Fostering support for non-democratic rule? Controlled political liberalization and popular support for non-democratic regimes

When the Cold War ended, many non-democratic regimes across the globe embarked on a course of controlled political liberalization, hoping to stabilize their autocratic rule by mitigating popular demands for democratization and increasing regime legitimacy. But does this strategy actually work? This article uses multi-level analyses to examine how the degree of political liberalization affects regime support in non-democratic political systems and to ascertain which mechanisms underlie this effect. Drawing on aggregate measures of political liberalization and comparative survey data from four regional survey projects and 31 non-democracies, the study's results indicate that the degree of liberalization has no decisively positive effect on regime support, suggesting controlled political liberalization might not be an effective legitimizing strategy after all.Nach Ende des Kalten Krieges haben viele nicht-demokratische Regime weltweit einen Kurs der begrenzten politischen Öffnung eingeschlagen, um öffentliche Forderungen nach Demokratisierung zu entschärfen und auf diese Weise die Legitimität ihrer autokratischen Herrschaft zu erhöhen. Doch ist diese Strategie tatsächlich effektiv? Der Beitrag verwendet Mehrebenenanalysen, um zu untersuchen wie der Grad an politischer Öffnung die Regimerunterstützung in nicht-demokratischen politischen Systemen beeinflusst. Auf Basis von Aggregatmaßen zur politischen Öffnung und Individualdaten aus vier regionalen Umfrageprojekten und 31 Autokratien kann kein klarer positiver Effekt des Grads der politischen Öffnung auf die Regimeunterstützung nachgewiesen werden, was eine begrenzte politische Öffnung als wenig effektive Legitimationsstrategie erscheinen lässt

The dopamine β-hydroxylase -1021C/T polymorphism is associated with the risk of Alzheimer's disease in the Epistasis Project

Contains fulltext : 88930.pdf (publisher's version ) (Open Access)BACKGROUND: The loss of noradrenergic neurones of the locus coeruleus is a major feature of Alzheimer's disease (AD). Dopamine beta-hydroxylase (DBH) catalyses the conversion of dopamine to noradrenaline. Interactions have been reported between the low-activity -1021T allele (rs1611115) of DBH and polymorphisms of the pro-inflammatory cytokine genes, IL1A and IL6, contributing to the risk of AD. We therefore examined the associations with AD of the DBH -1021T allele and of the above interactions in the Epistasis Project, with 1757 cases of AD and 6294 elderly controls. METHODS: We genotyped eight single nucleotide polymorphisms (SNPs) in the three genes, DBH, IL1A and IL6. We used logistic regression models and synergy factor analysis to examine potential interactions and associations with AD. RESULTS: We found that the presence of the -1021T allele was associated with AD: odds ratio = 1.2 (95% confidence interval: 1.06-1.4, p = 0.005). This association was nearly restricted to men < 75 years old: odds ratio = 2.2 (1.4-3.3, 0.0004). We also found an interaction between the presence of DBH -1021T and the -889TT genotype (rs1800587) of IL1A: synergy factor = 1.9 (1.2-3.1, 0.005). All these results were consistent between North Europe and North Spain. CONCLUSIONS: Extensive, previous evidence (reviewed here) indicates an important role for noradrenaline in the control of inflammation in the brain. Thus, the -1021T allele with presumed low activity may be associated with misregulation of inflammation, which could contribute to the onset of AD. We suggest that such misregulation is the predominant mechanism of the association we report here

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

Glibenclamide and HMR1098 normalize Cantú syndrome-associated gain-of-function currents

Cantú syndrome (CS) is caused by dominant gain-of-function mutation in ATP-dependent potassium channels. Cellular ATP concentrations regulate potassium current thereby coupling energy status with membrane excitability. No specific pharmacotherapeutic options are available to treat CS but IKATP channels are pharmaceutical targets in type II diabetes or cardiac arrhythmia treatment. We have been suggested that IKATP inhibitors, glibenclamide and HMR1098, normalize CS channels. IKATP in response to Mg-ATP, glibenclamide and HMR1098 were measured by inside-out patch-clamp electrophysiology. Results were interpreted in view of cryo-EM IKATP channel structures. Mg-ATP IC50 values of outward current were increased for D207E (0.71 ± 0.14 mmol/L), S1020P (1.83 ± 0.10), S1054Y (0.95 ± 0.06) and R1154Q (0.75 ± 0.13) channels compared to H60Y (0.14 ± 0.01) and wild-type (0.15 ± 0.01). HMR1098 dose-dependently inhibited S1020P and S1054Y channels in the presence of 0.15 mmol/L Mg-ATP, reaching, at 30 μmol/L, current levels displayed by wild-type and H60Y channels in the presence of 0.15 mmol/L Mg-ATP. Glibenclamide (10 μmol/L) induced similar normalization. S1054Y sensitivity to glibenclamide increases strongly at 0.5 mmol/L Mg-ATP compared to 0.15 mmol/L, in contrast to D207E and S1020P channels. Experimental findings agree with structural considerations. We conclude that CS channel activity can be normalized by existing drugs; however, complete normalization can be achieved at supraclinical concentrations only

Hyperlipidemic myeloma: review of 53 cases

Hyperlipidemic myeloma is a rare and poorly understood variant of multiple myeloma. We report the case of a 53-year-old woman with hyperlipidemic myeloma, skin xanthomas and hyperviscosity syndrome who underwent allogeneic bone marrow transplantation. A comprehensive literature search identified 52 additional cases with plasma cell disease and hyperlipidemia. A detailed analysis revealed several characteristics of these patients as compared to multiple myeloma with normal lipid status: (1) IgA paraprotein was present in the majority (53% vs. 21% in classical multiple myeloma). (2) Skin xanthomas, especially in the palmar creases, elbows, and knees were common (70%). (3) Hyperviscosity syndrome occurred more often (26% vs. 2-6%). While conventional lipid-lowering therapy had only marginal effects, successful anti-myeloma therapy also reduced hyperlipidemia. Analyses of the mechanisms leading to hyperlipidemia documented complexes of paraprotein and lipoprotein in 75% of the 32 cases tested, suggesting an inhibitory role of the paraprotein on lipid degradation. In conclusion, the clinical characteristics, the therapeutic options, and the pathophysiologic mechanisms of hyperlipidemic myeloma are comprehensively reported using the available data from all 53 published cases in the literature