bluuebunny/crossref_metadata_2025_split huggingface dataset:
Standing genetic variation of the AvrPm17 avirulence gene in powdery mildew limits the effectiveness of an introgressed rye resistance gene in wheat
Authors: Mueller Marion C. , Kunz Lukas , Schudel Seraina , Kammerecker Sandrine , Isaksson Jonatan , Wyler Michele , Graf Johannes , Sotiropoulos Alexandros G. , Praz Coraline R. , Wicker Thomas , Bourras Salim , Keller Beat 
Published: March 2021

AbstractIntrogressions of chromosomal segments from related species into wheat are important sources of resistance against fungal diseases. The durability and effectiveness of introgressed resistance genes upon agricultural deployment is highly variable - a phenomenon that remains poorly understood as the corresponding fungal avirulence genes are largely unknown. Until its breakdown, thePm17resistance gene introgressed from rye to wheat provided broad resistance against powdery mildew (Blumeria graminis). Here, we used QTL mapping to identify the corresponding wheat mildew avirulence effectorAvrPm17. It is encoded by two paralogous genes that exhibit signatures of re-occurring gene conversion events and are members of a mildew sub-lineage specific effector cluster. Extensive haplovariant mining in wheat mildew and related sub-lineages identified several ancient virulentAvrPm17variants that were present as standing genetic variation in wheat powdery mildew prior to thePm17introgression, thereby paving the way for the rapid breakdown of thePm17resistance. QTL mapping in mildew identified a second genetic component likely corresponding to an additional resistance gene present on the 1AL.1RS translocation carryingPm17. This gene remained previously undetected due to suppressed recombination within the introgressed rye chromosomal segment. We conclude that the initial effectiveness of 1AL.1RS was based on simultaneous introgression of two genetically linked resistance genes. Our results demonstrate the relevance of pathogen-based genetic approaches to disentangle complex resistance loci in wheat. We propose that identification and monitoring of avirulence gene diversity in pathogen populations becomes an integral part of introgression breeding to ensure effective and durable resistance in wheat.Significance StatementDomesticated and wild wheat relatives provide an important source of new immune receptors for wheat resistance breeding against fungal pathogens. The durability of these resistance genes is variable and difficult to predict, yet it is crucial for effective resistance breeding. We identified a fungal effector protein recognised by an immune receptor introgressed from rye to wheat. We found that variants of the effector allowing the fungus to overcome the resistance are ancient. They were already present in the wheat powdery mildew gene pool before the introgression of the immune receptor and are therefore responsible for the rapid resistance breakdown. Our study demonstrates that the effort to identify new resistance genes should be accompanied by studies of avirulence genes on the pathogen side.
Defining the scope of the European Antimicrobial Resistance Surveillance network in Veterinary medicine (EARS-Vet): a bottom-up and One Health approach
Authors: Mader Rodolphe , Bourély Clémence , Amat Jean-Philippe , Broens Els M. , Busani Luca , Callens Bénédicte , Crespo Paloma , Damborg Peter , Filippitzi Maria-Eleni , Fitzgerald William , Grönthal Thomas , Haenni Marisa , Heuvelink Annet , van Hout Jobke , Kaspar Heike , Munoz Cristina , Norström Madelaine , Pedersen Karl , Pokludova Lucie , Pozzo Fabiana Dal , Slowey Rosemarie , Urdahl Anne Margrete , Vatopoulos Alkiviadis , Zafeiridis Christos , Madec Jean-Yves 
Published: March 2021

AbstractBackgroundBuilding the European Antimicrobial Resistance Surveillance network in Veterinary medicine (EARS-Vet) was proposed to strengthen the European One Health antimicrobial resistance (AMR) surveillance approach.ObjectivesThe objectives were to (i) define the combinations of animal species, production types, age categories, bacterial species, specimens and antimicrobials to be monitored in EARS-Vet and to (ii) determine antimicrobial test panels able to cover most combinations.MethodsThe EARS-Vet scope was defined by consensus between 26 European experts. Decisions were guided by a survey of the combinations that are relevant and feasible to monitor in diseased animals in 13 European countries (bottom-up approach). Experts also considered the One Health approach and the need for EARS-Vet to complement existing European AMR monitoring systems coordinated by the European Centre for Disease Prevention and Control (ECDC) and the European Food Safety Authority (EFSA).ResultsEARS-Vet would monitor AMR in six animal species (cattle, swine, chicken (broiler and laying hen), turkey, cat and dog), for 11 bacterial species (Escherichia coli,Klebsiella pneumoniae,Mannheimia haemolytica,Pasteurella multocida,Actinobacillus pleuropneumoniae,Staphylococcus aureus,Staphylococcus pseudintermedius,Staphylococcus hyicus,Streptococcus uberis,Streptococcus dysgalactiaeandStreptococcus suis). Relevant antimicrobials for their treatment were selected (e.g. tetracyclines) and complemented with antimicrobials of more specific public health interest (e.g. carbapenems). Three test panels of antimicrobials were proposed covering most EARS-Vet combinations of relevance for veterinary antimicrobial stewardship.ConclusionsWith this scope, EARS-Vet would enable to better address animal health in the strategy to mitigate AMR and better understand the multi-sectoral AMR epidemiology in Europe.
RS-FISH: Precise, interactive, fast, and scalable FISH spot detection
Authors: Bahry Ella , Breimann Laura , Zouinkhi Marwan , Epstein Leo , Kolyvanov Klim , Long Xi , Harrington Kyle I S , Lionnet Timothée , Preibisch Stephan 
Published: March 2021

AbstractFluorescent in-situ hybridization (FISH)-based methods are powerful tools to study molecular processes with subcellular resolution, relying on accurate identification and localization of diffraction-limited spots in microscopy images. We developed the Radial Symmetry-FISH (RS-FISH) software that accurately, robustly, and quickly detects single-molecule spots in two and three dimensions, making it applicable to several key assays, including single-molecule FISH (smFISH), spatial transcriptomics, and spatial genomics. RS-FISH allows interactive parameter tuning and scales to large sets of images as well as tera-byte sized image volumes such as entire brain scans using straight-forward distributed processing on workstations, clusters, and in the cloud.
The FDA-approved drug cobicistat synergizes with remdesivir to inhibit SARS-CoV-2 replication
Authors: Shytaj Iart Luca , Fares Mohamed , Lucic Bojana , Gallucci Lara , Tolba Mahmoud M. , Zimmermann Liv , Ayoub Ahmed Taha , Cortese Mirko , Neufeldt Christopher J. , Laketa Vibor , Chlanda Petr , Fackler Oliver T. , Boulant Steeve , Bartenschlager Ralf , Stanifer Megan , Savarino Andrea , Lusic Marina 
Published: March 2021

AbstractCombinations of direct-acting antivirals are needed to minimize drug-resistance mutations and stably suppress replication of RNA viruses. Currently, there are limited therapeutic options against the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) and testing of a number of drug regimens has led to conflicting results. Here we show that cobicistat, which is an-FDA approved drug-booster that blocks the activity of the drug metabolizing proteins Cytochrome P450-3As (CYP3As) and P-glycoprotein (P-gp), inhibits SARS-CoV-2 replication. Cell-to-cell membrane fusion assays indicated that the antiviral effect of cobicistat is exerted through inhibition of spike protein-mediated membrane fusion. In line with this, incubation with low micromolar concentrations of cobicistat decreased viral replication in three different cell lines including cells of lung and gut origin. When cobicistat was used in combination with the putative CYP3A target and nucleoside analog remdesivir, a synergistic effect on the inhibition of viral replication was observed in cell lines and in a primary human colon organoid. The cobicistat/remdesivir combination was able to potently abate viral replication to levels comparable to mock-infected cells leading to an almost complete rescue of infected cell viability. These data highlight cobicistat as a therapeutic candidate for treating SARS-CoV-2 infection and as a potential building block of combination therapies for COVID-19.
Quantitative proteomics of hamster lung tissues infected with SARS-CoV-2 reveal host-factors having implication in the disease pathogenesis and severity
Authors: Suresh Voddu , Mohanty Varshasnata , Avula Kiran , Ghosh Arup , Singh Bharti , Reddy R. Rajendra Kumar , Suryawanshi Amol Ratnakar , Raghav Sunil K. , Chattopadhyay Soma , Prasad Punit , Swain Rajeeb Kumar , Dash Rupesh , Parida Ajay , Syed Gulam Hussain , Senapati Shantibhusan 
Published: March 2021

AbstractSyrian golden hamsters (Mesocricetus auratus) infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) manifests lung pathology that resembles human COVID-19 patients. In this study, efforts were made to check the infectivity of a local SARS-CoV-2 isolate in hamster model and evaluate the differential expression of lung proteins during acute infection and convalescence. The findings of this study confirm the infectivity of this isolatein vivo. Analysis of clinical parameters and tissue samples shows a similar type of pathophysiological manifestation of SARS-CoV-2 infection as reported earlier in COVID-19 patients and hamsters infected with other isolates. The lung-associated pathological changes were very prominent on the 4th day post-infection (dpi), mostly resolved by 14dpi. Here, we carried out quantitative proteomic analysis of the lung tissues from SARS-CoV-2-infected hamsters at day 4 and day 14 post infection. This resulted in the identification of 1,585 differentially expressed proteins of which 68 proteins were significantly altered among both the infected groups. Pathway analysis revealed complement and coagulation cascade, platelet activation, ferroptosis and focal adhesion as the top enriched pathways. In addition, we also identified altered expression of two pulmonary surfactant-associated proteins (Sftpd and Sftpb), known for their protective role in lung function. Together, these findings will aid in the identification of candidate biomarkers and understanding the mechanism(s) involved in SARS-CoV-2 pathogenesis.Graphical abstract
Effect of chronic JUUL aerosol inhalation on inflammatory states of the brain, lung, heart and colon in mice
Authors: Moshensky Alex , Brand Cameron , Alhaddad Hasan , Shin John , Masso-Silva Jorge A. , Advani Ira , Gunge Deepti , Sharma Aditi , Mehta Sagar , Jahan Arya , Nilaad Sedtavut , Almarghalani Daniyah , Pham Josephine , Perera Samantha , Park Kenneth , Al-Kolla Rita , Moon Hoyoung , Das Soumita , Byun Min , Shah Zahoor , Sari Youssef , Brown Joan Heller , Crotty Alexander Laura E. 
Published: March 2021

AbstractWhile health effects of conventional tobacco are well defined, data on vaping devices, including the most popular e-cigarette JUUL, are less established. Prior acute e-cigarette studies demonstrated inflammatory and cardiopulmonary physiology changes while chronic studies demonstrated extra-pulmonary effects, including neurotransmitter alterations in reward pathways. In this study we investigated effects of chronic flavored JUUL aerosol inhalation on inflammatory markers in brain, lung, heart, and colon. JUUL induced upregulation of cytokine and chemokine gene expression and increased HMGB1 and RAGE in the nucleus accumbens. Inflammatory gene expression increased in colon, and cardiopulmonary inflammatory responses to acute lung injury with lipopolysaccharide were exacerbated in the heart. Flavor-dependent changes in several responses were also observed. Our findings raise concerns regarding long-term risks of e-cigarette use as neuroinflammation may contribute to behavioral changes and mood disorders, while gut inflammation has been tied to poor systemic health and cardiac inflammation to development of heart disease.One Sentence SummaryChronic, daily inhalation of pod-based e-cigarette aerosols alters the inflammatory state across multiple organ systems in mice.
Vibrio cholerae’s mysterious Seventh Pandemic island (VSP-II) encodes novel Zur-regulated zinc starvation genes involved in chemotaxis and autoaggregation
Authors: Murphy Shannon G. , Johnson Brianna A. , Ledoux Camille M. , Dörr Tobias 
Published: March 2021

AbstractVibrio choleraeis the causative agent of cholera, a notorious diarrheal disease that is typically transmitted via contaminated drinking water. The current pandemic agent, the El Tor biotype, has undergone several genetic changes that include horizontal acquisition of two genomic islands (VSP-I and VSP-II). VSP-I and -2 presence strongly correlates with pandemicity; however, the contribution of these islands toV. cholerae’s life cycle, particularly the 26-kb VSP-II, remains poorly understood. VSP-II-encoded genes are not expressed under standard laboratory conditions, suggesting that their induction requires an unknown signal from the host or environment. One signal that bacteria encounter under both host and environmental conditions is metal limitation. While studyingV. cholerae’s zinc-starvation responsein vitro, we noticed that a mutant constitutively expressing zinc-starvation genes (Δzur) aggregates in nutrient-poor media. Using transposon mutagenesis, we found that flagellar motility, chemotaxis, and VSP-II encoded genes are required for aggregation. The VSP-II genes encode an AraC-like transcriptional activator (VerA) and a methyl-accepting chemotaxis protein (AerB). Using RNA-seq andlacZtranscriptional reporters, we show that VerA is a novel Zur target and activator of the nearby AerB chemoreceptor. AerB interfaces with the chemotaxis system to drive oxygen-dependent autoaggregation and energy taxis. Importantly, this work suggests a functional link between VSP-II, zinc-starved environments, and aerotaxis, yielding insights into the role of VSP-II in a metal-limited host or aquatic reservoir.Author SummaryThe Vibrio Seventh Pandemic island was horizontally acquired by El Tor pandemic strain, but its role in pathogenicity or environmental persistence is unknown. A major barrier to VSP-II study was the lack of stimuli favoring its expression. We show that zinc starvation induces expression of this island and describe a transcriptional network that activates a VSP-II encoded aerotaxis receptor. Importantly, aerotaxis may enableV. choleraeto locate more favorable microenvironments, possibly to colonize anoxic portions of the gut or environmental sediments.
Dual regulation of the actin cytoskeleton by CARMIL-GAP
Authors: Jung Goeh , Pan Miao , Alexander Chris , Jin Tian , Hammer John A. 
Published: March 2021

ABSTRACTCARMIL (Capping proteinArp2/3MyosinILinker) proteins are multi-domain scaffold proteins that regulate actin dynamics by regulating the activity of Capping Protein (CP). Here we characterize CARMIL-GAP, aDictyosteliumCARMIL isoform that contains a ~130 residue insert that, by homology, is a GTPase activating (GAP) domain for Rho-related GTPases. Consistently, this GAP domain bindsDictyosteliumRac1a and accelerates its rate of GTP hydrolysis. CARMIL-GAP concentrates with F-actin in phagocytic cups and at the leading edge of chemotaxing cells, and CARMIL-GAP null cells exhibit pronounced defects in phagocytosis and chemotactic streaming. Importantly, these defects are fully rescued by expressing GFP-tagged CARMIL-GAP in CARMIL-GAP null cells. Finally, rescue with versions of CARMIL-GAP that lack either GAP activity or the ability to regulate CP show that while both activities contribute significantly to CARMIL-GAP function, the GAP activity plays the bigger role. Together, our results add to the growing evidence that CARMIL proteins influence actin dynamics by regulating signaling molecules as well as CP, and that the continuous cycling of the Rho GTPase’s nucleotide state is often required to drive Rho-dependent biological processes.SUMMARY STATEMENTThe assembly of actin filaments supports a wide array of fundamental cellular functions, including cell migration and phagocytosis. Actin assembly is controlled by a host of regulatory proteins, with Capping Protein being one of the most important. Capping Protein is in turn regulated by the CARMIL family of proteins. Actin assembly is also controlled by signaling pathways that often converge on Rho-related GTPases like Rac1. These GTPases cycle between an active, GTP-bound state and an inactive, GDP-bound state. Guanine nucleotide exchange factors (GEFs) and guanine nucleotide activating proteins (GAPs) drive Rho-related GTPases to their GTP-bound and GDP-bound states, respectively. Here we characterized a version of CARMIL that contains within it a GAP domain for Rac1. We show that CARMIL-GAP supports the actin-based processes of cell migration and phagocytosis. We also show that while CARMIL-GAP’s ability to regulate Capping Protein and the nucleotide state of Rac1 are both important for its cellular functions, its ability to regulate Rac1 via its GAP domain plays the bigger role. Finally, our data support the emerging concept that the continuous cycling of Rho GTPases between their GTP- bound and GDP-bound states is often required to drive Rho-dependent biological processes.
Insights into the controls on metabolite distributions along a latitudinal transect of the western Atlantic Ocean
Authors: Johnson Winifred M. , Kido Soule Melissa C. , Longnecker Krista , Bhatia Maya P. , Hallam Steven J. , Lomas Michael W. , Kujawinski Elizabeth B. 
Published: March 2021

AbstractMetabolites, or the small organic molecules that are synthesized by cells during metabolism, comprise a complex and dynamic pool of carbon in the ocean. They are an essential form of information, linking genotype to phenotype at the individual, population and community levels of biological organization. Characterizing metabolite distributions inside microbial cells and dissolved in seawater is essential to understanding the controls on their production and fate, as well as their roles in shaping marine microbial food webs. Here, we apply a targeted metabolomics method to quantify particulate and dissolved distributions of a suite of biologically relevant metabolites including vitamins, amino acids, nucleic acids, osmolytes, and intermediates in biosynthetic pathways along a latitudinal transect in the western Atlantic Ocean. We find that, in the euphotic zone, most particulate or intracellular metabolites positively co-vary with the most abundant microbial taxa. In contrast, dissolved metabolites exhibited greater variability with differences in distribution between ocean regions. Although fewer particulate metabolites were detected below the euphotic zone, molecules identified in the deep ocean may be linked to preservation of organic matter or adaptive physiological strategies of deep-sea microbes. Based on the identified metabolite distributions, we propose relationships between certain metabolites and microbial populations, and find that dissolved metabolite distributions are not directly related to their particulate abundances.
Multiple resource limitations explain biomass-precipitation relationships in grasslands
Authors: Bharath Siddharth , Adler Peter B. , Fay Philip A. , Seabloom Eric W. , Hautier Yann , Biederman Lori , Bugalho Miguel N. , Caldeira Maria , Eskelinen Anu , Knops Johannes M.H. , McCulley Rebecca , Morgan John , Power Sally A , Risch Anita C. , Schuetz Martin , Stevens Carly J. , Ohlert Timothy , Virtanen Risto , Borer Elizabeth T. 
Published: March 2021

AbstractInterannual variability in grassland primary production is strongly driven by precipitation, nutrient availability and herbivory, but there is no general consensus on the mechanisms linking these variables. If grassland biomass is limited by the single most limiting resource at a given time, then we expect that nutrient addition will not affect biomass production at arid sites. We conducted a distributed experiment manipulating nutrients and herbivores at 44 grassland sites in 8 regions around the world, spanning a broad range in aridity. We estimated the effects of 5-11 years of nutrient addition and herbivore exclusion treatments on precipitation sensitivity of biomass (proportional change in biomass relative to proportional change in rainfall among years), and the biomass in the driest year (to measure treatment effects when water was most limiting) at each site. Grazer exclusion did not interact with nutrients to influence driest year biomass or sensitivity. Nutrient addition increased driest year biomass by 74% and sensitivity by 0.12 (proportional units), and that effect did not change across the range of aridity spanned by our sites. Grazer exclusion did not interact with nutrients to influence sensitivity or driest year biomass. At almost half of our sites, the previous year's rainfall explained as much variation in biomass as current year precipitation. Overall, our distributed fertilization experiment detected co-limitation between nutrients and water governing grasslands, with biomass sensitivity to precipitation being limited by nutrient availability irrespective of site aridity and herbivory. Our findings refute the classical ideas that grassland plant performance is limited by the single most limiting resource at a site. This suggests that nutrient eutrophication will destabilize grassland ecosystems through increased sensitivity to precipitation variation.
Longitudinal single-cell epitope and RNA-sequencing reveals the immunological impact of type 1 interferon autoantibodies in critical COVID-19
Authors: van der Wijst Monique G.P. , Vazquez Sara E. , Hartoularos George C. , Bastard Paul , Grant Tianna , Bueno Raymund , Lee David S. , Greenland John R. , Sun Yang , Perez Richard , Ogorodnikov Anton , Ward Alyssa , Mann Sabrina A. , Lynch Kara L. , Yun Cassandra , Havlir Diane V. , Chamie Gabriel , Marquez Carina , Greenhouse Bryan , Lionakis Michail S. , Norris Philip J. , Dumont Larry J. , Kelly Kathleen , Zhang Peng , Zhang Qian , Gervais Adrian , Voyer Tom Le , Whatley Alexander , Si Yichen , Byrne Ashley , Combes Alexis J. , Rao Arjun Arkal , Song Yun S. ,   UCSF COMET consortium, Fragiadakis Gabriela K. , Kangelaris Kirsten , Calfee Carolyn S. , Erle David J. , Hendrickson Carolyn , Krummel Matthew F. , Woodruff Prescott G. , Langelier Charles R. , Casanova Jean-Laurent , Derisi Joseph L. , Anderson Mark S. , Ye Chun Jimmie 
Published: March 2021

AbstractType I interferon (IFN-I) neutralizing autoantibodies have been found in some critical COVID-19 patients; however, their prevalence and longitudinal dynamics across the disease severity scale, and functional effects on circulating leukocytes remain unknown. Here, in 284 COVID-19 patients, we found IFN-I autoantibodies in 19% of critical, 6% of severe and none of the moderate cases. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 COVID-19 patients, 15 non-COVID-19 patients and 11 non-hospitalized healthy controls, revealed a lack of IFN-I stimulated gene (ISG-I) response in myeloid cells from critical cases, including those producing anti-IFN-I autoantibodies. Moreover, surface protein analysis showed an inverse correlation of the inhibitory receptor LAIR-1 with ISG-I expression response early in the disease course. This aberrant ISG-I response in critical patients with and without IFN-I autoantibodies, supports a unifying model for disease pathogenesis involving ISG-I suppression via convergent mechanisms.