Biology subjects

Srivastava, B.

Publications and source records attributed to Srivastava, B..

4 recordsLinked to original sources

bioRxiv2026

Corepressor NCoR1-mediated regulation of mucin dynamics governs gut inflammation

Inflammatory bowel disease (IBD), comprising Ulcerative colitis (UC) and Crohns Disease, is a chronic relapsing immune-mediated inflammatory disorder of the gut. The intestinal mucus layer is a protective barrier that safeguards direct exposure of epithelium to luminal microbes and antigens. A prolonged disruption of the mucus layer may contribute to the development of IBD. Loss of mucin-producing goblet cells is a hallmark of UC. The underlying molecular mechanism controlling goblet regulation remains poorly understood. In the current work, we show a key role for NCoR1 (Nuclear corepressor 1) in goblet cell regulation. A specific downregulation of NCoR1 in intestinal crypts and goblet cells was observed in human UC and mice models. While NCoR1 was upregulated during goblet cell differentiation, inflammatory cues downregulated its expression. Experimental loss of NCoR1 resulted in exacerbated disease in a murine model of colitis, whereas its upregulation via Vitamin D led to a rescue. ChIP-seq led to the identification of KLF-16, a transcription factor, as a target of NCoR1. NCoR1 -KLF16 regulatory axis regulated key goblet cell proteins, including MUC2. Mechanistically, the regulation of MUC2 is modulated by the NCoR1-KLF16 axis, via mTOR signalling. In conclusion, this work shows a critical involvement of NCoR1-KLF16 in governing goblet cell function and intestinal homeostasis.

molecular biology↗

bioRxiv2025

Sexual isolation maintains species boundaries between Hawaiian crickets in sympatry despite weak habitat isolation

Understanding the relative importance of different reproductive isolating barriers in maintaining species boundaries is fundamental to understanding how closely related species coexist without hybridizing. Habitat isolation and sexual isolation are often the first barriers between closely related species, yet they are rarely studied together, making their relative contributions to reproductive isolation unclear. We conducted the first comprehensive study of both barriers in Hawaiian swordtail crickets (Laupala), focusing on the recently diverged, sympatric species pair Laupala kona and Laupala hualalai. Using genomic data, we confirmed that the two species are genetically distinct, which can only be achieved by strong reproductive isolation through a prolonged time period. Through field surveys, we quantified microhabitat use, spatial distribution, and diets, and found extensive ecological overlap. Both species occupied similar substrates, elevations, and microclimates, and occurred in mixed-species aggregations. They only differ in their diets (inferred from stable isotopes), which might have some implications in reducing encounter rates. Despite this weak habitat isolation, they have divergent sexual traits and exhibit strong sexual isolation in lab assays. The species differ significantly in male pulse rate and cuticular hydrocarbon profiles, and females consistently preferred conspecific song stimuli. Mating trials showed almost complete sexual incompatibility between heterospecific pairs, with very rare interspecies copulations. Together, these results demonstrate that sexual isolation, rather than habitat partitioning, maintains species boundaries between L. hualalai and L. kona in sympatry. Our findings highlight the sufficiency of sexual isolation to prevent hybridization even in the absence of strong ecological divergence, providing rare empirical evidence that sexual barriers alone can maintain reproductive isolation in natural populations.

evolutionary biology↗

bioRxiv2024

Genotyping of paired clinical isolates using PvCSP, PvMSP3α PvMSP3βand exploring STRs to differentiate between relapse and reinfection in P. vivax

The challenge of eliminating Vivax malaria is due to the relapses caused by hypnozoites. Despite several attempts to identify molecular markers to differentiate between relapse and new infection, a reliable marker has not yet been established. To address this issue, a genomic study was conducted on paired samples of patients who had experienced Plasmodium vivax infection twice. Genotyping was performed on paired samples from 10 vivax malaria patients using five molecular markers to distinguish between relapse and new infection. Our findings indicate that one sample represented a second episode that was a relapse of the first, while another sample had three episodes, two of which were relapse episodes. We combined our clinical records with molecular inferences to identify each pair as a relapse. This particular study provides a momentary view of forthcoming research endeavors that could be undertaken to distinguish between a relapse and a novel infection. Given the notable genetic variability of Plasmodium vivax, it is crucial to harness various markers to discern between relapse and new infection. The findings of this study are poised to be of immense utility for upcoming marker research in the aforesaid aspect.

genomics↗

bioRxiv2023

Rab7 dependent regulation of goblet cell protein CLCA1 modulates gastrointestinal homeostasis

Inflammation in ulcerative colitis is typically restricted to the mucosal layer of distal gut. Disrupted mucus barrier coupled with microbial dysbiosis has been reported to occur prior to the onset of inflammation. Here, we show the involvement of vesicular trafficking protein Rab7 in regulating the colonic mucus system. We identified a lowered Rab7 expression in goblet cells of colon during human and murine colitis. In vivo Rab7 knocked down mice (Rab7KD) displayed a compromised mucus layer, increased microbial permeability and depleted gut microbiota with enhanced susceptibility to dextran sodium-sulfate induced colitis. These abnormalities emerged owing to altered mucus composition, as revealed by mucus proteomics, with increased expression of mucin protease Chloride channel accessory 1 (CLCA1). Mechanistically, Rab7 maintained optimal CLCA1 levels by controlling its lysosomal degradation, a process that was dysregulated during colitis. Overall, our work establishes a role for Rab7 dependent control of CLCA1 secretion required for maintaining mucosal homeostasis.

cell biology↗