Biology subjects

Yadav, U.

Publications and source records attributed to Yadav, U..

10 recordsLinked to original sources

bioRxiv2026

Decoding Chromosome Radiosensitivity in G0-Phase PBMCs: Genomic Determinants, Age, Sex effects, and Implications in Radiation Dose Assessment

Low-dose ionizing radiation from natural and anthropogenic sources is typically not of significant concern under normal conditions. However, in case of radiological incidents, it becomes an important environmental hazard, raising concern for public health and necessitating reliable biological indicators of exposure. Chromosomal aberrations are most reliable markers of radiation exposure and are more or less universally assessed in metaphases. Recently, rapid assessment of aberrations in G-phase lymphocytes using G-PCC-FISH has gained attention and is recognized as the most suitable method for dose assessment in cases of high-dose or partial-body exposure. This is first study in G-phase at such scale to establish baseline and radiation induced aberrations in peripheral blood mononuclear cells (PBMCs) from 24 healthy human donors (12 males, 12 females, 21-60 Y). Using whole chromosome painting (WCP) of Chromosomes 1, 2 & 4 and scoring across >8500 cells post 0, 2, and 4 Gy {gamma}-radiation exposure, we quantified 5586 aberrations and investigated their relationship with underlying genomic features. Our findings includeNo significant effect of age or sex on chromosomal radiosensitivity, supporting the robustness of pooled biodosimetric calibration curves for dose assessment within the studied age range of 21-60 years. Chromosome-specific radiosensitivity does not appear to be solely dependent on chromosome size and shows a potential association with gene density and total transcript length. From public health point of view the present data provides reference values for interphase chromosomal damage as well as radiation induced reference values for two important dose points across age groups and sexes. This approach enhances emergency preparedness for radiological events by enabling rapid biodosimetry, especially critical when metaphase cells are unavailable as in cases of accidental high-dose or partial exposures. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/728688v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@4f8a68org.highwire.dtl.DTLVardef@7ed80org.highwire.dtl.DTLVardef@7977bforg.highwire.dtl.DTLVardef@a4c0be_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract:C_FLOATNO A 24-donor study to assess baseline and radiation response age and sex. Additionally substantial data analysed to assess radiosensitivity of chromosomes and its genomic determinants. C_FIG

genomics↗

bioRxiv2025

Integrative Transcriptomics and Phytochemical Screening Reveal Pratenol B, Eriodictyol, Losbanine, and Isookanin, as Potential EGFR and HRAS Inhibitors in Indian Oral Squamous Cell Carcinoma Patients

Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer, with India contributing nearly one-third of the global cases. Management of OSCC remains difficult due to increasing risk factors, limited therapeutic options, severe side effects, and rising drug resistance. Therefore, novel and safer treatment strategies are urgently needed. This study explores the potential of phytochemicals as targeted inhibitors of key dysregulated biomarkers in Indian OSCC patients. RNA sequencing and pathway analysis revealed significant alterations in the MAPK signaling pathway, highlighting EGFR and HRAS as crucial therapeutic targets. Given the limited clinical success of existing EGFR-targeted therapies and the scarcity of HRAS inhibitors, a natural product-based approach was adopted. Molecular docking of 17,000 phytochemicals identified Pratenol B, Eriodictyol, Losbanine, and Isookanin as promising inhibitors, with Pratenol B showing dual inhibition of EGFR and HRAS. These compounds exhibited strong binding affinities, favorable pharmacokinetic profiles, high bioavailability, and low toxicity. Molecular dynamics simulations confirmed the stability of Pratenol B with both target proteins, surpassing reference inhibitors. Utilizing vast medicinal plant diversity presents a cost-effective and low-toxicity avenue for OSCC therapy. Further in vitro, in vivo, and clinical studies are warranted to validate these phytochemicals as potential therapeutics.

cancer biology↗

bioRxiv2024

Arv1 interacts with and regulates the first step of GPI biosynthesis in Candida albicans

The ubiquitous ARV1 gene shows significant functional conservation across eukaryotes. In humans, it is implicated in early onset epileptic encephalopathy. Evidence suggests that the phenotypes manifested in affected patients are probably due to the deficiency in expression of cell surface GPI anchored proteins. S. cerevisiae Arv1 is proposed to be the elusive GPI flippase that delivers the GPI intermediate from the cytoplasmic face to the luminal side of the ER for further elaboration by the first mannosyltransferase of the pathway. Human and fungal ARV1 complement S. cerevisiae ARV1. Overexpressing some of the GPI-N-acetylglucosamine transferase (GPI-GnT) subunits rescues the null strain of S. cerevisiae ARV1. In mammals and in T. brucei Arv1 co-immunoprecipitates with one or more subunits of the GPI-GnT. Based on these reports we hypothesized a cross-talk for ARV1 with the GPI biosynthetic pathway in the human pathogenic fungus, C. albicans. Using super resolution radial fluctuation (SRRF) analysis for co-localization, co-immunoprecipitation assays, and acceptor-photobleaching Forster resonance energy transfer (FRET) studies, we show that C. albicans Arv1 physically interacts with the GPI-GnT. It also transcriptionally regulates the expression of the GPI-GnT genes to control the GPI biosynthetic pathway via its very first step. Overexpression of one of the GPI-GnT subunits, CaGpi19, in C. albicans ARV1 null strain rescues its cold-sensitive growth, azole sensitivity, cell wall phenotype and GPI-GnT activity. Thus, our results suggest extensive interactions between Arv1 and GPI biosynthesis in C. albicans.

microbiology↗

bioRxiv2024

The ER-resident Ras Inhibitor 1 (Eri1) of Candida albicans inhibits hyphal morphogenesis via the Ras-independent cAMP-PKA pathway

Ras signaling and glycosylphosphatidylinositol (GPI) biosynthesis are mutually inhibitory in S. cerevisiae. The inhibition is mediated via an interaction of yeast Ras2 with the Eri1 subunit of its GPI-N-acetylglucosaminyl transferase (GPI-GnT), the enzyme catalyzing the very first GPI biosynthetic step. In contrast, Ras signaling and GPI biosynthesis in C. albicans are mutually activated and together control the virulence traits of the human fungal pathogen. What might be the role of Eri1 in this pathogen? The present manuscript addresses this question while simultaneously characterizing the cellular role of CaEri1. It is either non-essential or required at very low levels for cell viability in C. albicans. Severe depletion of CaEri1 results in reduced GPI biosynthesis and cell wall defects. It also produces hyperfilamentation phenotypes in Spider medium as well as in bicarbonate medium containing 5% CO2, suggesting that both the Ras-dependent and Ras-independent cAMP-PKA pathways for hyphal morphogenesis are activated in these cells. Pull-down and acceptor-photobleaching FRET experiments suggest that CaEri1 does not directly interact with CaRas1, but does so through CaGpi2, another GPI-GnT subunit. CaGpi2 is also downstream of CaEri1 in cross-talk with CaRas1 and control of hyphal growth in Spider medium. However, CaEri1 is downstream of all GPI-GnT subunits in inhibiting Ras-independent filamentation. CaERI1 also participates in the inter-subunit transcriptional cross-talk within the GPI-GnT, a feature unique to C. albicans. Virulence studies using G. mellonella larvae show that a heterozygous strain of CaERI1 is better cleared by the host and is attenuated in virulence.

microbiology↗

bioRxiv2022

Lipoate protein ligase B primarily recognizes the C8-phosphopantetheine arm of its donor substrate and weakly binds the acyl carrier protein

Lipoic acid is a sulfur containing cofactor, indispensable for the function of several metabolic enzymes. In microorganisms, lipoic acid can be salvaged from the surroundings by Lipoate protein ligase A (LplA), an ATP-dependent enzyme. Alternatively, it can be synthesized by the sequential action of Lipoate protein ligase B (LipB) and Lipoyl synthase (LipA), in a two-step reaction. LipB uptakes octanoyl-chain from C8-acyl carrier protein (C8-ACP), a byproduct of the type II fatty acid synthesis pathway, and transfers it to a conserved lysine of the lipoyl domain of a dehydrogenase. The molecular basis of substrate recognition by LipB is still not fully understood. Using E. coli LipB as a prototype, we show that the enzyme mainly recognizes the 4-phosphopantetheine tethered acyl-chain of its donor substrate, and weakly binds the apo-acyl carrier protein. It can accept octanoate-from its own ACP, noncognate ACPs, as well as C8-CoA. Further, our NMR studies demonstrate the presence of an adenine and phosphate binding site in LipB, akin to LplA. A loop containing 71RGG73 sequence, analogous to the lipoate binding loop of LplA is also conserved. Collectively, our studies highlight commonalities between LipB and LplA in their mechanism of substrate recognition. This knowledge might be of significance in the treatment of mitochondrial fatty acid synthesis related disorders.

biophysics↗

bioRxiv2021

Graphene Oxide reinforced Agarose-Hydroxyapatite Bioprinted 3-D Scaffolds for Bone Regeneration

Three-dimensional (3D) bioprinting is an emerging technology for fabricating cells, biomaterials and extracellular matrix (ECM) into customized shapes and patterns. Here, we report additive manufacturing to create a customized 3D bioactive constructs for regenerative medicine. We have attempted to emphasize the use of agarose and graphene oxide as a promising material for the conceptualization of bioink unpaid to its unique physicochemical properties. The 3D printed structure is able to regenerating bone tissues and regulates the cellular differentiation without any significant morphological changes. The presence of graphene oxide enhances the osteoinductive behavior of the developed scaffolds, which is further supplemented by encapsulating human mesenchymal stem cells (hMSCs) on the 3D printed scaffolds. A significant enhanced expression of early osteogenic markers like morphogenetic protein (BMP), Runx-2, collagen-1, osteopontin, osteocalcin as well as mineralized ECM are observed on agarose-hydroxyapatite and graphene oxide 3D printed scaffolds compared to agarose-hydroxyapatite 3D printed scaffolds. Thus, the outcomes of the developed 3D bioprinted scaffolds provide a promising strategy for development of personalized bone grafts for tissue regeneration.

bioengineering↗

bioRxiv2021

Evaluation of in vitro and in vivo toxicity of pristine molybdenum disulphide nanosheets in Swiss albino mice

The Molybdenum disulfide nanosheets (MoS2-NSs) thin films has received increasing attention recently due to their versatile multi functionality including catalytic properties, photoluminescence and flexibility, which suggests their future, uses for biomedical applications. However, there are no studies in detail related with biocompatibility of MoS2 thin sheets. Here, weevaluated the dose-dependent effects of MoS2-NSs on cell viability (MTT assay) and release of lactate dehydrogenase (LDH) into culture media using MG-63 cells, as well as haemolysis, hematological, serum biochemical, antioxidants and histopathological parameters in Swiss albino mice. The MoS2-NSs was synthesized via facile hydrothermal method and characterized using XRD, Raman, SEM, TEM and HRTEM. The in vitro study results suggest that at lower concentration MoS2-NSs does not causes any toxicity. The lethal dose (LD50) was evaluated by intraperitoneal administration with different concentrations and estimated as ~1.0 mg kg-1. The higher dose (1.5 mg kg-1) of MoS2-NSs showed significant alteration in hematological markers and serum biochemical enzymes, as compared to control. Lipid peroxidation also shows significant alteration with respect to the control. Histopathological, hematological and biochemical examination, revealed no remarkable changes at lower concentration (less than 1.0 mg kg-1), however, higher concentration (1.5 mg kg-1) causes significant histopathological, antioxidants and biochemical alterations in tissues and serum, respectively. The results suggest that the lower concentration of MoS2-NSs can be used in future biomedical applications.

bioengineering↗

bioRxiv2019

Molecular Screening of Hemoglobin S Variant in Anemia Patients of Eastern UP Population

Hemoglobinopathies are the most common type of inherited disease in human. in India the most frequent and clinically significant hemoglobin structural variants are HbS, HbD and HbE. The HbS mutation, in which a glutamic acid at position 6 in the {beta} chain is substituted for valine Sickle cell disease is a major health problem in some parts of India. 2 ml blood sample was collected from 350 anemia patient and PCR-RFLP method was used for hemoglobin S analysis. Out of 350 samples, in four individuals, HbS mutation was found in homozygous ({beta} 6/{beta} 6) condition. All four individuals are Sickle cell cases. In conclusion, the percentage of Sickle cell disease was observed as 1.14% in Eastern UP anemic patients.

molecular biology↗

bioRxiv2019

A Study of Association of ABO Blood Group types with Cancer Risk

More than 30 blood group systems have been recognized by International Society of Blood Transfusion (ISBT). ABO blood group is one of the most studied blood group system. ABO blood group system consist of three alleles A, B and O, out which A and B are co-dominant and O is recessive. Many researchers and investigators have found association between ABO blood group and cancer risk. It was found from the recent data that blood group A and AB is associated with increased pancreatic and gastric cancer risk. In the present study data of ABO blood group of 243 patients, both males and females, with confirmed cases of cancer was obtained from Sir Sunderlal hospital, Institute of Medical Science (IMS), Banaras Hindu University (BHU) and Apex hospital, DLW Road, Varanasi. 250 Samples of both males and females were taken as control. Out of 243 cancer patients 117 were males and 126 were females. In 243 cases enrolled in present study, highest number of cases were of breast cancer among women and lowest were rectal cancer. It was found that A blood group was associated with breast cancer, oral cancer, liver cancer and ovarian cancer as compared to other blood group and blood group O was associated with lung cancer, gastric cancer, colon cancer, skin cancer and endometrial cancer.

genetics↗

bioRxiv2019

DRD2 TaqI A polymorphism in Eastern Uttar Pradesh population

Dopamine receptor D2 (DRD2) encoded by DRD2 gene, is located on chromosome 11q22-23. Dopamine plays the central role in motivation, cognition, and reward seeking behaviour. Its dysfunction is implicated in numerous neurological and psychiatric disorders including drug abuse, schizophrenia, ADHD etc. The TaqI A polymorphism is localized 9.8 kb downstream from DRD2 gene in exon 8 of protein kinase gene (ANKK1). It is a SNP demonstrated to cause Glutamate to Lysine substitution at 713 amino acid residue in putative binding domain of ANKK1. Due to the central role of dopamine in reward seeking behavior, DRD2 TaqI A loci is a suitable candidate for investigation of molecular basis of addiction. The aim of the present study is to evaluate the frequency of DRD2 TaqI A polymorphism in Eastern Uttar Pradesh population. 3ml blood samples were collected from 50 individuals randomly selected from Eastern UP. Written informed consent along with profile detail was taken from each subject prior to blood sample collection. DRD2 TaqI A polymorphism analysis was done by PCR-RFLP method. Genomic DNA was extracted from each collected blood samples and amplified using DRD2 Taq1 region specific primers. PCR amplification produced 310bp long amplicon which was digested with Taq I enzyme for polymorphism analysis. In case of A2 allele, Taq1 enzyme cleaved 310bp long fragment into two fragments of 180bp and 130bp. In case of A1 allele, a C to T substitution demolished the restriction site of Taq1, so amplicon of A1 allele remained uncut. In total 50 sample analyzed in present study, A2/A2, A2/A1 and A1/A1 genotype were found in 12, 32 and 06 samples respectively. The genotypic frequencies of mutant homozygous (A1/A1) is 0.12, heterozygous (A2/A1) is 0.64 and normal homozygous (A2/A2) is 0.24. The allelic frequency of A1 is 0.44 and of A2 is 0.56. In conclusion, the results of present study suggests that in TaqI A polymorphism of DRD2 gene, the frequency of allele A2 is higher than that of A1 allele in population of Eastern Uttar Pradesh.

neuroscience↗