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RISS 인기검색어
- 검색키워드
- 저자 : Pritish Kumar Varadwaj (검색결과 4 건)
- 무료
- 기관 내 무료
- 유료
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Parameters Involved in Autophosphorylation in Chronic Myeloid Leukemia: a Systems Biology Approach
Kumar, Himansu,Tichkule, Swapnil,Raj, Utkarsh,Gupta, Saurabh,Srivastava, Swati,Varadwaj, Pritish Kumar Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.13
Background: Chronic myeloid leukemia (CML) is a stem cell disorder characterized by the fusion of two oncogenes namely BCR and ABL with their aberrant expression. Autophosphorylation of BCR-ABL oncogenes results in proliferation of CML. The study deals with estimation of rate constant involved in each step of the cellular autophosphorylation process, which are consequently playing important roles in the proliferation of cancerous cells. Materials and Methods: A mathematical model was proposed for autophosphorylation of BCR-ABL oncogenes utilizing ordinary differential equations to enumerate the rate of change of each responsible system component. The major difficulty to model this process is the lack of experimental data, which are needed to estimate unknown model parameters. Initial concentration data of each substrate and product for BCR-ABL systems were collected from the reported literature. All parameters were optimized through time interval simulation using the fminsearch algorithm. Results: The rate of change versus time was estimated to indicate the role of each state variable that are crucial for the systems. The time wise change in concentration of substrate shows the convergence of each parameter in autophosphorylation process. Conclusions: The role of each constituent parameter and their relative time dependent variations in autophosphorylation process could be inferred.
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Raj, Utkarsh,Kumar, Himansu,Gupta, Saurabh,Varadwaj, Pritish Kumar Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.9
Background: The human protein methyl-transferase DOT1L catalyzes the methylation of histone H3 on lysine 79 (H3K79) at homeobox genes and is also involved in a number of significant processes ranging from gene expression to DNA-damage response and cell cycle progression. Inhibition of DOT1L activity by shRNA or small-molecule inhibitors has been established to prevent proliferation of various MLL-rearranged leukemia cells in vitro, establishing DOT1L an attractive therapeutic target for mixed lineage leukemia (MLL). Most of the drugs currently in use for the MLL treatment are reported to have low efficacy, hence this study focused on various natural compounds which exhibit minimal toxic effects and high efficacy for the target receptor. Materials and Methods: Structures of human protein methyl-transferase DOT1L and natural compound databases were downloaded from various sources. Virtual screening, molecular docking, dynamics simulation and drug likeness studies were performed for those natural compounds to evaluate and analyze their anti-cancer activity. Results: The top five screened compounds possessing good binding affinity were identified as potential high affinity inhibitors against DOT1L's active site. The top ranking molecule amongst the screened ligands had a Glide g-score of -10.940 kcal/mol and Glide e-model score of -86.011 with 5 hydrogen bonds and 12 hydrophobic contacts. This ligand's behaviour also showed consistency during the simulation of protein-ligand complex for 20000 ps, which is indicative of its stability in the receptor pocket. Conclusions: The ligand obtained out of this screening study can be considered as a potential inhibitor for DOT1L and further can be treated as a lead for the drug designing pipeline.
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Saurabh Gupta,Vinod Kumar Mishra,Sunita Kumari,Raavi,Ramesh Chand,Pritish Kumar Varadwaj 한국유전학회 2019 Genes & Genomics Vol.41 No.1
WRKY transcription factors (TFs) act in regulating plant growth and development as well as in response to different stress. Some earlier studies done by individual researchers reported different wheat WRKY TFs. Although, the recently released wheat genome has opened an avenue to investigate wheat WRKYs (TaWRKY) TFs. Prime objective of this study to performed genome-wide classifications of TaWRKYs and their functional annotation. The classification of 107 individual identified characterized sequences of TaWRKY (IICS-TaWRKY) and 160 uncharacterized draft sequences of TaWRKY (UDS-TaWRKY), along with their gene structures and motifs analysis was performed. Along with comparative sequence analysis and microarray analysis was performed to mimic out TaWRKYs functions in response to different abiotic stresses, accompanied by in-vitro validation. The comparative phylogenetic analysis and estimation of Ka/Ks ratio with Triticum urartu, illustrate group based clasifications of TaWRKYs and evolutionary divergences. Furthermore, motif-based and protein-DNA interaction analysis of TaWRKYs helps to identify, their putative function in target DNA recognition sites. Subsequently, results of microarray and comparative sequence analysis provides the evidence of TaWRKYs involved in heat and/or drought stress. Further, in-vitro results validates that TaWRKY014, TaWRKY090 are found to participate in response of drought stress, whereas TaWRKY008, TaWRKY122, and WRKY45 are involved in response of heat and drought stress. These findings can be utilized in developing novel heat and drought-tolerant wheat cultivars using marker-assisted breeding and transgenic development.
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Saurabh Gupta,Vikas Gupta,Vishal Singh,Pritish Kumar Varadwaj 한국유전학회 2018 Genes & Genomics Vol.40 No.9
A wide range of plant species growth influenced when they exposed to solar UV-B radiation. Leaves of the plant are highly affected by UV-B radiation lead to the reduction in the growth of the plant. Current work demonstrates the comparative transcriptional changes and visible symptoms occurred in the maize leaf growth zone (GZ). Primary objective of this study was to identify differentially expressed genes (DEGs) responsible for leaf growth and their association in the transcriptional regulatory network under UV-B stress. Whole transcriptomic data was analysed and the quality check was tested for each sample and further genome-wide mapping and DEGs were performed. Gene Ontology (GO) based functional annotation, associated transcriptional networks and molecular pathways were annotated. Reduction in cell production due to UV-B stress causes a decrease in leaf’s length and size was observed. Further, the specific role of the DEGs, in UV-B signalling pathways and other molecular functions responsible for leaf cell death was discovered. Results also infer that the major changes occurred in the cell cycle, transcriptional regulation, post-transcriptional modification, phytohormones, flavonoids biosynthesis, and chromatin remodeling. UV-B signalling pathways and the transcriptional regulatory networks infer the different molecular steps along with downstream transcriptional and post-transcriptional control of metabolic enzymes used in long-term memory adoption and attainment resistance to UV-B stress identified. Effects of UV-B radiation on leaf growth was noted in this study. UV-B stress response genes and associated transcriptional regulatory networks were identified, can be used in developing the marker assist UB-B stress tolerant genotypes of the maize.
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