Biology subjects

Chaudhary, P.

Publications and source records attributed to Chaudhary, P..

8 recordsLinked to original sources

bioRxiv2026

CAMSAP3 loss of function models suggest causative role in generalized genetic epilepsy

Advancements in next generation sequencing have led to the discovery of hundreds of human epilepsy gene associations. Newly associated genes require functional validation to establish causation and to inform patient treatment in the clinic. A recent exome trio analysis identified predicted pathogenic variants in two patients with generalized epilepsy in the gene CAMSAP3. CAMSAP3 regulates non-centrosomal microtubule dynamics, and the acetylation necessary for normal axonal differentiation and migration. We show that overexpression of patient variants leads to protein degradation and dysregulation of microtubule acetylation in cultured HEK cells. Camsap3 knockout zebrafish also exhibit increased axonal microtubule acetylation as well as epileptic features such as seizure-like swimming behaviors, aberrant inhibitory interneuron development and epileptiform via local field potential. Together these data suggest that CAMSAP3 plays an important role in generalized genetic epilepsy.

neuroscience↗

bioRxiv2026

Synbiotic Yogurt with Lactobacillus plantarum and Stevia rebaudiana: Physicochemical, Microbiological, and Functional Evaluation

Functional dairy products are increasingly recognized for their ability to provide both essential nutrition and additional health benefits. This study aimed to develop and evaluate a synbiotic yogurt enriched with Lactobacillus plantarum as a probiotic and Stevia rebaudiana extract (1% w/v) as a prebiotic source. Thirteen lactic acid bacteria (LAB) strains were isolated from fermented dairy and vegetable samples and evaluated for probiotic potential through tests for acid and bile tolerance, hydrophobicity, aggregation abilities, and pathogen co-aggregation. Isolate PG1 (Lactobacillus plantarum) demonstrated the highest prebiotic growth stimulation index (49%) in the presence of stevia extract and was selected for yogurt formulation. Yogurt samples were prepared and stored at 4{degrees}C for 10 days. Physicochemical properties (pH, titratable acidity, and protein content), microbiological viability, total phenolic and flavonoid content, antioxidant activity (DPPH assay), and sensory attributes were monitored. The synbiotic yogurt (St-Y) showed enhanced functional properties, with a total phenolic content of 16.67 {micro}g GAE/g, a flavonoid content of 6.28 {micro}g QE/g, and 57.84% antioxidant activity. Additionally, it showed improved protein content and superior sensory scores compared to control samples. These findings suggest that S. rebaudiana fortified probiotic yogurt can serve as a nutritious, antioxidant-rich, and sensory-acceptable functional dairy product.

microbiology↗

bioRxiv2025

Early death and neuronal abnormalities in depdc5 loss-of-function mosaic zebrafish models

DEPDC5 (DEP domain-containing protein 5) encodes a repressor of the mTORC1 signaling pathway. Variants in DEPDC5 are associated with a range of focal epilepsies, including mosaic variants associated with focal cortical dysplasia (FCD) and other focal brain malformations with brain-only somatic mosaic variants. To investigate the role of DEPDC5 in human epilepsy related to mosaic variants, we have generated mosaic depdc5 loss-of-function zebrafish models using homology-based constructs acutely targeting depdc5 and labeled with tdTomato to allow for visualization of the degree of mosaicism. The resulting mosaic depdc5 CRISPants demonstrated early larval death, with [~]50% of CRISPants (vs. 10% of controls) dead by 7 days post fertilization (dpf), analogous to the early death sometimes associated with human DEPDC5-related epilepsy. We compared depdc5 CRISPants with uninjected and scrambled controls from the same clutches. Body and head size were reduced in the depdc5 CRISPants. Analysis of swimming behavior showed a striking reduction in distance traveled and maximum velocity in the depdc5 CRISPants vs. controls. Based on visual confirmation of mutational load, we categorized CRISPants into depdc5+ vs. depdc5++, reflecting weak vs. strong tdTomato fluorescence. We observed that depdc5++ CRISPants had increased episodes of posture loss, suggesting increased seizure-like behavior related to higher percentages of mutant cells. Local field potential recordings revealed increased neuronal hyperexcitability in depdc5 CRISPants vs. controls. Acridine orange staining demonstrated early apoptosis in the CRISPants vs. controls. Our mosaic depdc5 CRISPants provide a clinically relevant model to study the role of mosaic DEPDC5-related epilepsy and early death.

neuroscience↗

bioRxiv2025

Biofabrication of gold nanoparticles (GNPs) synthesized from Dillenia indica leaves with their anticancer, antibacterial, and antioxidant activities.

In this study, we describe the cytotoxic and antibacterial capabilities of gold nanoparticles (GNPs) synthesized from Dillenia indica leaves. Here, we used an environmentally friendly method to synthesize GNPs and then characterized them using techniques such as transmission electron microscopy (TEM), dynamic light scattering (DLS), UV-visible spectroscopy, XRD, and Fourier transform infrared spectroscopy. The Surface Plasmon Resonance of GNPs was identified by an absorption peak at 533 nm in the UV-visible spectroscopic studies. The biosynthesized GNPs had an average size of 83 nm and were spherical in shape, according to TEM examination. Its interesting to note that the biosynthesized GNPs exhibited antibacterial action against a variety of bacterial isolates, both Gram-positive and negative. By using an MTT assay, growth inhibition and the cytotoxic effect of the synthesized GNPs against Daltons lymphoma cell lines were also evaluated.

plant biology↗

bioRxiv2025

CIT tumor lines: A novel series of immunogenic squamous cell skin carcinoma cell lines derived from chemical carcinogenesis

Immunotherapy is now widely used to treat advanced-stage skin cancer, but it is effective for only approximately half of skin cancer patients, including both patients with melanoma and cutaneous squamous cell carcinoma (cSCC). To overcome current barriers, preclinical mouse models that faithfully recapitulate the tumor genetics, mutation burdens, and neoantigen patterns of specific human tumor types are essential. However, while many models exist for melanoma, there are currently relatively few transplantable murine models of cSCC, which is responsible for nearly as many deaths as melanoma each year. Here we describe a novel series of 11 cSCC tumor lines, the Carcinogen-Induced Tumor (CIT) lines, syngeneic to the FVB strain, that address this need. The CIT lines were established from skin carcinomas induced by DMBA and TPA treatment and harbor genetic drivers and overall tumor mutational burdens that recapitulate those found in cSCC. Each CIT line gives rise to tumors with a consistent immune infiltration pattern, ranging from T cell-rich "hot" tumors to T cell-poor "cold" tumors. Hot CIT lines exhibit partial responses to treatment with immune checkpoint inhibitors, and we have identified two neoantigens present in an immunotherapy-responsive CIT line. The CIT lines thus provide a valuable new series of preclinical models for studying anti-tumor immune responses and developing strategies to improve immunotherapy efficacy in cSCC.

cancer biology↗

bioRxiv2021

Development of a yeast-based assay for bioavailable phosphorous

Preventing eutrophication of inland freshwater ecosystems requires quantifying the phosphorus (P) content of the streams and rivers that feed them. Typical methods for measuring P assess soluble reactive P (SRP) or total P (TP) and require expensive analytical techniques that produce hazardous waste. Here we present a novel method for measuring the more relevant bioavailable P (BAP); this assay utilizes the growth of familiar bakers yeast, avoids production of hazardous waste, and reduces cost relative to measurements of SRP and TP. The yeast BAP (yBAP) assay takes advantage of the observation that yeast density at saturating growth increases linearly with provided P. We show that this relationship can be used to measure P in freshwater in concentration ranges relevant to eutrophication. In addition, we measured yBAP in water containing known amounts of fertilizer and in samples from agricultural waterways. We observed that the majority of yBAP values were between those obtained from standard SRP and TP measurements, demonstrating that the assay is compatible with real-world settings. The cost-effective and nonhazardous nature of the yeast-based assay suggests that it could have utility in a range of settings, offering added insight to identify water systems at risk of eutrophication from excess phosphorus.

ecology↗

bioRxiv2021

TREM2 is thyroid hormone regulated making the TREM2 pathway druggable with ligands for thyroid hormone receptor

Triggering receptor expressed on myeloid cells-2 (TREM2) is a cell surface receptor on macrophages and microglia that senses and responds to disease associated signals to regulate the phenotype of these innate immune cells. The TREM2 signaling pathway has been implicated in a variety of diseases ranging from neurodegeneration in the central nervous system to metabolic disease in the periphery. We report here that TREM2 is a thyroid hormone regulated gene and its expression in macrophages and microglia is stimulated by thyroid hormone. Both endogenous thyroid hormone and sobetirome, a synthetic thyroid hormone agonist drug, suppress pro-inflammatory cytokine production from myeloid cells including macrophages that have been treated with the SARS-CoV-2 spike protein which produces a strong, pro-inflammatory phenotype. Thyroid hormone agonism was also found to induce phagocytic behavior in microglia, a phenotype consistent with activation of the TREM2 pathway. The thyroid hormone antagonist NH-3 blocks the anti-inflammatory effects of thyroid hormone agonists and suppresses microglia phagocytosis. Finally, in a murine experimental autoimmune encephalomyelitis (EAE) multiple sclerosis model, treatment with Sob-AM2, a CNS-penetrating sobetirome prodrug, results in increased Trem2 expression in disease lesion resident myeloid cells which correlates with therapeutic benefit in the EAE clinical score and reduced damage to myelin. Our findings represent the first report of endocrine regulation of TREM2 and provide a unique opportunity to drug the TREM2 signaling pathway with orally active small molecule therapeutic agents.

immunology↗

bioRxiv2020

Thyroid hormone and thyromimetics inhibit myelin and axonal degeneration and oligodendrocyte loss in EAE

We have previously demonstrated that thyromimetics stimulate oligodendrocyte precursor cell differentiation and promote remyelination in murine demyelination models. We investigated whether a thyroid receptor-beta selective thyromimetic, sobetirome (Sob), and its CNS-targeted prodrug, Sob-AM2, could prevent myelin and axonal degeneration in experimental autoimmune encephalomyelitis (EAE). Compared to controls, EAE mice receiving triiodothyronine (T3, 0.4mg/kg), Sob (5mg/kg) or Sob-AM2 (5mg/kg) had reduced clinical disease and, within the spinal cord, less tissue damage, more normally myelinated axons, fewer degenerating axons and more oligodendrocytes. T3 and Sob also protected cultured oligodendrocytes against cell death. Thyromimetics thus might protect against oligodendrocyte death, demyelination and axonal degeneration as well as stimulate remyelination in multiple sclerosis. HighlightsO_LIThyroid hormone, the thyromimetic Sob and its CNS penetrating prodrug, Sob-AM2, reduce disease severity, reduce myelin and axonal degeneration and protect oligodendrocytes in EAE. C_LIO_LIThe benefits of Sob and Sob-AM2 may be via direct protective effects on oligodendrocytes and reduction in activity of microglia/macrophages. C_LI

neuroscience↗