Biology subjects

Kumar, J. S.

Publications and source records attributed to Kumar, J. S..

3 recordsLinked to original sources

bioRxiv2022

Understanding Lesion Progression in a Chronic Model of Cerebral Cavernous Malformations through Combined MRI and Histology

Cerebral cavernous malformations (CCM), also known as cavernous angiomas, are blood vessel abnormalities comprised of clusters of grossly enlarged and hemorrhage-prone capillaries. The prevalence in the general population, including asymptomatic cases, is estimated to be 0.5%. Some patients develop severe symptoms, including seizures and focal neurologic deficits, while others have no symptoms. The causes of this remarkable presentation heterogeneity within a primarily monogenic disease remain poorly understood. To address this problem, we have established a chronic mouse model of CCM, induced by postnatal ablation of Krit1 with Pdgfb-CreERT. These mice develop CCM lesions gradually over 4-6 months of age throughout of the brain. We examined lesion progression in these mice with T2-weighted 7T MRI protocols. Precise volumetric analysis of individual lesions revealed non-monotonous behavior, with some lesions temporarily growing smaller. However, the cumulative lesional volume invariably increased over time and accelerated after about 3 months. Next, we established a modified protocol for dynamic contrast enhanced (DCE) MR imaging and produced quantitative maps of gadolinium tracer MultiHance in the lesions, indicating a high degree of heterogeneity in lesional permeability. Multivariate comparisons of MRI properties of the lesions with cellular markers for endothelial cells, astrocytes, and microglia revealed that increased cell density surrounding lesions correlates with stability, while increased vasculature within and surrounding lesions may correlate with instability. Our results lay a foundation for better understanding individual lesion properties and provide a comprehensive pre-clinical platform for testing new drug and gene therapies for controlling CCM.

neuroscience↗

bioRxiv2020

Emergence and expansion of highly infectious spike:D614G mutant SARS-CoV-2 in central India

COVID 19 has emerged as global pandemic with largest damage to the economy and human psyche. The genomic signature deciphered during the ongoing pandemic period is valuable to understand the virus evolutionary patterns and spread across the globe. Increased availability of genome information of circulating strain in our country will enable to generate selective details in virulent and non virulent markers to prophylaxis and therapeutic interventions. The first case of SARS CoV-2 was detected in Chambal region of Madhya Pradesh state in mid of March 2020 followed by multiple introduction events and expansion of COVID-19 cases within 3 months in this region. We analyzed around 5000 COVID -19 suspected samples referred to Defence Research and Development Establishment, Gwalior, Madhya Pradesh. A total of 136 cases were found positive over a span of three months period this includes virus introduction to region and further spread. Whole genome sequences employing Oxford nanopore technology were deciphered for 26 SARS-CoV-2 circulating in 10 different districts in Madhya Pradesh State of India. The region witnessed index cases with multiple travel history responsible for introduction of COVID-19 followed by remarkable expansion of virus. The genome wide substitutions including in important viral proteins were observed. The detailed phylogenetic analysis revealed the circulating SARS-CoV-2 clustered in multiple clades A2a, A4 and B. The cluster wise segregation was observed suggesting multiple introduction links and evolution of virus in the region. This is the first comprehensive details of whole genome sequence analysis from central India region, which will add genome wide knowledge towards diagnostic and therapeutic interventions.

molecular biology↗

bioRxiv2019

Next-Gen sequencing of novel pandemic swine flu virus in India revealed novel mutations across the genome

The Influenza A H1N1 virus of 2009 was the first pandemic flu virus of the 21st century. Identifying the emergence of mutations in rapidly mutating Influenza viruses that allow increased transmission or confer resistance are invaluable to global outbreak response. Here we recovered 5 complete Influenza A genomes from 4 oropharygeal swabs and one cell culture isolate from a severe Indian outbreak of flu in early 2015. Multiple amino acids substitutions including those known to confer resistance to Oseltamivir and increased pathogenecity in mice were found in the Neuraminidase gene. Additional mutations both reported and novel were found throughout the genome compared to the vaccine strain (California/04/2009). All eight segments of the complete genomes were found to be genetically related to the 2009 pandemic strain, A(H1N1)pdm09 and belonging to the emerging genogroup 6B. This group was found to be of south East Asian origin by time scale phylogentic analysis. A phylogeographic analysis revealed 39 significant migration events among globally circulating viruses. This study is the first extensive complete genome and phylogeographic analysis of 2015 Indian A(H1N1) pdm09 viruses. We report several novel mutations in the 2015 Indian strains which need to be evaluated for effect on viral replication, transmission and resistance to therapy. The identification of mutant A(H1N1)pdm09 from India warrants continuous monitoring of viral evolution for implementation of suitable medical countermeasures.

genomics↗