bluuebunny/crossref_metadata_2025_split huggingface dataset:
Piezo1 potentially mediates inflammation in balloon-inflated rat brain and its bidirectional mechanosensitivity
Authors: Zhang Yichi , Wang Gang , Xie Minjie , Lian Lifei , Xiong Yongjie , Xu Feng , Li Guo , Tang Zhouping , Wang Furong , Zhu Suiqiang 
Published: July 2020

AbstractBrain injury after intracerebral hemorrhage is extremely complicated, and the exact mechanism remains puzzling. Piezo1, a novel mammalian mechanosensitive ion channel, has been identified to play important roles in several pathologic and physiologic procedures that involve cellular mechanotransduction. However, the role of Piezo1 in hematoma compression after intracerebral hemorrhage is still unclear. In the present study, we established a balloon-inflated rat brain model mimicking the pure mechanical compression of a hematoma and detected balloon compression in the basal ganglia region of the brain, resulting in abnormal behaviors and a significant increase in the expression of Piezo1 and proinflammatory cytokines. These effects were reversed by GsMTx4, an antagonist of Piezo1. Additionally, the balloon deflation time affected behavioral function and the levels of Piezo1 and proinflammatory cytokines. These results establish the firstin vivoevidence for the role of Piezo1 in blood-brain neuroinflammation after hematoma compression. Piezo1 may therefore be a potential therapeutic target for the treatment of intracerebral hemorrhage.
Interactive effects of aging and aerobic capacity on energy metabolism-related metabolites of serum, skeletal muscle, and white adipose tissue
Authors: Zhuang Haihui , Karvinen Sira , Zhang Xiaobo , Ojanen Xiaowei , Törmakangas Timo , Velagapudi Vidya , Alen Markku , Britton Steven L. , Koch Lauren G. , Kainulainen Heikki , Cheng Sulin , Wiklund Petri 
Published: July 2020

ABSTRACTAerobic capacity is a strong predictor of longevity. With aging, aerobic capacity decreases concomitantly with changes in whole body metabolism leading to increased disease risk. To address the role of aerobic capacity, aging and their interaction on metabolism, we utilized rat models of low and high intrinsic aerobic capacity (LCRs/HCRs) and assessed the metabolomics of serum, muscle, and white adipose tissue (WAT). We compared LCRs and HCRs at two time points: Young rats were sacrificed at 9 months, and old rats were sacrificed at 21 months. Targeted and semi-quantitative metabolomics analysis was performed on ultra-pressure Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS) platform. Interaction of aerobic capacity and aging was studied via regression analysis. Our results showed at young age, metabolites linked to amino acid metabolism differed in serum and muscle with aerobic capacity, whereas no difference were observed in WAT. In aged animals, most prominent changes in metabolites occurred in WAT. Aerobic capacity and aging interactively affected seven metabolites linked to energy metabolism. Our results support previous findings that high aerobic capacity is associated with more efficient amino acid metabolism in muscle. While impaired branched chain amino acids (BCAAs) and fatty acid metabolism in the muscle may associate to the high risk of metabolic disorders and shorter lifespan previously observed in LCRs. The interactive effects of aging and aerobic capacity on energy metabolism-related metabolites were largely driven by HCRs, reflecting the importance of inherited aerobic capacity in the aging process. Our results highlight that dysfunctional mitochondrial β-oxidation in WAT may be one key mechanism related to aging.
A genomic link in China roses: and they all lived prickly but water deficient ever after?
Authors: Zhong Mi-Cai , Jiang Xiao-Dong , Yang Guo-Qian , Cui Wei-Hua , Suo Zhi-Quan , Wang Wei-Jia , Sun Yi-Bo , Wang Dan , Cheng Xin-Chao , Li Xu-Ming , Dong Xue , Tang Kai-Xue , Li De-Zhu , Hu Jin-Yong 
Published: July 2020

AbstractPrickles act against herbivores, pathogens or mechanical injury, while also prevent water loss. However, whether prickles have new function and the molecular genetics of prickle patterning remains poorly explored. Here, we generated a high-quality reference genome assembly for ‘Basye’s Thornless’ (BT), a prickle-free cultivar ofRosa wichuraiana,to identify genetic elements related to stem prickle development. The BT genome harbors a high level of sequence diversity in itself and between cultivar ‘Old Blush’ (R. chinensis), a founder genotype in rose domestication. Inheritance of stem prickle density was determined and two QTL were identified. Differentially expressed genes in QTL were involved in water-related functions, suggesting that prickle density may hitchhike with adaptations to moist environments. While the prickle-related gene-regulatory-network (GRN) was highly conserved, the expression variation of key candidate genes was associated with prickle density. Our study provides fundamental resources and insights for genome evolution in the Rosaceae. Ongoing efforts on identification of the molecular bases for key rose traits may lead to the improvement of horticultural markets.
Probabilistic approaches for classifying highly variable anti-SARS-CoV-2 antibody responses
Authors: Dopico Xaquin C , Hanke Leo , Sheward Daniel J. , Muschiol Sandra , Aleman Soo , Grinberg Nastasiya F. , Adori Monika , Christian Murray , Vidakovics Laura Perez , Kim Changil , Khoenkhoen Sharesta , Pushparaj Pradeepa , Morro Ainhoa Moliner , Mandolesi Marco , Ahl Marcus , Forsell Mattias , Coquet Jonathan , Corcoran Martin , Rorbach Joanna , Dillner Joakim , Bogdanovic Gordana , McInerney Gerald M. , Allander Tobias , Murrell Ben , Wallace Chris , Albert Jan , Karlsson Hedestam Gunilla B. 
Published: July 2020

AbstractAntibody responses vary widely between individuals1, complicating the correct classification of low-titer measurements using conventional assay cut-offs. We found all participants in a clinically diverse cohort of SARS-CoV-2 PCR+ individuals (n=105) – and n=33 PCR+ hospital staff – to have detectable IgG specific for pre-fusion-stabilized spike (S) glycoprotein trimers, while 98% of persons had IgG specific for the receptor-binding domain (RBD). However, anti-viral IgG levels differed by several orders of magnitude between individuals and were associated with disease severity, with critically ill patients displaying the highest anti-viral antibody titers and strongest in vitro neutralizing responses. Parallel analysis of random healthy blood donors and pregnant women (n=1,000) of unknown serostatus, further demonstrated highly variable IgG titers amongst seroconverters, although these were generally lower than in hospitalized patients and included several measurements that scored between the classical 3 and 6SD assay cut-offs. Since the correct classification of seropositivity is critical for individual- and population-level metrics, we compared different probabilistic algorithms for their ability to assign likelihood of past infection. To do this, we used tandem anti-S and -RBD IgG responses from our PCR+ individuals (n=138) and a large cohort of historical negative controls (n=595) as training data, and generated an equal-weighted learner from the output of support vector machines and linear discriminant analysis. Applied to test samples, this approach provided a more quantitative way to interpret anti-viral titers over a large continuum, scrutinizing measurements overlapping the negative control background more closely and offering a probability-based diagnosis with potential clinical utility. Especially as most SARS-CoV-2 infections result in asymptomatic or mild disease, these platform-independent approaches improve individual and epidemiological estimates of seropositivity, critical for effective management of the pandemic and monitoring the response to vaccination.
Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome
Authors: Pandolfi Laura , Fossali Tommaso , Frangipane Vanessa , Bozzini Sara , Morosini Monica , D’Amato Maura , Lettieri Sara , Urtis Mario , Di Toro Alessandro , Saracino Laura , Percivalle Elena , Tomaselli Stefano , Cavagna Lorenzo , Cova Emanuela , Mojoli Francesco , Bergomi Paola , Ottolina Davide , Lilleri Daniele , Corsico Angelo Guido , Arbustini Eloisa , Colombo Riccardo , Meloni Federica 
Published: July 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. We conducted a prospective study to assess deep lung inflammatory status in patients with moderate to severe COVID-19.Diagnostic bronchoalveolar lavage (BAL) was performed in 33 adult patients with SARS-CoV-2 infection by real-time PCR on nasopharyngeal swab admitted to the Intensive care unit (ICU) (n=28) and to the Intermediate Medicine Ward (IMW) (n=5). We analyze the differential cell count, ultrastructure of cells and Interleukin(IL)6, 8 and 10 levels.ICU patients showed a marked increase in neutrophils (72%, 60-81), lower lymphocyte (8%, 4-12) and macrophages fractions (17%, 11-27) compared to IMW patients (3%, 2-17, 15%, 6-26 and 74%, 58-90, respectively) (p<0.01). Ultrastructural study from ICU patients showed viral-like particles in cytopathic mononuclear cells however extensive cytopathic damage in all cell lineages. Immunostaining with anti-viral capsid and spike antibodies specifically immunoreacted with BAL cells, mostly cytopathic ones. IL6 and IL8 were significantly higher in ICU patients than in IMW (IL6 p<0.01, IL8 p<0.0001), and also in patients who did not survive (IL6 p < 0.05, IL8 p = 0.05 vs. survivors). IL10 did not show a significant variation between groups. Dividing patients by treatment received, lower BAL concentrations of IL6 were found in patients treated with steroids as compared to those treated with tocilizumab (p<0.1) or antivirals (p<0.05).Alveolitis, associated with COVID-19, is mainly sustained by innate effectors which showed features of extensive activation. The burden of pro-inflammatory cytokines IL6 and IL8 in the broncho-alveolar environment is associated with clinical outcome.
Assessing the effects of non-pharmaceutical interventions on SARS-CoV-2 transmission in Belgium by means of an extended SEIQRD model and public mobility data
Authors: Alleman Tijs W. , Vergeynst Jenna , De Visscher Lander , Rollier Michiel , Torfs Elena , Nopens Ingmar , Baetens Jan M. 
Published: July 2020

AbstractWe present a compartmental extended SEIQRD metapopulation model for SARS-CoV-2 spread in Belgium. We demonstrate the robustness of the calibration procedure by calibrating the model using incrementally larger datasets and dissect the model results by computing the effective reproduction number at home, in workplaces, in schools, and during leisure activities. We find that schools are an important transmission pathway for SARS-CoV-2, with the potential to increase the effective reproduction number from Re = 0.66 ± 0.04 (95 % CI) to Re = 1.09 ± 0.05 (95 % CI) under lockdown measures. The model accounts for the main characteristics of SARS-CoV-2 transmission and COVID-19 disease and features a detailed representation of hospitals with parameters derived from a dataset consisting of 22 136 hospitalized patients. Social contact during the pandemic is modeled by scaling pre-pandemic contact matrices with Google Community Mobility data and with effectivity-of-contact parameters inferred from hospitalization data. The calibrated social contact model with its publically available mobility data, although coarse-grained, is a readily available alternative to social-epidemiological contact studies under lockdown measures, which were not available at the start of the pandemic.
The psychological impact of ‘mild lockdown’ in Japan during the COVID-19 pandemic: a nationwide survey under a declared state of emergency
Authors: Yamamoto Tetsuya , Uchiumi Chigusa , Suzuki Naho , Yoshimoto Junichiro , Murillo-Rodriguez Eric 
Published: July 2020

AbstractThis study examined the psychological distress caused by non-coercive lockdown (mild lockdown) in Japan. An online survey was conducted with 11,333 people (52.4% women; mean age = 46.3 ± 14.6 years, range = 18-89 years) during the mild lockdown in the seven prefectures most affected by COVID-19 infection. Over one-third (36.6%) of participants experienced mild-to-moderate psychological distress (Kessler Psychological Distress Scale [K6] score 5-12), while 11.5% reported serious psychological distress (K6 score ≥ 13). The estimated prevalence of depression (Patient Health Questionnaire-9 score ≥ 10) was 17.9%. Regarding the distribution of K6 scores, the proportion of individuals displaying psychological distress in this study was significantly higher compared to previous national survey data from 2010, 2013, 2016 and 2019. Healthcare workers, those with a history of treatment for mental illness, and younger participants (aged 18-19 or 20-39 years) were particularly vulnerable. Psychological distress severity was influenced by specific interactional structures of risk factors: high loneliness, poor interpersonal relationships, COVID-19-related sleeplessness and anxiety, deterioration of household economy, and work and academic difficulties. Flexible approaches that are optimised for the difficulties specific to each individual through cross-disciplinary public-private initiatives are important to combat lockdown-induced mental health problems.
Multisectoral collaboration for pandemic response and operational support of critical care and emergency departments
Authors: Christofferson RC , O’Neal Hollis R. , Jagneaux Tonya , O’Neal Catherine , Walsh Christine S. , Mayton E. Handly , Vu Luan D. , Fish Abigail I. , Phan Anh , Stoufflet Thaya E. , Schroeder Jonathan R. , Walker Morgan , Turner Erik A. , Pierce Christi G. , Wester K. Scott , DeLeo Connie , Tenreiro Edgardo , Ogden Beverly W. , Cormier Stephania A. 
Published: July 2020

AbstractBackgroundIn March 2020, an influx of admissions in COVID-19 positive patients threatened to overwhelm healthcare facilities in East Baton Rouge Parish, Louisiana. Exacerbating this problem was a shortage of diagnostic testing capability, resulting in a delay in time-to-result return. An improvement in diagnostic testing availability and timeliness was necessary to improve the allocation of resources and ultimate throughput of patients. The management of a COVID-19 positive patient or patient under investigation requires infection control measures that can quickly consume personal protective equipment (PPE) stores and personnel available to treat these patients. Critical shortages of both PPE and personnel also negatively impact care in patients admitted with non-COVID-19 illnesses.MethodsA multisectoral partnership of healthcare providers, facilities and academicians created a molecular diagnostic lab within an academic research facility dedicated to testing inpatients and healthcare personnel for SARS-CoV-2. The purpose of the laboratory was to provide a temporary solution to the East Baton Rouge Parish healthcare community until individual facilities were self-sustaining in testing capabilities. We describe the partnership and the impacts of this endeavor by developing a model derived from a combination of data sources, including electronic health records, hospital operations, and state and local resources.FindingsOur model demonstrates two important principles: the impact of reduced turnaround times (TAT) on potential differences in inpatient population numbers for COVID-19 and savings in PPE attributed to the more rapid TAT.InterpretationOverall, we provide rationale for and demonstration of the utility of multisectoral partnerships when responding to public health emergencies.
Calm on the surface, dynamic on the inside. Molecular homeostasis in response to regulatory and metabolic perturbation ofAnabaenasp. PCC 7120 nitrogen metabolism
Authors: Perin Giorgio , Fletcher Tyler , Sagi-Kiss Virag , Gaboriau David C. A. , Carey Mathew R. , Bundy Jacob G. , Jones Patrik R. 
Published: July 2020

AbstractNitrogen is a key macro-nutrient required for the metabolism and growth of biological systems. Although multiple nitrogen sources can serve this purpose, they are all converted into ammonium/ammonia as a first step of assimilation. It is thus reasonable to expect that molecular parts involved in the transport of ammonium/ammonia across biological membranes (i.e. catalysed by AMT transporters) connect with the regulation of both nitrogen and central carbon metabolism. In order to test this hypothesis, we applied both (1) genetic (i.e. Δamtmutation) and (2) environmental treatments to a target biological system, the cyanobacterium Anabaena sp. PCC 7120. Cyanobacteria have a key role in the global nitrogen cycle and thus represent a useful model system. The aim was to both (1) perturb sensing and low-affinity uptake of ammonium/ammonia and (2) induce multiple inner N states, followed by targeted quantification of key proteins, metabolites and enzyme activities, with experiments intentionally designed over a longer time-scale than the available studies in literature. We observed that the absence of AMT transporters triggered a substantial response at a whole-system level, affecting enzyme activities and the quantity of both proteins and metabolites, spanning both N and C metabolism. Moreover, the absence of AMT transporters left a molecular fingerprint indicating N-deficiency even under N replete conditions (i.e. greater GS activity, lower 2-OG content and faster nitrogenase activation upon N deprivation). Contrasting with all of the above dynamic adaptations was the striking near-complete lack of any externally measurable phenotype (i.e. growth, photosynthesis, pigments, metabolites). We thus conclude that this species evolved a highly robust and adaptable molecular network to maintain homeostasis, resulting in substantial internal but minimal external perturbations. The analytical data highlights several internal adaptations, including increased N assimilation (i.e. greater GS activity) and nitrogenase activity (i.e. faster activation upon N deprivation) together with altered amino acids metabolism, as indicated by changes in Gln, Glu and 2-OG, indicating an altered C/N balance. The analyses provides evidence for an active role of AMT transporters in the regulatory/signalling network of N metabolism in this biological system, and the existence of a novel fourth IF7A-independent regulatory mechanism controlling GS activity.
The enrichment of breakpoints in late-replicating chromatin provides novel insights into chromoanagenesis mechanisms
Authors: Chatron Nicolas , Giannuzzi Giuliana , Rollat-Farnier Pierre-Antoine , Diguet Flavie , Porcu Eleonora , Yammine Tony , Uguen Kevin , Bellil Zohra-Lydia , Zillhardt Julia Lauer , Sorlin Arthur , Ader Flavie , Afenjar Alexandra , Andrieux Joris , Bardel Claire , Calpena Eduardo , Chantot-Bastaraud Sandra , Callier Patrick , Chelloug Nora , Chopin Emilie , Cordier Marie-Pierre , Dubourg Christèle , Faivre Laurence , Girard Françoise , Heide Solveig , Herenger Yvan , Jaillard Sylvie , Keren Boris , Knight Samantha J. L. , Lespinasse James , Lohmann Laurence , Marle Nathalie , Maroofian Reza , Masurel-Paulet Alice , Mathieu-Dramard Michèle , Metay Corinne , Pagnamenta Alistair T. , Portnoï Marie-France , Prieur Fabienne , Rio Marlène , Siffroi Jean-Pierre , Valence Stéphanie , Taylor Jenny C. , Wilkie Andrew O. M. , Edery Patrick , Reymond Alexandre , Sanlaville Damien , Schluth-Bolard Caroline 
Published: July 2020

AbstractThe rise of pangenomic molecular assays allowed uncovering complex rearrangements namedchromoanagenesisthat were hypothesized to result from catastrophic shattering events. Constitutional cases have typically been reported individually preventing identification of common features and uncovering the mechanisms at play. We characterized 20 newchromoanagenesisand discovered yet undescribed features. While literature differentiateschromothripsisand its shattering event repaired through non-homologous end joining fromchromoanasynthesisborn to aberrant replicative processes, we identified shattered chromosomes repaired through a combination of mechanisms. In particular, three samples present with “rearrangement hubs” comprising a fragmented kilobase-long sequence threaded throughout the rearrangement.To assess the mechanisms at play, we merged our data with those of 20 published constitutional complex chromosomal rearrangement cases. We evaluated if the distribution of their 1032 combined breakpoints was distinctive using bootstrap simulations and found that breakpoints tend to keep away from haplosensitive genes suggesting selective pressure. We then compared their distribution with that of 13,310 and 468 breakpoints of cancer complex chromosomal rearrangements and constitutional simple rearrangement samples, respectively. Both complex rearrangement groups showed breakpoint enrichment in late replicating regions suggesting similar origins for constitutional and cancer cases. Simple rearrangement breakpoints but not complex ones were depleted from lamina-associated domains (LADs), possibly as a consequence of reduced mobility of DNA ends bound to lamina.The enrichment of breakpoints in late-replicating chromatin for both constitutional and cancerchromoanagenesisprovides an orthogonal support to the premature chromosome condensation hypothesis that was put forward to explainchromoanagenesis.
Delineation of a molecularly distinct terminally differentiated memory CD8 T cell population
Authors: Milner J. Justin , Nguyen Hongtuyet , Omilusik Kyla , Reina-Campos Miguel , Tsai Matthew , Toma Clara , Delpoux Arnaud D. , Boland Brigid S. , Hedrick Stephen M. , Chang John T. , Goldrath Ananda W. 
Published: July 2020

AbstractMemory CD8 T cells provide durable protection against diverse intracellular pathogens and can be broadly segregated into distinct circulating and tissue-resident populations. Paradigmatic studies have demonstrated circulating memory cells can be further divided into effector memory (Tem) and central memory (Tcm) populations based on discrete functional characteristics. Following resolution of infection, we identified a persisting antigen-specific CD8 T cell population that was simultaneously terminally-fated with potent effector function but maintained memory T cell qualities and conferred robust protection against reinfection. Notably, this terminally-differentiated effector memory CD8 T cell population (terminal-Tem) was conflated within the conventional Tempopulation, prompting redefinition of the classical characteristics of Temcells. Murine terminal-Temwere transcriptionally, functionally, and developmentally unique compared to Temcells. Through mass cytometry and single-cell RNAseq analyses of human peripheral blood from healthy individuals, we also identified an analogous terminal-Tempopulation of CD8 T cells that was transcriptionally distinct from Temand Tcm. A key finding of this study was that parsing of terminal-Temfrom conventionally defined Temchallenges classical characteristics of Tembiology, including enhanced presence in lymphoid tissues, robust IL-2 production and recall potential, greater than expected homeostatic fitness, refined transcription factor dependencies, and a distinct molecular phenotype. Classification of terminal-Temand clarification of Tembiology hold broad implications for understanding the molecular regulation of memory cell states and harnessing immunological memory to improve immunotherapies.