Biology subjects

Kamble, N.

Publications and source records attributed to Kamble, N..

7 recordsLinked to original sources

bioRxiv2026

An Integrated Computational Approach to Predict and Characterize Emerging Mutations in the Japanese Encephalitis Virus Envelope Protein

Japanese encephalitis virus (JEV) causes significant encephalitis across the Asia-Pacific region. Current vaccines target historical genotype III strains, but emerging genotypes,potentially driven by vaccine-mediated selective pressure, threaten vaccine effectiveness through altered envelope protein sequences that may reduce antibody cross-neutralisation. This study employed integrated sequence and structural analyses to identify E protein mutations affecting neutralising antibody binding and protein stability. The study curated JEV polyprotein sequences from NCBI, performed multiple sequence alignment, and used Shannon entropy to pinpoint highly variable positions. Mutations occurring at [≥]1% frequency within high-entropy regions were selected for analysis. From 34 initially identified mutations, four candidates were prioritized based on structural stabilization potential. Mutations were evaluated through FoldX stability predictions, molecular docking with antibody 2H4 using HADDOCK3, and molecular dynamics simulations. Binding energies were calculated using MM-GBSA analysis. Results demonstrated that all mutant E-2H4 complexes remained stable during simulations, with root-mean-square deviation plateauing after equilibration and minimal localized changes in root-mean-square fluctuation. These findings suggest that EDIII substitutions represent important candidates for further investigation to understand genotype-specific variations and inform next-generation vaccine development strategies against emerging JEV strains.

bioinformatics↗

bioRxiv2026

LRRK2 I1371V Impairs Astrocytic Glucose Metabolism and Triggers Multi-Organellar Dysfunction in PD

While LRRK2 mutations modulate systemic glucose homeostasis and metabolic dysfunction precedes Parkinsons disease (PD) motor-symptoms, the impact of pathogenic LRRK2-mutations on astrocytic glucose-uptake and organellar function remains unexplored. Here, we demonstrate that LRRK2-I1371V mutation causes profound metabolic and organellar dysfunction in LRRK2-I1371V PD-iPSC-derived astrocytes and U87 cells overexpressing I1371V variant. LRRK2-I1371V astrocytes exhibit significantly reduced GLUT1 expression and plasma membrane localization, resulting in impaired glucose-uptake and decreased lactate-production. This metabolic insufficiency correlates with cascading mitochondrial dysfunction, characterized by membrane depolarization, elevated reactive-oxygen-species, enhanced ubiquitination and reduced proteasomal-activity. Reduced LAMP1/LAMP2 expression, impaired lysosomal-acidification, and selective cathepsin D deficiency were observed. Accumulation of undegraded cargo was confirmed by transmission-electron-microscopy upon -synuclein exposure. ER stress was evident through upregulated GADD34/CHOP, increased phospho-PERK, and reduced nascent protein synthesis. Our results reveal that LRRK2-I1371V induces glucose-uptake deficits, causing energy depletion and multi-organellar dysfunction, identifying astrocytic metabolic restoration as a promising therapeutic target for I1371V-associated PD.

neuroscience↗

bioRxiv2025

Modulating Cardiac-Gut Microbiome Interaction Post-Myocardial Infarction with Engineered Bacteria

The gut microbiome plays a critical role in the pathophysiology of acute myocardial infarction (MI). MI events significantly impact intestinal integrity which results in leakage of bacterial products into the systemic circulation. We demonstrate that MI not only compromises intestinal integrity, leading to systemic leakage of bacterial products like LPS, but also results in the translocation and colonization of live, intact gut bacteria in the MI heart - a novel aspect of the heart-gut axis. Our initial findings with natural murine gut microbiome were substantiated using orally administered E. coli Nissle 1917 (EcN), as a tracer bacterium. Furthermore, we engineered EcN to express the microbial anti-inflammatory molecule (MAM) derived from the probiotic Faecalibacterium prausnitzii. Treatment with this engineered strain, EcN-MAM, led to significantly improved survival and cardiac function in MI mice. This was attributed to enhanced gut barrier integrity, resulting in reduced systemic bacterial permeation and subsequent inflammation. These findings shed light on a previously unrecognized dimension of the heart-gut axis and highlight the potential of microbiome-based interventions in MI management.

synthetic biology↗

bioRxiv2022

Single session of rTMS enhances brain metastability and intrinsic ignition

BackgroundEmerging evidence support the view that brain stimulation might improve essential tremor (ET) by altering brain networks and facilitating plasticity. Yet, we are still missing a mechanistic explanation of the whole brain dynamics underlying these plasticity defining changes. MethodIn this study, we explored the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) over left primary motor cortex (L-M1) on functional connectivity dynamics (FCD) in patients with ET. Resting-state fMRI (RsfMRI) was acquired before and after a single session of rTMS in 30 patients with ET and compared with RsfMRI of 20 age and gender matched healthy controls (HCs). We have measured the effect of brain stimulation using network topological re-organization through whole brain integration and segregation, brain stability and capacity of neural propagation through metastability and intrinsic ignition. ResultsPatients with ET had altered FCD measures compared to controls. After a single session rTMS, the brain connectivity measures approached normality and patients with ET revealed significantly higher integration, lower segregation with higher metastability and increased intrinsic ignition. ConclusionBrain metastability and intrinsic ignition measures could be valuable tools in appreciating mechanisms of brain stimulation in ET and other neurological diseases.

neuroscience↗

bioRxiv2021

Fibrinogen and Complement Factor H are promising CSF protein biomarker(s) for Parkinson's disease with cognitive impairment- A Proteomics and ELISA based study

Cognitive impairment is a debilitating non-motor symptom of Parkinsons disease (PD). The diagnosis of PD with cognitive impairment (PDCI) is essentially through clinical and neuropsychological examinations. There is an emerging need to identify biomarker(s) to foresee cognitive decline in PD patients, at an early stage. We performed label-free unbiased nontargeted proteomics (Q-TOF LC/MS-MS) in CSF of non-neurological control (NNC); PDCI; PD and normal pressure hydrocephalus (NPH), followed by targeted ELISA for validation. The diagnosis was confirmed by neuropsychological and MRI assessments prior to CSF collection. Of the 282 proteins identified by mass spectrometry, 42 were differentially altered in PD, PDCI and NPH. Further, 28 proteins were altered in PDCI and 25 in NPH. An interesting overlap of certain proteins was noted both in PDCI and NPH. Five significantly upregulated proteins in PDCI were fibrinogen, gelsolin, complement factor-H, apolipoprotein A-IV and apolipoprotein A-I. Whereas carnosine dipeptidase 1, carboxypeptidase E, dickkpof 3 and secretogranin 3 precursor proteins were down-regulated. NPH also had few uniquely altered proteins viz. insulin-like growth factor-binding protein, ceruloplasmin, -1 antitrypsin, VGF nerve growth factor, neural cell adhesion molecule L1 like protein. Interestingly, the ELISA-derived protein concentrations correlated well with the neuropsychological scores of certain cognitive domains. Executive function was affected both in PDCI and NPH. In PD, Wisconsin card sorting test (WCST) percentile correlated positively with ApoA-IV and negatively with the ratio of ApoAI: ApoA-IV. Thus assessment of a battery of proteins like fibrinogen--chain, CFAH and ApoAI: ApoA-IV ratio alongside neuropsychological could be reliable biomarkers to distinguish PDCI and NPH.

neuroscience↗

bioRxiv2021

Distribution of Huntington's disease Haplogroups in Indian population

Huntingtons disease (HD), a rare neurodegenerative disorder, is inherited in an autosomal dominant manner, and caused by a pathological trinucleotide expansion at exon1 of the HTT locus. Previous studies have described the haplogroups at the HTT locus that can explain the differences in prevalence of HD. We have selected three informative SNPs (rs762855, rs3856973 and rs4690073) to study these haplogroups in an Indian sample. Our results show that the genotype frequencies are significantly different between cases and controls for these SNPs. More than 90% of both cases and controls belong to Haplogroup A which is the predominant European haplogroup.

neuroscience↗

bioRxiv2018

Targeted induction of de novo Fatty acid synthesis enhances MDV replication in a COX-2/PGE2 dependent mechanism through EP2 and EP4 receptors engagement

Many viruses alter de novo Fatty Acid (FA) synthesis pathway, which can increase availability of energy for replication and provide specific cellular substrates for particle assembly. Mareks disease virus (MDV) is a herpesvirus that causes deadly lymphoma and has been linked to alterations of lipid metabolism in MDV-infected chickens. However, the role of lipid metabolism in MDV replication is largely unknown. We demonstrate here that infection of primary chicken embryonic fibroblast with MDV activates de novo lipogenesis, which is required for virus replication. In contrast, activation of Fatty Acid Oxidation (FAO) reduced MDV titer, while inhibition of FAO moderately increased virus replication. Thus optimized virus replication occurs if synthetized fatty acids are not used for generation of energy in the infected cells, and they are likely converted to lipid compounds, which are important for virus replication. We showed that infection with MDV activates COX-2/PGE2 pathway and increases the biosynthesis of PGE2, a lipid mediator generated from arachidonic acid. Inhibition of COX-2 or PGE2 receptors, namely EP2 and EP4 receptors, reduced MDV titer, indicating that COX-2/PGE2 pathway are involved in virus replication. Our data show that the FA synthesis pathway inhibitors reduce COX-2 expression level and PGE2 synthesis in MDV infected cells, arguing that there is a direct link between virus-induced fatty acid synthesis and activation of COX-2/PGE2 pathway. This notion was confirmed by the results showing that PGE2 can restore MDV replication in the presence of the FA synthesis pathway inhibitors. Taken together, our data demonstrate that MDV uses FA synthesis pathway to enhance PGE2 synthesis and promote MDV replication through EP2 and EP4 receptors engagement.

microbiology↗