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The impact of dietary sodium reduction on mouse models of type 2 diabetes is not well understood. Therefore, we analyzed the effect of a low-salt diet on obesity and parameters of type 2 diabetes in db/db mice. Five-week-old male db/db and lean db/m mice were fed a normal salt (0.19% Na+ , NS) or a low-salt diet (<0.03% Na+ , LS) for 5 weeks. Body and organ weight and parameters of glucose and insulin tolerance were analyzed. Plasma levels of steroids were determined by liquid chromatography tandem mass spectrometry. Body weight, glucose, and insulin tolerance were not affected by LS. The amount of gonadal adipose tissue showed a trend to be increased by LS whereas liver, pancreas, kidney, heart, and adrenal weight remained unaffected. LS reduced urinary sodium-to-creatinine ratio but did not affect plasma Na+ levels in both genotypes. Plasma and urinary potassium-to-creatinine ratio did not differ in all groups of mice. Aldosterone as a major determinant of changes in dietary sodium remained unaffected by LS in db/db mice as well as further investigated steroid hormones. The present study showed reduced sodium-to-creatinine ratio, but no additional effects of dietary sodium reduction on major metabolic parameters and steroid levels in obese and hyper-glycemic db/db mice. [ABSTRACT FROM AUTHOR]

Examines how gender, benevolent sexism, and the representational context shapes support for radical right parties (RRPs) in four countries: Germany, Sweden, Switzerland, and Norway. Employing the 8th wave of the European Social Survey (ESS), we find benevolent sexism is a key component of RRP support for men but not women. For men, it appears that sexist attitudes are at least partly a function of a more general orientation to outgroups. We also find that gender moderates the effects of immigration anxiety and authoritarian attitudes on an RRP vote. Finally, there is some evidence that the gender gap is largest where mainstream parties isolate an RRP and the gap is partly a function of the inability of RRPs to attract women with less progressive views on gender equality. [ABSTRACT FROM AUTHOR]

Inhibition of aldosterone synthase (CYP11B2) is an alternative treatment option to mineralocorticoid receptor antagonism to prevent harmful aldosterone effects. FAD286 is the best characterized aldosterone synthase inhibitor. However, to date, no study has used sensitive liquid chromatography-tandem mass spectrometry to characterize in detail the effect of FAD286 on the secreted steroid hormone profile of adrenocortical cells. Basal aldosterone production in NCI-H295R cells was detectable and 9-fold elevated after stimulation with angiotensin II. FAD286 inhibited this increase, showing a maximal effect at 10 nmol/l. Higher concentrations of FAD286 did not further reduce aldosterone concentrations, but showed a parallel reduction in corticosterone, cortisol and cortisone levels, reflecting additional inhibition of steroid-11β-hydroxylase (CYP11B1). Pregnenolone, progesterone and 17-OH-progesterone levels remained unaffected. In conclusion, the aldosterone synthase inhibitor FAD286 lowers angiotensin II-induced aldosterone concentrations in adrenocortical cells but the relative lack of selectivity over CYP11B1 is evident at higher FAD286 concentrations. [ABSTRACT FROM AUTHOR]

Inhibition of aldosterone synthase is an alternative treatment option to mineralocorticoid receptor antagonism to prevent harmful aldosterone actions. FAD286 is one of the best characterized aldosterone synthase inhibitors to date. FAD286 improves glucose tolerance and increases glucose-stimulated insulin secretion in obese and diabetic ZDF rats. However, there is limited knowledge about the dose-dependent effects of FAD286 on plasma aldosterone, corticosterone, and 11-deoxycorticosterone in ZDF rats and in db/db mice, a second important rodent model of obesity and type 2 diabetes. In addition, effects of FAD286 on plasma steroids in mice and rats are controversial. Therefore, obese Zucker diabetic fatty (ZDF) rats and db/db mice were treated with FAD286 for up to 15 weeks and plasma steroids were evaluated using highly sensitive liquid chromatography-tandem mass spectrometry. In ZDF rats, FAD286 (10 mg/kg/d) treatment resulted in nearly complete disappearance of plasma aldosterone while corticosterone levels remained unaffected and those of 11-deoxycorticosterone were increased ~4-fold compared to vehicle control. A lower dose of FAD286 (3 mg/kg/d) showed no effect on plasma aldosterone or corticosterone, but 11-deoxycorticosterone was again increased ~4-fold compared to control. In contrast to ZDF rats, a high dose of FAD286 (40 mg/kg/d) did not affect plasma aldosterone levels in db/db mice although 11-deoxycorticosterone increased ~2.5-fold. A low dose of FAD286 (10 mg/kg/d) increased plasma aldosterone without affecting corticosterone or 11-deoxycorticosterone. In conclusion, the aldosterone synthase inhibitor, FAD286, lowers plasma aldosterone in obese ZDF rats, but not in obese db/db mice. [ABSTRACT FROM AUTHOR]

Activation of the thick ascending limb (TAL) Na+-K+-2Cl- cotransporter (NKCC2) by the antidiuretic hormone arginine vasopressin (AVP) is an essential mechanism of renal urine concentration and contributes to extracellular fluid and electrolyte homeostasis. AVP effects in the kidney are modulated by locally and/or by systemically produced epoxyeicosatrienoic acid derivates (EET). The relation between AVP and EET metabolism has not been determined. Here, we show that chronic treatment of AVP-deficient Brattleboro rats with the AVP V2 receptor analog desmopressin (dDAVP; 5 ng/h, 3 days) significantly lowered renal EET levels (-56 ± 3% for 5,6-EET, -50 ± 3.4% for 11,12-EET, and -60 ± 3.7% for 14,15-EET). The abundance of the principal EET-degrading enzyme soluble epoxide hydrolase (sEH) was increased at the mRNA (+160 ± 37%) and protein levels (+120 ± 26%). Immunohistochemistry revealed dDAVP-mediated induction of sEH in connecting tubules and cortical and medullary collecting ducts, suggesting a role of these segments in the regulation of local interstitial EET signals. Incubation of murine kidney cell suspensions with 1 μM 14,15- EET for 30 min reduced phosphorylation of NKCC2 at the AVPsensitive threonine residues T96 and T101 (-66 ± 5%; P < 0.05), while 14,15-DHET had no effect. Concomitantly, isolated perfused cortical thick ascending limb pretreated with 14,15-EET showed a 30% lower transport current under high and a 70% lower transport current under low symmetric chloride concentrations. In summary, we have shown that activation of AVP signaling stimulates renal sEH biosynthesis and enzyme activity. The resulting reduction of EET tissue levels may be instrumental for increased NKCC2 transport activity during AVP-induced antidiuresis. [ABSTRACT FROM AUTHOR]

Aim: 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs) are cytochrome P450 (CYP)-dependent eicosanoids that play opposite roles in the regulation of vascular tone, inflammation, and apoptosis. 20-HETE aggravates, whereas EETs ameliorate ischemia/reperfusion (I/R)-induced organ damage. EETs are rapidly metabolized to dihydroxyeicosatrienoic acids (DHETs) by the soluble epoxide hydrolase (sEH). We hypothesized that sEH gene (EPHX2) deletion would increase endogenous EET levels and thereby protect against I/R-induced acute kidney injury (AKI). Methods: Kidney damage was evaluated in male wildtype (WT) and sEH-knockout (KO)-mice that underwent 22-min renal ischemia followed by two days of reperfusion. CYP-eicosanoids were analyzed by liquid chromatography tandem mass spectrometry. Results: Contrary to our initial hypothesis, renal function declined more severely in sEH-KO mice as indicated by higher serum creatinine and urea levels. The sEH-KO-mice also featured stronger tubular lesion scores, tubular apoptosis, and inflammatory cell infiltration. Plasma and renal EET/DHET-ratios were higher in sEH-KO than WT mice, thus confirming the expected metabolic consequences of sEH deficiency. However, CYP-eicosanoid profiling also revealed that renal, but not plasma and hepatic, 20-HETE levels were significantly increased in sEH-KO compared to WT mice. In line with this finding, renal expression of Cyp4a12a, the murine 20-HETE-generating CYP-enzyme, was up-regulated both at the mRNA and protein level, and Cyp4a12a immunostaining was more intense in the renal arterioles of sEH-KO compared with WT mice. Conclusion: These results indicate that the potential beneficial effects of reducing EET degradation were obliterated by a thus far unknown mechanism leading to kidney-specific up-regulation of 20-HETE formation in sEH-KO-mice. [ABSTRACT FROM AUTHOR]

The healthy functioning and long-term viability of the European Union ( EU) ultimately depend on its citizens finding common cause and developing a shared sense of political community. However, in recent years, scholars and pundits alike have expressed doubts about whether the EU's growing cultural, religious and economic diversity is undermining the development of citizens' shared sense of political community, especially following eastern expansion. In this article, this question is examined using data on a key aspect of political community: transnational dyadic trust. Drawing on a unique set of opinion surveys from the formative years of the EU to the first wave of eastward expansion (1954-2004), the development and sources of dyadic trust among EU Member States is studied. While recognising the importance of diversity for trust judgments in the short-term, the prevailing viewpoint that it is also a long-term obstacle to integration is challenged. Instead, it is argued that citizens from diverse cultural and economic backgrounds can learn to trust one another and build a sense of political community over time through greater cooperation and interconnectedness. This theory is tested with data on bilateral trade density, which is seen as a proxy and precursor for other forms of cross-national interconnectedness. Employing longitudinal models, the article also goes beyond existing research to test the theories over time. The study makes a contribution to the research on European integration, suggesting that over time mutual trust and a shared sense of political community can indeed develop in diverse settings. [ABSTRACT FROM AUTHOR]

The enduring legacy of Arend Lijphart's research has been to plant the seed of political institutions research that has grown and evolved over the past half century. This model of representative democracy is facing increasing challenges as citizens press for new means of political access and influence. This essay examines a dimension of democracy—direct democracy—that has expanded since Lijphart's initial studies. We use the 2004 International Social Survey Program study to examine the impact of direct democracy on political efficacy, citizen participation in politics, and satisfaction with the workings of democracy, comparing its effects to the kinder and gentler democracy that Lijphart posited for consensual democracy. We find that direct democracy apparently stimulates political interest, but has a negative effect on election turnout. In addition, we find little direct evidence of effects on efficacy, participation beyond elections, or satisfaction with democracy at the aggregate level. [ABSTRACT FROM AUTHOR]

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The article presents a study which investigated the role of oxidative protein modifications in 15-Deoxy-δ-Prostaglandin J2(15d-PGJ2)-mediated coronary vasodilation and define the distal signaling pathways leading to enhanced perfusion. Results showed novel vascular targets to which 15d-PGJ2 it adducts, with soluble epoxide hydrolase (sEH) as the most remarkable. Adduction of 15d-PGJ2 to sEH inhibits the hydrolase inducing vasorelaxation in response to hypoxia.

German unification was primarily a policy and economic challenge to unify two fundamentally different socio-political systems. In addition, it was a cultural challenge to unify two political cultures that had widely divergent histories. This article examines some of the basic aspects of cultural divide that were created by German unification. We first compare feelings of national identity between West and East, finding a lingering Eastern attachment to an Ostdeutsche identity. Second, we examine attitudes towards democracy, finding a convergence in support for democratic principles but persisting differences in approval of the functioning of the democratic process. Third, we describe attitudes toward the role of the state, demonstrating the more expansive role favoured by Easterners. We conclude that significant differences in these aspects of the political culture endure even 20 years after unification. Still, we are more sanguine that these differences do not pose fundamental political problems, and some Eastern sentiments might even benefit politics in the Federal Republic. [ABSTRACT FROM AUTHOR]

Political protest is seemingly a ubiquitous aspect of politics in advanced industrial societies, and its use may be spreading to less developed nations as well. Our research tests several rival theories of protest activity for citizens across an exceptionally wide range of polities. With data from the 1999-2002 wave of the World Values Survey, we demonstrate that the macro-level context - levels of economic and political development - significantly influences the amount of popular protest. Furthermore, a multi-level model examines how national context interacts with the micro-level predictors of protest activity. The findings indicate that contemporary protest is expanding not because of increasing dissatisfaction with government, but because economic and political development provide the resources for those who have political demands. [ABSTRACT FROM AUTHOR]

We aimed to identify genetic variants associated with heart failure by using a rat model of the human disease. We performed invasive cardiac hemodynamic measurements in F2 crosses between spontaneously hypertensive heart failure (SHHF) rats and reference strains. We combined linkage analyses with genome-wide expression profiling and identified Ephx2 as a heart failure susceptibility gene in SHHF rats. Specifically, we found that cis variation at Ephx2 segregated with heart failure and with increased transcript expression, protein expression and enzyme activity, leading to a more rapid hydrolysis of cardioprotective epoxyeicosatrienoic acids. To confirm our results, we tested the role of Ephx2 in heart failure using knockout mice. Ephx2 gene ablation protected from pressure overload–induced heart failure and cardiac arrhythmias. We further demonstrated differential regulation of EPHX2 in human heart failure, suggesting a cross-species role for Ephx2 in this complex disease. [ABSTRACT FROM AUTHOR]

Party identification, the psychological bond between citizens and a political party, is one of the central variables in understanding political behavior. This article argues that such party ties are also a measure of party system institutionalization from the standpoint of the public. We apply Converse's model of partisan learning to 36 nations surveyed as part of the Comparative Study of Electoral Systems. We find that electoral experience and parental socialization are strong sources of partisanship, but the third-wave democracies also display evidence of latent socialization carried over from the old regime. The results suggest that party identities can develop in new democracies if the party system creates the conditions to develop these bonds. [ABSTRACT FROM AUTHOR]

This study examines a long-standing concern in democratic theory: the relationship between polity size and democratic participation. Size is thought to have a direct effect on the individual's proclivity to take part in collective action, as well as indirect effects through increased bureaucratic complexity and group heterogeneity—two factors often related to group size. The study operates at two levels. At the nation-state level, it examines the relationship between size and party membership rates in 27 representative democracies. It then extends the analysis to the party organization level, examining the effect of party size on members' activism in 29 parties across 5 advanced industrial democracies. The results show that increasing size strongly diminishes participation at both levels. [ABSTRACT FROM AUTHOR]

The debate on citizen images of political parties is long standing, but recently it has taken on added importance as the evidence of party dealignment has spread across Western democracies. This article assembles an unprecedented cross-national array of public opinion data that describe current images of political parties. Sentiments are broadly negative, and this pessimism has deepened over the past generation. Then, we demonstrate how distrust of parties decreases voting turnout, contributes to the fragmentation of contemporary party systems and the electoral base of new protest parties, and stimulates broader cynicism towards government. Although political parties are the foundation of the system of representative democracy, fewer citizens today trust political parties, and this is reshaping the nature of democratic politics. [ABSTRACT FROM AUTHOR]