Biology subjects

Akter, H.

Publications and source records attributed to Akter, H..

4 recordsLinked to original sources

bioRxiv2026

HSD17B11 maintains FSP1 localization on lipid droplets to support ferroptosis defense

Ferroptosis is a regulated form of cell death driven by iron-dependent lipid peroxidation, and lipid droplets (LDs) are increasingly recognized as important regulators of this process. Consistent with this role, the anti-ferroptotic factor ferroptosis suppressor protein 1 (FSP1) is known localizing on LDs through N-myristoylation-dependent membrane targeting, where it protects LD lipids from peroxidation. Here, we identify the LD protein HSD17B11 as an additional factor required for maintaining both FSP1 localization on LDs and cellular FSP1 abundance. Silver staining followed by mass spectrometry analysis of purified LD proteins identified reduced LD-associated FSP1 in HSD17B11-deficient cells, which was further validated by immunoblotting and imaging analyses. Mechanistically, HSD17B11 physically interacted with FSP1 and was required to preserve FSP1 association with LDs. Mutational analyses further demonstrated that both FSP1 N-myristoylation and an intact HSD17B11 interaction interface are necessary for LD targeting. Correspondingly, HSD17B11 deficiency reduced LD-associated and total cellular FSP1 levels and increased cellular sensitivity to lipid oxidative stress. Together, our findings identify HSD17B11 as a previously unrecognized regulator of LD-associated FSP1 and reveal an additional mechanism controlling compartmentalized ferroptosis defense.

cell biology↗

bioRxiv2024

Horizon: CNV interpretation through rapid automated ACMG-aligned pathogenicity analysis

PurposeOur study assesses the Horizon model, a novel CNV classification tool developed in line with American College of Medical Genetics (ACMG) guidelines, to enhance the classification of pathogenicity in CNVs. MethodsHorizon utilizes a ranking-based algorithm, incorporating multiple proprietary databases and variant inheritance models as per ACMG standards. The models effectiveness was verified through Area Under the Curve (AUC) analyses on three datasets comprising 696 pathogenic inherited or de novo variants, as classified by clinical geneticists and several established tools. ResultsHorizon achieved an AUC of 0.97 in the discovery cohort, demonstrating high accuracy in CNV interpretation and proficiency in predicting pathogenicity. We observed an AUC of 0.87 in the de novo variant cohort and an overall AUC of 0.94 across all cohorts, surpassing tools like ClassifyCNV and AnnotSV. It showed particular effectiveness in interpreting duplication CNVs and the highest performance for CNVs sized 3-5 Mb. ConclusionThe Horizon model offers robust and accurate CNV interpretation, outperforming existing tools and aligning closely with clinical evaluations. Its comprehensive approach, integrating a range of genomic features and following ACMG guidelines, makes it a crucial tool in the genomic interpretation landscape, facilitating the rapid and accurate diagnosis of genetic disorders.

genomics↗

bioRxiv2022

Subtractive proteomics analysis to uncover the potent drug targets for distinctive drug design of Candida auris

Candida auris is a serious health concern of current world that possess serious global health threat and is emerging at a high rate. Available antifungal drugs are failing to combat this pathogen as they are growing resistance toward those drugs and some strains have already showed resistant to all three available antifungal drugs in the market. Finding alternative treatments is a must, therefore, to save lives from this foe. To make the way easier for developing new treatments, we have made some insilico analysis of this pathogen to identify suitable targets for designing drugs and also suggested some potential metabolites to test in vivo condition after some computational analysis. After the subtraction of duplicate, non-essential, human homologs, non-metabolic, human microbiome similar and druggable proteins we ended up with three proteins (XP_028890156.1, XP_028891672.1 and XP_028891858.1) from a total of 5441 C. auris proteins. Blocking those proteins will result in the destruction of the pathogen while the host will remain safe from unintentional blocking. Their subcellular locations and interaction with high number of proteins also indicate their suitability as drug target candidates. After analyzing in silico docking of 29 potential antifungal from plant origin with those three proteins we selected Caledonixanthone E, Viniferin, Glaucine, Jatrorrhizine as the most potent weapon to block those proteins as they showed higher binding affinity. Furthermore, they were predicted to be safe and also showed proper ADME properties (Figure 1). O_FIG O_LINKSMALLFIG WIDTH=179 HEIGHT=200 SRC="FIGDIR/small/487516v1_fig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@5ac4bcorg.highwire.dtl.DTLVardef@12a4b3eorg.highwire.dtl.DTLVardef@1b1d825org.highwire.dtl.DTLVardef@e581b3_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1:C_FLOATNO Schematic pipeline of the process C_FIG

bioinformatics↗

bioRxiv2020

Genome based Evolutionary study of SARS-CoV-2 towards the Prediction of Epitope Based Chimeric Vaccine

SARS-CoV-2 is known to infect the neurological, respiratory, enteric, and hepatic systems of human and has already become an unprecedented threat to global healthcare system. COVID-19, the most serious public condition caused by SARS-CoV-2 leads the world to an uncertainty alongside thousands of regular death scenes. Unavailability of specific therapeutics or approved vaccine has made the recovery of COVI-19 more troublesome and challenging. The present in silico study aimed to predict a novel chimeric vaccines by simultaneously targeting four major structural proteins via the establishment of ancestral relationship among different strains of coronaviruses. Conserved regions from the homologous protein sets of spike glycoprotein (S), membrane protein (M), envelope protein and nucleocapsid protein (N) were identified through multiple sequence alignment. The phylogeny analyses of whole genome stated that four proteins (S, E, M and N) reflected the close ancestral relation of SARS-CoV-2 to SARS-COV-1 and bat coronavirus. Numerous immunogenic epitopes (both T cell and B cell) were generated from the common fragments which were further ranked on the basis of antigenicity, transmembrane topology, conservancy level, toxicity and allergenicity pattern and population coverage analysis. Top putative epitopes were combined with appropriate adjuvants and linkers to construct a novel multiepitope subunit vaccine against COVID-19. The designed constructs were characterized based on physicochemical properties, allergenicity, antigenicity and solubility which revealed the superiority of construct V3 in terms safety and efficacy. Essential molecular dynamics and Normal Mode analysis confirmed minimal deformability of the refined model at molecular level. In addition, disulfide engineering was investigated to accelerate the stability of the protein. Molecular docking study ensured high binding affinity between construct V3 and HLA cells, as well as with different host receptors. Microbial expression and translational efficacy of the constructs were checked using pET28a(+) vector of E. coli strain K12. The development of preventive measures to combat COVID-19 infections might be aided the present study. However, the in vivo and in vitro validation might be ensured with wet lab trials using model animals for the implementation of the presented data.

immunology↗