Biology subjects

Mohsin, M.

Publications and source records attributed to Mohsin, M..

5 recordsLinked to original sources

bioRxiv2025

Type 2 Diabetes Mellitus pathogenesis and role of Peptidylglycine Alpha-Amidating Monooxygenase (PAM) Gene elaboration by In-silico Analysis

Type 2 Diabetes Mellitus (T2DM) is caused by pancreatic beta cell failure and alpha cell dysfunction that are central to this disease pathophysiology. For T2DM, the Peptidylglycine Alpha-Amidating Monooxygenase (PAM) gene has susceptible locus as identified by Genome-wide association studies (GWAS) though underlying molecular mechanisms remained poorly characterised. This study have explored comprehensive in-silico characterization of the PAM gene potential role in T2DM. InterPro was employed to identify protein family and it was observed it belongs to Peptidylglycine alpha-hydroxylating monooxygenase/peptidyl-hydroxyglycine alpha-amidating lyase family (IR000720), consisting of two catalytic domains and nine active regions. Clinically significant 153 genetic variants including non-synonymous SNPs within the locus were identified after analysis of dbSNP through UCSC Genome Browser. Intrinsically disrupted large region (aa 290-495) was observed during protein disorder prediction by utilizing IUPred-3. Ensembl and NCBI BLAST were used to analyse evolutionary conservation sites. This analysis resulted in high sequence similarity with common model organisms Mus musculus and Rattus norvegicus with similarity 90% and 89% respectively. These computational findings suggest specific PAM variants likely to disrupt protein function, providing validated future direction for experimental studies to confirm PAM gene pivotal role in T2DM.

bioinformatics↗

bioRxiv2025

Electrical Oscillations in Microtubules

Environmental perturbations and local changes in cellular electric potential can stimulate cytoskeletal filaments to transmit ionic currents along their surface. Advanced models and accurate experiments may provide a molecular understanding of these processes and reveal their role in cell electrical activities. This article introduces a multi-scale electrokinetic model incorporating atomistic protein details and biological environments to characterize electrical impulses along microtubules. We consider that condensed ionic layers on microtubule surfaces form two coupled asymmetric nonlinear electrical transmission lines. The model accounts for tubulin-tubulin interactions, dissipation, and a nanopore coupling between inner and outer surfaces, enabling luminal currents, energy transfer, amplification, and oscillatory dynamics that resemble the experimentally observed transistor properties of microtubules. The approach has been used to analyze how different electrolyte conditions and voltage stimuli affect electrical impulses shape, attenuation, oscillation, and propagation velocity along microtubules. Integrating transistor-like properties in the microtubules model has profound implications for intracellular communication and bioelectronic applications.

biophysics↗

bioRxiv2025

The study of differential expressions of MCPH and Seckel syndrome genes and their paralogues

Seckel syndrome and MCPH are single-gene neurodevelopmental disorders, with or without dwarfism. These genes are parts of essential cellular pathways but are regulated differently in both forms of microcephaly. These genes have diverged from single ancestral genes in to related but different gene paralogues during evolution. It is suggested that the paralogues might be redundant in other body organs and might rescue any abnormality in cases of MCPH, but not in Seckel syndrome. This study uncovers the spatio-temporal dynamics of these genes together with their paralogues at the mRNA level where the different tissues of embryos might exhibit different transcript variants or different levels of the various transcript variants to find the complementation in case of the MCPH but divergence in case of the Seckel syndrome. Here, we studied Cdk5Rap2-Pde4dip, Phc1-Phc3 (for MCPH) and Cep63-Ccdc67 (for Seckel) in the embryonic mouse tissues using RT-PCR throughout the peak of neurogenesis from E12.5 to E18.5. We found already known and novel spatio-temporal differential expression suggesting different regulation at the mRNA level. The results of PCR were analyzed on the agarose gel and were quantified by assigning relative intensity percentage scores to each band and plotting the cumulative expression of each gene in to the graphs for spatio-temporal dynamics and plotted each gene separately for temporal dynamics. For MCPH, Cdk5Rap2-Pde4dip had similar profiles and seemed to be redundant whereas Phc1-Phc3 seem to have complementary roles in brain development. The expression profiles of Cep63-Ccdc67 were very different indicating of their divergent and essential roles in development.

genetics↗

bioRxiv2025

A comprehensive water buffalo pangenome reveals extensive structural variation linked to population specific signatures of selection

Water buffalo is a cornerstone livestock species in many low- and middle-income countries, yet major gaps persist in its genomic characterization--complicated by the divergent karyotypes of its two sub-species (swamp and river). Such genomic complexity makes water buffalo a particularly good candidate for the use of graph genomics, which can capture variation missed by linear reference approaches. However, the utility of this approach to improve water buffalo has been largely unexplored. We present a comprehensive pangenome that integrates four newly generated, highly contiguous assemblies of Pakistani river buffalo with available assemblies from both sub- species. This doubles the number of accessible high-quality river buffalo genomes and provides the most contiguous assemblies for the sub-species to date. Using the pangenome to assay variation across 711 global samples, we uncovered extensive genomic diversity, including thousands of large structural variants absent from the reference genome, spanning over 140 Mb of additional sequence. We demonstrate the utility of these data by identifying putative functional indels and structural variants linked to selective sweeps in key genes involved in productivity and immune response across 26 populations. This study represents one of the first successful applications of graph genomics in water buffalo and offers valuable insights into how integrating assemblies can transform analyses of water buffalo and other species with complex evolutionary histories. We anticipate that these assemblies, and the pangenome and putative functional structural variants we have released, will accelerate efforts to unlock water buffalos genetic potential, improving productivity and resilience in this economically important species.

genomics↗

bioRxiv2021

Electrical impulse characterization along actin filaments in pathological conditions

We present an interactive Mathematica notebook that characterizes the electrical impulses along actin filaments in both muscle and non-muscle cells for a wide range of physiological and pathological conditions. The program is based on a multi-scale (atomic [->] monomer [->] filament) approach capable of accounting for the atomistic details of a protein molecular structure, its biological environment, and their impact on the travel distance, velocity, and attenuation of monovalent ionic wave packets propagating along microfilaments. The interactive component allows investigators to conduct original research by choosing the experimental conditions (intracellular Vs in vitro), nucleotide state (ATP Vs ADP), actin isoform (alpha, gamma, beta, and muscle or non-muscle cell), as well as, a conformation model that covers a variety of mutants and wild-type (the control) actin filament. The simplicity of the theoretical formulation and the high performance of the Mathematica software enable the analysis of multiple conditions without computational restrictions. These studies may provide an unprecedented molecular understanding of why and how age, inheritance, and disease conditions induce dysfunctions in the biophysical mechanisms underlying the propagation of electrical signals along actin filaments.

neuroscience↗