Biology subjects

Sarma, H.

Publications and source records attributed to Sarma, H..

3 recordsLinked to original sources

bioRxiv2025

Inhibition of the neurodevelopmental disorder-associated 16p11.2 gene QPRT leads to altered cell type distribution in human stem cell-derived cerebral organoids

The 16p11.2 gene QPRT, encoding a key enzyme of the kynurenine pathway, has been linked to neurodevelopmental disorders including autism spectrum disorder (ASD). To investigate its role in early human brain development, we inhibited QPRT in stem cell-derived cerebral organoids. QPRT inhibition resulted in reduced organoid size, driven by premature neural differentiation resulting in depleted progenitor populations. Single-cell transcriptomics revealed an excitation/inhibition imbalance, with reduced excitatory and increased inhibitory neuron populations. We observed metabolic stress signatures, including pseudo-hypoxia, oxidative stress, and mitochondrial dysfunction, likely linked to NAD+ depletion and QUIN accumulation following QPRT inhibition. Notably, downregulation of LHX2 and PRDX1 may underlie impaired neural patterning and excitotoxic vulnerability. In addition, we report astrocytic and radial glia dysfunctions, indicating broad effects across multiple cell types. Disease gene enrichment analyses showed significant overlap with ASD-associated genes, especially during early differentiation. These findings suggest the loss or reduction of QPRT to shift neural development and neuronal homeostasis towards an imbalance in excitatory and inhibitory neuronal populations, a mechanism previously associated with neurodevelopmental disorders.

cell biology↗

bioRxiv2023

Molecular Property Diagnostic Suite for COVID-19 (MPDSCOVID-19): An open access disease specific drug discovery portal

Computational drug discovery is intrinsically interdisciplinary and has to deal with the multifarious factors which are often dependent on the type of disease. Molecular Property Diagnostic Suite (MPDS) is a Galaxy based web portal which was conceived and developed as a disease specific web portal, originally developed for tuberculosis (MPDSTB). As specific computational tools are often required for a given disease, developing a disease specific web portal is highly desirable. This paper emphasises on the development of the customised web portal for COVID-19 infection and is referred to as MPDSCOVID-19. Expectedly, the MPDS suites of programs have modules which are essentially independent of a given disease, whereas some modules are specific to a particular disease. In the MPDSCOVID-19 portal, there are modules which are specific to COVID-19, and these are clubbed in SARS-COV-2 disease library. Further, the new additions and/or significant improvements were made to the disease independent modules, besides the addition of tools from galaxy toolshed. This manuscript provides a latest update on the disease independent modules of MPDS after almost 6 years, as well as provide the contemporary information and tool-shed necessary to engage in the drug discovery research of COVID-19. The disease independent modules include file format converter and descriptor calculation under the data processing module; QSAR, pharmacophore, scaffold analysis, active site analysis, docking, screening, drug repurposing tool, virtual screening, visualisation, sequence alignment, phylogenetic analysis under the data analysis module; and various machine learning packages, algorithms and in-house developed machine learning antiviral prediction model are available. The MPDS suite of programs are expected to bring a paradigm shift in computational drug discovery, especially in the academic community, guided through a transparent and open innovation approach. The MPDSCOVID-19 can be accessed at http://mpds.neist.res.in:8085.

bioinformatics↗

bioRxiv2018

Catch me if you can: Species interactions and moon illumination effect on mammals of tropical semi-evergreen forest of Manas National Park, Assam, India

Species interaction plays a vital role in structuring communities by stimulating behavioral responses in temporal niche affecting the sympatric associations and prey-predator relationships. We studied relative abundance indices (RAI) and activity patterns of each species, temporal overlap between sympatric species, and effects of moon cycle on predator-prey relationships, through camera-trapping in tropical semi-evergreen forests of Manas National Park. A total of 35 species were photo-captured with 16214 independent records over 7337 trap nights. Overall, relatively high number of photographs was obtained for large herbivores (11 species, n=13669), and low number of photographs were recorded for large carnivores (five species, n=657). Activity periods were classified into four categories: diurnal (day-time), nocturnal (night-time), crepuscular (twilight), and cathemeral (day and night time) of which 52% records were found in diurnal period followed by 37% in nocturnal phase whereas only 11% photographs during twilight. Small carnivores were strictly nocturnal (leopard cat and civets) or diurnal (yellow-throated marten and mongooses); whereas large carnivores were cathemeral (tiger, leopard, clouded leopard and Asiatic black bear). Analysis of activity patterns throughout the 24-h cycle revealed a high degree of temporal overlap (>60%) among most of the sympatric species; however, differences in the activity peaks were found between most of the species pairs. Moon phase was classified according to the percentage of visible moon surface as new (0-25%), waxing (25-50%), waning (50-75%) and full moon (75-100%). Moon phase did not have any correlation with activity of large carnivore and large prey. The large carnivore followed the feed and starve pattern of cyclic activity. The activity of small carnivore was influenced negatively by moonlight (partial correlation r = -0.221, p<0.01). The result suggests that large carnivores were active non-differentially across moon phases; however, small carnivores showed significantly high activity in darker nights. These patterns indicate that small predators may differ their activity temporally as an anti-predator strategy or otherwise to increase their foraging efficiency.

animal behavior and cognition↗