Search

Since the KCNB1 encoding Kv2.1 channel accounts for the majority of Kv currents modulating insulin secretion by pancreatic islet beta-cells, we postulated that KCNB1 is a plausible candidate gene for genetic variation contributing to the variable compensatory secretory function of beta-cells in type-2 diabetes (T2D). We conducted two studies, a case-control study and a cross-section study, to investigate the association of common single-nucleotide polymorphisms (SNPs) in KCNB1 with T2D and its linking traits. In the case-control study, we first examined the association of 20 tag SNPs of KCNB1 with T2D in a population with 226 T2D patients and non-diabetic subjects (screening study). We then identified the association in an enlarged population of 412 T2D patients and non-diabetic subjects (replication study). In the cross-sectional study, we investigated the linkage between the candidate SNP rs1051295 and T2D by comparing beta-cell function and insulin sensitivity among rs1051295 genotypes in a general population of 1051 subjects at fasting and after glucose loading (oral glucose tolerance tests, OGTT) in 84 fasting glucose impaired subjects, and several T2D-related traits. We found that among the 19 available tag SNPs, only the KCNB1 rs1051295 was associated with T2D (P = 0.027), with the rs1051295 TT genotype associated with an increased risk of T2D compared with genotypes CC (P = 0.009). At fasting, rs1051295 genotype TT was associated with a 9.8% reduction in insulin sensitivity compared to CC (P = 0.008); along with increased plasma triglycerides (TG) levels (TT/CC: P = 0.046) and increased waist/hip (W/H) ratio (TT/CC: P = 0.013; TT/TC: P = 0.002). OGTT confirmed that genotype TT exhibited reduced insulin sensitivity by 16.3% (P = 0.030) compared with genotype TC+CC in a fasting glucose impaired population. The KCNB1 rs1051295 genotype TT in the Chinese Han population is associated with decreased insulin sensitivity and increased plasma TG and W/H ratio, which together contribute to an increased risk for T2D. [ABSTRACT FROM AUTHOR]

Aspergillus flavus first gained scientific attention for its production of aflatoxin. The underlying regulation of aflatoxin biosynthesis has been serving as a theoretical model for biosynthesis of other microbial secondary metabolites. Nevertheless, for several decades, the DNA methylation status, one of the important epigenomic modifications involved in gene regulation, in A. flavus remains to be controversial. Here, we applied bisulfite sequencing in conjunction with a biological replicate strategy to investigate the DNA methylation profiling of A. flavus genome. Both the bisulfite sequencing data and the methylome comparisons with other fungi confirm that the DNA methylation level of this fungus is negligible. Further investigation into the DNA methyltransferase of Aspergillus uncovers its close relationship with RID-like enzymes as well as its divergence with the methyltransferase of species with validated DNA methylation. The lack of repeat contents of the A. flavus' genome and the high RIP-index of the small amount of remanent repeat potentially support our speculation that DNA methylation may be absent in A. flavus or that it may possess de novo DNA methylation which occurs very transiently during the obscure sexual stage of this fungal species. This work contributes to our understanding on the DNA methylation status of A. flavus, as well as reinforces our views on the DNA methylation in fungal species. In addition, our strategy of applying bisulfite sequencing to DNA methylation detection in species with low DNA methylation may serve as a reference for later scientific investigations in other hypomethylated species. [ABSTRACT FROM AUTHOR]

Oxidative and glycolytic myofibers have different structures and metabolic characteristics and their ratios are important in determining poultry meat quality. However, the molecular mechanisms underlying their differences are unclear. In this study, global gene expression profiling was conducted in oxidative skeletal muscle (obtained from the soleus, or SOL) and glycolytic skeletal muscle (obtained from the extensor digitorum longus, or EDL) of Chinese Qingyuan partridge chickens, using the Agilent Chicken Gene Expression Chip. A total of 1224 genes with at least 2-fold differences were identified (P < 0.05), of which 654 were upregulated and 570 were downregulated in SOL. GO, KEGG pathway, and co-expressed gene network analyses suggested that PRKAG3, ATP2A2, and PPARGC1A might play important roles in myofiber composition. The function of PPARGC1A gene was further validated. PPARGC1A mRNA expression levels were higher in SOL than in EDL muscles throughout the early postnatal development stages. In myoblast cells, shRNA knockdown of PPARGC1A significantly inhibited some muscle development and transition-related genes, including PPP3CA, MEF2C, and SM (P < 0.01 or P < 0.05), and significantly upregulated the expression of FWM (P < 0.05). Our study demonstrates strong transcriptome differences between oxidative and glycolytic myofibers, and the results suggest that PPARGC1A is a key gene involved in chicken myofiber composition and transition.

Tocotrienols have been shown many biologic functions such as antioxidant, anti-cancer, maintaining fertility and regulating the immune system and so on. In this study, after feeding with tocotrienol-rich fraction from palm oil (TRF) for 2 weeks, Balb/c nude mice were inoculated human colon SW620 cancer cell and then continued to feed TRF for 4 weeks. At termination of experiments, xenografts were removed and determined the expression of Wnt-pathways related protein by immunohistochemistry or western blotting. Liver tissues were homogenated for determining the levels of antioxidative enzymes activity or malondialdehyde (MDA). The results showed that TRF significantly inhibited the growth of xenografts in nude mice. TRF also affected the activity of antioxidative enzymes in the liver tissue of mice. These changes were partly contributed to activation of wnt pathways or affecting their related protein. Thus, these finding suggested that the potent anticancer effect of TRF is associated with the regulation of Wnt signal pathways.

Since the KCNB1 encoding Kv2.1 channel accounts for the majority of Kv currents modulating insulin secretion by pancreatic islet beta-cells, we postulated that KCNB1 is a plausible candidate gene for genetic variation contributing to the variable compensatory secretory function of beta-cells in type-2 diabetes (T2D). We conducted two studies, a case-control study and a cross-section study, to investigate the association of common single-nucleotide polymorphisms (SNPs) in KCNB1 with T2D and its linking traits. In the case-control study, we first examined the association of 20 tag SNPs of KCNB1 with T2D in a population with 226 T2D patients and non-diabetic subjects (screening study). We then identified the association in an enlarged population of 412 T2D patients and non-diabetic subjects (replication study). In the cross-sectional study, we investigated the linkage between the candidate SNP rs1051295 and T2D by comparing beta-cell function and insulin sensitivity among rs1051295 genotypes in a general population of 1051 subjects at fasting and after glucose loading (oral glucose tolerance tests, OGTT) in 84 fasting glucose impaired subjects, and several T2D-related traits. We found that among the 19 available tag SNPs, only the KCNB1 rs1051295 was associated with T2D (P = 0.027), with the rs1051295 TT genotype associated with an increased risk of T2D compared with genotypes CC (P = 0.009). At fasting, rs1051295 genotype TT was associated with a 9.8% reduction in insulin sensitivity compared to CC (P = 0.008); along with increased plasma triglycerides (TG) levels (TT/CC: P = 0.046) and increased waist/hip (W/H) ratio (TT/CC: P = 0.013; TT/TC: P = 0.002). OGTT confirmed that genotype TT exhibited reduced insulin sensitivity by 16.3% (P = 0.030) compared with genotype TC+CC in a fasting glucose impaired population. The KCNB1 rs1051295 genotype TT in the Chinese Han population is associated with decreased insulin sensitivity and increased plasma TG and W/H ratio, which together contribute to an increased risk for T2D.