Biology subjects

Choudhury, S.

Publications and source records attributed to Choudhury, S..

40 records · Page 3Linked to original sources

bioRxiv2020

SARS-CoV-2 transcriptome analysis and molecular cataloguing of immunodominant epitopes for multi-epitope based vaccine design

SARS-CoV-2 is a single-stranded RNA virus that has caused more than 0.29 million deaths worldwide as of May 2020, and influence of COVID-19 pandemic is increasing continuously in the absence of approved vaccine and drug. Moreover, very limited information is available about SARS-CoV-2 expressed regions and immune responses. In this paper an effort has been made, to facilitate vaccine development by proposing multiple epitopes as potential vaccine candidates by utilising SARS-CoV-2 transcriptome data. Here, publicly available RNA-seq data of SARS-CoV-2 infection in NHBE and A549 human cell lines were used to construct SARS-CoV-2 transcriptome to understand disease pathogenesis and immune responses. In the first step, epitope prediction, MHC class I and II gene identification for epitopes, population coverage, antigenicity, immunogenicity, conservation and crossreactivity analysis with host antigens were performed by using SARS-CoV-2 transcriptome, and in the second step, structural compatibility of identified T-and B-cell epitopes were evaluated with MHC molecules and B-cell receptors through molecular docking studies. Quantification of MHC gene expression was also performed that indicated high variation in allele types and expression level of MHC genes with respect to cell lines. In A549 cell line, HLA-A*30:01:01:01 and HLA-B*44:03:01:01 were highly expressed, whereas 92 variants of HLA-A*24 genes such as HLA-A*24:02:01:01, HLA-A*24:286, HLA-A*24:479Q, HLA-A*24:02:134 and HLA-A*24:02:116 were highly expressed in NHBE cell lines. Prevalence of HLA-A*24 alleles was suggested as risk factors for H1N1 infection, and associated with type-1 diabetes. HLA-C*03:03, linked with male infertility factors was also highly expressed in SARS-CoV-2 infected NHBE cell lines. Finally, three potential T-cell and five B-cell epitopes were selected for molecular docking studies with twenty-two MHC molecules and two B-cell receptors respectively. The results of in silico analysis indicated that proposed epitopes have high potential to recognize immune response of SARS-CoV-2 infection. This study will facilitate in vitro and in vivo vaccine related research studies.

bioinformatics↗

bioRxiv2019

Control of cytokinesis by β-adrenergic receptors indicates an approach for regulating cardiomyocyte endowment

ABSTRACT/SUMMARYOne million patients with congenital heart disease (CHD) live in the US. They have a lifelong risk of developing heart failure. Current concepts do not sufficiently address mechanisms of heart failure development specifically for these patients. We show that cardiomyocyte cytokinesis failure is increased in tetralogy of Fallot with pulmonary stenosis (ToF/PS), a common form of CHD. Labeling of a ToF/PS baby with isotope-tagged thymidine showed cytokinesis failure after birth. We used single-cell transcriptional profiling to discover that the underlying mechanism is repression of the cytokinesis gene ECT2, and show that this is downstream of {beta}-adrenergic receptors ({beta}-AR). Inactivation of the {beta}-AR genes and administration of the {beta}-blocker propranolol increased cardiomyocyte division in neonatal mice, which increased the endowment and conferred benefit after myocardial infarction in adults. Propranolol enabled the division of ToF/PS cardiomyocytes. These results suggest that {beta}-blockers should be evaluated for increasing cardiomyocyte division in patients with ToF/PS and other types of CHD.

cell biology↗

bioRxiv2019

Host-Microbial Interactions in Systemic Lupus Erythematosus and Periodontitis

Systemic lupus erythematosus (SLE) is a potentially fatal complex autoimmune disease, that is characterized by widespread inflammation manifesting tissue damage and comorbidities across the human body including heart, blood vessels, joints, skin, liver, kidneys, and periodontal tissues. The etiology of SLE is partially attributed to a deregulated inflammatory response to microbial dysbiosis and environmental changes. In the mouth, periodontal environment provides an optimal niche to assay local dynamic microbial ecological changes in health and disease important to systemic inflammation in SLE subjects. Our aim was to evaluate the reciprocal impact of periodontal subgingival microbiota on SLE systemic inflammation. Ninety-one female subjects were recruited, including healthy (n=31), SLE-inactive (n=29), and SLE-active (n=31). Patients were screened for probing depth (PD), bleeding on probing (BOP), clinical attachment level (CAL), and classified with or without periodontal dysbiosis, periodontitis. Serum inflammatory cytokines were measured by human cytokine panel and subgingival biofilm was examined by DNA-DNA checkerboard. The results showed significant upregulation of proinflammatory cytokines in individuals with SLE when compared to controls. Stratification of subjects into SLE-inactive (I) and SLE-active (A) phenotypes or periodontitis and non-periodontitis groups provided new insights into SLE pathophysiology. While low-grade inflammation was found in SLE-I subjects, a potent anti-inflammatory cytokine, IL-10 was found to control clinical phenotypes. Out of twenty-four significant differential oral microbial abundances found in SLE, fourteen unique subgingival bacteria profiles were found to be elevated in SLE. Pathogens from periodontal disease sites (Treponema denticola and Tannerella forsythia) showed increase abundance in SLE-A subjects when compared to controls. Cytokine-microbial correlations showed that periodontal pathogens dominating the environment increased proinflammatory cytokines systemically. Deeper clinical attachment loss and periodontal pathogens were found in SLE subjects, especially on SLE-I, likely due to long-term chronic and low-grade inflammation. Altogether, local periodontal pathogen enrichment was positively associated with high systemic inflammatory profiles, relevant to the overall health and SLE disease pathogenesis.

immunology↗

bioRxiv2019

Non-linear effects of socioeconomic status on brain development: associations between parental occupation, cortical thickness and language skills in childhood and adolescence

Studies have pointed to the role of the brain in mediating the effects of the social environment of the developing child on life outcomes. Since brain development involves nonlinear trajectories, these effects of the childs social context will likely have age-related differential associations with the brain. However, there is still a dearth of integrative research investigating the interplay between neurodevelopmental trajectories, social milieu and life outcomes. We set out to fill this gap, focusing specifically on the role of socioeconomic status, SES (indexed by parental occupation) on brain and cognitive development by analyzing MRI scans from 757 typically-developing subjects (age = 3-21 years). We observed nonlinear interaction of age and SES on cortical thickness, specifically a significant positive association between SES and thickness around 9-13 years at several cortical regions. Using a moderated mediation model, we observed that cortical thickness mediated the link between SES and language abilities, and this mediation was moderated by age in a quadratic pattern, indicating a pronounced SES-effect during early adolescence. Our results, drawn from cross-sectional data, provide a basis for further longitudinal studies to test whether early adolescence may be a sensitive time window for the impact of SES on brain and cognitive development.

neuroscience↗