Biology subjects

Bhat, N.

Publications and source records attributed to Bhat, N..

4 recordsLinked to original sources

bioRxiv2025

STUDIES ON INTERACTION OF MORIN WITH CURLI TO IDENTIFY AGGREGATION NATURE

Morin (3,5,7,2',4'-pentahydroxyflavone) is a flavonoid compound exhibited a range of biological functions, including anti-inflammatory, antioxidant, antiviral, and anti-allergic activities. It has the ability to disaggregate amyloid fibrils, making it a potential inhibitor of diseases caused by amyloid protein fibrillation. This study focuses on the interaction between Morin and Curli amyloid fibrils, which are produced by some Enterobacteriaceae, including Salmonella sp. And E. coli, as a major component of their biofilms. The Curli amyloid fibrils can lead to neurodegenerative diseases through a signalling cascade causing various human diseases, such as Alzheimers and Huntingtons diseases. Thioflavin T (ThT) fluorescence assays to purified Curli, and molecular docking between Morin and Curli indicates nature of binding at molecular level. The results showed that Morin quenched Curli fluorescence in a concentration-dependent manner, indicating dynamic quenching. Stern-Volmer analysis revealed that Morin binds to Curli with a binding constant of approximately 102 L/mol. This binding was found to be spontaneous, with hydrophobic interactions playing a significant role. ThT fluorescence assays confirmed that Morin inhibited Curli fibrillation, suggesting a potential therapeutic application. Molecular docking analysis revealed specific interactions between Morin and Curli, providing insights into their binding at the molecular level. In conclusion, this study demonstrates the dynamic quenching of Curli fluorescence by Morin and suggested that Morin may inhibit Curli fibrillation, making it a valuable candidate for the development of therapeutic drugs.

biochemistry↗

bioRxiv2020

Dyrk1b is a key Regulatory Kinase Integrating Fgf, Shh and mTORC1 signaling in Skeletal Muscle Development and Homeostasis

The advent of human genetics has provided unprecedented opportunities for discovery of novel disease pathways. Mutations in DYRK1B have been associated with metabolic syndrome and sarcopenic obesity in humans, underscoring the critical role of the encoded protein in skeletal muscle development and homeostasis. By the novel creation of Dyrk1b knockout zebrafish models we demonstrate that Dyrk1b kinase activity is critical for specification of the paraxial myoD. Mechanistically, Dyrk1b mediates and amplifies Fgf signaling in the paraxial domain by the transcriptional suppression of its negative feedback inhibitor sprouty1. In the adaxial myoD domain, Dyrk1b amplifies Shh signaling and partially rescues defects caused by its disruption. The investigations of C2C12 terminal differentiation revealed that Dyrk1b also plays a critical role in myofiber fusion. Combined biochemical and proteomic analysis of C2C12 myoblasts undergoing differentiation showed that Dyrk1b kinase activation is induced by shh inhibition, and triggers differentiation by inhibiting mTOR, subsequent upregulation of 4e-bp1 and induction of autophagy. In conclusion, we demonstrate that Dyrk1b plays a critical role in sustaining myocyte specification and differentiation by integrating Fgf, Shh and mTORC1 signaling pathways.

developmental biology↗

bioRxiv2019

Apcdd1 is a dual BMP/Wnt inhibitor in the developing nervous system and skin

Animal development and homeostasis depend on precise temporal and spatial intercellular signaling. Components shared between signaling pathways, generally thought to decrease specificity, paradoxically can also provide a solution to pathway coordination. Here we show that the Bone Morphogenetic Protein (BMP) and Wnt signaling pathways share Apcdd1 as a common inhibitor and that Apcdd1 is a taxon-restricted gene with novel domains and signaling functions. Previously, we showed that Apcdd1 inhibits Wnt signaling, here we find that Apcdd1 potently inhibits BMP signaling in body axis formation and neural differentiation in chicken, frog, zebrafish, and humans. Our results from experiments and modeling suggest that Apcdd1 may coordinate the outputs of two signaling pathways central to animal development and human disease. Significance StatementApcdd1 is a taxon-restricted gene that inhibits both BMP and Wnt intercellular signaling pathways in multiple organisms including mice, frog, zebrafish, and chicken. It encodes a bi-functional protein with a novel protein domain that can bind to Wnt and BMP receptors and block downstream signaling.

systems biology↗

bioRxiv2018

TCF7L2 Regulation of GATA6-dependent and -Independent Vascular Smooth Muscle Cell Plasticity and Intimal Hyperplasia

Genetic variations in Wnt-coreceptor LRP6 and Wnt-regulated transcription factor TCF7L2 have been among the strongest genetic signals for type2 diabetes (T2DM) and coronary artery disease (CAD). Mice with a CAD-linked LRP6 mutation exhibit obstructive coronary artery disease characterized by reduced TCF7L2 expression and dedifferentiation of vascular smooth muscle cell (VSMC). While TCF7L2 maintains stemness and promotes proliferation in embryonic tissues and adult stem cells, its role and mechanisms of action in VSMC differentiation is not understood. Using multiple mouse models, we demonstrate here that TCF7L2 promotes differentiation and inhibits proliferation of VSMCs. TCF7L2 accomplishes these effects by stabilization of GATA6 and upregulation of SM-MHC and cell cycle inhibitors. Accordingly, TCF7L2 haploinsufficient mice exhibited increased susceptibility to, while mice overexpressing TCF7L2 were protected against injury-induced intimal hyperplasia compared to wildtype littermates. Consequently, the overexpression of TCF7L2 in LRP6 mutant mice rescued the injury induced intimal hyperplasia. These novel findings imply cell type-specific functional role of TCF7L2 and provide critical insight into poorly understood mechanisms underlying pathogenesis of intimal hyperplasia.

molecular biology↗