Isoforms of the smooth muscle myosin phosphatase targeting subunit 1 (MYPT1) are generated by cassettetype alternative splicing of exons. Tissue-specific expression of these isoforms is thought to determine smooth muscle-relaxant properties and unique responses to signaling pathways. We used mini-gene deletion/mutation constructs to identify cis regulators of splicing of the chicken MYPT1 central alternative exon. Comparisons of alternative exon splicing were made between smooth muscle cells of the fast-phasic contractile phenotype (gizzard), in which the central alternative exon is skipped, and slow tonic contractile phenotype (aorta), in which the alternative exon is included. We demonstrate that splicing of the alternative exon requires a cis-enhancer complex in the vicinity of the alternative exon 5-splice site. This complex consists of two UCUU motifs in an intronic U-rich sequence (putative PTB (polypyrimidine tract binding) or T cell inhibitor of apoptosis-1 binding sites), an intronic 67-nucleotide enhancer that has similarities with the cardiac Troponin T MSE3 enhancer, and a potentially novel exonic splicing enhancer. The exonic enhancer contains the palindromic sequence UCCUACAUCCU present in many other transcripts where alternative splicing of exons occurs, suggesting that it may be more broadly active. The exonic enhancer is adjacent to a potentially novel exonic silencer element that contains a 13-nucleotide imperfect palindromic sequence. This silencer, in conjunction with a distal intronic silencer, is proposed to mediate the silencing of splicing of the MYPT1 central alternative exon in the fast phasic smooth muscle phenotype.Smooth muscle tissues show considerable phenotypic and functional diversity. Much of the phenotypic diversity in smooth muscle tissues is generated by the alternative splicing of exons from single gene transcripts. As many as 50% of vertebrate genes are estimated to have alternative splicing of exons as a mechanism by which multiple protein isoforms with different or modified functions are generated from a single gene (1-3). The process of splice site selection and exon definition for exons that are constitutively spliced has been well described (4 -7). Binding of U1 small nuclear ribonucleoprotein particle (snRNP) 1 to the consensus 5Ј-splice site sequence and binding of splicing factor 1 (SF1) and U2 snRNP auxiliary factor (U2AF) to the consensus 3Ј-splice site sequences (branchpoint and polypyrimidine tract, respectively) commits the exon to the splicing pathway (7,8). A number of factors are known to contribute to the "weakening" of the splicing reaction so that splicing of an exon may be regulated. These factors include exon and intron size, RNA secondary structure, and the extent to which the 5Ј-splice site, branchpoint, and polypyrimidine tract sequences match the consensus sequences for U1 snRNP, SF1, and U2AF binding, respectively (9 -11).A number of cis-elements that regulate the splicing of alternative exons have been identified (reviewed in Refs. 10, 12-14). W...

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<p><strong> </strong></p><p>Heart failure is a rapidly growing cardiovascular (CV) problem in Sudan due to affluence and lifestyle changes producing high rates of CV risk factors and consequent coronary heart disease in addition to the historical causes of hypertension and rheumatic heart disease.</p><p>This study is intended to measure the prevalence of heart failure (HF) among hospital admissions and study the recent trends in etiology, clinical features and methods of treatment.</p><p>Methods: All admissions at Sudan Heart Institute between January 2000 and June 2011 were studied. Patients went through detailed history taking and physical examination. Investigations included 12 lead ECG and chest X-ray, echocardiography and cardiac catheterization was also carried out where indicated.</p><p>Results: A total of 12453 cases were collected and 1073 were verified by the authors and an independent cardiologist, constituting 8.6% of CV disease admissions. Female to male ratio was 1:1.6 and age 15 to 96 years (median 58 years). 74.6 % of all patients were urban dwellers. Left ventricular (LV) systolic dysfunction accounted for 71.6% and preserved systolic function 28.4%.  Ischemic aetiology accounted for 44.6% of cases, hypertension 24.8 %, RHD 14.4% and idiopathic 12.4%. </p><p>Conclusion: Ischemic cardiomyopathy emerged as the main cause of HF among urban population probably due to changes in lifestyle. Treatment and prevention of these risk may reduce the prevalence of heart failure. </p>