Biology subjects

Subramani, J.

Publications and source records attributed to Subramani, J..

3 recordsLinked to original sources

bioRxiv2024

Combined analysis of somatic mutations and gene expression reveals nuclear speckles-associated enhanced stemness in gingivobuccal carcinoma under DNA damage response

Smokeless tobacco chewing habits in India lead to a high prevalence of Gingivobuccal oral squamous cell carcinoma (OSCC-GB). Cancer stem cells (CSCs) are a sub-population of cancer cells within a tumor with stem-like properties and are believed to contribute to tumor initiation, progression, increased resistance to drug therapy, and promote post-therapeutic cancer relapse. An RNA-seq data-based integrative analysis of somatic mutation and gene expression was performed to explore the role of CSCs in disease progression using the novel Indian-origin OSCC-GB cell line IIOC019 from a patient with tobacco-chewing habit. The identified DNA damage-related known mutational signature (ID1, SBS5) indicates the impact of smokeless tobacco-related carcinogens in the IIOC019 cell line. The differentially expressed somatic variants, functional impact predictions, and survival analysis reveal the role of DNA damage response (DDR)-related genes in OSCC-GB, with the SON gene as a significant player. The study suggests that the loss of function in a somatic variant of the SON gene is associated with enhanced stemness and increased risk of disease progression in OSCC-GB under DDR conditions. The newly identified CSC-associated somatic variants appear to promote cancer spread, local recurrence, and resistance to chemotherapy or radiotherapy, contributing to the high mortality rates among Indian OSCC-GB patients.

genomics↗

bioRxiv2021

Protein-based RBD-C-tag COVID-19 Vaccination Candidate Elicits Protection Activity against SARS-COV-2 Variant Infection

The identification of a vaccination candidate against COVID-19 providing protecting activity against emerging SARS-COV-2 variants remains challenging. Here, we report protection activity against a spectrum of SARS-COV-2 and variants by immunization with protein-based recombinant RBD-C-tag administered with aluminum-phosphate adjuvant intramuscularly. Immunization of C57BL/6 mice with RBD-C-tag resulted in the in vivo production of IgG antibodies recognizing the immune-critical spike protein of the SARS-COV-2 virus as well as the SARS-COV-2 variants alpha ("United Kingdom"), beta ("South Africa"), gamma ("Brazil/Japan"), and delta ("India") as well as wt-spike protein. RBD-C-tag immunization led to a desired Th1 polarization of CD4 T cells producing IFN{gamma}. Importantly, RBD-C-tag immunization educated IgG production delivers antibodies that exert neutralizing activity against the highly transmissible SARS-COV-2 virus strains "Washington", "South Africa" (beta), and "India" (delta) as determined by conservative infection protection experiments in vitro. Hence, the protein-based recombinant RBD-C-tag is considered a promising vaccination candidate against COVID-19 and a broad range of emerging SARS-COV-2 virus variants.

microbiology↗

bioRxiv2020

Detection of M-Protein in Acetonitrile Precipitates of Serum using MALDI-TOF Mass Spectrometry

Purpose of the researchMultiple myeloma and plasmacytomas belong to a group of disorders, namely plasma cell dyscrasias and are identified by the presence of a monoclonal protein (M-protein). MALDI-TOF-mass spectrometry (MS) has demonstrated superior analytical sensitivity for the detection of M-protein and is now used for screening of M-protein at some centres. We present the results of an alternative methodology for M-protein analysis by MALDI-TOF MS. MethodsSerum samples from patients with newly diagnosed multiple myeloma or plasmacytoma with positive M-protein detected by serum protein electrophoresis, immunofixation electrophoresis and serum free light chain analysis, underwent direct reagent-based extraction process using Acetonitrile (ACN) precipitation. Serum{kappa} and{lambda} light chains were validated using immunoenrichment by anti-{kappa} and anti-{lambda} biotin-labelled antibodies immobilised on streptavidin magnetic beads. MALDI-TOF MS measurements were obtained for intact proteins using alpha-cyano-4-hydroxycinnamic acid as matrix. The images obtained were overlaid on apparently healthy donor serum samples to confirm the presence of M-protein. Principle resultsCharacteristic M-protein peaks were observed in the ACN precipitates of serum in the predicted mass ranges for{kappa} and{lambda} . The{kappa} and{lambda} peaks were confirmed by immunoenrichment analysis. Twenty-seven patient samples with either newly diagnosed multiple myeloma or plasmacytoma with monoclonal gammopathy detected by the standard methods were chosen for Acetonitrile precipitation and analysed by MALDI-TOF MS. All 27 patient samples demonstrated a peak suggestive of M-protein with mass/charge (m/z) falling within the{kappa} and{lambda} range. The concordance rate with serum immunofixation electrophoresis and free light chain analysis was above 90%. Major conclusionsWe report the results of a low-cost reagent-based extraction process using Acetonitrile precipitation to enrich for{kappa} and{lambda} light chains, which can be used for the screening and qualitative analysis of M-protein.

biochemistry↗