Biology subjects

Trivedi, P.

Publications and source records attributed to Trivedi, P..

3 recordsLinked to original sources

bioRxiv2021

Enrichment analysis of GWAS data in autoimmunity delineates the multiple sclerosis-Epstein Barr virus association

We exploited genetic information to assess non-genetic influences in autoimmunity. We isolated gene modules whose products physically interact with environmental exposures related to autoimmunity, and analyzed their nominal statistical evidence of association with autoimmune and non-autoimmune diseases in genome-wide association studies (GWAS) data. Epstein Barr virus (EBV) and other Herpesviruses interactomes emerged as specifically associated with multiple sclerosis (MS), possibly under common regulatory mechanisms. Analyses of MS blood and brain transcriptomes, cytofluorimetric studies of endogenous EBV-infected lymphoblastoid lines, and lesion immunohistochemistry, confirmed a dysregulation of MS-associated EBV interactors, suggesting their contribution to CD40 signaling alterations in MS. These interactors resulted enriched in modules from inherited axonopathies-causing genes, supporting a link between EBV and neurodegeneration in MS, in accord with the observed transcriptomic dysregulations in MS brains. They were also enriched with top-ranked pharmaceutical targets prioritized on a genetic basis. This study delineates a disease-specific influence of herpesviruses on MS biology.

neuroscience↗

bioRxiv2020

The innate sensor ZBP1-IRF3 axis regulates cell proliferation in multiple myeloma

ZBP1 is an inducible, non-constitutively expressed cellular nucleic acid sensor that triggers type I interferon (IFN) responses via phosphorylation and activation of the transcription factor (TF) IRF3 by TBK1. However, the role of the ZBP1-IRF3 axis in cancer is not known. Here we show that ZBP1 is selectively and constitutively expressed in late B cell development and it is required for optimal T cell-dependent humoral immune responses. In the plasma cell (PC) cancer multiple myeloma, interaction of constitutively expressed ZBP1 with TBK1 and IRF3 results in IRF3 phosphorylation. Notably, rather than IFN type I response genes, IRF3 directly activates, in part through co-operation with the PC lineage-defining TF IRF4, cell cycle genes thus promoting myeloma cell proliferation. This generates a novel, potentially therapeutically targetable and relatively selective myeloma cell addiction to the ZBP1-IRF3 axis. These data expand our knowledge of the role of cellular immune sensors in cancer biology.

cancer biology↗

bioRxiv2020

Analysis of biosynthesis and composition of cuticular wax in wild type bilberry (Vaccinium myrtillus L.) and its glossy mutant

Cuticular wax plays an important role in fruits in protection against environmental stresses and desiccation. In this study, biosynthesis and chemical composition of cuticular wax in wild type (WT) bilberry fruit was studied during development and compared with its natural glossy type (GT) mutant. The cuticular wax load in GT fruit was comparable to WT fruit. In both fruits, triterpenoids were the dominant wax compounds with decreasing proportion during the fruit development accompanied with increasing proportion of aliphatic compounds. Gene expression studies supported the pattern of compound accumulation during fruit development. Genes CER26-like, FAR2, CER3-like, LTP, MIXTA, and BAS exhibited prevalent expression in fruit skin indicating role in cuticular wax biosynthesis and secretion. In GT fruit, higher proportion of triterpenoids in cuticular wax was accompanied by lower proportion of fatty acids and ketones compared to WT fruit as well as lower density of crystalloid structures on berry surface. Our results suggest that a marked reduction in ketones in cuticular wax may play a significant role in the formation of glossy phenotype leading to the loss of rod-like structures in epicuticular wax layer of GT fruit. HighlightChemical composition and morphology of cuticular wax along with gene expression for wax biosynthetic genes varied between glossy type mutant (GT) and wild type (WT) fruit.

plant biology↗