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https://www.readbyqxmd.com/read/28205229/linking-myofilaments-to-sudden-cardiac-death-recent-advances
#1
Sabine Huke
The major goal of this focused review is to highlight some of the open questions and recent advances about how a mutation in a myofilament protein leads to an increased risk for sudden cardiac death (SCD). The link between myofilaments and SCD is known for over 25 years, but identifying mutation carriers at risk for SCD is still a challenge and currently the only effective prevention is implantation of a defibrillator (ICD). In addition to recognized risk factors, other contributing factors need to be considered and assessed, e...
February 16, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28199794/the-cellular-stress-response-of-rat-skeletal-muscle-following-lengthening-contractions
#2
Evan Pollock-Tahiri, Marius Locke
The cellular stress response (CSR) of the rat tibialis anterior (TA) muscle was investigated following 20, 40 or 60 lengthening contractions (LCs) using an in-vivo model of electrical stimulation. Muscles were removed at 0, 1, 3, or 24 hours after LCs and assessed for HSF activation, HSP content and/or morphological evidence of muscle fibre damage. When compared to the first muscle contraction, peak muscle torque was reduced by 26% (p<0.05) after 20 LCs and further reduced to 56% and 60% (p<0.001) after 40 and 60 LCs, respectively...
February 15, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28194437/mitochondrial-quality-control-dysregulation-in-conditional-ho-1-mice
#3
Hagir B Suliman, Jeffrey E Keenan, Claude A Piantadosi
The heme oxygenase-1 (Hmox1; HO-1) pathway was tested for defense of mitochondrial quality control in cardiomyocyte-specific Hmox1 KO mice (HO-1[CM](-/-)) exposed to oxidative stress (100% O2). After 48 hours of exposure, these mice showed persistent cardiac inflammation and oxidative tissue damage that caused sarcomeric disruption, cardiomyocyte death, left ventricular dysfunction, and cardiomyopathy, while control hearts showed minimal damage. After hyperoxia, HO-1(CM)(-/-) hearts showed suppression of the Pgc-1α/nuclear respiratory factor-1 (NRF-1) axis, swelling, low electron density mitochondria by electron microscopy (EM), increased cell death, and extensive collagen deposition...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28193999/human-skeletal-muscle-plasmalemma-alters-its-structure-to-change-its-ca-2-handling-following-heavy-load-resistance-exercise
#4
Tanya R Cully, Robyn M Murphy, Llion Roberts, Truls Raastad, Robert G Fassett, Jeff S Coombes, Isuru D Jayasinghe, Bradley S Launikonis
High-force eccentric exercise results in sustained increases in cytoplasmic Ca(2+) levels ([Ca(2+)]cyto), which can cause damage to the muscle. Here we report that a heavy-load strength training bout greatly alters the structure of the membrane network inside the fibres, the tubular (t-) system, causing the loss of its predominantly transverse organization and an increase in vacuolation of its longitudinal tubules across adjacent sarcomeres. The transverse tubules and vacuoles displayed distinct Ca(2+)-handling properties...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28190577/dilated-cardiomyopathy
#5
REVIEW
Robert G Weintraub, Christopher Semsarian, Peter Macdonald
Dilated cardiomyopathy is defined by the presence of left ventricular dilatation and contractile dysfunction. Genetic mutations involving genes that encode cytoskeletal, sarcomere, and nuclear envelope proteins, among others, account for up to 35% of cases. Acquired causes include myocarditis and exposure to alcohol, drugs and toxins, and metabolic and endocrine disturbances. The most common presenting symptoms relate to congestive heart failure, but can also include circulatory collapse, arrhythmias, and thromboembolic events...
February 9, 2017: Lancet
https://www.readbyqxmd.com/read/28187528/ultrastructural-changes-in-human-masseter-muscles-after-botulinum-neurotoxin-a-injection
#6
Fushun Ma, Zhaohui Zhai, Shunwen Zhu, Shengjian Tang
INTRODUCTION: Botulinum neurotoxin A (BoNTA) has long been used as a therapeutic agent and has been widely accepted as a cosmetic agent in recent years. It can inhibit function and induce structural changes in skeletal muscle. METHODS: Specimens of fresh dissected human masseter muscle were used to observe the ultrastructural changes that occurred at 6 and 12 months following BoNTA injection. RESULTS: The findings observed were muscle fiber distortion, sarcomere shortening, mitochondrial vacuolar degeneration, glycogen accumulation, and H and M band disruption in the triad of tubules...
February 10, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28181243/proteasome-dysfunction-in-cardiomyopathies
#7
Jennifer E Gilda, Aldrin V Gomes
The ubiquitin-proteasome system (UPS) plays a critical role in removing unwanted intracellular proteins and is involved in protein quality control, signalling, and cell death. Because the heart is subject to continuous metabolic and mechanical stress, the proteasome plays a particularly important role in the heart, and proteasome dysfunction has been suggested as a causative factor in cardiac dysfunction. Proteasome impairment has been detected in cardiomyopathies, heart failure, myocardial ischemia, and hypertrophy...
February 8, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28176871/the-earliest-molecular-response-to-stretch-of-insect-flight-muscle-as-revealed-by-fast-x-ray-diffraction-recording
#8
Hiroyuki Iwamoto
Small insects drive their flight muscle at frequencies up to 1,000 Hz. This remarkable ability owes to the mechanism of stretch activation. However, it remains unknown as to what sarcomeric component senses the stretch and triggers the following force generation. Here we show that the earliest structural change after a step stretch is reflected in the blinking of the 111 and 201 reflections, as observed in the fast X-ray diffraction recording from isolated bumblebee flight muscle fibers. The same signal has also been observed in live bumblebee...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28174246/mechanical-tension-and-spontaneous-muscle-twitching-precede-the-formation-of-cross-striated-muscle-in-vivo
#9
Manuela Weitkunat, Martina Lindauer, Andreas Bausch, Frank Schnorrer
Muscle forces are produced by repetitive stereotyped acto-myosin units called sarcomeres. Sarcomeres are chained into linear myofibrils spanning the entire muscle fiber. In mammalian body muscles, myofibrils are aligned laterally resulting in their typical cross-striated morphology. Despite this detailed textbook knowledge about the adult muscle structure, it is still unclear how cross-striated myofibrils are built in vivo Here, we investigate the morphogenesis of Drosophila abdominal muscles and establish them as in vivo model for cross-striated muscle development...
February 7, 2017: Development
https://www.readbyqxmd.com/read/28155919/obtaining-spontaneously-beating-cardiomyocyte-like-cells-from-adipose-derived-stromal-vascular-fractions-cultured-on-enzyme-crosslinked-gelatin-hydrogels
#10
Gang Yang, Zhenghua Xiao, Xiaomei Ren, Haiyan Long, Kunlong Ma, Hong Qian, Yingqiang Guo
Heart failure often develops after acute myocardial infarction because the injured myocardial tissue fails to recover or regenerate. Stem cell transplantation using adult cell sources, such as adipose-derived stromal vascular fraction (SVF), draws extensive attention. In this study, SVF cells were isolated from rat adipose tissue and cultivated on enzyme-crosslinked gelatin hydrogels. Morphological features of cell development and spontaneous beating behavior from these cells were observed and recorded. Cardiac phenotypes were characterized via immunofluorescence staining, and the expression of cardiac-specific genes was measured via RT-PCR...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28151760/titin-truncating-mutations-in-dilated-cardiomyopathy-the-long-and-short-of-it
#11
Diane Fatkin, Inken G Huttner
PURPOSE OF REVIEW: Truncating variants in the TTN gene (TTNtv) are frequently identified in patients with dilated cardiomyopathy (DCM) but are also present in apparently healthy people in the general population. Consequently, there is considerable uncertainty about what it means for any single individual if a TTNtv is found. The aim of this review is to summarize current evidence implicating TTNtv in DCM pathogenesis and to provide some interpretative guidelines for clinical management...
February 1, 2017: Current Opinion in Cardiology
https://www.readbyqxmd.com/read/28151473/knockout-of-eva1a-leads-to-rapid-development-of-heart-failure-by-impairing-autophagy
#12
Shu Zhang, Xin Lin, Ge Li, Xue Shen, Di Niu, Guang Lu, Xin Fu, Yingyu Chen, Ming Cui, Yun Bai
EVA1A (Eva-1 homologue A) is a novel lysosome and endoplasmic reticulum-associated protein that can regulate cell autophagy and apoptosis. Eva1a is expressed in the myocardium, but its function in myocytes has not yet been investigated. Therefore, we generated inducible, cardiomyocyte-specific Eva1a knockout mice with an aim to determine the role of Eva1a in cardiac remodelling in the adult heart. Data from experiments showed that loss of Eva1a in the adult heart increased cardiac fibrosis, promoted cardiac hypertrophy, and led to cardiomyopathy and death...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28135003/modulation-of-skeletal-muscle-contraction-by-myosin-phosphorylation
#13
Rene Vandenboom
The striated muscle sarcomere is a highly organized and complex enzymatic and structural organelle. Evolutionary pressures have played a vital role in determining the structure-function relationship of each protein within the sarcomere. A key part of this multimeric assembly is the light chain-binding domain (LCBD) of the myosin II motor molecule. This elongated "beam" functions as a biological lever, amplifying small interdomain movements within the myosin head into piconewton forces and nanometer displacements against the thin filament during the cross-bridge cycle...
December 6, 2016: Comprehensive Physiology
https://www.readbyqxmd.com/read/28132108/towards-the-understanding-of-cytoskeleton-fluidisation-solidification-regulation
#14
Horacio López-Menéndez, José Félix Rodríguez
The understanding of the self-regulation of the mechanical properties in non-sarcomeric cells, such as lung cells or cells during tissue development, remains an open research problem with many unresolved issues. Their behaviour is far from the image of the traditionally studied sarcomeric cells, since the crosstalk between the signalling pathways and the complexity of the mechanical properties creates an intriguing mechano-chemical coupling. In these situations, the inelastic effects dominate the cytoskeletal structure showing phenomena like fluidisation and subsequent solidification...
January 28, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28131485/twente-spine-model-a-complete-and-coherent-dataset-for-musculo-skeletal-modeling-of-the-lumbar-region-of-the-human-spine
#15
Riza Bayoglu, Leo Geeraedts, Karlijn H J Groenen, Nico Verdonschot, Bart Koopman, Jasper Homminga
Musculo-skeletal modeling can greatly help in understanding normal and pathological functioning of the spine. For such models to produce reliable muscle and joint force estimations, an adequate set of musculo-skeletal data is necessary. In this study, we present a complete and coherent dataset for the lumbar spine, based on medical images and dissection measurements from one embalmed human cadaver. We divided muscles into muscle-tendon elements, digitized their attachments at the bones and measured morphological parameters...
January 12, 2017: Journal of Biomechanics
https://www.readbyqxmd.com/read/28125727/myosin-storage-myopathy-in-c-elegans-and-human-cultured-muscle-cells
#16
Martin Dahl-Halvarsson, Malgorzata Pokrzywa, Manish Rauthan, Marc Pilon, Homa Tajsharghi
Myosin storage myopathy is a protein aggregate myopathy associated with the characteristic subsarcolemmal accumulation of myosin heavy chain in muscle fibers. Despite similar histological findings, the clinical severity and age of onset are highly variable, ranging from no weakness to severe impairment of ambulation, and usually childhood-onset to onset later in life. Mutations located in the distal end of the tail of slow/ß-cardiac myosin heavy chain are associated with myosin storage myopathy. Four missense mutations (L1793P, R1845W, E1883K and H1901L), two of which have been reported in several unrelated families, are located within or closed to the assembly competence domain...
2017: PloS One
https://www.readbyqxmd.com/read/28122223/the-relaxation-properties-of-myofibrils-are-compromised-by-amino-acids-that-stabilize-%C3%AE-tropomyosin
#17
Beatrice Scellini, Nicoletta Piroddi, Alexander M Matyushenko, Dmitrii I Levitsky, Corrado Poggesi, Sherwin S Lehrer, Chiara Tesi
We investigated the functional impact of α-tropomyosin (Tm) substituted with one (D137L) or two (D137L/G126R) stabilizing amino acid substitutions on the mechanical behavior of rabbit psoas skeletal myofibrils by replacing endogenous Tm and troponin (Tn) with recombinant Tm mutants and purified skeletal Tn. Force recordings from myofibrils (15°C) at saturating [Ca(2+)] showed that Tm-stabilizing substitutions did not significantly affect the maximal isometric tension and the rates of force activation (kACT) and redevelopment (kTR)...
January 24, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28122221/force-responses-and-sarcomere-dynamics-of-cardiac-myofibrils-induced-by-rapid-changes-in-pi
#18
Robert Stehle
The second phase of the biphasic force decay upon release of phosphate from caged phosphate was previously interpreted as a signature of kinetics of the force-generating step in the cross-bridge cycle. To test this hypothesis without using caged compounds, force responses and individual sarcomere dynamics upon rapid increases or decreases in concentration of inorganic phosphate [Pi] were investigated in calcium-activated cardiac myofibrils. Rapid increases in [Pi] induced a biphasic force decay with an initial slow decline (phase 1) and a subsequent 3-5-fold faster major decay (phase 2)...
January 24, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28117999/analysis-of-longissimus-thoracis-protein-expression-associated-with-variation-in-carcass-quality-grade-and-marbling-of-beef-cattle-raised-in-the-pacific-northwestern-us
#19
Kara J Thornton, Kalyan C Chapalamadugu, Eric M Eldridge, Gordon K Murdoch
Longissimus thoracis (LD) samples from 500 cattle were screened for protein expression differences relative to carcass quality grade. The LD of the top 5% (low prime and high choice, HQ) and bottom 5% (low select, LQ) carcasses were analyzed using two-dimensional difference gel electrophoresis and western blot. Following initial screening, 11 candidate proteins were selected for Western blot analyses. Differentially expressed proteins were clustered into 4 groups: (1) heat shock proteins and oxidative protection, (2) sarcomeric proteins: muscle maturity and fiber type, (3) metabolism and energetics and (4) miscellaneous proteins...
January 24, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28117796/in-vitro-differentiation-of-mature-myofibers-for-live-imaging
#20
Mafalda R Pimentel, Sestina Falcone, Bruno Cadot, Edgar R Gomes
Skeletal muscles are composed of myofibers, the biggest cells in the mammalian body and one of the few syncytia. How the complex and evolutionarily conserved structures that compose it are assembled remains under investigation. Their size and physiological features often constrain manipulation and imaging applications. The culture of immortalized cell lines is widely used, but it can only replicate the early steps of differentiation. Here, we describe a protocol that enables easy genetic manipulation of myofibers originating from primary mouse myoblasts...
January 7, 2017: Journal of Visualized Experiments: JoVE
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