Deletion of TSPO causes dysregulation of cholesterol metabolism in mouse retina

Cholesterol dysregulation has been implicated in age-related macular degeneration (AMD), the most common cause of visual impairment in the elderly. The 18 KDa translocator protein (TSPO) is a mitochondrial outer membrane protein responsible for transporting cholesterol from the mitochondrial outer membrane to the inner membrane. TSPO is highly expressed in retinal pigment epithelial (RPE) cells, and TSPO ligands have shown therapeutic potential for the treatment of AMD. Here, we characterized retinal pathology of Tspo knockout (KO) mice using histological, immunohistochemical, biochemical and molecular biological approaches. We found that Tspo KO mice had normal retinal morphology (by light microscopy) but showed elevated levels of cholesterol, triglycerides and phospholipids with perturbed cholesterol efflux in the RPE cells of Tspo KO mice. Expression of cholesterol-associated genes (Nr1h3, Abca1, Abcg1, Cyp27a1 and Cyp46a1) was significantly downregulated, and production of pro-inflammatory cytokines was markedly increased in Tspo KO retinas. Furthermore, microglial activation was also observed in Tspo KO mouse retinas. These findings provide new insights into the function of TSPO in the retina and may aid in the design of new therapeutic strategies for the treatment of AMD

The effect of fight cost structure on fighting behaviour

A common feature of animal populations is the stealing by animals of resources such as food from other animals. This has previously been the subject of a range of modelling approaches, one of which is the so called "producer-scrounger" model. In this model a producer finds a resource that takes some time to be consumed, and some time later a (generally) conspecific scrounger discovers the producer with its resource and potentially attempts to steal it. In this paper we consider a variant of this scenario where each individual can choose to invest an amount of energy into this contest, and the level of investment of each individual determines the probability of it winning the contest, but also the additional cost it has to bear. We analyse the model for a specific set of cost functions and maximum investment levels and show how the evolutionarily stable behaviour depends upon them. In particular we see that for high levels of maximum investment, the producer keeps the resource without a fight for concave cost functions, but for convex functions the scrounger obtains the resource (albeit at some cost)

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Disrupted thalamic prefrontal pathways in patients with idiopathic dystonia

There are quantifiable abnormalities in water diffusion properties of the white matter in thalamic and prefrontal areas in patients with idiopathic dystonia (ID). However, it is unclear which pathways are disrupted in these patients. Using probabilistic tractography of high resolution DTI, we reconstructed thalamic prefrontal pathways in seven patients with ID and seven matched controls. Resulting fibers were registered onto the stereotaxic space and submitted to a voxel-wise statistical analysis comparing patients and controls. Patients with ID exhibited less thalamic prefrontal connections, particularly involving fibers traveling from the thalamus to the middle frontal gyrus. These results corroborate neurophysiologic findings of reduced and asynchronous thalamic prefrontal input, and emphasize the structural correlates of the pathophysiology of ID. (C) 2008 Elsevier Ltd. All rights reserved

Older adults’ experiences of group-based physical activity : A qualitative study from the ‘GOAL’ randomized controlled trial

Objectives: In this qualitative study, we examined older adults’ experiences of taking part in two 2 efficacious group-based physical activity programs as part of the GrOup-based physical Activity for 3 oLder adults (GOAL) randomized controlled trial. 4 Method: In the GOAL Trial, 627 older adults were randomized to one of three conditions: similar 5 age same gender (SASG), similar age mixed gender (SAMG), or ‘standard’ mixed age mixed 6 gender (MAMG) control exercise group conditions. Participants in this qualitative study (N = 31; 7 Nmen = 17, Nwomen = 14; Mage = 70 years) were purposively sampled from the two experimental 8 conditions (SASG, SAMG) and involved in semi-structured interviews. The data were analyzed 9 using thematic analysis. 10 Results: The results included 12 lower-order and three higher-order themes that reflected (a) the 11 benefits and challenges of exercising with peers, (b) the group as a means of mitigating social 12 isolation, and (c) group exercise and the physically active body. 13 Discussion: Findings highlight the importance of social connections that exist within the age-14 matched physical activity programs, as well as some of the challenges for older adults participating 15 in community-based physical activity programs. Implications for intervention, program planning, 16 and future research are discussed.Education, Faculty ofNon UBCKinesiology, School ofUnreviewedFacult