bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 infections and hospitalizations among immigrants in Norway – significance of occupation, household crowding, education, household income and medical risk. A nationwide register study
Authors: Labberton Angela S , Godøy Anna , Elgersma Ingeborg Hess , Heine Strand Bjørn , Telle Kjetil , Arnesen Trude , Nygård Karin Maria , Indseth Thor 
Published: May 2021

ABSTRACTBackgroundAs in other countries, the coronavirus disease 2019 (COVID-19) pandemic has affected Norway’s immigrant population disproportionately with significantly higher infection rates and hospitalizations. The reasons for this are uncertain.MethodsThrough the national emergency preparedness register, BeredtC19, we have studied laboratory-confirmed infections with SARS-CoV-2 and related hospitalizations in the entire Norwegian population, by birth-country background for the period 15 June 2020 – 31 March 2021, excluding the first-wave due to limited test capacity and restrictive test criteria. Straightforward linkage of individual-level data allowed adjustment for demographics, socioeconomic factors (occupation, household crowding, education, and household income), and underlying medical risk for severe COVID-19 in regression models.ResultsThe sample comprised 5.49 million persons, of which 0.91 million born outside of Norway, 82 532 confirmed cases, and 3088 hospitalizations. Confirmed infections in this period (per 100 000): foreign-born 3140, Norwegian-born with foreign-born parents 4799, Norwegian-born with Norwegian-born parent(s) 1011. Hospitalizations (per 100 000): foreign-born 147, Norwegian-born with foreign-born parents 47, Norwegian-born with Norwegian-born parent(s) 37. The addition of socioeconomic and medical factors to the base-model (age, sex, municipality of residence) attenuated excess infection rates by 12.0% and hospitalizations by 3.8% among foreign-born, and 10.9% and 46.2% respectively among Norwegian-born with foreign parents, compared to Norwegian-born with Norwegian-born parent(s).ConclusionThere were large differences in infection rates and hospitalizations by country background, and these do not appear to be fully explained by socioeconomic and medical factors. Our results may have implications for health policy, including the targeting of mitigation strategies.
A high-continuity and annotated tomato reference genome
Authors: Su Xiao , Wang Baoan , Geng Xiaolin , Du Yuefan , Yang Qinqin , Liang Bin , Meng Ge , Gao Qiang , Huang Sanwen , Yang Wencai , Zhu Yingfang , Lin Tao 
Published: May 2021

AbstractGenetic and functional genomics studies require a high-quality genome assembly. Tomato (Solanum lycopersicum), an important horticultural crop, is an ideal model species for the study of fruit development. Here, we assembled an updated reference genome ofS. lycopersicumcv. Heinz 1706 that was 799.09 Mb in length, containing 34,384 predicted protein-coding genes and 65.66% repetitive sequences. By comparing the genomes ofS. lycopersicumandS. pimpinellifoliumLA2093, we found a large number of genomic fragments probably associated with human selection, which may have had crucial roles in the domestication of tomato. Our results offer opportunities for understanding the evolution of the tomato genome and will facilitate the study of genetic mechanisms in tomato biology. Information for the assembled genome SLT1.0 was deposited both into the Genome Warehouse (GWH) database (https://bigd.big.ac.cn/gwh/) in the BIG Data Center under Accession Number GWHBAUD00000000.
Delta oscillations coordinate intra-cerebellar and cerebello-hippocampal network dynamics during sleep
Authors: Torres-Herraez A , Watson TC , Rondi-Reig L 
Published: May 2021

AbstractDuring sleep, the widespread coordination of neuronal oscillations across both cortical and subcortical brain regions is thought to support various physiological functions, including memory consolidation. However, how sleep-related activity within the brain’s largest sensorimotor structure, the cerebellum, is multiplexed with well described sleep-related mechanisms in regions such as the hippocampus remains unknown.To address this gap in knowledge, we simultaneously recorded from the dorsal hippocampus and three distinct regions of the cerebellum (Crus I, lobule VI and lobules II/III) during natural murine sleep. We found that LFP oscillations are coordinated between the two structures in a sleep-stage specific manner. Particularly during non-REM sleep, prominent delta frequency coherence was observed between lobule VI and hippocampus. We additionally observed that non-REM associated hippocampal sharp wave ripple activity can drive discrete LFP modulation in all the recorded cerebellar regions, with the shortest latency effects observed in lobule VI.We also describe discrete phasic sharp potentials, synchronized across cerebellar regions, which were strongly phase locked to the peak of ongoing cerebellar delta oscillations and found in greatest numbers during REM. These phasic sharp potentials recorded within the cerebellar cortex were found to be phase-locked to the trough of the hippocampal theta oscillation, further suggesting cross-structural coordination. During REM, cerebellar delta oscillation phase significantly modulated hippocampal theta frequency, and this effect was greatest when phasic sharp potentials were most abundant. Within all three cerebellar regions, prominent LFP oscillations were observed at both low (delta, <4 Hz) and very high frequencies (~ 250 Hz) during non-REM and REM sleep. Intra-cerebellar cross-frequency analysis revealed that delta frequency oscillations strongly modulate those in the very high frequency range.Together, these results reveal multiple candidate physiological mechanisms to support ‘offline’, bi-directional interaction within distributed cerebello-hippocampal networks. In particular, we describe a prominent cerebellar delta oscillation, which appears to act as a temporal coordinator of cerebellar activity at both local (intra-cerebellar) and distributed (cerebello-hippocampal) network levels.
Inter-laboratory automation of thein vitromicronucleus assay using imaging flow cytometry and deep learning
Authors: Wills John W. , Verma Jatin R. , Rees Benjamin J. , Harte Danielle S. G. , Haxhiraj Qiellor , Barnes Claire M. , Barnes Rachel , Rodrigues Matthew A. , Doan Minh , Filby Andrew , Hewitt Rachel E. , Thornton Catherine A. , Cronin James G. , Kenny Julia D. , Buckley Ruby , Lynch Anthony M. , Carpenter Anne E. , Summers Huw D. , Johnson George , Rees Paul 
Published: May 2021

ABSTRACTThein vitromicronucleus assay is a globally significant method for DNA damage quantification used for regulatory compound safety testing in addition to inter-individual monitoring of environmental, lifestyle and occupational factors. However it relies on time-consuming and user-subjective manual scoring. Here we show that imaging flow cytometry and deep learning image classification represents a capable platform for automated, inter-laboratory operation. Images were captured for the cytokinesis-block micronucleus (CBMN) assay across three laboratories using methyl methanesulphonate (1.25 – 5.0 µg/mL) and/or carbendazim (0.8 – 1.6 µg/mL) exposures to TK6 cells. Human-scored image sets were assembled and used to train and test the classification abilities of the “DeepFlow” neural network in both intra- and inter-laboratory contexts. Harnessing image diversity across laboratories yielded a network able to score unseen data from an entirely new laboratory without any user configuration. Image classification accuracies of 98%, 95%, 82% and 85% were achieved for ‘mononucleates’, ‘binucleates’, ‘mononucleates with MN’ and ‘binucleates with MN’, respectively. Successful classifications of ‘trinucleates’ (90%) and ‘tetranucleates’ (88%) in addition to ‘other or unscorable’ phenotypes (96%) were also achieved. Attempts to classify extremely rare, tri- and tetranucleated cells with micronuclei into their own categories were less successful (≤ 57%). Benchmark dose analyses of human or automatically scored micronucleus frequency data yielded quantitation of the same equipotent dose regardless of scoring method. We conclude that this automated approach offers significant potential to broaden the practical utility of the CBMN method across industry, research and clinical domains. We share our strategy using openly-accessible frameworks.
Flexible neural control of motor units
Authors: Marshall Najja J. , Glaser Joshua I. , Trautmann Eric M. , Amematsro Elom A. , Perkins Sean M. , Shadlen Michael N. , Abbott L.F. , Cunningham John P. , Churchland Mark M. 
Published: May 2021

SummaryVoluntary movement requires communication from cortex to the spinal cord, where a dedicated pool of motor units (MUs) activates each muscle. The canonical description of MU function rests upon two foundational tenets. First, cortex cannot control MUs independently but supplies each pool with a common drive. Second, MUs are recruited in a rigid fashion that largely accords with Henneman’s size principle. While this paradigm has considerable empirical support, a direct test requires simultaneous observations of many MUs across diverse force profiles. We developed an isometric task that allowed stable MU recordings even during rapidly changing forces. MU activity patterns were surprisingly behavior-dependent. MU activity could not be accurately described as reflecting common drive, but could be captured by assuming multiple drives. Neuropixels probe recordings revealed that, consistent with the requirements of flexible control, the motor cortex population response displays a great many degrees of freedom. Neighboring cortical sites recruited different MUs. Thus, MU activity is flexibly controlled to meet task demands, and cortex may contribute to this ability.
Telomeric 8-Oxoguanine Drives Rapid Premature Senescence In The Absence Of Telomere Shortening
Authors: Barnes Ryan P. , de Rosa Mariarosaria , Thosar Sanjana A. , Detwiler Ariana C. , Roginskaya Vera , Van Houten Bennett , Bruchez Marcel P. , Stewart-Ornstein Jacob , Opresko Patricia L. 
Published: May 2021

SUMMARYOxidative stress is a primary cause of cellular senescence and contributes to the pathogenesis of numerous human diseases. Oxidative damage to telomeric DNA is proposed to trigger premature senescence by accelerating telomere shortening. Here we tested this model directly using a precision tool to produce the common base lesion 8-oxo-guanine (8oxoG) exclusively at telomeres in human fibroblast and epithelial cells. A single induction of telomeric 8oxoG is sufficient to trigger multiple hallmarks of p53-dependent senescence. Telomeric 8oxoG activates ATM and ATR signaling, and enriches for markers of telomere dysfunction in replicating, but not quiescent cells. Acute 8oxoG production fails to shorten telomeres, but rather generates fragile sites and delayed mitotic DNA synthesis at telomeres, indicative of impaired replication. Based on our results we propose that oxidative stress promotes rapid senescence by producing oxidative base lesions which drive replication-dependent telomere fragility and dysfunction in the absence of shortening and shelterin loss.
Genetic determinism of phage-bacteria coevolution in natural populations
Authors: Piel Damien , Bruto Maxime , Labreuche Yannick , Blanquart Francois , Chenivesse Sabine , Lepanse Sophie , James Adèle , Barcia-Cruz Rubén , Dubert Javier , Petton Bruno , Lieberman Erica , Wegner K. Mathias , Hussain Fatima A. , Kauffman Kathryn M. , Polz Martin F. , Bikard David , Gandon Sylvain , Le Roux Frédérique 
Published: May 2021

ABSTRACTCoevolution between bacteriophage (or phage) and their bacterial host is thought to be key for the coexistence of these antagonists. Recent studies have revealed the major role of mobile genetic elements in the emergence of phage resistant hosts but how phage escape these defenses in the wild remained to be explored. Here we show a striking parallel in phage evolving counter defenses to host defenses in natural population. We established a large collection of phages and their bacterial hosts and we explored the genetic structure of their interaction. We find that clearly delineated genomic clusters of phage are specific for distinct clades within a bacterial species,Vibrio crassostreae, yet while all phages can adsorb, only a subset of hosts are killed due to intracellular defense mechanisms. Host genomes contain multiple mobile defense genes and susceptibility to phage is negatively correlated with genome size. Phages also display extensive gene content variation, but their genome size remains conserved. We show that this gene content variation in hosts and phage is due to rapid turnover of genes involved in defense and escape, and that by exchanging anti-defense genes, phages irreversibly switch host. This could be indicative of co-evolution following the matching-allele-model of specificity and the spatial and temporal variability of phage infectivity further suggests that negative-frequency dependent selection drives phage-vibrio coevolutionary dynamics. We propose a “pan-escape system” that can be shared among phages by homologous recombination within a population that infects a bacterial host.
Behavioral-transcriptomic landscape of engineered T cells targeting human cancer organoids
Authors: Dekkers Johanna F. , Alieva Maria , Cleven Astrid , Keramati Farid , Brazda Peter , Rebel Heggert G. , Wezenaar Amber K.L. , Puschhof Jens , Buchholz Maj-Britt , Román Mario Barrera , Johanna Inez , Meringa Angelo D. , Fasci Domenico , Geurts Maarten H. , Ariese Hendrikus C.R. , van Vliet Esmée J. , van Ineveld Ravian L. , Karaiskaki Effrosyni , Kopper Oded , Bar-Ephraim Yotam E. , Kretzschmar Kai , Eggermont Alexander M.M. , Wehrens Ellen J. , Stunnenberg Henk G. , Clevers Hans , Kuball Jürgen , Sebestyen Zsolt , Rios Anne C. 
Published: May 2021

SummaryCellular immunotherapies are rapidly gaining clinical importance, yet predictive platforms for modeling their mode of action are lacking. Here, we developed a dynamic immuno-organoid 3D imaging-transcriptomics platform; BEHAV3D, to unravel the behavioral and underlying molecular mechanisms of solid tumor targeting. Applied to an emerging cancer metabolome-sensing immunotherapy: TEGs, we first demonstrate targeting of multiple breast cancer subtypes. Live-tracking of over 120,000 TEGs revealed a diverse behavioral landscape and identified a ‘super engager’ cluster with serial killing capability. Inference of single-cell behavior with transcriptomics identified the gene signature of ‘super engager’ killer TEGs, which contained 27 genes with no previously described T cell function. Furthermore, guided by a dynamic type 1 interferon (IFN-I) signaling module induced by high TEG-sensitive organoids, we show that IFN-I can prime resistant organoids for TEG-mediated killing. Thus, BEHAV3D characterizes behavioral-phenotypic heterogeneity of cellular immunotherapies and holds promise for improving solid tumor-targeting in a patient-specific manner.
No evidence that lulworthioid fungi are dark septate endophytes in the roots of the dominant Mediterranean seagrassPosidonia oceanica
Authors: Vohník Martin 
Published: May 2021

AbstractA previous study from Sicily, Italy indicated that the dominant Mediterranean seagrassPosidonia oceanicaforms a dark septate endophytic (DSE) association with a lulworthioid fungus (“Lulwoanasp.”), which is in conflict with several other studies from the NW Mediterranean Sea that point at the recently described pleosporalean fungusPosidoniomyces atricolor.I collectedP. oceanicaroots at eight sites around Sicily and checked them for fungal colonization using light microscopy. At three sites, root fungal symbionts (=mycobionts) were isolated into pure cultures and identified using sequencing of the ITS rDNA gene.Posidoniomyces atricolorrepresented the most frequent mycobiont (56 isolates), closely followed by lulworthioid fungi (51). The obtained mycobiont spectrum also comprisedCladosporium(2),Alternaria(1),Corollospora(1),Fusarium(1),Penicillium(1) andVishniacozyma(1) isolates. The characteristic DSE root colonization similar to those occurring in terrestrial plants but not known from any other seagrass was found in all investigatedP. oceanicaindividuals. The microscopic screening suggests thatP. atricoloris indeed responsible for the observed DSE colonization.This study extends the known range ofP. atricolorand the DSE association characteristic forP. oceanicafor southern Tyrrhenian Sea/Sicily. While lulworthioid fungi regularly occur inP. oceanicatissues, including terminal fine roots, their significance and functioning are unknown and beg further investigation. However, there are currently no proofs that they belong among dark septate endophytes of this seagrass.One-sentence summaryThis paper corrects an opinion that “Lulwoanasp.” (Lulworthiales) is a dark septate endophyte of the dominant Mediterranean seagrassPosidonia oceanica, because all available evidence suggests that the dark septate endophytic association typical for this seagrass is formed by its specific root mycobiontPosidoniomyces atricolor(Pleosporales).
Ssl2/TFIIH function in Transcription Start Site Scanning by RNA Polymerase II in Saccharomyces cerevisiae
Authors: Zhao Tingting , Vvedenskaya Irina O. , Lai William K.M. , Basu Shrabani , Pugh B. Franklin , Nickels Bryce E. , Kaplan Craig D. 
Published: May 2021

ABSTRACTIn Saccharomyces cerevisiae, RNA Polymerase II (Pol II) selects transcription start sites (TSS) by a unidirectional scanning process. During scanning, a preinitiation complex (PIC) assembled at an upstream core promoter initiates at select positions within a window ∼40-120 basepairs downstream. Several lines of evidence indicate that Ssl2, the yeast homolog of XPB and an essential and conserved subunit of the general transcription factor (GTF) TFIIH, drives scanning through its DNA-dependent ATPase activity, therefore potentially controlling both scanning rate and scanning extent (processivity). To address questions of how Ssl2 functions in promoter scanning and interacts with other initiation activities, we leveraged distinct initiation-sensitive reporters to identify novel ssl2 alleles. These ssl2 alleles, many of which alter residues conserved from yeast to human, confer either upstream or downstream TSS shifts at the model promoter ADH1 and genome-wide. Specifically, tested ssl2 alleles alter TSS selection by increasing or narrowing the distribution of TSSs used at individual promoters. Genetic interactions of ssl2 alleles with other initiation factors are consistent with ssl2 allele classes functioning through increasing or decreasing scanning processivity but not necessarily scanning rate. These alleles underpin a residue interaction network that likely modulates Ssl2 activity and TFIIH function in promoter scanning. We propose that the outcome of promoter scanning is determined by two functional networks, the first being Pol II activity and factors that modulate it to determine initiation efficiency within a scanning window, and the second being Ssl2/TFIIH and factors that modulate scanning processivity to determine the width of the scanning widow.
Activation of Histone 3 Lysine 9 methyl writing and reading capabilities within the G9a-GLP heterodimer
Authors: Sanchez Nicholas A , Kallweit Lena M , Trnka Michael J , Clemmer Charles L , Al-Sady Bassem 
Published: May 2021

ABSTRACTUnique among metazoan repressive histone methyltransferases, G9a and GLP, which chiefly target histone 3 lysine 9 (H3K9), require dimerization for productive H3K9 mono (me1)- and dimethylation (me2)in vivo. Intriguingly, even though each enzyme can independently methylate H3K9, the predominant active formin vivois a heterodimer of G9a and GLP. How dimerization influences the central H3K9 methyl binding (“reading”) and deposition (“writing”) activity of G9a and GLP, and why heterodimerization is essentialin vivoremains opaque. Here, we examine the H3K9me “reading” and “writing” activities of defined, recombinantly produced homo- and heterodimers of G9a and GLP. We find that both reading and writing are significantly enhanced in the heterodimer. Compared to the homodimers, the heterodimer has higher recognition of H3K9me2, and a striking ∼ 10-fold increased turnover rate for nucleosomal substrates under multiple turnover conditions, which is not evident on histone tail peptide substrates. Crosslinking Mass Spectrometry suggests that differences between the homodimers and the unique activity of the heterodimer may be encoded in altered ground state conformations, as each dimer displays different domain contacts. Our results indicate that heterodimerization may be required to relieve autoinhibition of H3K9me reading and chromatin methylation evident in G9a and GLP homodimers. Relieving this inhibition may be particularly important in early differentiation when large tracts of H3K9me2 are deposited by G9a-GLP, which may require a more active form of the enzyme.
Immune priming can prevent WNV establishment inCulex quinquefasciatusmosquitoes: evidence for immune priming based reversal of WNV-mediated immune suppression
Authors: Blagrove Marcus , Barribeau Seth M 
Published: May 2021

AbstractMosquito-borne infectious diseases cause wide-spread loss of life and livelihood often in low-income settings. However, control of mosquito-vectored viral diseases such as West Nile virus (WNV) and Japanese encephalitis virus (JEV) remains challenging. Here we use an existing feature of the insect immune system to effectively vaccinateCulex quinquefasciatusmosquitoes against WNV infection. We find that priming mosquitoes by exposure to inactivated WNV reduces their likelihood of developing transmissible infections of WNV after live infection. We used RNA sequencing to identify gene expression in response to WNV and JEV infection, and the role of prior priming exposure on constitutive and induced expression on infection. Infection with either Flavivirus causes broad suppression of gene expression. WNV and JEV infection resulted in suppression of different suites of genes with notable immune genes, such as antimicrobial peptides, being strongly suppressed on WNV infection. We hypothesise that the increased resistance to WNV infection seen in primed mosquitoes may be the result of priming nullifying the immune suppression found in non-primed WNV-fed mosquitoes, potentially through greater expression of mRNA regulatory genes such as cap-binding proteins in primed mosquitoes.Author summaryMosquitoes vector many devastating infectious diseases. Two such vectored viral diseases are West Nile virus (WNV) and Japanese encephalitis virus (JEV). Control of these diseases remains challenging, and no vaccine exists for WNV. Here, we tested whether we could instead vaccinate the mosquitoes against WNV. By injecting mosquitoes with dead WNV we found that we could reduce the number of infected mosquitoes by half. We then used whole-genome RNA sequencing to identify which genes are transcribed, which will help us understand genes that are important for this form of insect immune priming, and for responses to normal WNV and JEV infection. We found that WNV suppresses the expression of many immune genes but these genes are expressed normally in vaccinated mosquitoes. Our findings expand our understanding of mosquito infection with these viruses but also demonstrate how prior exposure to a disease can produce lasting protection.