Biology subjects

Patel, J. R.

Publications and source records attributed to Patel, J. R..

7 recordsLinked to original sources

bioRxiv2026

Forest Owlet or Farmer's owlet: Scale-dependent habitat selection reveals conditional compatibility between Forest Owlet conservation and traditional agroforestry in Gujarat, India

Understanding how species that are threatened with extinction utilise human-modified landscapes is essential for evidence-based conservation. We investigated multi-scale habitat selection by the Forest Owlet (Athene blewitti), an Endangered species, endemic to central India with fewer than 1000 mature individuals, in the Dangs district of Gujarat, the westernmost extent of its range. Using a hierarchical Bayesian occupancy framework, we examined how forest cover and three agricultural land-use types (dry agriculture with trees, dry agriculture without trees, and intensive agriculture) affected occupancy across three nested spatial scales: regional (81 km2), landscape (4 km2), and territory (0.25 km2). At the regional scale, the forest x agriculture interaction term was significantly negative ({beta} = -6.82, 95% CI: -9.87 to -1.59), indicating that owlets favour agroforestry-dominated regions over forest-dominated landscapes. Conversely, at the landscape scale, a significant positive interaction ({beta} = 1.36, 95% CI: 0.41-2.50) revealed synergistic benefits from forest-agriculture mosaics. Agriculture type strongly influenced landscape-scale occupancy: dry agriculture with trees showed positive effects ({beta} = 1.17, 95% CI: 0.43-2.02), whereas dry agriculture without trees had significant negative effects ({beta} = -1.19, 95% CI: -2.28 to -0.29). These findings demonstrate that Forest Owlets are not forest-obligate specialists but occupy complex agroforestry mosaics, requiring multi-scale conservation strategies. We propose that the traditional Malki agroforestry system, which incentives tree retention on farmland, offers conditional compatibility with Forest Owlet conservation, provided that mature cavity-bearing trees and small forest patches are explicitly protected.

ecology↗

bioRxiv2026

Bidirectional fibrogenic cross-talk revealed in a human iPSC-derived epithelial-mesenchymal co-culture model of pulmonary fibrosis

Pulmonary fibrosis (PF) can arise from mutations in alveolar epithelial type 2 (AT2) cell-specific genes, but manifests in fibrotic activation of mesenchymal cells, thus involving fibrogenic epithelial-mesenchymal crosstalk. The ligand-receptor interactions underlying the onset and early progression of PF remain poorly understood. Induced pluripotent stem cell (iPSC)-derived models are powerful tools to study respiratory diseases, yet are currently limited to reductionist single lineage epithelial models or multi-lineage systems that lack purity and lung-specificity of the mesenchyme. Here we generate a human iPSC line carrying both a lung mesenchyme-specific reporter (TBX4-LERtdTomato) and a reporter for mesenchymal activation/differentiation (ACTA2GFP). Applying this line, we develop a directed differentiation protocol capable of generating cells that express key molecular and functional features of primary human developing lung mesenchyme across multiple iPSC genetic backgrounds. We then establish co-cultures of these iPSC-derived lung mesenchymal cells (iLM) with patient-specific iPSC-derived alveolar epithelial type 2 cells (iAT2s) carrying an SFTPCI73T mutation as a model for PF. We find increased expression of fibrotic markers in co-cultures with mutant iAT2s as compared to co-cultures with gene-corrected iAT2s. Moreover, mutant iAT2s express markers of alveolar-basal intermediate (ABI) cells only in the presence of iLM, suggesting that bidirectional crosstalk promotes this aberrant cell state. We identify ligand-receptor pairs enriched in co-cultures with mutant iAT2s, including TGF{beta}, multiple integrins, and additional genes that have not been previously linked to PF. Finally, we show that small molecule-mediated inhibition of TGF{beta} or integrins V{beta}1/V{beta}6 attenuates both fibrotic mesenchymal activation and the presence of ABI cells in iLM/iAT2 co-cultures. Thus, we have established a human iPSC-derived co-culture system that recapitulates key molecular hallmarks of bidirectional fibrogenic epithelial-mesenchymal crosstalk in pulmonary fibrosis, and enables the identification and study of potentially druggable pathways involved in disease initiation and progression.

molecular biology↗

bioRxiv2025

Generating functional plasmid origins with OriGen

While generative artificial intelligence (AI) has shown promise for biological design, no computational system has yet created and validated sequences capable of autonomous replication. Focusing on plasmids, one of the smallest types of replicating elements, we develop OriGen, a sequence model that generates new plasmid origins of replication while maintaining key elements essential for their replication. We experimentally validate OriGens ability to create functional origins that diverge from existing wild types, demonstrating the models capacity to capture the complex and often cryptic mechanisms of biological replication.

synthetic biology↗

bioRxiv2024

Connectivity of the neuronal network for contextual fear memory is disrupted in a mouse model of third-trimester binge-like ethanol exposure

BackgroundIn rodents, third-trimester equivalent alcohol exposure (TTAE) produces significant deficits in hippocampal-dependent memory processes such as contextual fear conditioning (CFC). The present study sought to characterize changes in both behavior and Fos+ neurons following CFC in ethanol (EtOH)-treated versus saline-treated mice using TRAP2:Ai14 mice that permanently label Fos+ neurons following a tamoxifen injection. We hypothesized that TTAE would produce long-lasting disruptions to the networks engaged following CFC with a particular emphasis on the limbic memory system. MethodsOn postnatal day 7, mice received either two injections of saline or 2.5 g/kg EtOH spaced 2 hours apart. The mice were left undisturbed until they reached adulthood, at which point they underwent CFC. After context exposure on day 2, mice received a tamoxifen injection. Brain tissue was harvested. Slides were automatically imaged using a Zeiss AxioScanner. Manual counts on a priori regions of interest were conducted. Automated counts were performed on the whole brain using the QUINT 2D stitching pipeline. Last, novel network analyses were applied to identify future regions of interest. ResultsTTAE reduced context recall on day 2 of CFC. Fos+ neural density increased in the CA1 and CA3. Fos+ counts were reduced in the anteroventral (AV) and anterodorsal thalamus. The limbic memory system showed significant hyperconnectivity in male TTAE mice and the AV shifted affinity towards hippocampal subregions. Last, novel regions such as a subparafascicular area and basomedial amygdalar nucleus were implicated as important mediators. DiscussionThese results suggest that CFC is mediated by the limbic memory system and is disrupted following TTAE. Given the increase in CA1 and CA3 activity, a potential hypothesis is that TTAE causes disruptions to memory encoding following day 1 conditioning. Future studies will aim to determine whether this disruption specifically affects the encoding or retrieval of fear memories.

neuroscience↗

bioRxiv2023

Genome-wide Characterization of Diverse Bacteriophages Enabled by RNA-Binding CRISPRi

Bacteriophages constitute one of the largest sources of unknown gene content in the biosphere. Even for well-studied model phages, robust experimental approaches to identify and study their essential genes remain elusive. We uncover and exploit the conserved vulnerability of the phage transcriptome to facilitate genome-wide protein expression knockdown via programmable RNA-binding protein dRfxCas13d (CRISPRi-ART) across diverse phages and their host. Establishing the first broad-spectrum phage functional genomics platform, we predict over 90 essential genes across four phage genomes, a third of which have no known function. These results highlight hidden infection strategies encoded in the most abundant biological entities on earth and provide a facile platform to study them.

microbiology↗

bioRxiv2023

Single-cell RNA sequencing reveals dysregulated fibroblast subclusters in prurigo nodularis

Prurigo nodularis (PN) is an intensely pruritic, chronic inflammatory skin disease that disproportionately affects black patients. However, the pathogenesis of PN is poorly understood. We performed single-cell transcriptomic profiling, ligand receptor analysis and cell trajectory analysis of 28,695 lesional and non-lesional PN skin cells to uncover disease-identifying cell compositions and genetic characteristics. We uncovered a dysregulated role for fibroblasts (FBs) and myofibroblasts as a key pathogenic element in PN, which were significantly increased in PN lesional skin. We defined seven unique subclusters of FBs in PN skin and observed a shift of PN lesional FBs towards a cancer-associated fibroblast (CAF)-like phenotype, with WNT5A+ CAFs increased in the skin of PN patients and similarly so in squamous cell carcinoma (SCC). A multi-center PN cohort study subsequently revealed an increased risk of SCC as well as additional CAF-associated malignancies in PN patients, including breast and colorectal cancers. Systemic fibroproliferative diseases were also upregulated in PN patients, including renal sclerosis and idiopathic pulmonary fibrosis. Ligand receptor analyses demonstrated increased FB1-derived WNT5A and periostin interactions with neuronal receptors MCAM and ITGAV, suggesting a fibroblast-neuronal axis in PN. Type I IFN responses in immune cells and increased angiogenesis/permeability in endothelial cells were also observed. As compared to atopic dermatitis (AD) and psoriasis (PSO) patients, increased mesenchymal dysregulation is unique to PN with an intermediate Th2/Th17 phenotype between atopic dermatitis and psoriasis. These findings identify a pathogenic role for CAFs in PN, including a novel targetable WNT5A+ fibroblast subpopulation and CAF-associated malignancies in PN patients.

bioinformatics↗

bioRxiv2018

Model colibactins exhibit human cell genotoxicity in the absence of host bacteria

Colibactins are genotoxic secondary metabolites produced in select Enterobacteriaceae, which induce downstream DNA double-strand breaks (DSBs) in human cell lines and are thought to promote the formation of colorectal tumors. Although key structural and functional features of colibactins have been elucidated, the full molecular mechanisms regulating these phenotypes remain unknown. Here, we demonstrate that free model colibactins induce DSBs in human cell cultures and do not require delivery by host bacteria. Through domain-targeted editing, we demonstrate that a subset of native colibactins generated from observed module skipping in the nonribosomal peptide synthetase-polyketide synthase (NRPS-PKS) biosynthetic assembly line share DNA alkylation phenotypes with the model colibactins in vitro. However, module skipping eliminates the strong DNA interstrand cross-links formed by the wildtype pathway in cell culture. This product diversification during the modular NRPS-PKS biosynthesis produces a family of metabolites with varying observed mechanisms of action - DNA alkylation versus crosslinking - in cell culture. The presence of membranes separating human cells from model colibactins attenuated genotoxicity, suggesting that membrane diffusion limits colibactin activity and could account for the observed bacteria-human cell-to-cell contact phenotype. Additionally, extracellular supplementation of the colibactin resistance protein ClbS was able to intercept colibactins in an E. coli-human cell transient infection model. Our studies demonstrate that free model colibactins recapitulate cellular phenotypes associated with moduleskipped products in the native colibactin pathway and define specific protein domains that are required for efficient DNA interstrand crosslinking in the native pathway.

cancer biology↗