A molecular mechanism for signaling between seven-transmembrane receptors: evidence for a redistribution of G proteins

Although activation of one seven-transmembrane receptor can influence the response of a separate seven-transmembrane receptor, e.g., the phenomenon of synergism, the underlying mechanism(s) for this signaling process is unclear. The present study investigated communication between two receptors that exhibit classical synergism, e.g., human platelet thrombin and thromboxane A2 receptors. Activation of thrombin receptors caused an increase in ligand affinity of thromboxane A2 receptors. This effect (i) was shown to be specific, since a similar increase in ligand affinity was not caused by ADP or A23187; (ii) did not require cytosolic components, e.g., kinases, proteases, phosphatases, etc., because it occurred in isolated platelet membranes; (iii) was G protein-mediated because it was blocked by an Gαq C terminus antibody; and (iv) was associated with a net increase in Gαq coupling to thromboxane A2 receptors. Collectively, these data provide evidence that seven-transmembrane receptors that share a common Gα subunit can communicate with each other via a redistribution of their G proteins. Thus, activation of thrombin receptors increases Gαq association with thromboxane A2 receptors thereby shifting them to a higher affinity state. This signaling phenomenon, which modulates receptor-ligand affinity, may serve as a molecular mechanism for cellular adaptive processes such as synergism.

Income distribution, socioeconomic status, and self rated health in the United States: multilevel analysis

Objective: To determine the effect of inequalities in income within a state on self rated health status while controlling for individual characteristics such as socioeconomic status.

Redistribution of synaptic vesicles and their proteins in temperature-sensitive shibire(ts1) mutant Drosophila.

From an extract of Drosophila melanogaster head homogenates, a membrane fraction can be isolated that has the same sedimentation properties as vertebrate synaptic vesicles and contains Drosophila synaptotagmin. The fraction disappears from homogenates of temperature-sensitive (ts) mutant shibire(ts1) (shi(ts1)) flies paralyzed by exposure to non-permissive temperatures, and reappears on return to permissive temperatures. Since reversible, temperature-dependent depletion of synaptic vesicles is known to occur in shibire(ts1) flies, we conclude that the fraction we have identified contains synaptic vesicles. We have examined the fate of synaptic vesicle membrane proteins in shibire flies at nonpermissive temperatures and found that all of these vesicle antigens are transferred to rapidly sedimenting membranes and codistribute with a plasma membrane marker by both glycerol velocity and metrizamide density sedimentation and by confocal microscopy. Three criteria were used to establish that other neuron-specific antigens--neuronal synaptobrevin and cysteine-string proteins--are legitimate components of synaptic vesicles: cosedimentation with Drosophila synaptotagmin, immunoadsorption, and disappearance of these antigens from the vesicle fractions in paralyzed shibire flies.

The Pursuit of Balanced Income An Economic Perspective on Wealth

The purpose of this thesis is to determine if households with moderate incomes have the opportunity to acquire pecuniary wealth. In an environment of increasing globalization, labor-eliminating technology, and an overburdened entitlement system, the position of wealth is necessary for households with a penchant for early retirement and particularly for those that will inevitably succumb to involuntary retirement. In these writings, qualitative and quantitative descriptions of wealth are offered; two microeconomic metrics are introduced to identify baseline wealth and to gauge proximity to this value; and strategies are devised to close the gap between these metrics. The construct of the economic intertemporal household budget was used as the basis for this research whereby conventional measures of wealth, i.e. net worth and liquid net worth, have been coupled with historical and empirical household data to define and extrapolate wealth and wealth proximity metrics. The major finding is wealth is a dynamic variable contingent upon consumption level rather than income or saving levels. And because households exercise a greater degree of autonomy over consumption, moderate earners are afforded the same opportunities as high earners. The position of wealth is necessary because it sustains consumption in the event of an unwelcomed retirement and it can assuage reliance on entitlement programs. For the majority of households, wealth is a matter of choice.

Consumer Driven Health Care: An Examination of the Disadvantages to Low Income Employees

As health care costs for companies continue to rise, more organizations are considering a consumer driven health plan option with the goal to engage employees so that they make better health care decisions. Although consumer driven health plan options present advantages to the employer and some employee groups, low income employees are negatively impacted by this option. Two major disadvantages include missed care and out of pocket obligations. This capstone reviews the current literature on consumer driven health care and discusses the disadvantages to low income employees. It also provides strategies and recommendations to employers who are considering a consumer driven health option plan to minimize the disadvantages to low income employees.

Income taxation of emigrants and immigrants under Spanish law

Análisis de las consecuencias tributarias de los cambios de residencia de las personas físicas.

Intimate partner violence among women in Spain: the impact of regional-level male unemployment and income inequality

Background: Intimate partner violence (IPV) against women is a complex worldwide public health problem. There is scarce research on the independent effect on IPV exerted by structural factors such as labour and economic policies, economic inequalities and gender inequality. Objective: To analyse the association, in Spain, between contextual variables of regional unemployment and income inequality and individual women’s likelihood of IPV, independently of the women’s characteristics. Method: We conducted multilevel logistic regression to analyse cross-sectional data from the 2011 Spanish Macrosurvey of Gender-based Violence which included 7898 adult women. The first level of analyses was the individual women’ characteristics and the second level was the region of residence. Results: Of the survey participants, 12.2% reported lifetime IPV. The region of residence accounted for 3.5% of the total variability in IPV prevalence. We determined a direct association between regional male long-term unemployment and IPV likelihood (P = 0.007) and between the Gini Index for the regional income inequality and IPV likelihood (P < 0.001). Women residing in a region with higher gender-based income discrimination are at a lower likelihood of IPV than those residing in a region with low gender-based income discrimination (odds ratio = 0.64, 95% confidence intervals: 0.55–0.75). Conclusions: Growing regional unemployment rates and income inequalities increase women’s likelihood of IPV. In times of economic downturn, like the current one in Spain, this association may translate into an increase in women’s vulnerability to IPV.

Redistribution of Soil Organic Matter by Permafrost Disturbance in the Canadian High Arctic

With increased warming in the Arctic, permafrost thaw may induce localized physical disturbance of slopes. These disturbances, referred to as active layer detachments (ALDs), redistribute soil across the landscape, potentially releasing previously unavailable carbon (C). In 2007–2008, widespread ALD activity was reported at the Cape Bounty Arctic Watershed Observatory in Nunavut, Canada. Our study investigated organic matter (OM) composition in soil profiles from ALD-impacted and undisturbed areas. Solid-state 13C nuclear magnetic resonance (NMR) and solvent-extractable biomarkers were used to characterize soil OM. Throughout the disturbed upslope profile, where surface soils and vegetation had been removed, NMR revealed low O-alkyl C content and biomarker analysis revealed low concentrations of solvent-extractable compounds suggesting enhanced erosion of labile-rich OM by the ALD. In the disturbed downslope region, vegetation remained intact but displaced material from upslope produced lateral compression ridges at the surface. High O-alkyl content in the surface horizon was consistent with enrichment of carbohydrates and peptides, but low concentrations of labile biomarkers (i.e., sugars) suggested the presence of relatively unaltered labile-rich OM. Decreased O-alkyl content and biomarker concentrations below the surface contrasted with the undisturbed profile and may indicate the loss of well-established pre-ALD surface drainage with compression ridge formation. However, pre-ALD profile composition remains unknown and the observed decreases may result from nominal pre-ALD OM inputs. These results are the first to establish OM composition in ALD-impacted soil profiles, suggesting reallocation of permafrost-derived soil C to areas where degradation or erosion may contribute to increased C losses from disturbed Arctic soils.

Essays in dynamic optimal taxation: working experience, unemployment scarring and poverty

This thesis investigates the design of optimal tax systems in dynamic environments. The first essay characterizes the optimal tax system where wages depend on stochastic shocks and work experience. In addition to redistributive and efficiency motives, the taxation of inexperienced workers depends on a second-best requirement that encourages work experience, a social insurance motive and incentive effects. Calibrations using U.S. data yield higher expected optimal marginal income tax rates for experienced workers for most of the inexperienced workers. They confirm that the average marginal income tax rate increases (decreases) with age when shocks and work experience are substitutes (complements). Finally, more variability in experienced workers' earnings prospects leads to increasing tax rates since income taxation acts as a social insurance mechanism. In the second essay, the properties of an optimal tax system are investigated in a dynamic private information economy where labor market frictions create unemployment that destroys workers' human capital. A two-skill type model is considered where wages and employment are endogenous. I find that the optimal tax system distorts the first-period wages of all workers below their efficient levels which leads to more employment. The standard no-distortion-at-the-top result no longer holds due to the combination of private information and the destruction of human capital. I show this result analytically under the Maximin social welfare function and confirm it numerically for a general social welfare function. I also investigate the use of a training program and job creation subsidies. The final essay analyzes the optimal linear tax system when there is a population of individuals whose perceptions of savings are linked to their disposable income and their family background through family cultural transmission. Aside from the standard equity/efficiency trade-off, taxes account for the endogeneity of perceptions through two channels. First, taxing labor decreases income, which decreases the perception of savings through time. Second, taxation on savings corrects for the misperceptions of workers and thus savings and labor decisions. Numerical simulations confirm that behavioral issues push labor income taxes upward to finance saving subsidies. Government transfers to individuals are also decreased to finance those same subsidies.