Role of Nrf2 in the regulation of CD36 and stress protein expression in murine macrophages - Activation by oxidatively modified LDL and 4-hydroxynonenal

CD36 is an important scavenger receptor mediating uptake of oxidized low- density lipoproteins ( oxLDLs) and plays a key role in foam cell formation and the pathogenesis of atherosclerosis. We report the first evidence that the transcription factor Nrf2 is expressed in vascular smooth muscle cells, and demonstrate that oxLDLs cause nuclear accumulation of Nrf2 in murine macrophages, resulting in the activation of genes encoding CD36 and the stress proteins A170, heme oxygenase- 1 ( HO- 1), and peroxiredoxin I ( Prx I). 4- Hydroxy- 2- nonenal ( HNE), derived from lipid peroxidation, was one of the most effective activators of Nrf2. Using Nrf2- deficient macrophages, we established that Nrf2 partially regulates CD36 expression in response to oxLDLs, HNE, or the electrophilic agent diethylmaleate. In murine aortic smooth muscle cells, expressing negligible levels of CD36, both moderately and highly oxidized LDL caused only limited Nrf2 translocation and negligible increases in A170, HO- 1, and Prx I expression. However, treatment of smooth muscle cells with HNE significantly enhanced nuclear accumulation of Nrf2 and increased A170, HO- 1, and Prx I protein levels. Because PPAR-gamma can be activated by oxLDLs and controls expression of CD36 in macrophages, our results implicate Nrf2 as a second important transcription factor involved in the induction of the scavenger receptor CD36 and antioxidant stress genes in atherosclerosis.

Can adapting the homes of older people and providing assistive technology pay its way?

Background: Adaptations and assistive technology (AT) have an important role in enabling older people to remain in their own homes. Objective: To measure the feasibility and cost of adaptations and AT, and the scope for these to substitute and supplement formal care. Design: Detailed design studies to benchmark the adaptability of 82 properties against the needs of seven notional users. Setting: Social rented housing sector. Main outcome measures: Measures of the adaptability of properties, costs of care, adaptations and AT, and relationships between these costs. Results: The adaptability of properties varies according to many design factors and the needs of occupiers. The most adaptable properties were ground floor flats and bungalows; the least were houses, maisonettes and flats in converted houses. Purpose-built sheltered properties were generally more adaptable than corresponding mainstream properties but the opposite was the case for bungalows. Adaptations and AT can substitute for and supplement formal care, and in most cases the initial investment in adaptations and AT is recouped through subsequently lower care costs within the average life expectancy of a user. Conclusion: Appropriately selected adaptations and AT can make a significant contribution to the provision of living environments which facilitate independence. They can both substitute for traditional formal care services and supplement these services in a cost-effective way.

Effect of chymosin and salt reduction on the quality of ultrafiltrated white-salted cheese

This study demonstrated that both chymosin and salt-in-moisture (SM) were important factors for proteolysis in the manufacture of ultrafiltrated white-salted cheese, with significant effects on water-soluble nitrogen and nitrogen soluble in trichloroacetic acid. In contrast, the levels of free amino acids were not significantly affected by chymosin and salt treatments. The cheeses made using high levels of chymosin with low SM had lower levels of residual α(s1)- and β-casein at the end of ripening. On texture profile analysis, the hardness and fracturability of the cheeses significantly increased with SM and decreased during ripening. Increases in chymosin significantly contributed to the overall weakening of the structure throughout ripening. Bitter flavour was detected after 12 weeks in the cheese made with the higher chymosin level and lower SM, which could be the result of accumulation of γ-casein fractions. The sensory data indicated that the hedonic responses for low chymosin with low SM cheeses were good and acceptable in flavour, which may be due to the moderate levels of proteolysis products.

Green noise or green value? Measuring the effects of environmental certification on office values

This study investigates the price effects of environmental certification on commercial real estate assets. It is argued that there are likely to be three main drivers of price differences between certified and noncertified buildings. These are additional occupier benefits, lower holding costs for investors and a lower risk premium. Drawing upon the CoStar database of U.S. commercial real estate assets, hedonic regression analysis is used to measure the effect of certification on both rent and price. The results suggest that, compared to buildings in the same submarkets, eco-certified buildings have both a rental and sale price premium.

The effect of term-time employment on UK higher education students

In the UK, participation in higher education has risen over the past two decades, along with a shift of the costs of higher education onto the individual and a move to widening participation among previously underrepresented groups. This has led to changes in the way individuals fund their higher education, in particular a rise in the incidence of term time employment. Term time employment potentially plays a much bigger role than in the past, both as a means for individuals to fund their education and reduce debt, and as a way to gain valuable work experience and increase employability. With the increase in the number of graduates in the UK labour market it is now more important for individuals to be able to differentiate themselves in the labour market.

The influence of ultraviolet radiation on growth, photosynthesis and phenolic levels of green and red lettuce: potential for exploiting effects of ultraviolet radiation in a production system

Studies have shown that natural ultraviolet (UV) radiation increases secondary products such as phenolics but can significantly inhibit biomass accumulation in lettuce plants. In the work presented here, the effect of UV radiation on phenolic concentration and biomass accumulation was assessed in relation to photosynthetic performance in red and green lettuce types. Lettuce plants in polythene clad tunnels were exposed to either ambient (UV transparent film) or UV-free conditions (UV blocking film). The study tested whether growth reduction in lettuce plants exposed to natural UV radiation is because of inhibition of photosynthesis by direct damage to the photosynthetic apparatus or by internal shading by anthocyanins. Ambient levels of UV radiation did not limit the efficiency of photosynthesis suggesting that phenolic compounds may effectively protect the photosynthetic apparatus. Growth inhibition does, however, occur in red lettuce and could be explained by the high metabolic cost of phenolic compounds for UV protection. From a commercial perspective, UV transparent and UV blocking films offer opportunities because, in combination, they could increase plant quality as well as productivity. Growing plants continuously under a UV blocking film, and then 6 days before the final harvest transferring them to a UV transparent film, showed that high yields and high phytochemical content can be achieved complementarily.

The influence of dietary fatty acid composition on N-ethyl-Nnitrosourea-induced mammary tumour incidence in the rat and on the composition of inositol- and ethanolamine-phospholipids of normal and tumour mammary tissue

This study has investigated the influence of dietary fatty acid composition on mammary tumour incidence in N-ethyl-N-nitrosourea (ENU)-treated rats and has compared the susceptibility to dietary fatty acid modification of the membrane phospholipids phosphatidyliuositol (PI) and phosphatidylethanolamine (PE) from normal and tumour tissue of rat mammary gland. The incidence of mammary tumours was significantly lower in fish oil- (29%), compared with olive oil- (75%; P < 0.04) but not maize oil- (63%; P < 0.1) fed animals. No differences in PI fatty acid composition were found in normal or tumour tissue between rats fed on maize oil, olive oil or fish oil in diets from weaning. When normal and tumour tissue PI fatty acids were compared, significantly higher amounts of stearic acid (18:O) were found in tumour than normal tissue in rats given olive oil (P < 0.05). A similar trend was found in animals fed on maize oil, although differences between normal and tumour tissue did not reach a level of statistical significance (P < 0.1). In mammary PE, maize oil-fed control animals had significantly higher levels of linoleic acid (18:2n-6) than either olive oil- or fish oil-fed animals (P < 0.05, both cases) and levels of arachidonic acid were also higher in maize oil- compared with fish oil-fed animals (P < 0.05). In tumourbearing animals no differences in PE fatty acid composition were found between the three dietary groups. When normal and tumour tissue PE fatty acids were compared, significantly lower amounts of liuoleic acid (18:2n-6; P < 0.01) and significantly greater amounts of arachidonic acid (20:4n-6; P < 0.05) were found in tumour than normal tissue of rats fed on maize oil. The present study shows that the fatty acid composition of PI from both normal and tumour tissue of the mammary gland is resistant to dietary fatty acid modification. The PE fraction is more susceptible to dietary modification and in this fraction there is evidence of increased conversion of linoleic acid to arachidonic acid in tumour compared with normal tissue. Lower tumour incidence rates in rats given fish oils may in part be due to alteration in prostanoid metabolism secondary to displacement of arachidonic acid by eicosapentaenoic acid, but PE rather than PI would appear to be the most likely locus for diet-induced alteration in prostanoid synthesis in this tissue. Effects of dietary fatty acids other than on the balance of n-6 and n-3 fatty acids, and on prostanoid metabolism, should also be considered. The significance of increased stearic acid content of PI in tumours of olive oil-fed animals and the possible influence of dietary fatty acids on the capacity for stearic acid accumulation requires further study.

On the determinants of optimal border enforcement

We extend the current immigration-enforcement literature by incorporating both the practice of people smuggling and a role for non-wage income into a two-country, dynamic general equilibrium model. We use the model economy to examine three questions. First, how does technological progress in the smuggling industry affect the level of migration and capital accumulation for a given level of enforcement? Second, do changes in border enforcement affect the level of migration, capital accumulation, and smuggling activity? Third, is the optimal level of enforcement sensitive to technological progress in the smuggling industry? We show that the government chooses to devote resources to border enforcement only if the deterrent effect on smugglers is large enough. Otherwise, it is not worth taxing host-country natives as the taxes paid will more than offset any income gain resulting from fewer migrants.

Comparing a discrete and continuum model of the intestinal crypt

The integration of processes at different scales is a key problem in the modelling of cell populations. Owing to increased computational resources and the accumulation of data at the cellular and subcellular scales, the use of discrete, cell-level models, which are typically solved using numerical simulations, has become prominent. One of the merits of this approach is that important biological factors, such as cell heterogeneity and noise, can be easily incorporated. However, it can be difficult to efficiently draw generalizations from the simulation results, as, often, many simulation runs are required to investigate model behaviour in typically large parameter spaces. In some cases, discrete cell-level models can be coarse-grained, yielding continuum models whose analysis can lead to the development of insight into the underlying simulations. In this paper we apply such an approach to the case of a discrete model of cell dynamics in the intestinal crypt. An analysis of the resulting continuum model demonstrates that there is a limited region of parameter space within which steady-state (and hence biologically realistic) solutions exist. Continuum model predictions show good agreement with corresponding results from the underlying simulations and experimental data taken from murine intestinal crypts.

The elasticity of demand is about occupancy, not prices: building European demand curves based on occupancy elasticity

The peak congestion of the European grid may create significant impacts on system costs because of the need for higher marginal cost generation, higher cost system balancing and increasing grid reinforcement investment. The use of time of use rates, incentives, real time pricing and other programmes, usually defined as Demand Side Management (DSM), could bring about significant reductions in prices, limit carbon emissions from dirty power plants, and improve the integration of renewable sources of energy. Unlike previous studies on elasticity of residential electricity demand under flat tariffs, the aim of this study is not to investigate the known relatively inelastic relationship between demand and prices. Rather, the aim is to assess how occupancy levels vary in different European countries. This reflects the reality of demand loads, which are predominantly determined by the timing of human activities (e.g. travelling to work, taking children to school) rather than prices. To this end, two types of occupancy elasticity are estimated: baseline occupancy elasticity and peak occupancy elasticity. These represent the intrinsic elasticity associated with human activities of single residential end-users in 15 European countries. This study makes use of occupancy time-series data from the Harmonised European Time Use Survey database to build European occupancy curves; identify peak occupancy periods; draw time use demand curves for video and TV watching activity; and estimate national occupancy elasticity levels of single-occupant households. Findings on occupancy elasticities provide an indication of possible DSM strategies based on occupancy levels and not prices.