Biology subjects

Hasan, M. N.

Publications and source records attributed to Hasan, M. N..

11 recordsLinked to original sources

bioRxiv2026

Neural microstates underlying categorical speech perception using Bayesian nonparametrics

Categorical perception (CP) reflects the human auditory systems ability to map continuous acoustic signals onto discrete categories. Understanding the relationship between neural dynamics and perceptual decisions is central to speech-language processing. Here, we implemented a data-driven approach using Bayesian nonparametrics and machine learning to characterize the relationship between auditory cortical responses and speech categorization behaviors. By applying a hierarchical Dirichlet process hidden Markov Model (HDP-HMM) to source-reconstructed event-related potential (ERP) data, we identified temporally distinct neural microstates that capture the evolving stages of speech categorization without imposing predefined temporal windows. Machine learning classifiers, including extreme gradient boosting (XGBoost), support vector machines, and random forests, were applied to decode prototypical (Tk1/5) versus ambiguous (Tk3) speech sound tokens from the microstate data. Using whole-brain activity, the XGBoost classifier achieved the highest decoding accuracy of 94.1% with an area under the curve (AUC) 94.1% within a specific encoding microstate occurring approximately 200-250 ms after stimulus onset. A reduced set of 15 informative brain regions identified via Shapley additive explanations (SHAP) yielded comparable classification performance (90.3% accuracy; AUC 90.0%), with many regions localized to frontal, temporal, and parietal regions in the left hemisphere. Furthermore, neural activity within these regions robustly predicted listeners behavioral identification slopes (R2 = 0.92, p < 0.00001), linking microstate-specific cortical dynamics to individual differences in perceptual gradiency of speech perception. These findings demonstrate that speech categorization emerges within temporally discrete neural microstates during early sensory-perceptual encoding and is supported by a selective, distributed cortical network with clear behavioral relevance.

neuroscience↗

bioRxiv2025

Hepatocyte and adipocyte CDO1-mediated intracellular cysteine catabolism differentially modulates diet-induced obesity and fatty liver in mice

Background and AimsPlasma cysteine has been positively linked to BMI in humans. Consistently, dietary cysteine restriction significantly decreases obesity in mice via mechanisms that are incompletely defined. Cysteine dioxygenase type 1 (CDO1) mediates the major cysteine catabolism pathway and is highly expressed in hepatocytes and adipocytes. The goal of this study is to determine the impact of this endogenous cysteine catabolism pathway on obesity and fatty liver disease. MethodsDiet-induced obesity and fatty liver disease were studied in hepatocyte-specific CDO1 knockout mice (L-CDO1-KO), hepatocyte-specific CDO1 transgenic mice (L-CDO1-Tg), adipocyte-specific CDO1 knockout mice (Ad-CDO1-KO), and adipocyte-specific CDO1 transgenic mice (Ad-CDO1-Tg). ResultsDeletion of hepatocyte CDO1 decreased cysteine conversion to cysteine sulfinic acid, and had modest impact on liver cysteine, GSH, or taurine abundance. When fed a Western diet (WD), L-CDO1-KO mice showed elevated liver injury markers and inflammatory infiltration independent of obesity or steatosis. When fed a fibrogenic high fat/cholesterol/fructose diet (HFCFr), L-CDO1-KO mice developed worsened liver fibrosis. In contrast, L-CDO1-Tg mice fed WD showed lower blood glucose, but similar degree of obesity and steatosis compared to WT mice. Deletion of CDO1 in white and brown adipocytes of Ad-CDO1-KO mice had no effect on WD-induced obesity. In contrast, overexpression of CDO1 in white and brown adipocytes attenuated WD-induced obesity, which resulted in reduced hepatic steatosis. ConclusionGenetic manipulation of intracellular cysteine catabolism in hepatocytes and adipocytes differentially modulates diet-induced obesity and fatty liver, which warrants future mechanistic investigation to better understand cellular cysteine sensing mechanisms and cysteine control of cell metabolism.

physiology↗

bioRxiv2024

Computational screening of potential AT1R inhibitors from Nigella sativa for diabetic-hypertensive therapy

Hypertension, frequently coexists with Type 2 diabetes mellitus, causes due to Angiotensin II. Inhibiting Angiotensin II by targeting AT1R can potentially improve hypertension-related complications in patients with T2DM. In this study, we perform an in-silico screening based on molecular docking and molecular dynamic of 305 compounds of Nigella sativa against Angiotensin-II Type1 Receptor (AT1R). Molecular docking studies were conducted to investigate the binding affinities of the selected ligands with the target receptor and compared against the Losartan (control drug). Top 5 ligands were selected based on binding affinity. Subsequently, we conducted an ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profiling to assess their pharmacokinetic and safety profiles. Our findings revealed two promising ligands Beta-amyrin (CID-73145) and Taraxerol (CID-92097), which exhibited strong binding affinities and favorable pharmacological profiles with no signs of acute toxicity. The molecular dynamic simulations (MD) including RMSD, RMSF, and MMGBSA binding free energy results showed that selected two ligands bind to AT1R more proficiently with good stability over 100 ns. The computational study serves as a foundational basis for subsequent laboratory and clinical research aimed at identifying selective, potent, and less toxic diabetic-hypertensive therapy targeting AT1R. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/610463v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@1b3fdf8org.highwire.dtl.DTLVardef@1e6dafforg.highwire.dtl.DTLVardef@133afd0org.highwire.dtl.DTLVardef@5b93c4_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2024

Targeting fatty acid synthase suppresses tumor development in NF2/CDKN2A-deficient malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is an uncommon yet deadly cancer linked to asbestos exposure. The lack of effective early diagnosis and treatment leads to reduced life expectancy among patients with MPM. This study is aimed to identify a novel molecular target inhibitor to develop more effective therapeutics for MPM. Our drug screening assay showed that the fatty acid synthase (FASN) inhibitor cerulenin demonstrates strong and selective anti-proliferative properties against NF2/CDKN2A(p16)-deficient MPM cells, surpassing the effects of cisplatin or pemetrexed. FASN protein is frequently detected in NF2/p16-deficient MPM tumor-derived tissues (15/15, 100%), but rarely in NF2/p16-intact MPM tumors (8/25, 32%). Notably, cerulenin administration successfully reduced the growth of NF2/p16-deficient MPM tumors in xenografted mice. Cerulenin inhibits mitochondrial fission by targeting dynamin-related protein 1 (DRP1) in NF2/p16-deficient cells. Moreover, the disruption of the FASN gene leads to increased ubiquitination of DRP1. These findings suggest that FASN might play a role in the tumorigenesis of MPM cells through the regulation of mitochondrial dynamics. This research offers a novel perspective on the potential development of precision medicine for MPM.

cancer 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↗

bioRxiv2023

Morpho-physiobiochemical dissection reveals insight into salt-induced differential responses in genetically modified Solanum melongena L. (Bt Brinjal) varieties using an indigenous hydroponic system

Salinity is a major abiotic constraint of crop production in many countries, including Bangladesh, where a significant amount of cultivable areas are diversely affected by rising salt concentrations. Therefore, it is of paramount importance to figure out the possible solutions to cope with this abiotic stress. So, the development of tolerant genotypes of various crop species can be the best alternative to enhance crop production as well as to improve the livelihoods of poor marginal farmers. With this in mind, the impact of different NaCl levels (50 mM, 100 mM, and 150 mM) on four different Bt Brinjal (Bacillus thuringiensis) genotypes (BARI Bt Begun-1, BARI Bt Begun-2, BARI Bt Begun-3, and BARI Bt Begun-4) was evaluated using morpho-physicochemical analyses at growth, harvesting, and postharvest stages by establishing a new indigenous cost-effective hydroponic system. Our results show that excess salt (> 100 mM) has a detrimental effect on plant growth and development and most of the traits measured across different growth stages. Based on the different measured traits, BARI Bt Begun-1 and BARI Bt Begun-2 varieties outperformed in terms of better morpho-physiological, biochemical, photosynthetic, and antioxidant capacity under salt stress when compared to BARI Bt Begun-3 and BARI Bt Begun-4. Therefore, we conclude that BARI Bt Begun-1 and BARI Bt Begun-2 are moderately tolerant varieties, while BARI Bt Begun-3 and Begun-4 were susceptible varieties to salinity stress. The identified salt-responsive contrasting varieties can serve as valuable genetic materials in comparative genomics for breeding salt-tolerant Brinjal varieties and the newly established hydroponic system could be utilized in translational research programs.

plant biology↗

bioRxiv2023

Genome-wide identification and characterization of major RNAi genes highlighting their regulatory factors in Cowpea (Vigna unguiculata (L.) Walp.)

In different regions of the world, cowpea (Vigna unguiculata (L.) Walp.) is an important vegetable and an excellent source of protein. It lessens the malnutrition of the underprivileged in developing nations and has some positive effects on health, such as a reduction in the prevalence of cancer and cardiovascular disease. However, occasionally, certain biotic and abiotic stresses caused a sharp fall in cowpea yield. Currently, short RNAs (sRNAs) are thought to play a crucial role in controlling how stress-related genes are expressed in plants as they go through various developmental phases. Major RNA interference (RNAi) genes like Dicer-like (DCL), Argonaute (AGO), and RNA-dependent RNA polymerase (RDR) are essential for sRNA synthesis processes and shield plants from biotic and abiotic stresses. In this study, applying BLASTP search and phylogenetic tree analysis with reference to the Arabidopsis RNAi (AtRNAi) genes, we discovered 28 VuRNAi genes, including 7 VuDCL, 14 VuAGO, and 7 VuRDR genes in cowpea. We looked at the domains, motifs, gene structures, chromosomal locations, sub-cellular locations, gene ontology (GO) terms and regulatory factors (transcription factors, micro-RNAs, and cis-acting factors) to characterize the VuRNAi genes and proteins in cowpea. Predicted VuDCL1, VuDCL2(a, b), VuAGO7, VuAGO10 and VuRDR6 genes might have an impact on cowpea growth, development of the vegetative and flowering stages and antiviral defense. The VuRNAi gene regulatory features miR395 and miR396 might contribute to grain quality improvement, immunity boosting, and pathogen infection resistance under salinity and drought conditions. Predicted cis-acting elements (CAEs) from the VuRNAi gene associated with light responsiveness (LR), stress responsiveness (SR) and hormone responsiveness (HR) might play a role in plant growth and development, improving grain quality and production and protecting plants from biotic and abiotic stresses. Therefore, our study provides crucial information about the functional roles of VuRNAi genes and their regulatory components, which would aid in the development of future cowpeas that are more resilient to biotic and abiotic stress.

bioinformatics↗

bioRxiv2022

Identification, characterization of Apyrase (APY) gene family in rice (Oryza sativa) and analysis of the expression pattern under various stress conditions

Apyrase (APY) is a nucleoside triphosphate (NTP) diphosphohydrolase (NTPDase) which is a member of the superfamily of guanosine diphosphatase 1 (GDA1) - cluster of differentiation 39 (CD39) nucleoside phosphatase. Under various circumstances like stress, cell growth, the extracellular adenosine triphosphate (eATP) level increases, causing a detrimental influence on cells such as cell growth retardation, ROS production, NO burst, and apoptosis. Apyrase hydrolyses eATP accumulated in the extracellular membrane during stress, wounds, into adenosine diphosphate (ADP) and adenosine monophosphate (AMP) and regulates the stress- responsive pathway in plants. This study was designed for the identification, characterization, and for analysis of APY gene expression in Oryza sativa. This investigation discovered nine APYs in rice, including both endo- and ecto-apyrase. According to duplication event analysis, in the evolution of OsAPYs, a significant role is performed by segmental duplication. Their role in stress control, hormonal responsiveness, and the development of cells is supported by the corresponding cis-elements present in their promoter regions. According to expression profiling by RNA-seq data, the genes were expressed in various tissues. Upon exposure to a variety of biotic as well as abiotic stimuli, including anoxia, drought, submergence, alkali, heat, dehydration, salt, and cold, they showed a differential expression pattern. The expression analysis from the RT-qPCR data also showed expression under various abiotic stress conditions, comprising cold, salinity, cadmium, drought, submergence, and especially heat stress. This finding will pave the way for future in-vivo analysis, unveil the molecular mechanisms of APY genes in stress response, and contribute to the development of stress- tolerant rice varieties.

bioinformatics↗

bioRxiv2022

LUZP1 regulates the constriction velocity of the contractile ring during cytokinesis

There has been a great deal of research on cell division and its mechanisms; however, its processes have not yet been entirely elucidated. To find novel proteins that regulate cell division, we performed the screening using siRNAs and/or the expression plasmid of the target genes and identified leucine zipper protein 1 (LUZP1). Recent studies have shown that LUZP1 interacts with various proteins and stabilizes the actin cytoskeleton; however, the function of LUZP1 in mitosis is not known. In this study, we found that LUZP1 colocalized with the chromosomal passenger complex (CPC) at the centromere in metaphase and at the central spindle in anaphase and that these LUZP1 localizations were regulated by CPC activity and kinesin family member 20A (KIF20A). Mass spectrometry analysis identified that LUZP1 interacted with death-associated protein kinase 3 (DAPK3), one regulator of the cleavage furrow ingression in cytokinesis. In addition, we found that LUZP1 also interacted with myosin light chain 9 (MYL9), a substrate of DAPK3, and comprehensively inhibited MYL9 phosphorylation by DAPK3. In line with a known role for MYL9 in the actin-myosin contraction, LUZP1 suppression accelerated the constriction velocity at the division plane in our timelapse analysis. Our study indicates that LUZP1 is a novel regulator for cytokinesis that regulates the constriction velocity of the contractile ring.

cell biology↗

bioRxiv2020

Robust Hierarchical Co-clustering to Explore Toxicogenomic Biomarkers and Their Regulatory Doses of Chemical Compounds

Toxicogenomics combines high throughput molecular technologies with statistical and machine learning approaches to discover a similar group of doses of chemical compounds (DCCs) and genes to explore toxicogenomic biomarkers and their regulatory DCCs. This is also very important in the toxicity study of environmental stressors, synthetic chemicals and drug discovery and development process. Different clustering algorithms are concerned with the discovering of interesting clusters/groups of row or column entities of a dataset. Among those hierarchical clustering (HC) and logistic probabilistic hidden variable model (LPHVM) can identify toxicogenomic biomarkers and their regulatory DCCs forming co-cluster. However, the HC method is very sensitive to outlying observations. On the other hand, though LPHVM is a robust approach, it consumes more time for calculation since it is Expectation-Maximization (EM) based iterative approach. Additionally, the LPHVM creates artificiality problem taking absolute value of the data matrix. Therefore, to overcome these problems in this paper, we proposed a robust hierarchical co-clustering (RHCOC) algorithm to co-cluster genes and DCCs simultaneously with a view to explore toxicogenomic biomarkers and their regulatory DCCs. The performance of the proposed RHCOC algorithm over the conventional HC for clustering genes and DCCs of toxicogenomic data has been investigated based on the simulation study. The results of the simulation study have shown that the RHCOC approaches produce far lower clustering error rate (ER) than the conventional HC approaches in presence of outlying observations in the dataset. Otherwise they perform equally in absence of outlier in the dataset. To explore biomarker co-clusters consisting of toxicogenomic biomarker genes and their regulatory DCCs we used control chart for individual measurement (CCIM). We have also investigated the performance of the proposed approach in the case of the pathway level real life fold change gene expression (FCGE) toxicogenomic data analysis. The biomarker co-clusters consisting of toxicogenomic biomarker genes and their regulatory DCCs and biomarker genes explored by the proposed approaches have been validated by the literature and functional annotation. Our method is implemented in R package "rhcoclust" available on github (https://github.com/mdbahadur/rhcoclust).

bioinformatics↗

bioRxiv2019

Contriving a chimeric polyvalent vaccine to prevent infections caused by Herpes Simplex Virus (Type-1 and Type-2): an exploratory immunoinformatic approach

Herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) cause a variety of infections including oral-facial infections, genital herpes, herpes keratitis, cutaneous infection and so on. To date, FDA-approved licensed HSV vaccine is not available yet. Hence, the study was conducted to identify and characterize an effective epitope based polyvalent vaccine against both types of Herpes Simplex Virus through targeting six viral proteins. The selected proteins were retrieved from viralzone and assessed to design highly antigenic epitopes by binding analyses of the peptides with MHC class-I and class-II molecules, antigenicity screening, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking approach. The final vaccine was constructed by the combination of top CTL, HTL and BCL epitopes from each protein along with suitable adjuvant and linkers. Physicochemical and secondary structure analysis, disulfide engineering, molecular dynamic simulation and codon adaptation were further employed to develop a unique multi-epitope peptide vaccine. Docking analysis of the refined vaccine structure with different MHC molecules and human immune TLR-2 receptor demonstrated higher interaction. Complexed structure of the modeled vaccine and TLR-2 showed minimal deformability at molecular level. Moreover, translational potency and microbial expression of the modeled vaccine was analyzed with pET28a(+) vector for E. coli strain strain K12. The study enabled design of a novel chimeric polyvalent vaccine to confer broad range immunity against both HSV serotypes. However, further wet lab based research using model animals are highly recommended to experimentally validate our findings.

bioinformatics↗