Biology subjects

Seshadri, A.

Publications and source records attributed to Seshadri, A..

5 recordsLinked to original sources

bioRxiv2025

GRAYU: Graph-based Database integrating Ayurvedic formulations, medicinal plants, phytochemicals and diseases

The translation of Indias extensive traditional knowledge on indigenous medicinal plants into modern therapeutic solutions is contingent upon a systematic framework. While traditional Indian medicine offers a rich source of therapeutic leads, this knowledge is often not structured for modern computational analysis, creating a barrier to systematic drug discovery. To this end, we present GRAYU, a curated and comprehensive online database that integrates data across multiple categories, connecting 1039 traditional formulations to 12,949 indigenous plants, 129,542 phytochemicals, and 13,480 indicated diseases. It also provides insights into 1,382,362 plant-phytochemical, 116,824 plant-disease, 2,405 plant-formulation, and 4,087 formulation-disease associations. Case studies on phytochemical analogs, sustainable plant substitution, and disease-network pharmacology showcased the potential of integrative graphs to decode shared molecular signatures and therapeutic networks across traditional Ayurvedic formulations. GRAYU represents a user-friendly resource for researchers to investigate complex bio-associations and formulate novel therapeutic hypotheses, with insights from traditional Indian medicine. GRAYU is available at https://caps.ncbs.res.in/GRAYU/.

bioinformatics↗

bioRxiv2025

Insights from U.S. beekeeper triage surveys following unusually high honey bee colony losses 2024-2025

In January of 2025, U.S. commercial beekeepers reported unusually high honey bee colony losses as they prepared colonies for almond pollination. Two industry groups launched nationwide surveys to document colony losses between June 2024 and March 2025 across all scales of beekeeping. This study analyzes these survey data to assess colony losses, estimate financial impacts, and identify correlations with beekeeper management practices and geographical locations. Unlike past surveys, commercial beekeepers experienced more severe losses than smaller-scale beekeepers during this period. Respondents, managing over half of U.S. colonies, most frequently cited Varroa mites as the cause for their losses. Varroa mites were followed by pesticides and pathogens in the case of commercial beekeepers and by queen failure and weather in the case of smaller-scale beekeepers. Although Varroa was the most frequently cited cause, losses did not significantly differ between users and non-users of amitraz, suggesting that rising amitraz resistance alone does not explain observed trends. Differences in protein and carbohydrate feeding frequencies also played a role in net losses. While colony loss rates and financial concern varied widely among respondents, commercial beekeepers understandably showed higher sensitivity to financial impacts, with concerns increasing linearly with loss severity. This study highlights the value of beekeeper surveys which, alongside direct analyses of bee samples and longitudinal studies, help identify effective management strategies and environmental risks. Such insights are crucial for addressing the leading causes of colony losses on a national scale, and ultimately aid in safeguarding honey bee health, pollination services, and agricultural production. HighlightsO_LIUnprecedented honey bee colony losses C_LIO_LIIndications of disease stress C_LIO_LIHigh economic pain for commercial beekeepers and growers C_LI

ecology↗

bioRxiv2025

A Multigenerational ''Dirty'' Mouse Model for Studying Trauma-Induced Immune Dysregulation and Infection Susceptibility

Trauma induces immune dysregulation in both humans and mice, increasing infection susceptibility. Mouse models are critical in research but have been criticized for lacking translational relevance. This study tested whether multigenerational "natural immune" (NI) mice - generated by co-housing C57BL/6 mice with "dirty" pet shop mice and breeding through multiple generations - would develop a more human-like immune response to trauma and infection than "clean" specific pathogen-free (SPF) C57BL/6 mice whose immune systems developed without normal flora. To address this gap, SPF and NI mice underwent burn trauma followed by Pseudomonas aeruginosa lung infection. Peripheral blood and bone marrow immune cells were characterized by flow cytometry and mass cytometry (CyTOF). Blood samples from trauma patients were analyzed for comparison. At baseline, NI mice exhibited more neutrophils compared to SPF mice, closer resembling human peripheral immune composition. Following injury, SPF mice demonstrated increased blood neutrophils and monocytes with reduced B and T cells, whereas NI mice exhibited a muted blood immune cell response. In contrast, NI mice showed a robust emergency granulopoiesis response and preserved hematopoietic stem cells (HSCs) following secondary infection, whereas HSCs decreased in SPF mice. Time-matched blood samples from human trauma patients revealed alterations more closely resembling those observed in NI mice. These findings support the hypothesis that NI mice develop a more human-like immune response to trauma and infection than SPF mice. This suggests that NI mice may provide a more translationally relevant platform for studying trauma-induced immune dysfunction and infection susceptibility mechanisms. Summary SentenceMultigenerational natural immune mice exhibit more human-like immune responses to trauma and infection that offer a model with significant translatable advantages for studying post-injury immune dysfunction in patients.

immunology↗

bioRxiv2024

Exonuclease action of replicative polymerase gamma drives damage-induced mitochondrial DNA clearance

Mitochondrial DNA (mtDNA) replication is essential for mitochondrial function. This is carried out by a dedicated DNA polymerase gamma, with 5-3 polymerase and 3-5 proofreading/ exonuclease activity. Perturbations to either properties can have pathological consequences. Predominant sources for replication stress are DNA lesions, such as those induced by oxidative damage. How mtDNA lesions affect the polymerase activity and mtDNA stability in vivo is not fully understood. To address this, we induce mtDNA-specific damage in S. cerevisiae. We observe that mtDNA damage results in significant mtDNA loss. This loss occurs independent of cell cycle progression or cell division, suggesting an active mechanism for damaged mtDNA clearance. We implicate the 3-5 exonuclease activity of the mtDNA polymerase in this clearance, with rates of loss being affected by cellular dNTP levels. Overall, our findings reveal context-dependent, selective regulation of two critical but opposing functions of polymerase gamma to ensure mitochondrial genome integrity.

microbiology↗

bioRxiv2022

Dynamic reorganization and selective segregation of mitochondria under DarT-mediated mtDNA damage

Mitochondria are dynamic organelles that play essential roles in cell growth and survival. Processes of fission and fusion are critical for distribution, segregation and maintenance of mitochondria and their genomes (mtDNA). While recent work has revealed the significance of mitochondrial organization for mtDNA maintenance, impact of mtDNA perturbations on mitochondrial dynamics remains less understood. Here we develop a tool to induce mitochondria-specific DNA damage, using a mitochondrial-targeted base modifying bacterial toxin, DarT. Following damage, we observe dynamic reorganization of mitochondrial networks, likely driven by mitochondrial dysfunction. Changes in organization are associated with loss of mtDNA, independent of mitophagy. Unexpectedly, perturbation to exonuclease function of mtDNA replicative polymerase, Mip1, results in rapid loss of mtDNA. Our data suggest that, under damage, partitioning of defective mtDNA and organelle are de-coupled, with emphasis on mitochondrial segregation independent of its DNA. Together, our works underscores the importance of genome maintenance on mitochondrial function, that can act as a modulator of organelle organization and segregation.

cell biology↗