Biology subjects

Tiwari, A. K.

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

5 recordsLinked to original sources

bioRxiv2026

Dietary fiber-type-specific gut microbiome preconditioning drives differential susceptibility to sporadic colon cancer development

Background: Dietary fiber intake is broadly associated with reduced colorectal cancer (CRC) risk, yet processed fiber supplements exert inconsistent and occasionally opposing effects on colon tumorigenesis. How structurally distinct dietary fibers differentially shape the gut microbiome-metabolome axis to influence carcinogenic susceptibility remains poorly understood. Objective: To determine whether structurally distinct dietary fibers differentially modulate colon tumor development and characterize the underlying gut microbiome and metabolic mechanisms. Design: Four-week-old male mice were maintained on low-fiber control or fiber-supplemented diets (7.5%w/w: cellulose, agar, pectin, or inulin) for 28 weeks and received eight intraperitoneal azoxymethane injections (AOM; 7.5 mg/kg). Temporal fecal microbiomes were profiled by 16S-rRNA sequencing, cecal metabolites quantified by H-NMR spectroscopy, and microbiome-metabolome interactions assessed by co-occurrence networks. Results: Refined inulin supplementation markedly elevated colon tumor incidence (~70%) compared with all other groups (~10-20%), and cecal extracts from inulin-fed mice promoted HT29 cancer-cell proliferation. Longitudinal microbiome profiling identified 36 inulin-specific microbial signatures converging on two axes: depletion of SCFAs and fermentation cross-feeding taxa and reprogramming of amino acid and nitrogen metabolism. Metabolomics confirmed succinate, fumarate, and lactate accumulation alongside propionate and amino acid depletion exclusively under AOM conditions, with no differences in carcinogen-naive animals. Two stable co-occurrence hubs were identified exclusively in AOM-treated animals, structurally integrating both functional axes. Conclusion: Inulin supplementation preconditions the gut microbiome toward functional vulnerability, characterized by disrupted fermentation throughput and reprogrammed amino acid metabolism, that is amplified by carcinogen exposure into a tumor-promoting ecosystem, providing a mechanistic basis for the disproportionately higher tumor prevalence in inulin-fed animals.

microbiology↗

bioRxiv2026

Decoding the role of ADAptor2 (ADA2) of HAT complex in autophagy and phospholipid metabolism to maintain ER homeostasis and triterpene regulation

In yeast, transcriptional adaptor 2 (ADA2; SAGA complex subunit ADA2), a member of histone acetyltransferase (HAT) complex, regulates transcription through cell signalling, but its precise role in cellular metabolism remains unclear. In this study, genetic loss of ADA2 (ada2{Delta}) induces squalene (SQ) accumulation, indicating aberrant triterpene metabolism, coupled with endoplasmic reticulum (ER)/nuclear ER (nER) expansion. Lipid analyses of ada2{Delta} revealed elevated phosphatidic acid (PA) and phosphatidylcholine (PC) levels, indicating disrupted phospholipid metabolism. The expanded ER causes basal autophagy elevation, cellular recycling, and nER phagy, suggesting a regulatory role for ADA2 in autophagy. Downregulation of phosphatidate cytidylyltransferase (CDS1) and inositol-3-phosphate synthase (INO1), coupled with elevated PA and PC in ada2{Delta}, points to a significant disruption in cytidine-diphosphate-diacylglycerol and phosphatidylinositol pathway. Overexpression of CDS1 or INO1, or the inositol supplementation, in ada2{Delta} restores SQ, basal autophagy and ER phagy. The observed target of rapamycin Ser/Thr kinase complex (TORC1) activity in ada2{Delta} is due to the high PA content. Rapamycin-mediated inhibition of TORC1 reduced SQ, PA and ER expansion while increasing lipid droplets. In contrast, a rapamycin-treated ada2{Delta}pah1{Delta} strain retained high PA, SQ and ER expansion, underscoring the functional role of TORC1-nuclear envelope morphology protein 1 (Nem1)/sporulation-specific protein SPO7 (Spo7)-Pah1 axis. Notably, SQ levels remained unchanged in a rapamycin-treated ada2{Delta}atg39{Delta} strain, suggesting that loss of nER-phagy receptor, Atg39, impairs the effectiveness of TORC1 inhibition. In conclusion, our data unveiled a critical role for Ada2 in maintaining the intricate relationship between lipid and triterpene/sterol metabolism and connecting autophagy and ER homeostasis.

biochemistry↗

bioRxiv2020

HSPs, Ubiquitins and Antioxidants aid in Heat Tolerance in Tharparkar Indicine cattle

Transcriptome profiling of Vrindavani and Tharparkar cattle revealed that more numbers of genes dysregulated in Vrindavani than in Tharparkar. A contrast in gene expression was observed with 18.5 % of upregulated genes in Vrindavani were downregulated in Tharparkar and 17.5% upregulated genes in Tharparkar were downregulated in Vrindavani. Functional annotation of genes differentially expressed in Tharparkar and Vrindavani revealed that the systems biology in Tharparkar is moving towards counteracting the effects due to heat stress. Unlike Vrindavani, Tharparkar is not only endowed with higher expression of the scavengers (UBE2G1, UBE2S, and UBE2H) of misfolded proteins but also with protectors (VCP, Serp1, and CALR) of naive unfolded proteins. Further, higher expression of the antioxidants in Tharparkar enables it to cope up with higher levels of free radicals generated as a result of heat stress. In this study we found relevant genes dysregulated in Tharparkar in the direction that can counter heat stress.

physiology↗

bioRxiv2019

Characterisation of l(3)tb as a novel tumour suppressor allele of DCP2 in Drosophila melanogaster

Mutants provide an excellent platform for the discovery and characterization of gene functions. The present communication is a pioneering treatise on a hitherto undescribed function of the gene coding for the mRNA decapping protein 2 (DCP2) in Drosophila melanogaster. DCP2, the gene coding for the mRNA decapping enzyme, has been studied in various model organisms in the light of maintenance of transcript abundance and stability but has never been implicated in tumourigenesis. Herein, we describe the mapping and characterization of a novel tumour suppressor allele of DCP2 (CG6169), which we named as lethal(3)tumorous brain [l(3)tb]. The homozygous mutant individuals show prolonged larval life, develop larval brain tumors and are lethal in the larval/pupal stages. The tumour is characterized by the presence of increased number of superficial neuroblasts, abnormal chromosomal condensation and causes overgrowth in the wing and the eye-antennal discs of the homozygous mutant larvae, all of which are rescued by the introduction of a functional copy of DCP2 in the mutant background, thereby establishing the causal role of the mutation and providing a genetic validation of the allelism. Our findings therefore ascribe a novel role of tumor suppression to DCP2 besides its cognate function of mRNA decapping and thereby identify it as a potential candidate for future research on tumorigenesis.

genetics↗

bioRxiv2018

Finding the difference between periosteal and endocortical bone adaptation by using Artificial Neural Networks

In silico models of bone adaptation successfully simulated in vivo periosteal bone apposition, however, there are instances where these models may have limited success in predicting the new bone formation at endocortical surface. In vivo studies have highlighted that cortical bone surfaces may have differences in their modeling or remodeling responses to mechanical loading. However, the principle which the two cortical surfaces follow in bone adaptation is not very clear. This work accordingly attempts to understand how periosteal and endocortical surfaces accommodate loading-induced new bone formation. A neural network model is used to serve the purpose. A relationship is established to compute new bone thickness as a function of mechanical parameters (normal and shear strains) and non-mechanical parameters (distances from the neutral axis and the centroid) at the two surfaces. Analytical results indicate that two cortical surfaces behave opposite to each other in order to achieve optimal distribution of newly formed bone. The outcomes may be useful in establishing a unifying principle to predict site-specific new bone formation.

bioengineering↗