Project description:Development, growth and adult survival are coordinated with available metabolic resources. The insulin/IGF and TOR signaling pathways relay nutritional status, thereby ascertaining that the organism responds appropriately to environmental conditions. MicroRNAs are short (21-23 nt) regulatory RNAs that confer specificity on the RNA-induced silencing complex (RISC) to inhibit a given set of mRNA targets. We profiled changes in miRNA expression during adult life in Drosophila melanogaster and determined that miR-277 is down-regulated with age. This miRNA controls branched-chain amino acid (BCAA) catabolism and the activity of the TOR kinase, a central growth regulator. Metabolite analysis suggests that the mechanistic basis may be an accumulation of BCKAs, rather than BCAAs, thus avoiding potentially detrimental consequences of increased branched chain amino acid levels on e.g. translational fidelity. Constitutive miR-277 expression as well as transgenic inhibition with a miRNA sponge construct shortens lifespan. Furthermore, constitutive miR-277 expression is synthetically lethal with reduced insulin signaling. Thus, optimal metabolic adaptation requires tuning of cellular BCAA catabolism by miR-277 to be concordant with systemic growth signaling.
Project description:We use RNAseq to compare the transcriptomes of wild type and aan1∆ cells to determine the mechanism behind AAN1 function in the actin cytoskeleton and lifespan. We find deleting AAN1 results in changes in expression of genes involved in branched-chain amino acid synthesis.
Project description:Postoperative insulin resistance refers to the phenomenon that the body’s glucose uptake stimulated by insulin is reduced due to stress effects such as trauma or the inhibitory effect of insulin on liver glucose output is weakened after surgery.
There is a clear link between postoperative insulin resistance and poor perioperative prognosis. Therefore, exploring interventions to reduce postoperative stress insulin resistance, stabilize postoperative blood glucose, and reduce postoperative complications are clinical problems that need to be solved urgently. In recent years, research on branched-chain amino acids and metabolic diseases has become a hot spot. Studies have found that in the rat model, preoperatively given a high branched-chain amino acid diet can inhibit postoperative insulin resistance and stabilize blood glucose levels. This research plan is to try to add branched-chain amino acids before surgery to observe the occurrence of postoperative insulin resistance in patients.
Project description:Gene expression profiling of Blastobotrys raffinosifermentans LS3 cells based on 6.025 annotated chromosomal Blastobotrys raffinosifermentans LS3 sequences and 36 putative mitochondrial gene oligos was performed following exposure to protocatechuic acid. Microarray data were successfully used to identify expression changes of main candidate genes involved in tannic acid degradation, protocatechuic acid degradation, β-oxidation, the glyoxylate cycle, the methyl citrate cycle and the catabolism of the branched-chain amino acids valine, leucine and isoleucine.
Project description:Gene expression profiling of Blastobotrys raffinosifermentans LS3 cells based on 6.025 annotated chromosomal Blastobotrys raffinosifermentans LS3 sequences and 36 putative mitochondrial gene oligos was performed following exposure to gallic acid. Microarray data were successfully used to identify expression changes of main candidate genes involved in tannic acid degradation, protocatechuic acid degradation, β-oxidation, the glyoxylate cycle, the methyl citrate cycle and the catabolism of the branched-chain amino acids valine, leucine and isoleucine.
Project description:Branched-chain aminotransferases (BCAT) are enzymes that initiate the catabolism of branched-chain amino acids (BCAA), such as leucine, thereby providing macromolecule precursors. In order to study the effect of BCAT1 inhibitor (ERG240) on LPS-polarized macrophage transcriptome, we stimulated monocyte derived macrophages (MDMs) with LPS for 8 hours, with or without the presence of ERG240. We then performed whole-genome transcriptome sequencing by RNA-sequencing (RNA-seq).
Project description:The blood-feeding behavior of Anopheles females delivers essential nutrients for egg development and drives parasite transmission between humans. Plasmodium growth is adapted to the vector reproductive cycle, but how changes in the reproductive cycle impact parasite development remains unclear. Here, we show that the bloodmeal-induced miR-276-5p fine-tunes the expression of branched-chain amino acid transferase to terminate the reproductive cycle. Silencing of miR-276 prolongs high rates of amino acid (AA) catabolism and increases female fertility, suggesting that timely termination of AA catabolism restricts mosquito investment into reproduction. Prolongation of AA catabolism in P. falciparum-infected females also compromises the development of the transmissible sporozoite forms. Our results suggest that Plasmodium sporogony exploits the surplus mosquito resources available after reproductive investment and demonstrate the crucial role of the mosquito AA metabolism in within-vector parasite proliferation and malaria transmission.
Project description:Our transcriptome data shows that the two-component system CesSR, which senses cell envelope stresses of different origins, is one of the major players when L. lactis is forced to overproduce the endogenous membrane protein BcaP, a branched-chain amino acid permease. Two-condition experiment: nisin induced overproduction of BcaP vs. control. Biological replicates: 2 controls, 2 overproduction cultures; independently grown and harvested; dye swaped on the second array.
Project description:Interventions: Patients assigned for intervention group take Branched-chain amino acid formula as late-evening snack for 2 weeks preoperatively in hepatic resction,and for 4 weeks in liver transplantation,respectively. Administration of BCAA formula would be maintained for 12 weeks postoperatively in both procedure.
Patients in the control group are observed without administration of BCAA formula.
Primary outcome(s): Body cell mass
Study Design: Parallel Non-randomized
