Nucleotide diversity on the ovine Y chromosome

To investigate the impact of male-mediated introgression during the evolution of sheep breeds, a sequencing approach was used to identify single nucleotide polymorphisms (SNPs) from the male-specific region of the ovine Y chromosome (MSY). A total of 4380 bp, which comprised nine fragments from five MSY genes was sequenced within a panel of 14 males from seven breeds. Sequence alignment identified a single segregating site, an A/G SNP located approximately 1685 bp upstream of the ovine SRY gene. The resulting estimation of nucleotide diversity (piY = 0.90 +/- 0.50 x 10(-4)) falls towards the lower end of estimates from other species. This was compared with the nucleotide diversity estimated from the autosomal component of the genome. Sequence analysis of 2933 bp amplified from eight autosomal genes revealed a nucleotide diversity (piA = 2.15 +/- 0.27 x 10(-3)) higher than previously reported for sheep. Following adjustment for the contrasting influence of effective population size and a male biased mutation rate, comparison revealed that approximately 10% of the expected nucleotide diversity is present on the ovine Y chromosome.     

Variable nuclear markers for a Sonoran Desert bark beetle, Araptus attenuatus Wood (Curculionidae: Scolytinae), with applications to related genera

We report eight new co-dominant nuclear markers for population genetics of the bark beetle Araptus attenuatus Wood. Several loci include introns from low-copy genes, and four cross-amplify in one or more related genera. The markers show moderate levels of polymorphism (2–19 alleles per locus), and no loci showed significant deviations from Hardy–Weinberg or linkage equilibrium across both of the two populations examined, consistent with Mendelian inheritance patterns.     

Fructose Mediated Non-Alcoholic Fatty Liver Is Attenuated by HO-1-SIRT1 Module in Murine Hepatocytes and Mice Fed a High Fructose Diet

Background

Oxidative stress underlies the etiopathogenesis of nonalcoholic fatty liver disease (NAFLD), obesity and cardiovascular disease (CVD). Heme Oxygenase-1 (HO-1) is a potent endogenous antioxidant gene that plays a key role in decreasing oxidative stress. Sirtuin1 (SIRT1) belongs to the family of NAD-dependent de-acyetylases and is modulated by cellular redox.

Hypothesis

We hypothesize that fructose-induced obesity creates an inflammatory and oxidative environment conducive to the development of NAFLD and metabolic syndrome. The aim of this study is to determine whether HO-1 acts through SIRT1 to form a functional module within hepatocytes to attenuate steatohepatitis, hepatic fibrosis and cardiovascular dysfunction.

Methods and Results

We examined the effect of fructose, on hepatocyte lipid accumulation and fibrosis in murine hepatocytes and in mice fed a high fructose diet in the presence and absence of CoPP, an inducer of HO-1, and SnMP, an inhibitor of HO activity. Fructose increased oxidative stress markers and decreased HO-1 and SIRT1 levels in hepatocytes (p<0.05). Further fructose supplementation increased FAS, PPARα, pAMPK and triglycerides levels; CoPP negated this increase. Concurrent treatment with CoPP and SIRT1 siRNA in hepatocytes increased FAS, PPARα, pAMPK and triglycerides levels suggesting that HO-1 is upstream of SIRT1 and suppression of SIRT1 attenuates the beneficial effects of HO-1. A high fructose diet increased insulin resistance, blood pressure, markers of oxidative stress and lipogenesis along with fibrotic markers in mice (p<0.05). Increased levels of HO-1 increased SIRT1 levels and ameliorated fructose-mediated lipid accumulation and fibrosis in liver along with decreasing vascular dysfunction (p<0.05 vs. fructose). These beneficial effects of CoPP were reversed by SnMP.

Conclusion

Taken together, our study demonstrates, for the first time, that HO-1 induction attenuates fructose-induced hepatic lipid deposition, prevents the development of hepatic fibrosis and abates NAFLD-associated vascular dysfunction; effects that are mediated by activation of SIRT1 gene expression.     

Bub3p Facilitates Spindle Checkpoint Silencing in Fission Yeast

Although critical for spindle checkpoint signaling, the role kinetochores play in anaphase promoting complex (APC) inhibition remains unclear. Here we show that spindle checkpoint proteins are severely depleted from unattached kinetochores in fission yeast cells lacking Bub3p. Surprisingly, a robust mitotic arrest is maintained in the majority of bub3Δ cells, yet they die, suggesting that Bub3p is essential for successful checkpoint recovery. During recovery, two defects are observed: (1) cells mis-segregate chromosomes and (2) anaphase onset is significantly delayed. We show that Bub3p is required to activate the APC upon inhibition of Aurora kinase activity in checkpoint-arrested cells, suggesting that Bub3p is required for efficient checkpoint silencing downstream of Aurora kinase. Together, these results suggest that spindle checkpoint signals can be amplified in the nucleoplasm, yet kinetochore localization of spindle checkpoint components is required for proper recovery from a spindle checkpoint-dependent arrest.