Biology subjects

Basak, P.

Publications and source records attributed to Basak, P..

13 recordsLinked to original sources

bioRxiv2026

G quadruplex DNA facilitates a pervasive path to homologous recombination

Homologous recombination (HR) requires efficient homology search and strand invasion, yet how homologous templates are identified within nuclear space remains unclear. Here, we identify G-quadruplex (G4) DNA structures as pervasive effectors of template strand invasion and uncover the G4 helicase DHX36 as a potent suppressor of this process. DHX36 loss stabilizes G4s, enhances HR, and accelerates repair of replication-associated DNA breaks. G4-mediated HR depends on the non-canonical strand invasion factors RAD51AP1, WDR48, and USP1, and requires G4 motifs within the homologous repair template. DHX36 loss partially restores HR and PARP inhibitor resistance in BRCA1-deficient cells, while promoting aberrant recombination and Alternative Lengthening of Telomeres (ALT). Together, our findings establish dynamic G4 regulation as a key determinant of homology search, genome maintenance, and recombination fidelity.

molecular biology↗

bioRxiv2026

The chromatin remodeling complex PRC2 safeguards cell fate in alveolar epithelial type 2 cells

Maintenance of the gas exchange surface throughout life and regeneration of the lung after injury requires tight regulation of epithelial cell fate and function. Alveolar epithelial type 2 (AT2) cells serve as the progenitors of the distal epithelium, differentiating into alveolar epithelial type 1 (AT1) cells or proliferating to maintain the quorum of AT2 cells. Here we describe the role of the chromatin regulator polycomb repressive complex 2 (PRC2) in the maintenance of AT2 cell fate in the adult alveolus. Cross-species single-cell transcriptomic analyses identified PRC2 activation in proliferative AT2 populations. PRC2 loss of function in human iPSC-derived AT2 (iAT2) cells and primary murine AT2 cells in vitro resulted in loss of AT2 cell state and emergence of programs reminiscent of alveolar-basal intermediate (ABI) cell states, while overexpression of the PRC2 enzymatic component EZH2 in human iAT2 cells augmented the AT2 cell program. Genetic loss of PRC2 function in the AT2 lineage in adult mice in vivo led to emphysematous remodeling of the lung and induced a time-dependent series of transitions of AT2 cells through an alveolar-basal intermediate (ABI) state into Krt5+ basal-like cells. Comparison of murine ABI cells to human disease-associated ABI cells demonstrates de-repression of canonical PRC2 targets during transition to ABI and basal-like states in human fibrosis, implicating PRC2 is a conserved regulator of AT2 cell fate. Together, these findings define PRC2 complex function during AT2 cell self-renewal as a critical guardrail for maintaining epithelial cell fate in the adult lung.

genetics↗

bioRxiv2026

Conformalized Multiview Learning

SO_SCPLOWUMMARYC_SCPLOWThere is an overwhelmingly large body of literature and numerous algorithms already available on "multimodal AI", based on different modeling and fusion paradigms. As multimodal AI becomes fully integrated into healthcare applications, the ability to say "Im not sure" or "I dont know" when uncertain is a necessary capability for safe clinical deployment, requiring the augmentation of current multimodal AI techniques. Our goal in this work is not to add yet another method to the growing toolbox of multimodal AI, but rather to (i) clarify how existing supervised multimodal AI methods can be understood through the lens of uncertainty quantification, and (ii) develop a unified framework that provides valid and interpretable uncertainty estimates for multimodal AI practitioners. We introduce Coracle, a conformalized framework for multimodal AI that seamlessly adapts to early, late, and intermediate fusion. Coracle provides theoretical marginal confidence guarantees and achieves valid finite-sample coverage without relying on distributional assumptions. Through extensive simulations and analyses of diverse biomedical multiview datasets, we demonstrate that Coracle consistently outperforms existing non-conformalized methods in both uncertainty estimation and calibration. By equipping published multiview models with valid, interpretable confidence measures, Coracle advances the development of trustworthy, uncertainty-aware statistical tools for biomedical decision support. Coracle is publicly available as an open-source R package at https://github.com/himelmallick/Coracle.

systems biology↗

bioRxiv2025

Bayesian Cooperative Learning for Multimodal Integration

Bayesian multimodal models that integrate data from multiple sources, studies, or modalities have garnered considerable attention in recent years. However, existing methods either rely on computationally expensive Markov chain Monte Carlo (MCMC) schemes or adopt variational approaches that forgo principled uncertainty quantification. To address this limitation and cater to practical needs, we abandon the MCMC framework and turn to resampling-based posterior inference for multimodal integration. Our method, Bayesian Cooperative Learning (BayesCOOP), embeds fast maximum a posteriori (MAP) estimation within a Bayesian bootstrap, combining a novel jittered group spike-and-slab prior with an efficient expectation-maximization (E M) coordinate descent algorithm under randomly weighted data perturbations. Averaging posterior summaries (MAP estimates) across bootstrap replicates yields approximate posterior samples that retain Bayesian interpretability while avoiding the computational burden of traditional sampling-based inference. We establish theoretical connections between BayesCOOPs pseudo-posterior averaging and posterior contraction principles, demonstrating near-optimal posterior consistency under sparsity. Extensive simulation studies and analyses of pregnancy multi-omics datasets demonstrate that BayesCOOP substantially outperforms state-of-the-art early, intermediate, and late fusion approaches in estimation, prediction, and uncertainty assessment. The open-source implementation of BayesCOOP is available at https://github.com/himelmallick/BayesCOOP.

bioinformatics↗

bioRxiv2025

A detailed study Biofilm forming Polyextremophilic Firmicutes from the Himalayas and exploration of their plant growth promoting potential.

Polyextremophily has been an intriguing point of interest among the scientists, a phenomenon in which organisms can thrive in combinations of multiple extreme conditions. In the foreseeable future, climatic conditions are predicted to change, and agriculture is bound to suffer with these changes in the environment. The situation necessitates some solutions that can ensure agricultural sustainability, in the changed, harsh environmental conditions without more toxic chemical intrusions in the agricultural fields. The bacterial strains Brevibacillus parabrevis BRAM_Y3 and Mesobacillus subterraneous BRAM_Y2 in this study, isolated from the waters of Yamunotri showed incredible properties of Polyextremophily like tolerance to not only temperatures as high as 70{degrees}C, pH range (4-10), saline, drought, UV and heavy metals such as mercury, iron, silver and arsenic but also their two-dimensional and three-dimensional combinations. The elevated levels of biofilm formation when subjected to stress revealed their property of using biofilm as their shield against harsh conditions. Furthermore, they were studied for their plant growth promotion like nutrient sequestration (N, P, K, plant hormone production etc.) biocontrol properties (cell wall degrading enzymes, siderophores, VOCs etc.) and the ability to confer abiotic stress resistance (ACC Deaminase) to plants. The in-vivo experiments conducted on Zea mays. L yielded conclusive and promising results. The use of these polyextremophiles for agriculture in harsh environments may serve as a solution for the global warming mediated climate and environmental changes.

microbiology↗

bioRxiv2025

Azadiradione regulates Heat Shock Factor 1 function by interacting with its DNA-binding domain independent of the oligomerization domain

Heat shock factor 1 (HSF1) masters cellular proteostasis under stress by upregulating the expression of molecular chaperones that help refold or degrade the misfolded proteins. HSF1 activation involves a monomer-to-oligomer transition and binding to its recognition sequence, the heat shock elements (HSEs) on its target gene promoters. HSF1 activity declines with age as well as in neurodegenerative disorders (NDs) such as Parkinsons disease, highlighting the need for strategies to restore its function. Azadiradione (AZD), a limonoid isolated from Azadirachta indica seeds, directly activates HSF1 in cellular and preclinical ND models, unlike other small-molecule activators reported elsewhere. We investigated the molecular basis of AZD-mediated HSF1 activation using purified variants of this protein including those without its oligomerization and transactivation domain. Fluorescence polarization and dynamic light scattering assays revealed that AZD promotes the oligomerization of monomeric HSF1 to enhance its HSE-binding affinity by engaging with its DNA-binding domain (DBD). The oligomerization domain known to be required for stress-induced activation, appears redundant in AZD-mediated activation. Furthermore, evidence suggests AZD-induced conformational alterations in the HSE facilitate its binding to the HSF1 monomer. Notably, AZD reduces the DNA-binding ability of pre-assembled oligomeric HSF1 by triggering its amyloid-like aggregation. This finding also highlighted a potential anticancer effect of AZD, as cancer cells heavily depend on this HSF1 population for rapid proliferation and survival. Overall, these findings offer novel insights into the functional regulation of HSF1 and suggest a framework for developing small-molecule HSF1 activators with therapeutic potential for protein conformation disorders.

biochemistry↗

bioRxiv2025

Repurposing without Reinventing the Wheel - Ensemble Models for Differential Analysis

Inspired by ensemble models in machine learning, we propose a general framework for aggregating multiple distinct base models to enhance the power of published differential association analysis (DAA) methods. We demonstrate this approach by augmenting popular DAA models with one or more biologically motivated alternatives. This creates an ensemble that bypasses the challenge of selecting an optimal model and instead combines the strengths of complementary statistical models to achieve superior performance. Our proposed ensemble learning approach is platform-agnostic and can augment any existing DAA method, providing a general and flexible framework for various downstream modeling tasks across domains and data types. We performed extensive benchmarking across both simulated and experimental datasets spanning single-cell gene expression, bulk transcriptomics, and microbiome metagenomics, where the ensemble strategy vastly outperformed non-ensemble methods, identified more differential patterns than the competing methods, and displayed good control of false positive and false discovery rates across diversified scenarios. In addition to highlighting a substantial performance boost for state-of-the-art DAA methods, this work has practical implications for mitigating the so-called reproducibility crisis in omics data science. An open-source R package implementing the ensemble strategy is publicly available at https://github.com/himelmallick/DAssemble.

bioinformatics↗

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↗

bioRxiv2024

Targeted pre-conditioning and cell transplantation in the murine lower respiratory tract

Transplantation of airway basal stem cells could achieve a durable cure for genetic diseases of the airway, such as cystic fibrosis and primary ciliary dyskinesia. Recent work demonstrated the potential of primary- and pluripotent stem cell (PSC)-derived basal cells to efficiently engrai into the mouse trachea aier injury. However, there are many hurdles to overcome in translating these approaches to humans including developing safe and efficient methods for delivery in larger animal models. We propose a model which targets preconditioning and cell-delivery to the intrapulmonary airways utilizing a micro- bronchoscope for delivery. The detergent polidocanol was adapted for distal lung pre-conditioning, inducing intrapulmonary airway epithelial denudation by 5 and 24-hours post-delivery. While initial re- epithelialization of airways occurred later than tracheas, complete repair was observed within 7-days. Both PSC-derived and primary basal cells delivered via micro-bronchoscope post-polidocanol injury engraied in tracheas and intrapulmonary airways, respectively. Transplanted cells differentiated into ciliated and secretory lineages while maintaining a population of basal cells. These findings demonstrate the utility of bronchoscopically targeted pre-conditioning and cell delivery to the conducting intra- pulmonary airways, providing an important framework for pre-clinical translation of approaches for engineered airway epithelial regeneration.

cell biology↗

bioRxiv2024

Co-existence of plasmid-mediated blaNDM-1 and blaNDM-5 in Escherichia coli sequence type 167 and ST101 and their discrimination through restriction digestion

The concurrent presence of multiple New Delhi metallo-{beta}-lactamase (blaNDM) variants within an isolate often goes undetected without the use of next-generation sequencing. This study detects and characterizes dual blaNDM-variants in Escherichia coli through Sanger and whole-genome sequencing. Additionally, a rapid identification method utilizing restriction digestion was designed for detecting variants carrying M154L mutation. Antibiotic susceptibility, minimal inhibitory concentration for meropenem and ertapenem, PCR and Sanger sequencing of blaNDM along with genome sequencing using Ilumina and Nanopore technology were conducted. Transmissibility and replicon types of blaNDM-harbouring plasmids were evaluated. Restriction digestion using restriction enzyme, BtsCI was developed to distinguish between blaNDM-1 and variants possessing M154L mutations. Two isolates belonging to phylogroups A; ST167 and B1; ST101 and resistant to meropenem and ertapenem ([≥]16mg/L) were recovered from the blood of a neonate and the rectal swab of a pregnant woman respectively. blaNDM was detected by PCR, and Sanger sequences of blaNDM showed two peaks at 262 (G & T) and 460 (A & C) nucleotide positions indicative of more than one blaNDM variant. Hybrid assembly confirmed co-existence of blaNDM-1 and blaNDM-5 in each isolate. blaNDM-1 was located on IncY (ST167) and IncHI1A/HI1B (ST101), while blaNDM-5 was on a IncFIA/FII (ST167) and IncC (ST101) plasmids. Digestion with BtsC1 could discriminate blaNDM-1 and blaNDM-5. Co-existence of multiple blaNDMS, blaNDM-1 and blaNDM-5 in epidemic clones of E. coli is concerning. Restriction digestion method and Sanger sequencing can facilitate quick identification of dual blaNDM variants in single isolate. ImportanceThe global dissemination of antimicrobial resistance genes is a serious concern. One such gene, blaNDM, has spread all across the globe via plasmids. blaNDM confers resistance against all {beta}-lactam antibiotics except monobactams. Most of the earlier literature reported presence of single blaNDM variants. However, this study reports the prevalence of dual blaNDM variants (blaNDM-1 and blaNDM-5) located on two separate plasmids identified in two distinct E. coli epidemic clones ST167 and ST101; isolated from a septicaemic neonate and a pregnant mother respectively. blaNDM-5 differs from blaNDM-1 due to presence of two point mutations i.e., V88L and M154L. This study detected dual blaNDM-variants through Sanger sequences and further validated through hybrid-genome assembly. Detection of multiple blaNDM-variants in a single isolate remains difficult until genome sequencing or southern blotting are carried out. Hence, a simple restriction digestion method was devised for rapid screening of dual blaNDM-variants containing M154L mutation.

microbiology↗

bioRxiv2024

The membrane-targeting-sequence motif is required for exhibition of recessive resurrection in Escherichia coli RNase E

The essential homo-tetrameric endoribonuclease RNase E of Escherichia coli participates in global RNA turnover as well as stable RNA maturation. The protomers N-terminal half (residues 1-529) bears the catalytic, allosteric and tetramerization domains, including the critical active site residues D303 and D346. The C-terminal half (CTH, residues 530-1061) is dispensable for viability. We have previously described a phenomenon of recessive resurrection in RNase E that requires the CTH, wherein the wild-type homo-tetramer apparently displays nearly identical activity in vivo as a hetero-tetramer comprised of three catalytically dead subunits (with D303A/D346A substitutions) and one wild-type subunit. Here we show that recessive resurrection is exhibited even in dimeric RNase E with the CTH, and that it is largely dependent on presence of the membrane-targeting-sequence motif (residues 565-582). A single F575E substitution also impaired recessive resurrection, whereas other CTH motifs (such as those for binding of RNA or of partner proteins) were dispensable. The phenomenon was independent of RNA 5-monophosphate sensing by the enzyme. We propose that membrane-anchoring of RNase E renders it processive for endoribonucleolytic action, and that recessive resurrection and dominant negativity associated with mutant protomers are mutually exclusive manifestations of, respectively, processive and distributive catalytic mechanisms in a homo-oligomeric enzyme.

microbiology↗

bioRxiv2022

Glycyrrhizin, an inhibitor of HMGB1 induces autolysosomal degradation function and inhibits H. pylori infection

Helicobacter pylori a key agent for causing gastric complications is linked with peptic ulcer, gastritis, and in severe cases gastric cancer. In response to infection, host cells stimulate autophagy to maintain cellular homeostasis. However, H. pylori have evolved the ability to usurp the hosts autophagic machinery. High mobility group box1 (HMGB1), an alarmin molecule is a regulator of autophagy and its expression is augmented in gastric cancer and many other cancers. Therefore, this study aims to explore the role of glycyrrhizin (a known inhibitor of HMGB1) in autophagy during H. pylori infection. Human gastric cancer (AGS) cells were infected with H. pylori SS1 strain and further treatment was done with glycyrrhizin. Western blot was used to examine the expression levels of autophagy proteins. Autophagy and lysosomal activity were monitored by immunofluorescence. We have performed knockdown of HMGB1 to verify the effect of glycyrrhizin by siRNA transfection method. H. pylori-infection in vivo C56BL/6 mice model was established and the effect of glycyrrhizin treatment was studied. We found that the autophagy-lysosomal pathway was impaired due to a significant increase in lysosomal membrane permeabilization during H. pylori infection in AGS cells. Subsequently, glycyrrhizin treatment restored the lysosomal membrane integrity, accompanied by an increase in cathepsin B activity and reduction of ROS and inflammatory cytokine IL-8. The recovered lysosomal function enhanced autolysosome formation and concomitantly attenuated the intracellular H. pylori growth by eliminating the pathogenic niche from gastric cells. Additionally, glycyrrhizin treatment inhibited inflammation and improved gastric tissue damages in mice.

microbiology↗

bioRxiv2016

Metagenomic Characteristics of Bacterial Response to Petroleum Hydrocarbon Contamination in Diverse Environments as Revealed by Functional Taxonomic Strategies

Microbial remediation of oil polluted habitats remains one of the foremost methods for restoration of petroleum hydrocarbon contaminated environments. The development of effective bioremediation strategies however, require an extensive understanding of the resident microbiome of these habitats. Recent developments such as high-throughput sequencing has greatly facilitated the advancement of microbial ecological studies in oil polluted habitats. However, effective interpretation of biological characteristics from these large datasets remains a considerable challenge. In this study, we have implemented recently developed bioinformatic tools for analyzing 65 publicly available 16S rRNA datasets from 12 diverse hydrocarbon polluted habitats to decipher metagenomic characteristics of bacterial communities of the same. We have comprehensively described phylogenetic and functional compositions of these habitats and additionally inferred a multitude of metagenomic features including 255 taxa and 414 functional modules which can be used as biomarkers for effective distinction between the 12 oil polluted sites. We have identified essential metabolic signatures and also showed that significantly over-represented taxa often contribute to either or both, hydrocarbon degradation and additional important functions. Our findings reveal significant differences between hydrocarbon contaminated sites and establishes the importance of endemic factors in addition to petroleum hydrocarbons as driving factors for sculpting hydrocarbon contaminated bacteriomes.

microbiology↗