Biomedical subjects

Ravi S Misra

Publications and source records attributed to Ravi S Misra.

3 recordsLinked to original sources

PubMed2025

Exploring endothelial cell environments across organs in spatially resolved omics data.

Endothelial cells are ubiquitously present in the human body and line the luminal surface of blood and lymphatic vessels. The oxygen-dependence of cells impacts their proximity to blood vessels, and consequently, to endothelial cells depending on their functional properties and priorities. This paper presents cell-to-nearest-endothelial-cell distance distributions for various cell types using 399 spatially resolved omics datasets from 14 studies comprising 12 tissue types with a total of 47,349,496 cells. Additionally, we developed an open-source web-based interactive tool, Cell Distance Explorer, that allows researchers to interactively visualize cell graphs and linkages in 2D and 3D datasets. Finally, we present a hierarchical neighborhood analysis focused on the endothelial cell neighborhoods in small and large intestine datasets. This paper provides an open-access resource (datasets, tools, and analyses) to characterize and compare cell distances and cell neighborhoods in spatially resolved omics data.

Journal Article↗

PubMed2006

Proteolytic regulation of nuclear factor of activated T (NFAT) c2 cells and NFAT activity by caspase-3.

The nuclear factor of activated T (NFAT) cell family of transcription factors is important in regulating the expression of a broad array of genes, including cytokines, T cell surface receptors, and other transcription factors. NFATc1 and NFATc2 are two principal NFAT members that are expressed in peripheral T cells. Levels of NFAT expression in T cells are partly transcriptionally regulated, but less is understood regarding their post-transcriptional control. We show here that NFATc1 and NFATc2 are rapidly degraded in apoptotic T cells. NFATc2 is highly sensitive to cleavage by caspase-3, whereas NFATc1 is only weakly sensitive to caspase-3 or caspase-8. Two potential caspase-3 cleavage sites were identified in the N-terminal transactivation domain. These sites were confirmed by in vitro caspase cleavage assays. Abolition of NFATc2 cleavage by mutation of these two cleavage sites resulted in augmented NFAT transcriptional activity. Furthermore, NFAT activity could be augmented in wild-type effector T cells by inhibition of caspase activity. Of particular interest was that non-apoptotic T cells from cellular FLIP long transgenic (c-FLIP(L)-Tg) mice that manifest elevated caspase activity have greatly reduced levels of NFATc2 protein and NFAT transcriptional activity. Our findings reveal a new post-transcriptional regulation of NFATc2 that operates, not only during apoptosis, but also in non-apoptotic effector T cells.

Amino Acid Chloromethyl Ketones↗

PubMed2005

Effector CD4+ T cells generate intermediate caspase activity and cleavage of caspase-8 substrates.

Caspase-8 activation promotes cell apoptosis but is also essential for T cell activation. The extent of caspase activation and substrate cleavage in these divergent processes remains unclear. We show that murine effector CD4(+) T cells generated levels of caspase activity intermediate between unstimulated T cells and apoptotic populations. Both caspase-8 and caspase-3 were partially activated in effector T cells, which was reflected in cleavage of the caspase-8 substrates, c-FLIP(L), receptor interacting protein 1, and to a lesser extent Bid, but not the caspase-3 substrate inhibitor of caspase-activated DNase. Th2 effector CD4(+) T cells manifested more caspase activity than did Th1 effectors, and caspase blockade greatly decreased initiation of cell cycling. The current findings define the level of caspase activity and substrates during initiation of T cell cycling.

Animals↗