Biology subjects

Tiwari, V. K.

Publications and source records attributed to Tiwari, V. K..

13 recordsLinked to original sources

bioRxiv2026

Molecular Characterization of Gene-Product Relationships in the Wheat Gluten Complex for Reduced Immunogenicity Wheat Development

Immune-mediated reactions to wheat gliadins, including celiac disease and wheat allergies, affect ~1% of the U.S. population and are prevalent worldwide. Reducing the risk of inadvertent gluten exposure for individuals with celiac disease or wheat allergies requires the development of reduced immunogenicity wheat varieties which are suitable for human consumption. This study was designed with a view to improve our understanding of gene protein relationships at the complex wheat Gli1/Glu3 and Gli2 loci, and to develop genetic and molecular resources for breeding reduced-immunogenicity wheat lines. We conducted comprehensive genomic, biochemical, and immunological analyses of diverse wheat genetic resources, including aneuploid stocks, chromosome deficiency and interstitial deletion lines, Wasko omega null, the landrace San Pastore, Pegaso near isogenic lines lacking Gli1/Glu3/Gli2 loci, and progenies derived from a Wasko mega null X Pegaso(6A/6D) alpha null. Genomic characterization involved the targeted GlutEnSeq approach and PCR based DNA markers while biochemical and immunological analyses employed acid-urea PAGE, SDS PAGE, and ELISA. Integration of these complementary approaches resolved gliadin gene protein relationships at an unprecedented level. Notably, two F2; lines exhibited substantial reductions (both omega and alpha gliadins) due to the successful stacking of parental mutations. The resulting F2; progenies and associated DNA markers represent valuable resources for breeding wheat for reduced immunogenicity

genomics↗

bioRxiv2025

Toward Predictive Modeling of Microneedle Design: Establishing a Correlation Between CAD Models, 3D Printed Arrays, and PDMS Molds

Microneedles are increasingly gaining traction in transdermal delivery systems, with precision in geometry being a key determinant of their efficacy. In this study, we aim to establish a quantitative and visual correlation between computer-aided design (CAD) models, 3D printed microneedle arrays fabricated using the Formlabs 3B SLA printer, and polydimethylsiloxane molds casted from the printed arrays. The goal is to develop a predictive framework that allows designers to fine-tune CAD geometries based on desired final outputs, bypassing iterative prototyping. The study presents a methodology involving dimensional analysis across fabrication stages and highlights deformation trends inherent in each stage, laying the groundwork for data-driven reverse design approaches.

bioengineering↗

bioRxiv2025

Contextual Science and Genome Analysis for Air-Gapped AI Research

Provided here is a study of large language models (LLMs) and retrieval augmented generation (RAG) frameworks in air-gapped environments for genome research on small grain crops. We developed two main applications: (1) a RAG-based system for contextual analysis of scientific literature, collecting over 5,000 PDFs on wheat pathogens, and (2) a GFF3 file analysis tool called Genoma that enables exploration of genome annotation through an interactive interface. Using the open-source framework Ollama, we compared the performance of multiple LLMs including Llama3.1, Deepseek-r1, and Qwen2.5 for biological data analysis. A LightRAG approach provided semantic visualization of document relationships, while the Genoma tool offered chromosome-level insights into genome annotations. These tools demonstrate the viability of powerful AI assistance for sensitive research environments, with potential applications for pangenome analysis and gene discovery. The code provides researchers with practical solutions for implementing AI in secure settings without sacrificing analytical power.

bioinformatics↗

bioRxiv2025

Associations between epilepsy-related polygenic risk and brain morphology in childhood

AO_SCPLOWBSTRACTC_SCPLOWTemporal lobe epilepsy with hippocampal sclerosis (TLE-HS) is associated with a complex genetic architecture, but the translation from genetic risk factors to brain vulnerability remains unclear. Here, we examined associations between epilepsy-related polygenic risk scores for HS (PRS-HS) and brain structure in a large sample of neurotypical children, and correlated these signatures with case-control findings in in multicentric cohorts of patients with TLE-HS. Imaging-genetic analyses revealed PRS-related cortical thinning in temporo-parietal and fronto-central regions, strongly anchored to distinct functional and structural network epicentres. Compared to disease-related effects derived from epilepsy case-control cohorts, structural correlates of PRS-HS mirrored atrophy and epicentre patterns in patients with TLE-HS. By identifying a potential pathway between genetic vulnerability and disease mechanisms, our findings provide new insights into the genetic underpinnings of structural alterations in TLE-HS and highlight potential imaging-genetic biomarkers for early risk stratification and personalized interventions.

neuroscience↗

bioRxiv2024

ZNFX1 is a Novel Master Regulator in Epigenetically-induced Pathogen Mimicry and Inflammasome Signaling in Cancer

DNA methyltransferase and poly(ADP-ribose) polymerase inhibitors (DNMTis, PARPis) induce a stimulator of interferon (IFN) genes (STING)-dependent pathogen mimicry response (PMR) in ovarian (OC) and other cancers. We now show that combining DNMTis and PARPis upregulates expression of a little-studied nucleic-acid sensor, NFX1-type zinc finger-containing 1 protein (ZNFX1). We demonstrate that ZNFX1 is a novel master regulator for PMR induction in mitochondria, serving as a gateway for STING-dependent PMR. In patient OC databases, high ZNFX1 expression levels correlate with advanced stage disease. ZNFX1 expression alone significantly correlates with an increase in overall survival in a phase 3 trial for therapy-resistant OC patients receiving bevacizumab in combination with chemotherapy. In correlative RNA-seq data, inflammasome signaling through ZNFX1 correlates with abnormal vasculogenesis. ZNFX1 controls PMR signaling through the mitochondria and may serve as a biomarker to facilitate offering personalized therapy in OC patients, highlighting the strong translational significance of our findings. Significance statementDNA methyltransferase and poly(ADP-ribose) polymerase inhibitors upregulate expression of a novel nucleic-acid sensor, ZNFX1 that serves as a mitochondrial gateway to STING-dependent interferon/inflammasome signaling with tumor suppressor properties in ovarian cancer.

cancer biology↗

bioRxiv2023

Changes in an Enzyme Ensemble During Catalysis Observed by High Resolution XFEL Crystallography

Enzymes populate ensembles of structures with intrinsically different catalytic proficiencies that are difficult to experimentally characterize. We use time-resolved mix-and-inject serial crystallography (MISC) at an X-ray free electron laser (XFEL) to observe catalysis in a designed mutant (G150T) isocyanide hydratase (ICH) enzyme that enhances sampling of important minor conformations. The active site exists in a mixture of conformations and formation of the thioimidate catalytic intermediate selects for catalytically competent substates. A prior proposal for active site cysteine charge-coupled conformational changes in ICH is validated by determining structures of the enzyme over a range of pH values. A combination of large molecular dynamics simulations of the enzyme in crystallo and time-resolved electron density maps shows that ionization of the general acid Asp17 during catalysis causes additional conformational changes that propagate across the dimer interface, connecting the two active sites. These ionization-linked changes in the ICH conformational ensemble permit water to enter the active site in a location that is poised for intermediate hydrolysis. ICH exhibits a tight coupling between ionization of active site residues and catalysis-activated protein motions, exemplifying a mechanism of electrostatic control of enzyme dynamics.

biochemistry↗

bioRxiv2023

Mapping the daily rhythmic transcriptome in the diabetic retina

Retinal function shows marked changes from day to night. Yet, clinical diagnosis, treatments, and experimental sampling occur during the day, leaving a significant gap in our understanding of the pathobiology occurring at night. While there is evidence that diabetes disrupts the circadian system that optimizes our physiology to the environmental light/dark cycle, the impact of such disruption is not well understood. This study investigates whether diabetes affects the retinas daily rhythm of gene expression to understand the pathobiology of diabetic retinopathy. Ins2Akita/J mice, a model of type 1 diabetes, were kept under a standard 12h:12h light/dark cycle until four months of age. Non-diabetic littermates were used as controls. Bulk mRNA sequencing was conducted in retinas collected every 4 hours throughout the 24 hr light/dark cycle. Computational approaches were used to detect rhythmicity, predict acrophase, identify differential rhythmic patterns, analyze phase set enrichment, and predict upstream regulators. The retinal transcriptome exhibited a tightly regulated rhythmic expression with a clear 12-hr axis of transcriptional rush, peaking at midday and midnight. The functions of day-peaking genes were enriched for DNA repair, RNA splicing, and ribosomal protein synthesis, whereas night-peaking genes were enriched for metabolic processes and growth factor signaling. Although the 12-hr transcriptional axis is retained in the diabetic retina, it was phase advanced by approximately 1-3 hours with a wider distribution. Upstream regulator analysis for the genes that showed phase shifts identified oxygen sensing mechanisms and HIF1alpha as regulators, but not the circadian clock, which remained in phase to the light/dark cycle. We propose a model in which early in diabetes, the retina experiences a jet lag caused by the entrained circadian clock and its output being in one phase and metabolic pathways related to neuronal dysfunction and hypoxia driving advancement of gene expression to a different phase. Further studies are now required to evaluate the chronic implications of such internal jet lag for development of diabetic retinopathy.

bioinformatics↗

bioRxiv2023

Deciphering the gene regulatory circuitry governing chemoresistance in Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, due in part to extensive intratumoral heterogeneity, high rates of metastasis and chemoresistance, leading to poor clinical outcomes. Despite progress, the mechanistic basis of chemotherapy resistance in TNBC patients remains poorly understood. Here, using single-cell transcriptome datasets of matched longitudinal TNBC chemoresponsive and chemoresistant patient cohorts, we discover cell subpopulations associated with chemoresistance and the signature genes defining these populations. Notably, we show that the expression of these chemoresistance genes is driven via a set of TNBC super-enhancers and transcription factor networks across TNBC subtypes. Furthermore, genetic screens reveal that a subset of these transcription factors is essential for the survival of TNBC cells and their loss increases sensitivity to chemotherapeutic agents. Overall, our study has revealed transcriptional regulatory networks underlying chemoresistance and suggests novel avenues to stratify and improve the treatment of patients with a high risk of developing resistance.

cancer biology↗

bioRxiv2023

Bearded or Smooth? Awns Improve Yield when Wheat Experiences Heat Stress During Grain Fill

The presence or absence of awns - whether wheat heads are "bearded" or "smooth"- is the most visible phenotype distinguishing wheat cultivars. Previous studies suggest that awns may improve yields in heat or water-stressed environments, but the exact contribution of awns to yield differences remains unclear. Here we leverage historical phenotypic, genotypic, and climate data to estimate the yield effects of awns under different environmental conditions over a 12-year period in the Southeast US. Lines were classified as awned or awnless based on sequence data, and observed heading dates were used to associate grain fill periods of each line in each environment with climatic data and grain yield. In most environments, awn suppression was associated with higher yields, but awns were associated with better performance in heat-stressed environments more common at southern locations. Wheat breeders in environments where awns are only beneficial in some years may consider selection for awned lines to reduce year-to-year yield variability, and with an eye towards future climates.

genetics↗

bioRxiv2022

A wheat kinase and immune receptor form the host-specificity barrier against the blast fungus

Since emerging in Brazil in 1985, wheat blast has spread throughout South America and recently appeared in Bangladesh and Zambia. We show that two wheat resistance genes, Rwt3 and Rwt4, acting as host-specificity barriers against non-Triticum blast pathotypes encode a nucleotide-binding leucine-rich repeat immune receptor and a tandem kinase, respectively. Molecular isolation of these genes allowed us to develop assays that will ensure the inclusion of these two genes in the wheat cultivars to forestall the recurrence of blast host jumps.

plant biology↗

bioRxiv2021

Whole genome resequencing and comparative genome analysis of three Puccinia striiformis f. sp. tritici pathotypes prevalent in India

Stripe rust disease of wheat, caused by Puccinia striiformis f. sp. tritici, (Pst) is one of the most serious diseases of wheat worldwide. In India, virulent stripe rust races have been constantly evolving in the North-Western Plains Zone leading to the failure of some of the most widely grown resistant varieties in the region. With the goal of studying the recent evolution of virulent races in this region, we conducted whole-genome sequencing of three prevalent Indian Pst pathotypes Pst46S119, Pst78S84 and Pst110S119. We assembled 58.62, 58.33 and 55.78 Mb of Pst110S119, Pst46S119 and Pst78S84 genome, respectively. Pathotypes were found to be highly heterozygous. Comparative phylogenetic analysis indicated the recent evolution of pathotypes Pst110S119 and Pst78S84 from Pst46S119. Pathogenicity-related genes classes (CAZyme, proteases, effectors, and secretome proteins) were identified and found to be under positive selection. Higher rate of gene family expansion was also observed in the three pathotypes. A strong association between the effector genes and transposable elements may be the source of the rapid evolution of these strains. Phylogenetic analysis differentiated the Indian races in this study from other known US, European, African and Asian races. Diagnostic markers developed for the identification of different Pst pathotypes will help tracking of yellow rust at farmers field and strategizing resistance gene deployment.

bioinformatics↗

bioRxiv2020

Discovery of a Promising Susceptibility Factor for Fusarium Head Blight in Wheat

Fusarium head blight (FHB) disease of wheat caused by Fusarium spp. deteriorates both quantity and quality of the crop. Manipulation of susceptibility factors, the genes facilitating disease development in plants, offers a novel and alternative strategy for enhancing FHB resistance in plants. In this study, a major effect susceptibility gene for FHB was identified on the short arm of chromosome 7A (7AS). Nullisomic-tetrasomic lines for homoeologous group-7 of wheat revealed dosage effect of the gene, with tetrasomic 7A being more susceptible than control Chinese Spring wheat, qualifying it as a bonafide susceptibility factor. The gene locus was conserved in six chromosome 7A inter-varietal wheat substitution lines of diverse origin and a tetraploid Triticum dicoccoides genotype. The susceptibility gene was named as SF7ASFHB and mapped on chromosome 7AS to 48.5-50.5 Mb peri-centromeric region between del7AS-3 and del7AS-8. Our results showed that deletion of SF7ASFHB imparts ~ 50-60% type 2 FHB resistance (against the spread of the fungal pathogen) and its manipulation may lead to enhanced resistance against FHB in wheat. HighlightDiscovery and mapping of a conserved susceptibility factor located on the short arm of wheat chromosome 7A whose deletion makes plants resistant to Fusarium Head Blight.

genetics↗

bioRxiv2018

Antifungal effects of 3-(4-Phenyl-thiazol-2-yl)-2-thioxo-2, 3-dihydro-1H-quinazolin-4-one against Aspergillus Species

Aspergillus infections have become an important health problem with the increasing number of patients. Available antifungal drugs are lack with their spectrum, toxic or immunosuppressive in nature, so that need to develop new compound with high efficacy. To evaluate antifungal efficacy of synthesized compound and to identify the protein profile of Aspergillus fumigatus treated with antifungal. Clinical isolates of A. fumigatus, A. flavus and A. niger were cultured and efficacy of compound were conducted by Disc Diffusion Assay (DDA), Microbroth Dilution Assay (MDA). Percent of spore germination inhibition assay (PSGI), Time kill analysis and toxicity assay. The culture filtrate containing secretory proteins was collected after 24 h growth and expression of downregulated proteins were identified. We developed a new and useful quinazoline derivatives expected to antifungal activity. The result of anti-Aspergillus evolution revealed that one of the 3-(4-Phenyl-thiazol-2-yl)-2-thioxo-2, 3-dihydro-1H-quinazolin-4-one (DDVKT4Q) exhibited appreciable activity. The potency of compound was found concentration of 3.125 {micro}g/disc by disc diffusion assay (DDA) and 15.625 {micro}g/ml. by Microbroth Dilution Assay (MDA). The compound was nontoxic up to concentration 625 {micro}g/ml and its lysed only 35.9% of human erythrocytes, at the highest dose tested. Its observed that the treatment of pathogen with DDVKT-4Q targeted the expression of four proteins having molecular weights 18 kDa 37 KDa and 43 KDa proteins was completely inhibited or down regulated by the compound the extra cellular. The novel compound DDVKT-4Q, having antifungal activity Can be exploited further to develop new ideal antimycotic drugs.

microbiology↗