bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid feedback on hospital onset SARS-CoV-2 infections combining epidemiological and sequencing data
Authors: Stirrup Oliver T , Hughes Joseph , Parker Matthew , Partridge David G , Shepherd James G , Blackstone James , Coll Francesc , Keeley Alexander J , Lindsey Benjamin B , Marek Aleksandra , Peters Christine , Singer Joshua B ,   The COVID-19 Genomics UK (COG-UK) consortium, Tamuri Asif , de Silva Thushan I , Thomson Emma C , Breuer Judith 
Published: November 2020

AbstractBackgroundRapid identification and investigation of healthcare-associated infections (HCAIs) is important for suppression of SARS-CoV-2, but the infection source for hospital onset COVID-19 infections (HOCIs) cannot always be readily identified based only on epidemiological data. Viral sequencing data provides additional information regarding potential transmission clusters, but the low mutation rate of SARS-CoV-2 can make interpretation using standard phylogenetic methods difficult.MethodsWe developed a novel statistical method and sequence reporting tool (SRT) that combines epidemiological and sequence data in order to provide a rapid assessment of the probability of HCAI among HOCI cases (defined as first positive test >48 hours following admission) and to identify infections that could plausibly constitute outbreak events. The method is designed for prospective use, but was validated using retrospective datasets from hospitals in Glasgow and Sheffield collected February-May 2020.ResultsWe analysed data from 326 HOCIs. Among HOCIs with time-from-admission ≥8 days the SRT algorithm identified close sequence matches from the same ward for 160/244 (65.6%) and in the remainder 68/84 (81.0%) had at least one similar sequence elsewhere in the hospital, resulting in high estimated probabilities of within-ward and within-hospital transmission. For HOCIs with time-from-admission 3-7 days, the SRT probability of healthcare acquisition was >0.5 in 33/82 (40.2%).ConclusionsThe methodology developed can provide rapid feedback on HOCIs that could be useful for infection prevention and control teams, and warrants further prospective evaluation. The integration of epidemiological and sequence data is important given the low mutation rate of SARS-CoV-2 and its variable incubation period.
Asymptomatic and symptomatic SARS-CoV-2 infections elicit polyfunctional antibodies
Authors: Dufloo Jérémy , Grzelak Ludivine , Staropoli Isabelle , Madec Yoann , Tondeur Laura , Anna François , Pelleau Stéphane , Wiedemann Aurélie , Planchais Cyril , Buchrieser Julian , Robinot Rémy , Ungeheuer Marie-Noëlle , Mouquet Hugo , Charneau Pierre , White Michael , Lévy Yves , Hoen Bruno , Fontanet Arnaud , Schwartz Olivier , Bruel Timothée 
Published: November 2020

AbstractA large proportion of SARS-CoV-2 infected individuals remains asymptomatic. Little is known about the extent and quality of their antiviral humoral response. Here, we analyzed antibody functions in 52 asymptomatic infected individuals, 119 mild and 21 hospitalized COVID-19 patients. We measured anti-Spike antibody levels with the S-Flow assay and mapped SARS-CoV-2 Spike- and N-targeted regions by Luminex. Neutralization, complement deposition and Antibody-Dependent Cellular Cytotoxicity (ADCC) were evaluated using replication-competent SARS-CoV-2 or reporter cell systems. We show that COVID-19 sera mediate complement deposition and kill infected cells by ADCC. Sera from asymptomatic individuals neutralize the virus, activate ADCC and trigger complement deposition. Antibody levels and activities are slightly lower in asymptomatic individuals. The different functions of the antibodies are correlated, independently of disease severity. Longitudinal samplings show that antibody functions follow similar kinetics of induction and contraction, with minor variations. Overall, asymptomatic SARS-CoV-2 infection elicits polyfunctional antibodies neutralizing the virus and targeting infected cells.-Sera from convalescent COVID-19 patients activate the complement and kill infected cells by ADCC.-Asymptomatic and symptomatic SARS-CoV-2-infected individuals harbor polyfunctional antibodies.-Antibody levels and functions are slightly lower in asymptomatic individuals-The different antiviral activities of anti-Spike antibodies are correlated regardless of disease severity.-Functions of anti-Spike antibodies have similar kinetics of induction and contraction.
SensitizingStaphylococcus aureusto antibacterial host defense by decoding and blocking the lipid flippase MprF
Authors: Slavetinsky Christoph J. , Hauser Janna N. , Gekeler Cordula , Slavetinsky Jessica , Geyer André , Kraus Alexandra , Heilingbrunner Doris , Wagner Samuel , Tesar Michael , Krismer Bernhard , Kuhn Sebastian , Ernst Christoph M. , Peschel Andreas 
Published: November 2020

AbstractThe pandemic of antibiotic resistance represents a major human health threat demanding new antimicrobial strategies. MprF is the synthase and flippase of the phospholipid lysyl-phosphatidylglycerol that increases virulence and resistance of methicillin-resistantStaphylococcus aureus(MRSA) and other pathogens to cationic host defense peptides and antibiotics. With the aim to design MprF inhibitors that could sensitize MRSA to both, human antimicrobials and antibiotics and support the clearance of staphylococcal infections with minimal selection pressure, we developed MprF-targeting monoclonal antibodies, which bound and blocked the MprF flippase subunit. Antibody M-C7.1 targeted a specific loop in the flippase domain that proved to be exposed at both sides of the bacterial membrane, thereby enhancing the mechanistic understanding into bacterial lipid translocation. M-C7.1 rendered MRSA susceptible to host antimicrobial peptides and antibiotics such as daptomycin. Moreover, it impaired MRSA survival in human phagocytes, which recommends MprF inhibitors for new anti-MRSA approaches. MprF-directed monoclonal antibodies provide a proof of concept for development of precisely targeted anti-virulence approaches, which block bacterial antimicrobial resistance mechanisms.
Sex-specific stress-related behavioral phenotypes and central amygdala dysfunction in a mouse model of 16p11.2 microdeletion
Authors: Giovanniello Jacqueline , Ahrens Sandra , Yu Kai , Li Bo 
Published: November 2020

AbstractSubstantial evidence indicates that a microdeletion on human chromosome 16p11.2 is linked to neurodevelopmental disorders including autism spectrum disorders (ASD). Carriers of this deletion show divergent symptoms besides the core features of ASD, such as anxiety and emotional symptoms. The neural mechanisms underlying these symptoms are poorly understood. Here we report mice heterozygous for a deletion allele of the genomic region corresponding to the human 16p11.2 microdeletion locus (i.e., the ‘16p11.2 del/+ mice’) have sex-specific anxiety-related behavioral and neural circuit changes. We found that female, but not male16p11.2 del/+ mice showed enhanced fear generalization – a hallmark of anxiety disorders – after auditory fear conditioning, and displayed increased anxiety-like behaviors after physical restraint stress. Notably, such sex-specific behavioral changes were paralleled by an increase in activity in central amygdala neurons projecting to the globus pallidus in female, but not male16p11.2 del/+ mice. Together, these results reveal female-specific anxiety phenotypes related to 16p11.2 microdeletion syndrome and a potential underlying neural circuit mechanism. Our study therefore identifies previously underappreciated sex-specific behavioral and neural changes in a genetic model of 16p11.2 microdeletion syndrome, and highlights the importance of investigating female-specific aspects of this syndrome for targeted treatment strategies.
Using the novel priority index in prioritizing the selection of inland water bodies for site-based fish species conservation
Authors: Basooma Anthony , Nakiyende Herbert , Olokotum Mark , Nkalubo Winnie , Musinguzi Laban , Natugonza Vianny 
Published: November 2020

AbstractFreshwater ecosystems occupy <1% of the Earth’s total surface area but provide an array of ecosystem services. However, these ecosystems are threatened by multiple stressors, including overexploitation, infrastructure developments, habitat alteration, and alien species introductions. The magnitude of these threats varies in different water bodies, requiring site-based conservation actions. In this paper, we aimed at developing a priority index (CPIw) that can be used to inform conservation managers in prioritizing the selection of a waterbody for site-based fish conservation purposes. We used data on distribution, diversity, and conservation status of fishes of Uganda, which were retrieved from the Global Biodiversity Information Facility (GBIF) and International Union Conservation for Nature (IUCN) databases. In the index, we incorporated the species richness, surface area of a waterbody, species rarity, and species IUCN status. A total of 288 fish species were recorded in 81 waterbodies (7 large lakes, 37 small lakes, and 37 rivers). Of these species, 110 were only found in large lakes, followed by rivers (19) and small lakes (6). Despite the higher species richness in large lakes relative to small lakes, the latter recorded significantly higher CPIw compared with the former (t = −2.8, df = 30, p-value = 0.008, d=0.7). This observation is consistent with the expectation, given the low ecological substitutability for the species and higher levels of exposure to human-induced threats in small water bodies compared with large systems. Therefore, we suggest that in situations where resources are limiting, small water bodies need to be given much attention, although we do not suggest ignoring water bodies with low CPIw values.
A comparison of DNA/RNA extraction protocols for high-throughput sequencing of microbial communities
Authors: Shaffer Justin P. , Marotz Clarisse , Belda-Ferre Pedro , Martino Cameron , Wandro Stephen , Estaki Mehrbod , Salido Rodolfo A. , Carpenter Carolina S. , Zaramela Livia S. , Minich Jeremiah J. , Bryant MacKenzie , Sanders Karenina , Fraraccio Serena , Ackermann Gail , Humphrey Gregory , Swafford Austin D. , Miller-Montgomery Sandrine , Knight Rob 
Published: November 2020

AbstractOne goal among microbial ecology researchers is to capture the maximum amount of information from all organisms in a sample. The recent COVID-19 pandemic, caused by the RNA virus SARS-CoV-2, has highlighted a gap in traditional DNA-based protocols, including the high-throughput methods we previously established as field standards. To enable simultaneous SARS-CoV-2 and microbial community profiling, we compare the relative performance of two total nucleic acid extraction protocols and our previously benchmarked protocol. We included a diverse panel of environmental and host-associated sample types, including body sites commonly swabbed for COVID-19 testing. Here we present results comparing the cost, processing time, DNA and RNA yield, microbial community composition, limit of detection, and well-to-well contamination, between these protocols.Accession numbersRaw sequence data were deposited at the European Nucleotide Archive (accession#: ERP124610) and raw and processed data are available at Qiita (Study ID: 12201). All processing and analysis code is available on GitHub (github.com/justinshaffer/Extraction_test_MagMAX).Methods summaryTo allow for downstream applications involving RNA-based organisms such as SARS-CoV-2, we compared the two extraction protocols designed to extract DNA and RNA against our previously established protocol for extracting only DNA for microbial community analyses. Across 10 diverse sample types, one of the two protocols was equivalent or better than our established DNA-based protocol. Our conclusion is based on per-sample comparisons of DNA and RNA yield, the number of quality sequences generated, microbial community alpha- and beta-diversity and taxonomic composition, the limit of detection, and extent of well-to-well contamination.
X-ray Irradiation activates immune response in human T-lymphocytes by eliciting a Ca2+signaling cascade
Authors: Tandl Dominique , Sponagel Tim , Fuck Sebastian , Smit Timo , Hehlgans Stephanie , Jakob Burkhard , Fournier Claudia , Rödel Franz , Roth Bastian , Moroni Anna , Thiel Gerhard 
Published: November 2020

AbstractRadiation therapy is efficiently employed for eliminating cancer cells and reducing tumor growth. To further improving its therapeutic application it is mandatory to unravel the molecular effects of ionizing irradiation and to understand whether they support or counteract tumor therapy. Here we examine the impact of X-ray irradiation on immune activation of human T cells with single doses typically employed in tumor therapy. We discover that exposing cells to radiation triggers in a population of leukemic Jurkat T cells and in peripheral blood mononuclear cells (PBMCs) a canonical Ca2+signaling cascade, which elicits immune activation of these cells. An early step in the signaling cascade is the initiation of sustained oscillations of the cytosolic Ca2+concentration, an event mediated by store operated Ca2+entry (SOCE) via an X-ray induced clustering of the Calcium Release-Activated Calcium Modulator 1 with the stromal interaction molecule 1 (Oari1/STIM1). A functional consequence of the Ca2+signaling cascade is the translocation of the transcription factor nuclear factor of activated T cells (NFAT) from the cytosol into the nucleus where it elicits the expression of genes required for immune activation. These data imply that a direct activation of blood immune cells by ionizing irradiation has an impact on toxicity and therapeutic effects of radiation therapy.
The cell fate controlling CLE40 peptide requires CNGC9 to trigger highly localized Ca2+transients inArabidopsis thalianaroot meristems
Authors: Breiden Maike , Olsson Vilde , Gustavo-Pinto Karine , Schultz Patrick , Denay Gregoire , Schlegel Jenia , Dietrich Petra , Butenko Melinka A. , Simon Rüdiger 
Published: November 2020

AbstractCommunication between plant cells and their biotic environment is largely dependent on the function of plasma membrane localized receptor-like kinases (RLKs). Major players in this communication within root meristems are secreted peptides, including CLAVATA3/EMBRYO SURROUNDING REGION40 (CLE40). In the distal root meristem, CLE40 acts through the receptor like kinase (RLK) ARABIDOPSIS CRINKLY4 (ACR4) and the leucine-rich repeat (LRR) RLK CLAVATA1 (CLV1) to promote cell differentiation. In the proximal meristem, CLE40 signalling requires the LRR receptor-like protein (RLP) CLAVATA2 (CLV2) and the membrane localized pseudokinase CORYNE (CRN), and serves to inhibit cell differentiation. The molecular components that act immediately downstream of the CLE40-activated receptors are not yet known. Here we show that active CLE40 signalling triggers the release of intracellular Ca2+leading to increased cytosolic Ca2+concentration ([Ca2+]cyt) in a subset of proximal root meristem cells. This rise in [Ca2+]cytdepends on the CYCLIC NUCLEOTIDE GATED CHANNEL 9 (CNGC9), CLV1, the CLV1-related BARELY ANY MERISTEM1 (BAM1), CLV2 and CRN. The precise function of changes in [Ca2+]cytare not yet known, but might form a central part of a fine-tuned response to CLE40 peptide that serves to integrate root meristem growth with stem cell fate decisions and initiation of lateral root primordia.
Template-independent genome editing and repairing correct frameshift diseasein vivo
Authors: Liu Lian , Li Kuan , Zou Linzhi , Hou Hanqing , Hu Qun , Liu Shuang , Wang Shufeng , Wang Yangzhen , Li Jie , Song Chenmeng , Chen Jiaofeng , Li Changri , Du Haibo , Li Jun-Liszt , Chen Fangyi , Xu Zhigang , Sun Wenzhi , Sun Qianwen , Xiong Wei 
Published: November 2020

AbstractFrameshift mutation caused by small insertions/deletions (indels) often generate truncated and non-functional proteins, which underlies 22% inherited Mendelian disorders in humans. However, there is no efficientin vivogene therapy strategies available to date, especially in postmitotic systems. Here, we leveraged the non-homologous end joining (NHEJ) mediated non-random editing profiles to compensate the frameshift mutation in a USH1F mouse model –av3j. After treatment by the selected gRNA, about 50% editing products showed reading-frame restoration, and more than 70% targeted hair cells recovered mechanotransduction.In vivotreatment ameliorated the hearing and balance symptoms in homozygous mutant mice. Furthermore, a scale-up analysis of 114 gRNAs targeting 40 frameshift deafness mutations reveals that 65% loci have at least one gRNA with predicted therapeutic potential. Together, our study demonstrates that the NHEJ-mediated frame restoration is a simple and highly efficient therapeutic strategy for small-indel induced frameshift mutations.
Analysis of the Dynamics and Distribution of SARS-CoV-2 Mutations and its Possible Structural and Functional Implications
Authors: Arévalo Santiago Justo , Sifuentes Daniela Zapata , Robles César Huallpa , Bianchi Gianfranco Landa , Chávez Adriana Castillo , Casas Romina Garavito-Salini , Chavarría Roberto Pineda , Uceda-Campos Guillermo 
Published: November 2020

ABSTRACTAfter eight months of the pandemic declaration, COVID-19 has not been globally controlled. Several efforts to control SARS-CoV-2 dissemination are still running including vaccines and drug treatments. The effectiveness of these procedures depends, in part, that the regions to which these treatments are directed do not vary considerably. Although, it is known that the mutation rate of SARS-CoV-2 is relatively low it is necessary to monitor the adaptation and evolution of the virus in the different stages of the pandemic. Thus, identification, analysis of the dynamics, and possible functional and structural implication of mutations are relevant. Here, we first estimate the number of COVID-19 cases with a virus with a specific mutation and then calculate its global relative frequency (NRFp). Using this approach in a dataset of 100 924 genomes from GISAID, we identified 41 mutations to be present in viruses in an estimated number of 750 000 global COVID-19 cases (0.03 NRFp). We classified these mutations into three groups: high-frequent, low-frequent non-synonymous, and low-frequent synonymous. Analysis of the dynamics of these mutations by month and continent showed that high-frequent mutations appeared early in the pandemic, all are present in all continents and some of them are almost fixed in the global population. On the other hand, low-frequent mutations (non-synonymous and synonymous) appear late in the pandemic and seems to be at least partially continent-specific. This could be due to that high-frequent mutation appeared early when lockdown policies had not yet been applied and low-frequent mutations appeared after lockdown policies. Thus, preventing global dissemination of them. Finally, we present a brief structural and functional review of the analyzed ORFs and the possible implications of the 25 identified non-synonymous mutations.
A zero inflated log-normal model for inference of sparse microbial association networks
Authors: Prost Vincent , Gazut Stéphane , Brüls Thomas 
Published: November 2020

AbstractThe advent of high-throughput metagenomic sequencing has prompted the development of efficient taxonomic profiling methods allowing to measure the presence, abundance and phylogeny of organisms in a wide range of environmental samples. Multivariate sequence-derived abundance data further has the potential to enable inference of ecological associations between microbial populations, but several technical issues need to be accounted for, like the compositional nature of the data, its extreme sparsity and overdispersion, as well as the frequent need to operate in under-determined regimes.The ecological network reconstruction problem is frequently cast into the paradigm of Gaussian Graphical Models (GGMs) for which efficient structure inference algorithms are available, like the graphical lasso and neighborhood selection. Unfortunately, GGMs or variants thereof can not properly account for the extremely sparse patterns occurring in real-world metagenomic taxonomic profiles. In particular, structural zeros (as opposed to sampling zeros) corresponding to true absences of biological signals fail to be properly handled by most statistical methods.We present here a zero-inflated log-normal graphical model (available athttps://github.com/vincentprost/Zi-LN) specifically aimed at handling such “biological” zeros, and demonstrate significant performance gains over state-of-the-art statistical methods for the inference of microbial association networks, with most notable gains obtained when analyzing taxonomic profiles displaying sparsity levels on par with real-world metagenomic datasets.
RNA polymerase backtracking results in the accumulation of fission yeast condensin at active genes
Authors: Rivosecchi Julieta , Jost Daniel , Vachez Laetitia , Gautier François , Bernard Pascal , Vanoosthuyse Vincent 
Published: November 2020

AbstractThe mechanisms leading to the accumulation of the SMC complexes condensins around specific transcription units remain unclear. Observations made in bacteria suggested that RNA polymerases (RNAP) constitute an obstacle to SMC translocation, particularly when RNAP and SMC travel in opposite directions. Here we show in fission yeast that gene termini harbour intrinsic condensin-accumulating features whatever the orientation of transcription, which we attribute to the frequent backtracking of RNAP at gene ends. Consistent with this, to relocate backtracked RNAP2 from gene termini to gene bodies was sufficient to cancel the accumulation of condensin at gene ends and to redistribute it evenly within transcription units, indicating that RNAP backtracking may play a key role in positioning condensin. Formalization of this hypothesis in a mathematical model suggests that the inclusion of a sub-population of RNAP with longer dwell-times is essential to fully recapitulate the distribution profiles of condensin around active genes. Taken together, our data strengthen the idea that dense arrays of proteins tightly-bound to DNA alter the distribution of condensin on chromosomes.
Metagenomic characterization of a harmful algal bloom using nanopore sequencing
Authors: Schafran Peter W. , Cai Victor , Yang Hsiao-Pei , Li Fay-Wei 
Published: November 2020

ABSTRACTWater bodies around the world are increasingly threatened by harmful algal blooms (HABs) under current trends of rising water temperature and nutrient load. Metagenomic characterization of HABs can be combined with water quality and environmental data to better understand and predict the occurrence of toxic events. However, standard short-read sequencing typically yields highly fragmented metagenomes, preventing direct connection of genes to a single genome. Using Oxford Nanopore long-read sequencing, we were able to obtain high quality metagenome-assembled genomes, and show that dominant organisms in a HAB are readily identified, though different analyses disagreed on the identity of rare taxa. Genes from diverse functional categories were found not only in the most dominant genera, but also in several less common ones. Using simulated datasets, we show that the Flongle flowcell may provide an option for HAB monitoring with less data, at the expense of failing to detect rarer organisms and increasing fragmentation of the metagenome. Based on these results, we believe that Nanopore sequencing provides a fast, portable, and affordable method for studying HABs.