Biology subjects

Ansari, S. A.

Publications and source records attributed to Ansari, S. A..

6 recordsLinked to original sources

bioRxiv2025

In Silico Evaluation and Therapeutic Targeting of LVDD9B Protein for WSSV Inhibition: Molecular and Ecological Insights for Aquaculture Solutions

BackgroundThis study aimed to investigate structural dynamics, binding interactions, stability, pharmacokinetics, ecological risks, and bioactivity of shrimp receptor protein LVDD9B to identify potential therapeutic candidates against White Spot Syndrome Virus (WSSV). MethodsLVDD9B proteins 3D structure was predicted using SWISS-MODEL and validated with ProSA and Ramachandran plots. Protein-protein docking between LVDD9B and VP26 (WSSV protein) was performed using HADDOCK 2.4 server. Molecular docking, dynamics simulations, binding-free energy calculations, principal component analysis (PCA), electrostatic, and vibrational frequency analyses evaluated binding affinity, stability and polarity of complexes. Results128-amino-acids of LVDD9B protein was predicted as predominantly cytoplasmic with stable, and hydrophilic, with structural analysis identified key secondary structures and conserved chitin-binding site. Docking studies revealed strong interactions between LVDD9B and VP26, supported by hydrogen-bonds and salt bridges. Molecular dynamics simulations demonstrated stable complexes with fluctuating RMSD values, and MM/GBSA calculations indicated favorable binding free energies. Pharmacokinetic analysis highlighted promising bioavailability and drug-like properties for Luteolin and Quercetin from Cuscuta reflexa, while ecological assessment identified Cosmosiin as least hazardous, with Quercetin and Luteolin showing higher toxicity. PCA revealed stable protein-ligand complexes with flexibility in Apo form. Isorhoifolin exhibited the lowest internal energy (-2099.4722 Hartree) and highest dipole moment (8.1833 Debye). Frontier orbital analysis showed HOMO-LUMO gaps (4.05-4.34 eV) influencing reactivity, while MEP and vibrational frequency analyses supported compound stability and bioactivity. ConclusionsThis study explores LVDD9Bs structural and interaction dynamics for developing antiviral therapy against WSSV, highlighting therapeutic potential of Cosmosiin, Isorhoifolin, Quercetin and Luteolin based on their pharmacokinetic and ecological profiles.

bioinformatics↗

bioRxiv2024

NEK9 ablation rewires docetaxel resistance through induction of ERK-mediated cancer cell pyroptosis

Docetaxel alone or in combination with other drugs is the most common chemotherapy regimen for several neoplasms including advanced OSCC. Unfortunately, chemoresistance leads to relapse and continued tumor growth. It is therefore important to explore the causative factors for docetaxel resistance. In this study, we performed a CRISPR-based kinome screening that identified Never In Mitosis Gene-A Related Kinase-9 (NEK9) as a major player of docetaxel resistance in OSCC, prostate, and pancreatic cancer lines. NEK9 expression was upregulated in tumor samples of chemotherapy non-responders compared to responder OSCC patients. Our validation data suggests selectively knocking out NEK9 sensitizes cancer cells to docetaxel. Mechanistically, we found that ablation of NEK9 induces DNA damage, activating ERK(p-T202/Y204) that leads to Gasdermin-E mediated Cancer Cell pyroptosis. The in-vitro kinase activity assay identified fostamatinib as a potent inhibitor of NEK9. The xenograft data suggest that fostamatinib restores docetaxel sensitivity and facilitates a significant reduction of tumor burden. Overall, our data suggests a novel combination of fostamatinib and docetaxel needs further clinical investigation in advanced OSCC.

cancer biology↗

bioRxiv2022

Genetic variation associated with relative resistance in teak (Tectona grandis L. f.) against the leaf skeletonizer, Eutectona machaeralis Walker

BackgroundPhotosynthesizing tissue of teak (Tectona grandis L. f.) foliage is damaged by a host-specific insect pest called leaf skeletonizer (Eutectona machaeralis Walker) that severely eclipses annual growth increment and carbon sequestration of natural populations and plantation of teak. Gene-assisted selection of relatively resistant teak clones may efficiently control the damage in the populations and plantations. The present investigation aimed to identify genetic variation associated with relative resistance in teak against the pest. MethodThe investigation was carried out on 106 teak plus tree clones assembled at the National Teak Germplasm Bank from the Indian meta-population of teak. Resistance data were obtained recording the ocular damage caused by the pest to teak accessions for four years. Genotyping of the teak accessions was performed with 21 co-dominant markers and marker-trait association mapping was performed confirming the genetic structure of the germplasm bank and linkage disequilibrium (LD) among the marker loci. ResultsThe sampled teak accessions exhibited a low albeit highly admixed genetic structure (FST=0.07) and low level of LD (16.66%) among loci, making them suitable for high-resolution association analysis. A significant correlation (p[≤]0.01, R2=0.67) was obtained between intra-specific heterozygosity and the relative resistance against the pest. A marker locus CCoAMT-1 representing the enzyme caffeoyl-CoA O-methyltransferase of phenylpropanoid pathway was also found significantly (p[≤]0.05) associated with the relative resistance against the pest explaining 6.6% of the phenotypic variation (R2=0.066) through positive effect (0.57) on the trait. ConclusionsThe present work exhibited a significant correlation of intra-specific heterozygosity with relative resistance in teak against a pest. It is the first report on teak identifying genetic markers associated with relative resistance against the pest. The marker can be applied for the selection of resistant planting stock for breeding and commercial plantation. Further investigation can be performed to understand the expression level polymorphism linked with the resistance applying next-generation sequencing approaches.

plant biology↗

bioRxiv2022

CMTM6 mediates cisplatin resistance in OSCC by regulating AKT/c-MYC driven ribosome biogenesis

CMTM6, a type 3 transmembrane protein, is known to stabilize the expression of programmed cell death ligand 1 (PD-L1) and hence facilitates the immune evasion of tumor cells. Recently, we demonstrated that CMTM6 is a major driver of cisplatin resistance in oral squamous cell carcinomas (OSCC). However, the detailed mechanism how CMTM6 rewires cisplatin resistance in OSCC is yet to be explored. RNA sequencing analysis of cisplatin resistant OSCC lines stably expressing NtShRNA and CMTM6 ShRNA revealed that CMTM6 might be a potential regulator of ribosome biogenesis network. Knocking down CMTM6 significantly inhibited transcription of 47S precursor rRNA and hindered the nucleolar structure, indicating reduced ribosome biogenesis. When CMTM6 was ectopically over expressed in CMTM6KD cells, almost all ribosomal machinery components were rescued. Mechanistically, CMTM6 induced the expression of C-Myc, which promotes RNA polymerase I mediated rDNA transcription. In addition to this, CMTM6 also found to regulate the AKT-mTORC1-dependent ribosome biogenesis and protein synthesis in cisplatin resistant lines. The nude mice and zebrafish xenograft experiments indicate that blocking ribosome synthesis either by genetic inhibitor (CMTM6KD) or by pharmacological inhibitor (CX-5461), significantly restores cisplatin medicated cell death in chemoresistant OSCC. Overall, our study suggests that CMTM6 is a major regulator of ribosome biogenesis network and targeting ribosome biogenesis network is a viable target to overcome chemoresistance in OSCC. The novel combination of CX-5461 and cisplatin deserves further clinical investigation in advanced OSCC.

cancer biology↗

bioRxiv2021

MINK1 modulates 5FU resistance in OSCC through AKT/MDM2 mediated regulation of p53

Cisplatin, 5FU and docetaxel (TPF) are the most common chemotherapy regimen used for advanced OSCC. However, many cancer patients experience relapse, continued tumor growth, and spread due to drug resistance, which leads to treatment failure and metastatic disease. Here, using a CRISPR/Cas9 based kinome knockout screening, Misshapen-like kinase 1 (MINK1) is identified as an important mediator of 5FU resistance in OSCC. Analysis of clinical samples demonstrated significantly higher MINK1 expression in the tumor tissues of chemotherapy non-responder as compared to chemotherapy responders. The nude mice and zebrafish xenograft experiments indicate that knocking out MINK1 restores 5FU mediated cell death in chemoresistant OSCC. An antibody based phosphorylation array screen revealed MINK1 as a negative regulator of p53. Mechanistically, MINK1 modulates AKT phosphorylation at Ser473, which enables p-MDM2 (Ser 166) mediated degradation of p53. We also identified lestaurtinib as a potent inhibitor of MINK1 kinase activity. The patient derived TPF resistant cell based xenograft data suggest that lestaurtinib restores 5FU sensitivity and facilitates a significant reduction of tumor burden. Overall, our study suggests that MINK1 is a major driver of 5FU resistance in OSCC. The novel combination of MINK1 inhibitor lestaurtinib and 5FU needs further clinical investigation in advanced OSCC.

cancer biology↗

bioRxiv2018

Comparison between QST and ΦST indices in an endangered Boswellia serrata Roxb: Implications for conservation

Boswellia serrata, an economically important indigenous tree of dry deciduous forests, provides oleoresin gum of pharmaceutical significance and excellent pulp for paper industries, but faces threat to extinction due to poor natural regeneration and commercial exploitation. 240 individuals of the species representing 12 locations of its natural distribution in central India were investigated to compare the genetic differentiation indices, QST for GBH and wood fiber length and {phi}ST for neutral (RAPD+ISSR) markers. The comparison for paired locations was more informative than for metapopulation. The most paired locations were either under the stabilizing selection (QST (L) < {Phi}ST (L)) or in the genetic drift (QST(L) = {Phi}ST (L)) whereas a relatively small number of paired locations was under the divergent selection (QS T(L) > {Phi}ST (L)). The comparison for the metapopulation generating only a single trend of QST (P) > {Phi}ST (P) is, therefore, misleading. For conservation, the genetically deficit locations (QST (L) < {Phi}ST (L) and QST (L) = {Phi}ST (L)) of B. serrata warrant for reinforcement of their genetic diversity by introduction of genotypes from other genetically divergent locations (QST (L) > {Phi}ST (L)), which would check the fragmentation and genetic drift, resulting in reproductive vigour, natural regeneration and reverse the endangered status of the species.

genetics↗