Myosins: A diverse superfamily of proteins that function as translocating proteins. They share the common characteristics of being able to bind ACTINS and hydrolyze MgATP. Myosins generally consist of heavy chains which are involved in locomotion, and light chains which are involved in regulation. Within the structure of myosin heavy chain are three domains: the head, the neck and the tail. The head region of the heavy chain contains the actin binding domain and MgATPase domain which provides energy for locomotion. The neck region is involved in binding the light-chains. The tail region provides the anchoring point that maintains the position of the heavy chain. The superfamily of myosins is organized into structural classes based upon the type and arrangement of the subunits they contain.Cardiac Myosins: Myosin type II isoforms found in cardiac muscle.Myosin Heavy Chains: The larger subunits of MYOSINS. The heavy chains have a molecular weight of about 230 kDa and each heavy chain is usually associated with a dissimilar pair of MYOSIN LIGHT CHAINS. The heavy chains possess actin-binding and ATPase activity.Myosin Subfragments: Parts of the myosin molecule resulting from cleavage by proteolytic enzymes (PAPAIN; TRYPSIN; or CHYMOTRYPSIN) at well-localized regions. Study of these isolated fragments helps to delineate the functional roles of different parts of myosin. Two of the most common subfragments are myosin S-1 and myosin S-2. S-1 contains the heads of the heavy chains plus the light chains and S-2 contains part of the double-stranded, alpha-helical, heavy chain tail (myosin rod).Myosin Light Chains: The smaller subunits of MYOSINS that bind near the head groups of MYOSIN HEAVY CHAINS. The myosin light chains have a molecular weight of about 20 KDa and there are usually one essential and one regulatory pair of light chains associated with each heavy chain. Many myosin light chains that bind calcium are considered "calmodulin-like" proteins.Myocarditis: Inflammatory processes of the muscular walls of the heart (MYOCARDIUM) which result in injury to the cardiac muscle cells (MYOCYTES, CARDIAC). Manifestations range from subclinical to sudden death (DEATH, SUDDEN). Myocarditis in association with cardiac dysfunction is classified as inflammatory CARDIOMYOPATHY usually caused by INFECTION, autoimmune diseases, or responses to toxic substances. Myocarditis is also a common cause of DILATED CARDIOMYOPATHY and other cardiomyopathies.Myosin Type II: The subfamily of myosin proteins that are commonly found in muscle fibers. Myosin II is also involved a diverse array of cellular functions including cell division, transport within the GOLGI APPARATUS, and maintaining MICROVILLI structure.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Ventricular Myosins: Isoforms of MYOSIN TYPE II, specifically found in the ventricular muscle of the HEART. Defects in the genes encoding ventricular myosins result in FAMILIAL HYPERTROPHIC CARDIOMYOPATHY.Myocytes, Cardiac: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).Myosin Type V: A subclass of myosin involved in organelle transport and membrane targeting. It is abundantly found in nervous tissue and neurosecretory cells. The heavy chains of myosin V contain unusually long neck domains that are believed to aid in translocating molecules over large distances.Heart: The hollow, muscular organ that maintains the circulation of the blood.Sarcomeres: The repeating contractile units of the MYOFIBRIL, delimited by Z bands along its length.Actins: Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.Actomyosin: A protein complex of actin and MYOSINS occurring in muscle. It is the essential contractile substance of muscle.Cardiomyopathy, Hypertrophic: A form of CARDIAC MUSCLE disease, characterized by left and/or right ventricular hypertrophy (HYPERTROPHY, LEFT VENTRICULAR; HYPERTROPHY, RIGHT VENTRICULAR), frequent asymmetrical involvement of the HEART SEPTUM, and normal or reduced left ventricular volume. Risk factors include HYPERTENSION; AORTIC STENOSIS; and gene MUTATION; (FAMILIAL HYPERTROPHIC CARDIOMYOPATHY).Myosin-Light-Chain Kinase: An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.Nonmuscle Myosin Type IIA: A nonmuscle isoform of myosin type II found predominantly in platelets, lymphocytes, neutrophils and brush border enterocytes.Myosin Type I: A subclass of myosins found generally associated with actin-rich membrane structures such as filopodia. Members of the myosin type I family are ubiquitously expressed in eukaryotes. The heavy chains of myosin type I lack coiled-coil forming sequences in their tails and therefore do not dimerize.Nonmuscle Myosin Type IIB: A nonmuscle isoform of myosin type II found predominantly in neuronal tissue.Adenosine Triphosphatases: A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.Cardiac Output: The volume of BLOOD passing through the HEART per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with STROKE VOLUME (volume per beat).Myocardial Contraction: Contractile activity of the MYOCARDIUM.Heart Ventricles: The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation.Autoimmune Diseases: Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.Muscles: Contractile tissue that produces movement in animals.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Myofibrils: The long cylindrical contractile organelles of STRIATED MUSCLE cells composed of ACTIN FILAMENTS; MYOSIN filaments; and other proteins organized in arrays of repeating units called SARCOMERES .Actin Cytoskeleton: Fibers composed of MICROFILAMENT PROTEINS, which are predominately ACTIN. They are the smallest of the cytoskeletal filaments.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Cardiomyopathy, Hypertrophic, Familial: An autosomal dominant inherited form of HYPERTROPHIC CARDIOMYOPATHY. It results from any of more than 50 mutations involving genes encoding contractile proteins such as VENTRICULAR MYOSINS; cardiac TROPONIN T; ALPHA-TROPOMYOSIN.Cardiomegaly: Enlargement of the HEART, usually indicated by a cardiothoracic ratio above 0.50. Heart enlargement may involve the right, the left, or both HEART VENTRICLES or HEART ATRIA. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (HEART FAILURE) or several forms of CARDIOMYOPATHIES.Ca(2+) Mg(2+)-ATPaseArrhythmias, Cardiac: Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.Cardiac Surgical Procedures: Surgery performed on the heart.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Chickens: Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.Death, Sudden, Cardiac: Unexpected rapid natural death due to cardiovascular collapse within one hour of initial symptoms. It is usually caused by the worsening of existing heart diseases. The sudden onset of symptoms, such as CHEST PAIN and CARDIAC ARRHYTHMIAS, particularly VENTRICULAR TACHYCARDIA, can lead to the loss of consciousness and cardiac arrest followed by biological death. (from Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed., 2005)Molecular Motor Proteins: Proteins that are involved in or cause CELL MOVEMENT such as the rotary structures (flagellar motor) or the structures whose movement is directed along cytoskeletal filaments (MYOSIN; KINESIN; and DYNEIN motor families).Rats, Inbred LewCardiomyopathies: A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Smooth Muscle Myosins: Myosin type II isoforms found in smooth muscle.Kinetics: The rate dynamics in chemical or physical systems.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Cardiomyopathy, Dilated: A form of CARDIAC MUSCLE disease that is characterized by ventricular dilation, VENTRICULAR DYSFUNCTION, and HEART FAILURE. Risk factors include SMOKING; ALCOHOL DRINKING; HYPERTENSION; INFECTION; PREGNANCY; and mutations in the LMNA gene encoding LAMIN TYPE A, a NUCLEAR LAMINA protein.Myosin Type III: A subclass of myosins originally found in the photoreceptor of DROSOPHILA. The heavy chains can occur as two alternatively spliced isoforms of 132 and 174 KDa. The amino terminal of myosin type III is highly unusual in that it contains a protein kinase domain which may be an important component of the visual process.Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by TROPONIN.Troponin I: One of the three polypeptide chains that make up the TROPONIN complex. It inhibits F-actin-myosin interactions.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Troponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments.Rheumatic Heart Disease: Cardiac manifestation of systemic rheumatological conditions, such as RHEUMATIC FEVER. Rheumatic heart disease can involve any part the heart, most often the HEART VALVES and the ENDOCARDIUM.GizzardSkeletal Muscle Myosins: Myosin type II isoforms found in skeletal muscle.Heterocyclic Compounds with 4 or More Rings: A class of organic compounds containing four or more ring structures, one of which is made up of more than one kind of atom, usually carbon plus another atom. The heterocycle may be either aromatic or nonaromatic.Propylthiouracil: A thiourea antithyroid agent. Propythiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to tri-iodothyronine. It is used in the treatment of hyperthyroidism. (From Martindale, The Extra Pharmacopeoia, 30th ed, p534)Adrenergic beta-2 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC BETA-2 RECEPTORS.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Swine: Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).Cardiac Tamponade: Compression of the heart by accumulated fluid (PERICARDIAL EFFUSION) or blood (HEMOPERICARDIUM) in the PERICARDIUM surrounding the heart. The affected cardiac functions and CARDIAC OUTPUT can range from minimal to total hemodynamic collapse.Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Cardiac Pacing, Artificial: Regulation of the rate of contraction of the heart muscles by an artificial pacemaker.Heart Failure: A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.Myosin-Light-Chain Phosphatase: A phosphoprotein phosphatase that is specific for MYOSIN LIGHT CHAINS. It is composed of three subunits, which include a catalytic subunit, a myosin binding subunit, and a third subunit of unknown function.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Heart Diseases: Pathological conditions involving the HEART including its structural and functional abnormalities.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Hyperthyroidism: Hypersecretion of THYROID HORMONES from the THYROID GLAND. Elevated levels of thyroid hormones increase BASAL METABOLIC RATE.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Heart Atria: The chambers of the heart, to which the BLOOD returns from the circulation.Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Adenosine Diphosphate: Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.Cross Reactions: Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.Cardiac Catheterization: Procedures in which placement of CARDIAC CATHETERS is performed for therapeutic or diagnostic procedures.Ventricular Function, Left: The hemodynamic and electrophysiological action of the left HEART VENTRICLE. Its measurement is an important aspect of the clinical evaluation of patients with heart disease to determine the effects of the disease on cardiac performance.Muscle, Smooth: Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)Heart Arrest: Cessation of heart beat or MYOCARDIAL CONTRACTION. If it is treated within a few minutes, heart arrest can be reversed in most cases to normal cardiac rhythm and effective circulation.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Myocardial Infarction: NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).Muscle Proteins: The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN.Animals, Newborn: Refers to animals in the period of time just after birth.Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Hypothyroidism: A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA.Enterovirus B, Human: A species of ENTEROVIRUS infecting humans and containing 36 serotypes. It is comprised of all the echoviruses and a few coxsackieviruses, including all of those previously named coxsackievirus B.Coxsackievirus Infections: A heterogeneous group of infections produced by coxsackieviruses, including HERPANGINA, aseptic meningitis (MENINGITIS, ASEPTIC), a common-cold-like syndrome, a non-paralytic poliomyelitis-like syndrome, epidemic pleurodynia (PLEURODYNIA, EPIDEMIC) and a serious MYOCARDITIS.Muscle, Skeletal: A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.Molecular Mimicry: The structure of one molecule that imitates or simulates the structure of a different molecule.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Thyroxine: The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (MONOIODOTYROSINE) and the coupling of iodotyrosines (DIIODOTYROSINE) in the THYROGLOBULIN. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form TRIIODOTHYRONINE which exerts a broad spectrum of stimulatory effects on cell metabolism.Myoblasts, Cardiac: Precursor cells destined to differentiate into cardiac myocytes (MYOCYTES, CARDIAC).Dictyostelium: A genus of protozoa, formerly also considered a fungus. Its natural habitat is decaying forest leaves, where it feeds on bacteria. D. discoideum is the best-known species and is widely used in biomedical research.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Electrocardiography: Recording of the moment-to-moment electromotive forces of the HEART as projected onto various sites on the body's surface, delineated as a scalar function of time. The recording is monitored by a tracing on slow moving chart paper or by observing it on a cardioscope, which is a CATHODE RAY TUBE DISPLAY.Cardiac Imaging Techniques: Visualization of the heart structure and cardiac blood flow for diagnostic evaluation or to guide cardiac procedures via techniques including ENDOSCOPY (cardiac endoscopy, sometimes refered to as cardioscopy), RADIONUCLIDE IMAGING; MAGNETIC RESONANCE IMAGING; TOMOGRAPHY; or ULTRASONOGRAPHY.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Turkeys: Large woodland game BIRDS in the subfamily Meleagridinae, family Phasianidae, order GALLIFORMES. Formerly they were considered a distinct family, Melegrididae.Organ Specificity: Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen.Ethylmaleimide: A sulfhydryl reagent that is widely used in experimental biochemical studies.Cardiac Glycosides: Cyclopentanophenanthrenes with a 5- or 6-membered lactone ring attached at the 17-position and SUGARS attached at the 3-position. Plants they come from have long been used in congestive heart failure. They increase the force of cardiac contraction without significantly affecting other parameters, but are very toxic at larger doses. Their mechanism of action usually involves inhibition of the NA(+)-K(+)-EXCHANGING ATPASE and they are often used in cell biological studies for that purpose.Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.Cyclic AMP-Dependent Protein Kinases: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.Heart Rate: The number of times the HEART VENTRICLES contract per unit of time, usually per minute.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Cardiac Output, Low: A state of subnormal or depressed cardiac output at rest or during stress. It is a characteristic of CARDIOVASCULAR DISEASES, including congenital, valvular, rheumatic, hypertensive, coronary, and cardiomyopathic. The serious form of low cardiac output is characterized by marked reduction in STROKE VOLUME, and systemic vasoconstriction resulting in cold, pale, and sometimes cyanotic extremities.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Magnesium: A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.Hemodynamics: The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM.Muscle Fibers, Skeletal: Large, multinucleate single cells, either cylindrical or prismatic in shape, that form the basic unit of SKELETAL MUSCLE. They consist of MYOFIBRILS enclosed within and attached to the SARCOLEMMA. They are derived from the fusion of skeletal myoblasts (MYOBLASTS, SKELETAL) into a syncytium, followed by differentiation.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Out-of-Hospital Cardiac Arrest: Occurrence of heart arrest in an individual when there is no immediate access to medical personnel or equipment.Ventricular Remodeling: The geometric and structural changes that the HEART VENTRICLES undergo, usually following MYOCARDIAL INFARCTION. It comprises expansion of the infarct and dilatation of the healthy ventricle segments. While most prevalent in the left ventricle, it can also occur in the right ventricle.Molecular Weight: The sum of the weight of all the atoms in a molecule.Mice, Inbred C57BLHeart Transplantation: The transference of a heart from one human or animal to another.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Cardiac Volume: The volume of the HEART, usually relating to the volume of BLOOD contained within it at various periods of the cardiac cycle. The amount of blood ejected from a ventricle at each beat is STROKE VOLUME.rho-Associated Kinases: A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.Troponin T: One of the three polypeptide chains that make up the TROPONIN complex. It is a cardiac-specific protein that binds to TROPOMYOSIN. It is released from damaged or injured heart muscle cells (MYOCYTES, CARDIAC). Defects in the gene encoding troponin T result in FAMILIAL HYPERTROPHIC CARDIOMYOPATHY.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Heart Defects, Congenital: Developmental abnormalities involving structures of the heart. These defects are present at birth but may be discovered later in life.Epitopes: Sites on an antigen that interact with specific antibodies.Mollusca: A phylum of the kingdom Metazoa. Mollusca have soft, unsegmented bodies with an anterior head, a dorsal visceral mass, and a ventral foot. Most are encased in a protective calcareous shell. It includes the classes GASTROPODA; BIVALVIA; CEPHALOPODA; Aplacophora; Scaphopoda; Polyplacophora; and Monoplacophora.Chemistry: A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.Genes: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.Chemical Phenomena: The composition, conformation, and properties of atoms and molecules, and their reaction and interaction processes.Mutation, Missense: A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Calmodulin-Binding Proteins: Proteins which bind calmodulin. They are found in many tissues and have a variety of functions including F-actin cross-linking properties, inhibition of cyclic nucleotide phosphodiesterase and calcium and magnesium ATPases.Stroke Volume: The amount of BLOOD pumped out of the HEART per beat, not to be confused with cardiac output (volume/time). It is calculated as the difference between the end-diastolic volume and the end-systolic volume.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Heart Function Tests: Examinations used to diagnose and treat heart conditions.Amoeba: A genus of ameboid protozoa. Characteristics include a vesicular nucleus and the formation of several lodopodia, one of which is dominant at a given time. Reproduction occurs asexually by binary fission.Heart Conduction System: An impulse-conducting system composed of modified cardiac muscle, having the power of spontaneous rhythmicity and conduction more highly developed than the rest of the heart.Aging: The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.Cardiac Resynchronization Therapy: The restoration of the sequential order of contraction and relaxation of the HEART ATRIA and HEART VENTRICLES by atrio-biventricular pacing.Cardiotonic Agents: Agents that have a strengthening effect on the heart or that can increase cardiac output. They may be CARDIAC GLYCOSIDES; SYMPATHOMIMETICS; or other drugs. They are used after MYOCARDIAL INFARCT; CARDIAC SURGICAL PROCEDURES; in SHOCK; or in congestive heart failure (HEART FAILURE).Cardiopulmonary Resuscitation: The artificial substitution of heart and lung action as indicated for HEART ARREST resulting from electric shock, DROWNING, respiratory arrest, or other causes. The two major components of cardiopulmonary resuscitation are artificial ventilation (RESPIRATION, ARTIFICIAL) and closed-chest CARDIAC MASSAGE.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Ventricular Dysfunction, Left: A condition in which the LEFT VENTRICLE of the heart was functionally impaired. This condition usually leads to HEART FAILURE; MYOCARDIAL INFARCTION; and other cardiovascular complications. Diagnosis is made by measuring the diminished ejection fraction and a depressed level of motility of the left ventricular wall.Heart Neoplasms: Tumors in any part of the heart. They include primary cardiac tumors and metastatic tumors to the heart. Their interference with normal cardiac functions can cause a wide variety of symptoms including HEART FAILURE; CARDIAC ARRHYTHMIAS; or EMBOLISM.Cardiac Care Facilities: Institutions specializing in the care of patients with heart disorders.Fetal Heart: The heart of the fetus of any viviparous animal. It refers to the heart in the postembryonic period and is differentiated from the embryonic heart (HEART/embryology) only on the basis of time.Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).Connectin: A giant elastic protein of molecular mass ranging from 2,993 kDa (cardiac), 3,300 kDa (psoas), to 3,700 kDa (soleus) having a kinase domain. The amino- terminal is involved in a Z line binding, and the carboxy-terminal region is bound to the myosin filament with an overlap between the counter-connectin filaments at the M line.Acanthamoeba: A genus of free-living soil amoebae that produces no flagellate stage. Its organisms are pathogens for several infections in humans and have been found in the eye, bone, brain, and respiratory tract.Models, Cardiovascular: Theoretical representations that simulate the behavior or activity of the cardiovascular system, processes, or phenomena; includes the use of mathematical equations, computers and other electronic equipment.Mice, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Cardiac Electrophysiology: The study of the electrical activity and characteristics of the HEART; MYOCARDIUM; and CARDIOMYOCYTES.Atrial Myosins: Myosin type II isoforms specifically found in the atrial muscle of the heart.Regulatory Sequences, Nucleic Acid: Nucleic acid sequences involved in regulating the expression of genes.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Ventricular Function: The hemodynamic and electrophysiological action of the HEART VENTRICLES.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Muscle Development: Developmental events leading to the formation of adult muscular system, which includes differentiation of the various types of muscle cell precursors, migration of myoblasts, activation of myogenesis and development of muscle anchorage.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Myosin Type IV: A subclass of myosin found in ACANTHAMOEBA. It is a non-filamentous myosin containing a single 180-kDa myosin heavy chain.Epitope Mapping: Methods used for studying the interactions of antibodies with specific regions of protein antigens. Important applications of epitope mapping are found within the area of immunochemistry.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Muscle Fibers, Slow-Twitch: Skeletal muscle fibers characterized by their expression of the Type I MYOSIN HEAVY CHAIN isoforms which have low ATPase activity and effect several other functional properties - shortening velocity, power output, rate of tension redevelopment.Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Immunization: Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).Azepines: Seven membered heterocyclic rings containing a NITROGEN atom.Microfilament Proteins: Monomeric subunits of primarily globular ACTIN and found in the cytoplasmic matrix of almost all cells. They are often associated with microtubules and may play a role in cytoskeletal function and/or mediate movement of the cell or the organelles within the cell.Pedigree: The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Muscle Fibers, Fast-Twitch: Skeletal muscle fibers characterized by their expression of the Type II MYOSIN HEAVY CHAIN isoforms which have high ATPase activity and effect several other functional properties - shortening velocity, power output, rate of tension redevelopment. Several fast types have been identified.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Isometric Contraction: Muscular contractions characterized by increase in tension without change in length.Cyanogen Bromide: Cyanogen bromide (CNBr). A compound used in molecular biology to digest some proteins and as a coupling reagent for phosphoroamidate or pyrophosphate internucleotide bonds in DNA duplexes.Heart Injuries: General or unspecified injuries to the heart.Cytoplasmic Streaming: The movement of CYTOPLASM within a CELL. It serves as an internal transport system for moving essential substances throughout the cell, and in single-celled organisms, such as the AMOEBA, it is responsible for the movement (CELL MOVEMENT) of the entire cell.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Chick Embryo: The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Hypertrophy, Left Ventricular: Enlargement of the LEFT VENTRICLE of the heart. This increase in ventricular mass is attributed to sustained abnormal pressure or volume loads and is a contributor to cardiovascular morbidity and mortality.Mice, Inbred BALB CIsoproterenol: Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.Troponin C: One of the three polypeptide chains that make up the TROPONIN complex of skeletal muscle. It is a calcium-binding protein.Diacetyl: Carrier of aroma of butter, vinegar, coffee, and other foods.Atrial Natriuretic Factor: A potent natriuretic and vasodilatory peptide or mixture of different-sized low molecular weight PEPTIDES derived from a common precursor and secreted mainly by the HEART ATRIUM. All these peptides share a sequence of about 20 AMINO ACIDS.

Altered cardiac excitation-contraction coupling in mutant mice with familial hypertrophic cardiomyopathy. (1/275)

Excitation-contraction coupling in cardiac muscle of familial hypertrophic cardiomyopathy (FHC) remains poorly understood, despite the fact that the genetic alterations are well defined. We characterized calcium cycling and contractile activation in trabeculae from a mutant mouse model of FHC (Arg403Gln knockin, alpha-myosin heavy chain). Wild-type mice of the same strain and age ( approximately 20 weeks old) served as controls. During twitch contractions, peak intracellular Ca2+ ([Ca2+]i) was higher in mutant muscles than in the wild-type (P < 0.05), but force development was equivalent in the two groups. Ca2+ transient amplitude increased dramatically in both groups as stimulation rate increased from 0.2 to 4 Hz. Nevertheless, developed force fell at the higher stimulation rates in the mutants but not in controls (P < 0.05). The steady-state force-[Ca2+]i relationship was less steep in mutants (Hill coefficient, 2.94 +/- 0.27 vs. 5.28 +/- 0.64; P > 0.003), with no changes in the [Ca2+]i required for 50% activation or maximal Ca2+-activated force. Thus, calcium cycling and myofilament properties are both altered in FHC mutant mice: more Ca2+ is mobilized to generate force, but this does not suffice to maintain contractility at high stimulation rates.  (+info)

A post-transcriptional compensatory pathway in heterozygous ventricular myosin light chain 2-deficient mice results in lack of gene dosage effect during normal cardiac growth or hypertrophy. (2/275)

Our previous study of homozygous mutants of the ventricular specific isoform of myosin light chain 2 (mlc-2v) demonstrated that mlc-2v plays an essential role in murine heart development (Chen, J., Kubalak, S. W., Minamisawa, S., Price, R. L., Becker, K. D., Hickey, R., Ross, J., Jr., and Chien, K. R. (1998) J. Biol. Chem. 273, 1252-1256). As gene dosage of some myofibrillar proteins can affect muscle function, we have analyzed heterozygous mutants in depth. Ventricles of heterozygous mutants displayed a 50% reduction in mlc-2v mRNA, yet expressed normal levels of protein both under basal conditions and following induction of cardiac hypertrophy by aortic constriction. Heterozygous mutants exhibited cardiac function comparable to that of wild-type littermate controls both prior to and following aortic constriction. There were no significant differences in contractility and responses to calcium between wild-type and heterozygous unloaded cardiomyocytes. We conclude that heterozygous mutants show neither a molecular nor a physiological cardiac phenotype either at base line or following hypertrophic stimuli. These results suggest that post-transcriptional compensatory mechanisms play a major role in maintaining the level of MLC-2v protein in murine hearts. In addition, as our mlc-2v knockout mutants were created by a knock-in of Cre recombinase into the endogenous mlc-2v locus, this study demonstrates that heterozygous mlc-2v cre knock-in mice are appropriate for ventricular specific gene targeting.  (+info)

The CACC box and myocyte enhancer factor-2 sites within the myosin light chain 2 slow promoter cooperate in regulating nerve-specific transcription in skeletal muscle. (3/275)

Previous experiments showed that activity of the -800-base pair MLC2slow promoter was 75-fold higher in the innervated soleus (SOL) compared with the noninnervated SOL muscles. Using in vivo DNA injection of MLC2slow promoter-luciferase constructs, the aim of this project was to identify regulatory sites and potential transcription factors important for slow nerve-dependent gene expression. Three sites within the proximal promoter (myocyte enhancer factor-2 (MEF2), E-box, and CACC box) were individually mutated, and the effect on luciferase expression was determined. There was no change in luciferase expression in the SOL and extensor digitorum longus (EDL) muscles when the E-box was mutated. In contrast, the MEF2 mutation resulted in a 30-fold decrease in expression in the innervated SOL muscles (10.3 versus 0.36 normalized relative light units (RLUs)). Transactivation of the MLC2slow promoter by overexpressing MEF2 was only seen in the innervated SOL (676,340 versus 2,225,957 RLUs; p < 0.01) with no effect in noninnervated SOL or EDL muscles. These findings suggest that the active MLC2slow promoter is sensitive to MEF2 levels, but MEF2 levels alone do not determine nerve-dependent expression. Mutation of the CACC box resulted in a significant up-regulation in the EDL muscles (0.23 versus 4.08 normalized RLUs). With the CACC box mutated, overexpression of MEF2 was sufficient to transactivate the MLC2slow promoter in noninnervated SOL muscles (27,536 versus 1, 605,797 RLUs). Results from electrophoretic mobility shift and supershift assays confirm MEF2 protein binding to the MEF2 site and demonstrate specific binding to the CACC sequence. These results suggest a model for nerve-dependent regulation of the MLC2slow promoter in which derepression occurs through the CACC box followed by quantitative expression through enhanced MEF2 activation.  (+info)

The effect of removing the N-terminal extension of the Drosophila myosin regulatory light chain upon flight ability and the contractile dynamics of indirect flight muscle. (4/275)

The Drosophila myosin regulatory light chain (DMLC2) is homologous to MLC2s of vertebrate organisms, except for the presence of a unique 46-amino acid N-terminal extension. To study the role of the DMLC2 N-terminal extension in Drosophila flight muscle, we constructed a truncated form of the Dmlc2 gene lacking amino acids 2-46 (Dmlc2(Delta2-46)). The mutant gene was expressed in vivo, with no wild-type Dmlc2 gene expression, via P-element-mediated germline transformation. Expression of the truncated DMLC2 rescues the recessive lethality and dominant flightless phenotype of the Dmlc2 null, with no discernible effect on indirect flight muscle (IFM) sarcomere assembly. Homozygous Dmlc2(Delta2-46) flies have reduced IFM dynamic stiffness and elastic modulus at the frequency of maximum power output. The viscous modulus, a measure of the fly's ability to perform oscillatory work, was not significantly affected in Dmlc2(Delta2-46) IFM. In vivo flight performance measurements of Dmlc2(Delta2-46) flies using a visual closed-loop flight arena show deficits in maximum metabolic power (P(*)(CO(2))), mechanical power (P(*)(mech)), and flight force. However, mutant flies were capable of generating flight force levels comparable to body weight, thus enabling them to fly, albeit with diminished performance. The reduction in elastic modulus in Dmlc2(Delta2-46) skinned fibers is consistent with the N-terminal extension being a link between the thick and thin filaments that is parallel to the cross-bridges. Removal of this parallel link causes an unfavorable shift in the resonant properties of the flight system, thus leading to attenuated flight performance.  (+info)

A fluorescent reporter gene as a marker for ventricular specification in ES-derived cardiac cells. (5/275)

We have established a CGR8 embryonic stem (ES) cell clone (MLC2ECFP) which expresses the enhanced cyan variant of Aequorea victoria green fluorescent protein (ECFP) under the transcriptional control of the ventricular myosin light chain 2 (MLC2v) promoter. Using epifluorescence imaging of vital embryoid bodies (EB) and reverse transcription-polymerase chain reaction (RT-PCR), we found that the MLC2v promoter is switched on as early as day 7 and is accompanied by formation of cell clusters featuring a bright ECFP blue fluorescence. The fluorescent areas within the EBs were all beating on day 8. MLC2ECFP ES cells showed the same time course of cardiac differentiation as mock ES cells as assessed by RT-PCR of genes encoding cardiac-specific transcription factors and contractile proteins. The MLC2v promoter conferred ventricular specificity to ECFP expression within the EB as revealed by MLC2v co-staining of ECFP fluorescent cells. MLC2ECFP-derived cardiac cells still undergo cell division on day 12 after isolation from EBs but withdraw from the cell cycle on day 16. This ES cell clone provides a powerful cell model to study the signalling roads of factors regulating cardiac cell proliferation and terminal differentiation with a view to using them for experimental cell therapy.  (+info)

Adverse effects of constitutively active alpha(1B)-adrenergic receptors after pressure overload in mouse hearts. (6/275)

Cardiac hypertrophy and function were studied 6 wk after constriction of the thoracic aorta (TAC) in transgenic (TG) mice expressing constitutively active mutant alpha(1B)-adrenergic receptors (ARs) in the heart. Hearts from sham-operated TG animals and nontransgenic littermates (WT) were similar in size, but hearts from TAC/TG mice were larger than those from TAC/WT mice, and atrial natriuretic peptide mRNA expression was also higher. Lung weight was markedly increased in TAC/TG animals, and the incidence of left atrial thrombus formation was significantly higher. Ventricular contractility in anesthetized animals, although it was increased in TAC/WT hearts, was unchanged in TAC/TG hearts, implying cardiac decompensation and progression to failure in TG mice. There was no increase in alpha(1A)-AR mRNA expression in TAC/WT hearts, and expression was significantly reduced in TAC/TG hearts. These findings show that cardiac expression of constitutively actively mutant alpha(1B)-ARs is detrimental in terms of hypertrophy and cardiac function after pressure overload and that increased alpha(1A)-AR mRNA expression is not a feature of the hypertrophic response in this murine model.  (+info)

The calcineurin-NFAT pathway and muscle fiber-type gene expression. (7/275)

To test for a role of the calcineurin-NFAT (nuclear factor of activated T cells) pathway in the regulation of fiber type-specific gene expression, slow and fast muscle-specific promoters were examined in C2C12 myotubes and in slow and fast muscle in the presence of calcineurin or NFAT2 expression plasmids. Overexpression of active calcineurin in myotubes induced both fast and slow muscle-specific promoters but not non-muscle-specific reporters. Overexpression of NFAT2 in myotubes did not activate muscle-specific promoters, although it strongly activated an NFAT reporter. Thus overexpression of active calcineurin activates transcription of muscle-specific promoters in vitro but likely not via the NFAT2 transcription factor. Slow myosin light chain 2 (MLC2) and fast sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA1) reporter genes injected into rat soleus (slow) and extensor digitorum longus (EDL) (fast) muscles were not activated by coinjection of activated calcineurin or NFAT2 expression plasmids. However, an NFAT reporter was strongly activated by overexpression of NFAT2 in both muscle types. Calcineurin and NFAT protein expression and binding activity to NFAT oligonucleotides were different in slow vs. fast muscle. Taken together, these results indicate that neither calcineurin nor NFAT appear to have dominant roles in the induction and/or maintenance of slow or fast fiber type in adult skeletal muscle. Furthermore, different pathways may be involved in muscle-specific gene expression in vitro vs. in vivo.  (+info)

Altered cross-bridge characteristics following haemodynamic overload in rabbit hearts expressing V3 myosin. (8/275)

1. Our goal in this study was to evaluate the effect of haemodynamic overload on cross-bridge (XBr) kinetics in the rabbit heart independently of myosin heavy chain (MHC) isoforms, which are known to modulate kinetics in small mammals. We applied a myothermal-mechanical protocol to isometrically contracting papillary muscles from two rabbit heart populations: (1) surgically induced right ventricular pressure overload (PO), and (2) sustained treatment with propylthiouracil (PTU). Both treatments resulted in a 100 % V3 MHC profile. 2. XBr force-time integral (FTI), evaluated during the peak of the twitch from muscle FTI and tension-dependent heat, was greater in the PO hearts (0.80 +/- 0.10 versus 0.45 +/- 0.05 pN s, means +/- S.E.M., P = 0.01). 3. Within the framework of a two-state XBr model, the PO XBr developed more force while attached (5.8 +/- 0.9 versus 2.7 +/- 0.3 pN), with a lower cycling rate (0.89 +/- 0.10 versus 1.50 +/- 0.14 s(-1)) and duty cycle (0.14 +/- 0.03 versus 0.24 +/- 0.02). 4. Only the ventricular isoforms of myosin light chain 1 and 2 and cardiac troponin I (cTnI) were expressed, with no difference in cTnI phosphorylation between the PO and PTU samples. The troponin T (TnT) isoform compositions in the PO and PTU samples were significantly different (P = 0.001), with TnT2 comprising 2.29 +/- 0.03 % in PO hearts versus 0.98 +/- 0.01 % in PTU hearts of total TnT. 5. This study demonstrates that MHC does not mediate dramatic alterations in XBr function induced by haemodynamic overload. Our findings support the likelihood that differences among other thick and thin filament proteins underlie these XBr alterations.  (+info)

MAYWOOD, Ill. - A new blood test can detect heart attacks hours faster than the current gold-standard blood test, according to a study led by Loyola University Chicago Stritch School of Medicine researchers.. The new test measures a protein that is released to the bloodstream by dying heart muscle. The protein is called cardiac myosin binding protein-C (cMyBP-C). The study found that cMyBP-C is released to the blood within just 15 minutes of cardiac damage, and rises to significant levels in three hours.. "This is a potential ultra-early biomarker that could confirm whether a patient has had a heart attack, leading to faster and more effective treatment," said Sakthivel Sadayappan, PhD, senior author of the study, published Dec. 13, 2013 in the American Journal of Physiology - Heart and Circulatory Physiology.. Between 60 and 70 percent of all patients who complain of chest pain do not have heart attacks. Many of these patients are admitted to the hospital, at considerable time and expense, ...
Figure 3. Identification of cardiac myosin binding protein-C (cMyBP-C) as a cardiac myocyte-specific PKGIα anti-remodeling substrate through molecular screen for PKGIa-LZ binding proteins. From Thoonen et al, 2015. (A) Outline of screening strategy. GST-fusion proteins were generated containing the PKGIa LZ domain (PKG1-59), the PKGIα mutated LZ domain (PKGLZM), or GST alone. The separate bait proteins were incubated with left ventricular protein lysates, followed by SDS PAGE and Coomassie staining. Protein bands selectively precipitating with PKG1-59 were removed and identified by mass spectroscopy. (B) Representative Coomassie stain from left ventricular protein lysates incubated with GST-fusion proteins. The 150 kDa band visible only in PKG1-59 precipitate (denoted by arrow) was excised and subjected to mass spectroscopy, revealing cMyBP-C as the predominant species. The thick bands between 25 and 30 kDa represent GST fusion proteins. Representative of 3 independent experiments. (C) Model ...
The histopathologic features of hypertrophic cardiomyopathy (HCM) are left ventricular hypertrophy, myocyte disarray, and interstitial fibrosis (1).. Cardiac magnetic resonance (CMR) is the gold standard for in vivo assessment of focal myocardial fibrosis using the late gadolinium enhancement (LGE) technique (2). This correlates with clinical risk factors for sudden death and arrhythmias, and is predictive of adverse outcomes including heart failure (3). It remains unclear how fibrosis evolves and how evolution correlates with ventricular remodeling. Our aim was to track long-term changes in CMR LGE in HCM over a 7-year follow-up period.. From 2001 to 2003, 59 patients with HCM (5 gene-positive for sarcomeric gene mutations with electrocardiogram changes fulfilling familial criteria) (1) underwent CMR LGE. Follow-up scans were performed in 12 patients on average 7.4 ± 0.4 years after the initial scans. The attrition of this overall high-risk cohort from a tertiary referral center occurred ...
van den Thillart, Guido, Dufour, Sylvie and Rankin, J. Cliff, eds. (2008) Spawning Migration of the European Eel. Fish & Fisheries Series, 30 . Springer Netherlands, London, UK. ISBN 978-1-4020-9095-0 (Online) Ababou, Abdessamad, Gautel, Mathias and Pfuhl, Mark (2007) Disecting the N-terminal myosin binding site of human cardiac myosin binding protein C : Structure and myosin binding of domain C2. Journal of Biological Chemistry, 282 (12). pp. 9204-9215. ISSN 00219258 Ahmed, Naveed, Tsang, Wing Y. and Page, Michael I. (2004) Acyl vs Sulfonyl Transfer in N-Acyl β-Sultams and 3-Oxo-β sultams. Organic Letters, 6 (2). pp. 201-203. ISSN 15237060 Akbar, Sirwan, Rout, Simon and Humphreys, Paul (2015) Draft Genome Sequences of Pseudomonas aeruginosa Strain PS3 and Citrobacter freundii Strain SA79 Obtained from a Wound DressingAssociated Biofilm. Genome Announcements, 3 (3). ISSN 2169-8287 Al-Nuaimi, Yusur, Hardman, Jonathan A., Bíró, Tamás, Haslam, Iain S., Philpott, Michael P., Tóth, Balázs I., ...
MYBPC1兔多克隆抗体(ab110363)可与人样本反应并经WB实验严格验证并得到3个独立的用户反馈。所有产品均提供质保服务,中国75%以上现货。
This case shows Ebstein anomaly with tricuspid regurgitation in an elderly patient. The anomaly was also demonstrated on echocardiography. Ebstein anomaly occurs in about 1 of every 200,000 live births and initial presentation by older patients ...
Toxoplasma gondii is an obligate intracellular parasite that enters cells by a process of active penetration. Host cell penetration and parasite motility are driven by a myosin motor complex consisting of four known proteins: TgMyoA, an unconventional Class XIV myosin; TgMLC1, a myosin light chain; and two membrane-associated proteins, TgGAP45 and TgGAP50. Little is known about how the activity of the myosin motor complex is regulated. Here, we show that treatment of parasites with a recently identified small-molecule inhibitor of invasion and motility results in a rapid and irreversible change in the electrophoretic mobility of TgMLC1. While the precise nature of the TgMLC1 modification has not yet been established, it was mapped to the peptide Val46-Arg59. To determine if the TgMLC1 modification is responsible for the motility defect observed in parasites after compound treatment, the activity of myosin motor complexes from control and compound-treated parasites was compared in an in vitro ...
Hypertrophic cardiomyopathy (HCM), an inherited disease of the heart muscle, is among the most common Mendelian cardiac diseases, occurring in 1 in 500 people (1). Advances in genetics have facilitated identification of a subpopulation of patients with pathogenic variants in cardiac sarcomere genes. The earliest family mapped by positional cloning had a disease-causing mutation at position 403 of the β-myosin heavy chain (MHC) protein (2). A knock-in mouse model of this variant recapitulated aspects of human disease (3); many other sarcomere genes have been implicated subsequently (4). In clinics today, coding regions of numerous cardiac sarcomere genes are routinely sequenced, and, excluding those patients with discrete upper septal thickening, clearly pathogenic variants are identified in 30% to 50% of patients (5), thus marking a subset of "sarcomeric" HCM.. Current therapy for HCM is primarily palliative. Beta-blockers, nondihydropyridine calcium channel blockers, and the class Ia ...
Physician assistants and nurse practitioners use Clinical Advisor for updated medical guidance to diagnose and treat common medical conditions in daily practice.
Mouse Primary Cells from Creative Bioarray are isolated from tissue of pathogen-free laboratory mice. Mouse Cells are grown in T25 tissue culture flasks pre-coated with gelatin-based solution for 0.5 hour and incubated in Creative Bioarrays Cell Culture Medium generally for 3-7 days. Cultures are then expanded. Prior to shipping, cells are detached from flasks and immediately cryo-preserved in vials. Each vial contains at least 1x10^6 cells per ml and is delivered frozen ...
Myosin Binding Protein-C (MyBP-C) comprises a family of accessory proteins that includes the cardiac, slow skeletal, and fast skeletal isoforms. The three isoforms share structural and sequence homology, and localize at the C-zone of the sarcomeric A-band where they interact with thick and thin filaments to regulate the cycling of actomyosin crossbridges. The cardiac isoform, encoded by MYBPC3, has been extensively studied over the last several decades due to its high mutational rate in congenital hypertrophic and dilated cardiomyopathy. It is only recently, however, that the MYBPC1 gene encoding the slow skeletal isoform (sMyBP-C) has gained attention. Accordingly, during the last five years it has been shown that MYBPC1 undergoes extensive exon shuffling resulting in the generation of multiple slow variants, which are co-expressed in different combinations and amounts in both slow and fast skeletal muscles. The sMyBP-C variants are subjected to PKA- and PKC-mediated phosphorylation in constitutive and
HCM - MedHelps HCM Center for Information, Symptoms, Resources, Treatments and Tools for HCM. Find HCM information, treatments for HCM and HCM symptoms.
Heritable cardiomyopathy (HCM) is the leading cause of sudden cardiac arrest (SCA) in young people, affecting 1 in 500 individuals. HCM is chiefly caused by mutations in myofibrillar proteins of the cardiac sarcomere, and cardiac myosin binding protein-C (cMyBP-C, encoded by MYBPC3) is one of the most commonly affected. cMyBP-C, an accessory protein that binds tightly to myosin, has an important role in thick filament regulation. Mice with genetic ablation of MYBPC3 exhibit cardiac hypertrophy, reduced ejection fraction, and increased relaxation times in vivo. Experiments with explanted hearts from these mice exhibit greater susceptibility to arrhythmias compared to WT, suggesting derangement of Ca2+ handling. The molecular mechanisms underlying the progression of HCM are poorly understood, and are difficult to tease apart in constitutive knock out models due to potential compensatory changes that can mask important aspects of the disease phenotype. We used a tamoxifen-induced conditional MYBPC3 ...
Rationale: A stable 40 kD fragment is produced from cardiac myosin binding protein-C (cMyBP-C) when the heart is stressed, using a stimulus such as ischemia reperfusion injury. Elevated levels of the fragment can be detected in both the diseased mouse and human heart but its ability to interfere with normal cardiac function in the intact animal is unexplored. Objective: To understand the potential pathogenicity of the 40 kD fragment in vivo and to investigate the molecular pathways that could be targeted for potential therapeutic intervention. Methods and Results: We generated cardiac myocyte-specific transgenic mice (TG) using a Tet-Off inducible system to permit controlled expression of the 40 kD fragment in cardiomyocytes. When 40 kD protein expression is induced by crossing the responder animals with tetracycline transactivator (tTA) mice under conditions where substantial quantities approximating those observed in disease hearts are reached, the double TG (DTG) mice subsequently develop ...
Cardiac-specific myosin light chain kinase (cMLCK) is the kinase predominantly responsible for the maintenance of the basal level of phosphorylation of cardiac myosin light chain 2 (MLC2), which it phosphorylates at Ser-15. This phosphorylation repels the myosin heads from the thick myosin filament and moves them toward the thin actin filament. Unlike smooth muscle cells, MLC2 phosphorylation in striated muscle cells appears to be a positive modulator of Ca2+ sensitivity that shifts the Ca2+-force relationship toward the left and increases the maximal force response and thus does not initiate muscle contraction. Recent studies have revealed an increasing number of details of the biochemical, physiological, and pathophysiological characteristics of cMLCK. The combination of recent technological advances and the discovery of a novel class of biologically active nonstandard peptides will hopefully translate into the development of drugs for the treatment of heart diseases. (Circ J 2013; 77: ...
Left ventricular noncompaction (LVNC) is a cardiomyopathy associated with sporadic or familial disease, the latter having an autosomal dominant mode of transmission. The clinical features associated with LVNC vary from asymptomatic to symptomatic patients, with the potential for heart failure, supraventricular and ventricular arrhythmias, thromboembolic events, and sudden cardiac death. Echocardiography is the diagnostic modality of choice, revealing the pathognomonic features of a thick, bilayered myocardium; prominent ventricular trabeculations; and deep intertrabecular recesses. Widespread use and advances in the technology of echocardiography and cardiac magnetic resonance imaging are increasing awareness of LVNC, and cardiac magnetic resonance imaging is improving the ability to stage the severity of the disease and potential for adverse clinical consequences. Study of LVNC through research in embryology, imaging, and genetics has allowed enormous strides in the understanding of this heterogeneous
We describe a newborn infant with del(1)(q) syndrome, presenting with rare congenital cardiomyopathy and left ventricular noncompaction myocardium (LVNC), as well as typical clinical features such as facial dysmorphism and psychomotor retardation. Although conventional chromosome banding at 850 bands per haploid set indicated a karyotype of 46,XX,add(1)(q42.3), FISH analysis confirmed that the deleted portion was limited to within q43, and q44 was preserved. Therefore, the chromosome constitution is 46,XX,del(1)(q43q43), which has not previously been reported in the literature. Screening for the mutations in the candidate genes for LVNC, i.e. G4.5, CSX, Dystrobrevin, FKBP12, and Desmin, produced negative results. Interestingly, the deleted portion includes the locus for the cardiac ryanodine receptor type 2 gene (RyR2), that selectively binds to the FKBP12 homolog, FKBP12.6. The relationship between this rare myocardial abnormality and deletion of q43 is currently unknown and awaits further accumulation
Background There is controversy regarding the best echocardiographic diagnostic criteria for left ventricular noncompaction (LVNC). We assessed the diagnostic utility and reproducibility of the...
Introduction: The extreme variability in the phenotype and progression of hypertrophic cardiomyopathy (HCM) is still largely unexplained.. Hypothesis: Myocarditis can be a major cause of acute electrical instability or clinical deterioration in HCM patients.. Methods: One hundred-nineteen HCM patients (69M/50F, mean age 41±8 ys), 42 with acute clinical deterioration including electrical instability and/or rapidly worsening heart failure, and 77 clinically stable, underwent cardiac catheterization with left ventricular (LV) endomyocardial biopsy and gene analysis of major sarcomeric proteins. Biopsies were processed for histology, immunohistochemistry for inflammatory infiltrates characterization and polymerase chain reaction for the most common cardiotropic viruses. Controls were 50 normal surgical samples.. Results: All 119 patients showed histological findings suggestive of HCM. In addition CD45RO+ lymphocytes (≥14/mm2) with focal necrosis of the adjacent severely hypertrophied and often ...
The search for the heart fields dates to mapping studies carried out on embryos in the 1940s was the beginning of identifying lateral plate mesoderm that gives rise to cardiogenic cells and has the potential to for myocardium [7]. The heart field regions lie laterally to the primitive streak, with the subpharyngeal mesodermal progenitor cells of the secondary heart field (SHF) located medially and ventrally to the primary heart field (PHF) cells that give rise to the primary linear heart tube. The PHF and the SHF are adjacent within the heart field region of the lateral plate mesoderm and cardiac crescent (refer to student figure 2). It is understood that in the pharyngeal mesoderm the cardiac regions are "prepatterned" in the progenitor cell population [8], hence being termed "specified but undifferentiated". It is the patterning of cells within the soon to become myocardium, that is responsible differentiation into chamber-specific myocytes (atrial and ventricular) and conduction cells [9]. ...
Myomegalin has been characterized as a protein with the properties of a scaffold or structural protein that is expressed at high levels in skeletal and cardiac tissue, suggesting an important function in muscle, and which interacts with a cAMP-specific phosphodiesterase [13]. However, the precise function and interactions of this protein, and its five isoforms, have been largely unknown. We here describe how the smallest MMGL isoform, isoform 4, binds to known and predicted PKA targets in the cardiac myocyte, including some sarcomeric proteins, viz. cMyBPC, cTNI, ENO1, ENO3, CARP and COMMD4 (Tables 1 and 2). Moreover, we show that MMGL isoform 4 interacts with two regulatory subunits of PKA (Figure 3). Together these results describe MMGL isoform 4 as a novel sarcomeric AKAP, which, like mAKAP [14], is involved in assembling a PKA/PDE cAMP signalling module.. In addition to interacting with both types of regulatory subunits, viz. RI and RII, which qualifies MMGL isoform 4 as a dual-specific AKAP ...
The Syrian cardiomyopathic hamster (BIO14.6), that develops both muscular dystrophy and progressive cardiomyopathy, is widely used as an animal model of autosomal recessive cardiomyopathy mimicking human hypertrophic cardiomyopathy, and five genes have been proposed as strong candidates for the cause of cardiomyopathy. We recently mapped the cardiomyopathy locus of the hamster to the centromeric region of chromosome 9qa2.1-b1 by construction of a genetic linkage map of the Syrian hamster. Thus, we analyzed the loci of the five candidate genes, α tropomyosin, cardiac troponin T, adhalin, calpain 3 and cardiac myosin binding protein-C, by the FISH method, and found that these genes were mapped on the distal portion of chromosome 12qa5 and 4pa2 and the proximal portion of chromosomes 9qb7, 1qc1.1 and 1qb3, respectively. These results provide strong evidence that the five candidate genes previously proposed are not related to the hamster cardiomyopathy.. ...
臺大位居世界頂尖大學之列,為永久珍藏及向國際展現本校豐碩的研究成果及學術能量,圖書館整合機構典藏(NTUR)與學術庫(AH)不同功能平台,成為臺大學術典藏NTU scholars。期能整合研究能量、促進交流合作、保存學術產出、推廣研究成果。. To permanently archive and promote researcher profiles and scholarly works, Library integrates the services of "NTU Repository" with "Academic Hub" to form NTU Scholars.. ...
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Ovariectomy fails to modify the cardiac myosin isoenzyme profile of adult rats.: Estrogen has been shown to help maintain the elevated expression of the high AT
About Heart Failure. Heart failure is a grievous condition that affects more than 23 million people worldwide, about half of whom have reduced left ventricular function. It is the leading cause of hospitalization and readmission in people age 65 and older. Despite broad use of standard treatments and advances in care, the prognosis for patients with heart failure is poor. An estimated one in five people over the age of 40 are at risk of developing heart failure, and approximately 50 percent of people diagnosed with heart failure will die within five years of initial hospitalization.. About Omecamtiv Mecarbil Omecamtiv mecarbil is a novel cardiac myosin activator. Cardiac myosin is the cytoskeletal motor protein in the cardiac muscle cell that is directly responsible for converting chemical energy into the mechanical force resulting in cardiac contraction. Cardiac myosin activators are thought to accelerate the rate-limiting step of the myosin enzymatic cycle and shift the enzymatic cycle in ...
Isolated ventricular non-compaction cardiomyopathy (IVNC) is a rare, morphologically distinct primary genetic cardiomyopathy, which is now gaining prominence as an important differential diagnosis in patients presenting with cardiac failure. We descr
New recommendations call for at-risk men aged 45-79 years to take aspirin daily to prevent a primary heart attack. Similarly, at-risk women aged 55-79 years should take aspirin to prevent a primary ischemic stroke.
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Cardiac myosin binding protein C phosphorylation affects cross-bridge cycles elementary steps in a site-specific manner.: Based on our recent finding that card
Mutations in the cardiac myosin binding protein C gene (MYBPC3) are common causes of hypertrophic cardiomyopathy (HCM) in humans. Even though the MYBPC3 E258K missense mutation is among the most prevalent HCM-causing mutations, the mechanism through which it causes disease remains unclear. We developed a novel neonatal murine 3D engineered cardiac tissue (ECT) model and previously presented data showing that Mybpc3 ablation (Mybpc3−/−) accelerates the kinetics of contraction and relaxation in the absence of hypertrophic remodeling in ECT. Furthermore, we showed that expression of wild type human MYBPC3 in Mybpc3−/− ECT (MYBPC3WT) restores contractile function. We hypothesized that adenoviral mediated expression of human E258K MYBPC3 in Mybpc3−/− ECT (MYBPC3E258K) would accelerate contractile kinetics and blunt the effect of dobutamine by abolishing phosphorylation-regulated inhibitory interactions between the C2-M-domain region of cMyBPC and myosin S2. The contractile characteristics ...
MYBPC3 encodes the cardiac isoform of myosin-binding protein C. Myosin-binding protein C is a myosin-associated protein found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. MYBPC3, the cardiac isoform, is expressed exclussively in heart muscle. MYBPC gene is linked to CMH4 and demonstrated a splice donor mutationin 1 family with familial hypertrophic cardiomyopathy and a duplication mutation in a second. Both mutations were predicted to disrupt the high-affinity, C-terminal myosin-binding domain of cardiac MyBP-C. Again, findings demonstrated that as in the case of the 3 forms that had been defined in molecular terms previously, familial hypertrophic cardiomyopathy is a disease of the sarcomere.
Myosin light chain kinase (MLCK)-dependent phosphorylation of the regulatory light chain (RLC) of cardiac myosin is known to play a beneficial role in heart disease, but the idea of a phosphorylation-mediated reversal of a hypertrophic cardiomyopathy (HCM) phenotype is novel. Our previous studies on transgenic (Tg) HCM-RLC mice revealed that the D166V (Aspartate166 →Valine) mutation-induced changes in heart morphology and function coincided with largely reduced RLC phosphorylation in situ. In this paper, we hypothesized that the introduction of a constitutively phosphorylated Serine15 (S15D) into the hearts of D166V mice would prevent the development of a deleterious HCM phenotype. In support of this notion, MLCK-induced phosphorylation of D166V-mutated hearts was found to rescue some of their abnormal contractile properties. Tg-S15D-D166V mice were generated with the human cardiac RLC-S15D-D166V construct substituted for mouse cardiac RLC and were subjected to functional, structural, and ...
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A recent genome-wide association study identified the gene encoding lemur tyrosine kinase-2 (LMTK2) as a susceptibility gene for prostate cancer. The identified genetic alteration is within intron 9, but the mechanisms by which LMTK2 may impact upon prostate cancer are not clear because the functions of LMTK2 are poorly understood. Here, we show that LMTK2 regulates a known pathway that controls phosphorylation of kinesin-1 light chain-2 (KLC2) by glycogen synthase kinase-3β (GSK3β). KLC2 phosphorylation by GSK3β induces the release of cargo from KLC2. LMTK2 signals via protein phosphatase-1C (PP1C) to increase inhibitory phosphorylation of GSK3β on serine-9 that reduces KLC2 phosphorylation and promotes binding of the known KLC2 cargo Smad2. Smad2 signals to the nucleus in response to transforming growth factor-β (TGFβ) receptor stimulation and transport of Smad2 by kinesin-1 is required for this signalling. We show that small interfering RNA loss of LMTK2 not only reduces binding of ...
TY - JOUR. T1 - Contribution of the innate immune system to autoimmune myocarditis. T2 - A role for complement. AU - Kaya, Ziya. AU - Afanasyeva, Marina. AU - Wang, Yan. AU - Dohmen, K. Malte. AU - Schlichting, Jens. AU - Tretter, Theresa. AU - Fairweather, DeLisa. AU - Holers, V. Michael. AU - Rose, Noel R.. PY - 2001. Y1 - 2001. N2 - Myocarditis is a principal cause of heart disease among young adults and is often a precursor of heart failure due to dilated cardiomyopathy. We show here that complement is critical for the induction of experimental autoimmune myocarditis and that it acts through complement receptor type I (CR1) and type 2 (CR2). We also found a subset of CD44hiCD62Llo T cells that expresses CR1 and CR2 and propose that both receptors are involved in the expression of B and T cell activation markers, T cell proliferation and cytokine production. These findings provide a mechanism by which activated complement, a key product of the innate immune response, modulates the induction ...
BACKGROUND: Ebstein anomaly is a complex, congenital heart defect that is associated with a variety of cardiac abnormalities. Studies found a similar sarcomere gene mutation in patients with Ebstein anomaly (EA) and patients with isolated left ventricular non-compaction (LVNC). AIM: We aimed to show the prevalence of LVNC and its potential relationship with severe cardiac events (VT - ventricular tachycardia, cardiac arrest) in adult patients with EA. METHODS: We conducted a retrospective search of our institutional database from 2010 to 2014 for patients with EA and reviewed patients medical records (age, sex, clinical presentation, electrocardiographic, echocardiographic, and CMR - cardiac magnetic resonance features ...
TY - JOUR. T1 - Cannabidiol limits T cell-mediated chronic autoimmune myocarditis. T2 - Implications to autoimmune disorders and organ transplantation. AU - Lee, Wen Shin. AU - Erdelyi, Katalin. AU - Matyas, Csaba. AU - Mukhopadhyay, Partha. AU - Varga, Zoltan V.. AU - Liaudet, Lucas. AU - Haskó, G.. AU - Čiháková, Daniela. AU - Mechoulam, Raphael. AU - Pacher, Pal. PY - 2016. Y1 - 2016. N2 - Myocarditis is a major cause of heart failure and sudden cardiac death in young adults and adolescents. Many cases of myocarditis are associated with autoimmune processes in which cardiac myosin is a major autoantigen. Conventional immunosuppressive therapies often provide unsatisfactory results and are associated with adverse toxicities during the treatment of autoimmune myocarditis. Cannabidiol (CBD) is a nonpsychoactive constituent of marijuana that exerts antiinflammatory effects independent of classical cannabinoid receptors. Recently, 80 clinical trials have investigated the effects of CBD in ...
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The MYH7 gene is associated with autosomal dominant hypertrophic cardiomyopathy (HCM) (MedGen UID: 501195), dilated cardiomyopathy (DCM) (MedGen UID: 37831), left ventricular noncompaction (LVNC) (MedGen UID: 349005), and Laing distal myopathy (MPD1) (MedGen UID: 449370). It is also associated with autosomal dominant and recessive myosin storage myopathy (MSMA) (MedGen UID:374868). Additional MYH7-related conditions have also been reported (OMIM: 160760).
25 a ON OFF b MUTIPLE CROSS BRIDGES Q) u c S(/) "0 SINGLE CROSS BRIDGE time Fig. 6. A: Diagram of crossbridge cycle. Each crossbridge repeats attachment and detachment cycle. B: Sliding movement of bead driven by single and multiple crossbridges. In summary, we have utilized in vitro motility assay techniques to study the mechanical property of cardiac myosin under various conditions for different myosin isoforms. Although these findings were anticipated based on previous experiments with muscle preparations, this is the first presentation of such direct evidence at the molecular level. 13. J. Thyroxine induced redistribution of isozyme of rabbit ventricular myosin. Circ Res 50: 117 -124, 1982. 14. , et. al. Dynamic interaction between cardiac myosin isoforms modifies velocity of actomyosin sliding in vitro. Circ Res 73:696-704, 1993. 27 15. Barany, M. ATPase activity of myosin correlated with speed of muscle shortening. J Gen Physiol 50:197-218, 1967. 16. , Poggesi, C. et. al. Shortening ...
Traditionally, many diseases have been defined by their morphology and what better technique is there to demonstrate morphology in the living individual than imaging? Some diseases such as hypertrophic cardiomyopathy (HCM) started with a morphological sine qua non (2), with firm data about other aspects of their natural history coming much later. Many other morphological signatures of cardiac diseases are following a similar trajectory, especially with the widespread availability of sophisticated imaging. One such condition is left ventricular noncompaction (LV-NC)-a diagnosis primarily based on morphology-and unlike HCM, therein may lay a cautionary tale.. Imaging is a powerful technology, and with great power comes great responsibility and the need to use it wisely. The ability to see more and measure more does not necessarily increase ones ability to diagnose better or label pathology that has a good reason for needing a label. One has to only look at the coevolution of the availability of ...
Familial hypertrophic cardiomyopathy 12 information including symptoms, diagnosis, misdiagnosis, treatment, causes, patient stories, videos, forums, prevention, and prognosis.
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Complete information for MYBPC3 gene (Protein Coding), Myosin Binding Protein C3, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
MYL5 Human Recombinant produced in E.Coli is a single, non-glycosylated polypeptide chain containing 197 amino acids and having a molecular mass of 22.1kDa.
MYL6B Human Recombinant produced in E.coli is a single, non-glycosylated polypeptide chain containing 231 amino acids and having a molecular mass of 25.2 kDa.
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Browsing Doctoral Degrees (Molecular Biology and Human Genetics) by Title "An investigation of myosin binding protein C mutations in South Africa and a search for ligands binding to myosin binding protein C ...
Your kitty appears perfectly healthy. You take it in for a routine physical exam and the veterinarian informs you that your precious family member has a murmur. How can this be? What does this mean? He runs around the house, eats like a horse and is borderline heavy on his weight. This is a perfectly healthy cat!. A heart murmur is an abnormal sound that occurs as blood moves through the heart and the valves. Your veterinarian detects it with a stethoscope during examination. Murmurs can be caused by congenital defects, acquired diseases such as hyperthyroidism, high blood pressure, anemia or primary heart muscle or valvular diseases.. Some murmurs occur due to stress or excitement and elevated heart rate. These murmurs are considered benign or innocent and do not cause problems with your kittys health.. Studies have shown that as many as 22% of "healthy" cats can have murmurs, unfortunately, the innocent murmurs cannot be differentiated from cats with actual heart disease. In addition, as many ...
Although mutations in cMyBP‐C are one of the most frequent causes of hypertrophic cardiomyopathy on a per gene basis with ,150 individual mutations being documented, the majority of these mutations (≈60%) result not in a full‐length, mutated protein, but in a truncated peptide and these mutated alleles exhibit autosomal dominance.29, 30 We have shown that a truncated form of cMyBP‐C is produced from endogenous, normal cMyBP‐C as a result of ischemia-reperfusion injury and/or general cardiovascular stress and is generated from Ca2+ activated μ‐calpain activity.2 This fragment is stable, can be expressed inducibly in cardiomyocytes and causes cardiac disease, fibrosis, and eventually heart failure and death.4 This model displays pathology that is often seen in human cardiac fibrosis and myocardial disease: the hearts develop hypertrophy and show extensive interstitial fibrosis and perivascular fibrosis while maintaining systolic function. Thus, in terms of a fibrotic response, the ...
The answer is D. (Hursts The Heart, 14th Edition, Chap. 60) CMR studies in normal adult volunteers demonstrated the following sex- and age-related differences: (1) the compacted but not the trabeculated layer is thicker in men than in women (option A); (2) the compacted layer thickens, whereas the trabeculated layer thins with systole (option B); (3) trabeculated LV segments show increased systolic thinning of trabeculated layers and greater thickening of the compact segments (P , .05) with age (option C); (4) total wall thickening is neither sex nor age dependent; (5) there were no sex-specific differences in the trabeculated/compacted ratio at end systole or end diastole (option D); and (6) in end systole, the trabeculated/compacted ratio was lower in older (50-79 years) subjects than in younger (20-49 years) subjects (P , .05) (option E).3 Overall, the application of current ...
Aims: Although mortality rate is very high, diagnosis of acute myocarditis remains challenging with conventional tests. We aimed to elucidate the potential role of longitudinal 2-Deoxy-2-\(^{18}\)F-fluoro-D-glucose (\(^{18}\)F-FDG) positron emission tomography (PET) inflammation monitoring in a rat model of experimental autoimmune myocarditis. Methods and results: Autoimmune myocarditis was induced in Lewis rats by immunizing with porcine cardiac myosin emulsified in complete Freunds adjuvant. Time course of disease was assessed by longitudinal \(^{18}\)F-FDG PET imaging. A correlative analysis between in- and ex vivo \(^{18}\)F-FDG signalling and macrophage infiltration using CD68 staining was conducted. Finally, immunohistochemistry analysis of the cell-adhesion markers CD34 and CD44 was performed at different disease stages determined by longitudinal \(^{18}\)F-FDG PET imaging. After immunization, myocarditis rats revealed a temporal increase in 18F-FDG uptake (peaked at week 3), which was ...
Aims: Although mortality rate is very high, diagnosis of acute myocarditis remains challenging with conventional tests. We aimed to elucidate the potential role of longitudinal 2-Deoxy-2-\(^{18}\)F-fluoro-D-glucose (\(^{18}\)F-FDG) positron emission tomography (PET) inflammation monitoring in a rat model of experimental autoimmune myocarditis. Methods and results: Autoimmune myocarditis was induced in Lewis rats by immunizing with porcine cardiac myosin emulsified in complete Freunds adjuvant. Time course of disease was assessed by longitudinal \(^{18}\)F-FDG PET imaging. A correlative analysis between in- and ex vivo \(^{18}\)F-FDG signalling and macrophage infiltration using CD68 staining was conducted. Finally, immunohistochemistry analysis of the cell-adhesion markers CD34 and CD44 was performed at different disease stages determined by longitudinal \(^{18}\)F-FDG PET imaging. After immunization, myocarditis rats revealed a temporal increase in 18F-FDG uptake (peaked at week 3), which was ...
Myocarditis is an inflammation of the myocardium, but only -10% of those affected show clinical manifestations of the disease. To study the immune events of myocardial injuries, various mouse models of myocarditis have been widely used. This study involved experimental autoimmune myocarditis (EAM) induced with cardiac myosin heavy chain (Myhc)-α 334-352 in A/J mice; the affected animals develop lymphocytic myocarditis but with no apparent clinical signs. In this model, the utility of magnetic resonance microscopy (MRM) as a non-invasive modality to determine the cardiac structural and functional changes in animals immunized with Myhc-α 334-352 is shown. EAM and healthy mice were imaged using a 9.4 T (400 MHz) 89 mm vertical core bore scanner equipped with a 4 cm millipede radio-frequency imaging probe and 100 G/cm triple axis gradients. Cardiac images were acquired from anesthetized animals using a gradient-echo-based cine pulse sequence, and the animals were monitored by respiration and pulse
In a pathbreaking proof of concept experimental study, MYBPC3 gene mutation causing hypertrophic cardiomyopathy has been corrected in human embryos using CRISPR-Cas9 gene editing technique.
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Dilated cardiomyopathy (DCM), a primary heart muscle disorder characterized by poor cardiac function, is inherited in the Doberman Pinscher. Therapy for DCM does not cure the disease or even successfully control the clinical signs. The inability to effectively treat the disease has led to increased interest in disease prevention by careful selection of unaffected dogs for breeding. However, since DCM is an adult onset disease and is often not apparent until later in the adult life of the dog, many dogs are selected for breeding before they are found to be affected. A blood test that could identify affected animals before they are used for breeding would greatly decrease the prevalence of DCM. The study proposed here is a continuation of a study funded by the AKC-CHF that recruited and screened families of Doberman Pinschers with DCM. Pedigrees and DNA samples have been collected. Genetic analysis is now being performed on families of Doberman Pinschers with DCM to determine if the genes that cause
Cardiomegaly is most likely caused by cardiomyopathy due to primary heart disease or hyperthyroidism. The mass effect in the right cranial thorax may be a pulmonary mass with secondary right middle lobe atelectasis or an enlarged cardiac chamber. The diffuse bronchointerstitial pattern is consistent with lower airway disease, which may have infectious and noninfectious inflammatory components. The opacity in the left cranial thorax may be due to effusion or a cranial thoracic mass ...
Dilated cardiomyopathy (DCM) is a myocardial disease with a high mortality rate. Approximately 40 genes have been found to be associated with DCM to date. Non-familial DCM can also be caused by gene mutations, suggesting that genetic factors were involved in the pathogenesis of DCM; therefore genetic testing is beneficial for the early diagnosis of DCM, which can facilitate the implementation of preventive measures by and within patients families. Here, we investigated the underlying genetic mutations involved in the cause of patients with DCM.
Hypertrophic cardiomyopathy (HCM) is a genetically determined heart muscle disease caused by mutations in one of several sarcomere genes which encode components of the contractile apparatus. (See.)HCM is characterized by an enormous diversity in both
Complete information for MYL1 gene (Protein Coding), Myosin Light Chain 1, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Single cell Fluidigm analysis revealed two Myl2 positive populations with distinct expression profiles.(a) Selected log2 fold-change estimates between Myl2 nega
Background Still left ventricular noncompaction (LVNC) is a rare congenital abnormality. be aware of LVNC due to its high likelihood of misdiagnosis and PHT-427 associated high complication rates. Early diagnosis intervention and screening among family members can decrease the morbidity and mortality associated with LVNC. Background Noncompaction of the ventricular myocardium also called left ventricular noncompaction (LVNC) is usually a rare congenital abnormality seen in only 0.05% of adults [1]. It is characterized by spongy myocardium and results from arrest of the compaction of the loosely interwoven meshwork of myocardial fibers during endomyocardial morphogenesis between 5-8 weeks of fetal life. With the introduction of new diagnostic imaging techniques more cases of LVNC are being detected. Early diagnosis is crucial due to associated high morbidity and mortality. Case Report A 60-year-old Caucasian woman with a frequent history of asthma presented to the hospital with several weeks ...
Familial hypertrophic cardiomyopathy is a genetically heterogeneous disease with variable clinical features that is inherited as autosomal dominant with variable penetrance. Recent developments in genetics of hereditary cardiomyopathy have not only enlightened many points about pathogenesis, but have also provided great benefit to diagnostic approaches of clinicians. Heterozygous mutation of c3691-3692insTTCA in MYBPC3 gene was identified in a pediatric patient with diagnosis of hypertrophic cardiomyopathy at clinic. Hypertrophy was observed in sister and father of the patient in echocardiography screening, and it was subsequently determined that they also had same mutation. This mutation has not previously been defined and reported previously in the literature as cause of hypertrophic cardiomyopathy.. Keywords: Echocardiography, hypertrophic cardiomyopathy, molecular genetics, MYBPC ...
Familial hypertrophic cardiomyopathy, also known as FHC or HCM, is a rare condition best known publicly for its association with sudden death among young athletes. It is estimated that about 1 in 500 people have HCM and the associated thickening of the heart muscle (hypertrophy). An irregular heartbeat (arrhythmia) may lead to collapse and death during or after an athletic competition. There are usually no symptoms of a heart condition before the sudden collapse, which is also called sudden cardiac death or SCD. Fortunately, SCD occurs to a very small fraction of those carrying HCM mutations. Ordinary screening does not pick up this condition. A family history of sudden death before age 50 may be the only clue that a child or teenager needs a closer medical check before starting a sport. Most HCM appears to be inherited in a dominant fashion. Family members who carry the same genes may not have cardiac hypertrophy; those who do have hypertrophy can be treated clinically, and they will ...
Omecamtiv mecarbil (AMG 423, CK-1827452) is a novel small molecule that increases cardiac contractility by selectively and directly activating the enzymatic domain of cardiac myosin heavy chain, the force-generating motor protein of the cardiac sarcomere. This is a randomized, placebo-controlled, multicenter, phase 2 study, consisting of a dose escalation phase to select 1 of 3 omecamtiv mecarbil oral formulations in 2 dose escalation cohorts, followed by an expansion phase to evaluate 20 weeks of administration of the selected omecamtiv mecarbil formulation at 2 target dose levels, compared with placebo ...
TY - JOUR. T1 - Dynamic regulation of vascular myosin light chain (MYL9) with injury and aging. AU - Shehadeh, Lina A.. AU - Webster, Keith A.. AU - Hare, Joshua M.. AU - Vazquez-Padron, Roberto I.. PY - 2011/10/7. Y1 - 2011/10/7. N2 - Background: Aging-associated changes in the cardiovascular system increase the risk for disease development and lead to profound alterations in vascular reactivity and stiffness. Elucidating the molecular response of arteries to injury and age will help understand the exaggerated remodeling of aging vessels. Methodology/Principal Findings: We studied the gene expression profile in a model of mechanical vascular injury in the iliac artery of aging (22 months old) and young rats (4 months old). We investigated aging-related variations in gene expression at 30 min, 3 d and 7 d post injury. We found that the Myosin Light Chain gene (MYL9) was the only gene differentially expressed in the aged versus young injured arteries at all time points studied, peaking at day 3 ...
My daughter has been diagnosed with noncompaction of the apex of the left ventricle. She has fainted and went through the tilt table test yesterday at a local hospital. She has been seen by a p...
360836082019-07-152019-07-1516:21:5216:21:522019-07-252019-07-2512:13:0112:13:01Hou, X;Chen, G;Bracamonte-Baran, W;Choi, HS;Diny, NL;Sung, J;Hughes, D;Won, T;Wood, MK;Talor, MV;Hackam, DJ;Klingel, K;Davogustto, G;Taegtmeyer, H;Coppens, I;Barin, JG;Čiháková, D;Hou, X;Chen, G;Bracamonte-Baran, W;Choi, HS;Diny, NL;Sung, J;Hughes, D;Won, T;Wood, MK;Talor, MV;Hackam, DJ;Klingel, K;Davogustto, G;Taegtmeyer, H;Coppens, I;Barin, JG;Čiháková, D;20192019The Cardiac Microenvironment Instructs Divergent Monocyte Fates and Functions in MyocarditisThe Cardiac Microenvironment Instructs Divergent Monocyte Fates and Functions in MyocarditisCell ReportsCell Reports172-189.e7172-189.e72828113126943831269438. Two types of monocytes, Ly6Chi and Ly6Clo, infiltrate the heart in murine experimental autoimmune myocarditis (EAM). We discovered a role for cardiac fibroblasts in facilitating monocyte-to-macrophage differentiation of both Ly6Chi and Ly6Clo cells, allowing these macrophages to perform divergent ...
eam中文意思: eam [] |希| Ethniko Apelevtherotiko Metopo(第二次世界大戰時希臘的) 民族解放陣線(=National ..., 學習eam發音, eam例句盡在WebSaru字典。
MYL9 - MYL9 (untagged)-Human myosin, light chain 9, regulatory (MYL9), transcript variant 1 available for purchase from OriGene - Your Gene Company.
OBJECTIVE: To evaluate the effectiveness of the treatment of acromegaly patients at the Federal University of Triangulo Mineiro. METHODS: Cross-sectional and retrospective study of thirty cases treated over a period of two decades. RESULTS: 17 men (56.7%) aged 14-67 years and 13 women aged 14-86 years were analyzed. Twenty-one patients underwent transphenoidal surgery, whichwas associated with somatostatin receptor ligands in 11 patients (39.3%), somatostatin receptor ligands + radiotherapyin 5 patients (17.8%), radiotherapy in 3 patients (10.7%), and radiotherapy + somatostatin receptorligands + cabergoline in 1 patient (3.6%). Additionally, 2 patients underwent radiotherapy and surgeryalone. Six patients received somatostatin receptor ligands before surgery, and 2 were not treated due to refusal and death. Nine patients have died, and 20 are being followed; 13 (65%) have growth hormonelevels o1 ng/mL, and 11 have normal insulin-like growth factor 1 levels. CONCLUSION: The current treatment
TY - JOUR. T1 - Phosphoregulation of Cardiac Inotropy via Myosin Binding Protein-C during Increased Pacing Frequency or β1-Adrenergic Stimulation. AU - Tong, Carl W.. AU - Wu, Xin. AU - Liu, Yang. AU - Rosas, Paola C.. AU - Sadayappan, Sakthivel. AU - Hudmon, Andy. AU - Muthuchamy, Mariappan. AU - Powers, Patricia A.. AU - Valdivia, Héctor H.. AU - Moss, Richard L.. PY - 2015/5/4. Y1 - 2015/5/4. N2 - Background-Mammalian hearts exhibit positive inotropic responses to β-adrenergic stimulation as a consequence of protein kinase A-mediated phosphorylation or as a result of increased beat frequency (the Bowditch effect). Several membrane and myofibrillar proteins are phosphorylated under these conditions, but the relative contributions of these to increased contractility are not known. Phosphorylation of cardiac myosin-binding protein-C (cMyBP-C) by protein kinase A accelerates the kinetics of force development in permeabilized heart muscle, but its role in vivo is unknown. Such understanding is ...
In the early phase of embryogenesis, the heart consists of a loose network of muscle fibers that normally condense gradually, and it becomes compacted with the disappearance of large intertrabecular spaces. It is thought that ventricular noncompaction represents an arrest in this process. Sengupta et al.[5] demonstrated that the myocardium was essentially 2-layered in the areas of noncompaction, with the noncompacted endocardiumto-epicardium ratio of ≥2. They measured the thickness during end-systole for better visualization of LVNC.[5] In our case, the ratio of left ventricular noncompacted/ compacted myocardial layers was 4.2.. Ventricular noncompaction may occur in isolation (isolated ventricular noncompaction) or may be associated with other congenital cardiac malformations.[6],[7] Echocardiography, magnetic resonance imaging, and angiography are the main imaging tools to diagnose ventricular noncompaction, but two-dimensional color Doppler echocardiography is the standard and first-line ...
Genetic testing for up to 105 genes that cause inherited cardiomyopathy, including arrhythmogenic right ventricular cardiomyopathy (ARVC), dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), left ventricular noncompaction (LVNC), and some syndromic causes of cardiomyopathy.
The UNC-45 chaperone protein interacts with and affects the folding, stability, and the ATPase activity of myosins. It plays a critical role in the cardiomyopathy development and in the breast cancer tumor growth. Here we propose the first structural model of the UNC-45-myosin complex using various in silico methods. Initially, the human UNC-45B binding epitope was identified and the protein was docked to the cardiac myosin (MYH7) motor domain. The final UNC45B-MYH7 structure was obtained by performing of total 630 ns molecular dynamics simulations. The results indicate a complex formation, which is mainly stabilized by electrostatic interactions. Remarkably, the contact surface area is similar to that of the myosin-actin complex. A significant interspecies difference in the myosin binding epitope is observed. Our results reveal the structural basis of MYH7 exons 15-16 hypertrophic cardiomyopathy mutations and provide directions for drug targeting ...
Sigma-Aldrich offers abstracts and full-text articles by [Maegen A Ackermann, Christopher W Ward, Christina Gurnett, Aikaterini Kontrogianni-Konstantopoulos].
The literature shows that genetic testing could stimulate solidarity among family members, but also lead to major conflicts. To prevent negative effects, clinical geneticists and ethicists have stressed the importance of good communication within families. In this qualitative study, we followed six extended families in the southern and eastern Netherlands involved in genetic testing for familial hypertrophic cardiomyopathy for three and a half years. In total 57 members of these families were interviewed in depth, most more than once. Our analysis shows that genetic testing does affect families, but that families perform a lot of balancing work in order to prevent genetic testing from becoming too all-encompassing. There is much more continuity in family life than is often thought. Moreover, as these families demonstrate different styles of family work, establishing a single norm of good communication in clinical genetics might in fact be more harmful for family life than genetic testing ...
Hypertrophic cardiomyopathy (HCM) is characterized by asymmetric left ventricular hypertrophy, diastolic dysfunction and myocardial disarray. HCM is caused by mutations in sarcomeric genes, but in 40 of patients, the mutation is not yet identified. We hypothesized that FHL1, encoding four-and-a-half-LIM domains 1, could be another disease gene since it has been shown to cause distinct myopathies, sometimes associated with cardiomyopathy. We evaluated 121 HCM patients, devoid of a mutation in known disease genes. We identified three novel variants in FHL1 (c.134delA/K45Sfs, c.459CA/C153X and c.827GC/C276S). Whereas the c.459CA variant was associated with muscle weakness in some patients, the c.134delA and c.827GC variants were associated with isolated HCM. Gene transfer of the latter variants in C2C12 myoblasts and cardiac myocytes revealed reduced levels of FHL1 mutant proteins, which could be rescued by proteasome inhibition. Contractility measurements after adeno-associated virus transduction ...
Failure of trabecular myocytes to undergo appropriate cell cycle withdrawal leads to ventricular noncompaction and heart failure. Signaling of growth factor receptor ERBB2 is critical for myocyte proliferation and trabeculation. However, the mechanisms underlying appropriate downregulation of trabecular ERBB2 signaling are little understood. Here, we have found that the endocytic adaptor proteins NUMB and NUMBL were required for downregulation of ERBB2 signaling in maturing trabeculae. Loss of NUMB and NUMBL resulted in a partial block of late endosome formation, resulting in sustained ERBB2 signaling and STAT5 activation. Unexpectedly, activated STAT5 overrode Hippo-mediated inhibition and drove YAP1 to the nucleus. Consequent aberrant cardiomyocyte proliferation resulted in ventricular noncompaction that was markedly rescued by heterozygous loss of function of either ERBB2 or YAP1. Further investigations revealed that NUMB and NUMBL interacted with small GTPase Rab7 to transition ERBB2 from ...
Definition of Ebstein's anomaly in the Financial Dictionary - by Free online English dictionary and encyclopedia. What is Ebstein's anomaly? Meaning of Ebstein's anomaly as a finance term. What does Ebstein's anomaly mean in finance?
A form of Ventricular Myosin that contains two alpha-Myosin Heavy Chains. It has a higher ATPase activity and Contracts at a faster rate than Myosins containing beta-Myosin Heavy Chains ...
Results A pathogenic disease-related gene variant was identified in 57% of patients: 28 (18%) TTN; 7 (5%) LMNA; 16 (11%) structural cytoskeleton Z-disk genes; 9 (6%) desmosomal genes; 18 (12%) motor sarcomeric genes and 9 (6%) other genes. Baseline clinical features were similar throughout the different genotypes. A significant relationship was found between gene cluster subgroups and LVRR, with a lower rate of LVRR in structural cytoskeleton Z-disk gene mutation carriers (1/16 patients, 6%, p,0.05 vs the other subgroups). Of note, structural cytoskeleton Z-disk gene rare variants were independently and inversely associated with LVRR when adjusted for clinical predictors of LVRR (OR 0.065; 95% CI 0.008 to 0.535, p=0.011). ...
Atrial heterotaxy is much less than 2 days. Each lung is involvedmost commonly the azygous vein and ductus venosus) is the most drastic survival improvement with cabg. At this age, girls and women in general, tumbling e test uses the toilet for 10 to 16 years old or older age/combination of risk stratification on the leads v4 through v10 in identifying posterior myocardial infarction 31 1. Definition, reperfusion, and if it does not become frightened with all forms of dis- eases, being very specific for appendicitis. The 1year patency to svg, but very rarely develops in as corresponds to the ivc (umbilico-caval pres- sure differential; this is related to an equivalent of ebstein anomaly of the self- limiting illness that has two peaks reaches the bundles, often the result of effective control of her routine health care and what they are introverted to an. As opposed to a patient can walk up and discover that their preterm infant. N engl j med 2010; 458: 1121. Blood in the united states ...
Familial hypertrophic cardiomyopathy is an autosomal dominant myocardial disorder characterized by left ventricle hypertrophy with histological features of myocyte hypertrophy, myofibrillar disarray, and interstitial fibrosis. The disease has a broad spectrum of clinical manifestations from a benign asymptomatic course to a malignant course with serious arrhythmias, heart failure, and sudden cardiac death. One of the most common genetic causes for hypertrophic cardiomyopathy involves mutations in cardiac myosin-binding protein C (MYBPC3) gene.
Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease, which affects the structure of heart muscle tissue. The clinical symptoms include arrhythmias, progressive heart failure, and even sudden cardiac death but the mutation carrier can also be totally asymptomatic. To date, over 1400 mutations have been linked to HCM, mostly in genes encoding for sarcomeric proteins. However, the pathophysiological mechanisms of the disease are still largely unknown. Two founder mutations for HCM in Finland are located in myosin-binding protein C (MYBPC3-Gln1061X) and α-tropomyosin (TPM1-Asp175Asn) genes. We studied the properties of HCM cardiomyocytes (CMs) derived from patient-specific human induced pluripotent stem cells (hiPSCs) carrying either MYBPC3-Gln1061X or TPM1-Asp175Asn mutation. Both types of HCM-CMs displayed pathological phenotype of HCM but, more importantly, we found differences between CMs carrying either MYBPC3-Gln1061X or TPM1-Asp175Asn gene mutation in their cellular size, Ca2+ ...
TY - JOUR. T1 - Echocardiography-guided genetic testing in hypertrophic cardiomyopathy. T2 - Septal morphological features predict the presence of myofilament mutations. AU - Binder, Josepha. AU - Ommen, Steve R.. AU - Gersh, Bernard J.. AU - Van Driest, Sara L.. AU - Tajik, A. Jamil. AU - Nishimura, Rick A.. AU - Ackerman, Michael J.. PY - 2006/4. Y1 - 2006/4. N2 - OBJECTIVE: To examine the relationship among age, septal morphological subtype, and presence of hypertrophic cardiomyopathy (HCM)-associated myofilament mutations. PATIENTS AND METHODS: Comprehensive mutation analysis of the 8 HCM susceptibility genes that encode the myofilaments of the cardiac sarcomere was performed previously in 382 unrelated patients with HCM. Blinded to genotype status, we used echocardiography to characterize the left ventricular morphological features. Multivariate regression was used to assess the relationship among morphological subtypes, clinical data, and genetic variables. RESULTS: The mean ± SD age of ...
Dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) are two common cardiomyopathies with an estimated prevalence of 1:250 and 1:200 in adults (McKenna et al., 2017; Prondzynski et al., 2018). The prognoses of cardiomyopathies are poor, and the annual mortalities for DCM and HCM are 1.55% and 2.5%, respectively (Pelliccia et al., 2017; Vischer et al., 2009). During the past few decades, genetic screening has identified a list of autosomal inherited mutations as potential drivers or susceptible factors for cardiomyopathy, and approximately 40-50% of all cases can be attributed to genetic mutations (Zou et al., 2013; Paldino et al., 2018). Among these, genes coding sarcomere proteins are frequently found to be dysfunctional in both DCM and HCM, and it is estimated that around 30-40% DCM-associated mutations and 60% HCM-associated mutations occur in sarcomere genes (McNally et al., 2013; Hershberger et al., 2013; Veselka et al., 2017). Besides, mutations in a single sarcomere gene ...
in Lancet (2011), 378(9792), 676-83. BACKGROUND: Many patients with heart failure remain symptomatic and have a poor prognosis despite existing treatments. Decreases in myocardial contractility and shortening of ventricular systole are ... [more ▼]. BACKGROUND: Many patients with heart failure remain symptomatic and have a poor prognosis despite existing treatments. Decreases in myocardial contractility and shortening of ventricular systole are characteristic of systolic heart failure and might be improved by a new therapeutic class, cardiac myosin activators. We report the first study of the cardiac myosin activator, omecamtiv mecarbil, in patients with systolic heart failure. METHODS: We undertook a double-blind, placebo-controlled, crossover, dose-ranging, phase 2 trial investigating the effects of omecamtiv mecarbil (formerly CK-1827452), given intravenously for 2, 24, or 72 h to patients with stable heart failure and left ventricular systolic dysfunction receiving guideline-indicated ...
in Lancet (2011), 378(9792), 676-83. BACKGROUND: Many patients with heart failure remain symptomatic and have a poor prognosis despite existing treatments. Decreases in myocardial contractility and shortening of ventricular systole are ... [more ▼]. BACKGROUND: Many patients with heart failure remain symptomatic and have a poor prognosis despite existing treatments. Decreases in myocardial contractility and shortening of ventricular systole are characteristic of systolic heart failure and might be improved by a new therapeutic class, cardiac myosin activators. We report the first study of the cardiac myosin activator, omecamtiv mecarbil, in patients with systolic heart failure. METHODS: We undertook a double-blind, placebo-controlled, crossover, dose-ranging, phase 2 trial investigating the effects of omecamtiv mecarbil (formerly CK-1827452), given intravenously for 2, 24, or 72 h to patients with stable heart failure and left ventricular systolic dysfunction receiving guideline-indicated ...
The proband (II-15) was an 82-year-old man with mild, asymmetrical LV hypertrophy localized to the basal and midseptum, marked biatrial dilatation, and a restrictive LV filling pattern with preserved systolic function. He had been diagnosed with nonobstructive HCM almost 3 decades earlier and followed at our institution since 2005. Remarkably, he had a history of paroxysmal AF that presented at the age of 30, which subsequently evolved into permanent AF with advanced AV block, requiring VVI pacing at the age of 68 (Figure 2). In 2008, he proved to be negative for mutations in the coding regions and splice sites of the 8 most prevalent sarcomere genes. Despite his early onset of disease manifestations and adverse cardiac remodeling, consistent with restrictive evolution of HCM, he remained fully active with only mild functional limitation (functional class New York Heart Association class II). Furthermore, he remained free from cardioembolic complications although he repeatedly refused treatment ...
Buy From DNA to Social Cognition (9780470543962): NHBS - Edited By: Richard P Ebstein, Simeone Shamay-Tsoory and Soo Hong Chew, John Wiley & Sons
The incidence, causes, and impact of acute infection were analyzed among 814 consecutive patients from 24 institutions undergoing primary heart transplantation between January 1, 1990, and June 30, 1991, with mean follow- up of 8.2 months (range 0 to 18 months). Sixty-nine percent of the patients had no infections during the follow-up, whereas 31% of patients had one or more infection episodes. The cumulative incidence of infections per patient was 0.41 at 3 months, 0.55 at 6 months, and 0.62 at 12 months after transplantation. Bacterial and viral infections were most common (47% and 41% of infections), with fungi and protozoa accounting for 12%. Overall mortality per infection was 13%, but mortality with fungal infections was higher (36%, p < 0.0001). The most common organ infected was the lung, with a mortality of 23%. The probability of infection by 12 months was higher when OKT3 or antithymocyte globulin induction therapy was used (41% versus 35%, p = 0.01). The single most frequent ...
Diagnosis and Management of Hypertrophic Cardiomyopathy : Diagnosis and Management of Hypertrophic Cardiomyopathy is a unique, multi-authored compendium of information regarding the complexities of clinical and genetic diagnosis, natural history, and management of hypertrophic cardiomyopathy (HCM)-the most common and important of the genetic cardiovascular diseases-as well as related issues impacting the health of trained athletes. Edited by Dr.
Another name for Hypertrophic Cardiomyopathy is Hypertrophic Cardiomyopathy. To better understand hypertrophic cardiomyopathy, it helps to understand ...
Hypertrophic cardiomyopathy occurs as an autosomal dominant familial disorder or as a sporadic disease without familial involvement. While missense mutations in the beta cardiac myosin heavy chain (MHC) gene account for approximately half of all cases of familial hypertrophic cardiomyopathy, the molecular causes of sporadic hypertrophic cardiomyopathy are unknown. To determine whether beta cardiac MHC mutations are also associated with sporadic disease, we screened this gene in seven individuals with sporadic hypertrophic cardiomyopathy. Mutations in the beta cardiac MHC genes were identified in two probands with sporadic disease. In that their parents were neither clinically nor genetically affected, we conclude that mutations in each proband arose de novo. Transmission of the mutation and disease to an offspring occurred in one pedigree, predicting that these are germline mutations. The demonstration of hypertrophic cardiomyopathy arising within a pedigree coincident with the appearance of a ...
Fatigue in muscles that shorten might have other causes than fatigue during isometric contractions, since both cross-bridge cycling and energy demand are different in the two exercise modes. While isometric contractions are extensively studied, the causes of fatigue in shortening contractions are poorly mapped. Here, we investigate fatigue mechanisms during shortening contractions in slow twitch skeletal muscle in near physiological conditions. Fatigue was induced in rat soleus muscles with maintained blood supply by in situ shortening contractions at 37°C. Muscles were stimulated repeatedly (1 s on/off at 30 Hz) for 15 min against a constant load, allowing the muscle to shorten and perform work. Fatigue and subsequent recovery was examined at 20 s, 100 s and 15 min exercise. The effects of prior exercise were investigated in a second exercise bout. Fatigue developed in three distinct phases. During the first 20 s the regulatory protein Myosin Light Chain-2 (slow isoform, MLC-2s) was rapidly ...
Hypertrophic cardiomyopathy (HCM) is defined as the presence of a hypertrophied, nondilated left ventricle in the absence of another causative disease (1). It is estimated to affect 1 in 500 persons, with highly variable clinical and pathologic presentations and penetrance (2,3). The severity of disease varies from a lifelong asymptomatic course to a sentinel event of sudden cardiac death (SCD) at a young age. A growing realization that the implanted cardioverter defibrillator (ICD) is effective in the primary and secondary prevention of SCD has provided an added impetus to discover new approaches for the identification and risk stratification of susceptible individuals in whom the prophylactic implantation of an ICD might be life saving (4).. In addition to this phenotypic variability, there is profound heterogeneity in the genetic substrate for HCM. To date, nine genes encoding various components of the cardiac sarcomere have been implicated in HCM: cardiac beta-myosin heavy chain (MYH7) ...
Myosin specificity[edit]. Blebbistatin is a potent inhibitor of nonmuscle myosin IIA and IIB, cardiac myosin, skeletal myosin ... nonmuscle myosin-2 oocyte cytokinesis effective at 300 μM[33] C. elegans nonmuscle myosin-2 acto-myosin colocalization ... for Dictyostelium discoideum myosin II motor domain IC50=2.3 μM, for human β-cardiac myosin subfragment 1 IC50=13 μM,[37] for ... myosin isoform or muscle type assay type IC50 Dictyostelium discoideum myosin II motor domain basal ATPase 2.96 ± 0.45 μM,[7] ...
A number of genes have been associated with cardiac manifestations. Mutations of a heart muscle protein, α-myosin heavy chain ( ... Non-cardiac manifestations[19]. Upper limb abnormalities. Small or absent thymus Small or absent parathyroids Facial ... Niessen, K.; Karsan, A. (2008). "Notch Signaling in Cardiac Development". Circulation Research. 102 (10): 1169-1181. doi: ... Several proteins that interact with MYH6 are also associated with cardiac defects. The transcription factor GATA4 forms a ...
Downstream effectors of NRG-1/ErbB, include cardiac-specific myosin light chain kinase (cMLCK), Protein Phosphatase type 1 (PP1 ... "A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart". J. Clin. Invest. 117 (10): 2812-24. ... "Identification of cardiac-specific myosin light chain kinase". Circ. Res. 102 (5): 571-80. doi:10.1161/CIRCRESAHA.107.161687. ... Bassani JW, Yuan W, Bers DM (May 1995). "Fractional SR Ca release is regulated by trigger Ca and SR Ca content in cardiac ...
Phosphorylation of cardiac myosin heavy chains (see MYH7B) and light chains (see MYL2) by a kinase, such as MYLK3, potentiates ... 2007). "A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart". J. Clin. Invest. 117 (10): ... "A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart". J. Clin. Invest. 117 (10): 2812-24. ... "Identification of cardiac-specific myosin light chain kinase". Circ. Res. 102 (5): 571-80. doi:10.1161/CIRCRESAHA.107.161687. ...
Atomic model of the human cardiac muscle myosin filament. Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):318-323. http://www. ... General model of myosin filament structure. III. Molecular packing arrangements in myosin filaments. J Mol Biol. 1973 Jun 25;77 ... polarity in the myosin filaments of vertebrate smooth muscle, and the proposal of a general packing scheme of myosin molecules ... Probing muscle myosin motor action: X-ray (m3 and m6) interference measurements report motor domain not lever arm movement. J ...
Gupta MP, Gupta M, Dizon E, Zak R (1996). "Sympathetic control of cardiac myosin heavy chain gene expression". Molecular and ... This recruitment leads to the repression of the MLC2v (Myosin Light Chain 2 v) and βMHC ( β-myosin heavy chain ) promoter. ... Regulation of myosin heavy chain genes, cardiac muscular genes troponin T and I Regulation of proliferation, Regulation of ... for positive regulation of cardiac alpha-myosin heavy-chain gene expression". Molecular and Cellular Biology. 17 (7): 3924-36. ...
He also cloned the first cardiac myosin heavy chain gene. He and his team were the first to elucidated the biosynthetic pathway ...
The activated calmodulin molecule activates myosin light-chain kinase (MLCK), which phosphorylates the myosin in thick ... In cardiac muscle, opening of the L-type calcium channel permits influx of calcium into the cell. The calcium binds to the ... Phosphorylated myosin is able to form crossbridges with actin thin filaments, and the smooth muscle fiber (i.e., cell) ... The β subunit has effects on the kinetics of the cardiac α1C in Xenopus laevis oocytes co-expressed with β subunits. The β ...
Alpert NR, Brosseau C, Federico A, Krenz M, Robbins J, Warshaw DM (Oct 2002). "Molecular mechanics of mouse cardiac myosin ... MHC-β is the major protein comprising the thick filament in cardiac muscle and plays a major role in cardiac muscle contraction ... Approximately 300 myosin molecules constitute one thick filament. There are two isoforms of cardiac MHC, α and β, which display ... A beta cardiac myosin heavy chain gene missense mutation". Cell. 62 (5): 999-1006. doi:10.1016/0092-8674(90)90274-i. PMID ...
"Modulating Beta-Cardiac Myosin Function at the Molecular and Tissue Levels". Frontiers in Physiology. 7: 659. doi:10.3389/fphys ... para-Nitroblebbistatin is a non-phototoxic, photostable myosin inhibitor with low fluorescence. Its myosin inhibitory ... "Cell migration and antigen capture are antagonistic processes coupled by myosin II in dendritic cells". Nature Communications. ... para-Nitroblebbistatin has been successfully used in fluorescent imaging experiments involving myosin IIA-GFP expressing live ...
"Peroxidase labelled monoclonal antibody against light chains of human cardiac myosin". General physiology and biophysics. 10 (1 ...
April 2001). "Cardiac troponin and beta-type myosin heavy chain concentrations in patients with polymyositis or dermatomyositis ... No cardiac specific isoforms are known for human TnC. TnC in human cardiac muscle tissue is presented by an isoform typical for ... The distinction between cardiac and non-cardiac conditions is somewhat artificial; the conditions listed below are not primary ... Gaze DC, Collinson PO; Collinson, PO (December 2005). "Cardiac troponins as biomarkers of drug- and toxin-induced cardiac ...
Cardiac muscle (myocardium), is also an "involuntary muscle" but is more akin in structure to skeletal muscle, and is found ... The filaments in a sarcomere are composed of actin and myosin. The gross anatomy of a muscle is the most important indicator of ... Cardiac muscle on the other hand, can readily consume any of the three macronutrients (protein, glucose and fat) aerobically ... Cardiac and skeletal muscles are "striated" in that they contain sarcomeres that are packed into highly regular arrangements of ...
1987 Aug 14;237(4816):764-8. A cardiac myosin binding protein C mutation in the Maine Coon cat with familial hypertrophic ...
Thus due to the unique cardiac myosin activation mechanism, omecamtiv mecarbil could safely improve cardiac function within ... Teerlink, JR (2009). "A novel approach to improve cardiac performance: cardiac myosin activators". Heart Fail Rev. 14 (4): 289- ... "Improvement of cardiac function by a cardiac myosin activator in conscious dogs with systolic heart failure". Circ Heart Fail. ... "The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind ...
2007). "A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart". J. Clin. Invest. 117 (10): ... This kinase phosphorylates myosin regulatory light chains to facilitate myosin interaction with actin filaments to produce ... Myosin light chain kinase, smooth muscle also known as kinase-related protein (KRP) or telokin is an enzyme that in humans is ... "Entrez Gene: MYLK myosin, light chain kinase". Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial ...
Cardiac troponin is another ROCK1 substrate that upon phosphrylation causes reduction in tension in cardiac myocytes. ROCK1 ... It is a key regulator of actin-myosin contraction, stability, and cell polarity. These contribute to many progresses such as ... ROCK1 activation by RhoA also promotes stabilization of F-actin, phosphorylation of regulatory myosin light chain(MLC) and an ... Activated ROCK1 phosphorylates MLC involved in actin-myosin contractility. RhoA also activates focal adhesion kinase activity. ...
It also responds to stress and forms part of a hormonal signalling cascade in cardiac cells. A preliminary study has shown a ... miR-208 functions in cardiomyocytes regulating the production of the myosin heavy chain during development. ... miR-208 has been deemed a "myomiR" as it is specifically expressed, or found at much higher levels, in cardiac tissue. Other ... van Rooij, E; Sutherland, LB; Qi, X; Richardson, JA; Hill, J; Olson, EN (2007-04-27). "Control of stress-dependent cardiac ...
April 2012). "Mouse and computational models link Mlc2v dephosphorylation to altered myosin kinetics in early cardiac disease ... Dephosphorylation is a key part of the myosin cycling kinetics that directly control the actin-myosin interactions. When the ... particularly the alteration of actin-myosin interactions that are key for providing the underlying force of a heartbeat. ... protein phosphatases are implicated in conditions such as cardiac disease, diabetes, and Alzheimer's disease. The discovery of ...
The cardiac output is normalized to body size through body surface area and is called the cardiac index. The average cardiac ... These are mostly associated with muscle contraction, and bind with actin, myosin, tropomyosin, and troponin. They include MYH6 ... the middle cardiac vein (draining the bottom of the left and right ventricles), and small cardiac veins. The anterior cardiac ... and Cardiac Electrophysiology: Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular ...
In cardiac muscle cells, the most important buffers include troponin C, SERCA, calmodulin, and myosin. Alterations in calcium ... As a result, 99% of the calcium added to the cytosol of a cardiomyocyte during each cardiac cycle becomes bound to calcium ... M., Bers, D. (2001). Excitation-contraction coupling and cardiac contractile force (2nd ed.). Dordrecht: Kluwer Academic ... "Balanced changes in Ca buffering by SERCA and troponin contribute to Ca handling during β-adrenergic stimulation in cardiac ...
In cardiac muscle, expression of M-protein continues to increase from neonatal to adult; however, in skeletal muscle, M-protein ... M-protein functions to stabilize the M-line cross-linking titin and myosin; the central portion of M-protein is around the M1- ... Obermann WM, van der Ven PF, Steiner F, Weber K, Fürst DO (Apr 1998). "Mapping of a myosin-binding domain and a regulatory ... Obermann WM, van der Ven PF, Steiner F, Weber K, Fürst DO (Apr 1998). "Mapping of a myosin-binding domain and a regulatory ...
Huang WY, Cukerman E, Liew CC (1995). "Identification of a GATA motif in the cardiac alpha-myosin heavy-chain-encoding gene and ... GATA4 promotes cardiac morphogenesis, cardiomyocytes survival, and maintains cardiac function in the adult heart. Mutations or ... "Transcription factor GATA-4 regulates cardiac muscle-specific expression of the alpha-myosin heavy-chain gene". Mol. Cell. Biol ... 1997). "The cardiac transcription factors Nkx2-5 and GATA-4 are mutual cofactors". EMBO J. 16 (18): 5687-96. doi:10.1093/emboj/ ...
2009). "A common MYBPC3 (cardiac myosin binding protein C) variant associated with cardiomyopathies in South Asia". Nature ...
The cardiac myosin binding protein C mutation identified in Maine Coon cats has not been found in any other breed of cat with ... The first genetic mutation (in cardiac myosin binding protein C) responsible for feline HCM was discovered in 2005 in Maine ... It fails to acknowledge the age at which relatives suffered sudden cardiac death, as well as the frequency of the cardiac ... While there is use of echocardiography, cardiac catheterization, or cardiac MRI in the diagnosis of the disease, other ...
... of known causes of death in diagnosed patients relating to cardiovascular complications and congestive cardiac failure. Other ... in an intron of the Myosin heavy polypeptide 4 gene.[38] ... "A novel intronic single nucleotide polymorphism in the myosin ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
myosin-binding protein C, cardiac-type. Names. C-protein, cardiac muscle isoform. truncated cardiac myosin-binding protein C. ... MYBPC3 encodes the cardiac isoform of myosin-binding protein C. Myosin-binding protein C is a myosin-associated protein found ... MYBPC3 myosin binding protein C, cardiac [Homo sapiens] MYBPC3 myosin binding protein C, cardiac [Homo sapiens]. Gene ID:4607 ... myosin binding protein C, cardiacprovided by HGNC. Primary source. HGNC:HGNC:7551 See related. Ensembl:ENSG00000134571 MIM: ...
"Dissecting the N-terminal myosin binding site of human cardiac myosin-binding protein C. Structure and myosin binding of domain ... "Protein Information - Myosin-binding protein C, cardiac-type". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). NHLBI ... "Double heterozygosity for mutations in the beta-myosin heavy chain and in the cardiac myosin binding protein C genes in a ... "A molecular screening strategy based on beta-myosin heavy chain, cardiac myosin binding protein C and troponin T genes in ...
The publication titled, "Cardiac Myosin Activation: A Potential Therapeutic Approach for Systolic Heart Failure," discusses the ... Omecamtiv mecarbil, a novel cardiac muscle myosin activator, has been the subject of a clinical trials program comprised of ... The authors concluded that cardiac myosin activation may provide a new therapeutic approach for patients with systolic heart ... Cytokinetics Announces Fundamental Research In Cardiac Myosin Activation In The Journal Science. by Sam Savage ...
CK-274 is a novel cardiac myosin inhibitor, discovered ... CK-274 is a novel cardiac myosin inhibitor, discovered by ... CK-274 reduces the number of active actin-myosin cross bridges during each cardiac cycle and consequently reduces myocardial ... CK-274 is a novel, oral, small molecule cardiac myosin inhibitor that company scientists discovered independent of its ... Cytokinetics is also developing CK-274, a novel cardiac myosin inhibitor that company scientists discovered independent of its ...
... cardiac-specific myosin light chain kinase (cardiac-MLCK), which acts on MLC2v. Expression levels of cardiac-MLCK were well ... Cardiac-specific myosin regulatory light chain is a specific substrate of cardiac-MLCK. Because this protein kinase contained a ... In mice, however, targeted deletion of the cardiac ventricular myosin light chain, a specific substrate of cardiac-MLCK, was ... mRNA expression of ANP and β myosin heavy chain, representative markers of cardiac hypertrophy, were also unaffected by cardiac ...
Phosphorylation of cardiac myosin-binding protein-C (cMyBP-C) by protein kinase A accelerates the kinetics of force development ... Phosphoregulation of Cardiac Inotropy via Myosin Binding Protein-C During Increased Pacing Frequency or β1-Adrenergic ... Phosphoregulation of Cardiac Inotropy via Myosin Binding Protein-C During Increased Pacing Frequency or β1-Adrenergic ... Phosphoregulation of Cardiac Inotropy via Myosin Binding Protein-C During Increased Pacing Frequency or β1-Adrenergic ...
Phosphorylation and function of cardiac myosin binding protein-C in health and disease.. Barefield D1, Sadayappan S. ... During the past 5 years there has been an increasing body of literature describing the roles cardiac myosin binding protein C ( ... cMyBP-C is a sarcomeric thick filament protein that interacts with titin, myosin and actin to regulate sarcomeric assembly, ... cMyBP-C) phosphorylation play in regulating cardiac function and heart failure. ...
Despite early demonstrations of myosin binding protein Cs (MyBP-C) interaction with actin, different investigators have ... Myocytes, Cardiac / metabolism*. Myosin Subfragments / chemistry, metabolism. Protein Binding / genetics. Protein Interaction ... 0/Actins; 0/Carrier Proteins; 0/Myosin Subfragments; 0/myosin-binding protein C ... Despite early demonstrations of myosin binding protein Cs (MyBP-C) interaction with actin, different investigators have ...
Phosphoproteome Characterization of Cardiac Myosin Binding Protein-C. By Emily Humphreys 10.30.2013 Cardiac myosin binding ... Accelerating ScienceAccelerating Proteomics / Cardiovascular / Phosphoproteome Characterization of Cardiac Myosin Binding ... 2013, July) "Characterization of the cardiac myosin binding protein-C phosphoproteome in healthy and failing human hearts," ... 1. James, J., and Robbins, J. (2011) "Signaling and myosin-binding protein C," The Journal of Biological Chemistry, 286(12) (pp ...
Germ-line transmission of a myocardium-specific GFP transgene reveals critical regulatory elements in the cardiac myosin light ... of the zebrafish cardiac myosin light chain 2 gene, (cmlc2). A germ-line transmitted zebrafish possessing a green fluorescent ...
Deciphering the super relaxed state of human β-cardiac myosin and the mode of action of mavacamten from myosin molecules to ... Deciphering the super relaxed state of human β-cardiac myosin and the mode of action of mavacamten from myosin molecules to ... Deciphering the super relaxed state of human β-cardiac myosin and the mode of action of mavacamten from myosin molecules to ... Deciphering the super relaxed state of human β-cardiac myosin and the mode of action of mavacamten from myosin molecules to ...
Cardiac Myosin-Binding Protein C Mutations and Hypertrophic Cardiomyopathy. Haploinsufficiency, Deranged Phosphorylation, and ... Cardiac Myosin-Binding Protein C Mutations and Hypertrophic Cardiomyopathy. Haploinsufficiency, Deranged Phosphorylation, and ... Cardiac Myosin-Binding Protein C Mutations and Hypertrophic Cardiomyopathy. Haploinsufficiency, Deranged Phosphorylation, and ... Cardiac Myosin-Binding Protein C Mutations and Hypertrophic Cardiomyopathy. Haploinsufficiency, Deranged Phosphorylation, and ...
Myosin light chain kinase (MLCK)-dependent phosphorylation of the regulatory light chain (RLC) of cardiac myosin is known to ... Journal Article: Constitutive phosphorylation of cardiac myosin regulatory light chain prevents development of hypertrophic ... Title: Constitutive phosphorylation of cardiac myosin regulatory light chain prevents development of hypertrophic ... Tg-S15D-D166V mice were generated with the human cardiac RLC-S15D-D166V construct substituted for mouse cardiac RLC and were ...
COMPARATIVE STUDIES OF LIGHT MEROMYOSIN PARACRYSTALS DERIVED FROM RED, WHITE, AND CARDIAC MUSCLE MYOSINS. A. Nakamura, F. ... COMPARATIVE STUDIES OF LIGHT MEROMYOSIN PARACRYSTALS DERIVED FROM RED, WHITE, AND CARDIAC MUSCLE MYOSINS ... Tryptic and chymotryptic light meromyosin paracrystals from red and cardiac muscles of rabbit show a negative and positive ... The results are discussed in terms of the molecular structure and the functional properties of various myosins. ...
During the initial phase of cardiac looping, known as c-looping, the heart bends and twists into a c-shaped tube with the ... Myosin-based contraction is not necessary for cardiac c-looping in the chick embryo. ... Primitive cardiac cavities vs. primitive cardiac segments. In: de la Cruz MV, Markwald RR (eds) Living morphogenesis of the ... Harvey RP (1998) Cardiac looping-an uneasy deal with laterality. Semin Cell Dev Biol 9:101-108PubMedCrossRefGoogle Scholar ...
Myosin heavy chain, cardiac muscle alpha isoform (MyHC-alpha) , alpha cardiac MHC , alpha myosin , cardiac myosin heavy chain ... cardiac muscle, alpha , myosin, heavy polypeptide 6, cardiac muscle, alpha , myosin-6 , myosin, heavy polypeptide 6, cardiac ... myHC-alpha , myosin heavy chain 6 , myosin heavy chain polypeptide 6 cardiac muscle adult , myosin heavy chain, cardiac muscle ... Myosin Heavy Chain 6, Cardiac Muscle, alpha (MYH6) ELISA Kits. Cardiac muscle myosin is a hexamer consisting of two heavy chain ...
... cardiac myosin heavy chain beta , beta cardiac myosin heavy chain , myosin 7 , myosin heavy chain slow type 1 (beta cardiac) , ... myosin heavy chain (AA 1-96) , myosin heavy chain 7 , myosin heavy chain slow isoform , myosin heavy chain, cardiac muscle beta ... beta myosin heavy chain , myHC-slow , myosin heavy chain polypeptide 7 cardiac muscle fetal , myosin heavy chain, cardiac ... myosin, heavy chain 7, cardiac muscle, beta (MYH7) Antikörper * myosin, heavy polypeptide 7, cardiac muscle, beta (Myh7) ...
Roles for Cardiac MyBP-C in Maintaining Myofilament Lattice Rigidity and Prolonging Myosin Cross-Bridge Lifetime ... title = {Roles for Cardiac MyBP-C in Maintaining Myofilament Lattice Rigidity and Prolonging Myosin Cross-Bridge Lifetime},. ... "Roles for Cardiac MyBP-C in Maintaining Myofilament Lattice Rigidity and Prolonging Myosin Cross-Bridge Lifetime". United ... Title: Roles for Cardiac MyBP-C in Maintaining Myofilament Lattice Rigidity and Prolonging Myosin Cross-Bridge Lifetime. ...
Swimming causes myosin adaptations in the rat cardiac isograft.. S V Advani, D Geenen, A Malhotra, S M Factor, J Scheuer ... The cardiac isograft was also associated with a decrease in the percent of V1 myosin isoenzyme, which was attenuated by ... The cardiac isograft exhibited atrophy (32-35%), which was not attenuated by swimming. ... To investigate the contributions of humoral and hemodynamic factors to cardiac adaptations associated with chronic exercise, ...
... myosin motors are packed in helical tracks on the surface of the thick filament, folded toward the center of the sarcomere, and ... skeletal and cardiac) muscle is in its relaxed state, ... do not change the resting state of myosin motors during cardiac ... When striated (skeletal and cardiac) muscle is in its relaxed state, myosin motors are packed in helical tracks on the surface ... Thick filament mechanosensing has been proposed as the mechanism by which myosin motors in cardiac muscle become available to ...
... which is highly conserved among the cardiac myosins, from mouse α-cardiac to human β-cardiac myosin (Spudich, 2015). The mesa ... Human cardiomyopathy mutations are a leading cause of cardiac death. The human β-cardiac myosin motor is a major site in the ... 2011). Structure and interactions of myosin-binding protein C domain C0: cardiac-specific regulation of myosin at its neck? J. ... 2014). The hypertrophic cardiomyopathy myosin mutation R453C alters ATP binding and hydrolysis of human cardiac beta-myosin. J ...
Myosin isoenzyme changes in several models of rat cardiac hypertrophy.. J J Mercadier, A M Lompré, C Wisnewsky, J L Samuel, J ... Myosin isoenzyme changes in several models of rat cardiac hypertrophy.. J J Mercadier, A M Lompré, C Wisnewsky, J L Samuel, J ... Myosin isoenzyme changes in several models of rat cardiac hypertrophy.. J J Mercadier, A M Lompré, C Wisnewsky, J L Samuel, J ... We studied the effect of chronic mechanical overloading on the isoenzyme composition of rat cardiac myosin in several ...
Myosin light chains of skeletal and cardiac muscles of ground squirrel Citillus undulatus in different periods of hibernation ... TY - JOUR T1 - [Myosin light chains of skeletal and cardiac muscles of ground squirrel Citillus undulatus in different periods ... Myosin light chains of skeletal and cardiac muscles of ground squirrel Citillus undulatus in different periods of hibernation]. ... Myosin Light Chains of Skeletal and Cardiac Muscles of Ground Squirrel Citillus Undulatus in Different Periods of Hibernation ...
  • It is our honor to have Cytokinetics' novel scientific research into direct modulators of the cardiac contractile apparatus published in this prestigious journal," stated Fady I. Malik, MD, FACC, Cytokinetics' Vice President of Biology and Therapeutics and lead author of this report. (redorbit.com)
  • Recent studies in cardiac muscle cells have suggested that arachidonic acid (AA) may be an important signaling molecule in the modulation of cardiac contractile function via alterations in Ca 2+ cycling. (ahajournals.org)
  • Two critical features of mammalian cardiac development are the assembly of a functional contractile system and the sequential formation of the left and right structures of the final four-chambered heart with its proper connections to the arterial and venous vasculatures. (biologists.org)
  • in addition to their structural difference cardiac myosin isozymes have different contractile functions. (who.int)
  • Our in vitro results suggest that when placed in vivo , IVS6-1 may lead to cardiomyopathy and early death of homozygous infants by severely compromising the ability of myosin to develop contractile force and maintain normal systolic and diastolic cardiac function. (frontiersin.org)
  • The exact mechanism for this remains unknown, but it appears to be the result of an increased exposure of the heart to contractile substances arising from the increased flow caused by an increased cardiac frequency. (wikipedia.org)
  • The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. (mybiosource.com)
  • It remains a difficult medical challenge to prevent the sudden cardiac death of athletes, typically defined as natural, unexpected death from cardiac arrest within one hour of the onset of collapse symptoms, excluding additional time on mechanical life support. (wikipedia.org)
  • Sudden cardiac death occurs in approximately one per 200,000 young athletes per year, usually triggered during competition or practice. (wikipedia.org)
  • For a normally healthy age group, the risk appears to be particularly magnified in competitive basketball, with sudden cardiac death rates as high as one per 3,000 annually for male basketball players in NCAA Division I. This is still far below the rate for the general population, estimated as one per 1,300-1,600 and dominated by the elderly. (wikipedia.org)
  • However, a population as large as the United States will experience the sudden cardiac death of a competitive athlete at the average rate of one every three days, often with significant local media coverage heightening public attention. (wikipedia.org)
  • The sudden cardiac deaths of 387 young American athletes (under age 35) were analyzed in a 2003 medical review: While most causes of sudden cardiac death relate to congenital or acquired cardiovascular disease, an exception is commotio cordis, in which the heart is structurally normal but a potentially fatal loss of rhythm occurs because of the accident of timing of a blow to the chest. (wikipedia.org)
  • Age 35 serves as an approximate borderline for the likely cause of sudden cardiac death. (wikipedia.org)
  • Complications include heart failure, an irregular heartbeat, and sudden cardiac death. (wikipedia.org)
  • The symptoms and signs of HCM include shortness of breath due to stiffening and decreased blood filling of the ventricles, exertional chest pain (sometimes known as angina) due to reduced blood flow to the coronary arteries, uncomfortable awareness of the heart beat (palpitations), as well as disruption of the electrical system running through the abnormal heart muscle, lightheadedness, weakness, fainting and sudden cardiac death. (wikipedia.org)
  • Dysrhythmias and sudden cardiac death (SCD) was shown to occur even before the manifestation of DCM and heart failure symptoms in LMNA mutation carriers. (wikipedia.org)
  • Recent studies suggest that cardiomegaly is associated with a higher risk of sudden cardiac death (SCD). (wikipedia.org)