keyword
MENU ▼
Read by QxMD icon Read
search

sarcomere

keyword
https://www.readbyqxmd.com/read/29053464/co-expression-network-approach-to-studying-the-effects-of-botulinum-neurotoxin-a
#1
Kavitha Mukund, Samuel R Ward, Richard L Lieber, Shankar Subramaniam
Botulinum Neurotoxin A (BoNT-A) is a potent neurotoxin with several clinical applications.The goal of this study was to utilize co-expression network theory to analyze temporal transcriptional data from skeletal muscle after BoNT-A treatment. Expression data for 2000 genes (extracted using a ranking heuristic) served as the basis for this analysis. Using weighted gene co-expression network analysis (WGCNA), we identified 19 co-expressed modules, further hierarchically clustered into 5 groups. Quantifying average expression and co-expression patterns across these groups revealed temporal aspects of muscle's response to BoNT-A...
October 16, 2017: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/29051544/estimating-prognosis-in-patients-with-acute-myocardial-infarction-using-personalized-computational-heart-models
#2
Hao Gao, Kenneth Mangion, David Carrick, Dirk Husmeier, Xiaoyu Luo, Colin Berry
Biomechanical computational models have potential prognostic utility in patients after an acute ST-segment-elevation myocardial infarction (STEMI). In a proof-of-concept study, we defined two groups (1) an acute STEMI group (n = 6, 83% male, age 54 ± 12 years) complicated by left ventricular (LV) systolic dysfunction; (2) an age- and sex- matched hyper-control group (n = 6, 83% male, age 46 ± 14 years), no prior history of cardiovascular disease and normal systolic blood pressure (SBP < 130 mmHg)...
October 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29050564/a-missense-variant-in-plec-increases-risk%C3%A2-of-atrial-fibrillation
#3
Rosa B Thorolfsdottir, Gardar Sveinbjornsson, Patrick Sulem, Anna Helgadottir, Solveig Gretarsdottir, Stefania Benonisdottir, Audur Magnusdottir, Olafur B Davidsson, Sridharan Rajamani, Dan M Roden, Dawood Darbar, Terje R Pedersen, Marc S Sabatine, Ingileif Jonsdottir, David O Arnar, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Hilma Holm, Kari Stefansson
BACKGROUND: Genome-wide association studies (GWAS) have yielded variants at >30 loci that associate with atrial fibrillation (AF), including rare coding mutations in the sarcomere genes MYH6 and MYL4. OBJECTIVES: The aim of this study was to search for novel AF associations and in doing so gain insights into the mechanisms whereby variants affect AF risk, using electrocardiogram (ECG) measurements. METHODS: The authors performed a GWAS of 14,255 AF cases and 374,939 controls, using whole-genome sequence data from the Icelandic population, and tested novel signals in 2,002 non-Icelandic cases and 12,324 controls...
October 24, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29046390/novel-sarcopenia-related-alterations-in-sarcomeric-protein-post-translational-modifications-in-skeletal-muscles-identified-by-top-down-proteomics
#4
Liming Wei, Zachery R Gregorich, Ziqing Lin, Wenxuan Cai, Yutong Jin, Susan H McKiernan, Sean McIlwain, Judd M Aiken, Richard L Moss, Gary M Diffee, Ying Ge
Sarcopenia, the age-related loss of skeletal muscle mass and strength, is a significant cause of morbidity in the elderly and is a major burden on health care systems. Unfortunately, the underlying molecular mechanisms in sarcopenia remain poorly understood. Herein, we utilized top-down proteomics to elucidate sarcopenia-related changes in the fast- and slow-twitch skeletal muscles of aging rats with a focus on the sarcomeric proteome, which includes both myofilament and Z-disc proteins-the proteins that constitute the contractile apparatuses...
October 18, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29037217/subtype-specific-differentiation-of-cardiac-pacemaker-cell-clusters-from-human-induced-pluripotent-stem-cells
#5
Patrick A Schweizer, Fabrice F Darche, Nina D Ullrich, Pascal Geschwill, Boris Greber, Rasmus Rivinius, Claudia Seyler, Karin Müller-Decker, Andreas Draguhn, Jochen Utikal, Michael Koenen, Hugo A Katus, Dierk Thomas
BACKGROUND: Human induced pluripotent stem cells (hiPSC) harbor the potential to differentiate into diverse cardiac cell types. Previous experimental efforts were primarily directed at the generation of hiPSC-derived cells with ventricular cardiomyocyte characteristics. Aiming at a straightforward approach for pacemaker cell modeling and replacement, we sought to selectively differentiate cells with nodal-type properties. METHODS: hiPSC were differentiated into spontaneously beating clusters by co-culturing with visceral endoderm-like cells in a serum-free medium...
October 16, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29030372/dose-dependent-effects-of-the-myosin-activator-omecamtiv-mecarbil-on-cross-bridge-behavior-and-force-generation-in-failing-human-myocardium
#6
Ranganath Mamidi, Jiayang Li, Kenneth S Gresham, Sujeet Verma, Chang Yoon Doh, Amy Li, Sean Lal, Cristobal G Dos Remedios, Julian E Stelzer
BACKGROUND: Omecamtiv mecarbil (OM) enhances systolic function in vivo by directly binding the myosin cross-bridges (XBs) in the sarcomere. However, the mechanistic details governing OM-induced modulation of XB behavior in failing human myocardium are unclear. METHODS AND RESULTS: The effects of OM on steady state and dynamic XB behavior were measured in chemically skinned myocardial preparations isolated from human donor and heart failure (HF) left ventricle. HF myocardium exhibited impaired contractile function as evidenced by reduced maximal force, magnitude of XB recruitment (Pdf), and a slowed rate of XB detachment (krel) at submaximal Ca(2+) activations...
October 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/29025768/action-potential-shortening-and-impairment-of-cardiac-function-by-ablation-of-slc26a6
#7
Padmini Sirish, Hannah A Ledford, Valeriy Timofeyev, Phung N Thai, Lu Ren, Hyo Jeong Kim, Seojin Park, Jeong Han Lee, Gu Dai, Maryam Moshref, Choong-Ryoul Sihn, Wei Chun Chen, Maria Valeryevna Timofeyeva, Zhong Jian, Rafael Shimkunas, Leighton T Izu, Nipavan Chiamvimonvat, Ye Chen-Izu, Ebenezer N Yamoah, Xiao-Dong Zhang
BACKGROUND: Intracellular pH (pHi) is critical to cardiac excitation and contraction; uncompensated changes in pHi impair cardiac function and trigger arrhythmia. Several ion transporters participate in cardiac pHi regulation. Our previous studies identified several isoforms of a solute carrier Slc26a6 to be highly expressed in cardiomyocytes. We show that Slc26a6 mediates electrogenic Cl(-)/HCO3(-) exchange activities in cardiomyocytes, suggesting the potential role of Slc26a6 in regulation of not only pHi, but also cardiac excitability...
October 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/29023566/cardiac-leiomodin2-binds-to-the-sides-of-actin-filaments-and-regulates-the-atpase-activity-of-myosin
#8
Dávid Szatmári, Beáta Bugyi, Zoltán Ujfalusi, László Grama, Réka Dudás, Miklós Nyitrai
Leiomodin proteins are vertebrate homologues of tropomodulin, having a role in the assembly and maintenance of muscle thin filaments. Leiomodin2 contains an N-terminal tropomodulin homolog fragment including tropomyosin-, and actin-binding sites, and a C-terminal Wiskott-Aldrich syndrome homology 2 actin-binding domain. The cardiac leiomodin2 isoform associates to the pointed end of actin filaments, where it supports the lengthening of thin filaments and competes with tropomodulin. It was recently found that cardiac leiomodin2 can localise also along the length of sarcomeric actin filaments...
2017: PloS One
https://www.readbyqxmd.com/read/29021349/activation-of-autophagy-ameliorates-cardiomyopathy-in-mybpc3-targeted-knockin-mice
#9
Sonia R Singh, Antonia T L Zech, Birgit Geertz, Silke Reischmann-Düsener, Hanna Osinska, Maksymilian Prondzynski, Elisabeth Krämer, Qinghang Meng, Charles Redwood, Jolanda van der Velden, Jeffrey Robbins, Saskia Schlossarek, Lucie Carrier
BACKGROUND: Alterations in autophagy have been reported in hypertrophic cardiomyopathy (HCM) caused by Danon disease, Vici syndrome, or LEOPARD syndrome, but not in HCM caused by mutations in genes encoding sarcomeric proteins, which account for most of HCM cases. MYBPC3, encoding cMyBP-C (cardiac myosin-binding protein C), is the most frequently mutated HCM gene. METHODS AND RESULTS: We evaluated autophagy in patients with HCM carrying MYBPC3 mutations and in a Mybpc3-targeted knockin HCM mouse model, as well as the effect of autophagy modulators on the development of cardiomyopathy in knockin mice...
October 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/29018006/%C3%AE-galactosidase-a-genotype-n215s-induces-a-specific-cardiac-variant-of-fabry-disease
#10
Daniel Oder, Dan Liu, Kai Hu, Nurcan Üçeyler, Tim Salinger, Jonas Müntze, Kristina Lorenz, Reinhard Kandolf, Hermann-Josef Gröne, Claudia Sommer, Georg Ertl, Christoph Wanner, Peter Nordbeck
BACKGROUND: Hypertrophic cardiomyopathy is the most common type of cardiomyopathy, but many patients lack sarcomeric/myofilament mutations. We studied whether cardio-specific α-galactosidase A gene variants are misinterpreted as hypertrophic cardiomyopathy because of the lack of extracardiac organ involvement. METHODS AND RESULTS: All subjects who tested positive for the N215S genotype (n=26, 13 females, mean age 49±17 [range, 14-74] years) were characterized in this prospective monocentric longitudinal cohort study to determine genotype-specific clinical characteristics of the N215S (c...
October 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28986452/care-in-specialized-centers-and-data-sharing-increase-agreement-in-hypertrophic-cardiomyopathy-genetic-test-interpretation
#11
Aisha Furqan, Patricia Arscott, Francesca Girolami, Allison L Cirino, Michelle Michels, Sharlene M Day, Iacopo Olivotto, Carolyn Y Ho, Euan Ashley, Eric M Green, Colleen Caleshu
BACKGROUND: Clinically impactful differences in the interpretation of genetic test results occur between laboratories and clinicians. To improve the classification of variants, a better understanding of why discrepancies occur and how they can be reduced is needed. METHODS AND RESULTS: We examined the frequency, causes, and resolution of discordant variant classifications in the Sarcomeric Human Cardiomyopathy Registry (SHaRe), a consortium of international centers with expertise in the clinical management and genetic architecture of hypertrophic cardiomyopathy...
October 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28982073/cardiac-specific-inactivation-of-lpp3-in-mice-leads-to-myocardial-dysfunction-and-heart-failure
#12
Mini Chandra, Diana Escalante-Alcalde, Md Shenuarin Bhuiyan, Anthony Wayne Orr, Christopher Kevil, Andrew J Morris, Hyung Nam, Paari Dominic, Kevin J McCarthy, Sumitra Miriyala, Manikandan Panchatcharam
Lipid Phosphate phosphatase 3 (LPP3), encoded by the Plpp3 gene, is an enzyme that dephosphorylates the bioactive lipid mediator lysophosphatidic acid (LPA). To study the role of LPP3 in the myocardium, we generated a cardiac specific Plpp3 deficient mouse strain. Although these mice were viable at birth in contrast to global Plpp3 knockout mice, they showed increased mortality ~ 8 months. LPP3 deficient mice had enlarged hearts with reduced left ventricular performance as seen by echocardiography. Cardiac specific Plpp3 deficient mice had longer ventricular effective refractory periods compared to their Plpp3 littermates...
September 28, 2017: Redox Biology
https://www.readbyqxmd.com/read/28978740/c-elegans-sorb-1-localizes-to-integrin-adhesion-sites-and-is-required-for-organization-of-sarcomeres-and-mitochondria-in-myocytes
#13
Timothy Loveless, Hiroshi Qadota, Guy M Benian, Jeff Hardin
We have identified and characterized sorb-1, the only Sorbin and SH3 domain-containing protein family member in C. elegans SORB-1 is strongly localized to integrin adhesion complexes in larvae and adults, including adhesion plaques and dense bodies (Z-disks) of striated muscles and attachment plaques of smooth muscles. SORB-1 is recruited to the actin-binding, membrane-distal regions of dense bodies via its C-terminal SH3 domains in an ATN-1(α-actinin)- and ALP-1(ALP/Enigma)-dependent manner, where it contributes to the organization of sarcomeres...
October 4, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28978639/molecular-plasticity-and-functional-enhancements-of-leg-muscles-in-response-to-hypergravity-in-the-fruit-fly-drosophila-melanogaster
#14
Rudolf J Schilder, Megan Raynor
Studies of organismal and tissue biomechanics have clearly demonstrated that musculoskeletal design is strongly dependent on experienced loads, which can vary in the short term, as a result of growth during life history and during the evolution of animal body size. However, how animals actually perceive and make adjustments to their load-bearing musculoskeletal elements that accommodate variation in their body weight is poorly understood. We developed an experimental model system that can be used to start addressing these open questions, and uses hypergravity centrifugation to experimentally manipulate the loads experienced by Drosophila melanogaster We examined effects of this manipulation on leg muscle alternative splicing of the sarcomere gene troponin T (Dmel\up; Fbgn0004169, herein referred to by its synonym TnT), a process that was previously demonstrated to precisely correlate with quantitative variation in body weight in Lepidoptera and rat...
October 1, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28974782/nkx2-5-%C3%A2-cardiomyoblasts-contribute-to-cardiomyogenesis-in-the-neonatal-heart
#15
Vahid Serpooshan, Yuan-Hung Liu, Jan W Buikema, Francisco X Galdos, Orlando Chirikian, Sharon Paige, Sneha Venkatraman, Anusha Kumar, David R Rawnsley, Xiaojing Huang, Daniël A Pijnappels, Sean M Wu
During normal lifespan, the mammalian heart undergoes limited renewal of cardiomyocytes. While the exact mechanism for this renewal remains unclear, two possibilities have been proposed: differentiated myocyte replication and progenitor/immature cell differentiation. This study aimed to characterize a population of cardiomyocyte precursors in the neonatal heart and to determine their requirement for cardiac development. By tracking the expression of an embryonic Nkx2.5 cardiac enhancer, we identified cardiomyoblasts capable of differentiation into striated cardiomyocytes in vitro...
October 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28973951/molecular-mechanisms-and-structural-features-of-cardiomyopathy-causing-troponin-t-mutants-in-the-tropomyosin-overlap-region
#16
Binnu Gangadharan, Margaret S Sunitha, Souhrid Mukherjee, Ritu Roy Chowdhury, Farah Haque, Narendrakumar Sekar, Ramanathan Sowdhamini, James A Spudich, John A Mercer
Point mutations in genes encoding sarcomeric proteins are the leading cause of inherited primary cardiomyopathies. Among them are mutations in the TNNT2 gene that encodes cardiac troponin T (TnT). These mutations are clustered in the tropomyosin (Tm) binding region of TnT, TNT1 (residues 80-180). To understand the mechanistic changes caused by pathogenic mutations in the TNT1 region, six hypertrophic cardiomyopathy (HCM) and two dilated cardiomyopathy (DCM) mutants were studied by biochemical approaches. Binding assays in the absence and presence of actin revealed changes in the affinity of some, but not all, TnT mutants for Tm relative to WT TnT...
October 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28972856/cardiac-actin-changes-in-the-actomyosin-interface-have-different-effects-on-myosin-duty-ratio
#17
Haidun Liu, Mary Evelyn Henein, Maria Anillo, John F Dawson
Hypertrophic cardiomyopathy (HCM) is an inherited cardiovascular disease (CD) that commonly causes an increased size of cardiomyocytes in the left ventricle. The proteins myosin and actin interact in the myocardium to produce contraction through the actomyosin ATPase cycle. The duty ratio (<i>r</i>) of myosin is the proportion of the actomyosin ATPase cycle that myosin is bound to actin and does work. A common hypothesis is that HCM mutations increase contraction in cardiac sarcomeres; however, the available data is not clear on this connection...
October 3, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28970245/differences-in-titin-segmental-elongation-between-passive-and-active-stretch-in-skeletal-muscle
#18
Michael M DuVall, Azim Jinha, Gudrun Schappacher-Tilp, Timothy R Leonard, Walter Herzog
Since the 1950's muscle contraction has been explained using a two filament system in which actin and myosin exclusively dictate active force in muscle sarcomeres. Decades later, a third filament called titin was discovered. This titin filament has recently been identified as an important regulator of active force, but has yet to be incorporated into contemporary theories of muscle contraction. When sarcomeres are actively stretched, a substantial and rapid increase in force occurs, which has been suggested to arise in part from titin-actin binding that is absent in passively stretched sarcomeres...
October 2, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28968385/a-continuum-mechanical-skeletal-muscle-model-including-actin-titin-interaction-predicts-stable-contractions-on-the-descending-limb-of-the-force-length-relation
#19
Thomas Heidlauf, Thomas Klotz, Christian Rode, Tobias Siebert, Oliver Röhrle
Contractions on the descending limb of the total (active + passive) muscle force-length relationship (i. e. when muscle stiffness is negative) are expected to lead to vast half-sarcomere-length inhomogeneities. This is however not observed in experiments-vast half-sarcomere-length inhomogeneities can be absent in myofibrils contracting in this range, and initial inhomogeneities can even decrease. Here we show that the absence of half-sarcomere-length inhomogeneities can be predicted when considering interactions of the semi-active protein titin with the actin filaments...
October 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28967302/development-of-in-vitro-drug-induced-cardiotoxicity-assay-by-using-three-dimensional-cardiac-tissues
#20
Maki Takeda, Shigeru Miyagawa, Satsuki Fukushima, Atsuhiro Saito, Emiko Ito, Akima Harada, Ryohei Matsuura, Hiroko Iseoka, Nagako Sougawa, Noriko Mochizuki-Oda, Michiya Matsusaki, Mitsuru Akashi, Yoshiki Sawa
An in vitro drug-induced cardiotoxicity assay is a critical step in drug discovery for clinical use. The use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is promising for this purpose. However, single hiPSC-CMs are limited in their ability to mimic native cardiac tissue structurally and functionally, and the generation of artificial cardiac tissue using hiPSC-CMs is an ongoing challenging. We therefore developed a new method of constructing three-dimensional (3D) artificial tissues in a short time by coating extracellular matrix components on cell surfaces...
October 1, 2017: Tissue Engineering. Part C, Methods
keyword
keyword
47474
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"