bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sampling SARS-CoV-2 proteomes for predicted CD8 T-cell epitopes as a tool for understanding immunogenic breadth and rational vaccine design
Authors: Hare Jonathan , Morrison David , Nielsen Morten 
Published: August 2020

AbstractPredictive models for vaccine design have become a powerful and necessary resource for the expeditiousness design of vaccines to combat the ongoing SARS-CoV-2 global pandemic. Here we use the power of these predicted models to assess the sequence diversity of circulating SARS-CoV-2 proteomes in the context of an individual’s CD8 T-cell immune repertoire to identify potential. defined regions of immunogenicity. Using this approach of expedited and rational CD8 T-cell vaccine design, it may be possible to develop a therapeutic vaccine candidate with the potential for both global and local coverage.
A SARS-CoV-2 neutralizing antibody protects from lung pathology in a COVID-19 hamster model
Authors: Kreye Jakob , Reincke S Momsen , Kornau Hans-Christian , Sánchez-Sendin Elisa , Corman Victor Max , Liu Hejun , Yuan Meng , Wu Nicholas C. , Zhu Xueyong , Lee Chang-Chun D. , Trimpert Jakob , Höltje Markus , Dietert Kristina , Stöffler Laura , von Wardenburg Niels , van Hoof Scott , Homeyer Marie A , Hoffmann Julius , Abdelgawad Azza , Gruber Achim D , Bertzbach Luca D , Vladimirova Daria , Li Lucie Y , Barthel Paula Charlotte , Skriner Karl , Hocke Andreas C , Hippenstiel Stefan , Witzenrath Martin , Suttorp Norbert , Kurth Florian , Franke Christiana , Endres Matthias , Schmitz Dietmar , Jeworowski Lara Maria , Richter Anja , Schmidt Marie Luisa , Schwarz Tatjana , Müller Marcel Alexander , Drosten Christian , Wendisch Daniel , Sander Leif E , Osterrieder Nikolaus , Wilson Ian A , Prüss Harald 
Published: August 2020

ABSTRACTThe emergence of SARS-CoV-2 led to pandemic spread of coronavirus disease 2019 (COVID-19), manifesting with respiratory symptoms and multi-organ dysfunction. Detailed characterization of virus-neutralizing antibodies and target epitopes is needed to understand COVID-19 pathophysiology and guide immunization strategies. Among 598 human monoclonal antibodies (mAbs) from ten COVID-19 patients, we identified 40 strongly neutralizing mAbs. The most potent mAb CV07-209 neutralized authentic SARS-CoV-2 with IC50of 3.1 ng/ml. Crystal structures of two mAbs in complex with the SARS-CoV-2 receptor-binding domain at 2.55 and 2.70 Å revealed a direct block of ACE2 attachment. Interestingly, some of the near-germline SARS-CoV-2 neutralizing mAbs reacted with mammalian self-antigens. Prophylactic and therapeutic application of CV07-209 protected hamsters from SARS-CoV-2 infection, weight loss and lung pathology. Our results show that non-self-reactive virus-neutralizing mAbs elicited during SARS-CoV-2 infection are a promising therapeutic strategy.
Multifractal Analysis of SARS-CoV-2 Coronavirus genomes using the wavelet transform
Authors: Ouadfeul Sid-Ali 
Published: August 2020

AbstractIn this paper, the 1D Wavelet Transform Modulus Maxima lines (WTMM) method is used to investigate the Long-Range Correlation (LRC) and to estimate the so-called Hurst exponent of 21 isolate RNA sequence downloaded from the NCBI database of patients infected by SARS-CoV-2, Coronavirus, the Knucleotidic, Purine, Pyramidine, Ameno, Keto and GC DNA coding are used. Obtained results show the LRC character in the most sequences; except some sequences where the anti-correlated or the Classical Brownian motion character is observed, demonstrating that the SARS-Cov2 coronavirus undergoes mutation from a country to another or in the same country, they reveals also the complexity and the heterogeneous genome structure organization far from the equilibrium and the self-organization.
Hydroxychloroquine Safety Outcome within Approved Therapeutic Protocol for Covid-19 Outpatients in Saudi Arabia
Authors: Mohana Abdulrhman , Sulaiman Tarek , Mahmoud Nagla , Hassanein Mustafa , Alfaifi Amel , Alenazi Eissa , Radwan Nashwa , AlKhalifah Nasser , Elkady Ehab , Almohaizeie Abdullah , AboGazalah Fouad , AbdulKareem Khaled , AlGhofaili Fahad , Jokdar Hani , Alrabiah Fahad 
Published: August 2020

ABSTRACTBackgroundHealthcare systems globally has been challenged following the COVID-19 pandemic, since late 2019. Multiple approaches and strategies have been performed to relieve the pressure and support existing healthcare systems. The Saudi Arabian Ministry of Health (MOH) launched an initiative to support the National Healthcare System. Since the 5th of June 2020, 238 outpatient fever clinics were established across Saudi Arabia.MethodsA cross-sectional study included 2,733 eligible patients subjected to MOH treatment protocol (hydroxychloroquine and zinc) and revisited the clinics within 3-7 days after treatment initiation. This study aimed to assess the safety outcome and reported adverse events from hydroxychloroquine use among suspected COVID-19 patients. The data was collected through an electronic link and cross-checked with that of the national database (Health Electronic Surveillance Network, HESN) and reports from the MOH Morbidity and Mortality (M&M) Committee.ResultsMajority of the cases were males (70.4%). Upon reassessing the studied participants within 3-7 days, 240 patients (8.8%) discontinued the treatment protocol because of the development of side effects (4.1%) and for non-clinical reasons in the remaining (4.7%). Medication side effects overall were reported among (6.7%) of all studied participants, including mainly cardiovascular adverse events (2.5%), followed by gastrointestinal (GI) symptoms (2.4%). No Intensive Care Unit (ICU) admission or death were reported among these patients.ConclusionIn our study, results show that the use of hydroxychloroquine for COVID-19 patients in mild to moderate cases in an outpatient setting, within the protocol recommendation and inclusion/exclusion criteria, is safe, highly tolerable, and with minimum side effects.
Histone demethylase complexes KDM3A and KDM3B cooperate with OCT4/SOX2 to construct pluripotency gene regulatory network
Authors: Zhu Zhenshuo , Wu Xiaolong , Li Qun , Zhang Juqing , Yu Shuai , Shen Qiaoyan , Zhou Zhe , Pan Qin , Yue Wei , Qin Dezhe , Zhang Ying , Zhao Wenxu , Zhang Rui , Peng Sha , Li Na , Zhang Shiqiang , Lei Anmin , Miao Yi-Liang , Liu Zhonghua , Chen Xingqi , Wang Huayan , Liao Mingzhi , Hua Jinlian 
Published: August 2020

AbstractThe pluripotency gene regulatory network of porcine-induced pluripotent stem cells (piPSCs), especially in epigenetics, remains elusive. To determine this biological function of epigenetics, we cultured piPSCs in different culture conditions. We found that activation of pluripotent gene- and pluripotency-related pathways requires the erasure of H3K9 methylation modification which was further influenced by mouse embryonic fibroblast (MEF) served feeder. By dissecting the dynamic change of H3K9 methylation during loss of pluripotency, we demonstrated that the H3K9 demethylases KDM3A and KDM3B regulated global H3K9me2/me3 level and that their co-depletion led to the collapse of the pluripotency gene regulatory network. Immunoprecipitation-mass spectrometry (IP-MS) provided evidence that KDM3A and KDM3B formed a complex to perform H3K9 demethylation. The genome-wide regulation analysis revealed that OCT4 (O) and SOX2 (S), the core pluripotency transcriptional activators, maintained the pluripotent state of piPSCs depending on the H3K9 hypomethylation. Further investigation revealed that O/S cooperating with histone demethylase complex containing KDM3A and KDM3B promoted pluripotency genes expression to maintain the pluripotent state of piPSCs. Together, these data offer a unique insight into the epigenetic pluripotency network of piPSCs.SummaryErasure of H3K9 methylation in porcine pluripotent stem cells depends on the complex of transcription factors OCT4/SOX2 and histone demethylase KDM3A/KDM3B.
Impacts ofDesulfobacteralesandChromatialeson sulfate reduction in the subtropical mangrove ecosystem as revealed by SMDB analysis
Authors: Mo Shuming , Li Jinhui , Li Bin , Yu Ran , Nie Shiqing , Zhang Zufan , Liao Jianping , Jiang Qiong , Yan Bing , Jiang Chengjian 
Published: August 2020

AbstractSulfate reduction is an important process in the sulfur cycle. However, the relationship between this process and the genotype of microorganisms involved in subtropical mangrove ecosystems is poorly understood. A dedicated and efficient gene integration database of sulfur metabolism has not been established yet. In this study, a sulfur metabolism gene integrative database (SMDB) had been constructed successfully. The database achieved high coverage, fast retrieval, and low false positives. Then the sulfate reduction by microorganisms in subtropical mangroves ecosystem had been evaluated quickly and accurately with SMDB database. Due to the environmental factors, dissimilatory sulfite reductase was significantly high in mangrove samples. Sulfide, Fe, and available sulfur were found to be the key environmental factors that influence the dissimilatory sulfate reduction, in which sulfur compounds could be utilized as potential energy sources for microorganism. Taxonomic assignment of dissimilatory sulfate-reduction genes revealed thatDesulfobacteralesandChromatialesare completely responsible for this process. Sulfite reductase can help the community cope with the toxic sulfite produced by these Bacteria order. Collectively, these findings demonstrated thatDesulfobacteralesandChromatialesplay essential roles in dissimilatory sulfate reduction.
A lesson from COVID-19 on inaccessibility of web-based information for disabled populations worldwide
Authors: Dror Amiel A. , Layous Eli , Mizrachi Matti , Daoud Amani , Eisenbach Netanel , Morozov Nicole G. , Srouji Samer , Avraham Karen B. , Sela Eyal 
Published: August 2020

AbstractMany government websites and mobile content are inaccessible for people with vision, hearing, and cognitive disabilities. The COVID-19 pandemic highlighted these disparities when health authority website information, critical in providing resources for curbing the spread of the virus, remained inaccessible for disabled populations. The Web Content Accessibility Guidelines provide comparatively universally accepted guidelines for website accessibility. We utilized these parameters to examine the number of countries with or without accessible health authority websites. The resulting data indicate a dearth of countries with websites accessible for persons with disabilities. Methods of information dissemination must take into consideration individuals with disabilities, particularly in times of global health crises.
Sweet chirality: the taste of l- and d-glucose stereoisomers
Authors: Dubovski Nitzan , Shoshan-Galeczki Yaron Ben , Malach Einav , Niv Masha Y 
Published: August 2020

AbstractChirality plays a key role in biomolecular recognition. Typically, a change in chirality will dramatically affect ligand–receptor binding. However, bothd-glucose and its enantiomerl-glucose elicit sweet taste in humans. We show thatl- andd-glucose are perceived as similarly sweet by humans, and that in cell-based functional assays, both enantiomers activate the human sweet taste receptor TAS1R2/TAS1R3. We hypothesize that bothl- andd-glucose occupy the orthosteric binding site in the VFT domain of TAS1R2. Using induced-fit docking to a homology model of this domain, we identify two subpockets in this binding site. The model suggests that glucose molecules can bind in either of these subpockets, which overlap with the predicted positions of monosaccharide units of sucrose. One subpocket is close to the hinge between the two lobes, and overlaps with aspartame and neotame site, the second subpocket overlaps with that described for sweetness enhancers. These findings suggest a framework for rational design of sweeteners combinations.
Structure and Dynamics of HIV-1 Env Trimers on Native Virions Engaged in Living T Cells
Authors: Carlon-Andres Irene , Malinauskas Tomas , Padilla-Parra Sergi 
Published: August 2020

AbstractThe HIV-1 envelope glycoprotein (Env) mediates viral entry into the host cell. Although the highly dynamic nature of Env intramolecular conformations has been shown with single molecule spectroscopy in vitro, the bona fide Env intra- and intermolecular mechanics when engaged in live T cells remains unknown. We used both, two photon fast fluorescence lifetime imaging detection of single-molecule Förster Resonance Energy Transfer and single molecule photobleaching to reveal transitions between intramolecular and intermolecular conformations that mediate Env clustering. Furthermore, we show that three broad neutralizing anti-Env antibodies directed to different epitopes destabilise Env intramolecular dynamics and their clusters when engaged to living T cells. Importantly, our results show that Env clustering is a common conformation across different HIV-1 Env strains, which depends on efficient virus maturation, and that is disrupted upon binding of Env to CD4 or to neutralizing antibodies. Thus, this study illuminates how different intramolecular conformations and clusters of Env mediate HIV-1 Env–T cell interactions in real time and therefore might control immune evasion.
SIMON: open-source knowledge discovery platform
Authors: Tomic Adriana , Tomic Ivan , Waldron Levi , Geistlinger Ludwig , Kuhn Max , Spreng Rachel L. , Dahora Lindsay C. , Seaton Kelly E. , Tomaras Georgia , Hill Jennifer , Duggal Niharika A. , Pollock Ross D. , Lazarus Norman R. , Harridge Stephen D.R. , Lord Janet M. , Khatri Purvesh , Pollard Andrew J. , Davis Mark M. 
Published: August 2020

AbstractData analysis and knowledge discovery has become more and more important in biology and medicine with the increasing complexity of the biological datasets, but necessarily sophisticated programming skills and in-depth understanding of algorithms needed pose barriers to most biologists and clinicians to perform such research. We have developed a modular open-source software SIMON to facilitate the application of 180+ state-of-the-art machine learning algorithms to high-dimensional biomedical data. With an easy to use graphical user interface, standardized pipelines, automated approach for machine learning and other statistical analysis methods, SIMON helps to identify optimal algorithms and provides a resource that empowers non-technical and technical researchers to identify crucial patterns in biomedical data.
Aspartate-phobia of thermophiles as a reaction to deleterious chemical transformations
Authors: Villain Etienne , Fort Philippe , Kajava Andrey V 
Published: August 2020

AbstractProkaryotes growing at high temperatures have a high proportion of charged residues in their proteins to stabilize their 3D structure. By mining 175 disparate bacterial and archaeal proteomes we found that, against the general trend for charged residues, the frequency of aspartic acid residues decreases strongly as natural growth temperature increases. In search of the explanation, we hypothesized that the reason for such unusual correlation is the deleterious consequences of spontaneous chemical transformations of aspartate at high temperatures. Our subsequent statistical analysis supported this hypothesis. First, knowing that these chemical modifications are higher in the unfolded polypeptide chains, we observed the most pronounced decrease of Asp frequency with temperature within intrinsically disordered regions. Second, it is known that the reaction rate of the chemical transformations of Asp is highest with the smallest downstream residue Gly and noticeably reduced for bulky residues. In agreement with this, the frequency of Gly residues downstream of Asp decreases with optimal growth temperature, while the frequency of bulky residues significantly increases. Thus, our analysis suggests that organisms have likely adapted to high temperatures by minimizing the harmful consequences of spontaneous chemical transformations of Asp residues.
MultiGWAS: An integrative tool for Genome Wide Association Studies (GWAS) in tetraploid organisms
Authors: Garreta L. , Cerón-Souza I. , Palacio M.R. , Reyes-Herrera P.H. 
Published: August 2020

AbstractSummaryThe Genome-Wide Association Studies (GWAS) are essential to determine the genetic bases of either ecological or economic phenotypic variation across individuals within populations of the model and non-model organisms. For this research question, the GWAS replication testing different parameters and models to validate the results’ reproducibility is common. However, straightforward methodologies that manage both replication and tetraploid data are still missing. To solve this problem, we designed the MultiGWAS, a tool that does GWAS for diploid and tetraploid organisms by executing in parallel four software, two designed for polyploid data (GWASpoly and SHEsis) and two for diploids data (GAPIT and TASSEL). MultiGWAS has several advantages. It runs either in the command line or in a graphical interface; it manages different genotype formats, including VCF. Moreover, it allows control for population structure, relatedness, and several quality control checks on genotype data. Besides, MultiGWAS can test for additive and dominant gene action models, and through a proprietary scoring function, select the best model to report its associations. Finally, it generates several reports that facilitate identifying false associations from both the significant and the best-ranked association SNP among the four software. We tested MultiGWAS with public tetraploid potato data for tuber shape and several simulated data under both additive and dominant models. These tests demonstrated that MultiGWAS is better at detecting reliable associations than using each of the four software individually. Moreover, the parallel analysis of polyploid and diploid software that only offers Multi-GWAS demonstrates its utility in understanding the best genetic model behind the SNP association in tetraploid organisms. Therefore, MultiG-WAS probed to be an excellent alternative for wrapping GWAS replication in diploid and tetraploid organisms in a single analysis environment.
Multiple regions of primate orofacial sensorimotor cortex encode bite force and gape
Authors: Arce-McShane Fritzie I. , Sessle Barry J. , Ram Yasheshvini , Balcer Carrie A. , Ross Callum F. , Hatsopoulos Nicholas G. 
Published: August 2020

AbstractThe precise control of bite force and gape is vital for effective breakdown and manipulation of food inside the oral cavity during feeding. Yet the role of the orofacial sensorimotor cortex (OSMcx) in the control of bite force and gape is still largely unknown. The aim of this study was to elucidate how individual neurons and populations of neurons in multiple regions of OSMcx differentially encode bite force and gape when subjects(Macaca mulatta)generated different levels of bite force at varying gapes. We examined neuronal activity recorded simultaneously from three microelectrode arrays implanted chronically in the primary motor (MIo), primary somatosensory (SIo), and cortical masticatory (CMA) areas of OSMcx. We used generalized linear models to evaluate encoding properties of individual neurons and utilized dimensionality reduction techniques to decompose population activity into components related to specific task parameters. Individual neurons encoded bite force more strongly than gape in all three OSMCx areas although bite force was a better predictor of spiking activity in MIo versus SIo. Population activity differentiated between levels of bite force and gape while preserving task-independent temporal modulation across the behavioral trial. While activation patterns of neuronal populations were comparable across OSMCx areas, the total variance explained by task parameters was context-dependent and differed across areas. These findings suggest that the cortical control of gape may rely on computations at the population level whereas the strong encoding of bite force at the individual neuron level allows for the precise and rapid control of bite force.Significance StatementBiting a piece off an apple requires precise sensorimotor control and coordination of bite force and gape by multiple brain regions. The cortical representations of bite force and gape by individual neurons and large populations of neurons across connected motor and somatosensory areas in orofacial cortex is unknown. Here we showed that bite force was more strongly encoded than gape by individual neurons in primary motor, somatosensory, and cortical masticatory areas. Moreover, bite force was more effectively represented in motor versus somatosensory cortices. At the population level, bite force and gape were distinguishable particularly when gape was randomized from trial-to-trial. The results are important for understanding neurophysiological processes underlying masticatory dysfunctions that may occur in aging, stroke, and Alzheimer’s disease.
Assembly of the algal CO2-fixing organelle, the pyrenoid, is guided by a Rubisco-binding motif
Authors: Meyer Moritz T. , Itakura Alan K. , Patena Weronika , Wang Lianyong , He Shan , Emrich-Mills Tom , Lau Chun S. , Yates Gary , Mackinder Luke C. M. , Jonikas Martin C. 
Published: August 2020

AbstractApproximately one-third of the Earth’s photosynthetic CO2assimilation occurs in a pyrenoid, an organelle containing the CO2-fixing enzyme Rubisco. How constituent proteins are recruited to the pyrenoid, and how the organelle’s sub-compartments - membrane tubules, a surrounding phase-separated Rubisco matrix, and a peripheral starch sheath - are held together is unknown. Using the model algaChlamydomonas reinhardtii, we discovered that pyrenoid proteins share a sequence motif. We show that the motif is sufficient to target proteins to the pyrenoid and that the motif binds to Rubisco, suggesting a mechanism for targeting. The presence of the Rubisco-binding motif on proteins that localize to the tubules and on proteins that localize to the matrix-starch sheath interface suggests that the motif holds the pyrenoid’s three sub-compartments together. Our findings advance our understanding of pyrenoid biogenesis and illustrate how a single protein motif can underlie the architecture of a complex multi-layered phase-separated organelle.One Sentence SummaryA ubiquitous Rubisco-binding motif targets proteins to the pyrenoid and holds together the pyrenoid’s three sub-compartments.