Beta-agonist- and prostaglandin E1-induced translocation of the beta-adrenergic receptor kinase: evidence that the kinase may act on multiple adenylate cyclase-coupled receptors.

beta-Adrenergic receptor kinase (beta-AR kinase) is a cytosolic enzyme that phosphorylates the beta-adrenergic receptor only when it is occupied by an agonist [Benovic, J. Strasser, R. H., Caron, M. G. & Lefkowitz, R. J. (1986) Proc. Natl. Acad. Sci. USA 83, 2797-2801.] It may be crucially involved in the processes that lead to homologous or agonist-specific desensitization of the receptor. Stimulation of DDT1MF-2 hamster smooth muscle cells or S49 mouse lymphoma cells with a beta-agonist leads to translocation of 80-90% of the beta-AR kinase activity from the cytosol to the plasma membrane. The translocation process is quite rapid, is concurrent with receptor phosphorylation, and precedes receptor desensitization and sequestration. It is also transient, since much of the activity returns to the cytosol as the receptors become sequestered. Stimulation of beta-AR kinase translocation is a receptor-mediated event, since the beta-antagonist propranolol blocks the effect of agonist. In the kin- mutant of the S49 cells (lacks cAMP-dependent protein kinase), prostaglandin E1, which provokes homologous desensitization of its own receptor, is at least as effective as isoproterenol in promoting beta-AR kinase translocation to the plasma membrane. However, in the DDT1MF-2 cells, which contain alpha 1-adrenergic receptors coupled to phosphatidylinositol turnover, the alpha 1-agonist phenylephrine is ineffective. These results suggest that the first step in homologous desensitization of the beta-adrenergic receptor may be an agonist-promoted translocation of beta-AR kinase from cytosol to plasma membrane and that beta-AR kinase may represent a more general adenylate cyclase-coupled receptor kinase that participates in regulating the function of many such receptors.

Impact of gene variants on sex-specific regulation of human Scavenger receptor class B type 1 (SR-BI) expression in liver and association with lipid levels in a population-based study.

BACKGROUND: Several studies have noted that genetic variants of SCARB1, a lipoprotein receptor involved in reverse cholesterol transport, are associated with serum lipid levels in a sex-dependent fashion. However, the mechanism underlying this gene by sex interaction has not been explored. METHODS: We utilized both epidemiological and molecular methods to study how estrogen and gene variants interact to influence SCARB1 expression and lipid levels. Interaction between 35 SCARB1 haplotype-tagged polymorphisms and endogenous estradiol levels was assessed in 498 postmenopausal Caucasian women from the population-based Rancho Bernardo Study. We further examined associated variants with overall and SCARB1 splice variant (SR-BI and SR-BII) expression in 91 human liver tissues using quantitative real-time PCR. RESULTS: Several variants on a haplotype block spanning intron 11 to intron 12 of SCARB1 showed significant gene by estradiol interaction affecting serum lipid levels, the strongest for rs838895 with HDL-cholesterol (p=9.2x10(-4)) and triglycerides (p=1.3x10(-3)) and the triglyceride:HDL cholesterol ratio (p=2.7x10(-4)). These same variants were associated with expression of the SR-BI isoform in a sex-specific fashion, with the strongest association found among liver tissue from 52 young women<45 years old (p=0.002). CONCLUSIONS: Estrogen and SCARB1 genotype may act synergistically to regulate expression of SCARB1 isoforms and impact serum levels of HDL cholesterol and triglycerides. This work highlights the importance of considering sex-dependent effects of gene variants on serum lipid levels.

The enduring impact of transient emotions on decision making

People often do not realize they are being influenced by an incidental emotional state. As a result, decisions based on a fleeting incidental emotion can become the basis for future decisions and hence outlive the original cause for the behavior (i.e., the emotion itself). Using a sequence of ultimatum and dictator games, we provide empirical evidence for the enduring impact of transient emotions on economic decision making. Behavioral consistency and false consensus are presented as potential underlying processes. © 2009 Elsevier Inc. All rights reserved.

The impact of geologic variability on capacity and cost estimates for storing CO 2 in deep-saline aquifers

While numerous studies find that deep-saline sandstone aquifers in the United States could store many decades worth of the nation's current annual CO 2 emissions, the likely cost of this storage (i.e. the cost of storage only and not capture and transport costs) has been harder to constrain. We use publicly available data of key reservoir properties to produce geo-referenced rasters of estimated storage capacity and cost for regions within 15 deep-saline sandstone aquifers in the United States. The rasters reveal the reservoir quality of these aquifers to be so variable that the cost estimates for storage span three orders of magnitude and average>$100/tonne CO 2. However, when the cost and corresponding capacity estimates in the rasters are assembled into a marginal abatement cost curve (MACC), we find that ~75% of the estimated storage capacity could be available for<$2/tonne. Furthermore, ~80% of the total estimated storage capacity in the rasters is concentrated within just two of the aquifers-the Frio Formation along the Texas Gulf Coast, and the Mt. Simon Formation in the Michigan Basin, which together make up only ~20% of the areas analyzed. While our assessment is not comprehensive, the results suggest there should be an abundance of low-cost storage for CO 2 in deep-saline aquifers, but a majority of this storage is likely to be concentrated within specific regions of a smaller number of these aquifers. © 2011 Elsevier B.V.

The impact of the developmental timing of trauma exposure on PTSD symptoms and psychosocial functioning among older adults.

The present study examined the impact of the developmental timing of trauma exposure on posttraumatic stress disorder (PTSD) symptoms and psychosocial functioning in a large sample of community-dwelling older adults (N = 1,995). Specifically, we investigated whether the negative consequences of exposure to traumatic events were greater for traumas experienced during childhood, adolescence, young adulthood, midlife, or older adulthood. Each of these developmental periods is characterized by age-related changes in cognitive and social processes that may influence psychological adjustment following trauma exposure. Results revealed that older adults who experienced their currently most distressing traumatic event during childhood exhibited more severe symptoms of PTSD and lower subjective happiness compared with older adults who experienced their most distressing trauma after the transition to adulthood. Similar findings emerged for measures of social support and coping ability. The differential effects of childhood compared with later life traumas were not fully explained by differences in cumulative trauma exposure or by differences in the objective and subjective characteristics of the events. Our findings demonstrate the enduring nature of traumatic events encountered early in the life course and underscore the importance of examining the developmental context of trauma exposure in investigations of the long-term consequences of traumatic experiences.

Impact of Kidney Function on Effects of the Dietary Approaches to Stop Hypertension (Dash) Diet.

OBJECTIVES: Although the Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure in adults with hypertension, how kidney function impacts this effect is not known. We evaluated whether Estimated Glomerular Filtration Rate (eGFR) modifies the effect of the DASH diet on blood pressure, markers of mineral metabolism, and markers of kidney function. METHODS: Secondary analysis of the DASH-Sodium trial, a multicenter, randomized, controlled human feeding study that evaluated the blood pressure lowering effect of the DASH diet at three levels of sodium intake. Data from 92 participants with pre-hypertension or stage 1 hypertension during the 3450 mg /day sodium diet assignment contributed to this analysis. Stored frozen plasma and urine specimens were used to measure kidney related laboratory outcomes. RESULTS: Effects of the DASH diet on blood pressure, phosphorus, intact parathyroid hormone, creatinine, and albuminuria were not modified by baseline eGFR (mean 84.5 ± 18.0 ml/min/1.73 m(2), range 44.1 to 138.6 ml/min/1.73 m(2)) or the presence of chronic kidney disease (N=13%). CONCLUSIONS: The impact of the DASH diet on blood pressure, markers of mineral metabolism, and markers of kidney function does not appear to be modified by eGFR in this small subset of DASH-Sodium trial participants with relatively preserved kidney function. Whether greater reduction in eGFR modifies the effects of DASH on kidney related measures is yet to be determined. A larger study in individuals with more advanced kidney disease is needed to establish the efficacy and safety of the DASH diet in this patient population.