Biology subjects

Barua, R.

Publications and source records attributed to Barua, R..

4 recordsLinked to original sources

bioRxiv2026

NgBR controls hepatic adiponectin signaling competence through KAT7-dependent chromatin regulation

Adiponectin signaling is essential for hepatic glucose homeostasis, yet the molecular basis of adiponectin receptor responsiveness remains incompletely understood. Here, we identify the Nogo-B receptor (NgBR; NUS1) as a regulator of hepatic adiponectin sensitivity. Across human, cynomolgus monkey, and mouse datasets, hepatic NgBR expression is consistently reduced in obesity-associated diabetes, indicating a conserved metabolic signature. Hepatocyte-specific NgBR deletion abolishes the metabolic effects of the adiponectin agonist AdipoRon, resulting in impaired AMPK activation, persistent gluconeogenesis, and ceramide accumulation. Mechanistically, NgBR loss suppresses KAT7 expression and reduces histone acetylation at AdipoR1 and AdipoR2 promoters, thereby limiting receptor expression. Adeno-associated virus (AAV)-mediated restoration of hepatic NgBR reinstates KAT7-dependent chromatin activation, adiponectin receptor expression, and glucose homeostasis. These findings support a hepatocellular mechanism in which NgBR maintains adiponectin receptor competence and suggest a potential therapeutic strategy for restoring adiponectin responsiveness in metabolic disease. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=115 SRC="FIGDIR/small/726643v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@117fa66org.highwire.dtl.DTLVardef@1385297org.highwire.dtl.DTLVardef@b64369org.highwire.dtl.DTLVardef@3dd55_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2024

FerroEnrich: An Interactive web tool for computing Ferroptosis index and gene enrichment.

Ferroptosis is an iron-dependent form of controlled cell death and is characterized by the formation of lipid peroxides. Understanding gene expressions associated with ferroptosis is critical for determining its function in illnesses and potential therapeutic approaches. Despite its significance, no computational model is currently available to accurately quantify the ferroptosis incident. FerroEnrich is a sophisticated web-based tool built using R Shiny application to enumerate the occurrence of ferroptosis based on the relevant gene expressions. This tool available at https://ferroenrich.shinyapps.io/ferroenrich/ processes the input gene expression file to identify genes that are resistant or prone to ferroptosis, calculates ferroptosis index value with dynamic colored heatmap and gene network plot. This manuscript describes the design, operation and usability of FerroEnrich, including examples and a discussion of its potential impact on ferroptosis research. FerroEnrich is a vital tool for researchers, allowing them to explore and analyze complicated gene expression data related to ferroptosis.

bioinformatics↗

bioRxiv2022

The association between transcriptional regulation of macrophage differentiation and activation and genetic susceptibility to inflammatory bowel disease

The abundant macrophage population of the intestinal lamina propria turns over rapidly and is replaced by blood monocytes. The differentiation and survival of resident intestinal macrophages depends upon signals from the macrophage colony-stimulating factor receptor (CSF1R). The response of human monocyte-derived macrophages (MDM) grown in macrophage colony-stimulating factor (CSF1) to bacterial lipopolysaccharide (LPS) has been proposed as a model for the differentiation and adaptation of monocytes entering the intestinal lamina propria. We hypothesized that dysregulation of this response leads to susceptibility to chronic inflammatory bowel disease (IBD). To address this hypothesis we analyzed transcriptomic variation in MDM from affected and unaffected sib pairs/trios from 22 IBD families and 6 healthy controls. There was no overall or inter-sib distinction between affected and unaffected individuals in basal gene expression or the stereotypical time course of the response to LPS. However, the basal or LPS-inducible expression of individual genes including inflammatory cytokines and many associated with IBD susceptibility in genome-wide association studies (GWAS) varied by as much as 100-fold between subjects. Extreme independent variation in the expression of pairs of HLA-associated transcripts (HLA-B/C, HLA-A/F and HLA-DRB1/DRB5) was associated with HLA genotype providing a novel explanation for the HLA association with disease susceptibility. The relationship between single nucleotide variant (SNV) genotype and gene expression at other loci was weaker and inconsistent suggesting that much of the variation arises from the integration of multiple trans-acting effects. For example, expression of IL1B at 2 hrs of LPS treatment was significantly associated with local SNV genotype and with peak expression of IL23A at 7 hrs. By contrast, there was no evidence of association between peak IL6 mRNA at 7hrs, IL6-associated SNV genotype or IL1B at 2 hrs. Our results support the view that gene-specific dysregulation in macrophage adaptation to the intestinal milieu provides a plausible explanation for genetic susceptibility to IBD. The analysis also suggests that the molecular basis of susceptibility is unique to each individual which may contribute to variation in the precise environmental trigger, the consequent pathology and response to treatment. Author summaryCells of the innate immune system called macrophages are abundant in the wall of the gut, providing a first line of defense against potential pathogens. These cells must also avoid an inappropriate or excessive response to the abundant microbial population (the microbiome) of the intestine. We have previously proposed that genetic differences between individuals in macrophage adaptation to the unique environment of the intestine underlie genetic susceptibility to inflammatory bowel disease (IBD). In this study we developed a model of the adaptation of macrophages and used that model to identify surprisingly extreme variation in the response amongst a cohort of affected and unaffected siblings in families with IBD. The response did not distinguish affected individuals from their unaffected siblings. Our results support the view that each individual within IBD-susceptible families carries a unique set of genetic variants of large effect that together predispose to uncontrolled gut inflammation in the face of an environmental trigger.

genetics↗

bioRxiv2020

Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: a computational biology approach

The newly identified SARS-CoV-2 has now been reported from around 183 countries with more than a million confirmed human cases including more than 68000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins have gotten substantial attention recently. Spike glycoprotein is widely considered as a possible target to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment tools. In this study, 483 unique variations have been identified among the genomes including 25 non-synonymous mutations and one deletion in the spike protein of SARS-CoV-2. Among the 26 variations detected, 12 variations were located at the N-terminal domain and 6 variations at the receptor-binding domain (RBD) which might alter the interaction with receptor molecules. In addition, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on our findings, potential inhibitors can be designed and tested targeting these proposed sites of variation.

bioinformatics↗