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https://www.readbyqxmd.com/read/28634611/micro-and-nano-patterned-conductive-graphene-peg-hybrid-scaffolds-for-cardiac-tissue-engineering
#1
Alec S T Smith, Hyok Yoo, Hyunjung Yi, Eun Hyun Ahn, Justin H Lee, Guozheng Shao, Ekaterina Nagornyak, Michael A Laflamme, Charles E Murry, Deok-Ho Kim
A lack of electrical conductivity and structural organization in currently available biomaterial scaffolds limits their utility for generating physiologically representative models of functional cardiac tissue. Here we report on the development of scalable, graphene-functionalized topographies with anisotropic electrical conductivity for engineering the structural and functional phenotypes of macroscopic cardiac tissue constructs. Guided by anisotropic electroconductive and topographic cues, the tissue constructs displayed structural property enhancement in myofibrils and sarcomeres, and exhibited significant increases in the expression of cell-cell coupling and calcium handling proteins, as well as in action potential duration and peak calcium release...
June 21, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28630914/deregulated-ca-2-cycling-underlies-the-development-of-arrhythmia-and-heart-disease-due-to-mutant-obscurin
#2
Li-Yen R Hu, Maegen A Ackermann, Peter A Hecker, Benjamin L Prosser, Brendan King, Kelly A O'Connell, Alyssa Grogan, Logan C Meyer, Christopher E Berndsen, Nathan T Wright, W Jonathan Lederer, Aikaterini Kontrogianni-Konstantopoulos
Obscurins are cytoskeletal proteins with structural and regulatory roles encoded by OBSCN. Mutations in OBSCN are associated with the development of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Specifically, the R4344Q mutation present in immunoglobulin domain 58 (Ig58) was the first to be linked with the development of HCM. To assess the effects of R4344Q in vivo, we generated the respective knock-in mouse model. Mutant obscurins are expressed and incorporated normally into sarcomeres...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28624812/extracorporeal-shock-wave-treatment-attenuated-left-ventricular-dysfunction-and-remodeling-in-mini-pig-with-cardiorenal-syndrome
#3
Jiunn-Jye Sheu, Hani E E Ali, Ben-Chung Cheng, Hsin-Ju Chiang, Pei-Hsun Sung, Kuan-Hung Chen, Chih-Chao Yang, Yen-Ta Chen, John Y Chiang, Pao-Yuan Lin, Sarah Chua, Han-Tan Chai, Sheng-Ying Chung, Cheuk-Kwan Sun, Hon-Kan Yip
This study tested the hypothesis that extracorporeal shock wave (ECSW) treatment can improve ischemia-induced left ventricular (LV) dysfunction in mini-pig with co-existing chronic kidney disease (CKD). LV ischemia in mini-pigs was induced by applying an ameroid constrictor over mid-left anterior descending artery (LAD), while model of CKD was established by right nephrectomy with partial ligation of left renal arterioles 2 weeks before LAD constriction. Thirty mini-pigs were randomly divided into group 1 (sham-control), group 2 (LV-ischemia), group 3 (LV-ischemia + CKD), Group 4 [LV-ischemia + ECSW (applied 1200 shots at 0...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28623958/knockdown-of-subunit-3-of-the-cop9-signalosome-inhibits-c2c12-myoblast-differentiation-via-nf-kappab-signaling-pathway
#4
Mariam A Ba, Jeffrey Surina, Cherie A Singer, Maria L Valencik
BACKGROUND: The COP9 signalosome (CSN) is a conserved protein complex composed of 8 subunits designated CSN1-CSN8. CSN3 represents the third subunit of the CSN and maintains the integrity of the complex. CSN3 binds to the striated muscle-specific β1D integrin tail, and its subcellular localization is altered in differentiated skeletal muscle cells. However, the role of CSN3 in skeletal muscle differentiation is unknown. The main goal of this study was to identify whether CSN3 participates in myoblast differentiation and the signalling mechanisms involved using C2C12 cells as a skeletal muscle cell model...
June 17, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28622706/electrical-stimulation-of-microengineered-skeletal-muscle-tissue-effect-of-stimulus-parameters-on-myotube-contractility-and-maturation
#5
Ramin Banan Sadeghian, Majid Ebrahimi, Sahar Salehi
Skeletal muscle tissues engineered in vitro are aneural, short in number of fibers required to function properly, and degenerate rapidly. Electrical stimulation has been widely used to compensate for such lack of neural activity, yet the relationship between the stimulation parameters and the tissue response is subject of debate. Here we study the effect of overnight electrical stimulation (training) on the contractility and maturity of aligned C2C12 myotubes developed on micropatterned gelatin methacryloyl (GelMA) substrates...
June 16, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28617969/conditionally-targeted-deletion-of-psen1-leads-to-diastolic-heart-dysfunction
#6
Xiao-Wei Song, Qing-Ning Yuan, Ying Tang, Mi Cao, Ya-Feng Shen, Zhen-Yu Zeng, Chang-Hai Lei, SongHua Li, Xian-Xian Zhao, Yong-Ji Yang
Recently, PSEN1 has been reported to have mutations in dilated cardiomyopathy pedigrees. However, the function and mechanism of PSEN1 in cardiomyopathy remains unresolved. Here, we established 4 types of genetically modified mice to determine the function of PSEN1 in cardiac development and pathology. PSEN1 null mutation resulted in perinatal death, retardation of heart growth, ventricular dilatation, septum defects, and valvular thickening. PSEN1 knockout in adults led to decreased muscle fibers, widened sarcomere Z lines and reduced lengths of sarcomeres in cardiomyocytes...
June 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28615380/leucine-differentially-regulates-gene-specific-translation-in-mouse-skeletal-muscle
#7
Micah J Drummond, Paul T Reidy, Lisa M Baird, Brian K Dalley, Michael T Howard
Background: Amino acids, especially leucine, are particularly effective in promoting protein synthesis. Leucine is known to increase the rate of protein synthesis in skeletal muscle through the mechanistic target of rapamycin complex 1-dependent, as well as -independent, signaling pathways. However, the overall translation program is poorly defined, and it is unknown how the activation of these pathways differentially controls the translation of specific mRNAs.Objective: Ribosome profiling and RNA sequencing were used to precisely define the translational program activated by an acute oral dose of leucine...
June 14, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28614723/single-muscle-fiber-proteomics-reveals-fiber-type-specific-features-of-human-muscle-aging
#8
Marta Murgia, Luana Toniolo, Nagarjuna Nagaraj, Stefano Ciciliot, Vincenzo Vindigni, Stefano Schiaffino, Carlo Reggiani, Matthias Mann
Skeletal muscle is a key tissue in human aging, which affects different muscle fiber types unequally. We developed a highly sensitive single muscle fiber proteomics workflow to study human aging and show that the senescence of slow and fast muscle fibers is characterized by diverging metabolic and protein quality control adaptations. Whereas mitochondrial content declines with aging in both fiber types, glycolysis and glycogen metabolism are upregulated in slow but downregulated in fast muscle fibers. Aging mitochondria decrease expression of the redox enzyme monoamine oxidase A...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28612341/cardiomyocyte-marker-expression-in-dogs-with-left-atrial-enlargement-due-to-dilated-cardiomyopathy-or-myxomatous-mitral-valve-disease
#9
Izabela Janus, Malgorzata Kandefer-Gola, Rafal Ciaputa, Agnieszka Noszczyk-Nowak, Urszula Paslawska, Massimiliano Tursi, Marcin Nowak
INTRODUCTION: Dilated cardiomyopathy (DCM) and myxomatous mitral valve disease (MMVD) are common heart conditions in dogs. They have different etiology and pathogenesis and although other studies focused on changes in the left ventricles of the affected hearts, the aim of our study was to assess the expressions of some intrinsic proteins in the enlarged left atria. MATERIAL AND METHODS: We performed an immunohistochemical analysis of left atrial specimens obtained from 15 dogs with DCM, 35 dogs with MMVD and six control dogs...
June 14, 2017: Folia Histochemica et Cytobiologica
https://www.readbyqxmd.com/read/28606303/effects-of-myosin-variants-on-interacting-heads-motif-explain-distinct-hypertrophic-and-dilated-cardiomyopathy-phenotypes
#10
Lorenzo Alamo, James S Ware, Antonio Pinto, Richard E Gillilan, Jonathan G Seidman, Christine E Seidman, Raúl Padrón
Cardiac β-myosin variants cause hypertrophic (HCM) or dilated (DCM) cardiomyopathy by disrupting sarcomere contraction and relaxation. The locations of variants on isolated myosin head structures predict contractility effects but not the prominent relaxation and energetic deficits that characterize HCM. During relaxation, pairs of myosins form interacting-heads motif (IHM) structures that with other sarcomere proteins establish an energy-saving, super-relaxed (SRX) state. Using a human β-cardiac myosin IHM quasi-atomic model, we defined interactions sites between adjacent myosin heads and associated protein partners, and then analyzed rare variants from 6112 HCM and 1315 DCM patients and 33,370 ExAC controls...
June 13, 2017: ELife
https://www.readbyqxmd.com/read/28603979/clinically-divergent-mutation-effects-on-the-structure-and-function-of-the-human-cardiac-tropomyosin-overlap
#11
Mark McConnell, Lauren Tal Grinspan, Michael R Williams, Melissa L Lynn, Benjamin A Schwartz, Ofer Z Fass, Steven D Schwartz, Jil C Tardiff
The progression of genetically inherited cardiomyopathies from an altered protein structure to clinical presentation of disease is not well understood. One of the main roadblocks to mechanistic insight remains a lack of high-resolution structural information about multiprotein complexes within the cardiac sarcomere. One example is the tropomyosin (Tm) overlap region of the thin filament that is crucial for the function of the cardiac sarcomere. To address this central question, we devised coupled experimental and computational modalities to characterize the baseline function and structure of the Tm overlap, as well as the effects of mutations causing divergent patterns of ventricular remodeling on both structure and function...
June 21, 2017: Biochemistry
https://www.readbyqxmd.com/read/28594468/application-of-an-advanced-maximum-likelihood-estimation-restoration-method-for-enhanced-resolution-and-contrast-in-second-harmonic-generation-microscopy
#12
Mayandi Sivaguru, Mohammad M Kabir, Manas Rangan Gartia, David S C Biggs, Barghav S Sivaguru, Vignesh A Sivaguru, Glenn A Fried, Gang Logan Liu, Sakthivel Sadayappan, Kimani C Toussaint
Second-harmonic generation (SHG) microscopy has gained popularity because of its ability to perform submicron, label-free imaging of noncentrosymmetric biological structures, such as fibrillar collagen in the extracellular matrix environment of various organs with high contrast and specificity. Because SHG is a two-photon coherent scattering process, it is difficult to define a point spread function (PSF) for this modality. Hence, compared to incoherent two-photon processes like two-photon fluorescence, it is challenging to apply the various PSF-engineering methods to improve the spatial resolution to be close to the diffraction limit...
June 8, 2017: Journal of Microscopy
https://www.readbyqxmd.com/read/28587156/differential-sarcomere-and-electrophysiological-maturation-of-human-ipsc-derived-cardiac-myocytes-in-monolayer-vs-aggregation-based-differentiation-protocols
#13
Dorota Jeziorowska, Vincent Fontaine, Charlène Jouve, Eric Villard, Sébastien Dussaud, David Akbar, Valérie Letang, Pauline Cervello, Jean-Michiel Itier, Marie-Pierre Pruniaux, Jean-Sébastien Hulot
Human induced pluripotent stem cells (iPSCs) represent a powerful human model to study cardiac disease in vitro, notably channelopathies and sarcomeric cardiomyopathies. Different protocols for cardiac differentiation of iPSCs have been proposed either based on embroid body formation (3D) or, more recently, on monolayer culture (2D). We performed a direct comparison of the characteristics of the derived cardiomyocytes (iPSC-CMs) on day 27 ± 2 of differentiation between 3D and 2D differentiation protocols with two different Wnt-inhibitors were compared: IWR1 (inhibitor of Wnt response) or IWP2 (inhibitor of Wnt production)...
June 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28581678/ttn-genotype-is-associated-with-fascicle-length-and-marathon-running-performance
#14
Georgina K Stebbings, Alun G Williams, Adam J Herbert, Sarah J Lockey, Shane M Heffernan, Robert M Erskine, Christopher I Morse, Stephen H Day
Titin provides a molecular blueprint for muscle sarcomere assembly and sarcomere length can vary according to titin isoform expression. If variations in sarcomere length influence muscle fascicle length, this may provide an advantage for running performance. Thus the aim of this study was to investigate if the titin (TTN) rs10497520 polymorphism was associated with muscle fascicle length in recreationally active men (RA; n = 137) and marathon personal best time in male marathon runners (MR; n = 141). Fascicle length of the vastus lateralis was assessed in vivo using B-mode ultrasonography at 50% of muscle length in RA...
June 5, 2017: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/28578654/progressive-resistance-training-in-head-and-neck-cancer-patients-during-concomitant-chemoradiotherapy-design-of-the-dahanca-31-randomized-trial
#15
Camilla K Lonkvist, Simon Lønbro, Anders Vinther, Bo Zerahn, Eva Rosenbom, Hanne Primdahl, Pernille Hojman, Julie Gehl
BACKGROUND: Head and neck cancer patients undergoing concomitant chemoradiotherapy (CCRT) frequently experience loss of muscle mass and reduced functional performance. Positive effects of exercise training are reported for many cancer types but biological mechanisms need further elucidation. This randomized study investigates whether progressive resistance training (PRT) may attenuate loss of muscle mass and functional performance. Furthermore, biochemical markers and muscle biopsies will be investigated trying to link biological mechanisms to training effects...
June 3, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28577375/moisture-migration-microstructure-damage-and-protein-structure-changes-in-porcine-longissimus-muscle-as-influenced-by-multiple-freeze-thaw-cycles
#16
Mingcheng Zhang, Fangfei Li, Xinping Diao, Baohua Kong, Xiufang Xia
This study investigated the effects of multiple freeze-thaw (F-T) cycles on water mobility, microstructure damage and protein structure changes in porcine longissimus muscle. The transverse relaxation time T2 increased significantly when muscles were subjected to multiple F-T cycles (P<0.05), which means that immobile water shifted to free water and the free water mobility increased. Multiple F-T cycles caused sarcomere shortening, Z line fractures, and I band weakening and also led to microstructural destruction of muscle tissue...
May 27, 2017: Meat Science
https://www.readbyqxmd.com/read/28577155/rbm20-a-potential-target-for-treatment-of-cardiomyopathy-via-titin-isoform-switching
#17
REVIEW
Wei Guo, Mingming Sun
Cardiomyopathy, also known as heart muscle disease, is an unfavorable condition leading to alterations in myocardial contraction and/or impaired ability of ventricular filling. The onset and development of cardiomyopathy have not currently been well defined. Titin is a giant multifunctional sarcomeric filament protein that provides passive stiffness to cardiomyocytes and has been implicated to play an important role in the origin and development of cardiomyopathy and heart failure. Titin-based passive stiffness can be mainly adjusted by isoform switching and post-translational modifications in the spring regions...
June 2, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28574610/costamere-protein-expression-and-tissue-composition-of-rotator-cuff-muscle-after-tendon-release-in-sheep
#18
Severin Ruoss, Christoph B Möhl, Mario C Benn, Brigitte von Rechenberg, Karl Wieser, Dominik C Meyer, Christian Gerber, Martin Flück
Previous studies suggested that degradation of contractile tissue requires cleavage of the costamere, a structural protein complex that holds sarcomeres in place. This study examined if costamere turnover is affected by a rotator cuff tear in a previously established ovine model. We found the activity of focal adhesion kinase (FAK), a main regulator of costamere turnover, was unchanged at 2 weeks but decreased by 27% 16 weeks after surgical release of the infraspinatus tendon. This was accompanied by cleavage of the costamere protein talin into a 190 kDa fragment while full length talin remained unchanged...
June 2, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28571807/dilated-cardiomyopathy-induced-disruption-of-basement-membrane-alters-the-lever-systems-acting-on-the-heart
#19
Iman A Mohamed, Nagwa El-Badri, Amr Zaher
Dilated cardiomyopathy (DCM) is considered the most common form of non-ischemic heart diseases. DCM, occurs in response to both non-genetic and genetic factors, and has been associated with cytoskeletal protein mutations, impairing the contractile apparatus of cardiac myocytes. However, the pathology underlying the marked left ventricular dilatation remains unclear. Moreover, patients with end-stage DCM show alterations in the composition of the extracellular matrix (ECM), and myocardial fibrosis even when the cardiac myocytes are intact...
June 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28569755/myomerger-induces-fusion-of-non-fusogenic-cells-and-is-required-for-skeletal-muscle-development
#20
Malgorzata E Quinn, Qingnian Goh, Mitsutoshi Kurosaka, Dilani G Gamage, Michael J Petrany, Vikram Prasad, Douglas P Millay
Despite the importance of cell fusion for mammalian development and physiology, the factors critical for this process remain to be fully defined, which has severely limited our ability to reconstitute cell fusion. Myomaker (Tmem8c) is a muscle-specific protein required for myoblast fusion. Expression of myomaker in fibroblasts drives their fusion with myoblasts, but not with other myomaker-expressing fibroblasts, highlighting the requirement of additional myoblast-derived factors for fusion. Here we show that Gm7325, which we name myomerger, induces the fusion of myomaker-expressing fibroblasts...
June 1, 2017: Nature Communications
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