Biology subjects

Dutta, A. K.

Publications and source records attributed to Dutta, A. K..

5 recordsLinked to original sources

bioRxiv2026

Computational Structure Modeling, Functional Characterization, and Identification of Potential Inhibitors for the cyclic-di-GMP Mediated Biofilm Forming Membrane Protein in Vibrio cholerae

Cholera, caused by Vibrio cholerae, continues to pose a serious global public health challenge, with its impact worsened by rising antibiotic resistance associated with bacterial biofilm formation. This study reveals the role of the hypothetical protein (HP) TYC33605.1 in cyclic-di-GMP (c-di-GMP)-mediated biofilm regulation and identifies natural inhibitors that disrupt this mechanism. Functional annotation revealed TYC33605.1 as a membrane-associated diguanylate cyclase (DGC) with GGDEF and sensory domains, critical for c-di-GMP synthesis and biofilm persistence. Homology modelling and molecular dynamics (MD) simulations validated its stable 3D structure (C-score: -1.22, Ramachandran favoured regions: 91.1%) and dynamic behaviour (average RMSD: 8.55 [A]). Virtual molecular docking screening of 1,092 natural compounds identified Luteolin (CID 5280445) and Sativanone (CID 13886678) as top candidates, exhibiting strong binding affinities (-9.1 and -9.0 kcal/mol, respectively) and forming hydrogen bonds, {pi}-cation, and hydrophobic interactions with key residues (Glu293, Arg364, Ala176). MD simulations (100 ns) confirmed complex stability, with Luteolin and Sativanone showing lower RMSD fluctuations (7.78 [A] and 8.13 [A]) compared to the control and apoprotein. The ADME/Tox profiles highlighted favourable pharmacodynamics (PD), pharmacokinetics (PK), high gastrointestinal absorption, no hepatotoxicity, and drug-likeness (Lipinski compliance). Principal component, probability density function, and binding free energy analyses underscore ligand-induced conformational stability. This study proposes the molecular characterisation of the HP and the bioactive compounds Luteolin and Sativanone as promising inhibitors targeting TYC33605.1, offering a novel strategy to combat biofilm-mediated antibiotic resistance and a framework for analogous antimicrobial discovery in Vibrio cholerae.

bioinformatics↗

bioRxiv2025

Targeting RUNX1 in Macrophages Facilitates Cardiac Recovery

Despite advances in disease treatment, our understanding of how damaged organs recover and the mechanisms governing this process remain poorly defined. Here, we mapped the transcriptional and regulatory landscape of human cardiac recovery using single cell multiomics. Macrophages emerged as the most reprogrammed cell type. Deep learning identified the transcription factor RUNX1 as a key regulator of this process. Macrophage-specific Runx1 deletion recapitulated the human cardiac recovery phenotype in a chronic heart failure model. Runx1 deletion reprogrammed macrophages to a reparative phenotype, reduced fibrosis, and promoted cardiomyocyte adaptation. RUNX1 chromatin profiling revealed a conserved regulon that diminished during recovery. Mechanistically, the epigenetic reader BRD4 controlled Runx1 expression in macrophages. Chromatin activity mapping, combined with CRISPR perturbations, identified the precise regulatory element governing Runx1 expression. Therapeutically, small molecule Runx1 inhibition was sufficient to promote cardiac recovery. Our findings uncover a druggable RUNX1 epigenetic mechanism that orchestrates recovery of heart function.

immunology↗

bioRxiv2024

Short lifespan is one's fate, long lifespan is one's achievement: lessons from Daphnia

Studies of longevity and senescence rely on baseline life expectancy of reference genotypes measured in standardized conditions such as food level and group size. Variation in baseline lifespan data across labs and protocols and among genotypes can make longevity intervention studies difficult to compare, particularly when GxE interactions exist. Furthermore, extending the lifespan of a short-lived genotype or of any genotype under suboptimal conditions may be of a lesser theoretical and translational value than extending the maximal possible lifespan. Daphnia is rapidly becoming a model organism of choice for longevity research complementing data obtained on traditional models. In this study we report baseline longevity of several genotypes (parthenogenetic clones) of a long-lived species D. magna under a variety of laboratory protocols, aiming to document the highest possible lifespan, factors reducing it, and physiological parameters that change with age and correlate with longevity. Combining data from 25 different experiments across two labs we report strong differences among clones of different geographic origin, moderate effects of group size and medium composition on longevity, and strong GxE with respect to food level. Specifically, short-lived clones that tend to originate from small intermittent habitats show little or no caloric restriction (CR) longevity extension, while long-lived ones expand their lifespan even further when maintained at 25% of the ad libitum food. We find no evidence of any trade-offs between longevity and fecundity across clones or correlations with age-specific feeding rate. We find that in the short-lived, CR non-responsive clones show little correlation between longevity and two measures of lipid peroxidation (LPO: lipid hydroperoxides and MDA abundance). In contrast, the long-lived, CR-responsive clones show a positive longevity correlation with lipid hydroperoxide abundance at any age, and a negative correlation with MDA concentration measured at about median lifespan. This indicates differences among genotypes in longevity-related accumulation of LPO targets, efficiency of detoxification of LPO products, and/or their effects on longevity. Our observations support the hypothesis that a long lifespan can be affected by food availability and levels of oxidative damage, while genetically determined short lifespan remains short regardless. We suggest a set of condition and genotypes to be used as a reference for longevity studies in Daphnia.

ecology↗

bioRxiv2022

Cinemeducation improves early clinical exposure to Inborn Errors of Metabolism

BackgroundCinemeducation has been shown to be an effective tool to help the students develop humanistic skills. However, there is a dearth of studies to find out if this can also be utilized to improve the interest and satisfaction of students learning about rare diseases such as the Inborn Errors of Metabolism. The aim was to introduce cinemeducation as part of early clinical exposure in teaching the inborn errors of metabolism for first-year MBBS students in the Department of Biochemistry. The Objectives were 1) to develop, validate and assess the feasibility of structured modules on Cinemeducation in teaching the Inborn Errors of Metabolism, 2) to study the impact of Cinemeducation on the satisfaction, interest, and academic performance of first-year MBBS students and 3) to study the perception of students and faculty towards Cinemeducation MethodsThis was a quasi-experimental, cross-over study involving 100 MBBS students in the Department of Biochemistry, AIIMS Kalyani. Movie clips prepared from Lorenzos Oil (for Lipid metabolism) and Extraordinary Measures (for Lysosomal Storage Disease) and corresponding paper-based cases; questionnaires and feedback forms were validated by expert group review. Analysis of quantitative data was performed in GraphPad, MS Excel and MAXQDA2022 software. Findings, Discussions and ConclusionsStudents academic performance was found to be improved in the groups where the Extraordinary Measures movie was used for Cinemeducation. Both learners and facilitators were satisfied with Cinemeducation. Cinemeducation was effectively introduced for teaching Inborn Errors of Metabolism in the Department of Biochemistry.

scientific communication and education↗

bioRxiv2018

Two bifunctional inositol pyrophosphate kinases/phosphatases control plant phosphate homeostasis.

Many eukaryotic proteins regulating phosphate (Pi) homeostasis contain SPX domains. We have previously shown that these domains act as cellular receptors for inositol pyrophosphate (PP-InsP) signaling molecules, suggesting that PP-InsPs may regulate Pi homeostasis. Here we report that simultaneous deletion of two diphosphoinositol pentakisphosphate kinases VIH1 and 2 in Arabidopsis impairs plant growth and leads to constitutive Pi starvation responses. We demonstrate that VIH1 and VIH2 are bifunctional cytosolic enzymes able to generate and break-down PP-InsPs. Point-mutants targeting the kinase and phosphatase active sites have opposing effects on plant Pi content and Pi starvation responses, while VIH1 and VIH2 protein levels remain constant in different Pi growth conditions. Enzymatic assays reveal that ATP-Mg2+ substrate levels can shift the relative kinase and phosphatase activities of full-length diphosphoinositol pentakisphosphate kinases. Deletion of phosphate starvation response transcription factors rescues vih1 vih2 mutant phenotypes, placing diphosphoinositol pentakisphosphate kinases and PP-InsPs in plant phosphate signal transduction cascades. We propose that VIH1 and VIH2 relay changes in cellular ATP concentration to changes in PPInsP levels, allowing plants to maintain cellular Pi concentrations constant and to trigger Pi starvation responses.

plant biology↗