Biology subjects

Joshi, Y.

Publications and source records attributed to Joshi, Y..

5 recordsLinked to original sources

bioRxiv2024

Construction of an Immunoinformatics-Based Multi-Epitope Vaccine Candidate targeting Kyasanur Forest Disease Virus

Kyasanur Forest Disease (KFD) is one of the neglected tick-borne viral zoonoses. KFD virus was initially considered endemic to the Western Ghats region of Karnataka. Still, over the years, there have been reports of its spread to newer areas within and outside Karnataka. The absence of an effective treatment for KFD expedites the need for further research and development of novel vaccines. The present study was designed to develop a multi-epitope vaccine candidate against KFDV using immunoinformatic tools. After analyzing 74 complete KFDV genome sequences for genetic recombination and phylogeny, different prioritized B and T cell epitopes were combined using various linkers to construct the vaccine candidate. Docking analysis of the designed vaccine construct revealed a stable interaction with the TLR2-TLR6 receptor complex. After confirming the stability of the vaccine receptor complex, codon optimization was done to ensure the efficient translation of the designed multi-epitope vaccine in the prokaryotic host system, and the subsequent in-silico cloning into the pET30b(+) expression vector was carried out. Immunoinformatics analysis of the multi-epitope vaccine in the current study is satisfactory as it can significantly accelerate the initial stages of vaccine development by narrowing down potential vaccine candidates and providing insights into their design. Experimental validation of the potential multi-epitope vaccine candidate remains crucial to confirm effectiveness and safety in real-world conditions.

bioinformatics↗

bioRxiv2022

Genome characterization of monkeypox cases detected in India: Identification of three sub clusters among A.2 lineage

Since May 2022, Monkeypox, a zoonotic Orthopox DNA virus was reported in more than 102 countries indicating expansion of its geographic range. We analyzed the complete genomes sequences of Monkeypox cases from Kerala (n=5 travelled from UAE) and Delhi (n=5 no travel history), India confirmed during July to August 2022. All the retrieved MPXV sequences from India covering 90 to 99% genome belong to A.2 lineage of clade IIb. The A.2 MPXV lineage divided in three sub clusters; first cluster Kerala n=5, Delhi n=2 aligned with the USA-2022 ON674051.1; while second of Delhi n=3 aligned with USA-2022 ON675438.1 and third consists of the UK, USA and Thailand. Recent update in MPXV lineage designated all the five sequences from Kerala as A.2.1. In addition to known 16 single nucleotide polymorphisms (SNPs) along with 13 APOBEC3 cytosine deaminase activity determined specific lineage defining mutations in A.2 lineage, 25 additional APOBEC3 mutations were found in 10 reported sequences. The study emphasizes need of enhancing genomic surveillance to understand the mutation and its linkage.

microbiology↗

bioRxiv2022

An in vitro and in vivo approach for the isolation of Omicron variant from human clinical specimens

Due to failure of virus isolation of Omicron variant in Vero CCL-81 from the clinical specimens of COVID-19 cases, we infected Syrian hamsters and then passage into Vero CCL-81 cells. The Omicron sequences were studied to assess if hamster could incorporate any mutation to changes its susceptibility. L212C mutation, Tyrosine 69 deletion, and C25000T nucleotide change in spike gene and absence of V17I mutation in E gene was observed in sequences of hamster passage unlike human clinical specimen and Vero CCL-81 passages. No change was observed in the furin cleavage site in any of the specimen sequence which suggests usefulness of these isolates in future studies.

microbiology↗

bioRxiv2020

Neural network dynamics underlying gamma synchronization deficits in schizophrenia

Gamma band (40-Hz) activity is associated with many sensory and cognitive functions, and is critical for cortico-cortical transmission and the integration of information across neural networks. The capacity to support gamma band activity can be indexed by the auditory steady-state response (ASSR); schizophrenia patients have selectively reduced synchrony to 40-Hz stimulation. While 40-Hz ASSR is a translatable electroencephalographic biomarker with emerging utility for therapeutic development for neuropsychiatric disorders, the spatiotemporal dynamics underlying the ASSR have not yet been characterized. In this study, a novel Granger causality analysis was applied to assess the propagation of gamma oscillations in response to 40-Hz steady-state stimulation across cortical sources in schizophrenia patients (n=426) and healthy comparison subjects (n=293). Results revealed distinct, hierarchically sequenced temporal and spatial response dynamics underlying gamma synchronization deficits in patients. During the response onset interval, patients exhibited abnormal connectivity of superior temporal and frontal gyri, followed by decreased information flow from superior temporal to middle cingulate gyrus. In the later (300-500 ms) interval of the ASSR response, patients showed significantly increased connectivity from superior temporal to middle frontal gyrus followed by broad failures to engage multiple prefrontal brain regions. In conclusion, these findings reveal the rapid disorganization of neural circuit functioning in response to simple gamma-frequency stimulation in schizophrenia patients. Deficits in the generation and maintenance of gamma-band oscillations in schizophrenia reflect a fundamental connectivity abnormality across a distributed network of temporo-frontal networks.

physiology↗

bioRxiv2020

VGLUT3-p.A211V variant fuses stereocilia bundle and elongates synaptic ribbons in the human deafness DFNA25

DFNA25 is an autosomal-dominant and progressive form of human deafness caused by mutations in the SLC17A8 gene, which encodes the vesicular glutamate transporter type 3 (VGLUT3). To resolve the mechanisms underlying DFNA25, we studied the phenotype of the mouse harboring the p.A221V mutation in human (corresponding to p.A224V in mouse). Using auditory brainstem response and distortion products of otoacoustic emissions, we showed that VGLUT3A224V/A224V mouse replicates the DFNA25 progressive hearing loss with intact cochlear amplification. Scanning electron microscopy examinations demonstrated fused stereocilia bundle of the inner hair cells (IHCs) as the primary cause for DFNA25. In addition, the IHC ribbon synapses undergo structural and functional modifications at later stages. Using super-resolution microscopy, we observed oversized synaptic ribbons associated with an increase in the rate of the sustained releasable pool of exocytosis. These results indicate that the primary defect in DFNA25 stems from a failure in the mechano-transduction followed by a change in synaptic transfer. The VGLUT3A224V/A224V mouse model opens the way to a deeper understanding and to a potential treatment of DFNA25.

neuroscience↗