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Pawar, K.

Publications and source records attributed to Pawar, K..

2 recordsLinked to original sources

Distinct trajectories of urbanization shape the human gut microbiome across South Asia

Human gut microbiomes respond to lifestyle transitions, yet the extent to which these responses are conserved across spatio-cultural contexts remains undercharacterized. We present the South Asian MicroBiome ARray (SAMBAR), a population-scale 16S gut microbiome study of 575 adults from ten geographically and socio-culturally diverse South Asian communities. Each community was sampled in ancestral villages and urban centers, enabling controlled comparisons of geography and lifestyle. Relative to global cohorts, SAMBAR microbiomes occupy a distinct compositional space with stronger correlation to geography and community membership than lifestyle. Although urbanization is consistently associated with increased abundance of disease-linked taxa, microbiome responses to lifestyle transitions are largely community-driven, including the acquisition of wheat- and dairying-associated microbial modules in some communities that may facilitate non-genetic adaptation to lactase non-persistence. Microbiome responses to urbanization are heterogeneous even at regional scales, reflecting local culture and geography and underscoring the need for community-specific investigations of health impacts.

microbiology↗

Allergen-induced tRNA halves repress focal adhesion of airway smooth muscle cells

The RNase A superfamily, one of the most extensively studied enzyme families, remains incompletely defined with respect to its endogenous RNA substrates, recognition mechanisms, and physiological functions. Here, we identify eosinophil-derived neurotoxin (EDN/RNase 2) as a principal endoribonuclease mediating tRNA cleavage in the asthmatic lung. Inhalation of house dust mite (HDM) in mice induces robust accumulation of tRNA halves in the lung, coinciding with exclusive upregulation of EDN, but not other ribonucleases. In human lung epithelial cells, internalized EDN cleaves specific tRNAs and generates multiple species of tRNA halves, including immunostimulatory species that activate Toll-like receptor 7 (TLR7). EDN also promotes the release of extracellular vesicles enriched in these RNAs, implicating them in cytokine production during asthma pathogenesis. Biochemical analyses and structural simulations reveal that EDN recognizes the anticodon loop of tRNA by anchoring the phosphate backbones flanking the cleavage site, thereby precisely positioning the C34-A35 phosphodiester bond for catalysis. Furthermore, the highly efficient cleavage by EDN is mediated by conserved elements, including Arg36 in EDN and U33 and C38 in the target tRNA. Together, these findings establish the endogenous RNA substrate of EDN and uncover a molecular mechanism that links RNase A superfamily activity to immune response.

molecular biology↗