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Vyas, H.

Publications and source records attributed to Vyas, H..

9 recordsLinked to original sources

Female song and breeding phenology of the Nilgiri Flycatcher (Eumyias albicaudatus) in the Shola Sky Islands

Assessing breeding phenology using singing intensity can potentially provide insights into a species' responses to climate or habitat change. Although male passerines are known to sing elaborate songs during the breeding season, females of several tropical passerines also sing. The Nilgiri Flycatcher (Eumyias albicaudatus) is an endemic dimorphic songbird found in the southern Western Ghats of India. Despite its limited distribution and its ecological significance as an indicator species of cloud forests, very little is known about its vocal behaviour and breeding ecology. To examine sex-specific differences in vocalisation patterns, we analysed 294 male and 102 female focal songs from two pairs of birds. We then used data from a year-long automated recorder placed near a breeding pair to study the species' singing phenology using the BirdNET Analyser. The two sexes broadly produced similar songs, although males' songs included more notes at a faster pace. The sex-specific detectors failed due to this high similarity among songs of the two sexes, but we were able to automate species-level detection (F1-score = 0.795 at a confidence threshold of 0.1). We found strong seasonality in vocal activity, with peaks in singing during the breeding season, and identified a diurnal peak at dawn. More data are required to parameterise differences in annual vocal activity between the sexes. These detection patterns provide a framework for a landscape-wide examination of Nilgiri Flycatcher phenology and occurrence. This study suggests that automatic detectors can be a reliable tool for assessing singing phenology in birds and provide insights into breeding periods.

ecology↗

Melatonin improves neuro-behavioral perturbations in diet/photoperiod induced chronodisruption

Endogenous circadian oscillators regulate learning, cognitive performance and memory are disrupted due to circadian shifts. High-fat-high-fructose (H) diet, photoperiodic shifts induced chronodisruption (CD) and a combination (HCD) causes neurobehavioral perturbations wherein; the merits of exogenous melatonin in alleviating the said behavioral deficits are studied herein. Indices of anxiety (marble burying test, elevated plus maze test and hole board test) and depressive behavior (sucrose preference test, forced swim test and tail suspension test) were elevated in H, CD and HCD groups. Significant increments in the titres of thyroid hormone levels (T3, T4 and TSH) and mRNA levels of hippocampal pro-inflammatory genes (Tnf-, Il-1{beta}, Il-4, Il-6, Il-10, Il-12, Il-17, Mcp-1 and Nf-{kappa}b) in the said experimental groups corroborates with the said changes. Exogenous melatonin treatment to the said experimental groups viz. HM, CDM and HCDM; accounted for moderate to significant improvement in the said neurobehavioral perturbations and hippocampal inflammatory markers. Hippocampal BDNF-TrkB pathway genes of H, CD and HCD had recorded a non-significant downregulation in mRNA but without prominent changes in proteins. Likewise, melatonin-treated groups showed moderate to significant improvement in transcripts of Bdnf, Trkb, Nt-3, Nt-4, Psd-95 and Syn-1. Herein, we report neurobehavioral perturbations caused by a combination of H and CD. Melatonin-mediated improvement in neurobehavior and the corrective changes in hippocampal BDNF-TrkB pathway implies towards the potential anxiolytic and anti-depressive activity as reported herein.

animal behavior and cognition↗

A Multi-omic Atlas of Human Choroid Plexus in Alzheimer's Disease

The choroid plexus (CP) regulates barrier integrity, cerebrospinal-fluid (CSF) dynamics, and immune surveillance, yet its role in Alzheimers disease (AD) remains poorly defined. We performed snRNA-seq on CP samples from 69 ROSMAP participants spanning normal cognition, mild cognitive impairment, and AD dementia, and integrated these data with spatial transcriptomics, snATAC-seq, and proteomics from CP tissue and CSF. We identified 17 CP cell states and uncovered widespread disease-associated transitions that converged into three major phenotypic axes. Along the inflammatory axis, epithelial cells and border-associated macrophages (BAMs) showed progressive immune activation, with BAMs shifting from inflammatory to stress-dominant states. In the barrier axis, epithelial cells, fibroblasts, and endothelial cells exhibited reduced junction-related gene expression and broad alterations in transport pathways. Epithelial cells also showed late-stage cilia loss and CSF-regulatory pathway impairment, indicating a breakdown in epithelial polarity and CSF sensing, consistent with abnormal CSF proteomic signatures. Along the remodeling axis, fibroblasts showed ECM alterations, while epithelial and stromal cells demonstrated aberrant cell-matrix adhesion pathways. Spatial neighborhood analysis revealed a multicellular signaling hub, with epithelial-rich niches showing the strongest dysregulation in AD. Together, these findings define a unified model of CP dysfunction in AD and position the CP as an active, multicellular contributor to AD pathophysiology.

genomics↗

Stress-Responsive Transcriptomic Signatures in Human iPSC-Derived Microglia Reveal Links to Alzheimer's Disease Risk Genes

Commercially available human iPSC lines with inducible CRISPR interference (CRISPRi) systems offer scalable platforms for gene function studies. One widely available line, the AICS-0090 dCas9-KRAB iPSC line developed by the Allen Institute, has been extensively validated for genomic integrity and stem cell potency. However, its utility in modeling specialized immune cell types such as microglia -- and in assessing their functional responses to disease-relevant stimuli -- has not been fully established. Here, we evaluated the AICS-0090 line for its ability to differentiate into microglia-like cells, support efficient gene knockdown, and respond to environmental stressors. We assessed its differentiation capacity by qPCR, flow cytometry, and immunocytochemistry, confirming reproducible expression of microglial surface markers at early and late timepoints. Gene knockdown efficiency was validated both at the single-gene level and in pooled CRISPRi screens. Focusing on functional responsiveness, we exposed the microglia-like cells to two distinct stimuli: amyloid-{beta} (A{beta}), a disease-associated trigger in Alzheimers disease, and lipopolysaccharide (LPS), a classical inflammatory signal. Transcriptomic and functional analyses revealed stimulus-specific responses: A{beta} induced limited activation of stress and inflammation pathways, whereas LPS elicited broader transcriptional reprogramming and cytokine release. Signatures from both conditions partially overlapped with ex vivo human and mouse microglial states. Together, these findings support the use of the AICS-0090 dCas9-KRAB iPSC-derived microglia-like cells as a flexible and tractable model for gene function interrogation under defined inflammatory contexts, with potential for future applications in neuroimmune modeling and perturbation-based screening.

neuroscience↗

TEAD1 is a novel regulator of NRF2 and oxidative stress response in cardiomyocytes

BACKGROUNDTEAD1, the mammalian Hippo pathway-regulated transcription factor, plays a critical and non-redundant role in maintaining cardiomyocyte (CM) homeostasis. However, the specific cellular pathways regulated by TEAD1 in CMs remain poorly defined. We hypothesized that TEAD1 has an essential, cell-autonomous role in the CM oxidative stress response by directly regulating the transcription of NRF2, the master regulator of oxidative stress response. METHODS AND RESULTSTamoxifen-induced conditional CM-specific TEAD1 deletion in adult mice leads to acute heart failure (HF) and altered expression of antioxidant genes. In silico analysis of publicly available RNA-seq data from human hearts with end-stage dilated (DCM) and ischemic (ICM) cardiomyopathy revealed significant downregulation of TEAD1 transcript levels and a positive correlation between TEAD1 and NRF2 gene expression. ChIP-seq and ATAC-seq in adult mouse hearts confirmed TEAD1 occupancy at promoter/enhancer elements within open chromatin regions of multiple antioxidant genes, including NRF2 and its targets. Ex vivo and in vitro TEAD1 knockout in primary neonatal and adult murine CMs, as well as in H9C2 cells, resulted in significantly increased cellular and mitochondrial ROS le, accompanied by a marked decrease in NRF2 expression and promoter-luciferase activity, under both basal and oxidative stress conditions. Mosaic, conditional deletion of TEAD1 in [~]40-50% of murine heart CMs provided a novel in vivo model for studying TEAD1-regulated pathways in the heart, independent of the confounding effects of HF. This model demonstrated reduced NRF2 expression and heightened oxidative stress in neonatal and adult TEAD1 mosaic knockout hearts. Notably, 8OHdG staining identified oxidative DNA damage in TEAD1-deficient CMs compared to TEAD1-expressing CMs within the mosaic knockout hearts. Upon in vivo AngII infusion, TEAD1 mosaic knockout hearts showed a significant increase in oxidative stress markers and an impaired NRF2 response. Overexpression of human TEAD1 restored NRF2 activity and mitigated ROS accumulation in TEAD1 knockout CMs in vitro. Furthermore, TEAD1 deletion in human iPSC-derived CMs resulted in increased oxidative stress and downregulation of NRF2 expression and functional activity, confirming the requirement of TEAD1 in NRF2-mediated oxidative stress response in human CMs. Collectively, these findings establish that TEAD1 is essential for NRF2 expression and activity under both basal and AngII-induced conditions and plays a crucial role in the oxidative stress response in CMs. CONCLUSIONSTEAD1 is a cell-autonomous, direct transcriptional regulator of NRF2 and the cardiomyocyte (CM) oxidative stress response. Its gene expression, which directly correlates with NRF2 transcript levels in the human myocardium, is significantly downregulated in human end-stage heart failure, potentially compromising the oxidative stress response in the failing heart.

molecular biology↗

Spatial Expression of Long Non-Coding RNAs in Human Brains of Alzheimer's Disease

BackgroundLong non-coding RNAs (lncRNAs) are critical regulators of physiological and pathological processes, with their dysregulation increasingly implicated in aging and Alzheimers disease (AD). To investigate the spatial and cellular distribution of lncRNAs in the aging brain, we leveraged published spatial transcriptomics (ST), single-nucleus RNA sequencing (snRNA-seq), and bulk RNA-seq datasets from the dorsolateral prefrontal cortex (DLPFC) of ROSMAP participants with and without pathological AD. ResultsLncRNAs exhibited greater subregion-specific expression than mRNAs, with enrichment in antisense and lincRNA biotypes. Subregion-enriched lncRNAs were generally not cell-type specific, and vice versa. Differential expression analysis of ST data identified AD-associated lncRNAs with distinct spatial patterns and moderate overlap with differentially expressed (DE) lncRNAs from bulk RNA-seq. Gene set enrichment revealed their involvement in chromatin remodeling, epigenetic regulation, and RNA metabolism. We also identified AD DE lncRNAs across major brain cell types using snRNA-seq but overlap with ST DE lncRNAs was limited. Among previously reported lncRNAs, OIP5-AS1 was consistently upregulated in AD in all cortical subregions. Antisense oligonucleotide (ASO) knockdown of OIP5-AS1 in iPSC-derived microglia led to upregulation of pro-inflammatory genes and downregulation of DNA replication and repair pathways. Immunoassays confirmed increased secretion of pro-inflammatory cytokines. The knockdown expression pattern was enriched for microglia-specific AD DE genes and microglia states. ConclusionsThis study provides a spatial and cellular map of lncRNAs in the aging human cortex and identifies subregion-and cell-type-enriched DE lncRNAs in AD. Our findings implicate OIP5-AS1 in microglial activation, suggesting its potential contribution to AD pathogenesis.

neuroscience↗

The YTHDF Proteins Shape the Brain Gene Signatures of Alzheimer's Disease

The gene signatures of Alzheimers Disease (AD) brains reflect an output of a complex interplay of genetic, epigenetic, epi-transcriptomic, and post-transcriptional regulation., yet the dominant factor shaping these signatures remains unclear. To identify the most significant factor that shapes the AD brain signatures, we integrated cellular and molecular features with differential gene expression in in an explainable machine learning framework. Our result indicates that YTHDF proteins, the canonical readers of N6-methyladenosine RNA modification (m6A), are the most influential predictors of the AD brain signatures. We then show that protein modules containing YTHDFs are downregulated in human AD brains, and knocking down and pharmacologically inhibiting YTHDFs in iPSC-derived 2D and 3D neuronal models recapitulate the AD-associated transcriptional signatures. Furthermore, eCLIP-seq analysis revealed that YTHDF proteins influence AD signatures through both m6A-dependent and independent pathways. These results highlight the central role of YTHDF proteins in shaping the gene signatures of AD brains.

neuroscience↗

Uncovering Plaque-Glia Niches in Human Alzheimer's Disease Brains Using Spatial Transcriptomics

Amyloid-beta (A{beta}) plaques and surrounding glial activation are prominent histopathological hallmarks of Alzheimers Disease (AD). However, it is unclear how A{beta} plaques interact with surrounding glial cells in the human brain. Here, we applied spatial transcriptomics (ST) and immunohistochemistry (IHC) for A{beta}, GFAP, and IBA1 to acquire data from 258,987 ST spots within 78 postmortem brain sections of 21 individuals. By coupling ST and adjacent-section IHC, we showed that low A{beta} spots exhibit transcriptomic profiles indicative of greater neuronal loss than high A{beta} spots, and high-glia spots present transcriptomic changes indicative of more significant inflammation and neurodegeneration. Furthermore, we observed that this ST glial response bears signatures of reported mouse gene modules of plaque-induced genes (PIG), oligodendrocyte (OLIG) response, disease-associated microglia (DAM), and disease-associated astrocytes (DAA), as well as different microglia (MG) states identified in human AD brains, indicating that multiple glial cell states arise around plaques and contribute to local immune response. We then validated the observed effects of A{beta} on cell apoptosis and plaque-surrounding glia on inflammation and synaptic loss using IHC. In addition, transcriptomic changes of iPSC-derived microglia-like cells upon short-interval A{beta} treatment mimic the ST glial response and mirror the reported activated MG states. Our results demonstrate an exacerbation of synaptic and neuronal loss in low-A{beta} or high-glia areas, indicating that microglia response to A{beta}-oligomers likely initiates glial activation in plaque-glia niches. Our study lays the groundwork for future pathology genomics studies, opening the door for investigating pathological heterogeneity and causal effects in neurodegenerative diseases.

genomics↗

Streptococcus pyogenes M1T1 variants induce an inflammatory phenotype in neutrophils

Invasive infections due to Group A Streptococcus (GAS) advance rapidly causing tissue degradation and unregulated inflammation. Neutrophils are the primary immune cells that respond to GAS. The neutrophil response to GAS was characterised in response to two M1T1 isolates; 5448 and animal passaged variant 5448AP. Neutrophil co-incubation with 5448AP allowed proliferation of GAS while it also lowered the production of reactive oxygen species by neutrophils when compared with 5448. Infection with both strains invoked neutrophil death, however apoptosis was reduced in response to 5448AP. Both strains induced neutrophil caspase-1 activation and caspase-4 expression in vitro, with caspase-1 activation detected in vivo. Thus, GAS infection of neutrophils corresponds to increased caspase-1 activity and caspase-4 expression, consistent with inflammasome activation and pyroptosis. GAS infections that promote an inflammatory neutrophil phenotype may contribute to increased inflammation yet ineffective bacterial eradication, contributing to the speed and severity of invasive GAS infections.

microbiology↗