Biology subjects

Patel, N. J.

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

4 recordsLinked to original sources

bioRxiv2026

BK Channels Orchestrate Cardiac Homeostasis Through Mitochondrial Uncoupling Proteins

BK channels, coded by the Kcnma1 gene, integrate voltage and intracellular Ca2+ signals and are recognized for their roles in smooth muscle and neuronal excitability. However, their contribution to baseline cardiac physiology remains poorly defined. Here we uncover a fundamental function for BK channels in maintaining normal cardiac performance, independent of pathological stress. Using non-invasive echocardiography, transcriptional profiling, and mechanistic analyses, we demonstrate that Kcnma1 deletion disrupts ventricular function, and remodels metabolic and stress-response pathways. Transcriptomic profiling revealed selective downregulation of mitochondrial uncoupling proteins (UCPs) and suppression of the PGC-1/FOXO3a axis, without broad loss of oxidative phosphorylation components. Enhancing UCP expression restored cardiac performance, indicating that mitochondrial uncoupling and redox control constitute key downstream effectors of BK signaling. Together, these results identify a physiological role for BK channels in maintaining myocardial function and define a mitochondrial BK-UCP axis, critical for cardiac homeostasis.

cell biology↗

bioRxiv2025

Distinct chromatin regulators downmodulate meiotic axis formation and DNA break induction at chromosome ends

In many organisms, meiotic crossover recombination is suppressed near the extreme ends of chromosomes. Here we show that multiple, often chromosome-specific, suppressive mechanisms with differing ranges contribute to the consistently low enrichment of recombination-promoting axis proteins and downregulation of DNA double-strand breaks (DSBs) within 20 kb of telomeres in Saccharomyces cerevisiae. Suppression of axis proteins is associated with cis-encoded signals and correlates with reduced coding density, although whether this sequence feature actively drives suppression remains to be determined. In addition, axis protein suppression requires the histone methyltransferase Dot1 and the Sir silencing complex. We show that Dot1 suppresses Sir complex activity at least in part independently of its canonical target, H3K79, to downmodulate axis protein deposition near chromosome ends. In parallel, the Sir complex, but not Dot1, suppresses the induction of DSBs at a small number of cryptic hotspots by limiting the openness of promoters, the preferred sites of meiotic DSB formation. Much of the reduced DSB induction near chromosome ends persists in dot1 and sir3 mutants, indicating that additional layers of regulation contribute to the robust reduction of meiotic recombination effectors near chromosome ends.

genetics↗

bioRxiv2022

Prescribed fire selects for a pyrophilous soil subcommunity in a northern California mixed conifer forest.

Low intensity prescribed fire is a critical strategy for mitigating the effects of catastrophic wildfires. The above-ground response to fire has been well-documented, including many ecosystem benefits associated with prescribed burning, but fewer studies have directly addressed the effect of prescribed fire on soil organisms. We aimed to understand how soil microbial communities respond to prescribed fire and to determine the ecological processes driving their dynamics. We extensively sampled four plots for 17 months in a mixed conifer forest in northern California, USA; immediately following a low-intensity prescribed fire, a higher-intensity prescribed fire, and two no-burn control plots. We found that prescribed fire significantly altered the community structure for both fungi (ITS) and bacteria (16S), which was sustained throughout the time-series. By comparing our community profiling results with a model of neutral community assembly, we found that the presence of most taxa across all experimental conditions could be explained by neutral processes. However, combining threshold indicator taxa analysis and correlation network analysis with the neutral model identified a cohort of taxa that responded deterministically to prescribed fire. The subcommunity identified through this series of analyses includes both known and new pyrophilous taxa. Beyond this, our analyses revealed network modules within postfire communities which were responsive to fire-intensity. Taken together, these results lay the foundation for building a process-driven understanding of microbial community assembly in the context of the classical disturbance regime of fire.

ecology↗

bioRxiv2020

SWR1-independent association of H2A.Z to the LINC complex promotes meiotic chromosome motion

ABSTRACTThe H2A.Z histone variant is deposited into chromatin by the SWR1 complex affecting multiple aspects of meiosis. Here we describe a SWR1-independent localization of H2A.Z at meiotic telomeres and the centrosome. We demonstrate that H2A.Z colocalizes and interacts with Mps3, the SUN component of the LINC complex that spans the nuclear envelope and links meiotic telomeres to the cytoskeleton promoting meiotic chromosome movement. H2A.Z also interacts with the meiosis-specific Ndj1 protein that anchors telomeres to the nuclear periphery via Mps3. Telomeric localization of H2A.Z depends on Ndj1 and the N-terminal domain of Mps3. Although telomeric attachment to the nuclear envelope is maintained in the absence of H2A.Z, the distribution of Mps3 is altered. The velocity of chromosome movement during meiotic prophase I is reduced in the htz1Δ mutant lacking H2A.Z, but it is unaffected in swr1Δ cells. We reveal that H2A.Z is an additional LINC-associated factor that contributes to promote telomere-driven chromosome motion critical for error-free gametogenesis.Competing Interest StatementThe authors have declared no competing interest.Non-standard abbreviationsBiFCBimolecular Fluorescence ComplementationDICDifferential Interference ContrastKAcPotassium AcetateNENuclear EnvelopeLINCLinker of the Nucleoskeleton and CytoskeletonrDNARibosomal DNASCSynaptonemal ComplexSIMStructured Illumination MicroscopySPBSpindle Pole BodyVCC-terminal moiety of the Venus fluorescent proteinVNN-terminal moiety of the Venus fluorescent proteinWCEWhole cell extractsView Full Text

cell biology↗