Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase

Fat tissue is the most important energy depot in vertebrates. The release of free fatty acids (FFAs) from stored fat requires the enzymatic activity of lipases. We showed that genetic inactivation of adipose triglyceride lipase (ATGL) in mice increases adipose mass and leads to triacylglycerol deposition in multiple tissues. ATGL-deficient mice accumulated large amounts of lipid in the heart, causing cardiac dysfunction and premature death. Defective cold adaptation indicated that the enzyme provides FFAs to fuel thermogenesis. The reduced availability of ATGL-derived FFAs leads to increased glucose use, increased glucose tolerance, and increased insulin sensitivity. These results indicate that ATGL is rate limiting in the catabolism of cellular fat depots and plays an important role in energy homeostasis.     

An immunohistochemical study of the role of matrix metalloproteinases and their tissue inhibitors in chronic mitral valvular disease (valvular endocardiosis) in dogs

While the pathogenesis of chronic valvular disease (CVD) in dogs remains unclear, alterations in the activity of specific metalloproteinase enzymes and their inhibitors within the valve stroma are suspected of having a role. This study describes the immunohistochemical distribution pattern of matrix metalloproteinase (MMP) types 2, 9 and 14 and their tissue inhibitors, termed tissue inhibitors of metalloproteinase (TIMP), types 2 and 3, in normal canine mitral valves (MVs) (n=10) and in dogs with mild (n=7), moderate (n=14) and severe (n=9) CVD. In normal MVs, MMP-2 and -14, and TIMP-2 were expressed in isolated stromal cells. Tissue inhibitor of metalloproteinase-3 exhibited moderate intracellular and mild extracellular expression. With increasing severity of CVD, the expression of MMP-2 decreased. The number of stromal cells expressing MMP-14 increased, predominantly in the margins of the nodular lesions. Tissue inhibitor of metalloproteinase-2 and -3 expression increased both intra- and extracellularly. Matrix metalloproteinase-9 was not detected in normal or diseased valves. In conclusion, CVD was characterised by alterations in the distribution and intensity of valvular MMP and TIMP expression, suggesting that depressed catabolism and the accumulation of extracellular matrix components within affected valves contributes to their structural alteration and consequent loss of function.     

The relationship between meal composition and long-term diet choice

When animals are offered a choice of feeds that are nutritionally complementary, they are able to select a consistent combination of these feeds over long periods of time. Analysis of how such consistent diet choice is achieved, in terms of short-term feeding behavior, may further our knowledge of how animals regulate nutrient intake. Previous work, on meal pattern analysis and on nutrient synchronization, led us to hypothesize that animals may select a consistent diet within a meal. In three experiments cows were offered a choice between high- (H) and low- (L) protein feeds and short-term feeding behavior data were collected using computerized feeders. Feeding behavior was first analyzed in terms of visit characteristics. A greater average daily intake of H, relative to L, was more closely related to the ratio of H visits to L visits than to differences in the intake per visit to feeders supplying H or L. Individual meal criteria were estimated using a mixed-distribution model, and visits were clustered into meals. Cows typically had approximately six meals per day. The observed frequency distribution of meal composition, in terms of the proportion of visits to H feeders, was determined. Subsequently, the observed visits were randomly reclustered into bouts consisting of the same number of visits as were observed in meals, and the frequency distribution of random bout composition was calculated. If frequency distributions of meals and random bouts coincide, then this is evidence that cows do not regulate diet choice within a meal. Comparison of the frequency distributions of meals and random bouts provided no evidence that cows attempted to achieve their long-term average diet composition within a meal. We also investigated whether cows tried to achieve a consistent diet choice within a meal by adjusting their intake per visit, depending on the feed type visited and the proportion of visits to H feeders in a meal. There was no evidence that this occurred. In conclusion, our analyses have shown that cows did not attempt to select within a meal a consistent diet in terms of protein to energy ratio. Indeed, our data and the literature suggest that the timeframe over which the intake of energy and protein is regulated must be greater than a meal in a number of animal species.     

Analysis and management of resistance to chemotherapeutants in salmon lice,Lepeophtheirus salmonis (Copepoda: Caligidae)

In Northern Europe and Canada, the salmon louse, Lepeophtheirus salmonis (Kr?yer), seriously affects the marine phase of salmon production. Although the problem is long-standing, the development of sustainable methods of pest management has been unable to keep pace with the intensification of production, leading to large-scale reliance on very few chemotherapeutants. This runs the risk of selecting for genetically determined resistance in target organisms. There are many examples of similar evolutionary adaptations in arthropod pests of arable crops, livestock and human health. Several hundred pest species are now documented as being resistant to one or more chemical classes of insecticides and acaricides. Many of these compounds are identical or closely related to ones currently employed against salmon lice. It is, therefore, opportune to consider what lessons have been learnt from contending with resistance in terrestrial organisms, the implications for sustainable use of chemotherapeutants in aquaculture, and the potential for developing effective resistance management strategies. An EU-funded project named SEARCH (QLK2-CT-2000-00809) has been initiated to explore in more detail the diagnosis, incidence, dynamics and management of resistance to chemotherapeutants in L salmonis.     

Characterization of step-edge barriers in organic thin-film growth

Detailed understanding of growth mechanisms in organic thin-film deposition is crucial for tailoring growth morphologies, which in turn determine the physical properties of the resulting films. For growth of the rodlike molecule para-sexiphenyl, the evolution of terraced mounds is observed by atomic force microscopy. Using methods established in inorganic epitaxy, we demonstrate the existence of an additional barrier (0.67 electron volt) for step-edge crossing-the Ehrlich-Schwoebel barrier. This result was confirmed by transition state theory, which revealed a bending of the molecule at the step edge. A gradual reduction of this barrier in the first layers led to an almost layer-by-layer growth during early deposition stage. The reported phenomena are a direct consequence of the complexity of the molecular building blocks versus atomic systems.