Glycation, oxidation, and lipoxidation in the development of the complications of diabetes: a carbonyl stress hypothesis

Modifications of extant plasma proteins, structural proteins,and other macromolecules are enhanced in diabetes because of increased glycation (secondary to increased glucose concentrations) and perhaps because of increased oxidative stress, Increased glycation is present from the time of onset of diabetes, but the relation between diabetes and oxidative stress is less clear: increased oxidative stress may occur later in the course of disease, as vascular damage becomes established, or it may be a feature of uncomplicated diabetes, The combined effects of protein modification by glycation and oxidation may contribute to the development of accelerated atherosclerosis in diabetes and to the development of microvascular complications, Thus, even if not increased by diabetes, variations in oxidative stress may modulate the consequences of hyperglycemia in individual diabetic patients, In this review, the close interaction between glycation and oxidative processes is discussed, and the theme is developed that the most significant modifications of proteins are the result of interactions with reactive carbonyl groups, While glucose itself contains a carbonyl group that is involved in the initial glycation reaction, the most important and reactive carbonyls are formed by free radical-oxidation reactions damaging either carbohydrates (including glucose itself) or lipids, The resulting carbonyl-containing intermediate products then modify proteins, yielding "glycoxidation" and "lipoxidation" products, respectively, This common pathway for glucose and lipid-mediated stress, which may contribute to diabetic complications, is the basis for the carbonyl stress hypothesis for the development of diabetic complications.

An allelic series reveals essential roles for FY in plant development in addition to flowering-time control.

The autonomous pathway functions to promote flowering in Arabidopsis by limiting the accumulation of the floral repressor FLOWERING LOCUS C (FLC). Within this pathway FCA is a plant-specific, nuclear RNA-binding protein, which interacts with FY, a highly conserved eukaryotic polyadenylation factor. FCA and FY function to control polyadenylation site choice during processing of the FCA transcript. Null mutations in the yeast FY homologue Pfs2p are lethal. This raises the question as to whether these essential RNA processing functions are conserved in plants. Characterisation of an allelic series of fy mutations reveals that null alleles are embryo lethal. Furthermore, silencing of FY, but not FCA, is deleterious to growth in Nicotiana. The late-flowering fy alleles are hypomorphic and indicate a requirement for both intact FY WD repeats and the C-terminal domain in repression of FLC. The FY C-terminal domain binds FCA and in vitro assays demonstrate a requirement for both C-terminal FY-PPLPP repeats during this interaction. The expression domain of FY supports its roles in essential and flowering-time functions. Hence, FY may mediate both regulated and constitutive RNA 3'-end processing.

You’re Wha…? Including young men in reproductive planning

The importance of including fathers in reproductive planning, pregnancy and childbirth cannot be overstated and it is increasingly recognised that addressing their sense of exclusion from maternity services requires further action. One very overlooked area, however, is in helping young men, alongside their partners, in preventing an unintended teenage pregnancy. The UK has the highest rate of teenage pregnancy in Western Europe and, while teenage men are seen as half of the problem, they are rarely regarded as half of the solution. We argue that education is an essential part of the process of increasing men's sense of inclusion and describe If I were Jack, an educational resource about unintended teenage pregnancy which has been developed specifically for young men.

The opportunities and limitations of using CFD in the development of wave energy converters

Most Wave Energy Converters (WECs) being developed are fundamentally different from known marine structures. Limited experience is a fundamental challenge for the design, especially issues concerning load assumptions and power estimates. Reynolds-Averaged Navier-Stokes (RANS) CFD methods are being used successfully in many areas of marine engineering. They have been shown to accurately simulate many hydrodynamic effects and are a helpful tool for investigating complex flows. The major drawback is the significant computational power required and the associated overhead with pre and post-processing. This paper presents the challenges and advantages in the application of RANS CFD methods in the design process of a wave energy converter and compares the time, labour and ultimately financial requirements for obtaining practical results.

Navigating Risk: Understanding the Impact of the Conflict on Children and Young People in Northern Ireland:Special Issue: Northern Ireland: 20 Years After the Cease-Fires

Twenty years on from the 1994 cease-fires, Northern Ireland is a markedly safer place for children and young people to grow up. However, for a significant number, growing up in post-conflict Northern Ireland has brought with it continued risks and high levels of marginalization. Many young people growing up on the sharp edge of the transition have continued to experience troubling levels of poverty, lower educational attainment, poor standards of childhood health, and sustained exposure to risk-laden environments. Reflecting on interdisciplinary research carried out since the start of the “transition” to peace, this article emphasizes the impact that embedded structural inequalities continue to have on the social, physical, mental, and emotional well-being of many children and young people. In shining a light on the enduring legacy of the conflict, this article moves to argue that greater attention needs to be given to the ongoing socioeconomic factors that result in limited lifetime opportunities, marginalization, and sustained poverty for many young people growing up in “peacetime” Northern Ireland.

Deoxynivalenol exposure assessment in young children in Tanzania

Scope: This study assessed deoxynivalenol (DON) exposure in children from three geographic locations within Tanzania, over three time points in 1 year, using a urinary biomarker of exposure.

Methods and results: A total of 166 children aged 6-14 months were studied at a maize harvest and followed up twice at 6-month intervals. On two consecutive days, morning urine was collected from each child and urinary DON was measured using an LC-MS method, with and without beta-glucuronidase hydrolysis in order to assess free DON (fDON) and glucuronide DON. Overall, urinary DON increased significantly along with the three visits (geometric mean 1.1, 2.3, and 5.7 ng/mL, at visits 1, 2, and 3, respectively, p <0.01). fDON was 22% of urinary total DON. Urinary DON excretion rate was 74% in village Kikelelwa based on food DON level and food consumption. Assuming 360 mL of urine excreted per day, 10, 19, and 29% of children at visits 1, 2, and 3, respectively, exceeded the provisional maximum tolerable daily intake of 1000 ng/kg b.w./day.

Conclusion: Young children in Tanzania are chronically exposed to DON due to eating contaminated maize, although exposure levels varied markedly by region and season.