bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombinant Fc-fusion vaccine of RBD induced protection against SARS-CoV-2 in non-human primate and mice
Authors: Sun Shihui , He Lei , Zhao Zhongpeng , Gu Hongjing , Fang Xin , Wang Tiecheng , Yang Xiaolan , Chen Shaolong , Deng Yongqiang , Li Jiangfan , Zhao Jian , Li Liang , Li Xinwang , He Peng , Li Ge , Li Hao , Zhao Yuee , Gao Chunrun , Lang Xiaolin , Wang Xin , Fei Guoqiang , Li Yan , Geng Shusheng , Gao Yuwei , Wei Wenjin , Hu Zhongyu , Han Gencheng , Sun Yansong 
Published: December 2020

AbstractThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to infect people globally. The increased COVID-19 cases and no licensed vaccines highlight the need to develop safe and effective vaccines against SARS-CoV-2 infection. Multiple vaccines candidates are under pre-clinical or clinical trails with different strengths and weaknesses. Here we developed a pilot scale production of a recombinant subunit vaccine (RBD-Fc Vacc) with the Receptor Binding Domain of SARS-CoV-2 S protein fused with the Fc domain of human IgG1. RBD-Fc Vacc induced SARS-CoV-2 specific neutralizing antibodies in non-human primates and human ACE2 transgenic mice. The antibodies induced in macaca fascicularis neutralized three divergent SARS-CoV2 strains, suggesting a broader neutralizing ability. Three times immunizations protected Macaca fascicularis (20ug or 40ug per dose) and mice (10ug or 20ug per dose) from SARS-CoV-2 infection respectively. These data support clinical development of SARS-CoV-2 vaccines for humans. RBD-Fc Vacc is currently being assessed in randomized controlled phase 1/II human clinical trails.SummaryThis study confirms protective efficacy of a SARS-CoV-2 RBD-Fc subunit vaccine.
GAPIT Version 3: Boosting Power and Accuracy for Genomic Association and Prediction
Authors: Wang Jiabo , Zhang Zhiwu 
Published: December 2020

AbstractGenome-Wide Association Study (GWAS) and Genomic Prediction/Selection (GP/GS) are the two essential enterprises in genomic research. Due to the great magnitude and complexity of genomic data, analytical methods and their associated software packages are frequently advanced. GAPIT is a widely used Genomic Association and Prediction Integrated Tool. The first version was released to the public in 2012 with the implementation of the general linear model (GLM), mixed linear model (MLM), compressed MLM, and genomic Best Linear Unbiased Prediction (gBLUP). The second version was released in 2016 with several new implementations, including Enriched Compressed MLM and Settlement of mixed linear models Under Progressively Exclusive Relationship (SUPER). All the GWAS methods are based on the single locus test. For the first time, in the current release of GAPIT, version 3 implemented three multiple loci test methods, including Multiple Loci Mixed Model (MLMM), Fixed and random model Circulating Probability Unification (FarmCPU), and Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK). Additionally, two GP/GS methods were implemented based on Compressed MLM, named compressed BLUP, and SUPER, named SUPER BLUP. These new implementations not only boost statistical power for GWAS and prediction accuracy for GP/GS, but also improve computing speed and increase the capacity to analyze big genomic data. Here, we document the current upgrade of GAPIT by describing the selection of the recently developed methods, their implementation, and potential impact. All documents, including source code, user manual, demo data, and tutorials, are freely available at the GAPIT website (http://zzlab.net/GAPIT).
Human cytomegalovirus infection changes the pattern of surface markers of small extracellular vesicles isolated from first trimester placental histocultures
Authors: Bergamelli Mathilde , Martin Hélène , Bénard Mélinda , Ausseil Jérôme , Mansuy Jean-Michel , Hurbain Ilse , Mouysset Maïlys , Groussolles Marion , Cartron Géraldine , Gac Yann Tanguy le , Moinard Nathalie , Suberbielle Elsa , Izopet Jacques , Tscherning Charlotte , Raposo Graça , Gonzalez-Dunia Daniel , D’Angelo Gisela , Malnou Cécile E. 
Published: December 2020

ABSTRACTCurrently, research on the use of non-invasive biomarkers as diagnosis and prognosis tools during pathological pregnancies is in full development. Among these, placenta-derived small extracellular vesicles (sEVs) are considered as serious candidates, since their composition is modified during many pregnancy pathologies. Moreover, sEVs are found in maternal serum and can thus be easily purified from a simple blood sample. In this study, we describe the isolation of sEVs from a histoculture model of first trimester placental explants. Using bead-based multiplex cytometry and electron microscopy combined with biochemical approaches, we characterized these sEVs and defined their associated markers and ultrastructure. We next examined the consequences of infection by human cytomegalovirus on sEVs secretion and characteristics. We observed that infection led to increased levels of expression of several surface markers, without any impact on the secretion and integrity of sEVs. Our findings open the prospect for the identification of new predictive biomarkers for the severity and outcome of this congenital infection early during pregnancy, which are still sorely lacking.
Genomic diversity, population structure and accessory genome analysis ofPasteurella multocida: New Insights into host adaptation and disease specialization
Authors: Carhuaricra Dennis , Hurtado Raquel , Luna Luis , Rosadio Raúl , Wheeler Jane C. , Azevedo Vasco , Maturrano Lenin 
Published: December 2020

AbstractPasteurella multocidais a multi-host pathogen that infects a wide spectrum of domestic and wild animals including humans. Despite its impact on health and economics,P. multocidais considered an enigmatic pathogen and the genetic basis of its pathogenicity and host adaptation still remains unclear. Here we present a detailed genomic framework based on 336 whole-genome sequences ofP. multocidaisolates from different animal species and countries. Our data provide genomic support of the existence of two very divergent phylogroups (PmI and PmII), which present a barrier to homologous recombination suggesting genetic isolation. Additionally, atorCADoperon, which reduces TMAO (trimethylamineN-oxide) to produce energy during bacterial anaerobic respiration, is present only in PmI and can act as a hypothetical driver of niche segregation between phylogroups. The PmI phylogroup harbors strains that infect a wider range of hosts than PmII, and shows a highly diverse phylogeny and accessory genome. We identified nine clonal lineages for PmI, seven of which are associated with specific hosts or diseases and contain distinct accessory gene pools that can confer ecologically relevant phenotypes. We found differential presence of a trehalose metabolism operon in the bovine lineage associated with pneumonic pasteurellosis; while, citrate, L-arabinose, L-fucose, and D-allose operons are only present in avian lineages. These findings suggest that alternative metabolic pathways may facilitate the establishment ofP. multocidaduring host colonization in the early stages of infection promoting the adaptation ofP. multocidalineages to certain hosts.
Monomethyl branched-chain fatty acid mediates amino acid sensing by mTORC1
Authors: Zhu Mengnan , Teng Fukang , Li Na , Zhang Li , Shao Jing , Sun Haipeng , Zhu Huanhu 
Published: December 2020

AbstractAnimals have developed various nutrient-sensing mechanisms for survival under fluctuating environments. Although extensive cultured cell-based analyses have discovered diverse mediators of amino acid sensing by mTOR, studies using animal models to illustrate intestine-initiated amino acid sensing mechanisms under specific physiological conditions are lacking. Here we developed aCaenorhabditis elegansmodel to examine the impact of amino acid deficiency on development. We discovered a leucine-derived monomethyl branched-chain fatty acid, and downstream glycosphingolipid, that critically mediate overall amino acid sensing by intestinal and neuronal mTORC1 that, in turn, regulates postembryonic development partly by controlling protein translation and ribosomal biogenesis. Additional data suggest that a similar mechanism may be conserved in mammals. This study uncovers an unexpected amino acid sensing mechanism mediated by a lipid biosynthesis pathway.
Controlling Cellular Arrangements via Stretched Bioprinting
Authors: He Chuanjiang , Liu Mengxue , Jiang Deming , Qin Chunlian , Liang Tao , Wu Pan , Han Chunmao , Huang Liquan , Hsia K. Jimmy , Wang Ping 
Published: December 2020

AbstractBioprinting is a common method to replicate geometrical architecture of native tissues. However, it usually fails to modulate cellular arrangements, which is critical for the tissue’s functionality. To our knowledge, no method has successfully addressed this challenge. Here, we report a method of controlling cellular orientation during the bioprinting process by integrating a stretch process into a modified bioprinting frame. We demonstrate that the cellular orientation is a result of cells’ sensing and responding to the tensile stress, instead of shear stress or topographical patterns. Moreover, our method shows a potent capability to induce myoblast differentiation, fusion and maturation without the presence of differentiation medium. As a potential clinical application, we demonstrate that aligned myofibers directly printed onto injured muscle in vivo, can not only repair the structure of damaged tissue, but also recover the muscle functionalities effectively. This study shows that the new method can produce tissues with precise control of cellular arrangements and more clinically viable functionalities.Significance StatementDue to no method could reproduce the exact cellular arrangements of native tissues in engineered tissues, tissue engineering facing difficult in fabricating 3D tissues that possess desirable biological and mechanical functionalities for biomedical applications. For the first time, we report a method of controlling cellular orientation during 3D bio-printing process. This method can be used to produce engineered tissues with controlled cellular arrangement with several different cell types. Moreover, this method shows a potent capability of fabricating fully mature and aligned myofibersin vitroin the absence of differentiation medium. As potential clinical applications, with this method, engineered tissues could be directly printedin vivowith high efficacy of tissue repair and function recovery.
No change in oxytocin level before a human intergroup competition: study among Polish players before rugby and handball matches
Authors: Koziel Slawomir , Kociuba Marek , Ignasiak Zofia , Rokita Andrzej , Cichy Ireneusz , Dutkowski Andrzej , Ściślak Marcin , Kochan Katarzyna , Sebastjan Anna , Spinek Anna , Lorek Daria , Chakraborty Raja , Bogin Barry 
Published: December 2020

AbstractObjectivesThe aim of the present study was to assess the changes in urinary oxytocin concentration during the period between five days before, and on the day of match, among rugby and handball players.MethodsThe study used a repeated measures design with the relative oxytocin level as the outcome variable measured at two subsequent points of time, viz., on five days before as well as on the days of matches. Nine male rugby players with a mean age of 27.62 years (SD = 4.21) and 18 male handball players with a mean age of 17.03 years (SD = 0.57) participated. Urinary oxytocin level was measured by ELISA immunoassay as a ratio to the concentration of creatinine [mg/ml] measured through colorimetric detection. Differences in oxytocin level were assessed by ANOVA with repeated measurements.ResultsThe OT/CRE levels significantly differed between the type of player (rugby or handball) but not between times of measurements. Tukey’s post-hoc tests revealed that significant differences were only between OT/CRE level in a day of match in rugby players and in 5 days before match in handball players (p<0.05).ConclusionThere was no change in oxytocin levels during the time periods between five days before and on the day of a match, in either of the two kinds of players. The change in oxytocin might be traceable during the match but not before a match and thus perhaps depends on a more subtle context of competition, but not on the assumption of competition.
Association between the extent of DNA methylation at the CpG sites ofHIF3Aand parameters of obesity in the general Japanese population
Authors: Mizuno Genki , Yamada Hiroya , Munetsuna Eiji , Yamazaki Mirai , Ando Yoshitaka , Fujii Ryosuke , Tsuboi Yoshiki , Teshigawara Atsushi , Kageyama Itsuki , Osakabe Keisuke , Sugimoto Keiko , Ishikawa Hiroaki , Ichino Naohiro , Ohta Yoshiji , Ohashi Koji , Hashimoto Shuji , Suzuki Koji 
Published: December 2020

AbstractObesity is a major public health problem worldwide owing to the substantial increase in risk of metabolic diseases. Hypoxia-inducible factors (HIFs) regulate transcriptional responses to hypoxic stress. DNA methylation in the CpG sites of intron 1 ofHIF3Ais associated with body mass index in the whole blood and adipose tissue. This study investigates the correlation between DNA methylation ofHIF3Aand parameters of obesity, including thickness of visceral (VAT) and subcutaneous adipose tissues, in the general Japanese population. Participants (220 men and 253 women) who underwent medical examination were enrolled in this cross-sectional study. We used pyrosequencing to quantify DNA methylation (CpG sites of cg16672562, cg22891070, and cg27146050) inHIF3A. DNA methylation ofHIF3Awas only different in women. Multiple regression analysis showed that DNA methylation level at cg27146050 was associated with thickness of VAT in women. DNA methylation level at cg27146050 also correlated with body mass index and percentage of body fat in women after excluding smokers and non-smokers who quit smoking with the last 5 years. DNA methylation in the CpG site (cg27146050) ofHIF3Acorrelated with parameters of obesity in Japanese women.
Modeling the circadian regulation of the immune system: sexually dimorphic effects of shift work
Authors: Abo Stéphanie M.C. , Layton Anita T. 
Published: December 2020

AbstractThe circadian clock exerts significance influence on the immune system and disruption of circadian rhythms has been linked to inflammatory pathologies. shift workers often experience circadian misalignment as their irregular work schedules disrupt the natural sleep-wake cycle, which in turn can cause serious health problems associated with alterations in genetic expressions of clock genes. In particular, shift work is associated with impairment in immune function, and those alterations are sex-specific. The goal of this study is to better understand the mechanisms that explain the weakened immune system in shift workers. To achieve that goal, we have constructed a mathematical model of the mammalian pulmonary circadian clock coupled to an acute inflammation model. shift work was simulated by an 8h-phase advance of the circadian system with sex-specific modulation of clock genes. The model reproduces the clock gene expression in the lung and the immune response to various doses of lipopolysaccharide (LPS). Under normal conditions, our model predicts that a host is more sensitive to LPS at CT12 versus CT0 due to a change in the dynamics of IL-10. We identify REV-ERB as a key modulator of IL-10 activity throughout the circadian day. The model also predicts a reversal of the times of lowest and highest sensitivity to LPS, with males and females exhibiting an exaggerated response to LPS at circadian time (CT) 0, which is countered by a blunted immune response at CT12. Overall, females produce fewer pro-inflammatory cytokines than males, but the extent of sequelae experienced by males and females varies across the circadian day. This model can serve as an essential component in an integrative model that will yield mechanistic understanding of how shift work-mediated circadian disruptions affect the inflammatory and other physiological responses.Author summaryShift work has a negative impact on health and can lead to chronic diseases and illnesses. Under regular work schedules, rest is a night time activity and work a daytime activity. Shift work relies on irregular work schedules which disrupt the natural sleep-wake cycle. This can in turn disrupt our biological clock, called the circadian clock, a network of molecular interactions generating biochemical oscillations with a near 24-hour period. Clock genes regulate cytokines before and during infection and immune agents can also impact the clock function. We provide a mathematical model of the circadian clock in the lung coupled to an acute inflammation model to study how the disruptive effect of shift work manifests itself in males and females during inflammation. Our results show that the extent of sequelae experienced by male and female mice depends on the time of infection. The goal of this study is to provide a mechanistic insight of the dynamics involved in the interplay between these two systems.
Estimating disease spread using structured coalescent and birth-death models: A quantitative comparison
Authors: Seidel Sophie , Stadler Tanja , Vaughan Timothy G. 
Published: December 2020

AbstractUnderstanding how disease transmission occurs between subpopulations is critically important for guiding disease control efforts irrespective of whether the subpopulations represent geographically separated people, age or risk groups. The structured coalescent (SC) and the multitype birth-death (MBD) model can both be used to infer migration rates between subpopulations from phylogenies reconstructed from pathogen genetic sequences. However, the two classes of phylodynamic methods rely on different assumptions.Here, we report on a simulation study which compares inferences made using these models for a variety of migration rates in both endemic diseases and epidemic outbreaks. For the epidemic outbreak, we found that the MBD recovers the true migration rates better than the SC regardless of migration rate. We hypothesize that the inaccurate SC estimates stem from the its assumption of a constant population size. For the endemic scenario, our analysis shows that both models obtain a similar coverage of the migration rates, while the SC provides slightly narrower posterior intervals. Irrespective of the scenario, both models estimate the root location with similar coverage.Our study provides concrete modelling advice for infectious disease analysts. For endemic disease either model can be used, while for epidemic outbreaks the MBD should be the model of choice. Additionally, our study reveals the need to develop the SC further such that varying population sizes can easily be taken into account.Author summaryControlling an infectious disease requires us to quantify and understand how it spreads through pools of susceptible individuals, defined by their belonging to different geographical regions, age or risk groups. Rates of pathogen movement between these pools can be inferred from pathogen phylogenies which are themselves reconstructed from pathogen genetic sequences collected from infected individuals. Two popular foundations for such models are the multitype birth-death model and the structured coalescent.Although these models fulfill the same purpose, they differ in their assumptions and can, hence, produce contrasting results. To assess the appropriateness of the models in different situations, we performed a simulation study. We find that, for endemic diseases, both models are able to estimate the migration parameters reliably. For epidemic outbreaks, however, the multitype birth-death model obtains better estimates of the migration rates. We hypothesize that the structured coalescent’s inaccurate estimates for the epidemic scenario arise because it assumes a constant number of infected individuals through time.
First computational design of Covid-19 coronavirus vaccine using lambda superstrings
Authors: Martínez Luis , Malaina Iker , Salcines David , Terán Héctor , Alegre Santos , De la Fuente I.M. , Lopez Elena Gonzalez , Vinyals Gonzalo Ocejo , Álvarez Carmen 
Published: December 2020

AbstractIn this work we have developed, by employing lambda superstrings, a map of candidate vaccines against SARS-CoV-2 with lengths between 9 and 200, based on estimations of the immunogenicity of the epitopes and the binding affinity of epitopes to MHC class I molecules using tools from the IEDB Analysis Resource, as well as the overall predictions obtained using the VaxiJen tool. We have synthesized one of the peptides, specifically the one of length 22, and we have carried out an immunogenicity assay and a cytokine assay, which has given positive results in both cases.
Remodeling and activation mechanisms of outer arm dyneins revealed by cryo-EM
Authors: Kubo Shintaroh , Yang Shun Kai , Black Corbin , Dai Daniel , Valente Melissa , Gaertig Jacek , Ichikawa Muneyoshi , Bui Khanh Huy 
Published: December 2020

AbstractCilia are thin microtubule-based protrusions of eukaryotic cells. The swimming of ciliated protists and sperm cells is propelled by the beating of cilia. Cilia propagate the flow of mucus in the trachea and protect the human body from viral infections. The main force generators of ciliary beating are the outer dynein arms (ODAs) which attach to the doublet microtubules. The bending of cilia is driven by the ODAs’ conformational changes caused by ATP hydrolysis. Here, we report the native ODA complex structure attaching to the doublet microtubule by cryoelectron microscopy. The structure reveals how the ODA complex is attached to the doublet microtubule via the docking complex in its native state. Combined with molecular dynamics simulations, we present a model of how the attachment of the ODA to the doublet microtubule induces remodeling and activation of the ODA complex.