Biology subjects

Guleria, R.

Publications and source records attributed to Guleria, R..

4 recordsLinked to original sources

bioRxiv2024

Correlating amino acid profiles with improved expression capability of superior CHO based expression platforms

A novel modified CHO cell line was constructed by expressing a three gene combination of Bclx(L), Aven and BECN1 which are critical targets of the apoptosis and autophagy pathways. This synergistic combination significantly improved cell viability as well as Rituximab (RTX) expression by 7.5 fold. A comparative amino acid analysis of the modified and control cultures both with and without RTX expression showed interesting changes in amino acid uptake rates. We first compared the utilization of amino acids in the control cells without RTX expression to the control cells with RTX expression where it declined significantly in the later half of the culture with the maximum decrease observed with tyrosine, which instead of uptake got secreted into the medium. The uptake of aspartic and glutamic acid also fell drastically during this period demonstrating the deleterious effect of RTX expression on cellular health. When the modified cells were used for RTX expression, there was conversely a slight increase in amino acid consumption in the later part of the culture with the maximum increase observed with alanine and tyrosine. The differential amino acid consumption rates provided us with an indirect measure of improved cellular health and ability of the modified cells to counter the cellular stress associated with RTX expression. Amino acid analysis could thus become a useful predictive tool to identify the critical features of better host expression platforms.

bioengineering↗

bioRxiv2022

SARS-CoV-2 Omicron Variant Wave in India: Advent, Phylogeny and Evolution

SARS-CoV-2 evolution has continued to generate variants, responsible for new pandemic waves locally and globally. Varying disease presentation and severity has been ascribed to inherent variant characteristics and vaccine immunity. This study analyzed genomic data from 305 whole genome sequences from SARS-CoV-2 patients before and through the third wave in India. Delta variant was responsible for disease in patients without comorbidity(97%), while Omicron BA.2 caused disease primarily in those with comorbidity(77%). Tissue adaptation studies brought forth higher propensity of Omicron variants to bronchial tissue than lung, contrary to observation in Delta variants from Delhi. Study of codon usage pattern distinguished the prevalent variants, clustering them separately, Omicron BA.2 isolated in February grouped away from December strains, and all BA.2 after December acquired a new mutation S959P in ORF1b (44.3% of BA.2 in the study) indicating ongoing evolution. Loss of critical spike mutations in Omicron BA.2 and gain of immune evasion mutations including G142D, reported in Delta but absent in BA.1, and S371F instead of S371L in BA.1 could possibly be due to evolutionary trade-off and explain very brief period of BA.1 in December 2021, followed by complete replacement by BA.2.

genomics↗

bioRxiv2021

Molecular signature of postmortem lung tissue from COVID-19 patients suggests distinct trajectories driving mortality

The precise molecular mechanisms behind life-threatening lung abnormalities during severe SARS-CoV-2 infections are still unclear. To address this challenge, we performed whole transcriptome sequencing of lung autopsies from 31 patients suffering from severe COVID-19 related complications and 10 uninfected controls. Using a metatranscriptome analysis of lung tissue samples we identified the existence of two distinct molecular signatures of lethal COVID-19. The dominant "classical" signature (n=23) showed upregulation of unfolded protein response, steroid biosynthesis and complement activation supported by massive metabolic reprogramming leading to characteristic lung damage. The rarer signature (n=8) potentially representing "Cytokine Release Syndrome" (CRS) showed upregulation of cytokines such IL1 and CCL19 but absence of complement activation and muted inflammation. Further, dissecting expression of individual genes within enriched pathways for patient signature suggests heterogeneity in host response to the primary infection. We found that the majority of patients cleared the SARS-CoV-2 infection, but all suffered from acute dysbiosis with characteristic enrichment of opportunistic pathogens such as Staphylococcus cohnii in "classical" patients and Pasteurella multocida in CRS patients. Our results suggest two distinct models of lung pathology in severe COVID-19 patients that can be identified through the status of the complement activation, presence of specific cytokines and characteristic microbiome. This information can be used to design personalized therapy to treat COVID-19 related complications corresponding to patient signature such as using the identified drug molecules or mitigating specific secondary infections.

molecular biology↗

bioRxiv2020

Association of IRS1 (Gly972Arg) and IRS2 (Gly1057Asp) genes polymorphisms with OSA and NAFLD in Asian Indians.

Aim and ObjectiveThe aim of the study was to investigate the relationships between insulin receptor substrate (IRS) 1 (Gly972Arg) and IRS2 (Gly1057Asp) genes with obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) in Asian Indians. MethodA total of 410 overweight/obese subjects (130 with OSA with NAFLD, 100 with OSA without NAFLD, 95 without OSA and with NAFLD and 85 without OSA and without NAFLD) were recruited. Degree of NAFLD was based on liver ultrasound and of OSA on overnight polysomnography. ResultIn IRS1 gene, the genotype frequency (%) of Arg/Arg was significantly higher in NAFLD and OSA subjects. In addition, Gly/Arg genotype of IRS1 gene was associated with significantly higher body mass index, fat mass, %body fat, triglycerides, cholesterol, alkaline phosphate, aspartate transaminase, fasting insulin and HOMA-IR levels in OSA and NAFLD subjects. No significant difference in genotype frequencies of IRS2 was observed between four groups. Further we found that subjects carrying IRS1 Gly/Arg (OR 4.49, 95% C.I. 1.06-12.52, p=0.002) genotype possess a much higher risk of OSA and NAFLD compared to IRS2 Gly/Asp (OR 1.01, 95% C.I. 0.8-2.56, p=0.05). ConclusionWe concluded that Asian Indian subject carrying the allele Gly972Arg polymorphism of IRS1 is predisposed to develop OSA and NAFLD.

biochemistry↗