The histone demethylase JMJD2A/KDM4A links ribosomal RNA transcription to nutrients and growth factors availability

The interplay between methylation and demethylation of histone lysine residues is an essential component of gene expression regulation and there is considerable interest in elucidating the roles of proteins involved. Here we report that histone demethylase KDM4A/JMJD2A, which is involved in the regulation of cell proliferation and is overexpressed in some cancers, interacts with RNA Polymerase I, associates with active ribosomal RNA genes and is required for serum-induced activation of rDNA transcription. We propose that KDM4A controls the initial stages of transition from 'poised', non-transcribed rDNA chromatin into its active form. We show that PI3K, a major signalling transducer central for cell proliferation and survival, controls cellular localization of KDM4A and consequently its association with ribosomal DNA through the SGK1 downstream kinase. We propose that the interplay between PI3K/SGK1 signalling cascade and KDM4A constitutes a mechanism by which cells adapt ribosome biogenesis level to the availability of growth factors and nutrients.

Evaluation of N (epsilon)-(3-formyl-3,4-dehydropiperidino)lysine as a novel biomarker for the severity of diabetic retinopathy.

AIMS/HYPOTHESIS: Recent studies suggest that oxidative stress should be monitored alongside HbA(1c) to identify subgroups of diabetic patients at high risk of initiation or progression of retinopathy. The acrolein-derived advanced lipoxidation end-product (ALE), [Formula: see text]-(3-formyl-3,4-dehydropiperidino)lysine (FDP-lysine), is a useful biomarker that reflects the cumulative burden of oxidative stress over long periods of time. The purpose of the present study was to investigate whether serum and haemoglobin levels of FDP-lysine are associated with the severity of diabetic retinopathy in type 1 and type 2 diabetic patients.

METHODS: Serum and haemoglobin levels of FDP-lysine were measured by competitive ELISA in 59 type 1 and 76 type 2 diabetic patients with no retinopathy, non-proliferative retinopathy or proliferative retinopathy (mean age [+/-SEM] 54.3 +/- 1.3 years), and in 47 non-diabetic control individuals (mean age 51.9 +/- 2.1 years).

RESULTS: Serum and haemoglobin levels of FDP-lysine were significantly increased in diabetic patients compared with control individuals (p = 0.04 and p = 0.002, respectively). However, no significant association was found between levels of serum FDP-lysine and the severity of diabetic retinopathy (p = 0.97). In contrast, increased haemoglobin FDP-lysine levels were observed in patients with proliferative retinopathy compared with patients without retinopathy and with non-proliferative retinopathy (p = 0.04). The relationship of FDP-lysine with proliferative retinopathy was unaltered after adjustment for HbA(1c), or other clinical parameters.

CONCLUSIONS/INTERPRETATION: Our data suggest that haemoglobin FDP-lysine may provide a useful risk marker for the development of proliferative diabetic retinopathy independently of HbA(1c), and that elevated intracellular ALE formation may be involved in the pathogenesis of this sight-threatening complication of diabetes.

Foraging ecology, fluctuating food availability and energetics of wintering brent geese

Changing energy requirements and dramatic shifts in food availability are major factors driving behaviour and distribution of herbivores. We investigate this in wintering East Canadian High Arctic light-bellied brent geese Branta bernicla hrota in Northern Ireland. They followed a sequential pattern of habitat use, feeding on intertidal Zostera spp. in autumn and early winter before moving to predominantly saltmarsh and farmland in late winter and early spring. Night-time feeding occurred throughout and made a considerable contribution to the birds' daily energy budget, at times accounting for > 50% of energy intake. Nocturnal feeding, however, is limited to the intertidal, possibly because of predation risk on terrestrial habitat, and increases with moonlight. The amount of Zostera spp., declined dramatically after the arrival of birds, predominantly, but not entirely, due to consumption by the birds. Birds gained fat reserves in the first 2 months but then this was dramatically lost as their major food source collapsed and their daily energy intake declined. Single birds consistently fared worse than paired birds and pairs with juveniles fared better than those without suggesting a benefit of having a family to compete for food. Many birds leave the Lough at this time of reduced Zostera spp. for other sea inlets in Ireland but some remain. Body condition of the latter gradually improved in early spring and reflected a heavy reliance on terrestrial habitats, particularly farmland, to meet the birds' daily energy requirements. However, even in the period immediately before migration to the breeding ground, the birds did not regain the amount of abdominal fatness observed in November. The dramatic changes in available food and requirements of the birds drive the major changes seen in foraging behaviour as the birds evade starvation in the wintering period.

The use of process simulation methods in support of organisational learning in availability contracting

Traditional business models in the aerospace industry are based on a conventional supplier to customer relationship based on the design, manufacture and subsequent delivery of the physical product. Service provision, from the manufacturer's perspective, is typically limited to the supply of procedural documentation and the provision of spare parts to the end user as the product passes through the latter stages of its intended lifecycle. Challenging economic and political conditions have resulted in end users re-structuring their core business activities, particularly in the defence sector. This has resulted in the need for original equipment manufacturers (OEMs) to integrate and manage support service activities in partnership with the customer to deliver platform availability. This improves the probability of commercial sustainability for the OEM through shared operational risks while reducing the cost of platform ownership for the customer. The need for OEMs to evolve their design, manufacture and supply strategies by focusing on customer requirements has revealed a need for reconstruction of traditional internal behaviours and design methodologies. Application of organisational learning is now a well recognised principle for innovative companies to achieve long term growth and sustained technical development, and hence, greater market command. It focuses on the process by which the organisation's knowledge and value base changes, leading to improved problem solving ability and capacity for action. From the perspective of availability contracting, knowledge and the processes by which it is generated, used and retained, become primary assets within the learning organisation. This paper will introduce the application of digital methods to asset management by demonstrating how the process of learning can benefit from a digital approach, how product and process design can be integrated within a virtual framework and finally how the approach can be applied in a service context.

Effect of Inhibitor Compounds on N-epsilon-(Carboxymethyl)lysine (CML) and N-epsilon-(Carboxyethyl)lysine (CEL) Formation in Model Foods

The possible adverse effects on health of diet-derived advanced glycation endproducts (AGES) and advanced lipoxidation endproducts (ALES) is of current interest. This study had the objective of determining the effects of the addition of AGE/ALE inhibitors and different types of sugar and cooking oil on N-epsilon-(carboxymethyl)lysine (CML) and N-epsilon-(carboxyethyl)lysine (CEL) formation in model foods (sponge cakes). The cake baked using glucose produced the highest level of CML (2.07 +/- 0.24 mmol/mol lysine), whereas the cake baked using fructose produced the highest concentration of CEL (25.1 +/- 0.15 mmol/mol lysine). There were no significant differences between CML concentrations formed in the cakes prepared using different types of cooking oil, but significant differences (P

N-epsilon-(carboxymethyl)lysine content of foods commonly consumed in a Western style diet

The potential adverse effects on health of diet-derived advanced glycation end-products (AGEs) is of current interest, due to their proposed involvement in the disease progression of diabetic and uraemic conditions. However, accurate information about levels of AGEs in foods is lacking. The objective of this investigation was to determine the level of one particular AGE, N-epsilon-(carboxymethyl)lysine (CML), a marker of AGE formation, in a wide range of foods commonly consumed in a Western style diet. Individual foods (n = 257) were mixed, lyophilised, ground, reduced, fat-extracted, hydrolysed, and underwent solid-phase extraction. Extracts were analysed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Cereal (2.6 mg/100 g food) and fruit and vegetable (0.13 mg/100 g food) categories had the highest and lowest mean level of CML, respectively, when expressed in mg/100 g food. These data can be used for estimating potential consumer intakes, and provide information that can be used to educated consumers on how to reduce their CML intake. (C) 2011 Elsevier Ltd. All rights reserved.

Availability of complementary and alternative medicine for people with cancer in the British National Health Service: Results of a national survey

This study assessed access to Complementary and Alternative Medicine (CAM) therapies for people with cancer within the British National Health Service. CAM units were identified through an internet search in 2009. A total of 142 units, providing 62 different therapies, were identified: 105 (74.0%) England; 23 (16.2%) Scotland; 7 (4.9%) each in Wales and Northern Ireland. Most units provide a small number of therapies (median 4, range 1–20), and focus on complementary, rather than alternative approaches. Counselling is the most widely provided therapy (available at 82.4% of identified units), followed by reflexology (62.0%), aromatherapy (59.1%), reiki (43.0%), massage (42.2%). CAM units per million of the population varied between countries (England: 2.2; Wales: 2.3; Scotland: 4.8; Northern Ireland: 5.0), and within countries. Better publicity for CAM units, greater integration of units in conventional cancer treatment centres may help improve access to CAMs.