cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.18134010
title: Characterization of tick salivary gland and saliva alphagalactome reveals candidate alpha-gal syndrome disease biomarkers

description: Ticks are obligate hematophagous arthropods that synthesize the glycan Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal) associated with the alpha-gal syndrome (AGS) or allergy to mammalian meat consumption. In this study, we used a proteomics approach to characterize tick proteins in salivary glands (sialome SG), secreted saliva (sialome SA) and with α-Gal modification (alphagalactome SG and SA) in model tick species associated with the AGS in the United States (<i>Amblyomma americanum</i>) and Australia (<i>Ixodes holocyclus</i>). Selected proteins reactive to sera (IgE) from patients with AGS were identified to advance in the identification of possible proteins associated with the AGS. For comparative analysis, the α-Gal content was measured in various tick species. The results confirmed that ticks produce proteins with α-Gal modifications and secreted into saliva during feeding. Proteins identified in tick alphagalactome SA by sera from patients with severe AGS symptomatology may constitute candidate disease biomarkers. The results support the presence of tick-derived proteins with α-Gal modifications in the saliva with potential implications in AGS and other disorders and protective capacity against tick infestations and pathogen infection. Future research should focus on the characterization of the function of tick glycoproteins with α-Gal in tick biology and AGS.
DOI: 10.6084/m9.figshare.18134010.v1
title: Characterization of tick salivary gland and saliva alphagalactome reveals candidate alpha-gal syndrome disease biomarkers

description: Ticks are obligate hematophagous arthropods that synthesize the glycan Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal) associated with the alpha-gal syndrome (AGS) or allergy to mammalian meat consumption. In this study, we used a proteomics approach to characterize tick proteins in salivary glands (sialome SG), secreted saliva (sialome SA) and with α-Gal modification (alphagalactome SG and SA) in model tick species associated with the AGS in the United States (<i>Amblyomma americanum</i>) and Australia (<i>Ixodes holocyclus</i>). Selected proteins reactive to sera (IgE) from patients with AGS were identified to advance in the identification of possible proteins associated with the AGS. For comparative analysis, the α-Gal content was measured in various tick species. The results confirmed that ticks produce proteins with α-Gal modifications and secreted into saliva during feeding. Proteins identified in tick alphagalactome SA by sera from patients with severe AGS symptomatology may constitute candidate disease biomarkers. The results support the presence of tick-derived proteins with α-Gal modifications in the saliva with potential implications in AGS and other disorders and protective capacity against tick infestations and pathogen infection. Future research should focus on the characterization of the function of tick glycoproteins with α-Gal in tick biology and AGS.
DOI: 10.6084/m9.figshare.12993593
title: Identification of destabilizing SNPs in SARS-CoV2-ACE2 protein and spike glycoprotein: implications for virus entry mechanisms

description: COVID-19 an outbreak of a novel corona virus originating from Wuhan, China in December 2019 has now spread across the entire world and has been declared a pandemic by WHO. Angiotensin converting enzyme 2 (ACE2) is a receptor protein that interacts with the spike glycoprotein of the host to facilitate the entry of coronavirus (SARS-CoV-2) hence causing the disease (COVID-19). Our experimental design is based on bioinformatics approach that combines sequence, structure and consensus based tools to label a protein coding single nucleotide polymorphism (SNP) as damaging/deleterious or neutral. The interaction of wildtype ACE2-spike glycoprotein and their variants were analyzed using docking studies. The mutations W461R, G405E and F588S in ACE2 receptor protein and population specific mutations P391S, C12S and G1223A in the spike glycoprotein were predicted as highly destabilizing to the structure of the bound complex. So far, no extensive in silico study has been reported that identifies the effect of SNPs on Spike glycoprotein-ACE2 interaction exploring both sequence and structural features. To this end, this study conducted an in-depth analysis that facilitates in identifying the mutations that blocks the interaction of two proteins that can result in stopping the virus from entering the host cell. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.12962627
title: Molecular basis of the potential interaction of SARS-CoV-2 spike protein to CD147 in COVID-19 associated-lymphopenia

description: Lymphopenia is considered one of the most characteristic clinical features of the coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects host cells via the interaction of its spike protein with the human angiotensin-converting enzyme 2 (hACE2) receptor. Since T lymphocytes display a very low expression level of hACE2, a novel receptor might be involved in the entry of SARS-CoV-2 into T cells. The transmembrane glycoprotein CD147 is highly expressed by activated T lymphocytes, and was recently proposed as a probable route for SARS-CoV-2 invasion. To understand the molecular basis of the potential interaction of SARS-CoV-2 to CD147, we have investigated the binding of the viral spike protein to this receptor in-silico. The results showed that this binding is dominated by electrostatic interactions involving residues Arg403, Asn481, and the backbone of Gly502. The overall binding arrangement shows the CD147 C-terminal domain interacting with the spike external subdomain in the grove between the short antiparallel β strands, β1’ and β2’, and the small helix α1’. This proposed interaction was further confirmed using MD simulation and binding free energy calculation. These data contribute to a better understanding of the mechanism of infection of SARS-CoV-2 to T lymphocytes and could provide valuable insights for the rational design of adjuvant treatment for COVID-19. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.12993593.v1
title: Identification of destabilizing SNPs in SARS-CoV2-ACE2 protein and spike glycoprotein: implications for virus entry mechanisms

description: COVID-19 an outbreak of a novel corona virus originating from Wuhan, China in December 2019 has now spread across the entire world and has been declared a pandemic by WHO. Angiotensin converting enzyme 2 (ACE2) is a receptor protein that interacts with the spike glycoprotein of the host to facilitate the entry of coronavirus (SARS-CoV-2) hence causing the disease (COVID-19). Our experimental design is based on bioinformatics approach that combines sequence, structure and consensus based tools to label a protein coding single nucleotide polymorphism (SNP) as damaging/deleterious or neutral. The interaction of wildtype ACE2-spike glycoprotein and their variants were analyzed using docking studies. The mutations W461R, G405E and F588S in ACE2 receptor protein and population specific mutations P391S, C12S and G1223A in the spike glycoprotein were predicted as highly destabilizing to the structure of the bound complex. So far, no extensive in silico study has been reported that identifies the effect of SNPs on Spike glycoprotein-ACE2 interaction exploring both sequence and structural features. To this end, this study conducted an in-depth analysis that facilitates in identifying the mutations that blocks the interaction of two proteins that can result in stopping the virus from entering the host cell. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.12962627.v1
title: Molecular basis of the potential interaction of SARS-CoV-2 spike protein to CD147 in COVID-19 associated-lymphopenia

description: Lymphopenia is considered one of the most characteristic clinical features of the coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects host cells via the interaction of its spike protein with the human angiotensin-converting enzyme 2 (hACE2) receptor. Since T lymphocytes display a very low expression level of hACE2, a novel receptor might be involved in the entry of SARS-CoV-2 into T cells. The transmembrane glycoprotein CD147 is highly expressed by activated T lymphocytes, and was recently proposed as a probable route for SARS-CoV-2 invasion. To understand the molecular basis of the potential interaction of SARS-CoV-2 to CD147, we have investigated the binding of the viral spike protein to this receptor in-silico. The results showed that this binding is dominated by electrostatic interactions involving residues Arg403, Asn481, and the backbone of Gly502. The overall binding arrangement shows the CD147 C-terminal domain interacting with the spike external subdomain in the grove between the short antiparallel β strands, β1’ and β2’, and the small helix α1’. This proposed interaction was further confirmed using MD simulation and binding free energy calculation. These data contribute to a better understanding of the mechanism of infection of SARS-CoV-2 to T lymphocytes and could provide valuable insights for the rational design of adjuvant treatment for COVID-19. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.12981936
title: <i>In silico</i> modeling for quick prediction of inhibitory activity against 3CL<sup>pro</sup> enzyme in SARS CoV diseases

description: As of 2 September 2020, the 2019 novel coronavirus or SARS CoV-2 has been responsible for more than 2,56,02,665 infections and 8,52,768 deaths worldwide. There has been an urgent need of newer drug discovery to tackle the situation. Severe acute respiratory syndrome-associated coronavirus 3C-like protease (or 3CL<sup>pro</sup>) is a potential target as anti-SARS agents as it plays a vital role in the viral life cycle. This study aims at developing a quantitative structure–activity relationship (QSAR) model against a group of 3CL<sup>pro</sup> inhibitors to study their structural requirements for their inhibitory activity. Further, molecular docking studies were carried out which helped in the justification of the QSAR findings. Moreover, molecular dynamics simulation study was performed for selected compounds to check the stability of interactions as suggested by the docking analysis. The current QSAR model was further used in the prediction and screening of large databases within a short time. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.12981936.v1
title: <i>In silico</i> modeling for quick prediction of inhibitory activity against 3CL<sup>pro</sup> enzyme in SARS CoV diseases

description: As of 2 September 2020, the 2019 novel coronavirus or SARS CoV-2 has been responsible for more than 2,56,02,665 infections and 8,52,768 deaths worldwide. There has been an urgent need of newer drug discovery to tackle the situation. Severe acute respiratory syndrome-associated coronavirus 3C-like protease (or 3CL<sup>pro</sup>) is a potential target as anti-SARS agents as it plays a vital role in the viral life cycle. This study aims at developing a quantitative structure–activity relationship (QSAR) model against a group of 3CL<sup>pro</sup> inhibitors to study their structural requirements for their inhibitory activity. Further, molecular docking studies were carried out which helped in the justification of the QSAR findings. Moreover, molecular dynamics simulation study was performed for selected compounds to check the stability of interactions as suggested by the docking analysis. The current QSAR model was further used in the prediction and screening of large databases within a short time. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.13050157
title: Molecular dynamics simulation study on <i>Thermotoga maritima</i> EngA: GTP/GDP bound state of the second G-domain influences the domain–domain interface interactions

description: EngA, a GTPase involved in the late steps of ribosome maturation, consists of two GTP binding domains (G-domains) [GD1, GD2] and a C-terminal domain. The combination of GTP/GDP in G-domains dictates its binding to the ribosomal subunits by altering its conformation. Studies and comparisons on the available structures of EngA enable us to understand the correlation between nucleotide bound states and its conformation. Using all-atom molecular dynamics (MD) simulations, we have explored the conformational behavior of EngA from <i>Thermotoga maritima</i> (TmDer) upon binding the various combinations of GTP and GDP. Analyses of Root Mean Square Deviation (RMSD), Radius of Gyration (Rg) and Root Mean Square Fluctuation (RMSF) emphasize the importance of the second G-domain nucleotide bound state. RMSD and Rg exhibit slightly lower values when GTP is embedded in GD2 compared to GDP. These lower values are due to Sw-II of GD2, which has been observed from RMSF plot. Further investigation on the effects of GD2 nucleotide bound state using Principal Component Analysis (PCA) and Free Energy Landscape (FEL) analysis manifests an allosteric connection between GD2 nucleotide bound state and the GD1–KH interface. This is further validated by extracting electrostatic interactions and H-bonds at the GD1–KH interface. <i>In silico</i> mutations at the GD1 interface of KH domain affect the Sw-II mobility of GD2 by showing inverted behavior. This suggests using the second G-domain as an antibacterial target and further simulation studies on different species of EngA are to be explored. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.13050157.v1
title: Molecular dynamics simulation study on <i>Thermotoga maritima</i> EngA: GTP/GDP bound state of the second G-domain influences the domain–domain interface interactions

description: EngA, a GTPase involved in the late steps of ribosome maturation, consists of two GTP binding domains (G-domains) [GD1, GD2] and a C-terminal domain. The combination of GTP/GDP in G-domains dictates its binding to the ribosomal subunits by altering its conformation. Studies and comparisons on the available structures of EngA enable us to understand the correlation between nucleotide bound states and its conformation. Using all-atom molecular dynamics (MD) simulations, we have explored the conformational behavior of EngA from <i>Thermotoga maritima</i> (TmDer) upon binding the various combinations of GTP and GDP. Analyses of Root Mean Square Deviation (RMSD), Radius of Gyration (Rg) and Root Mean Square Fluctuation (RMSF) emphasize the importance of the second G-domain nucleotide bound state. RMSD and Rg exhibit slightly lower values when GTP is embedded in GD2 compared to GDP. These lower values are due to Sw-II of GD2, which has been observed from RMSF plot. Further investigation on the effects of GD2 nucleotide bound state using Principal Component Analysis (PCA) and Free Energy Landscape (FEL) analysis manifests an allosteric connection between GD2 nucleotide bound state and the GD1–KH interface. This is further validated by extracting electrostatic interactions and H-bonds at the GD1–KH interface. <i>In silico</i> mutations at the GD1 interface of KH domain affect the Sw-II mobility of GD2 by showing inverted behavior. This suggests using the second G-domain as an antibacterial target and further simulation studies on different species of EngA are to be explored. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.13013241.v1
title: Pharmacophore based virtual screening, molecular docking, molecular dynamics and MM-GBSA approach for identification of prospective SARS-CoV-2 inhibitor from natural product databases

description: COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily appeared in Wuhan, China, in December 2019. At present, no proper therapy and vaccinations are available for the disease, and it is increasing day by day with a high mortality rate. Pharmacophore based virtual screening of the selected natural product databases followed by Glide molecular docking and dynamics studies against SARS-CoV-2 main protease was investigated to identify potential ligands that may act as inhibitors. The molecules <b>SN00293542</b> and <b>SN00382835</b> revealed the highest docking score of <b>−14.57</b> and <b>−12.42 kcal/mol,</b> respectively, when compared with the co-crystal ligands of PDB-6Y2F (O6K) and 6W63 (X77) of the SARS-CoV-2 M<sup>pro</sup>. To further validate the interactions of top scored molecules <b>SN00293542</b> and <b>SN00382835,</b> molecular dynamics study of 100 ns was carried out. This indicated that the protein-ligand complex was stable throughout the simulation period, and minimal backbone fluctuations have ensued in the system. Post-MM-GBSA analysis of molecular dynamics data showed free binding energy-<b>71.7004 +/− 7.98, −56.81+/− 7.54 kcal/mol,</b> respectively. The computational study identified several ligands that may act as potential inhibitors of SARS-CoV-2 M<sup>pro</sup>. The top-ranked molecules <b>SN00293542,</b> and <b>SN00382835</b> occupied the active site of the target, the main protease like that of the co-crystal ligand. These molecules may emerge as a promising ligands against SARS-CoV-2 and thus needs further detailed investigations. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.13019594
title: WD40 domain of RqkA regulates its kinase activity and role in extraordinary radioresistance of <i>D. radiodurans</i>

description: RqkA, a DNA damage responsive serine/threonine kinase, is characterized for its role in DNA repair and cell division in <i>D. radiodurans</i>. It has a unique combination of a kinase domain at N-terminus and a WD40 type domain at C-terminus joined through a linker. WD40 domain is comprised of eight β-propeller repeats held together via ‘tryptophan-docking motifs’ and forming a typical ‘velcro’ closure structure. RqkA mutants lacking the WD40 region (hereafter referred to as WD mutant) could not complement RqkA loss in γ radiation resistance in <i>D. radiodurans</i> and lacked γ radiation-mediated activation of kinase activity <i>in vivo</i>. WD mutants failed to phosphorylate its cognate substrate (e.g. DrRecA) in surrogate <i>E. coli</i> cells. Unlike wild-type enzyme, the kinase activity of its WD40 mutants was not stimulated by pyrroloquinoline quinine (PQQ) indicating the role of the WD motifs in PQQ interaction and stimulation of its kinase activity. Together, results highlighted the importance of the WD40 domain in the regulation of RqkA kinase signaling functions <i>in vivo,</i> and thus, the role of WD40 domain in the regulation of any STPK is first time demonstrated in bacteria. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.13013241
title: Pharmacophore based virtual screening, molecular docking, molecular dynamics and MM-GBSA approach for identification of prospective SARS-CoV-2 inhibitor from natural product databases

description: COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily appeared in Wuhan, China, in December 2019. At present, no proper therapy and vaccinations are available for the disease, and it is increasing day by day with a high mortality rate. Pharmacophore based virtual screening of the selected natural product databases followed by Glide molecular docking and dynamics studies against SARS-CoV-2 main protease was investigated to identify potential ligands that may act as inhibitors. The molecules <b>SN00293542</b> and <b>SN00382835</b> revealed the highest docking score of <b>−14.57</b> and <b>−12.42 kcal/mol,</b> respectively, when compared with the co-crystal ligands of PDB-6Y2F (O6K) and 6W63 (X77) of the SARS-CoV-2 M<sup>pro</sup>. To further validate the interactions of top scored molecules <b>SN00293542</b> and <b>SN00382835,</b> molecular dynamics study of 100 ns was carried out. This indicated that the protein-ligand complex was stable throughout the simulation period, and minimal backbone fluctuations have ensued in the system. Post-MM-GBSA analysis of molecular dynamics data showed free binding energy-<b>71.7004 +/− 7.98, −56.81+/− 7.54 kcal/mol,</b> respectively. The computational study identified several ligands that may act as potential inhibitors of SARS-CoV-2 M<sup>pro</sup>. The top-ranked molecules <b>SN00293542,</b> and <b>SN00382835</b> occupied the active site of the target, the main protease like that of the co-crystal ligand. These molecules may emerge as a promising ligands against SARS-CoV-2 and thus needs further detailed investigations. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.13019594.v1
title: WD40 domain of RqkA regulates its kinase activity and role in extraordinary radioresistance of <i>D. radiodurans</i>

description: RqkA, a DNA damage responsive serine/threonine kinase, is characterized for its role in DNA repair and cell division in <i>D. radiodurans</i>. It has a unique combination of a kinase domain at N-terminus and a WD40 type domain at C-terminus joined through a linker. WD40 domain is comprised of eight β-propeller repeats held together via ‘tryptophan-docking motifs’ and forming a typical ‘velcro’ closure structure. RqkA mutants lacking the WD40 region (hereafter referred to as WD mutant) could not complement RqkA loss in γ radiation resistance in <i>D. radiodurans</i> and lacked γ radiation-mediated activation of kinase activity <i>in vivo</i>. WD mutants failed to phosphorylate its cognate substrate (e.g. DrRecA) in surrogate <i>E. coli</i> cells. Unlike wild-type enzyme, the kinase activity of its WD40 mutants was not stimulated by pyrroloquinoline quinine (PQQ) indicating the role of the WD motifs in PQQ interaction and stimulation of its kinase activity. Together, results highlighted the importance of the WD40 domain in the regulation of RqkA kinase signaling functions <i>in vivo,</i> and thus, the role of WD40 domain in the regulation of any STPK is first time demonstrated in bacteria. Communicated by Ramaswamy H. Sarma
DOI: 10.34740/kaggle/dsv/3119721
title: COVID Vaccination in World (updated daily)
DOI: 10.17632/5zjkdkh65p.1
title: Efficient and safe correction of hemophilia A by lentiviral vector-transduced BOECs in an implantable device

description: Data for the paper of Olgasi et al 2021 (PMID: 34853801 , PMCID: PMC8606349 , DOI: 10.1016/j.omtm.2021.10.015)
DOI: 10.17028/rd.lboro.19096406.v1
title: Supplementary Information Files for: Body mapping of sweating patterns of pre-pubertal children during intermittent exercise in a warm environment

description: Supplementary Information Files for: Body mapping of sweating patterns of pre-pubertal children during intermittent exercise in a warm environment<br>PurposeTo determine sweating responses of pre-pubertal children during intermittent exercise in a warm environment and create whole-body maps of regional sweat rate (RSRs) distribution across the body.Methods<br>Thirteen pre-pubertal children; six girls and seven boys (8.1 ± 0.8 years) took part. Sweat was collected using the technical absorbent method in the last 5 min of a 30-min intermittent exercise protocol performed at 30 ℃, 40% relative humidity and 2 m·s−1 frontal wind.Results<br>Mean gross sweat loss (GSL) was 126 ± 47 g·m−2·h−1 and metabolic heat production was 278 ± 50 W·m2. The lower anterior torso area had the lowest RSR with a median (IQR) sweat rate (SR) of 40 (32) g·m−2·h−1. The highest was the forehead with a median SR of 255 (163) g·m−2·h−1. Normalised sweat maps (the ratio of each region’s SR to the mean SR for all measured pad regions) showed girls displayed lower ratio values at the anterior and posterior torso, and higher ratios at the hands, feet and forehead compared to boys. Absolute SRs were similar at hands and feet, but girls sweated less in most other areas, even after correction for metabolic rate.Conclusion<br>Pre-pubertal children have different RSRs across the body, also showing sex differences in sweat distribution. Distributions differ from adults. Hands and feet RSR remain stable, but SR across other body areas increase with maturation. These data can increase specificity of models of human thermoregulation, improve the measurement accuracy of child-sized thermal manikins, and aid companies during product design and communication