No abstract

Objective-Deletion of Akt1 leads to severe atherosclerosis and occlusive coronary artery disease. Vascular smooth muscle cells (VSMCs) are an important component of atherosclerotic plaques, responsible for promoting plaque stability in advanced lesions. Fibrous caps of unstable plaques contain less collagen and ECM components and fewer VSMCs than caps from stable lesions. Here, we investigated the role of Akt1 in VSMC proliferation, migration, and oxidative stress-induced apoptosis. In addition, we also characterized the atherosclerotic plaque morphology and cardiac function in an atherosclerosis-prone mouse model deficient in Akt1. Methods and Results-Absence of Akt1 reduces VSMC proliferation and migration. Mechanistically, the proliferation and migratory phenotype found in Akt1-null VSMCs was linked to reduced Rac-1 activity and MMP-2 secretion. Serum starvation and stress-induced apoptosis was enhanced in Akt1 null VSMCs as determined by flow cytometry using Annexin V/PI staining. Immunohistochemical analysis of atherosclerotic plaques from Akt1 Ϫ/ϪApoEϪ/Ϫ mice showed a dramatic increase in plaque vulnerability characteristics such as enlarged necrotic core and reduced fibrous cap and collagen content. Finally, we show evidence of myocardial infarcts and cardiac dysfunction in Akt1 Ϫ/ϪApoEϪ/Ϫ mice analyzed by immunohistochemistry and echocardiography, respectively. Conclusion-Akt1 is essential for VSMC proliferation, migration, and protection against oxidative stress-induced apoptosis. Absence of Akt1 induces features of plaque vulnerability and cardiac dysfunction in a mouse model of atherosclerosis.

Simple correlated random walk (CRW) models are rarely sufficient to describe movement of animals over more than the shortest time scales. However, CRW approaches can be used to model more complex animal movement trajectories by assuming individuals move in one of several different behavioural or movement states, each characterized by a different CRW. The spatial and social context an individual experiences may influence the proportion of time spent in different movement states, with subsequent effects on its spatial distribution, survival and fecundity. While methods to study habitat influences on animal movement have been previously developed, social influences have been largely neglected. Here, we fit a 'socially informed' movement model to data from a population of over 100 elk (Cervus canadensis) reintroduced into a new environment, radio-collared and subsequently tracked over a 4-year period. The analysis shows how elk move further when they are solitary than when they are grouped and incur a higher rate of mortality the further they move away from the release area. We use the model to show how the spatial distribution and growth rate of the population depend on the balance of fission and fusion processes governing the group structure of the population. The results are briefly discussed with respect to the design of species reintroduction programmes.

Identifying conservation units below the species level is becoming increasingly important, particularly when limited resources necessitate prioritization for conservation among such units. This problem is exemplified with caribou, a mammal with a circum-Arctic distribution that is exposed to a broad spectrum of ecological conditions, but is also declining in many parts of its range. We used microsatellite markers to evaluate the suitability of existing intra-specific taxonomic designations to act as population units for conservation and contrasted this with landscape features that were independent of taxonomy. We also quantified the relationship between genetic differentiation and subpopulation size, a factor that has been under-represented in landscape genetic research. Our data set included three subspecies and three ecotypes of caribou that varied in population size by five orders of magnitude. Our results indicated that genetic structure did not correspond to existing taxonomic designation, particularly at the level of ecotype. Instead, we found that major valleys and population size were the strongest factors associated with substructure. There was a negative exponential relationship between population size and F(ST) between pairs of adjacent subpopulations, suggesting that genetic drift was the mechanism causing the structure among the smallest subpopulations. A genetic assignment test revealed that movement among subpopulations was a fraction of the level needed to stabilize smaller subpopulations, indicating little chance for demographic rescue. Such results may be broadly applicable to landscape genetic studies, because population size and corresponding rates of drift have the potential to confound interpretations of landscape effects on population structure.