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Biology subjects

Sarin, A.

Publications and source records attributed to Sarin, A..

2 recordsLinked to original sources

PAN-INDIA 1000 SARS-CoV-2 RNA Genome Sequencing Reveals Important Insights into the Outbreak

The PAN-INDIA 1000 SARS-CoV-2 RNA Genome Sequencing Consortium has achieved its initial goal of completing the sequencing of 1000 SARS-CoV-2 genomes from nasopharyngeal and oropharyngeal swabs collected from individuals testing positive for COVID-19 by Real Time PCR. The samples were collected across 10 states covering different zones within India. Given the importance of this information for public health response initiatives investigating transmission of COVID-19, the sequence data is being released in GISAID database. This information will improve our understanding on how the virus is spreading, ultimately helping to interrupt the transmission chains, prevent new cases of infection, and provide impetus to research on intervention measures. This will also provide us with information on evolution of the virus, genetic predisposition (if any) and adaptation to human hosts. One thousand and fifty two sequences were used for phylodynamic, temporal and geographic mutation patterns and haplotype network analyses. Initial results indicate that multiple lineages of SARS-CoV-2 are circulating in India, probably introduced by travel from Europe, USA and East Asia. A2a (20A/B/C) was found to be predominant, along with few parental haplotypes 19A/B. In particular, there is a predominance of the D614G mutation, which is found to be emerging in almost all regions of the country. Additionally, mutations in important regions of the viral genome with significant geographical clustering have also been observed. The temporal haplotype diversities landscape in each region appears to be similar pan India, with haplotype diversities peaking between March-May, while by June A2a (20A/B/C) emerged as the predominant one. Within haplotypes, different states appear to have different proportions. Temporal and geographic patterns in the sequences obtained reveal interesting clustering of mutations. Some mutations are present at particularly high frequencies in one state as compared to others. The negative estimate Tajimas D (D = -2.26817) is consistent with the rapid expansion of SARS-CoV-2 population in India. Detailed mutational analysis across India to understand the gradual emergence of mutants at different regions of the country and its possible implication will help in better disease management.

genomics↗

Signaling activated by nucleolar localised Notch4 Intracellular Domain underlies protection from genomic damage

The assembly of signaling hierarchies and their spatiotemporal organization together, contribute to diverse signaling outcomes. This is evident in the Notch pathway, which regulates an array of cellular processes, despite a small number of core components. Here, we describe a Notch4 activated signaling cascade, dependent on the nucleolar localization of the Notch4 Intracellular Domain (NIC4), that protects cells from genotoxic damage. Localization was assessed by immune-staining for endogenous Notch4 and visualization by confocal microscopy, in breast cancer cell lines. Live-cell, imaging-based, biophysical analysis of NIC4-GFP expressing cells, indicated unhindered mobility between the nucleolus and nucleoplasm and a stable nucleolar pool of NIC4-GFP. RNAi-mediated ablations, coupled with analysis of recombinant forms of NIC4 with modifications of its nucleolar localization sequence, confirmed nucleolar localization and identified the nucleolar proteins, Nucleolin and Fibrillarin, as key intermediates in the NIC4-activated signaling cascade. The transcriptional control of ribosome biogenesis (47s and 45s pre-rRNA transcription), emerged as another unexpected consequence of the subcellular distribution of NIC4. Taken together, this study describes intrinsic features of NIC4 that confer spatial flexibility and expand the repertoire of Notch4 signaling.

cancer biology↗