bluuebunny/crossref_metadata_2025_split huggingface dataset:
German-wide interlaboratory study compares consistency, accuracy and reproducibility of whole-genome short read sequencing
Authors: Uelze Laura , Borowiak Maria , Brinks Erik , Deneke Carlus , Stingl Kerstin , Kleta Sylvia , Tausch Simon H. , Szabo Kathrin , Wöhlke Anne , Malorny Burkhard 
Published: April 2020

AbstractWe compared the consistency, accuracy and reproducibility of next-generation short read sequencing between ten laboratories involved in food safety (research institutes, state laboratories, universities and companies) from Germany and Austria. Participants were asked to sequence six DNA samples of three bacterial species (Campylobacter jejuni, Listeria monocytogenesandSalmonella enterica) in duplicate, according to their routine in-house sequencing protocol. Four different types of Illumina sequencing platforms (MiSeq, NextSeq, iSeq, NovaSeq) and one Ion Torrent sequencing instrument (S5) were involved in the study. Sequence quality parameters were determined for all data sets and centrally compared between laboratories. SNP / and cgMLST calling were performed to assess the reproducibility of sequence data collected for individual samples. Overall, we found Illumina short read data to be more accurate and consistent than Ion Torrent sequence data, with little variation between the different Illumina instruments. Two laboratories with Illumina instruments submitted sequence data with lower quality, probably due to the use of a library preparation kit, which shows difficulty in sequencing low GC genome regions. Differences in data quality were more evident after assembling short reads into genome assemblies, with Ion Torrent assemblies featuring a great number of allele differences to Illumina assemblies. Clonality of samples was confirmed through SNP calling, which proved to be a more suitable method for an integrated data analysis of Illumina and Ion Torrent data sets, than cgMLST calling.
Egg-surface bacteria deter oviposition by the oriental fruit flyBactrocera dorsalis
Authors: Li Huijing , Ren Lu , Xie Mingxue , Gao Yang , He Muyang , Hassan Babar , Lu Yongyue , Cheng Daifeng 
Published: April 2020

AbstractFinding a suitable oviposition site is a challenging task for a gravid female fly, since the hatched maggots have limited mobility, making it difficult to find an alternative host. The oriental fruit fly,Bactrocera dorsalis, oviposits on many types of fruits. Maggots hatching in a fruit that is already occupied by conspecific worms will face food competition. Here, we showed that maggot-occupied fruits deterB. dorsalisoviposition and that this deterrence is based on the increased β-caryophyllene concentration in fruits. Using a combination of bacterial identification, volatile content quantification, and behavioural analyses, we demonstrated that the egg-surface bacteria ofB. dorsalis, includingProvidencia sp. andKlebsiella sp., are responsible for this increase in the β-caryophyllene contents of host fruits. Our research shows a type of tritrophic interaction between microorganisms, insects, and insect hosts, which will provide considerable insight into the evolution of insect behavioural responses to volatile compounds.
Correlating glycoforms of DC-SIGN with stability using a combination of enzymatic digestion and ion mobility MS
Authors: Yen Hsin-Yung , Liko Idlir , Gault Joseph , Wu Di , Struwe Weston B. , Robinson Carol V. 
Published: April 2020

AbstractThe immune scavenger protein DC-SIGN interacts with glycosylated proteins and has a putative role in facilitating viral infection. How these recognition events take place with different viruses is not clear and the effects of glycosylation on the folding and stability of DC-SIGN have not been reported. Here, we develop and apply a mass spectrometry-based approach to both uncover and characterise the effects of O-glycans on the stability of DC-SIGN. We first quantify the Core 1 & 2 O-glycan structures on the carbohydrate recognition and extracellular domains of the protein via sequential exoglycosidase sequencing. We then use ion mobility mass spectrometry to show how specific O-glycans, and/or single monosaccharide substitutions, alter both the overall collision cross section and the gas-phase stability of the glycoprotein isoforms of DC-SIGN. We find that rather than the mass or length of glycoprotein modifications, the stability of DC-SIGN is better correlated with the number of glycosylation sites. Collectively, our results exemplify a combined multi-dimensional MS approach, proficient in evaluating protein stability in response to both glycoprotein macro- and micro-heterogeneity and adding structural detail to the infection enhancer DC-SIGN.
Tonic GABAergic activity facilitates dendritic calcium signaling and short-term plasticity
Authors: Chiu Chiayu Q. , Morse Thomas M. , Nani Francesca , Knoflach Frederic , Hernandez Maria-Clemencia , Jadi Monika , Higley Michael J. 
Published: April 2020

SummaryBrain activity is highly regulated by GABAergic activity, which acts via GABAARs to suppress somatic spike generation as well as dendritic synaptic integration and calcium signaling. Tonic GABAergic conductances mediated by distinct receptor subtypes can also inhibit neuronal excitability and spike output, though the consequences for dendritic calcium signaling are unclear. Here, we use 2-photon calcium imaging in cortical pyramidal neurons and computational modeling to show that low affinity GABAARs containing an α5 subunit mediate a tonic hyperpolarization of the dendritic membrane potential, resulting in deinactivation of voltage-gated calcium channels and a paradoxical boosting of action potential-evoked calcium influx. We also find that GABAergic enhancement of calcium signaling modulates short-term synaptic plasticity, augmenting depolarization-induced suppression of inhibition. These results demonstrate a novel role for GABA in the control of dendritic activity and suggest a mechanism for differential modulation of electrical and biochemical signaling.
HSV Forms an HCMV-like Viral Assembly Center in Neuronal Cells
Authors: White Shaowen , Kawano Hiroyuki , Harata N. Charles , Roller Richard J. 
Published: April 2020

AbstractHerpes simplex virus (HSV) is a neuroinvasive virus that has been used as a model organism for studying common properties of all herpesviruses. HSV induces host organelle rearrangement and forms dispersed assembly compartments in epithelial cells, which complicates the study of HSV assembly. In this study, we show that HSV forms a visually distinct unitary cytoplasmic viral assembly center (cVAC) in both cancerous and primary neuronal cells that concentrates viral structural proteins and is the site of capsid envelopment. The HSV cVAC also concentrates host membranes that are important for viral assembly, such as Golgi- and recycling endosome-derived membranes. Lastly, we show that HSV cVAC formation and/or maintenance depends on an intact microtubule network and a viral tegument protein, pUL51. Our observations suggest that the neuronal cVAC is a uniquely useful model to study common herpesvirus assembly pathways, and cell-specific pathways for membrane reorganization.SummaryThis study shows that HSV forms a viral assembly center in neuronal cells by reorganization of host membranes. This system is a novel and powerful tool to study herpesvirus assembly pathways and host cell membrane dynamics.
The SEM-4 transcription factor is required for regulation of the oxidative stress response inCaenorhabditis elegans
Authors: Rafikova Adilya , Hu Queenie , Kubiseski Terrance J. 
Published: April 2020

AbstractOxidative stress causes damage to cells by creating reactive oxygen species (ROS) and the overproduction of ROS have been linked to the onset of premature ageing. We previously found that abrap-2(BRCA1 associated protein 2) mutant significantly increases the expression of phase II detoxification enzymes inC. elegans.An RNAi suppression screen to identify transcription factors involved in the production ofgst-4mRNA inbrap-2worms identified SEM-4 as a potential candidate. Here, we show that knockdown ofsem-4suppresses the activation ofgst-4caused by the mutation inbrap-2.We also demonstrate thatsem-4 isrequired for survival upon exposure to oxidative stress and that SEM-4 is required for expression of the transcription factor SKN-1C. These findings identify a novel role for SEM-4 in ROS detoxification by regulating expression of SKN-1C and the phase II detoxification genes.Article SummaryReactive oxygen species have been implicated as a harmful agent in many age-related diseases as well as an important signaling molecule. The transcription factor SKN-1 in C. elegans is an important regulator of reactive oxygen species levels. Here we show that the transcription factor SEM-4 is required to activate the expression of skn-1c and promote phase II detoxification gene expression. These findings identify a novel role for SEM-4 in regulating reactive oxygen species levels.
Sharing of weak signals of positive selection across the genome
Authors: Harris Nathan S. , Rogers Alan R. 
Published: April 2020

AbstractSelection in humans often leaves subtle signatures at individual loci. Few studies have measured the extent to which these signals are shared among human populations. Here a new method is developed to compare weak signals of selection in aggregate across the genome using the 1000 Genomes Phase 3 Data. Results presented here show that selection producing weak selection serves to increase population differences around coding areas of the genome.
The hemolymph ofBiomphalariasnail vectors of schistosomiasis supports a diverse microbiome
Authors: Chevalier Frédéric D. , Diaz Robbie , McDew-White Marina , Anderson Timothy JC. , Le Clec’h Winka 
Published: April 2020

SUMMARYThe microbiome – the microorganism community that is found on or within an organism’s body – is increasingly recognized to shape many aspects of its host biology and is a key determinant of health and disease. Microbiomes modulate the capacity of insect disease vectors (mosquitos, tsetse flies, sandflies) to transmit parasites and disease. We investigate the diversity and abundance of microorganisms within the hemolymph (i.e.blood) ofBiomphalariasnails, the intermediate host forSchistosoma mansoni, using Illumina MiSeq sequencing of the bacterial 16S V4 rDNA. We sampled hemolymph from 5 snails from 6 different laboratory populations ofB. glabrataand one population ofB. alexandrina. We observed 279.84 ± 0.79 amplicon sequence variants (ASVs) per snail. There were significant differences in microbiome composition at the level of individual snails, snail populations and species. Snail microbiomes were dominated by Proteobacteria and Bacteroidetes while water microbiomes from snail tank were dominated by Actinobacteria. We investigated the absolute bacterial load using qPCR: hemolymph samples contained 2,784 ± 339 bacteria per μL. We speculate that the microbiome may represent a critical, but unexplored intermediary in the snail-schistosome interaction as hemolymph is in very close contact to the parasite at each step of its development.
Coronavirus surveillance of wildlife in the Lao People’s Democratic Republic detects viral RNA in rodents
Authors: McIver David J. , Silithammavong Soubanh , Theppangna Watthana , Gillis Amethyst , Douangngeun Bounlom , Khammavong Kongsy , Singhalath Sinpakone , Duong Veasna , Buchy Philippe , Olson Sarah H. , Keatts Lucy , Fine Amanda E. , Greatorex Zoe , Gilbert Martin , LeBreton Matthew , Saylors Karen , Joly Damien O. , Rubin Edward M. , Lange Christian E. 
Published: April 2020

AbstractCoronaviruses can become zoonotic as in the case of COVID-19, and hunting, sale, and consumption of wild animals in Southeast Asia facilitates an increased risk for such incidents. We sampled and tested rodents (851) and other mammals, and foundBetacoronavirusRNA in 12 rodents. The sequences belong to two separate genetic clusters, and relate closely to known rodent coronaviruses detected in the region, and distantly to human coronaviruses OC43 and HKU1. Considering close human-wildlife contact with many species in and beyond the region, a better understanding of virus diversity is urgently needed for the mitigation of future risks.
Spatio–temporal model reduces species misidentification bias of spawning eggs in stock assessment of spotted mackerel in the western North Pacific
Authors: Kanamori Yuki , Nishijima Shota , Okamura Hiroshi , Yukami Ryuji , Watai Mikio , Takasuka Akinori 
Published: April 2020

AbstractSpecies identification based on morphological characteristics includes species misidentification, leading to estimation bias of population size. The eggs of spotted mackerelScomber australicusand chub mackerelS. japonicusin the western North Pacific has been identified based on egg diameter. Recent density of spotted mackerel was considerably high despite its low stock biomass. A possibility of this phenomenon is due to overestimation because the difference in egg diameter has become ambiguous between two species. However, we cannot test this possibility using DNA analysis because the eggs are fixed with formalin. Here, we estimated the index of egg density of spotted mackerel using a spatio–temporal model that incorporates the effect of egg density of chub mackerel on the catchability of spotted mackerel, using 15 years data of spawning eggs. We then examined how retrospective biases in estimated stock abundance were reduced when using the index from the model. The index estimated from the model decreased temporal fluctuation and showed smooth patterns. Especially, the recent index was considerably revised down rather than the nominal index. Additionally, the retrospective bias decreased ca. half compared with the nominal index. Therefore, incorporating species misidentification bias should be an essential process for improving stock assessment.
Little Evidence of Modified Genetic Effect of rs16969968 on Heavy Smoking Based on Age of Onset of Smoking
Authors: Adjangba Christine , Border Richard , Romero Villela Pamela N. , Ehringer Marissa A. , Evans Luke M. 
Published: April 2020

ABSTRACTTobacco smoking is the leading cause of preventable death globally. Smoking quantity, measured in cigarettes per day (CPD), is influenced both by the age of onset of regular smoking (AOS) and by genetic factors, including a strong effect of the non-synonymous single nucleotide polymorphism rs16969968. A previous study by Hartz et al. reported an interaction between these two factors, whereby rs16969968 risk allele carriers who started smoking earlier showed increased risk for heavy smoking compared to those who started later. This finding has yet to be replicated in a large, independent sample. We performed a preregistered, direct replication attempt of the rs16969968×AOS interaction on smoking quantity in 128,383 unrelated individuals from the UK Biobank, meta-analyzed across ancestry groups. We fit statistical association models mirroring the original publication as well as formal interaction tests on multiple phenotypic and analytical scales. We replicated the main effects of rs16969968 and AOS on CPD but failed to replicate the interaction using previous methods. Nominal significance of the rs16969968×AOS interaction term depended strongly on the scale of analysis and the particular phenotype, as did associations stratified by early/late AOS. No interaction tests passed genome-wide correction (α=5e-8), and all estimated interaction effect sizes were much smaller in magnitude than previous estimates. We failed to replicate the strong rs16969968×AOS interaction effect previously reported. If such gene-moderator interactions influence complex traits, they likely depend on scale of measurement, and current biobanks lack the power to detect significant genome-wide associations given the minute effect sizes expected.IMPLICATIONSWe failed to replicate the strong rs16969968×AOS interaction effect on smoking quantity previously reported. If such gene-moderator interactions influence complex traits, current biobanks lack the power to detect significant genome-wide associations given the minute effect sizes expected. Furthermore, many potential interaction effects are likely to depend on the scale of measurement employed.
Causal analysis shows evidence of atopic dermatitis leading to an increase in vitamin D levels
Authors: Drodge Daniel R , Budu-Aggrey Ashley , Paternoster Lavinia 
Published: April 2020

AbstractAtopic dermatitis (AD) patients have been observed to have lower vitamin D levels. Previous studies have found little evidence that vitamin D levels causally influence the risk of AD, but the reverse direction has not yet been investigated.Here we used Mendelian Randomization to assess the causal relationship between AD and serum vitamin D levels, using genetic data from the most recent GWA studies of vitamin D and AD.There was little evidence for vitamin D levels causally influencing AD risk (odds per standard deviations increase in log-transformed vitamin D levels =1.233, 95% CI 0.927 to 1.639, P-value =0.150). However, genetic liability for AD raises serum vitamin D levels by 0.043 (95% CI 0.017 to 0.069) standard deviations per doubling of odds of disease (P-value =0.001). The AD-associated filaggrin (FLG) mutation R501X appears to show a particularly strong relationship with vitamin D. However, the relationship between AD and vitamin D holds when R501X is omitted (0.018, 95% CI 0.004 to 0.031, P-value =0.008).We found evidence that AD is causally associated with an increase in serum vitamin D levels. Whilst the AD-associated FLG gene has a particularly strong relationship with vitamin D, other AD SNPs show a consistent direction of effect, suggesting that AD more generally influences serum vitamin D levels.
Sorcin stimulates Activation Transcription Factor 6α (ATF6) transcriptional activity
Authors: Parks Steven , Gao Tian , Awuapura Natalia Jimenez , Ayathamattam Joseph , Chabosseau Pauline L. , Marchetti Piero , Johnson Paul , Bosco Domenico , Kalvakolanu Dhananjaya V. , Valdivia Héctor H. , Rutter Guy A. , Leclerc Isabelle 
Published: April 2020

ABSTRACTLevels of the transcription factor ATF6α, a key mediator of the unfolded protein response, that provides cellular protection during the progression endoplasmic reticulum (ER) stress, are markedly reduced in the pancreatic islet of patients with type 2 diabetes and in rodent models of the disease, including ob/ob and high fat-fed mice. Sorcin (gene nameSRI) is a calcium (Ca2+) binding protein involved in maintaining ER Ca2+homeostasis.We have previously shown that overexpressing sorcin under the rat insulin promoter in transgenic mice was protective against high fat diet-induced pancreatic beta cell dysfunction, namely preserving intracellular Ca2+homeostasis and glucose-stimulated insulin secretion during lipotoxic stress. Additionally, sorcin overexpression was apparently activating ATF6 signalling in MIN6 cells despite lowering ER stress.Here, in order to investigate further the relationship between sorcin and ATF6, we describe changes in sorcin expression during ER and lipotoxic stress and changes in ATF6 signalling after sorcin overexpression or inactivation, both in excitable and non-excitable cells.Sorcin mRNA levels were significantly increased in response to the ER stress-inducing agents thapsigargin and tunicamycin, but not by palmitate. On the contrary, palmitate caused a significant decrease in sorcin expression as assessed by both qRT-PCR and Western blotting despite inducing ER stress. Moreover, palmitate prevented the increase in sorcin expression induced by thapsigargin. In addition, sorcin overexpression significantly increased ATF6 transcriptional activity, whereas sorcin inactivation decreased ATF6 signalling. Finally, sorcin overexpression increased levels of ATF6 immunoreactivity and FRET imaging experiments following ER stress induction by thapsigargin showed a direct sorcin-ATF6 interaction.Altogether, our data suggest that sorcin down-regulation during lipotoxicity may prevent full ATF6 activation and a normal UPR during the progression of obesity and insulin resistance, contributing to beta cell failure and type 2 diabetes.
STAT2 signaling as double-edged sword restricting viral dissemination but driving severe pneumonia in SARS-CoV-2 infected hamsters
Authors: Boudewijns Robbert , Thibaut Hendrik Jan , Kaptein Suzanne J. F. , Li Rong , Vergote Valentijn , Seldeslachts Laura , De Keyzer Carolien , Bervoets Lindsey , Sharma Sapna , Van Weyenbergh Johan , Liesenborghs Laurens , Ma Ji , Jansen Sander , Van Looveren Dominique , Vercruysse Thomas , Jochmans Dirk , Wang Xinyu , Martens Erik , Roose Kenny , De Vlieger Dorien , Schepens Bert , Van Buyten Tina , Jacobs Sofie , Liu Yanan , Martí-Carreras Joan , Vanmechelen Bert , Wawina-Bokalanga Tony , Delang Leen , Rocha-Pereira Joana , Coelmont Lotte , Chiu Winston , Leyssen Pieter , Heylen Elisabeth , Schols Dominique , Wang Lanjiao , Close Lila , Matthijnssens Jelle , Van Ranst Marc , Compernolle Veerle , Schramm Georg , Van Laere Koen , Saelens Xavier , Callewaert Nico , Opdenakker Ghislain , Maes Piet , Weynand Birgit , Cawthorne Christopher , Velde Greetje Vande , Wang Zhongde , Neyts Johan , Dallmeier Kai 
Published: April 2020

Introductory paragraphSince the emergence of SARS-CoV-2 causing COVID-19, the world is being shaken to its core with numerous hospitalizations and hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that productive SARS-CoV-2 infection in the lungs of mice is limited and restricted by early type I interferon responses. In contrast, we show that Syrian hamsters are highly permissive to SARS- CoV-2 and develop bronchopneumonia and a strong inflammatory response in the lungs with neutrophil infiltration and edema. Moreover, we identify an exuberant innate immune response as a key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Finally, we assess SARS-CoV- 2-induced lung pathology in hamsters by micro-CT alike used in clinical practice. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients.