Measuring our universe from galaxy redshift surveys

Galaxy redshift surveys have achieved significant progress over the last couple of decades. Those surveys tell us in the most straightforward way what our local universe looks like. While the galaxy distribution traces the bright side of the universe, detailed quantitative analyses of the data have even revealed the dark side of the universe dominated by non-baryonic dark matter as well as more mysterious dark energy (or Einstein's cosmological constant). We describe several methodologies of using galaxy redshift surveys as cosmological probes, and then summarize the recent results from the existing surveys. Finally we present our views on the future of redshift surveys in the era of Precision Cosmology.Comment: 82 pages, 31 figures, invited review article published in Living Reviews in Relativity, http://www.livingreviews.org/lrr-2004-

Stabilization of integrin-linked kinase by the Hsp90-CHIP axis impacts cellular force generation, migration and the fibrotic response

Integrin-linked kinase (ILK) is an adaptor protein required to establish and maintain the connection between integrins and the actin cytoskeleton. This linkage is essential for generating force between the extracellular matrix (ECM) and the cell during migration and matrix remodelling. The mechanisms by which ILK stability and turnover are regulated are unknown. Here we report that the E3 ligase CHIP-heat shock protein 90 (Hsp90) axis regulates ILK turnover in fibroblasts. The chaperone Hsp90 stabilizes ILK and facilitates the interaction of ILK with a-parvin. When Hsp90 activity is blocked, ILK is ubiquitinated by CHIP and degraded by the proteasome, resulting in impaired fibroblast migration and a dramatic reduction in the fibrotic response to bleomycin in mice. Together, our results uncover how Hsp90 regulates ILK stability and identify a potential therapeutic strategy to alleviate fibrotic diseases

Three-Dimensional Imaging of Drosophila melanogaster

The major hindrance to imaging the intact adult Drosophila is that the dark exoskeleton makes it impossible to image through the cuticle. We have overcome this obstacle and describe a method whereby the internal organs of adult Drosophila can be imaged in 3D by bleaching and clearing the adult and then imaging using a technique called optical projection tomography (OPT). The data is displayed as 2D optical sections and also in 3D to provide detail on the shape and structure of the adult anatomy.We have used OPT to visualize in 2D and 3D the detailed internal anatomy of the intact adult Drosophila. In addition this clearing method used for OPT was tested for imaging with confocal microscopy. Using OPT we have visualized the size and shape of neurodegenerative vacuoles from within the head capsule of flies that suffer from age-related neurodegeneration due to a lack of ADAR mediated RNA-editing. In addition we have visualized tau-lacZ expression in 2D and 3D. This shows that the wholemount adult can be stained without any manipulation and that this stain penetrates well as we have mapped the localization pattern with respect to the internal anatomy.We show for the first time that the intact adult Drosophila can be imaged in 3D using OPT, also we show that this method of clearing is also suitable for confocal microscopy to image the brain from within the intact head. The major advantage of this is that organs can be represented in 3D in their natural surroundings. Furthermore optical sections are generated in each of the three planes and are not prone to the technical limitations that are associated with manual sectioning. OPT can be used to dissect mutant phenotypes and to globally map gene expression in both 2D and 3D

Gender differences and determinants of health related quality of life in coronary patients: a follow-up study

<p>Abstract</p> <p>Background</p> <p>The role of gender differences in Health Related Quality Life (HRQL) in coronary patients is controversial, so understanding the specific determinants of HRQL in men and women might be of clinical importance. The aim of this study was to know the gender differences in the evolution of HRQL at 3 and 6 months after a coronary event, and to identify the key clinical, demographic and psychological characteristics of each gender associated with these changes.</p> <p>Methods</p> <p>A follow-up study was carried out, and 175 patients (112 men and 63 women) with acute myocardial infarction (AMI) or unstable angina were studied. The SF-36v1 health questionnaire was used to assess HRQL, and the GHQ-28 (General Health Questionnaire) to measure mental health during follow-up. To study the variables related to changes in HRQL, generalized estimating equation (GEE) models were performed.</p> <p>Results</p> <p>Follow-up data were available for 55 men and 25 women at 3 months, and for 35 men and 12 women at 6 months. Observations included: a) Revascularization was performed later in women. b) The frequency of rehospitalization between months 3 and 6 of follow-up was higher in women c) Women had lower baseline scores in the SF-36. d) Men had progressed favourably in most of the physical dimensions of the SF-36 at 6 months, while at the same time women's scores had only improved for Physical Component Summary, Role Physical and Social Functioning; e) the variables determining the decrease in HRQL in men were: worse mental health and angina frequency; and in women: worse mental health, history of the disease, revascularization, and angina frequency.</p> <p>Conclusions</p> <p>There are differences in the evolution of HRQL, between men and women after a coronary attack. Mental health is the determinant most frequently associated with HRQL in both genders. However, other clinical determinants of HRQL differed with gender, emphasizing the importance of individualizing the intervention and the content of rehabilitation programs. Likewise, the recognition and treatment of mental disorders in these patients could be crucial.</p

Haploinsufficiency of the E3 Ubiquitin Ligase C-Terminus of Heat Shock Cognate 70 Interacting Protein (CHIP) Produces Specific Behavioral Impairments

The multifunctional E3 ubiquitin ligase CHIP is an essential interacting partner of HSP70, which together promote the proteasomal degradation of client proteins. Acute CHIP overexpression provides neuroprotection against neurotoxic mitochondrial stress, glucocorticoids, and accumulation of toxic amyloid fragments, as well as genetic mutations in other E3 ligases, which have been shown to result in familial Parkinson's disease. These studies have created a great deal of interest in understanding CHIP activity, expression and modulation. While CHIP knockout mice have the potential to provide essential insights into the molecular control of cell fate and survival, the animals have been difficult to characterize in vivo due to severe phenotypic and behavioral dysfunction, which have thus far been poorly characterized. Therefore, in the present study we conducted a battery of neurobehavioral and physiological assays of adult CHIP heterozygotic (HET) mutant mice to provide a better understanding of the functional consequence of CHIP deficiency. We found that CHIP HET mice had normal body and brain weight, body temperature, muscle tone and breathing patterns, but do have a significant elevation in baseline heart rate. Meanwhile basic behavioral screens of sensory, motor, emotional and cognitive functions were normative. We observed no alterations in performance in the elevated plus maze, light-dark preference and tail suspension assays, or two simple cognitive tasks: novel object recognition and spontaneous alternation in a Y maze. Significant deficits were found, however, when CHIP HET mice performed wire hang, inverted screen, wire maneuver, and open field tasks. Taken together, our data indicate a clear subset of behaviors that are altered at baseline in CHIP deficient animals, which will further guide whole animal studies of the effects of CHIP dysregulation on cardiac function, brain circuitry and function, and responsiveness to environmental and cellular stress

A microsporidian impairs Plasmodium falciparum transmission in Anopheles arabiensis mosquitoes

A possible malaria control approach involves the dissemination in mosquitoes of inherited symbiotic microbes to block Plasmodium transmission. However, in the Anopheles gambiae complex, the primary African vectors of malaria, there are limited reports of inherited symbionts that impair transmission. We show that a vertically transmitted microsporidian symbiont (Microsporidia MB) in the An. gambiae complex can impair Plasmodium transmission. Microsporidia MB is present at moderate prevalence in geographically dispersed populations of An. arabiensis in Kenya, localized to the mosquito midgut and ovaries, and is not associated with significant reductions in adult host fecundity or survival. Field-collected Microsporidia MB infected An. arabiensis tested negative for P. falciparum gametocytes and, on experimental infection with P. falciparum, sporozoites aren’t detected in Microsporidia MB infected mosquitoes. As a microbe that impairs Plasmodium transmission that is non-virulent and vertically transmitted, Microsporidia MB could be investigated as a strategy to limit malaria transmission

Oxidative stress causes ERK phosphorylation and cell death in cultured retinal pigment epithelium: Prevention of cell death by AG126 and 15-deoxy-delta 12, 14-PGJ(2)

BACKGROUND: The retina, which is exposed to both sunlight and very high levels of oxygen, is exceptionally rich in polyunsaturated fatty acids, which makes it a favorable environment for the generation of reactive oxygen species. The cytotoxic effects of hydrogen peroxide (H(2)O(2)) induced oxidative stress on retinal pigment epithelium were characterized in this study. METHODS: The MTT cell viability assay, Texas-Red phalloidin staining, immunohistochemistry and Western blot analysis were used to assess the effects of oxidative stress on primary human retinal pigment epithelial cell cultures and the ARPE-19 cell line. RESULTS: The treatment of retinal pigment epithelial cells with H(2)O(2 )caused a dose-dependent decrease of cellular viability, which was preceded by a significant cytoskeletal rearrangement, activation of the Extracellular signal-Regulated Kinase, lipid peroxidation and nuclear condensation. This cell death was prevented partially by the prostaglandin derivative, 15d-PGJ(2 )and by the protein kinase inhibitor, AG126. CONCLUSION: 15d-PGJ(2 )and AG126 may be useful pharmacological tools in the future capable of preventing oxidative stress induced RPE cell death in human ocular diseases

It Costs to Be Clean and Fit: Energetics of Comfort Behavior in Breeding-Fasting Penguins

), seabirds known to fast for up to one month during incubation shifts ashore.A time budget was estimated from focal and scan sampling field observations and the energy cost of comfort activities was calculated from the associated increase in heart rate (HR) during comfort episodes, using previously determined equations relating HR to energy expenditure. We show that incubating birds spent 22% of their daily time budget in comfort behavior (with no differences between day and night) mainly devoted to preening (73%) and head/body shaking (16%). During comfort behavior, energy expenditure averaged 1.24 times resting metabolic rate (RMR) and the corresponding energy cost (i.e., energy expended in excess to RMR) was 58 kJ/hr. Energy expenditure varied greatly among various types of comfort behavior, ranging from 1.03 (yawning) to 1.78 (stretching) times RMR. Comfort behavior contributed 8.8–9.3% to total daily energy expenditure and 69.4–73.5% to energy expended daily for activity. About half of this energy was expended caring for plumage.This study is the first to estimate the contribution of comfort behavior to overall energy budget in a free-living animal. It shows that although breeding on a tight energy budget, king penguins devote a substantial amount of time and energy to comfort behavior. Such findings underline the importance of comfort behavior for the fitness of colonial seabirds