bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preexisting memory CD4 T cells in naïve individuals confer robust immunity upon hepatitis B vaccination
Authors: Elias George , Meysman Pieter , Bartholomeus Esther , De Neuter Nicolas , Keersmaekers Nina , Suls Arvid , Jansens Hilde , Souquette Aisha , De Reu Hans , Smits Evelien , Lion Eva , Thomas Paul G. , Mortier Geert , Van Damme Pierre , Beutels Philippe , Laukens Kris , Van Tendeloo Viggo , Ogunjimi Benson 
Published: August 2020

SummaryAntigen recognition through the T cell receptor (TCR) αβ heterodimer is one of the primary determinants of the adaptive immune response. Vaccines activate naïve T cells with high specificity to expand and differentiate into memory T cells. However, antigen-specific memory CD4 T cells exist in unexposed antigen-naïve hosts. In this study, we use high-throughput sequencing of memory CD4 TCRβ repertoire and machine learning to show that individuals with preexisting vaccine-reactive memory CD4 T cell clonotypes elicited earlier and higher antibody titers and mounted a more robust CD4 T cell response to hepatitis B vaccine. In addition, integration of TCRβ sequence patterns into a hepatitis B vaccine specific model can predict which individuals will have an early and more vigorous vaccine-elicited immunity. Thus, the presence of preexisting memory T clonotypes has a significant impact on immunity and can be used to predict immune responses to vaccination.
BDNF/TrkB signaling endosomes in axons coordinate CREB/mTOR activation and protein synthesis in the cell body to induce dendritic growth in cortical neurons
Authors: Moya-Alvarado Guillermo , Guerra Miguel V. , Wu Chengbiao , Mobley William C. , Perlson Eran , Bronfman Francisca C 
Published: August 2020

ABSTRACTBrain-derived neurotrophic factor (BDNF) and its receptors tyrosine kinase receptor B (TrkB) and the p75 neurotrophin receptor (p75) are the primary regulators of dendritic growth in the central nervous system (CNS). After being bound by BDNF, TrkB and p75 are endocytosed into endosomes and continue signaling within the cell soma, dendrites, and axons. We studied the functional role of BDNF axonal signaling in cortical neurons derived from different transgenic mice using compartmentalized cultures in microfluidic devices. We found that axonal BDNF increased dendritic growth from the neuronal cell body in a cAMP response element-binding protein (CREB)-dependent manner. These effects were dependent on axonal TrkB but not p75 activity. Dynein-dependent BDNF-TrkB-containing endosome transport was required for long-distance induction of dendritic growth. Axonal signaling endosomes increased CREB and mTOR kinase activity in the cell body, and this increase in the activity of both proteins was required for general protein translation and the expression of Arc, a plasticity-associated gene, indicating a role for BDNF-TrkB axonal signaling endosomes in coordinating the transcription and translation of genes whose products contribute to learning and memory regulation.
Mask Wearing and Control of SARS-CoV-2 Transmission in the United States
Authors: Rader Benjamin , White Laura F. , Burns Michael R. , Chen Jack , Brilliant Joe , Cohen Jon , Shaman Jeffrey , Brilliant Larry , Hawkins Jared B. , Scarpino Samuel V. , Astley Christina M. , Brownstein John S. 
Published: August 2020

IntroductionCloth face coverings and surgical masks have become commonplace across the United States in response to the SARS-CoV-2 epidemic. While evidence suggests masks help curb the spread of respiratory pathogens, research is limited. Face masks have quickly become a topic of public debate as government mandates have started requiring their use. Here we investigate the association between self-reported mask wearing, social distancing and community SARS-CoV-2 transmission in the United States, as well as the effect of statewide mandates on mask uptake.MethodsSerial cross-sectional surveys were administered June 3 through July 27, 2020 via web platform. Surveys queried individuals’ likelihood to wear a face mask to the grocery store or with family and friends. Responses (N=378,207) were aggregated by week and state and combined with measures of the instantaneous reproductive number (Rt), social distancing proxies, respondent demographics and other potential sources of confounding. We fit multivariate logistic regression models to estimate the association between mask wearing and community transmission control (Rt <1) for each state and week. Multiple sensitivity analyses were considered to corroborate findings across mask wearing definitions, Rt estimators and data sources. Additionally, mask wearing in 12 states was evaluated two weeks before and after statewide mandates.ResultsWe find an upward trend in mask usage across the U.S., although uptake varies by geography and demographic groups. A multivariate logistic model controlling for social distancing and other variables found a 10% increase in mask wearing was associated with a 3.53 (95% CI: 2.03, 6.43) odds of transmission control (Rt <1). We also find that communities with high mask wearing and social distancing have the highest predicted probability of a controlled epidemic. These positive associations were maintained across sensitivity analyses. Segmented regression analysis of mask wearing found no statistical change following mandates, however the positive trend of increased mask wearing over time was preserved.ConclusionWidespread utilization of face masks combined with social distancing increases the odds of SARS-CoV-2 transmission control. Mask wearing rose separately from government mask mandates, suggesting supplemental public health interventions are needed to maximize mask adoption and disrupt the spread of SARS-CoV-2, especially as social distancing measures are relaxed.
SARS-CoV-2 specific memory B cells frequency in recovered patient remains stable while antibodies decay over time
Authors: Vaisman-Mentesh A. , Dror Y. , Tur-Kaspa R. , Markovitch D. , Kournos Tatiana , Dicker D. , Wine Y. 
Published: August 2020

AbstractThe breadth of the humoral immune response following SARS-CoV-2 infection was indicated to be important for recovery from COVID-19. Recent studies have provided valuable insights regarding the dynamics of the antibody response in symptomatic COVID-19 patients. However, the information regarding the dynamics of the serological and cellular memory in COVID-19 recovered patients in scarce. It is imperative to determine the persistence of humoral memory in COVID-19 recovered patients as it will help to evaluate the susceptibility of recovered patients to re-infection. Here, we describe the dynamics of both the SARS-CoV-2 specific serological and B cell response in COVID-19 recovered patients. We found that symptomatic SARS-CoV-2 patients mount a robust antibody response following infection however, the serological memory decays in recovered patients over the period of 6 months. On the other hand, the B cell response as observed in the SARS-CoV-2 specific memory B cell compartment, was found to be stable over time. Moreover, the frequency of SARS-CoV-2 specific B cell plasmablasts was found to be associated with the SARS-CoV-2 specific antibody levels. These data, suggests that the differentiation of short-lived plasmablasts to become long-lived plasma cells is impaired and the main contributor of antibody production are the short-lived plasmablasts.Overall, our data provides insights regarding the humoral memory persistence in recovered COVID-19 patients. Notwithstanding the insights from this study, it is still to be determined if the persistence of SARS-CoV-2 memory B cells can be considered as a correlate of protection in the absence of serological memory.
Impact of nonpharmaceutical governmental strategies for prevention and control of COVID-19 in São Paulo State, Brazil
Authors: Fortaleza Cristiane Ravagnani , Vilches Thomas Nogueira , Berg de Almeida Gabriel , Ferreira Claudia Pio , Grotto Rejane Maria Tommasini , Guimarães Raul Borges , Souza Lenice do Rosário de , Fortaleza Carlos Magno Castelo Branco 
Published: August 2020

AbstractInterrupted time series analyses (ITSA) were performed to measure the impact of social distancing policies (instituted 22/03/2020) and subsequent mandatory masking in the community (instituted 04/05/2020) on the incidence and effective reproductive number (Rt) of COVID-19 in São Paulo State, Brazil. Overall, the impact of social distancing both on incidence and Rt was greater than the incremental effect of mandatory masking. Those findings may reflect either a small impact of face masking or the loosening of social distancing after mandatory use of masks.
Epidemiologically most successful SARS-CoV-2 variant: concurrent mutations in RNA-dependent RNA polymerase and spike protein
Authors: Ilmjärv Sten , Abdul Fabien , Acosta-Gutiérrez Silvia , Estarellas Carolina , Galdadas Ioannis , Casimir Marina , Alessandrini Marco , Gervasio Francesco Luigi , Krause Karl-Heinz 
Published: August 2020

AbstractThe D614G mutation of the Spike protein is thought to be relevant for SARS-CoV-2 infection. Here we report biological and epidemiological aspects of this mutation. Using pseudotyped lentivectors, we were able to confirm that the G614 variant of the Spike protein is markedly more infectious than the ancestral D614 variant. We demonstrate by molecular modelling that the replacement of aspartate by glycine in position 614 facilitates the transition towards an open state of the Spike protein. To understand whether the increased infectivity of the D614 variant explains its epidemiological success, we analysed the evolution of 27,086 high-quality SARS-CoV-2 genome sequences from GISAID. We observed striking coevolution of D614G with the P323L mutation in the viral polymerase. Importantly, exclusive presence of G614 or L323 did not become epidemiologically relevant. In contrast, the combination of the two mutations gave rise to a viral G/L variant that has all but replaced the initial D/P variant. There was no significant correlation between reported COVID mortality in different countries and the prevalence of the Wuhan versus G/L variant. However, when comparing the speed of emergence and the ultimate predominance in individual countries, the G/L variant displays major epidemiological supremacy. Our results suggest that the P323L mutation, located in the interface domain of the RNA-dependent RNA polymerase (RdRp), is a necessary alteration that led to the epidemiological success of the present variant of SARS-CoV-2.
Bayesian Estimation of the Seroprevalence of Antibodies to SARS-CoV-2
Authors: Dong Qunfeng , Gao Xiang 
Published: August 2020

ABSTRACTAccurately estimating the seroprevalence of antibodies to SARS-CoV-2 requires the use of appropriate methods. Bayesian statistics provides a natural framework for considering the variabilities of specificity and sensitivity of the antibody tests, as well as for incorporating prior knowledge of viral infection prevalence. We present a full Bayesian approach for this purpose, and we demonstrate the utility of our approach using a recently published large-scale dataset from the U.S. CDC.
Antiviral activity of lambda-carrageenan against influenza viruses in mice and severe acute respiratory syndrome coronavirus 2in vitro
Authors: Jang Yejin , Shin Heegwon , Lee Myoung Kyu , Kwon Oh Seung , Shin Jin Soo , Kim Yongil , Kim Meehyein 
Published: August 2020

ABSTRACTInfluenza virus and coronavirus, belonging to enveloped RNA viruses, are major causes of human respiratory diseases. The aim of this study was to investigate the broad spectrum antiviral activity of a naturally existing sulfated polysaccharide, lambda-carrageenan (λ-CGN), purified from marine red algae. Cell culture-based assays revealed that the macromolecule efficiently inhibited both influenza A and B viruses, as well as currently circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with EC50values ranging from 0.3–1.4 μg/ml. No toxicity to host cells was observed at concentrations up to 300 μg/ml. Plaque titration and western blot analysis verified that λ-CGN reduced expression of viral proteins in cell lysates and suppressed progeny virus production in culture supernatants in a dose-dependent manner. This polyanionic compound exerts antiviral activity by targeting viral attachment to cell surface receptors and preventing entry. Moreover, intranasal administration to mice during influenza A viral challenge not only alleviated infection-mediated reductions in body weight but also protected 60% of mice from virus-induced mortality. Thus, λ-CGN could be a promising antiviral agent for preventing infection by several respiratory viruses.
Training Infrastructure as a Service
Authors: Rasche Helena , Grüning Björn 
Published: August 2020

AbstractBackgroundHands-on training, whether it is in Bioinformatics or other scientific domains, requires significant resources and knowledge to setup and run. Trainers must have access to infrastructure that can support the sudden spike in usage, with classes of 30 or more trainees simultaneously running resource intensive tools. For efficient classes, the jobs must run quickly, without queuing delays, lest they disrupt the timetable set out for the class. Often times this is achieved via running on a private server where there is no contention for the queue, and therefore no or minimal waiting time. However, this requires the teacher or trainer to have the technical knowledge to manage compute infrastructure, in addition to their didactic responsibilities. This presents significant burdens to potential training events, in terms of infrastructure cost, person-hours of preparation, technical knowledge, and available staff to manage such events.FindingsGalaxy Europe has developed Training Infrastructure as a Service (TIaaS) which we provide to the scientific commnuity as a service built on top of the Galaxy Platform. Training event organisers request a training and Galaxy administrators can allocate private queues specifically for the training. Trainees are transparently placed in a private queue where their jobs run without delay. Trainers access the dashboard of the TIaaS Service and can remotely follow the progress of their trainees without in-person interactions.ConclusionsTIaaS on Galaxy Europe provides reusable and fast infrastructure for Galaxy training. The instructor dashboard provides visibility into class progress, making in-person trainings more efficient and remote training possible. In the past 24 months, > 110 trainings with over 3000 trainees have used this infrastructure for training, across scientific domains, all enjoying the accessibility and reproducibility of Galaxy for training the next generation of bioinformaticians. TIaaS itself is an extension to Galaxy which can be deployed by any Galaxy administrator to provide similar benefits for their users.https://galaxyproject.eu/tiaas
Drosophilamacrophage self-renewal is regulated by transient expression of PDGF- and VEGF-related factor 2
Authors: Bakopoulos Daniel , Whisstock James C. , Warr Coral G. , Johnson Travis K. 
Published: August 2020

AbstractMacrophages are an ancient animal blood cell lineage critical for tissue homeostasis and defence against pathogens. Until recently, their numbers were thought to be sustained solely by specialised hematopoietic organs. It is now clear that many macrophages are instead replenished by self-renewal, yet the signals that regulate this remain poorly understood. InDrosophila melanogaster, macrophages (known as plasmatocytes) undergo a phase of rapid population expansion via self-renewal, makingDrosophilaan attractive model for revealing the signals and regulatory mechanisms involved. However, no central self-renewal pathway has been identified inDrosophila. Here, we investigated the PDGF-/VEGF-receptor pathway as a candidate for playing this role. Analysis of larvae deficient for each of the three PDGF-/VEGF-receptor ligands Pvf1-3 revealed Pvf2 as a major driver of macrophage self-renewal inDrosophila. We further found that only a small proportion of blood cells expressPvf2, and knockdown experiments implicate these cells as a major source ofPvf2in self-renewal. Lineage tracing studies support the idea thatPvf2expression in blood cells occurs transiently throughout the macrophage self-renewal period, and in response to an as yet unidentified cue. These data define the regulation ofPvf2expression in blood cells as a central mechanism by which macrophage self-renewal is controlled. Given the strong parallels that exist betweenDrosophilaand vertebrate macrophage systems, it is likely that similar mechanisms are at play across animal phyla.
Avalanche criticality in individuals, fluid intelligence and working memory
Authors: Xu Longzhou , Yu Lianchun , Feng Jianfeng 
Published: August 2020

AbstractThe critical brain hypothesis suggests that efficient neural computation can be realized through dynamics of the brain characterized by scale-free avalanche activities. However, the relation between human cognitive performance and the avalanche criticality in large-scale brain networks remains unclear. In this study, we analyzed the mean synchronization and synchronization entropy of blood oxygenation level signals from resting-state fMRI. We found that the scale-free avalanche activity was associated with intermediate synchronization and maximal synchronization entropy. The complexity of functional connectivity, as well as structure-function coupling, is maximized by criticality, which is consistent with theoretical predictions. We observed order-disorder phase transitions in resting-state brain dynamics and found that there were longer times spent in the subcritical regime. These results support the hypothesis that large-scale brain networks lie in the vicinity of a critical point. Finally, we showed evidence that the neural dynamics of human participants with higher fluid intelligence and working memory scores are closer to criticality. We identified brain regions whose critical dynamics showed significant positive correlations with fluid intelligence performance, and found these regions were located in the prefrontal cortex and inferior parietal cortex, which are believed to be important nodes of brain networks underlying human intelligence. Our results reveal the role that avalanche criticality plays in cognitive performance, and provide a simple method to identify the critical point and map cortical states on a spectrum of neural dynamics, ranging from subcriticality to supercriticality.
On the diversity of F420-dependent oxidoreductases: a sequence- and structure-based classification
Authors: Mascotti María Laura , Ayub Maximiliano Juri , Fraaije Marco W. 
Published: August 2020

AbstractThe F420deazaflavin cofactor is an intriguing molecule as it structurally resembles the canonical flavin cofactor, although biochemically behaves as a nicotinamide cofactor. Since its discovery, numerous enzymes relying on it have been described. The known deazaflavoproteins are taxonomically restricted to Archaea and Bacteria. The biochemistry of the deazaflavoenzymes is diverse and they exhibit some degree of structural variability as well. In this study a thorough sequence and structural homology evolutionary analysis was performed in order to generate an overarching classification of all known F420-dependent oxidoreductases. Five different superfamilies are described: Superfamily I, TIM-barrel F420-dependent enzymes; Superfamily II, Rossmann fold F420-dependent enzymes; Superfamily III, β-roll F420-dependent enzymes; Superfamily IV, SH3 barrel F420-dependent enzymes and Superfamily V, 3 layer ββα sandwich F420-dependent enzymes. This classification aims to be the framework for the identification, the description and the understanding the biochemistry of novel deazaflavoenzymes.
Tumor genotype dictates radiosensitization afterAtmdeletion in brainstem gliomas
Authors: Deland Katherine M. , Starr Bryce F. , Mercer Joshua S. , Byemerwa Jovita , Crabtree Donna M. , Williams Nerissa T. , Luo Lixia , Ma Yan , Chen Mark , Becher Oren J. , Kirsch David G. 
Published: August 2020

AbstractDiffuse intrinsic pontine glioma (DIPG) kills more children than any other type of brain tumor. Despite clinical trials testing many chemotherapeutic agents, radiotherapy remains the standard treatment. Here, we utilized Cre/loxP technology to show that deletingAtaxia telangiectasia mutated(Atm) in primary mouse models of DIPG can enhance tumor radiosensitivity. Genetic deletion ofAtmimproved survival of mice withp53deficient but notp53wild-type gliomas following radiotherapy. Similar to patients with DIPG, mice withp53wild-type tumors had improved survival after radiotherapy independent ofAtmdeletion.p53wild-type tumor cell lines induced proapoptotic genes after radiation and repressed the NRF2 target,Nqo1. Tumors lackingp53andInk4a/Arfexpressed the highest level ofNqo1and were most resistant to radiation, but deletion ofAtmenhanced the radiation response. These results suggest that tumor genotype may determine whether inhibition of ATM during radiotherapy will be an effective clinical approach to treat DIPGs.