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The sarcomeric M-region anchors thick filaments and withstands the mechanical stress of contractions by deformation, thus enabling distribution of physiological forces along the length of thick filaments. While the role of the M-region in supporting myofibrillar structure and contractility is well established, its role in mediating additional cellular processes has only recently started to emerge. As such, M-region is the hub of key protein players contributing to cytoskeletal remodeling, signal transduction, mechanosensing, metabolism, and proteasomal degradation. Mutations in genes encoding M-region related proteins lead to development of severe and lethal cardiac and skeletal myopathies affecting mankind. Herein, we describe the main cellular processes taking place at the M-region, other than thick filament assembly, and discuss human myopathies associated with mutant or truncated M-region proteins.
The sarcomeric M-region anchors thick filaments and withstands the mechanical stress of contractions by deformation, thus enabling distribution of physiological forces along the length of thick filaments. While the role of the M-region in supporting myofibrillar structure and contractility is well established, its role in mediating additional cellular processes has only recently started to emerge. As such, M-region is the hub of key protein players contributing to cytoskeletal remodeling, signal transduction, mechanosensing, metabolism, and proteasomal degradation. Mutations in genes encoding M-region related proteins lead to development of severe and lethal cardiac and skeletal myopathies affecting mankind. Herein, we describe the main cellular processes taking place at the M-region, other than thick filament assembly, and discuss human myopathies associated with mutant or truncated M-region proteins.
Takotsubo cardiomyopathy is a recently described clinical entity characterized by acute but rapidly reversible left ventricular systolic dysfunction in the absence of atherosclerotic coronary artery disease. There is typically balloon-like asynergy of the ventricular apical region, ST elevation in multiple leads, and minimal elevation of cardiac enzymes. Pathological features of this cardiomyopathy and guidelines for diagnosis have not been fully clarified.To clarify pathological features of Takotsubo (ampulla) cardiomyopathy, and the guideline development process, light microscopical examination was performed 9 autopsied cases, and 15 cases that underwent myocardial biopsy or aneurysmectomy (cases were from several institutes in Japan).Results: 1) Myocardial injury was present, but the incidence was relatively low. Damage of single myocytes or aggregate of single myocytes was observed diffusely throughout the ventricles. 2) Extensive damage of single myocytes included. Lesion were dated based on the following findings: hypereosinophilia, myofibrillar degeneration and myocytolysis. 3) Dated on the following histological findings: hypereosinophilia, myofibrillar degeneration, myocytolysis, cell infiltration → fibroblasts → collagen fibers (fibrosis). 4) The fraction of damaged myocytes was significantly higher in the apical than the basal regions. There was focal myocyte injury, including hypereosinophilia of myocytes, myofibrillar degeneration (contraction band formation), myocytolysis, focal fibrosis, and cell infiltrates. Discussion: The main pathological findings in autopsied hearts from patients with Takotsubo cardiomyopathy was injury of single myocyte that appeared as myofibrillar degeneration and its sequelae. The guideline development process was clarified.
The goal of this research is to introduce an improved method for detecting atrial fibrillation (AF). The foundation of our algorithm is the irregularity of the RR intervals in the electrocardiogram (ECG) signal, and their correlation with AF. Three statistical techniques, including root mean squares of successive differences (RMSSD), turning points ratio (TPR), and Shannon entropy (SE), are used to detect RR interval irregularity. We use the Massachusetts Institution of Technology / Beth Israel Hospital (MIT-BIH) atrial fibrillation databases and their annotations to tune the parameters of the statistical methods by biogeography-based optimization (BBO), which is an evolutionary optimization algorithm. We trained each statistical method to diagnose AF on each database. Then each trained method was tested on the rest of the databases. We were able to obtain accuracy levels as high as 99% for the detection of AF in the trained databases. We obtained accuracy levels of up to 75% in the tested databases. v
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