Biology subjects

Khalique, A.

Publications and source records attributed to Khalique, A..

3 recordsLinked to original sources

bioRxiv2023

Enhancing farmed striped catfish (Pangasianodon hypophthalmus) robustness using dietary β-glucan

{beta}-glucan is a well-documented feed additive for its potent immunostimulatory properties in many farmed fish species. This study examined how it can also be a promising growth promoter, modulate antioxidant enzyme activities, and act as an anti-stress agent in striped catfish (Pangasianodon hypophthalmus). A 12-week feeding experiment was untaken to determine the effects of dietary {beta}-glucan supplementation at graded levels (0, 0.5, 1.0, and 1.5 g kg-1). Measured indicators suggest that a dietary inclusion level of 1.5 g kg-1 {beta}-glucan gave the highest positive responses: weight gain (120.10 g fish-1), survival (98.30 %), and lower FCR (1.70) (P<0.05). Whole body proximate analysis had only revealed that crude protein was significantly affected by the dietary inclusion of {beta}-glucan (P<0.05), with the highest protein content (19.70 %) being in fish that were fed with 1.5 g kg-1 {beta}-glucan. Although other inclusion levels (i.e., 0.5 and 1 g kg-1) of {beta}-glucan did not enhance body protein content (P>0.05). The assessment of fatty acid composition in muscle, liver, and adipose tissues showed modifications with the inclusion of {beta}-glucan. Antioxidative-related enzyme activities (inc. catalase, glutathione peroxidase, and superoxide dismutase) that were measured in the liver had higher levels when fed with {beta}-glucan inclusion diets (P<0.05). Following the feed trial, fish were subjected to crowding stress treatment. It was subsequently found that catfish fed with {beta}-glucan-based diet groups had lower levels of blood stress-related indicators compared to the control group with no dietary {beta}-glucan. The use of 1.5 g kg-1 of dietary {beta}-glucan resulted in the lowest measured levels of cortisol (43.13 ng mL-1) and glucose (50.16 mg dL-1). This study has demonstrated that the dietary inclusion of {beta}-glucan can have functional benefits beyond the immunological enhancements in striped catfish. Furthermore, its use can increase production levels and mitigate the stress associated with intensive farming practices.

zoology↗

bioRxiv2022

Prolonged exposure to insulin causes epigenetic alteration leading to insulin resistance

Glucose homeostasis is maintained by insulin. It has been observed that hyperinsulinemia precedes insulin resistance and Type 2 diabetes. Insulin resistance is caused by multiple factors including genetic and diet. The molecular mechanism underlying insulin resistance (IR) is not completely understood. Using Glut4 and insulin receptor-expressing CHO cells we had previously shown that prolonged exposure of these cells to insulin in the absence of high levels of glucose led to insulin resistance in the cells. In the present study, we have shown that the underlying cause for the impaired GLUT4 trafficking is the defective PI3K/AKT pathway. This insulin resistance is likely due to epigenetic alterations as it is stable and can be maintained for several generations even when insulin is not provided, and epigenetic modifiers can reverse the insulin resistance. We extended these studies to liver cell line (BRL-3A) and show that these cells also develop impaired insulin signaling upon exposure to insulin in the absence of high levels of glucose. Transcriptomic analysis of the insulin-sensitive and -resistance cells uncover altered signaling networks involved in chromatin remodelling, Rho GTPases, and ubiquitination. Pathway analysis reveals the role of demethylase Kdm5b and lysine methyltransferase (Kmt2a and Kmt2e) in the development of insulin resistance. It is also observed that trimethylation of histone H3 at lysine 4 (H3K4me3) is increased in insulin resistance cellular models. We further showed that mice injected with low doses of insulin when fasting develop insulin resistance with impaired glucose tolerance and increased HOMA-IR index. Altogether, these findings suggest dysregulated synthesis of insulin in the absence of glucose stimulus could lead to epigenetic alterations that may lead to insulin resistance. Summary StatementInsulin stimulation in the absence of glucose leads to insulin resistance. We have developed a cell and mouse model of insulin resistance in this study to characterise the molecular signalling involved in insulin resistance and early onset of type 2 diabetes. The transcriptomic analysis provides new insights on epi-transcriptomic regulation in insulin resistance.

molecular biology↗

bioRxiv2019

Targeting of mitochondrial and cytosolic substrates of tRNA isopentenyltransferases: selection of differential tRNA-i6A37 identity subsets

tRNA isopentenyltransferases (IPTases), which add an isopentenyl group to N6 of adenosine-37 (i6A37) of certain tRNAs, are among a minority of modification enzymes that act on both cytosolic and mitochondrial substrates. The Caenorhabditis elegans mitochondrial IPTase impacts life expectancy, and pathogenic mutations to human IPTase (TRIT1) that decrease i6A37 levels cause mitochondrial insufficiency and neurodevelopmental disease. Understanding of IPTase broad function should consider the differential identities of the tRNAs selected for i6A37 formation and their cognate codons, which vary among species in both their nuclear- and mitochondria-encoded tRNAs. Substrate selection is principally by recognition of the A36-A37-A38 sequence but can be negatively impacted by certain anticodons, and by ill-defined properties of the IPTase. Thus, tRNAs-i6A37 comprise a modification code system whose principles are incompletely understood. While Saccharomyces cerevisiae uses alternative translation initiation to target IPTase to mitochondria, our analyses indicate that TRIT1 uses a single initiation site to produce a mitochondrial targeting sequence (MTS) that we demonstrate by point mutagenesis using GFP imaging in human cells. We also examined cytosolic and mitochondrial tRNA modification by TRIT1 in Schizosaccharomyces pombe using tRNA-mediated suppression and i6A37-sensitive northern blotting. The TRIT1 MTS mutations indeed decrease mitochondrial-tRNA modification in S. pombe. We also show TRIT1 modification deficiency specific for tRNATrpCCA despite A36-A37-A38, consistent with the negative effect of the CCA anticodon as was described for Mod5 IPTase. This TRIT1 deficiency can be countered by over-expression. We propose a model of tRNA-i6A37 identity selection in eukaryotes that includes sensitivity to substrates with YYA anticodons.\n\nAUTHOR SUMMARYtRNA isopentenyltransferases (IPTases) are tRNA modification enzymes that are conserved in bacteria and eukaryotes. They add an isopentenyl group to the Adenosine base at position 37, adjacent to the anticodon of specific subsets of tRNAs that decode codons that begin with Uridine. This modification stabilizes the otherwise weak adjacent codon-anticodon basepair and increases the efficiency of decoding of the corresponding codons of the genetic code. IPTases belong to a group of enzymes that modify both cytoplasmic and mitochondrial tRNAs of eukaryotic cells. Interestingly, during evolution there were changes in the way that IPTases are targeted to mitochondria as well as changes in the relative numbers and identities of IPTase tRNA substrates in the cytoplasm vs. mitochondria, the latter consistent with phenotypic consequences of IPTase deficiencies in fission and budding yeasts, and mammals. Pathogenic mutations to human IPTase (TRIT1) cause mitochondrial insufficiency and neurodevelopmental disease, principally due to decreased modification of the mt-tRNA substrates. In this study, we identify the way human TRIT1 is targeted to mitochondria. We also show that TRIT1 exhibits a tRNA anticodon identity-specific substrate sensitivity. The work leads to new understanding of the IPTases and the variable codon identities of their tRNA substrates found throughout nature.

genetics↗