Biology subjects

Mittal, R.

Publications and source records attributed to Mittal, R..

7 recordsLinked to original sources

bioRxiv2026

Drought Response and Recovery in Wild, Feral, and Domesticated Brassica rapa: Implications for Crop Climate Resilience

Drought poses a serious threat to agricultural production and food security. Wild relatives of crops, including pre-domesticated and feral varieties, contain genetic diversity that can serve as a breeding resource for increasing desirable crop traits such as drought resilience, but little is known about the relative ability of wild varieties to cope with climate change in most species. In this study, we investigated the drought response of wild, feral, and domesticated varieties of Brassica rapa, an important crop and model species. Twenty-five accessions were subjected to experimental drought and recovery, and variation in traits such as biomass retention, photosynthetic rate, and water use efficiency were quantified. We found several wild accessions of B. rapa had high biomass retention under drought and full recovery of maximum assimilation rate after rewatering, challenging the assumption that feralization produces stress-resilient phenotypes and suggesting that populations of wild crop progenitors are especially promising reservoirs of drought-response diversity. Our results also showed taproot biomass was positively associated with water use efficiency. Our findings provide candidate traits and genotypes for agricultural breeding aimed at increasing drought resilience in domesticated B. rapa cultivars and give insights into evolution under domestication and feralization in the context of climate change.

plant biology↗

bioRxiv2026

Pharmacologic Targeting of ZNF281 Suppresses Metastatic Prostate Cancer Beyond Androgen Receptor Dependence

Metastatic prostate cancer remains a lethal disease, with most treatments focusing on the androgen receptor (AR) axis. We identified the zinc finger protein 281 (ZNF281) as a previously unrecognized driver of metastatic prostate cancer that promotes both AR-related transcriptional output and distinct AR-independent tumor-promoting pathways. It increases AR expression and acts as a coactivator to promote AR transcriptional activity. Independent of AR, ZNF281 promotes prostate cancer by upregulating SMURF1 to sustain tumor growth and by promoting SNAIL-mediated metastasis. We developed an orally bioavailable, ZNF281 Interfering Molecule (Oral ZIM) that disrupts its DNA binding and AR protein interaction. Knockout of ZNF281 as well as treatment with oral ZIM potently inhibited prostate cancer growth and metastasis in orthotopic xenograft models of castration-sensitive and castration-resistant prostate cancers (without detectable systemic toxicity), and ZIM outperformed enzalutamide treatment in patient-derived prostate cancer organoids.

cancer biology↗

bioRxiv2026

Nucleosome-resolution inference of chromatin interaction landscapes from Micro-C data using maximum entropy modeling

Chromatin contact maps report population-averaged frequencies that obscure the physical principles of genome folding. Here we show that a sparse, signed interaction landscape - a matrix of Lagrange multipliers,{lambda} , inferred by maximum entropy from Micro-C contact probabilities at nucleosome resolution, encodes regulatory and structural information beyond contact statistics. Sign decomposition reveals context-dependent associations with chromatin state. Attractive interactions ({lambda}-) are enriched at active regulatory elements, whereas repulsive interactions ({lambda}+) identify genomic positions whose contacts are depleted relative to the polymer reference, including Polycomb-associated domains. Top-ranked{lambda} bins show substantially greater enrichment for regulatory chromatin marks than O/E-normalised bins across active, architectural, and repressive classes, demonstrating that{lambda} preferentially identifies regulatory regions over contact-based rankings. Structural information is hierarchically encoded: the strongest 2% of interactions recover domain boundaries, the top 10% reproduces average contact statistics, yet reconstructing the conformational free-energy landscape, including dominant structural sub-populations and occupancies requires the full interaction spectrum. Nucleosome perturbation experiments show that{lambda} detects positional information contact maps largely miss, and targeted removal of CTCF/RAD21-associated{lambda} interactions selectively disrupts loop architecture without altering global polymer statistics. Together, these results establish{lambda} as a physically interpretable intermediate layer linking chromatin contact maps to three-dimensional structural ensembles.

biophysics↗

bioRxiv2025

Uncovering High-Resolution Organization of Genomic Loci using Experimentally Informed Polymer Model

The functionality of an organism depends on gene expression patterns, which are governed by the hierarchical organization of the genome. Numerous efforts, leveraging both polymer physics-based models and experimental imaging technologies, have sought to elucidate the structure-function relationship of chromatin fibers. However, a major challenge remains: the intrinsically multi-scale nature of chromatin organization, which has yet to be fully explored. Here, we present an experimentally informed, polymer physics-based model capable of reconstructing chromatin structural ensembles by integrating low-resolution contact data with MNase-derived nucleosome positioning information. We applied this model to multiple human genomic loci. Our analysis uncovered distinct structural features associated with active and inactive chromatin states, providing key insights into the relationship between genomic organization and transcriptional activity. These findings offer a promising framework for understanding genome structure-function relationships and their implications in developmental disorders and gene misregulation-related diseases.

biophysics↗

bioRxiv2025

DAF-16/FOXO maintains genome integrity following genotoxic stress

Preserving genomic integrity is crucial for the accurate transmission of genetic information across generations, as well as for preventing precocious ageing. The DNA Damage Response (DDR) safeguards the genome from genotoxic stress through a coordinated system of sensors, relay proteins, and repair mechanisms. Since DNA repair is an energy-intensive activity, the process is tightly regulated and coordinated with various metabolic pathways. The nutrient-sensing insulin/IGF signalling (IIS) pathway has been extensively studied for its role in ageing and lifespan regulation in C. elegans through its downstream FOXO transcription factor DAF-16. However, there is limited understanding of its involvement in maintaining genomic integrity through the regulation of the DDR. In this study, we demonstrate the role of DAF-16/FOXO in preserving genome integrity by activating the expression of DDR repair genes in C. elegans. Activated DAF-16/FOXO directly binds to the promoter of DDR genes under conditions of low IIS, ensuring that their expression is maintained at a higher level, which is crucial for prompt DNA damage repair. Interestingly, we find that DAF-16 functions both cell autonomously as well as non-autonomously to support DNA integrity. We also determine that the DAF-16(d/f) isoform, but not the DAF-16(a) isoform, is essential for maintaining germline genome integrity. Furthermore, DAF-16 activation enhances the DDR primarily through the canonical DDR components and, to a lesser extent, via apoptosis-mediated clearance of damaged cells. Overall, our study highlights a new role for DAF-16/FOXO in the DDR and the preservation of genome integrity.

cell biology↗

bioRxiv2025

Is Aedes nr. albopictus synonymous with Aedes pseudalbopictus?

A recent study reported a putative cryptic species of Aedes albopictus, provisionally named Aedes nr. albopictus, from Tripura, India, based on molecular data from mitochondrial cytochrome c oxidase subunit I (COI) and nuclear internal transcribed spacer 2 (ITS2) regions. However, our reanalysis, incorporating COI and ITS2 sequences of the co-occurring species Aedes pseudalbopictus and employing maximum likelihood phylogenetic analysis, albeit with a limited number of available sequences, suggests that this lineage is conspecific with Ae. pseudalbopictus. Given the morphological similarities and overlapping habitat use of Ae. albopictus and Ae. pseudalbopictus in India and Southeast Asia, we hypothesize that the reported cryptic species could potentially be attributed to Ae. pseudalbopictus. Our findings underscore the need for comprehensive taxonomic assessments, integrating morphological and molecular analyses of all sympatric Stegomyia species, to ensure accurate species delimitation and support effective vector surveillance and control.

zoology↗

bioRxiv2023

Reconstructing the pressure field around a swimming fish using a physics-informed neural network

Hydrodynamic pressure is a physical quantity that is utilized by fish and many other aquatic animals to generate thrust and sense the surrounding environment. To advance our understanding of how fish react to unsteady flows, it is necessary to intercept the pressure signals sensed by their lateral line system. In this study, the authors propose a new, non-invasive method for reconstructing the instantaneous pressure field around a swimming fish from 2D particle image velocimetry (PIV) measurements. The method uses a physics-informed neural network (PINN) to predict an optimized solution for the velocity and pressure fields that satisfy in an [L]2 sense both the Navier Stokes equations and the constraints put forward by the measurements. The method was validated using a direct numerical simulation of a swimming mackerel, Scomber scombrus, and was applied to empirically obtained data of a turning zebrafish, Danio rerio. The results demonstrate that when compared to traditional methods that rely on directly integrating the pressure gradient field, the PINN is less sensitive to the spatio-temporal resolution of the velocity field measurements and provides a more accurate pressure reconstruction, particularly on the surface of the body.

animal behavior and cognition↗