Significance of peroxisome proliferator-activated receptors in the cardiovascular system in health and disease.

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear transcription factors that belong to the nuclear receptor superfamily. Three isoforms of PPAR have been identified, alpha, delta and gamma, which play distinct roles in the regulation of key metabolic processes, such as glucose and lipid redistribution. PPARalpha is expressed predominantly in the liver, kidney and heart, and is primarily involved in fatty acid oxidation. PPARgamma is mainly associated with adipose tissue, where it controls adipocyte differentiation and insulin sensitivity. PPARdelta is abundantly and ubiquitously expressed, but as yet its function has not been clearly defined. Activators of PPARalpha (fibrates) and gamma (thiazolidinediones) have been used clinically for a number of years in the treatment of hyperlipidaemia and to improve insulin sensitivity in diabetes. More recently, PPAR activation has been found to confer additional benefits on endothelial function, inflammation and thrombosis, suggesting that PPAR agonists may be good candidates for the treatment of cardiovascular disease. In this regard, it has been demonstrated that PPAR activators are capable of reducing blood pressure and attenuating the development of atherosclerosis and cardiac hypertrophy. This review will provide a detailed discussion of the current understanding of basic PPAR physiology, with particular reference to the cardiovascular system. It will also examine the evidence supporting the involvement of the different PPAR isoforms in cardiovascular disease and discuss the current and potential future clinical applications of PPAR activators.

Testing the palaeoclimatic significance of the Northern Irish bog oak record

We present an analysis of the Northern Irish bog oak record presented in Turney et al. (2005) for the last 4500 years. The record is compared with a compiled peatland water table record from the same region and palaeohydrological data from northern England and mid-latitude Europe. It is apparent that there is no consistent relationship between the population frequency of Irish bog oaks and the palaeohydrological reconstructions, illustrating that the record is not reflecting wetness changes in peatlands. We suggest that the bog oaks should be scrutinised on a within-site and a site-by-site basis to assess the spatial coherency of the shifts in tree populations and the synchronicity of phases of germination and dying off (GDO). Further work is needed to critically examine the controls on the establishment and demise of bog oaks on Irish peatlands before these data can be used as a palaeoclimate proxy. Only then can they be used to test solar forcing of Holocene climate change.

Costs, outputs and outcomes in school PFI contracts and the significance of project size

This article examines operational Private Finance Initiative (PFI) school projects and reports the experiences of UK headteachers. It considers the impact of project size on value for money (VFM). Headteachers involved in small projects are more satisfied with costs than those involved in large projects, but headteachers involved in larger projects are more satisfied with affordability. Generally, heads are more satisfied with the buildings than with the services. The authors question the government’s recent policy changes to increase the size of PFI projects.

Age and palaeoenvironmental significance of an inter-tidal peat bed at Ballywoolen, Bann estuary, Co. Londonderry.

A recently exposed inter-tidal peat bed at Ballywoolen, Bann estuary, Co. Londonderry, has yielded new information about mid-Holocene coastal environmental change in the northeast of Ireland. Pollen analytical data and wood detritus demonstrate that peat accumulation occurred in a terrestrial environment that was free from marine influence. Radiocarbon dates suggest that the peat accumulated rapidly during a period of low relative sea level subsequent to the maximum of Holocene relative sea-level rise along the north coast of Northern Ireland. The absence of marine/brackish indicator taxa at the site suggests that the tidal range was somewhat less than that at present and/or that the channel of the river was located some distance east of its present alignment. The dates indicate that the low stand lasted for at least ~0.2 ka and possibly for ~1.1 ka. Stable, woodland-dominated landscapes are indicated at both this site and neighbouring ones around ~6.4-5.3 cal ka BP. There is no evidence for large-scale aeolian sand movement or human impact on the landscape during the period of peat accumulation.

Clinical significance of sperm DNA damage in assisted reproduction outcome

Background: Sperm DNA damage shows great promise as a biomarker of infertility. The study aim is to determine the usefulness of DNA fragmentation (DF), including modified bases (MB), to predict assisted reproduction treatment (ART) outcomes. Methods: DF in 360 couples (230 IVF and 130 ICSI) was measured by the alkaline Comet assay in semen and in sperm following density gradient centrifugation (DGC) and compared with fertilization rate (FR), embryo cumulative scores (ECS1) for the total number of embryos/treatment, embryos transferred (ECS2), clinical pregnancy (CP) and spontaneous pregnancy loss. MB were also measured using formamidopyrimidine DNA glycosylase to convert them into strand breaks. Results: In IVF, FR and ECS decreased as DF increased in both semen and DGC sperm, and couples who failed to achieve a CP had higher DF than successful couples (+12.2 semen, P = 0.004; +9.9 DGC sperm, P = 0.010). When MB were added to existing strand breaks, total DF was markedly higher (+17.1 semen, P = 0.009 and +13.8 DGC sperm, P = 0.045). DF was not associated with FR, ECS or CP in either semen or DGC sperm following ISCI. In contrast, by including MB, there was significantly more DNA damage (+16.8 semen, P = 0.008 and +15.5 DGC sperm, P = 0.024) in the group who did not achieve CP. Conclusion: SDF can predict ART outcome for IVF. Converting MB into further DNA strand breaks increased the test sensitivity, giving negative correlations between DF and CP for ICSI as well as IVF. © 2010 The Author.