bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex-biased gene expression and recent sex chromosome turnover
Authors: Lichilín Nicolás , El Taher Athimed , Böhne Astrid 
Published: July 2021

Cichlids are well known for their propensity to radiate generating arrays of morphologically and ecologically diverse species in short evolutionary time. Following this rapid evolutionary pace, cichlids show high rates of sex chromosome turnover. We here studied the evolution of sex-biased gene (SBG) expression in 14 recently diverged taxa of the Lake Tanganyika Tropheini cichlids, which show different XY sex chromosomes. Across species, sex chromosome sequence divergence predates divergence in expression between the sexes. Only one sex chromosome, the oldest, showed signs of demasculinization in gene expression and potentially contribution to the resolution of sexual conflict. SBGs in general showed high rates of turnovers and evolved mostly under drift. Sexual selection did not shape the rapid evolutionary changes of SBGs. Male-biased genes evolved faster than female-biased genes, which seem to be under more phylogenetic constraint. We found a relationship between the degree of sex bias and sequence evolution driven by sequence differences among the sexes. Consistent with other species, strong sex bias towards sex-limited expression contributes to resolving sexual conflict in cichlids.This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part II)’.
The avian W chromosome is a refugium for endogenous retroviruses with likely effects on female-biased mutational load and genetic incompatibilities
Authors: Peona Valentina , Palacios-Gimenez Octavio M. , Blommaert Julie , Liu Jing , Haryoko Tri , Jønsson Knud A. , Irestedt Martin , Zhou Qi , Jern Patric , Suh Alexander 
Published: July 2021

It is a broadly observed pattern that the non-recombining regions of sex-limited chromosomes (Y and W) accumulate more repeats than the rest of the genome, even in species like birds with a low genome-wide repeat content. Here, we show that in birds with highly heteromorphic sex chromosomes, the W chromosome has a transposable element (TE) density of greater than 55% compared to the genome-wide density of less than 10%, and contains over half of all full-length (thus potentially active) endogenous retroviruses (ERVs) of the entire genome. Using RNA-seq and protein mass spectrometry data, we were able to detect signatures of female-specific ERV expression. We hypothesize that the avian W chromosome acts as a refugium for active ERVs, probably leading to female-biased mutational load that may influence female physiology similar to the ‘toxic-Y’ effect inDrosophilamales. Furthermore, Haldane's rule predicts that the heterogametic sex has reduced fertility in hybrids. We propose that the excess of W-linked active ERVs over the rest of the genome may be an additional explanatory variable for Haldane's rule, with consequences for genetic incompatibilities between species through TE/repressor mismatches in hybrids. Together, our results suggest that the sequence content of female-specific W chromosomes can have effects far beyond sex determination and gene dosage.This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part II)’.
Characterization of A Novel Autoimmune Encephalitis Associated Antibody against CRMP2
Authors: Xu Kaibiao , Wang Dongmei , He Yan , Wang Shengnan , Liu Guanghui , Pan Yue , Jiang Haishan , Peng Yu , Xiao Fenliang , Huang Yihua , Wang Qiqi , Wu Yongming , Pan Suyue , Hu Yafang 
Published: July 2021

ABSTRACTObjectiveAutoimmune encephalitis (AE) is a large category disorder urging antibody characterization. The aim was to identify a novel AE related autoantibody targeting an intracellular synaptic protein.MethodsSuspected AE patients had negative conventional antibodies screening but strong immunolabel signals on rat brain sections with the serum and cerebrospinal fluid (CSF) samples were considered burdening unkown antibody. Immunoprecipitation from the rat brain protein lysate followed by mass spectrometry analysis was used to identify the targeting antigen. Western blotting and/or cell-based assay (CBA) with antigen-overexpressing HEK293T cells were used for antibody specificity, epitope and IgG subtype determination. Patients with similar immunostaining pattern on rat brain sections were retrospectively screened for the antibody.ResultsThe antibody against collapsin response mediator protein 2 (CRMP2), a synaptic protein involved in axon guidance, was identified in a patient with suspected AE. The patient samples reactivated with HEK293T cell overexpressed CRMP2, rather than CRMP1, 3, 4, and 5. The patient samples mainly stained neuronal cytoplasm of the cortex, hippocampus and cerebellum Purkinje cells. This reactivity was eliminated by pre-immunoabsorption with CRMP2-overexpressing HEK293T cells. CRMP2 truncation experiments indicated that 536 amino acids at C-terminus was necessary for the epitope. Subtype analysis showed that anti-CRMP2 antibody was IgG4. Moreover, screening from 19 suspected AE patients led to identification of anti-CRMP2 antibody in another patient with a diagnosis of encephalomyelitis. The two patients responded to immunotherapy.ConclusionsThis study discovered a novel anti-CRMP2 antibody associated with AE. Testing of the antibody might be promising for AE diagnosis and treatment.
A Wastewater-Based Epidemic Model for SARS-CoV-2 with Application to Three Canadian Cities
Authors: Nourbakhsh Shokoofeh , Fazil Aamir , Li Michael , Mangat Chand S. , Peterson Shelley W. , Daigle Jade , Langner Stacie , Shurgold Jayson , D’Aoust Patrick , Delatolla Robert , Mercier Elizabeth , Pang Xiaoli , Lee Bonita E. , Stuart Rebecca , Wijayasri Shinthuja , Champredon David 
Published: July 2021

1AbstractThe COVID-19 pandemic has stimulated wastewater-based surveillance, allowing public health to track the epidemic by monitoring the concentration of the genetic fingerprints of SARS-CoV-2 shed in wastewater by infected individuals. Wastewater-based surveillance for COVID-19 is still in its infancy. In particular, the quantitative link between clinical cases observed through traditional surveillance and the signals from viral concentrations in wastewater is still developing and hampers interpretation of the data and actionable public-health decisions.We present a modelling framework that includes both SARS-CoV-2 transmission at the population level and the fate of SARS-CoV-2 RNA particles in the sewage system after faecal shedding by infected persons in the population.Using our mechanistic representation of the combined clinical/wastewater system, we perform exploratory simulations to quantify the effect of surveillance effectiveness, public-health interventions and vaccination on the discordance between clinical and wastewater signals. We also apply our model to surveillance data from three Canadian cities to provide wastewater-informed estimates for the actual prevalence, the effective reproduction number and incidence forecasts. We find that wastewater-based surveillance, paired with this model, can complement clinical surveillance by supporting the estimation of key epidemiological metrics and hence better triangulate the state of an epidemic using this alternative data source.
Characterization of SARS-CoV-2 Genetic Material in Wastewater
Authors: Robinson Carolyn A , Hsieh Hsin-Yeh , Hsu Shu-Yu , Wang Yang , Salcedo Braxton T , Klutts Jessica , Zemmer Sally , Belenchia Anthony , Reynolds Melissa , Semkiw Elizabeth , Foley Trevor , Wan XiuFeng , Wieberg Chris G. , Wenzel Jeff , Lin Chung-Ho , Johnson Marc C 
Published: July 2021

ABSTRACTSARS-CoV-2 genetic material has been detected in raw wastewater around the world throughout the COVID-19 pandemic and has served as a useful tool for monitoring community levels of SARS-CoV-2 infections. SARS-CoV-2 genetic material is highly detectable in a patient’s feces and the household wastewater for several days before and after a positive COVID-19 qPCR test from throat or sputum samples. Here, we characterize genetic material collected from raw wastewater samples and determine recovery efficiency during a concentration process. We find that pasteurization of raw wastewater samples did not reduce SARS-CoV-2 signal if RNA is extracted immediately after pasteurization. On the contrary, we find that signal decreased by approximately half when RNA was extracted 24-36 hours post-pasteurization and ∼90% when freeze-thawed prior to concentration. As a matrix control, we use an engineered enveloped RNA virus. Surprisingly, after concentration, the recovery of SARS-CoV-2 signal is consistently higher than the recovery of the control virus leading us to question the nature of the SARS-CoV-2 genetic material detected in wastewater. We see no significant difference in signal after different 24-hour temperature changes; however, treatment with detergent decreases signal ∼100-fold. Furthermore, the density of the samples is comparable to enveloped retrovirus particles, yet, interestingly, when raw wastewater samples were used to inoculate cells, no cytopathic effects were seen indicating that wastewater samples do not contain infectious SARS-CoV-2. Together, this suggests that wastewater contains fully intact enveloped particles.
Expanding the genotype and phenotype spectrum of SYT1-associated neurodevelopmental disorder
Authors: Melland Holly , Bumbak Fabian , Kolesnik-Taylor Anna , Ng-Cordell Elise , John Abinayah , Constantinou Panayiotis , Joss Shelagh , Larsen Martin , Fagerberg Christina , Thies Jenny , Emslie Frances , Willemsen Marjolein , Kleefstra Tjitske , Pfundt Rolf , Barrick Rebekah , Chang Richard , Loong Lucy , Alfadhel Majid , van der Smagt Jasper , Nizon Mathilde , Kurian Manju , Scott Daniel J , Ziarek Joshua J , Gordon Sarah , Baker Kate 
Published: July 2021

AbstractPurposeSynaptotagmin-1 (SYT1) is a critical mediator of neurotransmitter release in the central nervous system. Previously reported missense SYT1 variants in the C2B domain are associated with severe intellectual disability, movement disorders, behavioural disturbance and EEG abnormalities. Here, we expand the genotypes and phenotypes and identify discriminating features of this disorder.MethodsWe describe 22 individuals with 15 de novo missense SYT1 variants. Evidence for pathogenicity is discussed, including ACMG criteria, known structure-function relationships, and molecular dynamics simulations. Quantitative behavioural data for 14 cases are compared to other monogenic neurodevelopmental disorders.ResultsFour variants lie in the C2A domain with the remainder in the C2B. We classify 6 variants as pathogenic, 4 as likely pathogenic, and 5 as variants of uncertain significance. Prevalent clinical phenotypes include delayed developmental milestones, ophthalmic problems, abnormal EEG, movement disorders and sleep disturbance. Discriminating behavioural characteristics were severity of motor and communication impairment, presence of motor stereotypies and mood instability.ConclusionSYT1 variants associated with neurodevelopmental disorder extend beyond previously reported regions, and the phenotypic spectrum encompasses a broader range of severity than initially reported. This work guides diagnosis and molecular understanding of this rare neurodevelopmental disorder, and highlights a key role for SYT1 function in emotional regulation, motor control and emergent cognitive function.
The effect of transcranial direct current stimulation (tDCS) combined with cognitive training on EEG spectral power in adolescent boys with ADHD: a double-blind, randomised, sham-controlled trial
Authors: Westwood Samuel J. , Bozhilova Natali , Criaud Marion , Lam Sheut-Ling , Lukito Steve , Wallace-Hanlon Sophie , Kowalczyk Olivia S. , Kostara Afroditi , Mathew Joseph , Wexler Bruce E. , Kadosh Roi Cohen , Asherson Philip , Rubia Katya 
Published: July 2021

ABSTRACTTranscranial direct current stimulation (tDCS) is a possible neurotherapeutic alternative to psychostimulants in Attention-Deficit/Hyperactivity Disorder (ADHD). However, very little is known regarding the mechanisms of action of tDCS in children and adolescents with ADHD. We conducted the first multi-session, sham-controlled study of anodal tDCS over right inferior frontal cortex (rIFC), a consistently under-functioning region in ADHD, combined with cognitive training (CT) in 50 children/adolescents with ADHD. This study investigated the underlying mechanisms of action on resting and Go/No-Go Task-based QEEG measures in a subgroup of 23 participants with ADHD (n, sham=10; anodal tDCS=13). We found no significant sham versus anodal tDCS group differences in QEEG spectral power during rest and Go/No-Go Task performance, no correlation between the QEEG and Go/No-Go Task performance, and no effect on clinical and cognitive outcome measures. These findings extend the null clinical or cognitive effects in our whole sample of 50 children/adolescents with ADHD. Our findings do not indicate multi-session anodal tDCS with CT over rIFC as a treatment for children/adolescents with ADHD. Larger RCTs should explore different protocols titrated to the individual and using comprehensive measures to assess cognitive, clinical, and neural effects of tDCS and its underlying mechanisms of action in ADHD.
Widespread germline genetic heterogeneity of human ribosomal RNA genes
Authors: Fan Wenjun , Eklund Eetu , Sherman Rachel M. , Liu Hester , Pitts Stephanie , Ford Brittany , Rajeshkumar NV , Laiho Marikki 
Published: July 2021

AbstractPolymorphism drives survival under stress and provides adaptability. Genetic polymorphism of ribosomal RNA (rRNA) genes derives from internal repeat variation of this multicopy gene, and from interindividual variation. A considerable amount of rRNA sequence heterogeneity has been proposed but has been challenging to estimate given the scarcity of accurate reference sequences. We identified four rDNA copies on chromosome 21 (GRCh38) with 99% similarity to recently introduced reference sequence KY962518.1. Pairwise alignment of the rRNA coding sequences of these copies showed differences in sequence and length. We customized a GATK bioinformatics pipeline using the four rDNA loci, spanning a total 145 kb, for variant calling. We employed whole genome sequencing (WGS) data from the 1000 Genomes Project phase 3 and analyzed variants in 2,504 individuals from 26 populations. Using the pipeline, we identified a total of 3,790 variant positions. The variants positioned non-randomly on the rRNA gene. Invariant regions included the promoter, early 5’ ETS, 5.8S, ITS1 and certain regions of the 28S rRNA, and large areas of the intragenic spacer. 18S rRNA coding region had very few variants, while a total of 470 variant positions were observed on 28S rRNA. The majority of the 28S rRNA variants located on highly flexible human-expanded rRNA helical folds ES7L and ES27L, suggesting that these represent positions of diversity and are potentially under continuous evolution. These findings provide a genetic view for rRNA heterogeneity and raise the need to functional assess how the 28S rRNA variants affect ribosome functions.
Proton pump inhibitor use is not associated with severe COVID-19 related outcomes: A propensity score weighted analysis of a national veteran cohort
Authors: Shah Shailja C. , Halvorson Alese E. , McBay Brandon , Dorn Chad , Wilson Otis , Denton Jason , Tuteja Sony , Chang Kyong-Mi , Cho Kelly , Hauger Richard L. , Suzuki Ayako , Hunt Christine M. , Siew Edward , Matheny Michael E. , Hung Adriana , Greevy Robert A. , Roumie Christianne L. 
Published: July 2021

AbstractBackground and AimsLow pH deactivates most pathogens, including coronaviruses. Proton pump inhibitors (PPIs) are potent gastric acid suppressing medications. Whether PPI use vs non-use is associated with severe Coronavirus disease-2019 (COVID-19) outcomes remains uncertain. We aimed to compare severe COVID-19 outcomes between current outpatient PPI users and non-users.MethodsWe conducted a retrospective propensity score-weighted analysis of a national cohort of US veterans with established care who tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) through January 9, 2021, and who had 60 days of follow-up. The positive test date was the index date. Current outpatient PPI use up to and including the index date (primary exposure) was compared to non-use, defined as no PPI prescription fill in the 365 days prior to the index date. The primary outcome was a composite of use of mechanical ventilation or death within 60 days. Weighted logistic regression models evaluated severe COVID-19 outcomes between current PPI users vs non-users.ResultsOf 97,674 Veterans with SARS-CoV-2 testing, 14,958 tested positive (6262 [41.9%] current PPI users, 8696 [58.1%] non-users) and comprised the analytic cohort. After weighting, all covariates were well-balanced. In the weighted cohort, there was no difference in the primary composite outcome (8.2% vs 8.0%; OR 1.03, 95% CI 0.91-1.16), secondary composite outcome, nor individual component outcomes between current PPI users and non-users. There was no significant interaction between age and PPI use on outcomes.ConclusionAmong patients with SARS-CoV-2 infection, current PPI use vs non-use is not associated with severe COVID-19 outcomes.
Identification and functional characterisation of a rare MTTP variant underlying hereditary non-alcoholic fatty liver disease
Authors: Grove Jane I. , Kiu Lo Peggy Cho , Shrine Nick , Barwell Julian , Wain Louise V. , Tobin Martin D. , Salter Andrew M. , Bennett Neil , John Catherine , Ntalla Ioanna , Jones Gabriela E. , Neal Christopher P. , Thomas Mervyn G. , Kuht Helen , Gupta Pankaj , Vemala Vishwaraj M. , Grant Allister , Adewoye Adeolu B. , Shenoy Kotacherry T. , Balakumaran Leena K. , Hollox Edward J. , Hannan Nicholas R.F. , Aithal Guruprasad P. 
Published: July 2021

AbstractBackground and aimsNon-alcoholic fatty liver disease (NAFLD) is a complex trait that has a global prevalence estimated as 25%. We aimed to identify the genetic variant underlying a four-generation family with progressive NAFLD leading to cirrhosis, decompensation and development of hepatocellular carcinoma in the absence of common risk factors such as obesity and type 2 diabetes.MethodsExome sequencing and genome comparisons were used to identify the likely causal variant. We extensively characterised the clinical phenotype and post-prandial metabolic responses of family members with the identified novel variant in comparison to healthy non-carriers and wild type patients with NAFLD. Variant-expressing hepatocyte-like cells (HLCs) were derived from human induced pluripotent stem cells generated from homozygous donor skin fibroblasts. The phenotype was assessed using imaging, targeted RNA analysis and molecular expression arrays.ResultsWe identified a rare causal variant in MTTP, c.1691T>C p.I564T (rs745447480) encoding microsomal triglyceride transfer protein (MTP) associated with progressive non-alcoholic fatty liver disease, unrelated to metabolic syndrome. Although other described mutations in MTTP cause abetalipoproteinemia, neither homozygotes nor heterozygotes exhibited characteristic manifestations of this severe disease. HLCs derived from a homozygote donor had lower lipoprotein ApoB secretion, compared to wild type cells. Cytoplasmic triglyceride accumulation in HLCs triggered endoplasmic reticulum stress, secretion of pro-inflammatory mediators and production of reactive oxygen species.ConclusionWe have identified and characterized a rare causal variant in MTTP and homozygosity for MTTP p.I564T is associated with progressive NAFLD without any other manifestations of abetalipoproteinemia.
Willingness to receive vaccination against COVID-19: results from a large nationally representative Australian population survey
Authors: Davis Sharon R , Ampon Rosario D , Poulos Leanne M , Marks Guy B , Toelle Brett G , Reddel Helen K 
Published: July 2021

AbstractWe surveyed 10,024 Australians regarding COVID-19 vaccine willingness. Overall, 59.9% indicated yes, 13.9% no and 26.3% unsure/don’t know. Vaccine willingness was higher in males, and increased with increasing education and socioeconomic advantage. Results contrast with earlier, smaller Australian surveys regarding vaccination willingness and confirm the need for targeted vaccination information.
An ergonomic assessment tool for evaluating the effect of back exoskeletons on injury risk
Authors: Zelik Karl E. , Nurse Cameron A. , Schall Mark C. , Sesek Richard F. , Marino Matthew C. , Gallagher Sean 
Published: July 2021

ABSTRACTLow back disorders (LBDs) are a leading injury in the workplace. Back exoskeletons (exos) are wearable assist devices that complement traditional ergonomic controls and reduce LBD risks by alleviating musculoskeletal overexertion. However, there are currently no ergonomic assessment tools to evaluate risk for workers wearing back exos. Exo-LiFFT, an extension of the Lifting Fatigue Failure Tool, is introduced as a means to unify the etiology of LBDs with the biomechanical function of exos. We present multiple examples demonstrating how Exo-LiFFT can assess or predict the effect of exos on LBD risk without costly, time-consuming electromyography studies. For instance, using simulated and real-world material handling data we show an exo providing a 30 Nm lumbar moment is projected to reduce cumulative back damage by ∼70% and LBD risk by ∼20%. Exo-LiFFT provides a practical, efficient ergonomic assessment tool to assist safety professionals exploring back exos as part of a comprehensive occupational health program.HIGHLIGHTSBack exos are wearable assist devices that complement ergonomic controls for reducing low back disorder (LBD) risksHowever, no ergonomic assessment tools exist to evaluate LBD risks for workers wearing back exosWe introduce Exo-LiFFT, an ergonomic assessment tool adapted from the Lifting Fatigue Failure ToolExo-LiFFT is a practical tool that unifies the etiology of LBDs and biomechanical function of exosExo-LiFFT can be used to assess or predict the effect of exos on LBD risk without EMG testing