Advanced glycation end products regulate extracellular matrix protein and protease expression by human glomerular mesangial cells

Advanced glycation end products (AGEs) may play a role in the pathogenesis of diabetic nephropathy, by modulating extracellular matrix turnover. AGEs are known to activate specific membrane receptors, including the receptor for AGE (RAGE). In the present study, we analyzed the various receptors for AGEs expressed by human mesangial cells and we studied the effects of glycated albumin and of carboxymethyl lysine on matrix protein and remodelling enzyme synthesis. Membrane RAGE expression was confirmed by FACS analysis. Microarray methods, RT-PCR, and Northern blot analysis were used to detect and confirm specific gene induction. Zymographic analysis and ELISA were used to measure the induction of tPA and PAI-1. We show herein that cultured human mesangial cells express AGE receptor type 1, type 2 and type 3 and RAGE. AGEs (200 microg/ml) induced at least a 2-fold increase in mRNA for 10 genes involved in ECM remodelling, including tPA, PAI-1 and TIMP-3. The increase in tPA synthesis was confirmed by fibrin zymography. The stimulation of PAI-1 synthesis was confirmed by ELISA. AGEs increased PAI-1 mRNA through a signalling pathway involving reactive oxygen species, the MAP kinases ERK-1/ERK-2 and the nuclear transcription factor NF-kappaB, but not AP-1. Carboxymethyl lysine (CML, 5 microM), which is a RAGE ligand, also stimulated PAI-1 synthesis by mesangial cells. In addition, a blocking anti-RAGE antibody partially inhibited the AGE-stimulated gene expression and decreased the PAI-1 accumulation induced by AGEs and by CML. Inhibition of AGE receptors or neutralization of the protease inhibitors TIMP-3 and PAI-1 could represent an important new therapeutic strategy for diabetic nephropathy.

A facile route to the synthesis of novel 2-amino-1,4,5,6-tetrahydropyrimidines from Baylis-Hillman products of acrylonitrile

A facile route for the synthesis of novel 5-substituted-2-amino-1,4,5,6-tetrahydro pyrimidines from the Baylis-Hillman adducts obtained from reaction of aldehydes and acrylonitrile is described.

Valorization of agrobiodiversity products and strengthening of local identities in the Peruvian Andes: Experiences from the BioAndes Programme

In the Peruvian Andes, a long history of interaction between the local populations and their natural environment has led to extraordinary levels of agrobiodiversity. However, in sharp contrast with this biological wealth, Andean indigenous populations live under most precarious conditions. Moreover, natural resources are undergoing severe degradation processes and local knowledge about biodiversity management is under serious pressure. Against this background, the BioAndes Programme is developing initiatives based on a biocultural approach that aim at fostering biodiversity through the enhancement of cultural processes. On the basis of intercultural dialogue, joint learning and capacity development, and transdisciplinary action-research, indigenous communities, development practitioners, and researchers strive for the creation of innovative ways to contribute to more sustainable economic, socio-cultural, and political valorization of Andean biodiversity. Project activities are diverse and range from the cultivation, transformation, and commercialization of organic Andean fruits in San Marcos, Cajamarca Department, to the recuperation of natural dying techniques for alpaca wool and traditional weaving in Pitumarca, Cusco Department, and the promotion of responsible ecotourism in both regions. Based on the projects’ first two-years of experience, the following lessons learnt will be presented and discussed: 1. The economic valorization and commercialization of local products can be a powerful tool for the revival and innovation of eroded know-how; at the same time it contributes to the strengthening of local identities, in parallel with the empowerment of marginalized groups such as smallholders and women. 2. Such initiatives are only successful when they are embedded within activities that go beyond the focus on local products and seek the valorization of the entire natural and cultural landscape (e.g. through the promotion of agrotourism and local gastronomy, more sustainable management of local resources including the restoration of ecosystems, and the realization of inventories of local agrobiodiversity and the knowledge related to it). 3. The sustainability of these initiatives, which are often externally induced, is conditioned by the ability of local actors to acquire ownership of projects and access to the knowledge required to carry them out, which also means developing the personal and institutional capacities for handling the whole chain from production to commercialization. 4. The confrontation of different economic rationalities and their underlying worldviews that occur when local or indigenous people integrate into the market economy implies the need for a dialogical co-production of knowledge and collective action by local people, experts from NGOs, and political authorities in order to better control the conditions relating to the market economy. The valorization of local agrobiodiversity shows much potential for enhancing natural and cultural diversity in Southern countries, but only when local communities can participate in the shaping of the conditions under which this happens. Such activities should be designed in the mid- to long-term as part of social learning processes that are carefully embedded in the local context. Supporting institutions play a crucial role in these processes, but should see themselves only as facilitators, while ensuring that control and ownership remain with the local actors.

Risk scoring for setting priorities in a monitoring of antimicrobial resistance in meat and meat products

Meat and meat products can be contaminated with different species of bacteria resistant to various antimicrobials. The human health risk of a type of meat or meat product carry by emerging antimicrobial resistance depends on (i) the prevalence of contamination with resistant bacteria, (ii) the human health consequences of an infection with a specific bacterium resistant to a specific antimicrobial and (iii) the consumption volume of a specific product. The objective of this study was to compare the risk for consumers arising from their exposure to antibiotic resistant bacteria from meat of four different types (chicken, pork, beef and veal), distributed in four different product categories (fresh meat, frozen meat, dried raw meat products and heat-treated meat products). A semi-quantitative risk assessment model, evaluating each food chain step, was built in order to get an estimated score for the prevalence of Campylobacter spp., Enterococcus spp. and Escherichia coli in each product category. To assess human health impact, nine combinations of bacterial species and antimicrobial agents were considered based on a published risk profile. The combination of the prevalence at retail, the human health impact and the amount of meat or product consumed, provided the relative proportion of total risk attributed to each category of product, resulting in a high, medium or low human health risk. According to the results of the model, chicken (mostly fresh and frozen meat) contributed 6.7% of the overall risk in the highest category and pork (mostly fresh meat and dried raw meat products) contributed 4.0%. The contribution of beef and veal was of 0.4% and 0.1% respectively. The results were tested and discussed for single parameter changes of the model. This risk assessment was a useful tool for targeting antimicrobial resistance monitoring to those meat product categories where the expected risk for public health was greater.

Lean-Production-Methods for XXL-Products

This paper discusses the different characteristics used to describe XXL-products and, furthermore, presents fundamental aspects concerning the construction (e.g. principles, methods) of production systems. A survey of experts at XXL-producers is used to identify the most commonly implemented Lean-Production-Methods of production systems. The article presents the survey results and finally concludes with an outlook on further steps.

Using Dynamic Programming Decomposition for Revenue Management with Opaque Products

Opaque products enable service providers to hide specific characteristics of their service fulfillment from the customer until after purchase. Prominent examples include internet-based service providers selling airline tickets without defining details, such as departure time or operating airline, until the booking has been made. Owing to the resulting flexibility in resource utilization, the traditional revenue management process needs to be modified. In this paper, we extend dynamic programming decomposition techniques widely used for traditional revenue management to develop an intuitive capacity control approach that allows for the incorporation of opaque products. In a simulation study, we show that the developed approach significantly outperforms other well-known capacity control approaches adapted to the opaque product setting. Based on the approach, we also provide computational examples of how the share of opaque products as well as the degree of opacity can influence the results.

Effects of Supplementing High or Low Quality Forages with Corn or Corn Processing Co-Products Upon Digestibility of Dry Matter and Energy by Steers

A digestibility trial, utilizing eight crossbred steers weighing initially 741 lbs. was conducted in an 8 x 8 Latin square design. High-fiber corn by-products were compared with corn as energy sources when fed in mixed diets with either lowor high-quality forage. Ground, dry corn stover and ground alfalfa hay were both fed alone or with corn grain, dried corn gluten feed (CGF), and dried corn distillers grains plus solubles (DDG) in a 1:1 ratio (dry basis). Total tract dry matter digestibility (DMD) was increased for both forages when fed with concentrates. Total tract DMD was similar in stover-based and alfalfa-based diets fed with CGF and DDG. However, stover+corn was lower in DMD than either stover+CGF and stover+DDG. Conversely, alfalfa+corn was higher in DMD than alfalfa+CGF or alfalfa+DDG. Feeding stover with corn tended to decrease digestibility of neutral detergent fiber (NDF), while feeding stover with CGF or DDG increased NDFD. There was no effect upon NDF digestion of alfalfa-based diets when fed with any of the concentrates. Feeding either forage with a concentrate increased digestible energy (DE). Stover+CGF and stover+DDG were similar in DE and were both higher in DE than stover+corn. Alfalfa+DDG tended to be higher than alfalfa+CGF and was similar to alfalfa+corn in DE. Alfalfa+CGF was lower in DE compared with alfalfa+corn. Results are interpreted to indicate that stover is more susceptible to negative feed interactions caused by corn grain than is alfalfa. Additionally, highfiber corn co-products fed with stover resulted in a positive associative effect but essentially had no associative effect when fed with alfalfa.

Effects of different types of solid feeds on health status and performance of Swiss veal calves. I. Basic feeding with milk by-products

The objective of this study was to identify a suitable alternative to the current practice of complementing the feeding of milk by-products with straw. The influence of 5 different types of solid feeds on health and performance of Swiss veal calves was investigated in 2 production cycles of 200 veal calves each with a mean initial age of 40 days (d). The calves were housed in groups of 40 in stalls with outside pen. Liquid feeding consisted of a milk by-product combined with an additional skim milk powder ad libitum. Groups were assigned to 1 of the 5 following experimental solid feeds provided ad libitum: mix (composition: soy flakes, corn, barley, wheat, oat, barley middling, plant oil, molasses), whole plant corn pellets, corn silage, hay, and wheat straw as control. Daily dry matter intake per calf averaged 2.25 kg of the liquid food, 0.16 kg of straw, 0.33 kg of mix, 0.47 kg of corn silage, 0.38 kg of corn pellets, and 0.39 kg of hay. No significant differences (P > 0.05) among groups were found in calf losses that amounted to 4.8 % (68 % because of gastrointestinal disorders). Four percent of the calves were slaughtered prematurely. Daily doses of antibiotics were higher in the mix (36.9 d, P < 0.01) and in the corn silage groups (35 d, P < 0.01) compared to control. Compared to the 4 other groups, calves of the straw group showed the highest prevalence of abnormal ruminal content (73 %, P < 0.05), of abnormal ruminal papillae (42 %, P < 0.05), of abomasal fundic lesions (13.5 %, P < 0.1), and the lowest number of chewing movements per bolus (45, P < 0.05). The hemoglobin concentration averaged 85 g/l at the beginning and 99 g/l at the end of the fattening period with no significant differences among groups (P > 0.1). The duration of the fattening period averaged 114 d, slaughter age 157 d, and carcass weight 122 kg. The average daily weight gain (ADG) was highest in the control group straw (1.35 kg), and lowest in the hay group (1.22 kg, P < 0.01). The number of carcasses classified as C, H, and T (very high to medium quality) was lower in the hay group compared to straw (P < 0.01). No significant differences between groups were found in meat color (P > 0.1): 73 % of the carcasses were assessed as pale (267/364), 18 % as pink (66/364), and 9 % (31/364) as red. The results reveal that whole-plant corn pellets are most consistent with an optimal result combining the calves' health and fattening performance. Therefore, it can be recommended as an additional solid feed for veal calves under Swiss conditions.

Thermal release rate studies of nuclear reaction products from polycrystalline metal matrices

The thermal release rate of nuclear reaction products was investigated in offline annealing experiments. This work was motivated by the search for a high melting catcher material for recoiling products from heavy ion induced nuclear fusion reactions. Polycrystalline refractory metal foils of Ni, Y, Zr, Nb, Mo, Hf, W, and Re were investigated as catcher metals. Diffusion data for various tracer/host combinations were deduced from the measured release rates. This work focuses on the diffusion and the release rate of volatile p-elements from row 5 and 6 of the periodic table as lighter homologues of the superheavy elements with Z ≥ 113 to be studied in future experiments. A massive radiation damage enhancement of the diffusion velocity was observed. Diffusion trends have been established along the groups and rows of the periodic table based on the dependence of diffusion velocity on atomic sizes.