Biology subjects

Nair, T.

Publications and source records attributed to Nair, T..

5 recordsLinked to original sources

bioRxiv2024

Distinct mechanisms of non-autonomous UPRER mediated by GABAergic, glutamatergic, and octopaminergic neurons.

The capacity to deal with stress declines during the aging process, and preservation of cellular stress responses is critical to healthy aging. The unfolded protein response of the endoplasmic reticulum (UPRER) is one such conserved mechanism, which is critical for the maintenance of several major functions of the ER during stress, including protein folding and lipid metabolism. Hyperactivation of the UPRER by overexpression of the major transcription factor, xbp-1s, solely in neurons drives lifespan extension as neurons send a neurotransmitter-based signal to other tissue to activate UPRER in a non-autonomous fashion. Previous work identified serotonergic, dopaminergic, and tyraminergic neurons in this signaling paradigm. To further expand our understanding of the neural circuitry that underlies the non-autonomous signaling of ER stress, we activated UPRER solely in glutamatergic, octopaminergic, and GABAergic neurons in C. elegans and paired whole-body transcriptomic analysis with functional assays. We found that UPRER-induced signals from glutamatergic neurons increased expression of canonical protein homeostasis pathways and octopaminergic neurons promoted pathogen response pathways; while minor, statistically significant changes were observed in lipid metabolism-related genes with GABAergic UPRER activation. These findings provide further evidence for the distinct role neuronal subtypes play in driving the diverse response to ER stress.

cell biology↗

bioRxiv2024

Harmonising distributed tree inventory datasets across India can fill critical gaps in tropical ecology

AO_SCPLOWBSTRACTC_SCPLOWO_LIGlobal analyses of tree diversity and function are strongly biased geographically, with poor representation from forests of the Indian subcontinent. Even though data from India - representing two-thirds of the subcontinent and spanning a wide range of tree-based biomes - exists, a barrier to syntheses is the absence of accessible and standardised data. Further, with increasing human footprint across ecosystems, data from Indian landscapes, with their long history of human-nature interactions is a key link to understand the future of tropical forested landscapes. Given the long history of human-nature interactions and high human footprint in the region, accessible and standardized data from the subcontinent can enable understanding the future of tropical landscapes under increasing human footprints globally. C_LIO_LICombining literature searches with manual data retrieval, we assembled the INdia Tree Inventory dataset, INvenTree. INvenTree is the largest meta-dataset of peer-reviewed publications (n = 465) from 1991-2023 on geolocated plot-based tree inventories of multispecies communities from Indian ecosystems, in aggregate covering 4653.64 ha and all of its woody biomes. C_LIO_LIUsing INvenTree, we show extensive sampling across tropical moist and dry forests, the dominant ecosystem types in the country. However, most studies have low sampling effort (median sampled area = 2 ha) and data across studies is not openly accessible (73.33 % of studies representing 83.43% of the sampled area), potentially hindering inclusion into regional or global syntheses. C_LIO_LISignificantly, we show majority authorship from within the country; 82.8% of corresponding authors were from India and 73.33% of the studies had all authors affiliated with Indian institutions. We also identify ecological and conservation sampling priority regions based on forest cover and forest loss and set a blueprint for future sampling efforts in the country. C_LIO_LIBased on extensive Indian scholarship in forest ecology showcased through the INvenTree dataset, we see opportunity for regional collaboration to create scientific inferences that are larger and scalable, while prioritising data and knowledge equity. Harmonising these existing datasets, and synthesising historic and grey literature, will contribute enormously to understanding the human dimension of tropical ecology as well as informing regional management and conservation. C_LI

ecology↗

bioRxiv2024

Methionine cycle in a pair of serotonergic neurons regulates diet-dependent behavior and longevity through a neuron-gut signaling

The folate-methionine cycle (Met-C) is a central metabolic pathway that is regulated by vitamin B12 (B12), a micronutrient obtained exclusively from diet and microbiota. This metabolic hub supports amino acid, nucleotide and lipid biosynthesis apart from its central role of providing one carbon (-CH3) moiety for methylation reactions. While deficiency of B12 as well as polymorphism in enzymes of the Met-C has been clinically attributed to neurological and metabolic disorders, how this pathway cell non-autonomously regulates systemic physiological processes is less understood. Using a B12-sensitive mutant of Caenorhabditis elegans, we show that the neuronal Met-C responds to differential B12 content in diet to regulate p38-MAPK activation in intestinal cells, thereby modulating cytoprotective gene expression, stress tolerance and longevity. Mechanistically, B12-driven changes in the metabolic flux through the Met-C in the serotonergic ADF neurons of the mutant lead to the release of serotonin (5-hydroxytryptamine, 5-HT). 5-HT activates its receptor, MOD-1, in the post-synaptic interneurons that then secretes the neuropeptide FLR-2. FLR-2 binds to FSHR-1, its cognate receptor in the intestine, and induces the phase transition of the SARM domain protein TIR-1, thereby activating the p38-MAPK pathway. Importantly, this cascade influences the foraging behaviour of the mutant worms such that they prefer a B12-rich diet. Together, our study reveals a dynamic neuron-gut signaling axis that helps an organism modulate behaviour and life history traits based on the neuronal Met-C metabolic flux determined by B12 availability in its diet. Understandably, disruption of the optimum functioning of this axis may have debilitating effects on the health of an organism and the survival of the species.

cell biology↗

bioRxiv2024

Serotonin deficiency from constitutive SKN-1 activation drives pathogen apathy.

When an organism encounters a pathogen, the host innate immune system activates to defend against pathogen colonization and toxic xenobiotics produced. C. elegans employ multiple defense systems to ensure survival when exposed to Pseudomonas aeruginosa including activation of the cytoprotective transcription factor SKN-1/NRF2. Although wildtype C. elegans quickly learn to avoid pathogens, here we describe a peculiar apathy-like behavior towards PA14 in animals with constitutive activation of SKN-1, whereby animals choose not to leave and continue to feed on the pathogen even when a non-pathogenic and healthspan-promoting food option is available. Although lacking the urgency to escape the infectious environment, animals with constitutive SKN-1 activity are not oblivious to the presence of the pathogen and display the typical pathogen-induced intestinal distension and eventual demise. SKN-1 activation, specifically in neurons and intestinal tissues, orchestrates a unique transcriptional program which leads to defects in serotonin signaling that is required from both neurons and non-neuronal tissues. Serotonin depletion from SKN-1 activation limits pathogen defense capacity, drives the pathogen-associated apathy behaviors and induces a synthetic sensitivity to selective serotonin reuptake inhibitors. Taken together, our work reveals new insights into how animals perceive environmental pathogens and subsequently alter behavior and cellular programs to promote survival. KEY POINTSO_LIIdentify an apathy-like behavioral response for pathogens resulting from the constitutive activation of the cytoprotective transcription factor SKN-1. C_LIO_LIUncover the obligate role for serotonin synthesis in both neuronal and non-neuronal cells for the apathy-like state and ability of serotonin treatment to restore normal behaviors. C_LIO_LICharacterize the timing and tissue specificity of SKN-1 nuclear localization in neurons and intestinal cells in response to pathogen exposure. C_LIO_LIDefine the unique and context-specific transcriptional signatures of animals with constitutive SKN-1 activation when exposed to pathogenic environments. C_LIO_LIReveal necessity for both neuronal and non-neuronal serotonin signaling in host survival from pathogen infection. C_LI

genetics↗

bioRxiv2022

Prioritizing landscapes to reconcile biodiversity conservation, ecosystem services, and human well-being in India

Biodiversity conservation and human well-being are tightly interlinked; yet mismatches in the scale at which both priorities are planned and implemented have exacerbated biodiversity loss, erosion of ecosystem services, and declining human quality of life. India houses the second largest human population on the planet, while <5% of the countrys land area is effectively protected for conservation. This warrants landscape-level conservation planning through a judicious mix of land-sharing and land-sparing approaches, and co-production of ecosystem services. Through a multi-faceted assessment, we prioritize spatial extents of land parcels that, in the face of anthropogenic threats, can safeguard conservation landscapes across Indias biogeographic zones. We find that only a fraction (~15%) of such priority areas identified here are encompassed under Indias extant PA network, and several landscapes of high importance were omitted in all previous global-scale assessments. We then examined the spatial congruence of priority areas with administrative units earmarked for economic development by the Indian government, and propose management-zoning through state-driven and participatory approaches. Our spatially explicit insights can help meet the twin goals of biodiversity conservation and sustainable development in India and other countries across the Global South.

ecology↗