bluuebunny/crossref_metadata_2025_split huggingface dataset:
ENVIRONMENTAL SAFETY EVALUATION OF THE PROTECTION AND ISOLATION SYSTEM FOR PATIENTS WITH COVID-19
Authors: Almeida Quadros Claudio , Bezerra Di Medeiros Leal Maria Carolina , Baptista Sobrinho Carlos de Almeida , Vasques Nonaka Carolina Kymie , Freitas Souza Bruno Solano de , Milan-Mattos Juliana Cristina , Catai Aparecida Maria , Pires Di Lorenzo Valéria Amorim , Ferreira Antonio Gilberto 
Published: June 2020

AbstractBackgroundSARS-CoV-2 has high transmissibility through respiratory droplets and aerosol, making COVID-19 a worldwide pandemic. In its severe form, patients progress to respiratory failure. Non-invasive mechanical ventilation restrictions and early orotracheal intubation have collapsed health systems due to insufficient intensive care unit beds and mechanical ventilators. COVID-19 dedicated healthcare professionals have high infection rates. This publication describes experimental testing of the Protection and Isolation System for Patients with COVID-19 (PISP/COVID-19).MethodPISP/COVID-19 is a disposable transparent polyethylene plastic that covers the patient’s entire hospital bed, with its internal air aspirated by the hospital’s vacuum system attached to a microparticle filter. Experiments validated PISP/COVID-19’s ability to block aerosolized microparticles dissemination. Caffeine was used as a molecular marker, with leakage evaluation through sensors analysis using nuclear magnetic resonance spectroscopy. The biological marker was synthetic SARS-CoV-2 RNA, using Reverse Transcription Polymerase Chain Reaction (RT-PCR) as the detection method.ResultsPISP/COVID-19 was effective against molecular and biological markers environmental dispersion in simulations of non-invasive ventilation, high-flow nasal cannula oxygen and mechanical ventilation isolation. Caffeine was not detected in any of the sensors positioned at points outside the PISP/COVID-19. The ability of PISP/COVID-19 to retain virus particles and protect the surrounding environment was confirmed by detection and gradients quantification of synthetic SARS-CoV-2 RNA by RT-PCR.ConclusionPISP/COVID-19 was effective in the retention of the molecular and biological markers in all tested simulations. Considering the current pandemic, PISP/COVID-19 might increase the use of non-invasive ventilation, high-flow nasal cannula oxygen and provide additional protection to healthcare professionals.
Knockdown of the E3 Ubiquitin ligase UBR5 and its role in skeletal muscle anabolism
Authors: Turner Daniel C. , Hughes David C. , Baehr Leslie M. , Seaborne Robert A. , Viggars Mark , Jarvis Jonathan C. , Gorski Piotr P. , Stewart Claire E. , Owens Daniel J. , Bodine Sue C. , Sharples Adam P. 
Published: June 2020

AbstractUBR5 is an E3-ubiquitin-ligase positively associated with anabolism, hypertrophy and recovery from atrophy in skeletal muscle. The precise mechanisms underpinning UBR5’s role in the regulation of skeletal muscle mass remain unknown. The present study aimed to elucidate these mechanisms by silencing the UBR5 genein-vitroandin-vivo. The siRNA-induced reduction (−77%) in UBR5 gene expression in human myotubes was prevented by mechanical loading, suggesting that UBR5 gene expression may be regulated via mechano-transduction signalling. Therefore, we electroporated a UBR5-RNAi plasmid into mouse tibialis anterior musclein-vivoto investigate the impact of reduced UBR5 on mechano-transduction signalling MEK/ERK/p90RSK and Akt/p70S6K/4E-BP1/rpS6 pathways. Seven days post UBR5 RNAi electroporation, while reductions in overall muscle mass were not detected, mean CSA of GFP-positive fibers was reduced (−9.5%) and the number of large fibers was lower versus the control. Importantly, UBR5-RNAi significantly reduced total RNA, muscle protein synthesis, ERK1/2 and Akt phosphorylation. Whilst p90RSK phosphorylation significantly increased, total p90RSK protein levels demonstrated a 45% reduction with UBR5-RNAi. Finally, these early signalling events after 7 days of UBR5 knockdown culminated in significant reductions in muscle mass (−4.6%) and larger reductions in fiber CSA (−18.5%) after 30 days. This was associated with increased levels of the phosphatase, PP2Ac, and inappropriate chronic elevation of p70S6K and rpS6 between 7 and 30 days, and corresponding reductions in eIF4e. This study demonstrates UBR5 plays an important role in anabolism/hypertrophy, whereby knockdown of UBR5 culminates in skeletal muscle atrophy.
Crowdsourcing assessment of maternal blood multi-omics for predicting gestational age and preterm birth
Authors: Tarca Adi L. , Pataki Bálint Ármin , Romero Roberto , Sirota Marina , Guan Yuanfang , Kutum Rintu , Gomez-Lopez Nardhy , Done Bogdan , Bhatti Gaurav , Yu Thomas , Andreoletti Gaia , Chaiworapongsa Tinnakorn ,   The DREAM Preterm Birth Prediction Challenge Consortium, Hassan Sonia S. , Hsu Chaur-Dong , Aghaeepour Nima , Stolovitzky Gustavo , Csabai Istvan , Costello James C. 
Published: June 2020

AbstractIdentification of pregnancies at risk of preterm birth (PTB), the leading cause of newborn deaths, remains challenging given the syndromic nature of the disease. We report a longitudinal multi-omics study coupled with a DREAM challenge to develop predictive models of PTB. We found that whole blood gene expression predicts ultrasound-based gestational ages in normal and complicated pregnancies (r=0.83), as well as the delivery date in normal pregnancies (r=0.86), with an accuracy comparable to ultrasound. However, unlike the latter, transcriptomic data collected at <37 weeks of gestation predicted the delivery date of one third of spontaneous (sPTB) cases within 2 weeks of the actual date. Based on samples collected before 33 weeks in asymptomatic women we found expression changes preceding preterm prelabor rupture of the membranes that were consistent across time points and cohorts, involving, among others, leukocyte-mediated immunity. Plasma proteomic random forests predicted sPTB with higher accuracy and earlier in pregnancy than whole blood transcriptomic models (e.g. AUROC=0.76 vs. AUROC=0.6 at 27-33 weeks of gestation).
Kinetic Modeling of West Nile Virus Fusion Indicates an Off-pathway State
Authors: Park Abraham , Rawle Robert J. 
Published: June 2020

AbstractWest Nile virus (WNV) is a prominent mosquito-borne flavivirus that causes febrile illness in humans. To infect host cells, WNV virions first bind to plasma membrane receptors, then initiate membrane fusion following endocytosis. The viral transmembrane E protein, triggered by endosomal pH, catalyzes fusion while undergoing a dimer-to-trimer transition. Previously, single-particle WNV fusion data was interrogated with a stochastic cellular automaton simulation, which modeled the E proteins during the fusion process. The results supported a linear fusion mechanism, with E protein trimerization being rate-limiting. Here, we present corrections to the previous simulation, and apply them to the WNV fusion data. We observe that a linear mechanism is no longer sufficient to fit the data. Instead, an off-pathway state is necessary; these results are corroborated by chemical kinetics modeling. When compared with a similar Zika virus fusion model, this suggests that off-pathway fusion mechanisms may characterize flaviviruses more broadly.
Bidirectional introgression betweenBetula tianshanicaandBetula microphyllaand its implications for conservation
Authors: Ding Junyi , Hua Donglai , Borrell James S. , Buggs Richard J.A. , Wang Luwei , Wang Feifei , Li Zheng , Wang Nian 
Published: June 2020

SummaryMolecular markers can allow us to differentiate species that occupy a morphological continuum, and detect patterns of allele sharing that can help us understand the dynamics of geographic zones where they meet.Betula microphyllais a declining wetland species in NW China that forms a continuum of leaf morphology with its relativeBetula tianshanica.We use ecological niche models (ENM) to predict the distribution ofB. microphylla, B. tianshanicaand the more commonly occurringB. platyphylla. We use restriction-site associated DNA sequencing and SSRs to resolve their genetic structure and patterns of allele sharing.ENM predicted an expansion of suitable range ofB. tianshanicaintoB. microphyllasince the Last Glacial Maximum and the contraction ofB. microphylla’srange in the future. We resolved the species identification of some intermediate morphotypes. We found signatures of bidirectional introgression betweenB. microphyllaandB. tianshanicawith SNPs showing more admixture than SSRs. Introgression fromB. microphyllaintoB. tianshanicawas greater in the Tianshan Mountains where the two species have occurred in proximity. Unexpectedly, introgression fromB. tianshanicaintoB. microphyllawas widespread in the Altay Mountains where there are no records ofB. tianshanicaoccurrence.This presence ofB. tianshanica-derivedalleles far beyond the species’ current range could be due to unexpectedly high pollen flow, undiscovered populations ofB. tianshanicain the region, incomplete lineage sorting, or selection for adaptive introgression inB. microphylla. These different interpretations have contrasting implications for the conservation ofB. microphylla.
TheDrosophilaIndividual Activity Monitoring and Detection System (DIAMonDS)
Authors: Seong Ki-Hyeon , Matsumura Taishi , Shimada-Niwa Yuko , Niwa Ryusuke , Kang Siu 
Published: June 2020

AbstractHere, we have developed DIAMonDS (DrosophilaIndividual Activity Monitoring and Detection System) comprising time-lapse imaging by a charge-coupled device (CCD) flatbed scanner and Sapphire, a novel algorithm and web application. DIAMonDS automatically and sequentially identified the transition time points of multiple life cycle events such as pupariation, eclosion, and death in individual flies at high temporal resolution and on a large scale. DIAMonDS performed simultaneous multiple scans to measure individual deaths (≤ 1,152 flies per scanner) and pupariation and eclosion timings (≤ 288 flies per scanner) under various chemical exposures, environmental conditions, and genetic backgrounds. DIAMonDS correctly identified 74–85% of the pupariation and eclosion events and ∼92% of the death events within ±10 scanning frames. This system is a powerful tool for studying the influences of genetic and environmental factors on fruit flies and efficient, high-throughput genetic and chemical screening in drug discovery.
Paternal obesity and epigenetic inheritance of breast cancer: The role of systemic effects and transmission to the second generation
Authors: Fontelles Camile C. , da Cruz Raquel Santana , Gonsiewski Alexandra K. , Barin Ersilia , Tekmen Volkan , Jin Lu , Cruz M. Idalia , Loudig Olivier , Warri Anni , de Assis Sonia 
Published: June 2020

AbstractBackgroundWhile genetics explains some familial breast cancer cases, we showed that environmentally-induced epigenetic inheritance of breast cancer can also occur in rodent models. We previously reported that paternal consumption of a high-fat diet and ensuing obesity increased breast cancer susceptibility in the offspring (F1). Nevertheless, it is still unclear whether paternal-induced programming of breast cancer in daughters is associated with systemic alterations or mammary epithelium-specific factors. It also remains to be determined whether the ancestrally programmed breast cancer predisposition in F1 progeny can be transmitted to subsequent generations.MethodsMale mice (F0) were fed either a control (CO) diet or an obesity-inducing diet (OID) for seven weeks and then mated with female mice (F0) reared on a CO diet. The resulting offspring (F1), also exclusively fed CO diet, were either used for mammary gland and tumor transplantation surgeries or to generate the F2 generation. To induce the mammary tumors, female mice were treated with 7,12 dimethylbenz[a]anthracene (DMBA). Total RNA extracted from F0 or F1 males sperm was used for small RNA-Seq analysis.ResultsMammary glands from F1 CO female offspring exhibited enhanced development when transplanted into OID females [OID(CO-MG)], as shown by higher mammary gland area, epithelial branching and elongation, compared to CO females that received a CO mammary gland [CO(CO-MG)]. Similarly, mammary tumors from F1 CO female offspring transplanted into OID females [OID(CO.T)] displayed improved growth with a higher proliferation/apoptosis rate. We also found that granddaughters (F2) from the OID grand-paternal germline showed accelerated tumor growth compared to COxCO granddaughters (F2). Transmission of breast cancer predisposition to the F2 generation through OID male germline was associated with alterations in specific sperm tRNA fragments (tRF) in both F0 and F1 males.ConclusionsOur findings indicate that systemic metabolic and mammary stromal alterations are the most significant contributors to paternal programming of mammary gland development and cancer predisposition in female offspring rather than mammary epithelium confined factors. Our data also show breast cancer predisposition in OID daughters can be transmitted to subsequent generations and could explain some familial cancers, if confirmed in humans.
Monocyte-specific changes in gene expression implicateLACTB2andPLIN2in Alzheimer’s disease
Authors: Harwood Janet C. , Leonenko Ganna , Sims Rebecca , Escott-Price Valentina , Williams Julie , Holmans Peter 
Published: June 2020

AbstractMore than 50 genetic loci have been identified as being associated with Alzheimer’s disease (AD) from genome-wide association studies (GWAS) and many of these are involved in immune pathways and lipid metabolism. Therefore, we performed a transcriptome-wide association study (TWAS) of immune-relevant cells, to study the mis-regulation of genes implicated in AD. We used expression and genetic data from naive and induced CD14+ monocytes and two GWAS of AD to study genetically controlled gene expression in monocytes at different stages of differentiation and compared the results with those from TWAS of brain and blood. We identified nine genes with statistically independent TWAS signals, seven are known AD risk genes from GWAS:BIN1, PTK2B, SPI1, MS4A4A, MS4A6E, APOEandPVRand two,LACTB2andPLIN2/ADRP, are novel candidate genes for AD. Three genes,SPI1, PLIN2andLACTB2, are TWAS significant specifically in monocytes. LACTB2 is a mitochondrial endoribonuclease and PLIN2/ADRP associates with intracellular neutral lipid storage droplets (LSDs) which have been shown to play a role in the regulation of the immune response. Notably,LACTB2andPLIN2were not detected from GWAS alone.
sPLINK: A Federated, Privacy-Preserving Tool as a Robust Alternative to Meta-Analysis in Genome-Wide Association Studies
Authors: Nasirigerdeh Reza , Torkzadehmahani Reihaneh , Matschinske Julian , Frisch Tobias , List Markus , Späth Julian , Weiß Stefan , Völker Uwe , Heider Dominik , Wenke Nina Kerstin , Kacprowski Tim , Baumbach Jan 
Published: June 2020

ABSTRACTGenome-wide association studies (GWAS) have been widely used to unravel connections between genetic variants and diseases. Larger sample sizes in GWAS can lead to discovering more associations and more accurate genetic predictors. However, sharing and combining distributed genomic data to increase the sample size is often challenging or even impossible due to privacy concerns and privacy protection laws such as the GDPR. While meta-analysis has been established as an effective approach to combine summary statistics of several GWAS, its accuracy can be attenuated in the presence of cross-study heterogeneity. Here, we presentsPLINK(safe PLINK), a user-friendly tool, which performs federated GWAS on distributed datasets while preserving the privacy of data and the accuracy of the results.sPLINKneither exchanges raw data nor does it rely on summary statistics. Instead, it performs model training in a federated manner, communicating only model parameters between cohorts and a central server. We verify that the federated results fromsPLINKare the same as those from aggregated analyses conducted withPLINK. We demonstrate thatsPLINKis robust against heterogeneous data (phenotype and confounding factors) distributions across cohorts while existing meta-analysis tools considerably lose accuracy in such scenarios. We also show thatsPLINKachieves practical runtime, in order of minutes or hours, and acceptable network bandwidth consumption for chi-square and linear/logistic regression tests. Federated analysis withsPLINK, thus, has the potential to replace meta-analysis as the gold standard for collaborative GWAS. The user-friendly, readily usablesPLINKtool is available athttps://exbio.wzw.tum.de/splink.
Ocean acidification induces subtle shifts in gene expression and DNA methylation in mantle tissue of the Eastern oyster (Crassostrea virginica)
Authors: Downey-Wall Alan M. , Cameron Louise P. , Ford Brett M. , McNally Elise M. , Venkataraman Yaamini R. , Roberts Steven B. , Ries Justin B. , Lotterhos Katie E. 
Published: June 2020

AbstractEarly evidence suggests that DNA methylation can mediate phenotypic responses of marine calcifying species to ocean acidification (OA). Few studies, however, have explicitly studied DNA methylation in calcifying tissues through time. Here, we examined the phenotypic and molecular responses in the extrapallial fluid and mantle (fluid and tissue at the calcification site) in the Eastern oyster (Crassostrea virginica) exposed to experimental OA over 80 days. Oysters were reared under three experimental pCO2treatments (‘control’, 580 μatm; ‘moderate OA’, 1000 uatm; ‘high OA’, 2800 μatm) and sampled at 6 time points (24 hours - 80 days). We found that high OA initially induced changes in the pH of the extrapallial fluid (pHEPF) relative to the external seawater, but the magnitude of this difference was highest at 9 days and diminished over time. Calcification rates were significantly lower in the high OA treatment compared to the other treatments. To explore how oysters regulate their extrapallial fluid, gene expression and DNA methylation were examined in the mantle-edge tissue of oysters from day 9 and 80 in the control and high OA treatments. Mantle tissue mounted a significant global molecular response (both in the transcriptome and methylome) to OA that shifted through time. Although we did not find individual genes that were significantly differentially expressed to OA, the pHEPFwas correlated with the eigengene expression of several co-expressed gene clusters. A small number of OA-induced differentially methylated loci were discovered, which corresponded with a weak association between OA-induced changes in genome-wide gene body DNA methylation and gene expression. Gene body methylation, however, was not significantly correlated with the eigengene expression of pHEPFcorrelated gene clusters. These results suggest that inC. virginica, OA induces a subtle response in a large number of genes, but also indicates that plasticity at the molecular level may be limited. Our study highlights the need to re-assess the plasticity of tissue-specific molecular responses in marine calcifiers, as well as the role of DNA methylation and gene expression in mediating physiological and biomineralization responses to OA.
From gas to sugar: Trehalose production inCupriavidus necatorfrom CO2and hydrogen gas
Authors: Löwe Hannes , Beentjes Marleen , Pflüger-Grau Katharina , Kremling Andreas 
Published: June 2020

AbstractThe paradigm of a fossil based, non-renewable economy will have to change in the future due to environmental concerns and the inevitable depletion of resources. Therefore, the way we produce and consume chemicals has to be rethought: The bio-economy offers such a concept for the sustainable production of commodity chemicals using waste streams or renewable electricity and CO2. Residual biomass or organic wastes can be gasified to energy rich mixtures that in turn can be used for synthesis gas fermentation.Within this scope, we present a new process for the production of trehalose from gaseous substrates with the hydrogen-oxidizing bacteriumCupriavidus necatorH16. We first show thatC. necatoris a natural producer of trehalose, accumulating up to 3.6% of its cell dry weight as trehalose when stressed with 150 mM sodium chloride. Bioinformatic investigations revealed a so far unknown mode of trehalose and glycogen metabolism in this organism. Next, we evaluated different concepts for the secretion of trehalose and found that expression of the sugar efflux transporter A (setA) fromEscherichia coliwas able to lead to a trehalose-leaky phenotype. Finally, we characterized the strain under autotrophic conditions using a H2/CO2/O2-mixture and other substrates. Even without overexpressing trehalose synthesis genes, titers of 0.47 g/L and yields of around 10% were reached, which shows the great potential of this process.Taken together, this process represents a new way to produce sugars with a higher areal efficiency than photosynthesis by crop plants. With further metabolic engineering, we anticipate an application of this technology for the renewable production of trehalose and other sugars, as well as for the synthesis of13C-labeled sugars.Graphical abstract
Pain sensitivity does not differ between obese and healthy weight individuals
Authors: Emerson Nichole M. , Nahman-Averbuch Hadas , Coghill Robert C. 
Published: June 2020

AbstractThere is emerging evidence suggesting a relationship between obesity and chronic pain. We investigated whether pain-free obese individuals display altered pain responses to acute noxious stimuli, thus raising the possibility of greater pain sensitivity and potential susceptibility for chronic pain development. Psychophysical and anthropometric data were collected from 39 individuals with an obese body mass index (BMI) classification (BMI≥30) and 40 age/sex-matched individuals of a healthy BMI (BMI<24.9). Since BMI may be an inaccurate index of obesity, additional anthropometric parameters of central adiposity, and percent body fat (BF%) were examined. Pain responses to supra-threshold noxious heat and cold stimuli were examined. Subjects provided pain intensity and unpleasantness ratings to noxious heat (49°C) applied at varying durations (5s, 12s, 30s) and locations (ventral forearm/lower leg). Cold pain ratings, thresholds, and tolerances were obtained following immersion of the hand in a cold-water bath (0-2°C). Between-group differences in pain responses, as well as relationships between pain responses and obesity parameters were examined. Importantly, confounds that may influence pain such as anxiety, depression, impulsivity, sleepiness, and quality of life were assessed. No between-group differences in pain sensitivity to noxious heat and cold stimuli were found. After controlling for sex, no relationships were found between BMI, central adiposity, or BF% and pain responses to noxious heat or cold stimuli. These results indicate that obesity, BF%, and central adiposity have little influence on pain sensitivity in obese individuals. Accordingly, it is unlikely that obesity alone increases susceptibility for chronic pain development via amplification of nociceptive processes.
An innovative approach for HLA typing, molecular tumor testing and the validation of tumor exclusive antigens
Authors: Ghosh Michael , Bichmann Leon , Scheid Jonas , Güler Gizem , Schuster Heiko , Di Marco Moreno , Marcu Ana , Beyer Meret , Nelde Annika , Freudenmann Lena K. , Mühlenbruch Lena , Löffler Markus W. , Kohlbacher Oliver , Rammensee Hans-Georg , Stevanović Stefan 
Published: June 2020

DisclaimerThis manuscript has been withdrawn by the corresponding author, as it was submitted and made public in bioRxiv without knowledge and the full consent of all the authors listed. The co-authors are therefore not responsible for the contents of this manuscript. For this reason, the submitting author has chosen to withdraw this preprint as a precautionary measure and would like to state that this work should not be cited as a reference. For any related questions that may arise, please contact the corresponding author.