bluuebunny/crossref_metadata_2025_split huggingface dataset:
A model of antigen processing improves prediction of MHC I-presented peptides
Authors: O’Donnell Timothy , Rubinsteyn Alex , Laserson Uri 
Published: March 2020

SummaryComputational prediction of the peptides presented on MHC class I proteins is an important tool for studying T cell immunity. The data available to develop such predictors has expanded with the use of mass spec to identify naturally-presented MHC ligands. In addition to elucidating binding motifs, the identified ligands also reflect the antigen processing steps that occur prior to MHC binding. Here, we developed an integrated predictor of MHC I presentation that combines new models for MHC I binding and antigen processing. Considering only peptides first predicted by the binding model to bind strongly to MHC, the antigen processing model is trained to discriminate published mass spec-identified MHC I ligands from unobserved peptides. The integrated model outperformed the two individual components as well as NetMHCpan 4.0 and MixMHCpred 2.0.2 on held-out mass spec experiments. Our predictors are implemented in the MHCflurry package, version 1.6.0 (github.com/openvax/mhcflurry).
OverlappingoriCand centromere-like functions in secondary genome replicons determine their maintenance independent of chromosome I inDeinococcus radiodurans
Authors: Maurya Ganesh K , Misra Hari S. 
Published: March 2020

AbstractTheDeinococcus radioduransmultipartite genome system (MGS) consists of chromosome I (ChrI) and secondary genome elements; Chr II and megaplasmid (MP). The sequences upstream toparABoperons in Chr II (cisII) and MP(cisMP) helped anE. coliplasmid maintenance inD. radioduransand showed sequence specific interactions with DnaA and ParBs. The cells devoid ofcisII(ΔcisII) orcisMP(ΔcisMP) showed reduced γ radiation resistance and copy number of Chr II and MP.FluorescentReporter-Operator System (FROS) developed for ChrI, ChrII and MP in ΔcisIIor ΔcisMPmutants showed no change in wild type pattern of Chr I localization. However, the relative copy numbers of Chr II and MP had reduced while anucleate cells had increased in mutants. These results suggested thatcisIIandcisMPelements contain bothoriand centromere-like functions, and like other MGS bacteria, the Chr I and secondary genome are maintained independently inD. radiodurans.
In-flight Transmission Cluster of COVID-19: A Retrospective Case Series
Authors: Yang Naibin , Shen Yuefei , Shi Chunwei , Yan Ma Ada Hoi , Zhang Xie , Jian Xiaomin , Wang Liping , Shi Jiejun , Wu Chunyang , Li Guoxiang , Fu Yuan , Wang Keyin , Lu Mingqin , Qian Guoqing 
Published: March 2020

AbstractObjectivesNo data were available about in-flight transmission of SARS-CoV-2. Here, we report an in-flight transmission cluster of COVID-19 and describe the clinical characteristics of these patients.MethodsAfter a flight, laboratory-confirmed COVID-19 was reported in 12 patients. Ten patients were admitted to the designated hospital. Data were collected from 25th January to 28th February 2020. Clinical information was retrospectively collected.ResultsAll patients are passengers without flight attendants. The median age was 33 years, and 70% were females. None was admitted to intensive care unit, and no patients succumbed through 28th February. The median incubation period was 3.0 days and from illness onset to hospital admission was 2 days. The most common symptom was fever. Two patients were asymptomatic and negative for chest CT scan throughout the disease courses. On admission, initial RT-PCR were positive in 9 patients, however initial chest CT were positive in only half patients. The median lung “total severity score” of chest CT was 6. Notably, “Crazy-Paving” pattern, pleural effusion, and ground-glass nodules were also seen.ConclusionIt is potential for COVID-19 transmission by airplane, but the symptoms are mild. Passengers and attendants must be protected during the flight.
Stabilization of the coronavirus pandemic in Italy and global prospects
Authors: Nesteruk Igor 
Published: March 2020

ABSTRACTThe pandemic caused by coronavirus COVID-19 are of great concern. A detailed scientific analysis of this phenomenon is still to come, but now it is urgently needed to evaluate the parameters of the disease dynamics in order to make some preliminary estimations of the number of cases and possible duration of the pandemic. The corresponding mathematical models must be simple enough, since their parameters are unknown and have to be estimated using limited statistical data sets. The SIR model, statistical approach to the parameter identification and the official WHO daily data about the confirmed cumulative number of cases were used to calculate the SIR curves and make some estimations and predictions. New cases in Italy could stop to appear after May 12, 2020, and the final number of such accumulated cases could be around 112 thousand. Some prospects for the global pandemic dynamics are discussed.
Brief Report: Correlation cannot be used to compare sequencing panels used for the assessment of tumor mutational burden in non-small cell lung cancer
Authors: Heeke Simon , Benzaquen Jonathan , Hofman Véronique , Long-Mira Elodie , Lespinet Virginie , Bordone Olivier , Marquette Charles-Hugo , Delingette Hervé , Ilié Marius , Hofman Paul 
Published: March 2020

AbstractIntroductionTumor mutational burden (TMB) has been proposed as a novel predictive biomarker for the stratification of patients undergoing immune-checkpoint inhibitor (ICI) treatment in non-small cell lung cancer (NSCLC) patients. The assessment of TMB has recently been established using large targeted sequencing panels and numerous studies are ongoing to harmonize the TMB assessment. However, usually “correlation” has been used to evaluate the association between the respective panels and we hypothesized that correlation might overestimate the comparability especially in lower TMB values, thus limiting the joint analysis of targeted sequencing panels for the assessment of TMB.MethodsThirty NSCLC samples from patients undergoing ICI treatment were consecutively sequenced using three large targeted sequencing panels: FoundationOne, Oncomine TML and QiaSeq TMB, respectively. TMB values were compared in the whole patient population and in a subset of patients where the TMB assessed by FoundationOne was between 5-25 mutations/Mb. Prediction of durable clinical benefit (DCB; >6 months no progression) was assessed using receiver operator characteristics and optimal cut-off values were calculated using Youden’s J.ResultsCorrelation between the targeted sequencing panels was strong in the whole patient population between the three panels (R2 > 0.79) but was dramatically reduced in the subset of patients with TMB 5 – 25 mutations/Mb. All panels were able to predict DCB in the TMB high population.ConclusionsAssessment of TMB using the three targeted sequencing panels was possible and predictive of response to ICI treatment but “correlation” was an inappropriate measurement to assess the association between the respective panels.
Genetically controlled membrane synthesis in liposomes
Authors: Blanken Duco , Foschepoth David , Serrão Adriana Calaça , Danelon Christophe 
Published: March 2020

ABSTRACTLipid membrane, nucleic acids, proteins, and metabolism are essential ingredients for life. Synthetic cellular systems emulating the fundamental properties of living cells must therefore be built upon these functional elements. In this work, phospholipid-producing enzymes encoded in a synthetic minigenome are cell-free expressed within liposome compartments. The de novo synthesized metabolic pathway converts precursors into a variety of lipids, including the constituents of the parental liposome. Balanced production of phosphatidylethanolamine and phosphatidylglycerol is realized, owing to transcriptional regulation of specific genes activity combined with a metabolic feedback mechanism. Fluorescence-based methods are developed to image the synthesis and membrane incorporation of phosphatidylserine at the single liposome level. Our results provide experimental evidence for DNA-programmed membrane synthesis in a minimal cell model. Strategies are discussed to alleviate current limitations toward more effective liposome growth and self-reproduction.
Isolation and characterization of two bacterial strains from textile effluents having Malachite Green dye degradation ability
Authors: Roy Dipankar Chandra , Sheam Md. Moinuddin , Hasan Md. Rockybul , Saha Ananda Kumar , Roy Apurba Kumar , Haque Md. Enamul , Rahman Md. Mizanur , Swee-Seong Tang , Biswas Sudhangshu Kumar 
Published: March 2020

AbstractWater pollution from textile effluent is now one of the major issues all over the world. Malachite Green dye of the triphenylmethane group is a key component of textile effluents. This study aimed to isolate and identify potential Malachite Green dye degrading bacteria from textile effluents. Different growth and culture parameters such as temperature, pH, inoculum-size and dye concentration were optimized to perform the dye-degradation assay using different concentrations of Malachite Green dye in mineral salt medium. A photo-electric-colorimeter was used to measure the decolorizing activity of bacteria at different time intervals after aerobic incubation. Two competent bacterial strains ofEnterobacterspp. (CV-S1 and CM-S1) were isolated from textile effluents showing potential degradation efficiency against Malachite Green dye. The RAPD analysis and 16S rRNA sequencing confirmed the genetical difference of the isolated strainsEnterobactersp. CV–S1 andEnterobactersp. CM–S1. The two bacterial strains CV-S1 and CM-S1 showed complete Malachite Green dye degradation up to 15 mg/l under shaking condition with 5% (v/v) inoculums at pH 6.50 and temperature 35°C within 72 and 144 hours respectively. These findings indicate that the two potential bacterial strains can be used in large scale treatment of textile effluents in the future.
Genome-wide, time-sensitive interrogation of the heat shock response under diverse stressors via ReporterSeq
Authors: Alford Brian D. , Valiant Gregory , Brandman Onn 
Published: March 2020

AbstractInterrogating cellular stress response pathways is challenging because of the complexity of regulatory mechanisms and response dynamics, which can vary with both time and the type of stress. We developed a reverse genetic method called ReporterSeq to comprehensively identify genes regulating a stress-induced transcription factor under multiple conditions in a time-resolved manner. ReporterSeq links RNA-encoded barcode levels to pathway-specific output under genetic perturbations, allowing pooled pathway activity measurements via DNA sequencing alone and without cell enrichment or single cell isolation. Here, we used ReporterSeq to identify regulators of the heat shock response (HSR), a conserved, poorly understood transcriptional program that protects cells from proteotoxicity and is misregulated in disease. We measured genome-wide HSR regulation in budding yeast across thirteen stress conditions, uncovering novel stress-specific, time-specific, and constitutive regulators. ReporterSeq can assess the genetic regulators of any transcriptional pathway with the scale of pooled genetic screens and the precision of pathway-specific readouts.
Mitofusin2 cooperates with Nuage-associated proteins and involves mRNA translational machinery in controlling mRNA fates during spermatogenesis
Authors: Wang Xiaoli , Wen Yujiao , Zhang Jin , Guo Shuangshuang , Cao Congcong , Krawetz Stephen A , Zhang Zhibing , Yuan Shuiqiao 
Published: March 2020

AbstractMitochondria play a critical role in spermatogenesis and regulated by several mitochondrial fusion proteins. Its interaction with other organelles forms several unique structures, including mitochondria-associated ER membrane (MAM) and a specific type of Nuage close to mitochondria. However, the importance of mitochondria functions and mitochondrial fusion proteins in its associated-structure formation and mRNA translation during spermatogenesis remain unclear. Here, we show that Mitofusin 2 (MFN2), a mitochondrial fusion GTPase protein, cooperates with Nuage-associated proteins, including MIWI, DDX4, TDRKH and GASZ and involves translational machinery to control the fates of gamete-specific mRNAs in spermatogenesis. Conditional mutation ofMfn2in postnatal germ cells results in male sterility due to germ cell developmental defects characterized by disruption of mitochondrial morphology, abnormal MAMs structure, aberrant mRNA translational processes, and anomalous splicing events. Moreover, MFN2 interacts with MFN1, another mitochondrial fusion protein with high-sequence similar to MFN2, in testes to facilitate spermatogenesis. Mutation ofMfn1andMfn2simultaneously in testes causes very severe infertile phenotypes. Importantly, we further show that MFN2 is enriched in polysome fractions in testes and interacts with MSY2, a germ cell-specific DNA/RNA-binding protein, and eukaryotic elongation factor 1 alpha (eEF1A) to control gamete-specific mRNA translational delay during spermatogenesis. Collectively, our findings demonstrate that MFN2 works with Nuage-associated proteins and involves translational secession to regulate gamete-specific mRNA fates. Our data reveal a novel molecular link among Mitofusins, Nuage-associated proteins, and mRNA translational processes in controlling male germ cell development.
Erythrocyte n-6 polyunsaturated fatty acids, gut microbiota and incident type 2 diabetes: a prospective cohort study
Authors: Miao Zelei , Lin Jie-sheng , Mao Yingying , Chen Geng-dong , Zeng Fang-fang , Dong Hong-li , Jiang Zengliang , Wang Jiali , Xiao Congmei , Shuai Menglei , Gou Wanglong , Fu Yuanqing , Imamura Fumiaki , Chen Yu-ming , Zheng Ju-Sheng 
Published: March 2020

AbstractObjectiveTo examine the association of erythrocyte n-6 polyunsaturated fatty acid (PUFA) biomarkers with incident type 2 diabetes (T2D) and explore the potential role of gut microbiota in the association.DesignWe evaluated 2,731 non-T2D participants recruited between 2008-2013 in the Guangzhou Nutrition and Health Study, China. T2D cases were identified with clinical and biochemical information collected at follow-up visits. Using stool samples collected during the follow-up in the subset (n=1,591), 16S rRNA profiling was conducted. Using multivariable-adjusted Poisson or linear regression, we examined associations of erythrocyte n-6 PUFA biomarkers with incident T2D, and diversity and composition of gut microbiota.ResultsOver 6.2 years of follow-up, 276 T2D cases were identified (risk=0.10). Higher levels of erythrocyte γ-linolenic acid (GLA), but not linoleic or arachidonic acid, were associated with higher T2D incidence. Comparing the top to the bottom quartile groups of GLA levels, relative risk was 1.72 (95% confidence intervals: 1.21, 2.44) adjusted for potential confounders. Baseline GLA was inversely associated with gut microbial richness and diversity (α-diversity, both p<0.05) during follow-up, and significantly associated with microbiota β-diversity (p=0.002). Seven genera (Butyrivibrio, Blautia, Oscillospira, Odoribacter, S24-7 other, Rikenellaceae other, and Clostridiales other) were enriched in quartile 1 of GLA, and in participants without T2D.ConclusionRelative concentrations of erythrocyte GLA were positively associated with incident T2D in a Chinese population and also with gut microbial profiles. These results highlight that gut microbiota may play an important role linking n-6 PUFA metabolism and T2D etiology.
Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2-mediated complement over-activation
Authors: Gao Ting , Hu Mingdong , Zhang Xiaopeng , Li Hongzhen , Zhu Lin , Liu Hainan , Dong Qincai , Zhang Zhang , Wang Zhongyi , Hu Yong , Fu Yangbo , Jin Yanwen , Li Kaitong , Zhao Songtao , Xiao Yongjiu , Luo Shuping , Li Lufeng , Zhao Lingfang , Liu Junli , Zhao Huailong , Liu Yue , Yang Weihong , Peng Jing , Chen Xiaoyu , Li Ping , Liu Yaoning , Xie Yonghong , Song Jibo , Zhang Lu , Ma Qingjun , Bian Xiuwu , Chen Wei , Liu Xuan , Mao Qing , Cao Cheng 
Published: March 2020

AbstractAn excessive immune response contributes to SARS-CoV, MERS-CoV and SARS-CoV-2 pathogenesis and lethality, but the mechanism remains unclear. In this study, the N proteins of SARS-CoV, MERS-CoV and SARS-CoV-2 were found to bind to MASP-2, the key serine protease in the lectin pathway of complement activation, resulting in aberrant complement activation and aggravated inflammatory lung injury. Either blocking the N protein:MASP-2 interaction or suppressing complement activation can significantly alleviate N protein-induced complement hyper-activation and lung injury in vitro and in vivo. Complement hyper-activation was also observed in COVID-19 patients, and a promising suppressive effect was observed when the deteriorating patients were treated with anti-C5a monoclonal antibody. Complement suppression may represent a common therapeutic approach for pneumonia induced by these highly pathogenic coronaviruses.One Sentence SummaryThe lectin pathway of complement activation is a promising target for the treatment of highly pathogenic coronavirus induced pneumonia.
Exploratory Analysis of Electronic Intensive Care Unit (eICU) Database
Authors: Rajabalizadeh Atefeh , Nia Javad Norouzi , Safaei Nima , Talafidaryani Mojtaba , Bijari Reyhaneh , Zarindast Atousa , Fotouhi Fateme , Salehi Masoud , Moqri Mahdi 
Published: March 2020

AbstractThe monitoring of severely ill patients is a crucial procedure for every intensive care unit (ICU). By applying different data exploration methods on monitoring data, some perspective can be gained. In the present research, such monitoring data were explored in the electronic ICU (eICU) Collaborative Research Database—an ICU database collected from more than 200 hospitals and over 139,000 ICU patients across the United States. The eICU database, with its enormous quantity of remote monitoring data, could be a great resource for extracting insightful information that can help to identify potential areas of improvement in the quality of patient treatment. Important information such as patients’ vital signs, care plan documentation, stage of illness, diagnosis, and treatment is available in the database. In the present study, we explore the distribution of the data, including demographics, conditions, and diseases, and identify important patterns and relationships between features of the data. Through an exploratory analysis of the data, including the relationships between gender, ethnicity, diseases, and quality of care and mortality rates, remarkable insights were obtained. To the best of our knowledge, this is the first comprehensive exploratory analysis of the eICU database. A deep understanding of the ICU data provides the foundation for further predictive and prescriptive analyses of the data with the ultimate goal of improving ICU treatment procedures for future patients.
Presence of SARS-Coronavirus-2 in sewage
Authors: Medema Gertjan , Heijnen Leo , Elsinga Goffe , Italiaander Ronald , Brouwer Anke 
Published: March 2020

AbstractIn the current COVID-19 pandemic, a significant proportion of cases shed SARS-Coronavirus-2 (SARS-CoV-2) with their faeces. To determine if SARS-CoV-2 is present in sewage during the emergence of COVID-19 in the Netherlands, sewage samples of 7 cities and the airport were tested using RT-PCR against three fragments of the nucleocapsid protein gene (N1-3) and one fragment of the envelope protein gene (E). No SARS-CoV-2 was detected in samples of February 6, three weeks before the first case was reported in the Netherlands on February 27. On March 5, the N1 fragment was detected in sewage of five sites. On March 15/16, the N1 fragment was detected in sewage of six sites, and the N3 and E fragment were detected at 5 and 4 sites respectively. This is the first report of detection of SARS-CoV-2 in sewage. The detection of the virus in sewage, even when the COVID-19 prevalence is low, indicates that sewage surveillance could be a sensitive tool to monitor the circulation of the virus in the population.
Scaling analysis of COVID-19 spreading based on Belgian hospitalization data
Authors: Smeets Bart , Watté Rodrigo , Ramon Herman 
Published: March 2020

AbstractWe analyze the temporal evolution of accumulated hospitalization cases due to COVID-19 in Belgium. The increase of hospitalization cases is consistent with an initial exponential phase, and a subsequent power law growth. For the latter, we estimate a power law exponent of ≈ 2.2, which is consistent with growth kinetics of COVID-19 in China and indicative of the underlying small world network structure of the epidemic. Finally, we fit an SIR-X model to the experimental data and estimate the effect of containment policies in comparison to their effect in China. This model suggests that the base reproduction rate has been significantly reduced, but that the number of susceptible individuals that is isolated from infection is very small. Based on the SIR-X model fit, we analyze the COVID-19 mortality and the number of patients requiring ICU treatment over time.
Phenotypically independent profiles relevant to mental health are genetically correlated
Authors: Roelfs Daniel , Alnæs Dag , Frei Oleksandr , van der Meer Dennis , Smeland Olav B. , Andreassen Ole A. , Westlye Lars T. , Kaufmann Tobias 
Published: March 2020

AbstractGenome-wide association studies (GWAS) and family-based studies have revealed partly overlapping genetic architectures between various psychiatric disorders. Given clinical overlap between disorders, our knowledge of the genetic architectures underlying specific symptom profiles and risk factors is limited. Here, we aimed to derive distinct profiles relevant to mental health in healthy individuals and to study how these genetically relate to each other and to common psychiatric disorders. Using independent component analysis, we decomposed self-report mental health questionnaires from 136,678 healthy individuals of the UK Biobank, excluding data from individuals with a diagnosed neurological or psychiatric disorder, into thirteen distinct profiles relevant to mental health, capturing different symptoms as well as social and risk factors underlying reduced mental health. Utilizing genotypes from 117,611 of those individuals with White English ancestry, we performed GWAS for each mental health profile and assessed genetic correlations between these profiles, and between the profiles and common psychiatric disorders and cognitive traits. We found that mental health profiles were genetically correlated with a wide range of psychiatric disorders and cognitive traits, with strongest effects typically observed between a given mental health profile and a disorder for which the profile is common (e.g. depression symptoms and major depressive disorder, psychosis and schizophrenia). Strikingly, although the profiles were phenotypically uncorrelated, many of them were genetically correlated with each other. This study provides evidence that statistically independent mental health profiles partly share genetic underpinnings and show genetic overlaps with psychiatric disorders, suggesting that shared genetics across psychiatric disorders cannot be exclusively attributed to the known overlapping symptomatology between the disorders.