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Biology subjects

Surendran, V.

Publications and source records attributed to Surendran, V..

3 recordsLinked to original sources

Senataxin is required for optimal class switch recombination to the immunoglobulin A isotype

Senataxin (SETX) is an RNA/DNA helicase that plays a pivotal role in transcription, R-loop resolution, and the DNA damage response (DDR). Dysfunction of SETX, however, has been implicated in neurodegenerative diseases, including amyotrophic lateral sclerosis and ataxia with oculomotor apraxia type 2. Importantly, both R-loop resolution and the DDR are essential for class switch recombination (CSR) in B cells, a critical step in generating antibody diversity. Here we demonstrate that ex vivo polyclonal stimulation of SETX+/+ and SETX-/- mouse splenocytes results in equivalent amounts of IgM- and IgG-secreting B cells but significantly fewer IgA-producing B cells in SETX-/- mice. Additionally, SETX-/- mice generate significantly reduced antigen specific IgA titers following infection with influenza A virus. Sequencing of the IgA-secreting B cell repertoire revealed reduced clonal diversity in SETX-/- mice. SETX-/- mice also had increased R-loop formation within the IgA locus. Collectively, these data highlight an important role for SETX in mediating CSR to IgA. As such, a further understanding of SETXs role in the immune response is important for expanding our knowledge of both the general immunobiology relating to CSR as well as the immunological phenotypes associated with neurodegenerative diseases associate with mutations in SETX. One sentence summaryA deficiency in senataxin results in impaired class switching to IgA in vitro with decreased IgA response to infection and IgA repertoire diversity in vivo.

immunology↗

Mycelium Biocomposites from Agricultural and Paper waste: Sustainable alternative to plastic foam based secondary packaging

Plastic foams, which were once lauded as a breakthrough invention in packaging and insulation industries, have gradually evolved into a global problem and are more concerning in developing nations because of ineffective waste management systems. The convenience and pervasiveness of these come at a high cost with adverse effects on human health and our planets ecosystems as they are not biodegradable. It is pivotal that an alternative and sustainable solution is found to address this problem. Mycelium-based biocomposites, made up of root-like networks called hyphae are sought out as a potential substitute for plastic-based foams as they are biodegradable. They employ a waste-to-value strategy by using agricultural wastes as a growing media for the mycelium. The study primarily focuses on the comparative analysis of mycelium-based biocomposites with existing foam materials such as Expanded PolyStyrene (EPS) and evaluates their efficacy as a biodegradable packaging material. Thus, we plan to identify the efficacious strain of mycelium from Pleurotus ostreatus or Ganoderma lucidum and also explore various substrate materials such as cocopith, cardboard, paper, and sawdust. Our preliminary compression results show that the biocomposites can be engineered to have Youngs modulus ranging from 1-3 MPa for both strains. These results show that mycelium-based biocomposites can be a promising alternative to EPS /Styrofoam and move towards a sustainable solution that can reduce the dependence on non-biodegradable foam-based materials in developing nations like India.

bioengineering↗

Acute Viral Infection Accelerates Neurodegeneration in a Mouse Model of ALS

While several viral infections have been associated with amyotrophic lateral sclerosis (ALS), the mechanism(s) through which they promote disease has remained almost entirely elusive. This study investigated the impact of common, acute viral infections prior to disease onset on ALS progression in the SOD1G93A mouse model. A single sublethal infection prior to onset of ALS clinical signs was associated with markedly accelerated ALS disease progression characterized by rapid loss of hindlimb function. Prior infection resulted in gliosis in the lumbar spine and upregulation of transcriptional pathways involved in inflammatory responses, metabolic dysregulation, and muscular dysfunction. Therapeutic suppression of gliosis with an anti-inflammatory small molecule, or administration of a direct-acting antiviral, was associated with significantly improved ALS clinical signs, akin to what was observed in uninfected animals. This study provides causal and mechanistic evidence that the immune response elicited by acute viral infections may be an important etiological factor that alters ALS disease trajectory, and provides insight into novel therapeutic and preventative strategies for ALS. One Sentence SummaryAcute viral infection with influenza A virus and SARS-CoV-2 accelerates the progression of ALS in SOD1G93A mice.

immunology↗