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https://www.readbyqxmd.com/read/28912181/hypertrophic-cardiomyopathy-genetics-pathogenesis-clinical-manifestations-diagnosis-and-therapy
#1
REVIEW
Ali J Marian, Eugene Braunwald
Hypertrophic cardiomyopathy (HCM) is a genetic disorder that is characterized by left ventricular hypertrophy unexplained by secondary causes and a nondilated left ventricle with preserved or increased ejection fraction. It is commonly asymmetrical with the most severe hypertrophy involving the basal interventricular septum. Left ventricular outflow tract obstruction is present at rest in about one third of the patients and can be provoked in another third. The histological features of HCM include myocyte hypertrophy and disarray, as well as interstitial fibrosis...
September 15, 2017: Circulation Research
https://www.readbyqxmd.com/read/28903042/distortion-of-the-actin-a-triad-results-in-contractile-disinhibition-and-cardiomyopathy
#2
Meera C Viswanathan, William Schmidt, Michael J Rynkiewicz, Karuna Agarwal, Jian Gao, Joseph Katz, William Lehman, Anthony Cammarato
Striated muscle contraction is regulated by the movement of tropomyosin over the thin filament surface, which blocks or exposes myosin binding sites on actin. Findings suggest that electrostatic contacts, particularly those between K326, K328, and R147 on actin and tropomyosin, establish an energetically favorable F-actin-tropomyosin configuration, with tropomyosin positioned in a location that impedes actomyosin associations and promotes relaxation. Here, we provide data that directly support a vital role for these actin residues, termed the A-triad, in tropomyosin positioning in intact functioning muscle...
September 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/28899987/heart-failure-related-hyperphosphorylation-in-the-cardiac-troponin-i-c-terminus-has-divergent-effects-on-cardiac-function-in-vivo
#3
Yuejin Li, Guangshuo Zhu, Nazareno Paolocci, Pingbo Zhang, Cyrus Takahashi, Nazli Okumus, Amir Heravi, Gizem Keceli, Genaro Ramirez-Correa, David A Kass, Anne M Murphy
BACKGROUND: In human heart failure, Ser199 (equivalent to Ser200 in mouse) of cTnI (cardiac troponin I) is significantly hyperphosphorylated, and in vitro studies suggest that it enhances myofilament calcium sensitivity and alters calpain-mediated cTnI proteolysis. However, how its hyperphosphorylation affects cardiac function in vivo remains unknown. METHODS AND RESULTS: To address the question, 2 transgenic mouse models were generated: a phospho-mimetic cTnIS200D and a phospho-silenced cTnIS200A, each driven by the cardiomyocyte-specific α-myosin heavy chain promoter...
September 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28894417/myosin-v-induces-cargo-immobilization-and-clustering-at-the-axon-initial-segment
#4
Anne F J Janssen, Roderick P Tas, Petra van Bergeijk, Rosalie Oost, Casper C Hoogenraad, Lukas C Kapitein
The selective transport of different cargoes into axons and dendrites underlies the polarized organization of the neuron. Although it has become clear that the combined activity of different motors determines the destination and selectivity of transport, little is known about the mechanistic details of motor cooperation. For example, the exact role of myosin-V in opposing microtubule-based axon entries has remained unclear. Here we use two orthogonal chemically-induced heterodimerization systems to independently recruit different motors to cargoes...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28893906/n-terminal-splicing-extensions-of-the-human-myo1c-gene-fine-tune-the-kinetics-of-the-three-full-length-myosin-ic-isoforms
#5
Lilach Zattelman, Ronit Regev, Marko Ušaj, Patrick Y A Reinke, Sven Giese, Abraham O Samson, Manuel H Taft, Dietmar J Manstein, Arnon Henn
The MYO1C gene produces three alternatively spliced isoforms, differing only in their N-terminal regions (NTRs). These isoforms, which exhibit both specific and overlapping nuclear and cytoplasmic functions, have different expression levels and nucleo-cytoplasmic partitioning. To investigate the effect of NTR extensions on the enzymatic behavior of individual isoforms, we over-expressed and purified the three full-length human isoforms from suspension-adapted HEK cells. MYO1C(C) favored the actomyosin closed state (AM(C)), MYO1C(16) populated the actomyosin open state (AM(O)) and AM(C) equally, and MYO1C(35) favored the AM(O) state...
September 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28892557/the-basis-of-differences-in-thermodynamic-efficiency-among-skeletal-muscles
#6
C J Barclay
Muscles convert chemical free energy into mechanical work. The energy conversion occurs in two steps. First, free energy obtained from oxidation of metabolic substrates (ΔGS ) is transferred to ATP and, second, free energy from ATP hydrolysis (ΔGATP ) is converted into work by myosin cross-bridges. The fraction of ΔGS transferred to ATP is called mitochondrial efficiency (ηM ) and the fraction of ΔGATP converted into work is called cross-bridge efficiency (ηCB ). Overall cross-bridge efficiency varies among muscles from ~20% and 35% and the analysis presented in the current studies shows that this variation is largely due to differences in ηCB whereas ηM is similar (~80%) in all the muscles assessed...
September 11, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28873601/production-and-assessment-of-pacific-hake-merluccius-productus-hydrolysates-as-cryoprotectants-for-frozen-fish-mince
#7
Peter J Jenkelunas, Eunice C Y Li-Chan
The aim of this study was to investigate application of fish protein hydrolysates (FPHs) as cryoprotectants for cod fish mince subjected to freeze-thaw abuse. Response surface methodology revealed little difference in cryoprotectant ability between FPHs produced from Pacific hake muscle within the range of conditions studied, namely Flavourzyme® enzyme/substrate ratio (E/S 1-4%), time (1-6h) and pH (5-7). When added at 4% or higher concentrations, FPH minimized expressible moisture and cook loss, while maximizing salt extractable protein from freeze-thaw abused fish mince, providing similar or better cryoprotection compared to an 8% sucrose-sorbitol blend, and a stabilizing effect of FPH on myosin was observed by differential scanning calorimetry...
January 15, 2018: Food Chemistry
https://www.readbyqxmd.com/read/28873544/importance-of-salt-and-temperature-in-myosin-polymerization-during-surimi-gelation
#8
Ruth Núñez-Flores, Deysi Cando, A Javier Borderías, Helena M Moreno
To address the effect of absence of NaCl on myosin heavy chain polymerization during two-step surimi gelation (different setting temperatures/times -5°C/24h and 30°C/30min-followed by heating at 90°C/30min) were considered. In gel samples made without salt (Lot A), no myosin heavy chain (MHC) polymerization was observed, only aggregation, as indicated by the electrophoresis in polyacrylamide/agarose gel profile. Moreover, these gels were characterized by weakly stabilized protein networks as denoted by the dynamic oscillatory measurement and FTIR analysis, resulting in poor quality gels...
January 15, 2018: Food Chemistry
https://www.readbyqxmd.com/read/28871043/mmi-0100-inhibits-cardiac-fibrosis-in-a-mouse-model-overexpressing-cardiac-myosin-binding-protein-c
#9
Qinghang Meng, Bidur Bhandary, Hanna Osinska, Jeanne James, Na Xu, Kritton Shay-Winkler, James Gulick, Monte S Willis, Cynthia Lander, Jeffrey Robbins
BACKGROUND: Cardiac stress can trigger production of a 40-kDa peptide fragment derived from the amino terminus of the cardiac myosin-binding protein C. Cardiac stress, as well as cMyBP-C mutations, can trigger production of 1 such truncated protein fragment, a 40-kDa peptide fragment derived from the amino terminus of cMyBP-C. Genetic expression of this 40-kDa fragment in mouse cardiomyocytes (cMyBP-C(40k)) leads to cardiac disease, fibrosis, and death within the first year. Fibrosis can occur in many cardiovascular diseases, and mitogen-activated protein kinase--activated protein kinase-2 signaling has been implicated in a variety of fibrotic processes...
September 4, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28868097/feline-hypertrophic-cardiomyopathy-a-spontaneous-large-animal-model-of-human-hcm
#10
REVIEW
Lisa M Freeman, John E Rush, Joshua A Stern, Gordon S Huggins, Martin S Maron
Hypertrophic cardiomyopathy (HCM) is a common disease in pet cats, affecting 10-15% of the pet cat population. The similarity to human HCM, the rapid progression of disease, and the defined and readily determined endpoints of feline HCM make it an excellent natural model that is genotypically and phenotypically similar to human HCM. The Maine Coon and Ragdoll cats are particularly valuable models of HCM because of myosin binding protein-C mutations and even higher disease incidence compared to the overall feline population...
August 2017: Cardiology Research
https://www.readbyqxmd.com/read/28867610/muscle-lim-protein-and-myosin-binding-protein-c-form-a-complex-regulating-muscle-differentiation
#11
Demetrios A Arvanitis, Elizabeth Vafiadaki, Vasiliki Papalouka, Despina Sanoudou
Muscle Lim Protein (MLP) is a protein with multiple functional roles in striated muscle physiology and pathophysiology. Herein, we demonstrate that MLP directly binds to slow, fast, and cardiac myosin-binding protein C (MyBP-C) during myogenesis, as shown by yeast two-hybrid, and a range of protein-protein interaction assays. The minimal interacting domains involve MLP inter-LIM and MyBP-C C4. The interaction is sensitive to cytosolic Ca(2+) concentrations changes and to MyBP-C phosphorylation by PKA or CaMKII...
August 31, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28864942/a%C3%A2-dutch-myh7-founder-mutation-p-asn1918lys-is-associated-with-early-onset-cardiomyopathy-and-congenital-heart-defects
#12
I H M van der Linde, Y L Hiemstra, R Bökenkamp, A M van Mil, M H Breuning, C Ruivenkamp, S W Ten Broeke, R F Veldkamp, J I van Waning, M A van Slegtenhorst, K Y van Spaendonck-Zwarts, R H Lekanne Deprez, J C Herkert, L Boven, P A van der Zwaag, J D H Jongbloed, M Bootsma, D Q C M Barge-Schaapveld
BACKGROUND: Mutations in the myosin heavy chain 7 (MYH7) gene commonly cause cardiomyopathy but are less frequently associated with congenital heart defects. METHODS: In this study, we describe a mutation in the MYH7 gene, c. 5754C > G; p. (Asn1918Lys), present in 15 probands and 65 family members. RESULTS: Of the 80 carriers (age range 0-88 years), 46 (57.5%) had cardiomyopathy (mainly dilated cardiomyopathy (DCM)) and seven (8...
September 1, 2017: Netherlands Heart Journal
https://www.readbyqxmd.com/read/28861149/posttranslational-modifications-of-calcium-calmodulin-dependent-protein-kinase-ii%C3%AE-and-its-downstream-signaling-in-human-failing-hearts
#13
Tomas Rajtik, Eva Goncalvesova, Zoltan V Varga, Przemyslaw Leszek, Mariusz Kusmierczyk, Michal Hulman, Jan Kyselovic, Peter Ferdinandy, Adriana Adameova
BACKGROUND: In human failing hearts (HF) of different origin (coronary artery disease-CAD, dilated-DCM, restrictive and hypertrophic cardiomyopathy-OTHER), we investigated the active forms of Ca(2+)/calmodulin-dependent protein kinase IIδ (p-Thr(287)-CaMKIIδ, oxMet(281/282)-CaMKIIδ) and their role in phenotypes of the disease. METHODS AND RESULTS: Although basic diagnostic and clinical markers indicating the attenuated cardiac contractility and remodeling were comparable in HF groups, CaMKIIδ-mediated axis was different...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28856513/emerging-pharmacologic-and-structural-therapies-for-hypertrophic-cardiomyopathy
#14
REVIEW
Daniel J Philipson, Eugene C DePasquale, Eric H Yang, Arnold S Baas
Hypertrophic cardiomyopathy is the most common inherited heart disease. Although it was first described over 50 years ago, there has been little in the way of novel disease-specific therapeutic development for these patients. Current treatment practice largely aims at symptomatic control using old drugs made for other diseases and does little to modify the disease course. Septal reduction by surgical myectomy or percutaneous alcohol septal ablation are well-established treatments for pharmacologic-refractory left ventricular outflow tract obstruction in hypertrophic cardiomyopathy patients...
August 31, 2017: Heart Failure Reviews
https://www.readbyqxmd.com/read/28856282/the-occurrence-of-autoantibodies-in-patients-with-chronic-hcv-infection-including-patients-dialyzed-and-after-kidney-transplantation
#15
Tadeusz W Łapiński, Magdalena Rogalska-Płońska, Anna Parfieniuk-Kowerda, Magdalena Świderska, Robert Flisiak
INTRODUCTION: There are reports suggesting that hepatitis C virus (HCV) may stimulate the autoimmune process. Studies have been undertaken to evaluate the occurrence and type of autoantibodies in HCV-infected patients with and without immunosuppression. Results were analyzed according to HCV genotype, intensity of inflammation and liver fibrosis stage. MATERIAL AND METHODS: The study included 105 patients chronically infected with HCV, including 25 with immunological suppression administered for kidney disease or kidney transplantation...
December 2016: Clin Exp Hepatol
https://www.readbyqxmd.com/read/28835844/polar-bears-experience-skeletal-muscle-atrophy-in-response-to-food-deprivation-and-reduced-activity-in-winter-and-summer
#16
John P Whiteman, Henry J Harlow, George M Durner, Eric V Regehr, Bryan C Rourke, Manuel Robles, Steven C Amstrup, Merav Ben-David
When reducing activity and using stored energy during seasonal food shortages, animals risk degradation of skeletal muscles, although some species avoid or minimize the resulting atrophy while experiencing these conditions during hibernation. Polar bears may be food deprived and relatively inactive during winter (when pregnant females hibernate and hunting success declines for other demographic groups) as well as summer (when sea ice retreats from key foraging habitats). We investigated muscle atrophy in samples of biceps femoris collected from free-ranging polar bears in the Southern Beaufort Sea (SBS) throughout their annual cycle...
2017: Conservation Physiology
https://www.readbyqxmd.com/read/28835694/coherent-raman-imaging-of-live-muscle-sarcomeres-assisted-by-sfg-microscopy
#17
Hyunmin Kim, Do-Young Kim, Kyung-Il Joo, Jung-Hye Kim, Soon Moon Jeong, Eun Seong Lee, Jeong-Hoon Hahm, Kyuhyung Kim, Dae Woon Moon
In this study, we used spectrally focused coherent anti-Stokes Raman scattering (spCARS) microscopy assisted by sum-frequency generation (SFG) to monitor the variations in the structural morphology and molecular vibrations of a live muscle of Caenorhabditis elegans. The subunits of the muscle sarcomeres, such as the M-line, myosin, dense body, and α-actinin, were alternatively observed using spCARS microscopy for different sample orientations, with the guidance of a myosin positional marker captured by SFG microscopy...
August 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28834398/er-golgi-trafficking-is-facilitated-by-unbranched-actin-filaments-containing-tpm4-2
#18
Anthony J Kee, Nicole S Bryce, Lingyan Yang, Elena Polishchuk, Galina Schevzov, Roberto Weigert, Roman Polishchuk, Peter W Gunning, Edna C Hardeman
We have identified novel actin filaments defined by tropomyosin Tpm4.2 at the ER. EM analysis of mouse embryo fibroblasts (MEFs) isolated from mice expressing a mutant Tpm4.2 (Tpm4(Plt53/Plt53) ), incapable of incorporating into actin filaments, revealed swollen ER structures compared to wild-type (WT) MEFs (Tpm4(+/+) ). ER-to-Golgi, but not Golgi-to-ER trafficking was altered in the Tpm4(Plt53/Plt53) MEFs following the transfection of the temperature sensitive ER-associated ts045-VSVg construct. Exogenous Tpm4...
August 22, 2017: Cytoskeleton
https://www.readbyqxmd.com/read/28821934/whole-exome-sequencing-to-identify-the-cause-of-congenital-sensorineural-hearing-loss-in-carriers-of-a-heterozygous-gjb2-mutation
#19
Thomas Parzefall, Alexandra Frohne, Martin Koenighofer, Andreas Kirchnawy, Berthold Streubel, Christian Schoefer, Klemens Frei, Trevor Lucas
Bi-allelic variations in the gap junction protein beta-2 (GJB2) gene cause up to 50% of cases of newborn hearing loss. Heterozygous pathogenic GJB2 variations are also fivefold overrepresented in idiopathic patient groups compared to the normal-hearing population. Whether hearing loss in this group is due to unidentified additional variations within GJB2 or variations in other deafness genes is unknown in most cases. Whole-exome sequencing offers an effective approach in the search for causative variations in patients with Mendelian diseases...
August 18, 2017: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/28820846/noninvasive-assessment-of-skeletal-muscle-myosin-heavy-chain-expression-in-trained-and-untrained-men
#20
Andrew C Fry, Terry J Housh, Joel B Cramer, Joseph P Weir, Travis W Beck, Brian K Schilling, Jonathan D Miller, Justin X Nicoll
Fry, AC, Housh, TJ, Cramer, JB, Weir, JP, Beck, TW, Schilling, BK, Miller, JD, and Nicoll, JX. Noninvasive assessment of skeletal muscle myosin heavy chain expression in trained and untrained men. J Strength Cond Res 31(9): 2355-2362, 2017-Numerous conditions and types of physical activity (e.g., exercise, aging, and muscle-related diseases) can influence muscle fiber types and the proteins expressed. To date, muscle fibers can only be characterized by actually obtaining a tissue sample using the invasive muscle biopsy procedure...
September 2017: Journal of Strength and Conditioning Research
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