impact.Methods and FindingsWe present a mathematical modeling framework to evaluate the expected reductions in the reproductive number, R, from test-trace-isolate programs. This framework is implemented in a publicly available R package and an online application. We evaluated the effects of case detection, speed of isolation, contact tracing completeness and speed of quarantine using parameters consistent with COVID-19 transmission (R0 = 2.5, generation time 6.5 days). We show that R is most sensitive to changes to the proportion of infections detected in almost all scenarios, and other metrics have a reduced impact when case detection levels are low (< 30%). Although test-trace-isolate programs can contribute substantially to reducing R, exceptional performance across all metrics is needed to bring R below one through test-trace-isolate alone, highlighting the need for comprehensive control strategies. Formally framing the dynamical process also indicates that metrics used to evaluate performance of test-trace-isolate, such as the proportion of identified infections among traced contacts, may be misleading. While estimates of program performance are sensitive to assumptions about COVID-19 natural history, our qualitative findings are robust across numerous sensitivity analyses.ConclusionsEffective test-trace-isolate programs first need to be strong in the “test” component, as case detection underlies all other program activities. Even moderately effective test-trace-isolate programs are an important tool for controlling the COVID-19 pandemic, and can alleviate the need for more restrictive social distancing measures.
Exostosin-1 Glycosyltransferase Regulates Endoplasmic Reticulum Architecture and Dynamics
Authors: Kerselidou Despoina , Dohai Bushra Saeed , Nelson David R. , Daakour Sarah , De Cock Nicolas , Kim Dae-Kyum , Olivet Julien , El Assal Diana C. , Jaiswal Ashish , Saha Deeya , Pain Charlotte , Matthijssens Filip , Lemaitre Pierre , Herfs Michael , Chapuis Julien , Ghesquiere Bart , Vertommen Didier , Kriechbaumer Verena , Knoops Kèvin , Lopez-Iglesias Carmen , van Zandvoort Marc , Lambert Jean-Charles , Hanson Julien , Desmet Christophe , Thiry Marc , Lauersen Kyle J. , Vidal Marc , Van Vlierberghe Pieter , Dequiedt Franck , Salehi-Ashtiani Kourosh , Twizere Jean-Claude 
Published: September 2020

SUMMARYThe endoplasmic reticulum (ER) is a central eukaryotic organelle with a tubular network made of hairpin proteins linked by hydrolysis of GTP nucleotides. Among post-translational modifications initiated at the ER level, glycosylation is the most common reaction. However, our understanding of the impact of glycosylation on ER structure remains unclear. Here, we show that Exostosin-1 (EXT1) glycosyltransferase, an enzyme involved inN-glycosylation, is a key regulator of ER morphology and dynamics. We have integrated multi-omics data and super-resolution imaging to characterize the broad effect of EXT1 inactivation, including ER shape-dynamics-function relationships in mammalian cells. We have observed that, inactivating EXT1 induces cell enlargement and enhances metabolic switches such as protein secretion. In particular, suppressing EXT1 in mouse thymocytes causes developmental dysfunctions associated to ER network extension. Our findings suggest that EXT1 drives glycosylation reactions involving ER structural proteins and high-energy nucleotide sugars, which might also apply to other organelles.
BrainPhys neuronal medium optimized for imaging and optogenetics in vitro
Authors: Zabolocki Michael , McCormack Kasandra , van den Hurk Mark , Milky Bridget , Shoubridge Andrew , Adams Robert , Tran Jenne , Mahadevan-Jansen Anita , Reineck Philipp , Thomas Jacob , Hutchinson Mark R , Mak Carmen , Añonuevo Adam , Harold Chew Leon , Hirst Adam J. , Lee Vivian M. , Knock Erin , Bardy Cedric 
Published: September 2020

AbstractThe capabilities of imaging technologies, fluorescent sensors, and optogenetics tools for cell biology have improved exponentially in the last ten years. At the same time, advances in cellular reprogramming and organoid engineering have quickly expanded the use of human neuronal modelsin vitro. Altogether this creates an increasing need for tissue culture conditions better adapted to live-cell imaging. Here, we identified multiple caveats of traditional media when used for live imaging and functional assays on neuronal cultures (e.g., phototoxicity, suboptimal fluorescence signals, and unphysiological neuronal activity). To overcome these issues, we developed a new neuromedium, “BrainPhys™ Imaging”, in which we adjusted fluorescent and phototoxic compounds. The new medium is based on the formulation of the original BrainPhys medium, which we designed to better support the neuronal activity of human neuronsin vitro1. We tested the new imaging-optimized formulation on human neurons cultured in monolayers or organoids, and rat primary neurons. BrainPhys Imaging enhanced fluorescence signals and reduced phototoxicity throughout the entire light spectrum. Importantly, consistent with standard BrainPhys, we showed that the new imaging medium optimally supports the electrical and synaptic activity of midbrain and human cortical neurons in culture. We also benchmarked the capacity of the new medium for functional calcium imaging and optogenetic control of human neurons. Altogether, our study shows that the new BrainPhys Imaging improves the quality of a wide range of fluorescence imaging applications with live neuronsin vitrowhile supporting cell viability and neuronal functions.
Local neuronal secretory trafficking dynamics revealed with zapERtrap: a light-inducible ER release system
Authors: Bourke Ashley M. , Schwartz Samantha L. , Bowen Aaron B. , Gutnick Amos , Schwarz Thomas L. , Kennedy Matthew J. 
Published: September 2020

SummaryFor normal synapse and circuit function, neurons must regulate the abundance and localization of transmembrane receptor, channel and adhesion proteins over vast cellular expanses, including remote sites in dendrites and axons. Whether the secretory network can support long-range trafficking of synaptic proteins synthesized in the cell body or precise trafficking of locally generated proteins at remote sites remains poorly characterized. We developed an approach for locally triggering secretory trafficking from specific subcellular domains to explore the rate, activity dependence and cargo-specificity of central and remote trafficking networks. Surprisingly, different postsynaptic proteins processed in the cell body were transported deep into dendrites, but with strikingly different kinetics, spatial distributions and activity dependencies. Proteins locally processed in dendrites were broadly dispersed prior to surface insertion, but could be directed locally to synapses. These results provide a novel interrogation of compartmentalized trafficking and reveal basic principles for protein targeting in complex cellular environments.
SNP-to-gene linking strategies reveal contributions of enhancer-related and candidate master-regulator genes to autoimmune disease
Authors: Dey Kushal K. , Gazal Steven , van de Geijn Bryce , Kim Samuel Sungil , Nasser Joseph , Engreitz Jesse M. , Price Alkes L. 
Published: September 2020

AbstractGene regulation is known to play a fundamental role in human disease, but mechanisms of regulation vary greatly across genes. Here, we explore the contributions to disease of two types of genes: genes whose regulation is driven by enhancer regions as opposed to promoter regions (enhancer-related) and genes that regulate other genes in trans (candidate master-regulator). We link these genes to SNPs using a comprehensive set of SNP-to-gene (S2G) strategies and apply stratified LD score regression to the resulting SNP annotations to draw three main conclusions about 11 autoimmune diseases and blood cell traits (average Ncase=13K across 6 autoimmune diseases, average N =443K across 5 blood cell traits). First, several characterizations of enhancer-related genes defined in blood using functional genomics data (e.g. ATAC-seq, RNA-seq, PC-HiC) are conditionally informative for autoimmune disease heritability, after conditioning on a broad set of regulatory annotations from the baseline-LD model. Second, candidate master-regulator genes defined using trans-eQTL in blood are also conditionally informative for autoimmune disease heritability. Third, integrating enhancer-related and candidate master-regulator gene sets with protein-protein interaction (PPI) network information magnified their disease signal. The resulting PPI-enhancer gene score produced >2x stronger conditional signal (maximum standardized SNP annotation effect size (τ*) = 2.0 (s.e. 0.3) vs. 0.91 (s.e. 0.21)), and >2x stronger gene-level enrichment for approved autoimmune disease drug targets (5.3x vs. 2.1x), as compared to the recently proposed Enhancer Domain Score (EDS). In each case, using functionally informed S2G strategies to link genes to SNPs that may regulate them produced much stronger disease signals (4.1x-13x larger τ* values) than conventional window-based S2G strategies. We conclude that our characterizations of enhancer-related and candidate master-regulator genes identify gene sets that are important for autoimmune disease, and that combining those gene sets with functionally informed S2G strategies enables us to identify SNP annotations in which disease heritability is concentrated.
Zinc dysregulation inslc30a8(znt8) mutant zebrafish leads to blindness and disrupts bone mineralisation
Authors: Mackay Eirinn W , Molero Sofía Ibañez , Tirathdas Lavitasha Harjani , Peterson-Maduro Josi , Zang Jingjing , Neuhauss Stephan C.F. , Schulte-Merker Stefan , Wilson Stephen W. 
Published: September 2020

AbstractZinc is an essential cofactor for many cellular processes including gene transcription, insulin secretion and retinal function. Excessive free Zn2+is highly toxic and consequently intracellular zinc is tightly controlled by a system of transporters, metallothioneins (MTs) and storage vesicles. Here we describe the developmental consequences of a missense allele of zinc efflux transporterslc30a8(znt8)in zebrafish. Homozygousslc30a8hu1798larvae are virtually blind and develop very little or no bone mineral. We show that zinc is stored in pigmented cells (melanophores) of healthy larvae but inslc30a8hu1798mutants it instead accumulates in the bone and brain. Supporting a role for pigment cells in zinc homeostasis,nacrezebrafish, which lack melanophores, also show disrupted zinc homeostasis. The photoreceptors ofslc30a8hu1798fish are severely depleted while those ofnacrefish are enriched with zinc. We propose that developing zebrafish utilise pigmented cells as a zinc storage organ, and that Slc30a8 is required for transport of zinc into these cells and into photoreceptors.
Translational profiling of mouse dopaminoceptive neurons reveals a role of PGE2 in dorsal striatum
Authors: Montalban Enrica , Giralt Albert , Taing Lieng , Nakamura Yuki , Martin Claire , de Pins Benoit , Pelosi Assunta , Goutebroze Laurence , Castell Laia , Wang Wei , Neiburga Kathrina Daila , Vestito Letizia , Nairn Angus C. , Valjent Emmanuel , Hervé Denis , Heintz Nathaniel , Le Novère Nicolas Gambardella , Greengard Paul , Roussarie Jean-Pierre , Girault Jean-Antoine 
Published: September 2020

ABSTRACTForebrain dopaminoceptive neurons play a key role in movement, action selection, motivation, and working memory. Their activity is dysregulated in addiction, Parkinson’s disease and other conditions. To characterize the diverse dopamine target neuronal populations, we compare translating mRNAs in neurons of dorsal striatum and nucleus accumbens expressing D1 or D2 dopamine receptor and prefrontal cortex expressing D1 receptor. We identify D1/D2 and striatal dorso-ventral differences in the translational and splicing landscapes, which establish the characteristics of dopaminoceptive neurons. Expression differences and network analyses identify novel transcription factors with presumptive roles in these differences. Prostaglandin E2 appears as a candidate upstream regulator in the dorsal striatum, a hypothesis supported by converging functional evidence indicating its role in enhancing D2 dopamine receptor action. Our study provides powerful resources for characterizing dopamine target neurons, new information about striatal gene expression patterns, and reveals the unforeseen role of prostaglandin E2 in the dorsal striatum.
Schizophrenia, autism spectrum disorders and developmental disorders share specific disruptive coding mutations
Authors: Rees Elliott , Creeth Hugo D. J. , Hwu Hai-Gwo , Chen Wei J. , Tsuang Ming , Glatt Stephen J. , Rey Romain , Kirov George , Walters James T. R. , Holmans Peter , Owen Michael J. , O’Donovan Michael C. 
Published: September 2020

AbstractGenes enriched for rare disruptive coding variants in schizophrenia overlap those in which disruptive mutations are associated with neurodevelopmental disorders (NDDs), particularly autism spectrum disorders and intellectual disability. However, it is unclear whether this implicates the same specific variants, or even variants with the same functional effects on shared risk genes. Here, we show thatde novomutations in schizophrenia are generally of the same functional category as those that confer risk for NDDs, and that the specificde novomutations in NDDs are enriched in schizophrenia. These findings indicate that, in part, NDDs and schizophrenia have shared molecular aetiology, and therefore likely overlapping pathophysiology. We also observe pleiotropic effects for variants known to be pathogenic for several syndromic developmental disorders, suggesting that schizophrenia should be included among the phenotypes associated with these mutations. Collectively, our findings support the hypothesis that at least some forms of schizophrenia lie within a continuum of neurodevelopmental disorders.
A feedback loop between the androgen receptor and 6-phosphogluoconate dehydrogenase (6PGD) drives prostate cancer growth
Authors: Gillis Joanna L. , Hinneh Josephine A. , Ryan Natalie , Irani Swati , Moldovan Max , Shrestha Raj , Quek Lake Ee , Hoy Andrew J. , Holst Jeff , Centenera Margaret M. , Mills Ian G. , Lynn David J. , Selth Luke A. , Butler Lisa M. 
Published: September 2020

ABSTRACTAlterations to androgen receptor (AR) signalling and cellular metabolism are hallmarks of prostate cancer. This study uncovers a novel link between AR and the pentose phosphate pathway (PPP) through 6-phosphogluoconate dehydrogenase (6PGD), an androgen-regulated gene that is upregulated in prostate cancer. Knockdown of 6PGD impairs growth and elicits death of prostate cancer cells, at least in part due to oxidative stress. Targeting 6PGD using 2 specific inhibitors, physcion and S3, was efficacious in multiple models of prostate cancer, including aggressive castration-resistant models. Importantly, S3 also suppressed proliferation of clinical patient-derived explants (PDEs). Mechanistically, 6PGD decreased expression and activity of AR in cell lines and PDEs, revealing a novel positive feedback loop between these factors. The enhanced efficacy of co-targeting AR and 6PGD further supported the biological relevance of this feedback. This work provides insight into the dysregulated metabolism of prostate cancer and supports investigation of co-targeting AR and the PPP.
A connectome-based prediction model of long-term memory
Authors: Lin Qi , Yoo Kwangsun , Shen Xilin , Constable R Todd , Chun Marvin M 
Published: September 2020

AbstractAlthough many studies have investigated the neural basis of intra-individual fluctuations in long-term memory (LTM), few have explored the differences across individuals. Here, we characterize a whole-brain functional connectivity (FC) network based on fMRI data in an n-back task that robustly predicts individual differences in LTM. Critically, although FC during the n-back task also predicted working memory (WM) performance and the two networks had some shared components, they are also largely distinct from each other: the LTM model performance remained robust when we controlled for WM and vice versa. Furthermore, regions important for LTM such as the medial temporal lobe did contribute, but only partially, to predicting LTM. These results demonstrate that individual differences in LTM are dependent on the configuration of a whole-brain functional network including but not limited to regions traditionally associated with LTM during encoding and that such a network is separable from what supports WM.
Atypical Neocortical Development in theCited2Conditional Knockout Leads to Behavioral Deficits Associated with Neurodevelopmental Disorders
Authors: Wagner Nikolaus , MacDonald Jessica L. 
Published: September 2020

AbstractThe mammalian neocortex develops from a single layer of neuroepithelial cells to form a six-layer heterogeneous mosaic of differentiated neurons and glial cells. This process requires a complex choreography of temporally and spatially restricted transcription factors and epigenetic regulators. Even subtle disruptions in this regulation can alter the way the neocortex forms and functions, leading to a neurodevelopmental disorder. One epigenetic regulator that is essential for the precise development of the neocortex is CITED2 (CBP/p300InteractingTransactivator withED-rich termini).Cited2is highly expressed by intermediate progenitor cells in the subventricular zone during the generation of the superficial layers of the neocortex. A forebrain-specific conditional knockout ofCited2(cKO) exhibits reduced proliferation of intermediate progenitor cells embryonically, leading to reduced thickness of the superficial layers and a specific reduction in the somatosensory neocortical length postnatally. Further, theCited2cKO displays decreased corpus callosum volume and dysregulation of precise neuronal connectivity within the somatosensory cortex. Here, we explore the behavioral consequences resulting from this aberrant neocortical development. We demonstrate thatCited2cKO mice display decreased maternal separation-induced ultrasonic vocalizations as neonates, and an increase in the repetitive behavior of rearing and lack of habituation following repeated acoustic startle as adults. They do not display alterations in anxiety-like behavior, overall locomotor activity or social interactions. Together with the morphological, molecular, and connectivity disruptions, these results identify theCited2cKO neocortex as an ideal system to study mechanisms underlying neurodevelopmental and neuroanatomical disruptions with relevance to human neurodevelopmental disorders.
Development of a copper-graphene nanocomposite based transparent coating with antiviral activity against influenza virus
Authors: Das Jana Indrani , Kumbhakar Partha , Banerjee Saptarshi , Gowda Chinmayee Chowde , Kedia Nandita , Kuila Saikat Kumar , Banerjee Sushanta , Das Narayan Chandra , Das Amit Kumar , Manna Indranil , Tiwary Chandra Sekhar , Mondal Arindam 
Published: September 2020

AbstractRespiratory infections by RNA viruses are one of the major burdens upon global health and economy. Viruses like influenza or coronaviruses can be transmitted through respiratory droplets or contaminated surfaces. An effective antiviral coating can decrease the viability of the virus particles in the outside environment significantly, hence reducing their transmission rate. In this work, we have screened a series of nanoparticles and their composites for antiviral activity using Nano Luciferase based highly sensitive influenza A reporter virus. Using this screening system, we have identified copper-graphene (Cu-Gr) nanocomposite shows strong antiviral activity. Extensive material and biological characterization of the nanocomposite suggested a unique metal oxide embedded graphene sheet architecture that can inactivate the virion particles only within 30 minutes of pre-incubation and subsequently interferes with the entry of these virion particles into the host cell. This ultimately results in reduced viral gene expression, replication and production of progeny virus particles, slowing down the overall pace of progression of infection. Using PVA as a capping agent, we have been able to generate a Cu-Gr nanocomposite based highly transparent coating that retains its original antiviral activity in the solid form.