Biology subjects

Alam, T.

Publications and source records attributed to Alam, T..

6 recordsLinked to original sources

bioRxiv2026

Comprehensive analysis of non-synonymous single-nucleotide polymorphism of human TSC1 and TSC2 genes: an in silico approach.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in the TSC1 and TSC2 genes and is characterized by benign hamartoma formation in multiple organs. The TSC1-TSC2 complex regulates mTORC1 signaling in response to cellular growth conditions. This study aims to predict the structural stability and functional effects of non-synonymous single-nucleotide polymorphisms (nsSNPs) in human TSC1 and TSC2 using computational approaches. Twelve computational tools were assessed using receiver operating characteristic (ROC) analysis and applied to identify deleterious nsSNPs. Protein stability was predicted using I-Mutant 2.0 and MUpro, while evolutionary conservation was analyzed with ConSurf. NetPhos 3.1 identified potential PTM sites, and MutPred2.0 evaluated their functional impact. Project HOPE assessed mutation-induced physicochemical changes. Structural models were validated using multiple tools, visualized in ChimeraX 1.9, and further evaluated by molecular dynamics simulation to confirm wild-type and mutant stability. All twelve tools had AUC values above 0.90. A combined in silico analysis identified twelve high-risk nsSNPs in TSC1 and sixteen in TSC2, all reducing protein stability, located in conserved regions, and potentially disrupting phosphorylation sites. MutPred and Project HOPE confirmed their impact on protein function. Functional analysis showed TSC1 and TSC2 affect mTORC1 and PI3K-Akt pathways. RMSF and RMSD analyses revealed that TSC1 variants rs1846545280 (G236E), and rs2132135678 (V234E), and TSC2 variants rs45517223 (S758C), rs2151354925 (T836P), and rs45517365 (R1570W) had the largest structural fluctuations. Substitution with glutamic acid, a negatively charged and bulkier residue, may disrupt local folding of TSC1. Similarly, replacement of arginine with tyrosine at position 1570 may impair Rheb binding at the GAP domain of TSC2. These findings highlight potentially pathogenic nsSNPs in TSC1 and TSC2.

bioinformatics↗

bioRxiv2022

UVC-based air disinfection system for rapid inactivation of SARS-CoV-2 present in the air

The novel coronavirus disease 2019 (COVID-19) infections have rapidly spread throughout the world, and the virus has acquired an ability to spread via aerosols even at long distances. Hand washing, face-masking, and social distancing are the primary preventive measures against infections. With mounting scientific evidence, World Health Organisation (WHO) declared COVID-19 an air-borne disease. This ensued the need to disinfect air to reduce the transmission. Ultraviolet C (UVC) comprising the light radiation of 200-280 nm range is a commonly used method for inactivation of pathogens. The heating, ventilation, and air conditioning (HVAC) systems are not beneficial in closed spaces due to poor or no ability to damage circulating viruses. Therefore, standard infection-prevention practices coupled with a strategy to reduce infectious viral load in air substantially might be helpful in reducing virus transmissibility. In this study, we implemented UV light-based strategies to combat COVID-19 and future pandemics. We tested various disinfection protocols by using UVC-based air purification systems and currently installed such a system in workspaces, rushed out places, hospitals and healthcare facilities for surface, air, and water disinfection. In this study, we designed a prototype device to test the dose of UVC required to inactivate SARS-CoV-2 in aerosols and demonstrate that the radiation rapidly destroys the virus in aerosols. The UVC treatment renders the virus non-infectious due to chemical modification of nucleic acid. We also demonstrate that UVC treatment alters the Spike protein conformation that may further affect the infectivity of the virus. We show by using a mathematical model based on the experimental data that UVC-based air disinfection strategy can substantially reduce the risk of virus transmission. The systematic treatment by UVC of air in the closed spaces via ventilation systems could be helpful in reducing the active viral load in the air.

microbiology↗

bioRxiv2021

Functional annotation of human long noncoding RNAs using chromatin conformation data

The human genome is pervasively transcribed and produces a wide variety of long non-coding RNAs (lncRNAs), constituting the majority of transcripts across human cell types. Studying lncRNAs is challenging due to their low expression level, cell type-specific occurrence, poor sequence conservation between orthologs, and lack of information about RNA domains. LncRNAs direct the regulatory factors in the locations that are in cis to their transcription sites. We designed a model to predict if an lncRNA acts in cis based on its features and trained it using RNA-chromatin interaction data. The trained model is cell type-independent and does not require RNA-chromatin data. Combining RNA-chromatin and Hi-C data, we showed that lncRNA-chromatin binding sites are determined by chromosome conformation. For each lncRNA, the spatially proximal genes were identified as their potential targets by combining Hi-C and Cap Analysis Gene Expression (CAGE) data in 18 human cell types. RNA-protein and RNA-chromatin interaction data suggested that lncRNAs act as scaffolds to recruit regulatory proteins to target promoters and enhancers. We provide the data through an interactive visualization web portal at https://fantom.gsc.riken.jp/zenbu/reports/#F6_3D_lncRNA.

genomics↗

bioRxiv2020

ShearFAST: a user-friendly in vitro toolset for high throughput, inexpensive fluid shear stress experiments.

Fluid shear stress is a key modulator of cellular physiology in vitro and in vivo, but its effects are under-investigated due to requirements for complicated induction methods. Herein we report the validation of ShearFAST; a smartphone application that measures the rocking profile on a standard laboratory cell rocker and calculates the resulting shear stress arising in tissue culture plates. ShearFAST measured rocking profiles were validated against a graphical analysis and also against measures reported by an 8-camera motion tracking system. ShearFAST angle assessments correlated well with both analyses (r [≥]0.99, p [≤]0.001) with no significant differences in pitch detected across the range of rocking angles tested. Rocking frequency assessment by ShearFAST also correlated well when compared to the two independent validatory techniques (r [≥]0.99, p [≤]0.0001), with excellent reproducibility between ShearFAST and video analysis (mean frequency measurement difference of 0.006 {+/-} 0.005Hz) and motion capture analysis (mean frequency measurement difference of 0.008 {+/-} 0.012Hz) These data make the ShearFAST assisted cell rocker model make it an attractive approach for economical, high throughput fluid shear stress experiments. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/929513v3_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@1d8c1eborg.highwire.dtl.DTLVardef@1a346eborg.highwire.dtl.DTLVardef@8503a8org.highwire.dtl.DTLVardef@b31a3f_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2019

Biosynthesis of Iron Oxide Nanoparticles via Crocus sativus and their Antifungal Efficacy against Verticillium Wilt Pathogen Verticillium dahliae

Plant diseases pose threat to global food security. The excessive use of synthetic agro-chemical engender pesticide resistance. The exploration of alternative sustainable diseases management practices are crucial to overcome the devastative plant diseases. In this study, a facile innocuous approach was adopted for biogenic synthesis of Fe2O3-CsNPs via Crocus sativus corm aqueous extract and was evaluated for their antifungal efficacy against the Verticillium wilt pathogen Verticillium dahliae. The physico-chemical characterization of biosynthesized nanoparticles were performed through UV-visible Spectroscopy, Fourier Transform Infrared Spectroscopy, Energy Dispersive X-ray Spectroscopy, X-Ray Diffraction, and Scanning Electron Microscopy. The fungus mycelium growth was significantly inhibited in the media containing 3mg/mL Fe2O3-CsNPs. Degenerated, concentrated and shriveled hyphae were revealed in Scanning Electron Microscopy. The overall results demonstrated that the biogenic Fe2O3-CsNPs have the efficacy to control devastative phytopathogens.

plant biology↗

bioRxiv2018

Proteome-level assessment of origin, prevalence and function of Leucine-Aspartic Acid (LD) motifs

Short Linear Motifs (SLiMs) contribute to almost every cellular function by connecting appropriate protein partners. Accurate prediction of SLiMs is difficult due to their shortness and sequence degeneracy. Leucine-aspartic acid (LD) motifs are SLiMs that link paxillin family proteins to factors controlling (cancer) cell adhesion, motility and survival. The existence and importance of LD motifs beyond the paxillin family is poorly understood. To enable a proteome-wide assessment of these motifs, we developed an active-learning based framework that iteratively integrates computational predictions with experimental validation. Our analysis of the human proteome identified a dozen proteins that contain LD motifs, all being involved in cell adhesion and migration, and revealed a new type of inverse LD motif consensus. Our evolutionary analysis suggested that LD motif signalling originated in the common unicellular ancestor of opisthokonts and amoebozoa by co-opting nuclear export sequences. Inter-species comparison revealed a conserved LD signalling core, and reveals the emergence of species-specific adaptive connections, while maintaining a strong functional focus of the LD motif interactome. Collectively, our data elucidate the mechanisms underlying the origin and adaptation of an ancestral SLiM.

bioinformatics↗