University of North Texas

About: University of North Texas is a education organization based out in Denton, Texas, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 11866 authors who have published 26984 publications receiving 705376 citations. The organization is also known as: Fight, North Texas & UNT.

Cardiomyopathy in zebrafish due to mutation in an alternatively spliced exon of titin

Abstract: The zebrafish embryo is transparent and can tolerate absence of blood flow because its oxygen is delivered by diffusion rather than by the cardiovascular system. It is therefore possible to attribute cardiac failure directly to particular genes by ruling out the possibility that it is due to a secondary effect of hypoxia. We focus here on pickwickm171 (pikm171), a recessive lethal mutation discovered in a large-scale genetic screen. There are three other alleles in the pik complementation group with this phenotype (pikm242, pikm740, pikm186; ref. 3) and one allele (pikmVO62H) with additional skeletal paralysis. The pik heart develops normally but is poorly contractile from the first beat. Aside from the edema that inevitably accompanies cardiac dysfunction, development is normal during the first three days. We show by positional cloning that the 'causative' mutation is in an alternatively-spliced exon of the gene (ttn) encoding Titin. Titin is the biggest known protein and spans the half-sarcomere from Z-disc to M-line in heart and skeletal muscle. It has been proposed to provide a scaffold for the assembly of thick and thin filaments and to provide elastic recoil engendered by stretch during diastole. We found that nascent myofibrils form in pik mutants, but normal sarcomeres are absent. Mutant cells transplanted to wildtype hearts remain thin and bulge outwards as individual cell aneurysms without affecting nearby wildtype cardiomyocytes, indicating that the contractile deficiency is cell-autonomous. Absence of Titin function thus results in blockage of sarcomere assembly and causes a functional disorder resembling human dilated cardiomyopathies, one form of which is described in another paper in this issue.

The Political Economy of Attitudes toward Polity and Society in Western European Democracies

Abstract: This article employs 1976-1986 Euro-Barometer data to investigate the political economy of public attitudes toward prevailing political and social arrangements in eight Western European countries. Pooled cross-sectional time series analyses reveal that the effects of economic conditions extend beyond their impact on governing party support to influence feelings of life and democracy satisfaction and demands for radical and reformist social change. Attitudes toward democracy and social change also respond to important political events such as the occurrence and outcomes of national elections. We conclude by arguing that the political economy of attitudes toward polity and society in contemporary Western democracies is real, but limited by widely shared beliefs that have become key elements in the political cultures of these countries.