Melanocortin‐1 receptor structure and functional regulation

The melanogenic actions of the melanocortins are mediated by the melanocortin‐1 receptor (MC1R). MC1R is a member of the G‐protein‐coupled receptors (GPCR) superfamily expressed in cutaneous and hair follicle melanocytes. Activation of MC1R by adrenocorticotrophin or α‐melanocyte stimulating hormone is positively coupled to the cAMP signaling pathway and leads to a stimulation of melanogenesis and a switch from the synthesis of pheomelanins to the production of eumelanic pigments. The functional behavior of the MC1R agrees with emerging concepts in GPCR signaling including dimerization, coupling to more than one signaling pathway and a high agonist‐independent constitutive activity accounting for inverse agonism phenomena. In addition, MC1R displays unique properties such as an unusually high number of natural variants often associated with clearly visible phenotypes and the occurrence of endogenous peptide antagonists. Therefore MC1R is an ideal model to study GPCR function. Here we review our current knowledge of MC1R structure and function, with emphasis on information gathered from the analysis of natural variants. We also discuss recent data on the regulation of MC1R function by paracrine and endocrine factors and by external stimuli such as ultraviolet light.     

How Can the Eco‐efficiency of a Region be Measured and Monitored?

The concept of eco-efficiency is commonly referred to as a business link to sustainable development. In this article, ecoefficiency is examined at a regional level as an approach to promoting the competitiveness of economic activities in the Finnish Kymenlaakso region and mitigating their harmful impacts on the environment. The aim is to develop appropriate indicators for monitoring changes in the eco-efficiency of the region. A starting point is to produce indicators for the environmental and economic dimensions of regional development and use them for measuring regional eco-efficiency. The environmental impact indicators are based on a life-cycle assessment method, producing different types of environmental impact indicators: pressure indicators (e.g., emissions of CO₂), impact category indicators (e.g., CO₂ equivalents in the case of climate change), and a total impact indicator (aggregating different impact category indicator results into a single value). Environmental impact indicators based on direct material input, total material input, and total material requirement of the Kymenlaakso region are also assessed. The economic indicators used are the gross domestic product, the value added, and the output of the main economic sectors of Kymenlaakso. In the eco-efficiency assessment, the economic and environmental impact indicators are monitored in the same graph. In a few cases eco-efficiency ratios can also be calculated (the economic indicators are divided by the environmental indicators). Output (= value added + intermediate consumption) is used as an economic indicator related to the environmental impact indicators, which also cover the upstream processes of the region's activities. In the article, we also discuss the strengths and weaknesses of using the different environmental impact indicators.     

Role of Asp-9 and Glu-36 in the active site of the pneumococcal CPL1 lysozyme: an evolutionary perspective of lysozyme mechanism.

The role of carboxylic amino acids Asp-9 and Glu-36 in the activity of CPL1 lysozyme was investigated by site-directed mutagenesis. The enzymatic activity of the single mutants D9E, D9N, D9H, D9K, D9A, E36D, E36Q, E36K, and E36A and of the double mutant D9A-E36A was analyzed using a highly sensitive radioactive assay. All mutants but D6K showed detectable activities. Interestingly, the mutants E36D and E36Q retained 67% and 37% activity, respectively. Amino acid replacements at position 9 turned out to be more critical for activity than at position 36. In analogy to the mechanism described for hen egg-white lysozyme, where the proton donor play a central role, we propose that, in the CPL1 lysozyme, Asp-9 might act as the proton donor for activation of the substrate, and Glu-36 could help in the stabilization of the intermediate oxocarbocation. The residual activity of lysozyme mutants lacking one or two of the acidic amino acids may be explained by the participation of a water molecule as proton donor and/or to electrostatic contributions in the active center stabilizing the transition state of the reaction. Our results are in agreement with the hypothesis that enzymes have been optimized during evolution from an ancestral protein able to bind more tightly the transition state of the substrate than the substrate itself, by the acquisition of amino acids serving a function in catalysis.     

Effects of changes in circulating volume and in arterial pressure on plasma renin activity in the intact rat

The effects of changes in arterial pressure and in circulating volume on Plasma Renin Activity (PRA) in the intact rat were compared by two experimental procedures. Gradual volume depletion was induced by intraperitoneal injection of a hyperoncotic polyethyleneglycol solution (PEG) in absence of acute changes in Systolic Arterial Pressure (SAP). SAP was measured in the conscious state by the tail cuff technique. Plasma Protein Concentration (PPC) and Hematocrit (Hct) increases after PEG injection were compared as the index for measuring the Plasma Volume Reduction (PVR). PRA showed a significant (p less than 0.001) linear relationship with PPC, suggesting a direct dependence of renin secretion on volume depletion. Acute changes in the circulating volume were induced by controlled hemorrhages of 5.0, 10.0, 15.0 and 20.0 ml of blood/kg body weight. The increase in PRA showed a significant relationship with the changes in circulating volume, but it did not show any dependence on the changes in Mean Arterial Pressure (MAP). Our results suggest that, in the intact and conscious rat, renin secretion responds to the information from the cardiopulmonary volume receptors rather than to that from the high pressure receptors.     

Some meteorological conditions associated with forest fires in Galicia (Spain)

The present paper offers data on the effect of certain meteorological parameters on the outbreak of forest fires in Galicia (Spain). In a day-to-day analysis, the values of the stability of the air column and the saturation deficit at the lower levels are related to the number of fires occurring in the following 24 h.     

Peroxisomes and peroxisomal enzymes along the crypt-villus axis of the rat intestine

Abstract. The development of peroxisomes and expression of their enzymes were investigated in differentiating intestinal epithelial cells during their migration along the crypt-villus axis. Sequential cell populations harvested by a low-temperature method were identified by microscopy, determination of alkaline phosphatase and sucrase activities and incorporation of [³H]-thymidine into DNA. Ultrastructural cytochemistry after staining for catalase activity, revealed the presence of peroxisomes in undifferentiated stem cells located in the crypt region. Morphometry indicated that the number of these organelles increased as intestinal epithelial cells differentiate. Catalase activity was higher in the crypt cells than in the mature enterocytes harvested from villus tips. On the other hand, an increasing gradient of activity was observed from crypts to villus tips for peroxisomal oxidases, i.e. fatty acyl coA oxidase, D-amino acid oxidase and polyamine oxidase. These findings indicate that biogenesis of peroxisomes occurs during migration of intestinal epithelial cells along the crypt-villus axis and that peroxisomal oxidases contribute substantially to the biochemical maturation of enterocytes.