Biology subjects

Chakraborty, G.

Publications and source records attributed to Chakraborty, G..

7 recordsLinked to original sources

bioRxiv2026

WebCalEM: a browser-based tool for routine and accurate pixel size calibration in cryo-EM

Accurate determination of the image pixel size is critical for quantitative cryo-electron microscopy analyses, yet existing calibration methods remain under-utilized because installation barriers and workflow complexity discourage routine adoption. To fill in this gap, a web-based application, WebCalEM, was developed to transform specialized calibration procedures into an accessible routine practice. Micrographs of any specimen with a known crystalline lattice, such as gold or graphene-oxide, are uploaded through a standard browser, processed entirely client-side, and analyzed with real-time visualization and downloadable statistical outputs. The application is delivered as a single self-contained HTML file that runs in any modern web browser without server-side computation, a configuration well suited to isolated core-facility microscope workstations. Cross-standard consistency between gold and graphene-oxide measurements across two microscopes and ten magnification settings yields a Bland-Altman bias of -0.005% of nominal with 95% limits of agreement of [-0.30%, +0.29%]. By delivering this workflow with no local installation, WebCalEM lowers the practical barrier to documented per-dataset magnification calibration in routine cryo-EM operation. SynopsisWebCalEM is a browser-based, install-free application that performs routine cryo-EM pixel-size calibration directly from gold or graphene-oxide reflections in standard sample-support grids using sub-pixel Fourier-space peak localization; it reproduces the precision of established command-line calibration tools while removing the installation barrier and supporting retrospective per-region calibration on archived datasets.

molecular biology↗

bioRxiv2026

A Unified Agent-Enabled Platform for Drug Repurposing across Molecular, Phenotypic, and Clinical Scales

Drug repurposing offers an effective path to new therapies, yet existing computational approaches rely on a single line of evidence and are rarely validated across biological scales. We present LinkD, an integrated framework that unifies diffusion-based affinity prediction, proteome-wide selectivity scoring, phenotypic validation, and population-scale clinical evidence. LinkD-Bind predicts binding across 14,981 drugs and 20,385 human targets, ranking first in 8 of 9 BindingDB, Davis, and KIBA evaluations, with the largest gains under cold-start conditions. LinkD-Select recovers 95.3% of known drug-target pairs by combining selectivity scoring and molecular docking. LinkD-Pheno integrates drug-sensitivity and CRISPR dependency data across 960 cancer cell lines, identifying 34 novel drug-gene pairs and recovering [~]85% of known targets among the top 50 candidates. Across 11.5 million individuals from Mount Sinai and UK Biobank, LinkD-prioritized {beta}-blockers propranolol (HR 0.82) and carvedilol (HR 0.92) reduced 5-year prostate cancer incidence relative to metoprolol, corroborated by ADRB2 docking and LNCaP growth inhibition. LinkD-Agent, which can effectively orchestrate all evidence layers, is served on a publicly available web platform (https://linkd-agent.onrender.com/), enabling a wide range of users to derive new drug repurposing opportunities through natural language queries.

bioinformatics↗

bioRxiv2025

Parkia javanica extracts exhibits tissue regeneration potential in Zebrafish (Danio rerio)

Parkia javanica is a medicinal plant acknowledged for its diverse pharmacological features, but its biological effects, like regeneration and wound-healing properties, in the zebrafish animal model (Danio rerio) is unexplored. The purpose of this study was to determine the caudal fin tissue regeneration and antioxidant potential in response to Parkia javanica fruit and bark extracts on Danio rerio. The Danio rerio caudal fin was amputated and subsequently was treated with Parkia javanica fruit and bark extracts at 0.346{micro}g/mL and 2.86{micro}g/mL respectively. The regenerative effects of Parkia javanica fruit and bark extracts were evaluated through morphological analysis and dorso-ventral patterning. Additionally, the antioxidant properties of Parkia javanica fruit and bark extracts, along with the mechanistic insights, were evaluated using qRT-PCR. We found that both the Parkia javanica fruit and bark extracts displayed substantial antioxidant capacity with upregulation of key genes like Cat and Sod1. Further, the extracts demonstrated significant fin regeneration compared to the control group. We observed that both the Parkia javanica fruit and bark extracts possess tissue regeneration properties by upregulating key genes, like Anxa2a, Anxa2b, and Wnt3a. All these findings provide novel insights into the molecular mechanisms underlying the tissue repair and regeneration effects of Parkia javanica fruit and bark extracts and may pave the way for the development of novel regenerative therapeutic strategies. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=128 SRC="FIGDIR/small/681930v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@9a579org.highwire.dtl.DTLVardef@14edd37org.highwire.dtl.DTLVardef@9d7addorg.highwire.dtl.DTLVardef@ed79da_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2025

Structural insights into the mechanism of C3 side chain fragmentation in cephalosporins with SME-1 class A carbapenemase

Cephalosporins remain one of the largest classes of antibiotics used clinically, with a diverse group of dual substituents at C3 and C7 positions. The fragmentation of the C-3 side chain from the C3 position after hydrolysis by Serine or metallo-{beta} lactamase leaving an exo-methylene group has been introduced in the literature recently, but the exact mechnism by which it happens remains unclear until now. Our incrystallo findings suggest that the fragmentation of the C3 side chain will depend on the C3 atom and its hybridization state. A C3 carbon with sp2 hybridization will not allow fragmentation, but a sp3 hybridized carbon will facilitate the detachment of the side chain. Furthermore, heteroatoms like Sulfur, on C3 position, bearing vacant d-orbitals participate in {pi}-cloud delocalization, making the detachment of C3 side chain energetically unfeasible. For the sp3 hybridized carbon at C3, the fragmentation of the bond was independent of the C3 atom. We observed fragmentation of the C3-C3 bond for all three heteroatoms, Nitrogen, Oxygen, and sulfur, at the C3 position. We validated our crystallographic findings with mass spectrometry to confirm the fragmentation of the C3 side chain in sp3 carbon and the unfragmented side chain in sp2 carbon and sulfur at C3 position. QM/MM simulations on three types of enzyme-cephalosporin complexes with different C3 side chains confirm the mechanism of fragmentation. Beyond revealing C3 side chain fragmentation in cephalosporins, useful for inhibitor and diagnostic design, our QM/MM methods are useful on incrystallo complexes to show the enzyme catalysis.

biochemistry↗

bioRxiv2023

Tri-n-butyl phosphate inhibits neurogenesis and motor functions during embryonic development in zebrafish

Tri-n-butyl phosphate (TBP), an organophosphate ester (OPE), is heavily used as a solvent in synthetic resins, inks, and adhesives and as an antifoaming agent in detergents and emulsion products. Further, it is used as a flame retardant and plasticizer in the fabric and electronics industry. Further, TBP is used to extract uranium, plutonium, and thorium. Thus, widespread uses of TBP in industrialized countries led to the release of TBP and its metabolites, dibutyl phosphate (DBP) and monobutyl phosphate (MBP), in the environment, including air, soil, and water, and get detected in human samples. Accumulating these OPEs over time in humans and other animals may develop toxicological effects. The reports also say OPEs contaminants pass through the mother-fetal transmission route and may affect embryonic development. However, the impact of TBP and its metabolites on vertebrate development has been poorly studied. Ex-Utero development, short generation time, high fecundity, optical transparency, and genetic and physiological similarity to humans make the zebrafish a preferred model for studying vertebrate development, organogenesis, small molecule screening, toxicological evaluation, etc. Thus, we aim to explore the toxic effects of TBP, DBP, and MBP on vertebrate organogenesis and overall embryonic development using zebrafish as a model organism. Our study found that TBP inhibits neural growth resulting in decreased spontaneous movements frequency at 22 and 28 hpf without altering the somite and overall embryonic growth in lower doses. In contrast, in lower concentrations, DBP-treated embryos showed normal neuronal and embryonic development and increased spontaneous movement frequency at 22 and 28 hpf. Further, we found that in higher concentrations, TBP is teratogenic, DBP is lethal to the embryos, and MBP did not show detectable toxic effects in the developing embryos. Altogether, we found that TBP inhibits neurogenesis, and its metabolite DBP is neuroexcitatory during embryonic development. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=86 SRC="FIGDIR/small/564317v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1855d5corg.highwire.dtl.DTLVardef@b470eeorg.highwire.dtl.DTLVardef@623b78org.highwire.dtl.DTLVardef@12e6e8f_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2021

Transcriptional Inactivation of TP53 and the BMP Pathway Mediates Therapy-induced Dedifferentiation and Metastasis in Prostate Cancer

Unsupervised clustering and deconvolution analysis identifies a novel subtype of M-CRPC endowed with hybrid epithelial/mesenchymal (E/M) and luminal progenitor-like traits (Mesenchymal and Stem-like PC, MSPC). Analysis of patient datasets and mechanistic studies indicate that MSPC arises as a consequence of therapy-induced lineage plasticity. AR blockade instigates two separate and complementary processes: 1) transcriptional silencing of TP53 and hence acquisition of hybrid E/M and stem-like traits; and 2) inhibition of the BMP signaling, which promotes resistance to the pro-apoptotic and anti-proliferative effects of AR inhibition. The drug-tolerant prostate cancer cells generated through reprogramming are rescued by neuregulin and generate metastases in mice. Combined inhibition of HER2/3 and AR or mTORC1 exhibit efficacy in preclinical models of mixed ARPC/MSPC or MSPC, respectively. These results identify a novel subtype of M-CRPC, trace its origin to therapy-induced lineage plasticity, and reveal its dependency on HER2/3 signaling.

cancer biology↗

bioRxiv2020

A simple strategy to reduce the salivary gland and kidney uptake of PSMA targeting small molecule radiopharmaceuticals

The past five years have seen an increasing acceptance of peptide-based prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (TRT) agents for treatment of metastatic castration-resistant prostate cancer (mCRPC), with [177Lu]-DKFZ-PSMA-617 ([177Lu]-PSMA-617) emerging as the leading candidate. [177Lu]-PSMA-617 and other PSMA ligands have shown efficacy in reducing the tumor burden in mCRPC patients but irradiation to salivary gland and kidneys is a concern and dose limiting factor. Therefore, methods to reduce non-target organ toxicity are needed to safely treat patients and preserve their quality of life. Here, we report the effects of the addition of the cold PSMA ligand DKFZ-PSMA-11 (PSMA-11) on the uptake of [177Lu]-PSMA-617 in tumor, salivary glands and kidneys. Groups of athymic nude mice (n = 4) bearing PC3-PIP (PSMA+) tumor xenografts were administered with [177Lu]-PSMA-617 along with 0, 5, 100, 500, 1000 and 2000 pmoles of PSMA-11. Biodistribution studies 1 h post-administration revealed that [177Lu]-PSMA-617 uptake in PSMA-expressing PC3-PIP tumors was 21.71{+/-}6.13, 18.7{+/-}2.03, 26.44{+/-}2.94, 16.21{+/-}3.5, 13.52{+/-}3.68, and 12.03{+/-}1.96 %ID/g when 0, 5, 100, 500, 1000 and 2000 pmoles of PSMA-11 were added, respectively. Corresponding kidney uptake values were 123.14{+/-}52.52, 132.31{+/-}47.4, 84.29{+/-}78.25, 2.12{+/-}1.88, 1.16{+/-}0.36, 0.64{+/-}0.23 %ID/g, respectively. Corresponding salivary gland uptake values were 0.48{+/-}0.11, 0.45{+/-}0.15, 0.38{+/-}0.3, 0.08{+/-}0.03, 0.09{+/-}0.07, 0.05{+/-}0.02 % ID/g, respectively. Thus, uptake of PSMA TRT agents in salivary gland and kidney can be substantially reduced without impact on tumor uptake by adding cold PSMA-11. Our data provides proof-of-concept and we propose that similar strategy be pursued in future clinical trials to prevent xerostomia and renal toxicity arising from [177Lu]-PSMA-617.

pharmacology and toxicology↗