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Biology subjects

Ahsan, S.

Publications and source records attributed to Ahsan, S..

5 recordsLinked to original sources

Diet-Associated Differences in the Rumen Microbiome and Resistome of Bangladeshi Cattle

Diet influences the composition, diversity, and functional capacity of the cattle gut microbiome. However, the extent to which feeding practices affect the microbial community and resistome under real-world conditions remains poorly understood, particularly in low- and middle-income settings. Here, we applied metagenomics to fecal samples from Bangladeshi cattle fed either a natural or a mixed diet to examine differences in microbial composition, functional potential, and resistome associated with feed type. Natural-fed cattle harbored higher microbial diversity and distinct bacterial phyla, including Bacteroidota, Campylobacteriota, and Mycoplasmatota. Acinetobacter, Aliarcobacter, Comamonas, Dysosmobacter, and Sharpea were enriched in natural-fed cattle, whereas Anaerotignum, Aristaeella, Oscillibacter, and Clostridium were more abundant in the mixed-fed group. Notably, the emerging zoonotic genus Aliarcobacter was detected in the natural-fed cohort. Alpha diversity analysis showed higher richness and evenness in natural-fed cattle, and a clear separation between dietary groups in beta diversity analysis (PERMANOVA, p = 0.01). Differential analysis identified Oscillibacter ruminantium as a biomarker of natural feeding, while Succinivibrio faecicola and Anaerovibrio slackiae for mixed feeding. Resistome profiles demonstrated clear differences. Mixed-fed cattle showed a consistent enrichment of tetracycline resistance genes, whereas the natural-fed group displayed a more variable resistome. Functional analysis suggested diet-associated differences in metabolic potential, with glutathione metabolism enriched in natural-fed cattle (p<0.05) and bile secretion and fatty acid metabolism moderately enriched in the mixed-fed group. These findings indicate that feeding practices are associated with differences in rumen microbial communities and resistome profiles in Bangladeshi cattle, providing baseline insights into microbiome-resistome relationships under field conditions.

microbiology↗

Designing a Multi-Epitope Vaccine Candidate against Salmonella Typhi Using Immunoinformatics Approach

Salmonella enterica subsp. enterica serovar Typhi (Salmonella Typhi) is the causative agent of typhoid. A large population living in developing and under-developed countries are mainly susceptible to the infection of this pathogen. The use of an effective vaccine targeting the highest-risk populations could be an extremely useful approach in the prevention of typhoid. The currently licenced and widely used typhoid conjugate vaccine (Vi-TCV) can promote emergence of Vi antigen negative strains, necessitating the design of alternative vaccine candidates. Vaccine consisting of multiple epitopes from different surface proteins can serve as a solution to this problem. In this study, 10 Salmonella Typhi whole genome sequences were retrieved from NCBI database. From the proteomes of these organisms, epitopes from four surface proteins such as peptidoglycan-associated lipoprotein (Accession No. AYU85048.1), outer membrane protein S1 (Accession No. AYU86170.1), outer membrane protein F (Accession No. AYU85220.1 and outer membrane porin L (Accession No. AYU87629.1) returned better results than some other surface proteins in terms of antigenicity, promiscuity to interact with MHC alleles, non-allergenicity, non-similarity with human proteins, conservation and population coverage. These epitopes were joined together using suitable adjuvant and linkers, resulting in a vaccine candidate comprising 201 amino acids. This multi epitope vaccine candidate exhibited promising results in molecular docking, molecular dynamics simulation and immune simulation. BLAST search revealed that the chosen epitopes for vaccine development against Salmonella Typhi are 100% identical with corresponding epitopes of Salmonella Paratyphi A, Salmonella Typhimurium and Salmonella Enteritidis, indicating that the proposed vaccine might give cross protection against major Salmonella pathogenic serovars. The prospective results in this dry laboratory work demonstrates potential positive outcomes in the future for in vivo animal model testing and clinical analyses.

bioinformatics↗

Mutations in SIX1 associated with Branchio-oto-renal Syndrome (BOR) differentially affect otic expression of putative target genes

Single nucleotide mutations in SIX1 are causative in some individuals diagnosed with branchio-otic/branchio-oto-renal (BOR) syndrome. To test whether these mutations have differential effects on otic gene expression, we engineered four BOR mutations in Xenopus six1 and targeted mutant protein expression to the neural crest and cranial placode precursor cells in wild-type embryos. Changes in the otic expression of putative Six1 targets and/or co-factors were monitored by qRT-PCR and in situ hybridization. We found that each mutant had a different combination of effects. The V17E mutant reduced eya2, tspan13, zbtb16 and pa2g4 otic vesicle expression at a frequency indistinguishable from wild-type Six1, but reduced prdm1 more and spry1 less compared to wild-type Six1. For most of these genes, the R110W, W122R and Y129C mutants were significantly less repressive compared to wild-type Six1. Their individual effects varied according to the level at which they were expressed. The R110W, W122R and Y129C mutants also often expanded prdm1 otic expression. Since previous studies showed that all four mutants are transcriptionally deficient and differ in their ability to interact with co-factors such as Eya1, we propose that altered co-factor interactions at the mutated sites differentially interfere with their ability to drive otic gene expression.

developmental biology↗

Metabolism of glucose and glutamine is critical for skeletal muscle stem cell activation.

Injury to muscle tissue induces the resident, quiescent, skeletal muscle stem cells (MuSCs) to activate - to exit quiescence and enter the cell cycle. Previous work has shown that MuSC activation is associated with significant metabolic changes, however the substrates that MuSCs consume to support activation are poorly understood. Here, we show that MuSCs generate the majority of their energy through mitochondrial respiration, and that oxidative phosphorylation is required for MuSC activation. Furthermore, we have found that while glucose, glutamine, and fatty acids all significantly, and roughly equally, contribute to ATP production in MuSCs during activation, they do not have equal functional role in the dynamics of MuSC activation. Pharmacologic suppression of glycolysis, using 2-deoxy-D-glucose, or glutaminolysis, using BPTES, significantly impairs MuSC cell cycle entry. However, etomoxir-mediated inhibition of mitochondrial fatty acid transport has minimal effect on MuSC cell cycle progression. Our findings suggest that apart from their roles in fueling ATP production by the mitochondria, glucose and glutamine may generate metabolic intermediates needed for MuSC activation.

cell biology↗

PDH Mediated Mitochondrial Respiration Controls the Speed of Muscle Stem Cell Activation in Muscle Repair and Aging

Decline in the skeletal muscle stem cell (MuSC) function is a major contributor to age-associated impairments in muscle regeneration and function. The ability of MuSCs to activate (i.e. exit quiescence, enter the cell cycle, and divide) following injury is a critical step that initiates muscle regeneration. However, the mechanisms that regulate MuSC activation function are poorly understood. Here, we show that the activation function, specifically the speed by which cells progress through G0-G1, declines tremendously with age in mouse MuSCs. Using a number of in vivo models and ex vivo assays of MuSC activation and muscle regenerative functions, live cell metabolic flux analyses, and metabolomics we present data indicating that changes in MuSC mitochondrial flux underlie age-associated changes in MuSC activation. We show that, in the course of MuSC activation, there is a profound,16-fold, increase in ATP production rates, which is fueled largely by increases in pyruvate flux into mitochondria. We found that MuSCs from aged mice display progressive defects in the ability to increase mitochondrial flux during activation and that this correlates with higher levels of phosphorylated, inactivated, pyruvate dehydrogenase (PDH). Importantly, we demonstrate that pharmacologic and physiologic methods to induce dephosphorylation and activation of PDH in MuSCs are sufficient to rescue the activation and muscle regenerative functions of MuSCs in aged mice. Collectively the data presented show that MuSC mitochondrial function is a central regulator of MuSC activation and muscle regenerative functions. Moreover, our results suggest that approaches to increase MuSC pyruvate oxidation may have therapeutic potential to promote muscle repair and regeneration.

cell biology↗