cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.22047458
title: <i>In silico</i> analysis reveals hypoxia-induced miR-210-3p specifically targets SARS-CoV-2 RNA

description: Human coronaviruses (HCoVs) until the emergence of SARS in 2003 were associated with mild cold and upper respiratory tract infections. The ongoing pandemic caused by SARS-CoV-2 has enhanced the potential for infection and transmission as compared to other known members of this family. MicroRNAs (miRNA) are 21-25 nucleotides long non-coding RNA that bind to 3' UTR of genes and regulate almost every aspect of cellular function. Several human miRNAs have been known to target viral genomes, mostly to downregulate their expression and sometimes to upregulate also. In some cases, host miRNAs could be sequestered by the viral genome to create a condition for favourable virus existence. The ongoing SARS CoV-2 pandemic is unique based on its transmissibility and severity and we hypothesised that there could be a unique mechanism for its pathogenesis. In this study, we exploited <i>in silico</i> approach to identify human respiratory system-specific miRNAs targeting the viral genome of three highly pathogenic HCoVs (SARS-CoV-2 Wuhan strain, SARS-CoV, and MERS-CoV) and three low pathogenic HCoVs (OC43, NL63, and HKU1). We identified ten common microRNAs that target all HCoVs studied here. In addition, we identified unique miRNAs which targeted specifically one particular HCoV. miR-210-3p was the single unique lung-specific miRNA, which was found to target the NSP3, NSP4, and NSP13 genes of SARS-CoV-2. Further miR-210-NSP3, miR-210-NSP4, and miR-210-NSP13 SARS-CoV-2 duplexes were docked with the hAGO2 protein (PDB ID 4F3T) which showed Z-score values of −1.9, −1.7, and −1.6, respectively. The role of miR-210-3p as master hypoxia regulator and inflammation regulation may be important for SARS-CoV-2 pathogenesis. Overall, this analysis advocates that miR-210-3p be investigated experimentally in SARS-CoV-2 infection. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.22047458.v1
title: <i>In silico</i> analysis reveals hypoxia-induced miR-210-3p specifically targets SARS-CoV-2 RNA

description: Human coronaviruses (HCoVs) until the emergence of SARS in 2003 were associated with mild cold and upper respiratory tract infections. The ongoing pandemic caused by SARS-CoV-2 has enhanced the potential for infection and transmission as compared to other known members of this family. MicroRNAs (miRNA) are 21-25 nucleotides long non-coding RNA that bind to 3' UTR of genes and regulate almost every aspect of cellular function. Several human miRNAs have been known to target viral genomes, mostly to downregulate their expression and sometimes to upregulate also. In some cases, host miRNAs could be sequestered by the viral genome to create a condition for favourable virus existence. The ongoing SARS CoV-2 pandemic is unique based on its transmissibility and severity and we hypothesised that there could be a unique mechanism for its pathogenesis. In this study, we exploited <i>in silico</i> approach to identify human respiratory system-specific miRNAs targeting the viral genome of three highly pathogenic HCoVs (SARS-CoV-2 Wuhan strain, SARS-CoV, and MERS-CoV) and three low pathogenic HCoVs (OC43, NL63, and HKU1). We identified ten common microRNAs that target all HCoVs studied here. In addition, we identified unique miRNAs which targeted specifically one particular HCoV. miR-210-3p was the single unique lung-specific miRNA, which was found to target the NSP3, NSP4, and NSP13 genes of SARS-CoV-2. Further miR-210-NSP3, miR-210-NSP4, and miR-210-NSP13 SARS-CoV-2 duplexes were docked with the hAGO2 protein (PDB ID 4F3T) which showed Z-score values of −1.9, −1.7, and −1.6, respectively. The role of miR-210-3p as master hypoxia regulator and inflammation regulation may be important for SARS-CoV-2 pathogenesis. Overall, this analysis advocates that miR-210-3p be investigated experimentally in SARS-CoV-2 infection. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.21952919
title: Synthesis of thiazole-based-thiourea analogs: as anticancer, antiglycation and antioxidant agents, structure activity relationship analysis and docking study

description: This work reports the convenient approach for the synthesis of thiazole based thiourea derivatives <b>(1-21)</b> from 2-bromo-1-(4-fluorophenyl)thiazole-1-one and phenyl isothiocyanates. The scope and diversity were achieved from readily available phenyl isothiocyanates. This protocol involves an oxidative C-S bond formation. Moreover, hybrid thiazole based thiourea scaffolds <b>(1-21)</b> according to literature known protocol were screened in vitro for anticancer Potential against breast cancer, antiglycation and antioxidant inhibitory profile. All newly developed scaffolds were showed moderate to good inhibitory potentials ranging from 0.10 ± 0.01 µM to 11.40 ± 0.20 µM, 64.20 ± 0.40 µM to 385.10 ± 1.70 µM and 8.90 ± 0.20 µM to 39.20 ± 0.50 µM against anticancer, antiglycation and antioxidant respectively. Among the series, compounds <b>12</b> (IC<sub>50</sub> = 0.10 ± 0.01 µM), 10 (IC<sub>50</sub> = 64.20 ± 0.40 µM) and <b>12</b> (IC<sub>50</sub> = 8.90 ± 0.20 µM) with flouro substitution at phenyl ring of thiourea were identified to be the most potent among the series having excellent anticancer, antiglycation and antioxidant potential. The structure of all the newly synthetics scaffolds were confirmed by using different types of spectroscopic techniques such as HREI-MS, <sup>1</sup>H- and <sup>13</sup>C-NMR spectroscopy. To find structure-activity relationship, molecular docking studies were carried out to understand the binding mode of active inhibitors with active site of enzymes and results supported the experimental data. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.21952919.v1
title: Synthesis of thiazole-based-thiourea analogs: as anticancer, antiglycation and antioxidant agents, structure activity relationship analysis and docking study

description: This work reports the convenient approach for the synthesis of thiazole based thiourea derivatives <b>(1-21)</b> from 2-bromo-1-(4-fluorophenyl)thiazole-1-one and phenyl isothiocyanates. The scope and diversity were achieved from readily available phenyl isothiocyanates. This protocol involves an oxidative C-S bond formation. Moreover, hybrid thiazole based thiourea scaffolds <b>(1-21)</b> according to literature known protocol were screened in vitro for anticancer Potential against breast cancer, antiglycation and antioxidant inhibitory profile. All newly developed scaffolds were showed moderate to good inhibitory potentials ranging from 0.10 ± 0.01 µM to 11.40 ± 0.20 µM, 64.20 ± 0.40 µM to 385.10 ± 1.70 µM and 8.90 ± 0.20 µM to 39.20 ± 0.50 µM against anticancer, antiglycation and antioxidant respectively. Among the series, compounds <b>12</b> (IC<sub>50</sub> = 0.10 ± 0.01 µM), 10 (IC<sub>50</sub> = 64.20 ± 0.40 µM) and <b>12</b> (IC<sub>50</sub> = 8.90 ± 0.20 µM) with flouro substitution at phenyl ring of thiourea were identified to be the most potent among the series having excellent anticancer, antiglycation and antioxidant potential. The structure of all the newly synthetics scaffolds were confirmed by using different types of spectroscopic techniques such as HREI-MS, <sup>1</sup>H- and <sup>13</sup>C-NMR spectroscopy. To find structure-activity relationship, molecular docking studies were carried out to understand the binding mode of active inhibitors with active site of enzymes and results supported the experimental data. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.21840359
title: Structural systems biology approach delineate the functional implications of SNPs in exon junction complex interaction network

description: In eukaryotes, transcripts that carry premature termination codons (PTC) leading to truncated proteins are degraded by the Nonsense Mediated Decay (NMD) machinery. Missense and nonsense Single Nucleotide Polymorphisms (SNPs) in proteins belonging to Exon junction complex (EJC) and up-frameshift protein (UPF) will compromise NMD leading to the accumulation of truncated proteins in various diseases. The EJC and UPF which are involved in NMD is a good model system to study the effect of SNPs at a system level. Despite the availability of crystal structures, computational tools, and data on mutational and deletion studies, with functional implications, an integrated effort to understand the impact of SNPs at the systems level is lacking. To study the functional consequences of missense SNPs, sequence-based techniques like SIFT and PolyPhen which classify SNPs as deleterious or non-deleterious and structure-based methods like FoldX which calculate the Delta Delta G, (ddGs, ∆∆G) are used. Using FoldX, the ddG for mutations with experimentally validated functional effects is calculated and compared with those calculated for SNPs in the same protein–protein interaction interface. Further, a model is conceived to explain the functional implications of SNPs based on the effects observed for known mutants. The results are visualized in a network format. The effects of nonsense mutations are discerned by comparing with deletion mutation studies and loss of interaction in the crystal structure. The present work not only integrates genomics, proteomics, and classical genetics with ‘Structural Biology’ but also helps to integrate it into a ‘systems-level functional network’. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.21840359.v2
title: Structural systems biology approach delineate the functional implications of SNPs in exon junction complex interaction network

description: In eukaryotes, transcripts that carry premature termination codons (PTC) leading to truncated proteins are degraded by the Nonsense Mediated Decay (NMD) machinery. Missense and nonsense Single Nucleotide Polymorphisms (SNPs) in proteins belonging to Exon junction complex (EJC) and up-frameshift protein (UPF) will compromise NMD leading to the accumulation of truncated proteins in various diseases. The EJC and UPF which are involved in NMD is a good model system to study the effect of SNPs at a system level. Despite the availability of crystal structures, computational tools, and data on mutational and deletion studies, with functional implications, an integrated effort to understand the impact of SNPs at the systems level is lacking. To study the functional consequences of missense SNPs, sequence-based techniques like SIFT and PolyPhen which classify SNPs as deleterious or non-deleterious and structure-based methods like FoldX which calculate the Delta Delta G, (ddGs, ∆∆G) are used. Using FoldX, the ddG for mutations with experimentally validated functional effects is calculated and compared with those calculated for SNPs in the same protein–protein interaction interface. Further, a model is conceived to explain the functional implications of SNPs based on the effects observed for known mutants. The results are visualized in a network format. The effects of nonsense mutations are discerned by comparing with deletion mutation studies and loss of interaction in the crystal structure. The present work not only integrates genomics, proteomics, and classical genetics with ‘Structural Biology’ but also helps to integrate it into a ‘systems-level functional network’. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.21814609
title: <i>In silico</i> drug screen reveals potential competitive MTHFR inhibitors for clinical repurposing

description: MTHFR (Methylenetetrahydrofolate reductase) is a pivotal enzyme involved in one-carbon metabolism, which is critical for the proliferation of cancer cells. In line with this, published literature showed that MTHFR knockdown caused impaired growth of multiple types of cancer cells. Moreover, higher MTHFR expression levels were linked to shorter overall survival in hepatocellular carcinoma, adrenocortical carcinoma, and low-grade glioma, bringing the need to design MTHFR inhibitors as a possible treatment option. No competitive inhibitors of MTHFR have been reported as of today. This study aimed to identify potential competitive MTHFR inhibitor candidates using an <i>in silico</i> drug screen. A total of 30470 molecules containing biogenic compounds, FDA-approved drugs, and those in clinical trials were screened against the catalytic pocket of MTHFR in the presence and absence of cofactors. Binding energy and ADMET analysis revealed that Vilanterol (β2-adrenergic agonist), Selexipag (prostacyclin receptor agonist), and Ramipril Diketopiperazine (ACE inhibitor) are potential competitive inhibitors of MTHFR. Molecular dynamics analyses and MM-PBSA calculations with these compounds particularly revealed the amino acids between 285-290 for ligand binding and highlighted Vilanterol as the strongest candidate for MTHFR inhibition. Our results could guide the development of novel MTHFR inhibitor compounds, which could be inspired by the drugs brought into the spotlight here. More importantly, these potential candidates could be quhickly tested as a repurposing strategy in pre-clinical and clinical studies of the cancers mentioned above. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.21814609.v1
title: <i>In silico</i> drug screen reveals potential competitive MTHFR inhibitors for clinical repurposing

description: MTHFR (Methylenetetrahydrofolate reductase) is a pivotal enzyme involved in one-carbon metabolism, which is critical for the proliferation of cancer cells. In line with this, published literature showed that MTHFR knockdown caused impaired growth of multiple types of cancer cells. Moreover, higher MTHFR expression levels were linked to shorter overall survival in hepatocellular carcinoma, adrenocortical carcinoma, and low-grade glioma, bringing the need to design MTHFR inhibitors as a possible treatment option. No competitive inhibitors of MTHFR have been reported as of today. This study aimed to identify potential competitive MTHFR inhibitor candidates using an <i>in silico</i> drug screen. A total of 30470 molecules containing biogenic compounds, FDA-approved drugs, and those in clinical trials were screened against the catalytic pocket of MTHFR in the presence and absence of cofactors. Binding energy and ADMET analysis revealed that Vilanterol (β2-adrenergic agonist), Selexipag (prostacyclin receptor agonist), and Ramipril Diketopiperazine (ACE inhibitor) are potential competitive inhibitors of MTHFR. Molecular dynamics analyses and MM-PBSA calculations with these compounds particularly revealed the amino acids between 285-290 for ligand binding and highlighted Vilanterol as the strongest candidate for MTHFR inhibition. Our results could guide the development of novel MTHFR inhibitor compounds, which could be inspired by the drugs brought into the spotlight here. More importantly, these potential candidates could be quhickly tested as a repurposing strategy in pre-clinical and clinical studies of the cancers mentioned above. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.21840384
title: Integrative transcriptome analysis of triple negative breast cancer profiles for identification of druggable targets

description: As triple negative breast cancer (TNBC) lacks a specific target, exploration of abnormally expressed genes during the progression of TNBC is important for a better understanding of tumorigenesis and to find a specific target. We intended to figure out genes associated with TNBC, which can provide unique insights into gene dysregulation in TNBC while also pointing to new possible therapeutic targets for TNBC. A meta-analysis of multiple TNBC mRNA profiles was performed to identify consistently differentially expressed genes (CDGs). The pathways involved in modulating these genes were analyzed by MsigDB, and the interaction map was constructed. These CDGs were evaluated for their expression in cell lines, and drugs that could modulate the expression of CDGs were obtained using the connectivity map. CDGs were docked with doxorubicin and anethole, which is a phytocompound. The expression of selected CDGs was analyzed in MDA-MB-231 cells after treatment with doxorubicin and anethole. We found 45 CDGs, out of which 36 were upregulated and 9 were downregulated. MDA-MB-231 cell line was found to have high expression of CDGs, and drug that could modulate the expression of CDGs was doxorubicin. Docking results revealed that anethole and doxorubicin had good interaction with the CDGs especially with the genes <i>AURKA</i>, <i>CDC6</i>, <i>DEPDC1</i>, <i>KIF23</i>, <i>KPNA2</i>, <i>MELK</i>, <i>CTNNB1</i>, <i>FLI1</i> and <i>E2F1</i>. Gene expression studies of the selected CDGs showed that the synergistic effect of anethole and doxorubicin effectively downregulated the expression. The CDGs identified from multiple cohorts have clinical significance and may be effectively exploited in the targeted therapy for TNBC. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.21840384.v1
title: Integrative transcriptome analysis of triple negative breast cancer profiles for identification of druggable targets

description: As triple negative breast cancer (TNBC) lacks a specific target, exploration of abnormally expressed genes during the progression of TNBC is important for a better understanding of tumorigenesis and to find a specific target. We intended to figure out genes associated with TNBC, which can provide unique insights into gene dysregulation in TNBC while also pointing to new possible therapeutic targets for TNBC. A meta-analysis of multiple TNBC mRNA profiles was performed to identify consistently differentially expressed genes (CDGs). The pathways involved in modulating these genes were analyzed by MsigDB, and the interaction map was constructed. These CDGs were evaluated for their expression in cell lines, and drugs that could modulate the expression of CDGs were obtained using the connectivity map. CDGs were docked with doxorubicin and anethole, which is a phytocompound. The expression of selected CDGs was analyzed in MDA-MB-231 cells after treatment with doxorubicin and anethole. We found 45 CDGs, out of which 36 were upregulated and 9 were downregulated. MDA-MB-231 cell line was found to have high expression of CDGs, and drug that could modulate the expression of CDGs was doxorubicin. Docking results revealed that anethole and doxorubicin had good interaction with the CDGs especially with the genes <i>AURKA</i>, <i>CDC6</i>, <i>DEPDC1</i>, <i>KIF23</i>, <i>KPNA2</i>, <i>MELK</i>, <i>CTNNB1</i>, <i>FLI1</i> and <i>E2F1</i>. Gene expression studies of the selected CDGs showed that the synergistic effect of anethole and doxorubicin effectively downregulated the expression. The CDGs identified from multiple cohorts have clinical significance and may be effectively exploited in the targeted therapy for TNBC. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.21967288
title: Robust anti-inflammatory activity of genistein against neutrophil elastase: a microsecond molecular dynamics simulation study

description: Human Neutrophil Elastase (HNE) is one of the major causes of tissue destruction in numerous chronic and inflammatory disorders and has been reported as a therapeutic target for inflammatory diseases. Overexpression of this enzyme plays a critical role in the pathogenesis of rheumatoid arthritis (RA). The focus of this study is to identify potent natural inhibitors that could target the active site of the HNE through the use of computational methods. The molecular structure of small molecules was retrieved from several natural compound databases. This was followed by structure-based virtual screening, molecular docking, ADMET property predictions and molecular dynamic simulation studies to screen potential HNE inhibitors. In total, 1881 natural compounds were extracted and subjected to molecular docking studies, and 10 compounds were found to have good interactions, exhibiting the best docking scores. Genistein showed higher binding efficacy (-10.28 Kcal/mol) to HNE in comparison to other natural compounds. The conformational stability of the docked complex of the ELANE gene (HNE) with genistein was assessed using 1-microsecond molecular dynamic simulation (MDs), which reliably revealed the unique stereochemical alteration of the complex, indicating its conformational stability and flexibility. Alterations in the enzyme structure upon complex formation were further characterized through clustering analysis and linear interaction energy (LIE) calculation. The outcomes of this research propose novel potential candidates against target HNE. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.21967288.v1
title: Robust anti-inflammatory activity of genistein against neutrophil elastase: a microsecond molecular dynamics simulation study

description: Human Neutrophil Elastase (HNE) is one of the major causes of tissue destruction in numerous chronic and inflammatory disorders and has been reported as a therapeutic target for inflammatory diseases. Overexpression of this enzyme plays a critical role in the pathogenesis of rheumatoid arthritis (RA). The focus of this study is to identify potent natural inhibitors that could target the active site of the HNE through the use of computational methods. The molecular structure of small molecules was retrieved from several natural compound databases. This was followed by structure-based virtual screening, molecular docking, ADMET property predictions and molecular dynamic simulation studies to screen potential HNE inhibitors. In total, 1881 natural compounds were extracted and subjected to molecular docking studies, and 10 compounds were found to have good interactions, exhibiting the best docking scores. Genistein showed higher binding efficacy (-10.28 Kcal/mol) to HNE in comparison to other natural compounds. The conformational stability of the docked complex of the ELANE gene (HNE) with genistein was assessed using 1-microsecond molecular dynamic simulation (MDs), which reliably revealed the unique stereochemical alteration of the complex, indicating its conformational stability and flexibility. Alterations in the enzyme structure upon complex formation were further characterized through clustering analysis and linear interaction energy (LIE) calculation. The outcomes of this research propose novel potential candidates against target HNE. Communicated by Ramaswamy H. Sarma
DOI: 10.6073/pasta/0bdd19d81ed61bccd589af0d29b4c21d
title: Vascular Plant Species at Harvard Forest 1992

description: This dataset contains a list of vascular plant species found in 269 22.5 x 22.5 m plots sampled in the 1992 Prospect Hill vegetation survey. The species list was compiled on 5 May 1993.
DOI: 10.18112/openneuro.ds004640.v1.0.2
title: Sustaining wakefulness: Brainstem connectivity in human consciousness
DOI: 10.6073/pasta/15e3fe73fde72869b5adb2a65ffca93b
title: Bryophyte Species at Harvard Forest 1994

description: This dataset contains a list of bryophyte species found in 105 11.25 x 11.25 m plots on the Prospect Hill Tract, Harvard Forest, Petersham, Massachusetts in 1994.
DOI: 10.6073/pasta/1b096594a8047f6a3f8911c3e40dd414
title: Breeding Bird Species at Harvard Forest 1993

description: This dataset contains a list of breeding bird species observed on the Prospect Hill Tract, Harvard Forest, Petersham, Massachusetts from 31 May to 11 August 1993.
DOI: 10.6073/pasta/fffde8ec33a7e647852281cb1b6ab6cf
title: Canopy Photosynthesis Study at Harvard Forest 1991-1992

description: Tree photosynthesis measurements were made from two canopy access towers on the Prospect Hill Tract, Harvard Forest, Petersham, Massachusetts between July 1991 and October 1992. Four species were observed: Oak - red oak (Quercus rubra); RM - red maple (Acer rubrum); WB - white birch (Betula papyrifera); YB- yellow birch (Betula alleghaniensis).
DOI: 10.34683/sr955
title: StoneRounds Case: SR955
title: Occult Macular Dystrophy

description: StoneRounds Case SR955 was diagnosed with Occult Macular Dystrophy likely caused by mutations in the gene: RP1L1.