Biology subjects

Bhattarai, G.

Publications and source records attributed to Bhattarai, G..

4 recordsLinked to original sources

bioRxiv2026

Supplemental deinoxanthin ameliorates bone marrow microenvironmental impairments and recovers functional damage of bone marrow-retained cells in total body irradiation-exposed mice

Total body irradiation (TBI) can impair the bone marrow (BM) microenvironment and dysregulate the fates of BM-residing cells by overproducing reactive oxygen species (ROS) and inflammatory mediators. This study aims to investigate the potency and mechanism of Deinococcus radiodurans-derived deinoxanthin (DEIX) in mitigating TBI-mediated injuries in the BM microenvironment and BM-resident cells. C57BL/6 mice were divided into control, TBI, TBI+DEIX, and/or DEIX groups, in which the mice were exposed to sub-lethal TBI (5 Gy) or in combination with oral DEIX supplementation (25 mg/kg body weight). While the DEIXs effect on BM and BM-resident cells was determined after five weeks of TBI, RNA sequence profiling on the mouse group-derived BM cells was performed after two weeks of TBI. Supplementation with DEIX protected mice against TBI-mediated decrease in bone mineral density of trabecular bones. Supplemental DEIX suppressed BM microenvironmental impairment and the induction of oxidative stress and senescence in BM cells of TBI-exposed mice. That suppression was orchestrated by the DEIX-induced restoration of TBI-stimulated disorders in osteogenic, osteoclastogenic, and adipogenic activation in the BM. Ex vivo assays using BM cells supported the notion that DEIX restores TBI-mediated defects in BM cell function, including colony formation, migration, and differentiation. RNA sequence profiling demonstrated DEIXs potency to modulate the expression of genes that regulate cellular and systemic immune responses, cell proliferation and differentiation, and bone metabolism. Collectively, our results highlight the roles and associated mechanisms of DEIX in mitigating TBI-mediated microenvironmental impairment and in regulating BM-resident cells.

cell biology↗

bioRxiv2026

An omega glutathione S-transferase in Apis mellifera contributes to chemical adaptation through pesticide sequestration and antioxidant defense

The European honey bee (Apis mellifera L.) is a key agricultural pollinator frequently exposed to pesticide residues, yet the molecular basis of its chemical adaptation, particularly glutathione S-transferases (GSTs) involved in xenobiotic detoxification, remain incompletely understood. In this study, AmGSTO1 was structurally and functionally characterized to evaluate its role in agrochemical interaction and protection against oxidative stress. The crystal structure of AmGSTO1 in complex with glutathione revealed its 3D architecture and key active-site residues were identified by structural analysis and site-directed mutagenesis. Fluorescence binding assays demonstrated measurable affinity for multiple agrochemicals, including TCP, fenoprop, 2,4-D, tetramethrin, nicotine, and 3-phenoxybenzaldehyde. However, HPLC analysis showed no detectable substrate depletion, suggesting ligand binding to AmGSTO1 without catalytic turnover. AmGSTO1 exhibited antioxidant activity toward cumene hydroperoxide, hydrogen peroxide, and paraquat, as well as dehydroascorbate reductase activity. These findings indicate that AmGSTO1 may contribute to agrochemical tolerance through ligand sequestration and redox protection mechanisms.

biochemistry↗

bioRxiv2025

Leveraging species-wide variation and patterns of adaptation to inform pecan crop improvement efforts

The genetic basis of adaptation is a fundamental question in evolutionary biology, and understanding how species will be able to adapt to changing conditions across their range has important implications for conservation and agriculture. To accurately interrogate the genetics of adaptation and assess the adaptive capacity of a species requires also characterizing the ways other mechanisms, including geographic distance and population dynamics, shape genetic variation. Pecan is an ecologically, culturally, and economically important North American tree, and a broader understanding of the genetics of environment adaptation will aid pecan conservation, breeding, and commercial management. Here, we use an expansive set of more than 700 pecan genotypes in combination with the first haplotype-resolved genome assembly for pecan to assess species-wide genetic variation and evaluate environmental adaptation across the native distribution. We identify five gene pools in pecan, with the lowest diversity in southern gene pools, and present evidence that gene pools began differentiating during multiple glacial cycles. Using complementary genotype-environment association approaches, we infer species-wide patterns of environmental adaptation. With these results, we predict mismatches in adaptation for pecan genotypes to different environments, including future environment scenarios. We see that in all locations, present-day genotypes incur some level of predicted maladaptation to simulated future environments, but current genetic diversity may provide a valuable source of resilience to future conditions through assisted migration. These results expand the understanding of environmental adaptation in pecan and provide insight into how long-lived species will be able to adapt to future conditions.

evolutionary biology↗

bioRxiv2023

Contribution of the delta-class glutathione S-transferase to agrochemical adaptation in Apis mellifera

The European honey bee, Apis mellifera, serves as the principle managed pollinator species globally. In recent decades, honey bee populations have been facing serious health threats from combined biotic and abiotic stressors, including diseases, limited nutrition, and agrochemical exposure. Understanding the molecular mechanisms underlying xenobiotic adaptation of A. mellifera is critical, considering its extensive exposure to phytochemicals and agrochemicals present in flowers, propolis, hives, and the environment. In this study, we conducted a comprehensive structural and functional characterization of AmGSTD1, a delta class glutathione S-transferase (GST) enzyme, to unravel its roles in agrochemical detoxification and antioxidative stress responses. Significantly, we determined the 3D structure of a honey bee GST using protein crystallography for the first time, providing new insights into its molecular structure. Our investigations revealed that AmGSTD1 efficiently metabolizes model substrates, including 1-chloro-2,4-dinitrobenzene (CDNB), p-nitrophenyl acetate (PNA), phenylethyl isothiocyanate (PEITC), propyl isothiocyanate (PITC), and the oxidation byproduct 4-hydroxynonenal (4-HNE). Moreover, we discovered that AmGSTD1 exhibits binding affinity with the fluorophore 8-Anilinonaphthalene-1-sulfonic acid (ANS), which can be inhibited with various herbicides, fungicides, insecticides, and their metabolites. These findings highlight the potential contribution of AmGSTD1 in safeguarding honey bee health against various agrochemicals and their metabolites, while also mitigating oxidative stress resulting from exposure to these substances.

pharmacology and toxicology↗