Biology subjects

Bag, S.

Publications and source records attributed to Bag, S..

5 recordsLinked to original sources

bioRxiv2026

Selective Stabilization of HRAS2 i-Motif DNA by TMPyP4: A Multimodal Biophysical and Thermodynamic Investigation

I-motif (iM) DNA structures, formed by cytosine-rich sequences, are increasingly acknowledged for their involvement in gene regulation, maintenance of genomic stability, and their emerging potential as therapeutic targets, particularly in cancer. Despite their biological relevance, the discovery of selective small-molecule probes that can specifically recognize and interact with iM DNA remains an ongoing challenge. In this study, we have used TMPyP4 and screened for its ability to bind various iM DNA constructs, including HRAS1, HRAS2, VEGF, CMYC, CKIT and H-Telo. Structure-activity relationship analyses revealed that specific substitution patterns conferred selectivity towards HRAS2 iM target. Comprehensive spectroscopic investigations, including UV-Vis absorption, steady-state and time-resolved fluorescence, and fluorescence anisotropy, uncovered key photophysical signatures of binding, including significant hypochromic and bathochromic shifts, enhanced fluorescence emission, and prolonged fluorescence lifetimes. Circular dichroism (CD),thermal denaturation (UV-melting) and thermodynamic investigations confirmed that TMPyP4 effectively stabilized the HRAS2 iM structures without disrupting their native topologies. Meanwhile, FT-IR spectroscopy revealed local structural rearrangements upon TMPyP4 binding, offering further evidence of molecular interaction. Collectively, these findings provide valuable insights into the molecular recognition of iM DNA by TMPyP4 and highlight its promise as both selective HRAS2 iM-binding agent and responsive fluorescent probe. This work lays a strong foundation for the development of novel tools for studying iM structures in biological systems and for designing future therapeutics targeting iM DNA in cancer and related diseases.

biophysics↗

bioRxiv2025

Breaking barriers: A new phytomedicine based treatment approach for targeted unrevealed non-canonical DNA structures in tuberculosis bacteria.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a critical global health issue, complicated by the emergence of multi-drug-resistant (MDR) and extensively drug-resistant (XDR) strains. Current treatments involve prolonged use of first- and second-line drugs, which are associated with severe side effects and poor patient adherence. Non-canonical DNA structures, such as G-quadruplexes (GQ) and i-Motifs (iM), play a vital role in regulating Mtbs virulence, stress responses, and drug resistance mechanisms, making them attractive targets for therapy. Flavonoids, naturally occurring polyphenolic compounds found in various fruits and vegetables have demonstrated the ability to enhance the effectiveness of traditional TB drugs while minimizing cytotoxicity. By employing biophysical techniques including UV-Vis absorption spectroscopy, binding constant determination, and thermal melting experiments, this study investigates the interaction between two flavonoids, quercetin and kaempferol and non-canonical DNA structures (GQ and iM) within the Mtb genome. Key GQ/iM sequences from Mtb genes associated with drug resistance were identified and evaluated for their binding with flavonoids. Results revealed that quercetin and kaempferol preferentially interact with specific cyp51 GQ, dnaB GQ, espB GQ, espE GQ, SigA iM, fabH iM, psk5 iM DNA sequences, as indicated by significant changes in absorption spectra. The calculated binding constants showed strong affinities for these specific DNA structures. Thermal melting experiments further indicated that flavonoids increased the thermal stability of these particular GQ and iM DNA, suggesting stabilization via strong stacking interactions. These findings highlight the potential of flavonoids as promising agents to target GQ/iM DNA structures, offering a new strategy for addressing Mtb drug resistance and virulence.

biophysics↗

bioRxiv2021

Recombinant binder of sperm protein1 (rec-BSP1) as a potent fertility factor mediates its effect on embryo production

ObjectiveTo understand the effect of recombinant BSP1 (rec-BSP1) on in vitro capacitation of sperm and fertilization study Method(s)Articles were screened for reports including rec-BSP1, Capacitation, in vitro fertilization InterventionNone Main Outcome Measure(s)Reproductive outcomes, effect on gametes and embryos Result(s)Here we report an optimization of condition for rec-BSP1 production which was used for in vitro capacitation and enhancement of buffalo embryo production. The sequence of the protein was used for multiple sequence alignment which has 99% similarity with PDC 109 protein. The expression of rec-BSP1 was carried out successfully with 1 mM IPTG at 160 C for 22 hrs and purified it in soluble form. The structure of rec-BSP1 was generated using 3D modelling and analysed its mode of binding with heparin and PC by molecular docking and the structural stability of rec-BSP1-PC and rec-BSP1-heparin complexes by using molecular dynamic (MD) simulation. The effect of rec-BSP1 was observed on in vitro capacitation of spermatozoa and buffalo blastocyst production. It was found that the rec-BSP1 enhanced the sperm motility at a concentration of 50 g/ml for 1 h of incubation without having any detrimental effect on the sperm morphology and a significant increase in blastocyst production at concentration of 50 g/ml rec-BSP1. Hence this finding represents a new insight and advance the prospective approach to develop a potential fertility factor in reproduction. Conclusion(s)The purified rec-BSP1 may enhance on male fertility and mediated its effect on in vitro blastocyst production in buffalo.

bioengineering↗

bioRxiv2020

Integrated genomic view of SARS-CoV-2 in India

India first detected SARS-CoV-2, causal agent of COVID-19 in late January-2020, imported from Wuhan, China. March-2020 onwards; importation of cases from rest of the countries followed by seeding of local transmission triggered further outbreaks in India. We used ARTIC protocol based tiling amplicon sequencing of SARS-CoV-2 (n=104) from different states of India using a combination of MinION and MinIT from Oxford Nanopore Technology to understand introduction and local transmission. The analyses revealed multiple introductions of SARS-CoV-2 from Europe and Asia following local transmission. The most prevalent genomes with patterns of variance (confined in a cluster) remain unclassified, here, proposed as A4-clade based on its divergence within A-cluster. The viral haplotypes may link their persistence to geo-climatic conditions and host response. Despite the effectiveness of non-therapeutic interventions in India, multipronged strategies including molecular surveillance based on real-time viral genomic data is of paramount importance for a timely management of the pandemic.

microbiology↗

bioRxiv2018

Rat bone marrow derived mesenchymal stem cells differentiate to germ cell like cells

Summary StatementThe in vitro differentiation of rMSCs provides an excellent model for studying cell commitment and their potential in stem cell technology. We have demonstrated that rat bone marrow derived MSCs are able to differentiate into germ-line cells in vitro which has an enormous scope in the advancement of fertility research. In future, this technique can be utilized in different domestic animal species for propagation of elite germ plasm.\n\nAbstractGerm cells undergo distinctive male or female pathways to produce spermatozoa or oocyte respectively essential for sexual reproduction. Mesenchymal stem cells (MSCs) have the capacity of trans-differentiation to form the multiple lineages of cells of mesoderm, endoderm, and ectoderm origin. Herein, MSCs were isolated from rat bone marrow and characterized by their morphological features, expression of surface markers by immunophenotyping and molecular biology tools as well as self renewal and differentiation capability. Thereafter, by inducing these cells with retinoic acid we could able to show that bone marrow derived MSCs are able to trans-differentiate into male germ cell-like cells which were further characterized by the expressions of germ cell specific markers. This in vitro study for the generation of germ-like cells suggests that bone marrow MSCs can be a potential source of germ cells that could be a sustainable source of sperm / oocyte production for potential therapeutic applications in future. Moreover, this technique can be applied in different domestic animal species for propagation of elite germ plasm.

cell biology↗