bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational methods to develop potential neutralizing antibody Fab region against SARS-CoV-2 as therapeutic and diagnostic tool
Authors: Manikyam Hemanth K. , Joshi Sunil K. 
Published: May 2020

AbstractSARS-CoV-2, a global pandemic originated from Wuhan city of China in the month of December 2019. There is an urgency to identify potential antibodies to neutralize the virus and also as a diagnostic tool candidate. At present palliative treatments using existing antiviral drugs are under trails to treat SARS-CoV-2.Whole Genome sequence of Wuhan market sample of SARS-CoV-2 was obtained from NCBI Gene ID MN908947.3.Spike protein sequence PDB ID 6VSB obtained from RCSB database. Spike protein sequence had shown top V gene match with IGLV1-44*01, IGLV1-47*02 and has VL type chain. Whole Genome sequence had shown top V gene match with IGHV1-38-4*01 and has VH type chain. VD chain had shown link to allele HLA-A0206 80%, HLA-A0217 80%, HLA-A2301 75%, HLA-A0203 75%, HLA-A0202 70% and HLA-A0201 55% of binding levels. Some conserved regions of spike protein had shown strong binding affinity with HLA-A-0*201, HLA-A24, HLA-B-5701 and HLA-B-5703 alpha chains. Synthetic Fab construct BCR type antibody IgG (CR5840) had shown Polyspecific binding activity with spike glycoprotein when compared with available Anti-SARS antibody CR3022.Thus we propose CR5840 Fab constructed antibody as potential neutralizing antibody for SARS-CoV-2. Based on germline analysis we also propose cytotoxic T lymphocyte epitope peptide selective system as effective tool for the development of SARS-CoV-2 vaccine.
Previous experience with depression in others and self: a cross-sectional study of the impact on stigma and help-seeking attitudes
Authors: Conceição Virgínia da , Rothes Inês , Severo Milton , Griffiths Kathy , Hegerl Ulrich , Gusmão Ricardo 
Published: May 2020

AbstractBackgroundStigma has been considered a significant barrier both in treatment, rehabilitation and help-seeking behaviours of people diagnosed with depression. This study aimed to assess the influence of the type of previous experience with depression on depression stigma, identify the effects of previous experience with depression on stigma and to analyse the effects of stigma on help-seeking attitudes.MethodsA total of 1693 participants with a mean age of 47.2 (SD=18.17) completed the Depression Stigma Scale (DSS), the Attitude Toward Seeking Professional Psychological Help (ATSPPH), and a sociodemographic questionnaire. We categorised participants into four comparison groups: no previous experience with depression (n=479), indirect experience with depression (n=661), direct experience with depression (n=137), and both direct and indirect experience with depression (n=416). Data were analysed using SPSS 24.0.ResultsLevels of personal stigma were lower in people who had family and friends experiencing depression in comparison with individuals with no history of depression experience. Better attitudes towards help-seeking were evident in those with lower personal stigma, and worse help-seeking attitudes were associated with higher perceived stigma in the indirect previous experience group.LimitationsDuration of participant exposure to depression was not collected.ConclusionsThe individual’s experience with depression influences the development of personal stigmatisation towards depression and plays a role in help-seeking behaviours. Addressing people’s experience of depression might be a practical way of reducing depression stigma and improve help-seeking behaviours.
Predicting amphibian intraspecific diversity with machine learning: Challenges and prospects for integrating traits, geography, and genetic data
Authors: Barrow Lisa N. , Masiero da Fonseca Emanuel , Thompson Coleen E. P. , Carstens Bryan C. 
Published: May 2020

AbstractThe growing availability of genetic datasets, in combination with machine learning frameworks, offer great potential to answer long-standing questions in ecology and evolution. One such question has intrigued population geneticists, biogeographers, and conservation biologists: What determines intraspecific genetic diversity? This question is challenging to answer because many factors may influence genetic variation, including life history traits, historical influences, and geography, and the relative importance of these factors varies across taxonomic and geographic scales. Furthermore, interpreting the influence of numerous, potentially correlated variables is difficult with traditional statistical approaches. To address these challenges, we combined repurposed data with machine learning and investigated predictors of genetic diversity, focusing on Nearctic amphibians as a case study. We aggregated species traits, range characteristics, and >42,000 genetic sequences for 299 species using open-access scripts and various databases. After identifying important predictors of nucleotide diversity with random forest regression, we conducted follow-up analyses to examine the roles of phylogenetic history, geography, and demographic processes on intraspecific diversity. Although life history traits were not important predictors for this dataset, we found significant phylogenetic signal in genetic diversity within amphibians. We also found that salamander species at northern latitudes contain lower genetic diversity. Data repurposing and machine learning provide valuable tools for detecting patterns with relevance for conservation, but concerted efforts are needed to compile meaningful datasets with greater utility for understanding global biodiversity.
Mesenchymal stem cells with overexpression of Angiotensin-converting enzyme-2 improved the microenvironment and cardiac function in a rat model of myocardial infarction
Authors: Liu Chao , Fan Yue , Zhu Hong-Yi , zhou Lu , Wang Yu , Li Qing-Ping 
Published: May 2020

AbstractBackgroundAngiotensin-converting enzyme-2 (ACE2) overexpression improves left ventricular remodeling and function in diabetic cardiomyopathy; however, the effect of ACE2-overexpressed mesenchymal stem cells (MSCs) on myocardial infarction (MI) remains unexplored. This study aimed to investigate the effect of ACE2-overexpression on the function of MSCs and the therapeutic efficacy of MSCs for MI.MethodsMSCs were transfected with Ace2 gene using lentivirus, and then transplanted into the border zone of ischemic heart. The renin-angiotensin system (RAS) expression, nitric oxide synthase (NOS) expression, paracrine factors, anti-hypoxia ability, tube formation of MSCs, and heart function were determined.ResultsMSCs expressed little ACE2. ACE2-overexpression decreased the expression of AT1 and VEGF apparently, up-regulated the paracrine of HGF, and increased the synthesis of Angiotensin 1-7 in vitro. ACE2-overexpressed MSCs showed a cytoprotective effect on cardiomyocyte, and an interesting tube formation ability, decreased the heart fibrosis and infarct size, and improved the heart function.ConclusionTherapies employing MSCs with ACE2 overexpression may represent an effective treatment for improving the myocardium microenvironment and the cardiac function after MI.
Trapped Topoisomerase II initiates formation ofde novoduplicationsviathe nonhomologous end-joining pathway in yeast
Authors: Stantial Nicole , Rogojina Anna , Gilbertson Matthew , Sun Yilun , Miles Hannah , Shaltz Samantha , Berger James , Nitiss Karin C. , Jinks-Robertson Sue , Nitiss John L. 
Published: May 2020

ABSTRACTTopoisomerase II (Top2) is an essential enzyme that resolves catenanes between sister chromatids as well as supercoils associated with the over- or under-winding of duplex DNA. Top2 alters DNA topology by making a double-strand break (DSB) in DNA and passing an intact duplex through the break. Each component monomer of the Top2 homodimer nicks one of the DNA strands and forms a covalent phosphotyrosyl bond with the 5’ end. Stabilization of this intermediate by chemotherapeutic drugs such as etoposide leads to persistent and potentially toxic DSBs. We describe the isolation of a yeasttop2mutant (top2- F1025Y,R1128G) whose product generates a stabilized cleavage intermediatein vitro. In yeast cells, overexpression of thetop2- F1025Y,R1128Gallele is associated with a novel mutation signature that is characterized byde novoduplications of DNA sequence that depend on the nonhomologous end-joining pathway of DSB repair. Top2-associated duplications are promoted by the clean removal of the enzyme from DNA ends and are suppressed when the protein is removed as part of an oligonucleotide.TOP2cells treated with etoposide exhibit the same mutation signature, as do cells that over-express the wild-type protein. These results have implications for genome evolution and are relevant to the clinical use of chemotherapeutic drugs that target Top2.SIGNIFICANCE STATEMENTDNA-strand separation during transcription and replication creates topological problems that are resolved by topoisomerases. These enzymes nick DNA strands to allow strand passage and then reseal the broken DNA to restore its integrity. Topoisomerase II (Top2) nicks complementary DNA strands to create double-strand break (DSBs) intermediates that can be stabilized by chemotherapeutic drugs and are toxic if not repaired. We identified a mutant form of yeast Top2 that forms stabilized cleavage intermediates in the absence of drugs. Over- expression of the mutant Top2 was associated with a unique mutation signature in which small (1-4 bp), unique segments of DNA were duplicated. Thesede novoduplications required the nonhomologous end-joining pathway of DSB repair, and their Top2-dependence has clinical and evolutionary implications.
RLP23 is required for Arabidopsis immunity against the grey mould pathogenBotrytis cinerea
Authors: Ono Erika , Mise Kazuyuki , Takano Yoshitaka 
Published: May 2020

AbstractNecrosis- and ethylene-inducing-like proteins (NLPs) are secreted by fungi, oomycetes and bacteria. Conserved nlp peptides derived from NLPs are recognized as pathogen-associated molecular patterns (PAMPs), leading to PAMP-triggered immune responses. RLP23 is the receptor of the nlp peptides inArabidopsis thaliana; however, its actual contribution to plant immunity is unclear. Here, we report that RLP23 is required for Arabidopsis immunity against the necrotrophic fungal pathogenBotrytis cinerea. Arabidopsisrlp23mutants exhibited enhanced susceptibility toB. cinereacompared with the wild-type plants. Notably, microscopic observation of theB. cinereainfection behaviour indicated the involvement of RLP23 in pre-invasive resistance to the pathogen.B. cinereacarried twoNLPgenes,BcNEP1andBcNEP2;BcNEP1was expressed preferentially before/during invasion into Arabidopsis, whereasBcNEP2was expressed at the late phase of infection. Importantly, the nlp peptides derived from both BcNEP1 and BcNEP2 induced the production of reactive oxygen species in an RLP23-dependent manner. In contrast, other necrotrophic fungusAlternaria brassicicoladid not express theNLPgene in the early infection phase and exhibited no enhanced virulence in therlp23mutants. Collectively, these results strongly suggest that RLP23 contributes to Arabidopsis pre-invasive resistance toB. cinereavia NLP recognition at the early infection phase.
Computational analysis on the ACE2-derived peptides for neutralizing the ACE2 binding to the spike protein of SARS-CoV-2
Authors: Lupala Cecylia S. , Kumar Vikash , Li Xuanxuan , Su Xiao-dong , Liu Haiguang 
Published: May 2020

ABSTRACTThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19, is spreading globally and has infected more than 3 million people. It has been discovered that SARS-CoV-2 initiates the entry into cells by binding to human angiotensin-converting enzyme 2 (hACE2) through the receptor binding domain (RBD) of its spike glycoprotein. Hence, drugs that can interfere the SARS-CoV-2-RBD binding to hACE2 potentially can inhibit SARS-CoV-2 from entering human cells. Here, based on the N-terminal helix α1 of human ACE2, we designed nine short peptides that have potential to inhibit SARS-CoV-2 binding. Molecular dynamics simulations of peptides in the their free and SARS-CoV-2 RBD-bound forms allow us to identify fragments that are stable in water and have strong binding affinity to the SARS-CoV-2 spike proteins. The important interactions between peptides and RBD are highlighted to provide guidance for the design of peptidomimetics against the SARS-CoV-2.
igv.js: an embeddable JavaScript implementation of the Integrative Genomics Viewer (IGV)
Authors: Robinson James T. , Thorvaldsdóttir Helga , Turner Douglass , Mesirov Jill P. 
Published: May 2020

Abstractigv.js is an embeddable JavaScript implementation of the Integrative Genomics Viewer (IGV). It can be easily dropped into any web page with a single line of code and has no external dependencies. The viewer runs completely in the web browser, with no backend server and no data pre-processing required.
COVIDier: A Deep-learning Tool For Coronaviruses Genome And Virulence Proteins Classification
Authors: Habib Peter T. , Alsamman Alsamman M. , Saber-Ayad Maha , Hassanein Sameh E. , Hamwieh Aladdin 
Published: May 2020

AbstractCOVID-19, caused by SARS-CoV-2 infection, has already reached pandemic proportions in a matter of a few weeks. At the time of writing this manuscript, the unprecedented public health crisis caused more than 2.5 million cases with a mortality range of 5-7%. The SARS-CoV-2, also called novel Coronavirus, is related to both SARS-CoV and bat SARS. Great efforts have been spent to control the pandemic that has become a significant burden on the health systems in a short time. Since the emergence of the crisis, a great number of researchers started to use the AI tools to identify drugs, diagnosing using CT scan images, scanning body temperature, and classifying the severity of the disease. The emergence of variants of the SARS-CoV-2 genome is a challenging problem with expected serious consequences on the management of the disease. Here, we introduce COVIDier, a deep learning-based software that is enabled to classify the different genomes of Alpha coronavirus, Beta coronavirus, MERS, SARS-CoV-1, SARS-CoV-2, and bronchitis-CoV. COVIDier was trained on 1925 genomes, belonging to the three families of SARS retrieved from NCBI Database to propose a new method to train deep learning model trained on genome data using Multi-layer Perceptron Classifier (MLPClassifier), a deep learning algorithm, that could blindly predict the virus family name from the genome of by predicting the statistically similar genome from training data to the given genome. COVIDier able to predict how close the emerging novel genomes of SARS to the known genomes with accuracy 99%. COVIDier can replace tools like BLAST that consume higher CPU and time.
Effect of viewing distance on object responses in macaque areas 45B, F5a and F5p
Authors: Caprara I , Janssen P 
Published: May 2020

AbstractTo perform real-world tasks like grasping, the primate brain has to process visual object information so that the grip aperture can be adjusted before contact with the object is made. Previous studies have demonstrated that the posterior subsector of the Anterior Intraparietal area (pAIP) is connected to frontal area 45B, and the anterior subsector of AIP (aAIP) to F5a (Premereur et al., 2015). However, the role of area 45B and F5a in visually-guided object grasping is poorly understood. Here, we investigated the role of area 45B, F5a and F5p in visually-guided grasping. If a neuronal response to an object during passive fixation represents the activation of a motor command related to the preshaping of the hand, such neurons should prefer objects presented within reachable distance. Conversely, neurons encoding a pure visual representation of an object should be less affected by viewing distance. Contrary to our expectations, we found that the majority of neurons in area 45B were object- and viewing distance selective, with a clear preference for the near viewing distance. Area F5a showed much weaker object selectivity compared to 45B, with a similar preference for objects presented at the Near position emerging mainly in the late epoch. Finally, F5p neurons were less object selective and frequently preferred objects presented at the Far position. Therefore, contrary to our expectations, neurons in area 45B – but not F5p neurons – prefer objects presented in peripersonal space.Significance statementThe current experiment provides the first evidence on the neural representation of distance in frontal areas that are active during visually-guided grasping. Area 45B and F5a neurons were object- and distance-selective, and preferred the near viewing distance even for objects with identical retinal size. In area F5p we observed strong visual responses with an unexpected preference for the Far viewing distance, suggesting that the motor-related object representation was still active during the presentation of objects outside reaching distance.
Evaluating the sensitivity of functional connectivity measures to motion artifact in resting-state fMRI data
Authors: Mahadevan Arun S. , Tooley Ursula A. , Bertolero Maxwell A. , Mackey Allyson P. , Bassett Danielle S. 
Published: May 2020

AbstractFunctional connectivity (FC) networks are typically inferred from resting-state fMRI data using the Pearson correlation between BOLD time series from pairs of brain regions. However, alternative methods of estimating functional connectivity have not been systematically tested for their sensitivity or robustness to head motion artifact. Here, we evaluate the sensitivity of six different functional connectivity measures to motion artifact using resting-state data from the Human Connectome Project. We report that FC estimated using full correlation has a relatively high residual distance-dependent relationship with motion compared to partial correlation, coherence and information theory-based measures, even after implementing rigorous methods for motion artifact mitigation. This disadvantage of full correlation, however, may be offset by higher test-retest reliability and system identifiability. FC estimated by partial correlation offers the best of both worlds, with low sensitivity to motion artifact and intermediate system identifiability, with the caveat of low test-retest reliability. We highlight spatial differences in the sub-networks affected by motion with different FC metrics. Further, we report that intra-network edges in the default mode and retrosplenial temporal sub-networks are highly correlated with motion in all FC methods. Our findings indicate that the method of estimating functional connectivity is an important consideration in resting-state fMRI studies and must be chosen carefully based on the parameters of the study.
SMARCB1 loss interacts with neuronal differentiation state to block maturation and impact cell stability
Authors: Parisian Alison D. , Koga Tomoyuki , Miki Shunichiro , Johann Pascal D. , Kool Marcel , Crawford John R. , Furnari Frank B. 
Published: May 2020

AbstractAtypical teratoid rhabdoid tumors (ATRT) are challenging pediatric brain cancers which are predominantly associated with inactivation of the gene SMARCB1, a conserved subunit of the chromatin remodeling BAF complex, which has known contributions to developmental processes. To identify potential interactions between SMARCB1 loss and the process of neural development, we introduced an inducible SMARCB1 loss of function system into human induced pluripotent stem cells (iPSCs) which were subjected to either directed neuronal differentiation or differentiation into cerebral organoids. Using this system, we have identified substantial differences in the downstream effects of SMARCB1 loss depending on differentiation state and identified an interaction between SMARCB1 loss and neural differentiation pressure which causes a resistance to terminal differentiation and a defect in maintenance of a normal cell state. Our results provide insight into how SMARCB1 loss might interact with neural development in the process of ATRT tumorigenesis.
Direct and specific assessment of axonal injury and spinal cord microenvironments using diffusion correlation imaging
Authors: Benjamini Dan , Hutchinson Elizabeth B. , Komlosh Michal E. , Comrie Courtney J. , Schwerin Susan C. , Zhang Guofeng , Pierpaoli Carlo , Basser Peter J. 
Published: May 2020

AbstractWe describe a practical two-dimensional (2D) diffusion MRI framework to deliver specificity and improve sensitivity to axonal injury in the spinal cord. This approach provides intravoxel distributions of correlations of water mobilities in orthogonal directions, revealing sub-voxel diffusion components. Here we use it to investigate water diffusivities along axial and radial orientations within spinal cord specimens with confirmed, tract-specific axonal injury. First, we show using transmission electron microscopy and immunohistochemistry that tract-specific axonal beading occurs following Wallerian degeneration in the cortico-spinal tract as direct sequelae to closed head injury. We demonstrate that although some voxel-averaged diffusion tensor imaging (DTI) metrics are sensitive to this axonal injury, they are non-specific, i.e., they do not reveal an underlying biophysical mechanism of injury. Then we employ 2D diffusion correlation imaging (DCI) to improve discrimination of different water microenvironments by measuring and mapping the joint water mobility distributions perpendicular and parallel to the spinal cord axis. We determine six distinct diffusion spectral components that differ according to their microscopic anisotropy and mobility. We show that at the injury site a highly anisotropic diffusion component completely disappears and instead becomes more isotropic. Based on these findings, an injury-specific MR image of the spinal cord was generated, and a radiological-pathological correlation with histological silver staining % area was performed. The resulting strong and significant correlation (r= 0.70,p <0.0001) indicates the high specificity with which DCI detects injury-induced tissue alterations. We predict that the ability to selectively image microstructural changes following axonal injury in the spinal cord can be useful in clinical and research applications by enabling specific detection and increased sensitivity to injury-induced microstructural alterations. These results also encourage us to translate DCI to higher spatial dimensions to enable assessment of traumatic axonal injury, and possibly other diseases and disorders in the brain.
Determinants of RNA recognition by the FinO domain of theEscherichia coliProQ protein
Authors: Stein Ewa M. , Kwiatkowska Joanna , Basczok Maciej M. , Gravel Chandra M. , Berry Katherine E. , Olejniczak Mikołaj 
Published: May 2020

ABSTRACTThe regulation of gene expression by small RNAs inEscherichia colidepends on RNA binding proteins Hfq and ProQ, which bind mostly distinct RNA pools. To understand how ProQ discriminates between RNA substrates, we compared its binding to six different RNA molecules. Full-length ProQ bound all six RNAs similarly, while the isolated N-terminal FinO domain (NTD) of ProQ specifically recognized RNAs with Rho-independent terminators. Analysis ofmalM3’-UTR mutants showed that tight RNA binding by the ProQ NTD required a terminator hairpin of at least two base pairs preceding an 3’ oligoU tail of at least four uridine residues. Substitution of an A-rich sequence on the 5’ side of the terminator to uridines strengthened the binding of several ProQ-specific RNAs to the Hfq protein, but not to the ProQ NTD. Substitution of the motif in themalM-3’ andcspE-3’ RNAs also conferred the ability to bind Hfq inE. colicells, as measured using a three-hybrid assay. In summary, these data suggest that the ProQ NTD specifically recognizes 3’ intrinsic terminators of RNA substrates, and that the discrimination between RNA ligands byE. coliProQ and Hfq depends both on positive determinants for binding to ProQ and negative determinants against binding to Hfq.