Eukaryote ribosomal translation is terminated when release factor eRF1, in a complex with eRF3, binds to one of the three stop codons. The tertiary structure and dimensions of eRF1 are similar to that of a tRNA, supporting the hypothesis that release factors may act as molecular mimics of tRNAs. To identify the yeast eRF1 stop codon recognition domain (analogous to a tRNA anticodon), a genetic screen was performed to select for mutants with disabled recognition of only one of the three stop codons. Nine out of ten mutations isolated map to conserved residues within the eRF1 N-terminal domain 1. A subset of these mutants, although wild-type for ribosome and eRF3 interaction, differ in their respective abilities to recognize each of the three stop codons, indicating codon-specific discrimination defects. Five of six of these stop codon-specific mutants define yeast domain 1 residues (I32, M48, V68, L123, and H129) that locate at three pockets on the eRF1 domain 1 molecular surface into which a stop codon can be modeled. The genetic screen results and the mutant phenotypes are therefore consistent with a role for domain 1 in stop codon recognition; the topology of this eRF1 domain, together with eRF1-stop codon complex modeling further supports the proposal that this domain may represent the site of stop codon binding itself.

The objective of this study was to perform a systematic review of the literature to determine whether there is an association between polycystic ovary syndrome (PCOS) and gynaecological malignancy. Medline and Embase databases (1968-2008) were searched to identify publications on the association between PCOS and gynaecological cancers including breast cancer. Studies were selected that examined the association between PCOS and all types of gynaecological malignancies. A total of 19 studies exploring the association between PCOS and breast, endometrial and ovarian cancer were identified. Of these, only eight could be included after review. The data showed variability in the definition of PCOS. A meta-analysis of the data suggests that women with PCOS are more likely to develop cancer of the endometrium (OR 2.70, 95% CI 1.00-7.29) and ovarian cancer (OR 2.52, 95% CI 1.08-5.89) but not breast cancer (OR 0.88, 95% CI 0.44-1.77). Women with PCOS appear to be three times more likely to develop endometrial cancer but are not at increased risk of breast cancer. There is insufficient evidence to implicate PCOS in the development of vaginal, vulval, cervical or ovarian cancers. The paucity of studies investigating the association between PCOS and gynaecological cancers is likely to affect the reliability of the conclusions.

It is possible for a man with non-mosaic Klinefelter to father a child. However, before these techniques are offered, some ethical issues need to be explored.

Objective To assess the outcomes of pregnancy following postpartum haemorrhage (PPH) in the first pregnancy.Design Cohort study.Setting Aberdeen Maternity Hospital, Scotland, UK.Population All women with first deliveries recorded in the Aberdeen Maternity and Neonatal Databank (AMND) between 1986 and 2005.Methods All women identified from the AMND were classified into exposed and unexposed cohorts, according to whether or not they had PPH in their first delivery. They were then linked to any records of a second pregnancy.Main outcome measures Any second pregnancy, time to second pregnancy, early or late pregnancy loss, and prevalence of PPH in the second pregnancy.Results Out of 34 334 women, 10% had a PPH in their first pregnancy. There was no statistically significant difference in the time to a second pregnancy, nor in the outcome of that second pregnancy, between women who had experienced a PPH in their first pregnancy and women who had not. For women with a caesarean delivery, there was a significant reduction in the proportion conceiving again, comparing the exposed and unexposed cohorts.Conclusions From this cohort study we can conclude that if a PPH occurs in a first pregnancy, there is no delay in achieving a second pregnancy, and no detrimental effect on the outcome of that pregnancy. Significantly fewer women conceive a second pregnancy if they have a caesarean section in their first pregnancy that is complicated by PPH.

Background In contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity. Methods and results CLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia, and Africa in 2009–2010, and followed up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischaemia, or prior revascularization procedure. Among 32 694 patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to ∼60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome (cardiovascular death, myocardial infarction, or stroke) with an adjusted hazard ratio of 1.28 (95% confidence interval 1.18, 1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest. Conclusion In patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes. ClinicalTrials identifier ISRCTN43070564