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Luiz H P Silva, Pedro V R Paulino, Gutierrez J F Assis, Debora E F Assis, Mauricio M Estrada, Matheus C Silva, Jaqueline C Silva, Taiane S Martins, Sebastião C Valadares Filho, Mário F Paulino, Mario L Chizzotti
This study evaluated the effects of growth rate during post-weaning growing phase on carcass traits and beef quality. Thirty-four Nellore young bulls were randomly assigned to one of three treatments: LOW, MEDIUM or HIGH growth rate during post-weaning growing phase followed by high growth rate in the finishing phase. The growth rate affected (P<0.05) all carcass traits evaluated at the end of post-weaning growing phase, except ultimate pH. Carcass dressing was greatest (P<0.05) for the HIGH growth rate group in both phases...
October 12, 2016: Meat Science
Daniel Pelaez, Zenith Acosta Torres, Tsz Kin Ng, Kwong Wai Choy, Chi Pui Pang, Herman S Cheung
Cellular therapies for the treatment of myocardial infarction have proven to be an invaluable tool in recent years and provide encouraging evidence for the possibility to restore normal heart function. However, questions still remain as to the optimal cell source, pre-conditioning methods and delivery techniques for such an application. This study explores the use of a population of stem cells arising from the neural crest and isolated from adult human periodontal ligament along with short-term mechanical strain as an inducer of cardiomyogenesis and possibly pre-conditioning stimulus for cellular cardiomyoplasty...
October 17, 2016: Cell and Tissue Research
Gina L O'Grady, Heather A Best, Tamar E Sztal, Vanessa Schartner, Myriam Sanjuan-Vazquez, Sandra Donkervoort, Osorio Abath Neto, Roger Bryan Sutton, Biljana Ilkovski, Norma Beatriz Romero, Tanya Stojkovic, Jahannaz Dastgir, Leigh B Waddell, Anne Boland, Ying Hu, Caitlin Williams, Avnika A Ruparelia, Thierry Maisonobe, Anthony J Peduto, Stephen W Reddel, Monkol Lek, Taru Tukiainen, Beryl B Cummings, Himanshu Joshi, Juliette Nectoux, Susan Brammah, Jean-François Deleuze, Viola Oorschot Ing, Georg Ramm, Didem Ardicli, Kristen J Nowak, Beril Talim, Haluk Topaloglu, Nigel G Laing, Kathryn N North, Daniel G MacArthur, Sylvie Friant, Nigel F Clarke, Robert J Bryson-Richardson, Carsten G Bönnemann, Jocelyn Laporte, Sandra T Cooper
This study establishes PYROXD1 variants as a cause of early-onset myopathy and uses biospecimens and cell lines, yeast, and zebrafish models to elucidate the fundamental role of PYROXD1 in skeletal muscle. Exome sequencing identified recessive variants in PYROXD1 in nine probands from five families. Affected individuals presented in infancy or childhood with slowly progressive proximal and distal weakness, facial weakness, nasal speech, swallowing difficulties, and normal to moderately elevated creatine kinase...
September 28, 2016: American Journal of Human Genetics
Natalie Weber, Kristin Schwanke, Stephan Greten, Meike Wendland, Bogdan Iorga, Martin Fischer, Cornelia Geers-Knörr, Jan Hegermann, Christoph Wrede, Jan Fiedler, Henning Kempf, Annika Franke, Birgit Piep, Angelika Pfanne, Thomas Thum, Ulrich Martin, Bernhard Brenner, Robert Zweigerdt, Theresia Kraft
Human pluripotent stem cell (hPSC)-derived cardiomyocytes hold great potential for in vitro modeling of diseases like cardiomyopathies. Yet, knowledge about expression and functional impact of sarcomeric protein isoforms like the myosin heavy chain (MyHC) in hPSC-cardiomyocytes is scarce. We hypothesized that ventricular β-MyHC expression alters contraction and calcium kinetics and drives morphological and electrophysiological differentiation towards ventricular-like cardiomyocytes. To address this, we (1) generated human embryonic stem cell-derived cardiomyocytes (hESC-CMs) that switched towards exclusive β-MyHC, and (2) functionally and morphologically characterized these hESC-CMs at the single-cell level...
November 2016: Basic Research in Cardiology
Daniel F Gudbjartsson, Hilma Holm, Patrick Sulem, Gisli Masson, Asmundur Oddsson, Olafur Th Magnusson, Jona Saemundsdottir, Hafdis Th Helgadottir, Hannes Helgason, Hrefna Johannsdottir, Solveig Gretarsdottir, Sigurjon A Gudjonsson, Inger Njølstad, Maja-Lisa Løchen, Larry Baum, Ronald C W Ma, Gunnlaugur Sigfusson, Augustine Kong, Guðmundur Thorgeirsson, Jon Th Sverrisson, Unnur Thorsteinsdottir, Kari Stefansson, David O Arnar
AIMS: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in man, causing substantial morbidity and mortality with a major worldwide public health impact. It is increasingly recognized as a highly heritable condition. This study aimed to determine genetic risk factors for early-onset AF. METHODS AND RESULTS: We sequenced the whole genomes of 8453 Icelanders and imputed genotypes of the 25.5 million sequence variants we discovered into 1799 Icelanders with early-onset AF (diagnosed before 60 years of age) and 337 453 controls...
October 14, 2016: European Heart Journal
Audrey N Chang, Kristine E Kamm, James T Stull
Maintenance of contractile performance of the heart is achieved in part by the constitutive 40% phosphorylation of myosin regulatory light chain (RLC) in sarcomeres. The importance of this extent of RLC phosphorylation for optimal cardiac performance becomes apparent when various mouse models and resultant phenotypes are compared. The absence or attenuation of RLC phosphorylation results in poor performance leading to heart failure, whereas increased RLC phosphorylation is associated with cardiac protection from stresses...
October 11, 2016: Journal of Molecular and Cellular Cardiology
Holly Tiffany, Kanchan Sonkar, Matthew J Gage
The giant sarcomere protein titin is the third filament in muscle and is integral to maintaining sarcomere integrity as well as contributing to both active and passive tension. Titin is a multi-domain protein that contains regions of repeated structural elements. The N2A region sits at the boundary between the proximal Ig region of titin that is extended under low force and the PEVK region that is extended under high force. Multiple binding interactions have been associated with the N2A region and it has been proposed that this region acts as a mechanical stretch sensor...
October 11, 2016: Biochimica et Biophysica Acta
Beatriz Piva E Mattos, Fernando Luís Scolari, Marco Antonio Rodrigues Torres, Laura Simon, Valéria Centeno de Freitas, Roberto Giugliani, Úrsula Matte
Background: Mutations in sarcomeric genes are found in 60-70% of individuals with familial forms of hypertrophic cardiomyopathy (HCM). However, this estimate refers to northern hemisphere populations. The molecular-genetic profile of HCM has been subject of few investigations in Brazil, particularly in the south of the country. Objective: To investigate mutations in the sarcomeric genes MYH7, MYBPC3 and TNNT2 in a cohort of HCM patients living in the extreme south of Brazil, and to evaluate genotype-phenotype associations...
September 2016: Arquivos Brasileiros de Cardiologia
Alexandra Pérez-Serra, Rocio Toro, Georgia Sarquella-Brugada, David de Gonzalo-Calvo, Sergi Cesar, Esther Carro, Vicenta Llorente-Cortes, Anna Iglesias, Josep Brugada, Ramon Brugada, Oscar Campuzano
Dilated cardiomyopathy is a rare cardiac disease characterized by left ventricular dilatation and systolic dysfunction leading to heart failure and sudden cardiac death. Currently, despite several conditions have been reported as aetiologies of the disease, a large number of cases remain classified as idiopathic. Recent studies determine that nearly 60% of cases are inherited, therefore due to a genetic cause. Progressive technological advances in genetic analysis have identified over 60 genes associated with this entity, being TTN the main gene, so far...
September 21, 2016: International Journal of Cardiology
Junqi Huang, Ting Gang Chew, Ying Gu, Saravanan Palani, Anton Kamnev, Douglas S Martin, Nicholas J Carter, Robert Anthony Cross, Snezhana Oliferenko, Mohan K Balasubramanian
Many eukaryotes assemble a ring-shaped actomyosin network that contracts to drive cytokinesis. Unlike actomyosin in sarcomeres, which cycles through contraction and relaxation, the cytokinetic ring disassembles during contraction through an unknown mechanism. Here we find in Schizosaccharomyces japonicus and Schizosaccharomyces pombe that, during actomyosin ring contraction, actin filaments associated with actomyosin rings are expelled as micron-scale bundles containing multiple actomyosin ring proteins. Using functional isolated actomyosin rings we show that expulsion of actin bundles does not require continuous presence of cytoplasm...
October 13, 2016: ELife
Daniel A Hernandez, Christina M Bennett, Lyubov Dunina-Barkovskaya, Tatjana Wedig, Yassemi Capetanaki, Harald Herrmann, Gloria M Conover
In the hearts of patients bearing nebulette mutations, a severe general disorganization in cardiomyocytes of the extrasarcomeric desmin intermediate filament system is frequently observed. However, the molecular and functional relationship between the desmin cytoskeleton and nebulette-containing sarcomeres is still unclear. Here we report a high-affinity in vitro interaction between nebulette and desmin filaments. A major interaction site has been mapped to the desmin α-helical rod domain indicating that the filament core is directly involved in the binding of nebulette...
October 12, 2016: Molecular Biology of the Cell
Arkadi Shwartz, Nagaraju Dhanyasi, Eyal D Schejter, Ben-Zion Shilo
Actin-based thin filament arrays constitute a fundamental core component of muscle sarcomeres. We have used formation of the Drosophila indirect flight musculature for studying the assembly and maturation of thin-filament arrays in a skeletal muscle model system. Employing GFP-tagged actin monomer incorporation, we identify several distinct phases in the dynamic construction of thin-filament arrays. This sequence includes assembly of nascent arrays after an initial period of intensive microfilament synthesis, followed by array elongation, primarily from filament pointed-ends, radial growth of the arrays via recruitment of peripheral filaments and continuous barbed-end turnover...
October 12, 2016: ELife
Iman A Mohamed, Navaneethakrishnan T Krishnamoorthy, Gheyath K Nasrallah, Sahar Da'as
Hypertrophic cardiomyopathy (HCM) is a common autosomal dominant genetic cardiovascular disorder marked by genetic and phenotypic heterogeneity. Mutations in the gene encodes the cardiac myosin-binding protein C, cMYBPC3 is amongst the various sarcomeric genes that are associated with HCM. These mutations produce mutated mRNAs and truncated cMyBP-C proteins. In this review, we will discuss the implications and molecular mechanisms involved in MYBPC3 different mutations. Further, we will highlight the novel targets that can be developed into potential therapeutics for the treatment of HMC...
October 12, 2016: Journal of Cellular Physiology
Richard Cv Tyser, Antonio Ma Miranda, Chiann-Mun Chen, Sean M Davidson, Shankar Srinivas, Paul R Riley
The mammalian heartbeat is thought to begin just prior to the linear heart tube stage of development. How the initial contractions are established and the downstream consequences of the earliest contractile function on cardiac differentiation and morphogenesis have not been described. Using high-resolution live imaging of mouse embryos, we observed randomly distributed spontaneous asynchronous Ca(2+)-oscillations (SACOs) in the forming cardiac crescent (stage E7.75) prior to overt beating. Nascent contraction initiated at around E8...
October 11, 2016: ELife
Christopher P Jackman, Aaron L Carlson, Nenad Bursac
Engineered cardiac tissues hold promise for cell therapy and drug development, but exhibit inadequate function and maturity. In this study, we sought to significantly improve the function and maturation of rat and human engineered cardiac tissues. We developed dynamic, free-floating culture conditions for engineering "cardiobundles", 3-dimensional cylindrical tissues made from neonatal rat cardiomyocytes or human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) embedded in fibrin-based hydrogel. Compared to static culture, 2-week dynamic culture of neonatal rat cardiobundles significantly increased expression of sarcomeric proteins, cardiomyocyte size (∼2...
September 30, 2016: Biomaterials
Mayra de A Marques, Guilherme A P de Oliveira
Inherited myopathies affect both skeletal and cardiac muscle and are commonly associated with genetic dysfunctions, leading to the production of anomalous proteins. In cardiomyopathies, mutations frequently occur in sarcomeric genes, but the cause-effect scenario between genetic alterations and pathological processes remains elusive. Hypertrophic cardiomyopathy (HCM) was the first cardiac disease associated with a genetic background. Since the discovery of the first mutation in the β-myosin heavy chain, more than 1400 new mutations in 11 sarcomeric genes have been reported, awarding HCM the title of the "disease of the sarcomere...
2016: Frontiers in Physiology
Katharine A Michie, Ann H Kwan, Chang-Shung Tung, J Mitchell Guss, Jill Trewhella
The nuclear magnetic resonance (NMR) structure of the tri-helix bundle (THB) of the m-domain plus C2 (ΔmC2) of myosin-binding protein C (MyBP-C) has revealed a highly flexible seven-residue linker between the structured THB and C2. Bioinformatics shows significant patterns of conservation across the THB-linker sequence, with the linker containing a strictly conserved serine in all MyBP-C isoforms. Clinically linked mutations further support the functional significance of the THB-linker region. NMR, small-angle X-ray scattering, and binding studies show the THB-linker plus the first ten residues of C2 undergo dramatic changes when ΔmC2 binds Ca(2+)-calmodulin, with the linker and C2 N-terminal residues contributing significantly to the affinity...
October 4, 2016: Structure
Lauren J Dupuis, Joost Lumens, Theo Arts, Tammo Delhaas
We developed a model of cardiac sarcomere contraction to study the calcium-tension relationship in cardiac muscle. Calcium mediates cardiac contraction through its interactions with troponin (Tn) and subsequently tropomyosin molecules. Experimental studies have shown that a slight increase in intracellular calcium concentration leads to a rapid increase in sarcomeric tension. Though it is widely accepted that the rapid increase is not possible without the concept of cooperativity, the mechanism is debated. We use the hypothesis that there exists a base level of cooperativity intrinsic to the thin filament that is boosted by mechanical tension, i...
October 2016: PLoS Computational Biology
Na Zhang, Feiming Ye, Wei Zhu, Dexing Hu, Changchen Xiao, Jinliang Nan, Sheng'an Su, Yingchao Wang, Mingfei Liu, Kanglu Gao, Xinyang Hu, Jinghai Chen, Hong Yu, Xiaojie Xie, Jian'an Wang
Cardiac ankyrin repeat protein (CARP) is a nuclear transcriptional co-factor that has additional functions in the myoplasm as a component of the muscle sarcomere. Previous studies have demonstrated increased expression of CARP in cardiovascular diseases, however, its role in cardiomyocyte apoptosis is unclear and controversial. In the present study, we investigated possible roles of CARP in hypoxia/reoxygenation (H/R) -induced cardiomyocyte apoptosis and the underlying mechanisms. Neonatal mouse ventricular cardiomyocytes were isolated and infected with adenovirus encoding Flag-tagged CARP (Ad-CARP) and lentivirus encoding CARP targeted shRNA (sh-CARP), respectively...
October 3, 2016: Biochimica et Biophysica Acta
Henry G Zot, Javier E Hasbun
To explain disparate decay rates of cytosolic Ca(2+) and structural changes in the thin filaments during a twitch, we model the time course of Ca(2+)-bound troponin (Tn) resulting from the free Ca(2+) transient of fast skeletal muscle. In fibers stretched beyond overlap, the decay of Ca(2+) as measured by a change in fluo-3 fluorescence is significantly slower than the intensity decay of the meridional 1/38.5 nm(-1) reflection of Tn; this is not simply explained by considering only the Ca(2+) binding properties of Tn alone (Matsuo et al...
2016: Frontiers in Physiology
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