DNA Methylation Is Linked to Deacetylation of Histone H3, but Not H4, on the Imprinted Genes Snrpn and U2af1-rs1

The relationship between DNA methylation and histone acetylation at the imprinted mouse genes U2af1-rs1 and Snrpn is explored by chromatin immunoprecipitation (ChIP) and resolution of parental alleles using single-strand conformational polymorphisms. The U2af1-rs1 gene lies within a differentially methylated region (DMR), while Snrpn has a 5' DMR (DMR1) with sequences homologous to the imprinting control center of the Prader-Willi/Angelman region. For both DMR1 of Snrpn and the 5' untranslated region (5'-UTR) and 3'-UTR of U2af1-rs1, the methylated and nonexpressed maternal allele was underacetylated, relative to the paternal allele, at all H3 lysines tested (K14, K9, and K18). For H4, underacetylation of the maternal allele was exclusively (U2af1-rs1) or predominantly (Snrpn) at lysine 5. Essentially the same patterns of differential acetylation were found in embryonic stem (ES) cells, embryo fibroblasts, and adult liver from F1 mice and in ES cells from mice that were dipaternal or dimaternal for U2af1-rs1. In contrast, in a region within Snrpn that has biallelic methylation in the cells and tissues analyzed, the paternal (expressed) allele showed relatively increased acetylation of H4 but not of H3. The methyl-CpG-binding-domain (MBD) protein MeCP2 was found, by ChIP, to be associated exclusively with the maternal U2af1-rs1 allele. To ask whether DNA methylation is associated with histone deacetylation, we produced mice with transgene-induced methylation at the paternal allele of U2af1-rs1. In these mice, H3 was underacetylated across both the parental U2af1-rs1 alleles whereas H4 acetylation was unaltered. Collectively, these data are consistent with the hypothesis that CpG methylation leads to deacetylation of histone H3, but not H4, through a process that involves selective binding of MBD proteins.     

Clinical and angiographic results with the beStent: the Registry for Optimal beStent Evaluation (ROSE) trial

BACKGROUND: Although safety and efficacy of the beStent (Medtronic Inc., Santa Rosa, CA, USA) have been described, the long-term angiographic and clinical outcomes have yet to be investigated. The ROSE (Registry for Optimal beStent Evaluation) trial was designed to assess the procedural safety of single 15 mm beStent implantation, and the six-month angiographic and 12-month clinical outcomes of patients treated with this novel coronary stent. METHODS: Patients with angina and a single de novo lesion in a native coronary artery of >/=2.75 mm diameter were included in this multicenter, prospective, observational trial. Clinical follow-up was obtained at one, six and 12 months. Angiography was performed before and after the stent implantation and at six months. The primary end-point included major adverse cardiac events (death, myocardial infarction and target lesion revascularization), major bleeding complications, and thrombotic occlusions at one-month follow-up. Secondary end-points were major cardiac-event-free survival at six- and 12-month follow-up and angiographic restenosis at six months. A total of 120 patients (80% male, mean age 58.6 +/- 10.6 years) with stable (48%) or unstable (44%) angina pectoris were allocated. The target vessel reference diameter pre-procedure was 2.85 +/- 0.52 mm. RESULTS: Minimal lumen diameter pre/post and at follow-up was 0.97 +/- 0.28 mm, 2.53 +/- 0.40 mm and 1.86 +/- 0.63 mm, respectively. Restenosis rate according to the >50% diameter stenosis criterion at six-month follow-up was 21.5%. At 12 months, the event-free survival rate was 75% (no deaths, two Q-wave and seven non-Q-wave infarctions, five bypass surgery interventions and 16 target lesion revascularizations), whilst 87% of the patients were free of angina pectoris. CONCLUSION: Despite the relatively high percentage of small vessels, the outcome of the ROSE trial is comparable to those observed in previous stent trials, indicating that the coronary beStent is safe and effective as a primary device for the treatment of native coronary artery lesions in patients with (un)stable angina pectoris.     

Associations of myostatin gene polymorphisms with performance and mortality traits in broiler chickens

Myostatin is a negative regulator of skeletal muscle growth. We evaluated effects of myostatin polymorphisms in three elite commercial broiler chicken lines on mortality, growth, feed conversion efficiency, ultrasound breast depth, breast percentage, eviscerated carcass weight, leg defects, blood oxygen level, and hen antibody titer to infectious bursal disease virus vaccine. Progeny mean data adjusted for fixed and mate effects and DNA from 100 sires per line were used. Single nucleotide polymorphisms (SNPs) of the myostatin gene segregating in these lines were identified by designing specific primers, amplifying individual DNA in each line by polymerase chain reaction, cloning, sequencing and aligning the corresponding products. Individual sires were genotyped for five identified SNPs which contributed to eight haplotypes. Frequencies of SNP alleles and haplotypes differed between lines. Using the allele substitution effect model, the myostatin SNPs were found to have significant (P < 0.031) associations with growth, mortality, blood oxygen and hen antibody titer to infectious bursal disease virus vaccine, although the associations were not often consistent across lines. These results suggest that the myostatin gene has pleiotropic effects on broiler performance.     

Functional implications of the microbial community structure of undefined mesophilic starter cultures

This review describes the recent advances made in the studies of the microbial community of complex and undefined cheese starter cultures. We report on work related to the composition of the cultures at the level of genetic lineages, on the presence and activity of bacteriophages and on the population dynamics during cheese making and during starter culture propagation. Furthermore, the link between starter composition and starter functionality will be discussed. Finally, recent advances in predictive metabolic modelling of the multi-strain cultures will be discussed in the context of microbe-microbe interactions.     

New clinically relevant,orthotopic mouse models of human chondrosarcoma with spontaneous metastasis

Background  

Chondrosarcoma responds poorly to adjuvant therapy and new, clinically relevant animal models are required to test targeted therapy.