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.     

Using gene expression noise to understand gene regulation

Phenotypic variation is ubiquitous in biology and is often traceable to underlying genetic and environmental variation. However, even genetically identical cells in identical environments display variable phenotypes. Stochastic gene expression, or gene expression "noise," has been suggested as a major source of this variability, and its physiological consequences have been topics of intense research for the last decade. Several recent studies have measured variability in protein and messenger RNA levels, and they have discovered strong connections between noise and gene regulation mechanisms. When integrated with discrete stochastic models, measurements of cell-to-cell variability provide a sensitive "fingerprint" with which to explore fundamental questions of gene regulation. In this review, we highlight several studies that used gene expression variability to develop a quantitative understanding of the mechanisms and dynamics of gene regulation.     

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.     

Estimates of prevalence of hip dysplasia in Golden Retrievers and Rottweilers and the influence of bias on published prevalence figures

OBJECTIVE: To estimate prevalence of canine hip dysplasia (CHD) in Golden Retrievers and Rottweilers and identify sources of bias in published reports. DESIGN: Prospective study. ANIMALS: 200 clinically normal Golden Retrievers and 140 clinically normal Rottweilers between 24 and 60 months of age referred for hip evaluation (group 1) and 93 clinically normal dogs evaluated for Orthopedic Foundation for Animals (OFA) hip certification (group 2). PROCEDURE: Hip-extended pelvic radiographs from group 1 dogs were screened for CHD. Radiographs were evaluated twice; the first interpretation used an OFA-type subjective 7-point scoring system, and the second included the caudolateral curvilinear osteophyte as an additional sign of degenerative joint disease. The OFA submission rate of group 2 dogs was determined from the number of official reports returned from the OFA. RESULTS: Prevalence of CHD in Golden Retrievers ranged from 53% to 73% and in Rottweilers ranged from 41% to 69%. Among dogs referred for OFA evaluation, radiographs from 49 (53%) were submitted to OFA. Of submitted radiographs, 45 (92%) were normal; of radiographs not submitted, 22 (50%) were normal. Radiographs with normal-appearing hips were 8.2 times as likely to be submitted to the OFA. Compared with Golden Retrievers, Rottweiler radiographs were significantly more likely to be submitted for OFA certification. CONCLUSIONS AND CLINICAL RELEVANCE: Prevalence of CHD in these 2 breeds may be much higher than previously reported in the United States. Results suggest substantial bias in the OFA database, which causes lower estimates of prevalence of CHD.     

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.