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https://www.readbyqxmd.com/read/28333386/myofilaments-movers-and-rulers-of-the-sarcomere
#1
Brian Leei Lin, Taejeong Song, Sakthivel Sadayappan
Striated cardiac and skeletal muscles play very different roles in the body, but they are similar at the molecular level. In particular, contraction, regardless of the type of muscle, is a precise and complex process involving the integral protein myofilaments and their associated regulatory components. The smallest functional unit of muscle contraction is the sarcomere. Within the sarcomere can be found a sophisticated ensemble of proteins associated with the thick filaments (myosin, myosin binding protein-C, titin, and obscurin) and thin myofilaments (actin, troponin, tropomyosin, nebulin, and nebulette)...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28320300/chronic-alcohol-intoxication-is-not-accompanied-by-an-increase-in-calpain-proteolytic-activity-in-cardiac-muscle-of-rats
#2
Yu V Gritsyna, N N Salmov, A G Bobylev, I S Fadeeva, N I Fesenko, D G Sadikova, N I Kukushkin, Z A Podlubnaya, I M Vikhlyantsev
Enzymatic activity of Ca2+-dependent calpain proteases as well as the content and gene expression of μ-calpain (activated by micromolar calcium ion concentrations), calpastatin (inhibitor of calpains), and titin (substrate for calpains) were investigated in cardiac muscles of rats subjected to chronic alcoholization for 3 and 6 months. There was no increase in the "heart weight/body weight" parameter indicating development of heart hypertrophy in the alcoholized rats, while a decreasing trend was observed for this parameter in the rats after 6-month modeling of alcoholic cardiomyopathy, which indicated development of atrophic changes in the myocardium...
February 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28317377/3d-printed-ultratough-hydrogel-structures-with-titin-like-domains
#3
Fengbo Zhu, Libo Cheng, Zhi Jian Wang, Wei Hong, Zi Liang Wu, Jun Yin, Jin Qian, Qiang Zheng
Titin is composed of repeated modular domains which unfold and dissipate energy upon loading. Here we employed such molecular-level paradigm to fabricate macroscopic ultratough hydrogel structures with titin-like domains, enabled by three-dimensional printing with multiple nozzles. Under stretch, the relatively thin and weak gel fibers in the printed structures break first and the hidden lengths postpone the failure of the main structures, mimicking the toughening principle in titin. These titin-like folded domains have been incorporated into a synthetic spider-web, which shows significantly enhanced extensibility and toughness...
March 22, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28315399/truncating-titin-ttn-variants-in-chemotherapy-induced-cardiomyopathy
#4
M Linschoten, A J Teske, A F Baas, A Vink, D Dooijes, H F Baars, F W Asselbergs
Chemotherapy-induced cardiomyopathy (CCMP) is a complication of chemotherapy treatment occurring in 9% of patients treated with anthracyclines. Currently, risk stratification is based on clinical risk factors that do not adequately explain the variable individual susceptibility. This points towards the presence of other determinants. In this case series, we describe two women with breast cancer that developed severe heart failure within months after chemotherapy. Genetic screening revealed truncating frameshift mutations in TTN, encoding the myofilament titin, in both women...
March 14, 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/28298172/potential-prognostic-biomarkers-of-cardiovascular-disease-in-fetal-macrosomia-the-impact-of-gestational-diabetes
#5
Despina D Briana, Κleopatra Germanou, Μaria Boutsikou, Theodora Boutsikou, Νikolaos Athanasopoulos, Αntonios Μarmarinos, Dimitrios Gourgiotis, Αriadne Malamitsi-Puchner
OBJECTIVE: Fetal macrosomia is associated with cardiac hypertrophy and increased cardiovascular risk. Cardiac biomarkers may play diagnostic/prognostic role in cardiovascular disease. We tested whether cardiac biomarkers are differentially expressed in cord blood samples of full-term singleton large-for-gestational-age (LGA), as compared to appropriate-for-gestational-age (AGA) pregnancies. METHODS: Cardiotrophin-1 (CT-1), Titin, pentraxin (PTX-3) and soluble CD36 (sCD36) concentrations were determined in 80 cord blood samples from a) LGA pregnancies due to maternal diabetes (n = 8), overweight/obese (n = 11), excessive weight gain (n = 7), without specific pathology (n = 14), b) AGA normal pregnancies (controls, n = 40)...
March 15, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28295036/a-novel-recessive-ttn-founder-variant-is-a-common-cause-of-distal-myopathy-in-the-serbian-population
#6
Stojan Perić, Jelena Nikodinović Glumac, Ana Töpf, Dušanka Savić-Pavićević, Lauren Phillips, Katherine Johnson, Marcus Cassop-Thompson, Liwen Xu, Marta Bertoli, Monkol Lek, Daniel MacArthur, Miloš Brkušanin, Sanja Milenković, Vedrana Milić Rašić, Bojan Banko, Ružica Maksimović, Hanns Lochmüller, Vidosava Rakočević Stojanović, Volker Straub
Variants in the TTN gene have been associated with distal myopathies and other distinctive phenotypes involving skeletal and cardiac muscle. Through whole-exome sequencing we identified a novel stop-gain variant (c.107635C>T, p.(Gln35879Ter)) in the TTN gene, coding a part of the M-line of titin, in 14 patients with autosomal recessive distal myopathy and Serbian ancestry. All patients share a common 1 Mb core haplotype associated with c.107635C>T, suggesting a founder variant. In compound heterozygotes, nine other TTN variants were identified: four stop-gain, three frameshift, one missense and one splice donor variant...
March 15, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28272024/multidomain-proteins-under-force
#7
Jessica Valle Orero, Jaime Rivas-Pardo, Ionel Popa
Advancements in single molecule force spectroscopy techniques such as atomic force microscopy and magnetic tweezers allow investigating how domain folding under force can have physiological roles. Combining these techniques with protein engineering and HaloTag covalent attachment, we investigate similarities and differences between four model proteins: I10 and I91 - two immunoglobulin-like domains from the muscle protein titin, and two α+β fold proteins - ubiquitin and protein L. These proteins show a different mechanical response and have unique extensions under force...
March 8, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28242778/%C3%AE-b-crystallin-reverses-high-diastolic-stiffness-of-failing-human-cardiomyocytes
#8
Constantijn Franssen, Jeroen Kole, René Musters, Nazha Hamdani, Walter J Paulus
BACKGROUND: Cardiomyocytes with a less distensible titin and interstitial collagen contribute to the high diastolic stiffness of failing myocardium. Their relative contributions and mechanisms underlying loss of titin distensibility were assessed in failing human hearts. METHODS AND RESULTS: Left ventricular tissue was procured in patients with aortic stenosis (AS, n=9) and dilated cardiomyopathy (DCM, n=6). Explanted donor hearts (n=8) served as controls. Stretches were performed in myocardial strips, and an extraction protocol differentiated between passive tension (Fpassive) attributable to cardiomyocytes or to collagen...
March 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28228157/genetics-and-genomics-of-dilated-cardiomyopathy-and-systolic-heart-failure
#9
REVIEW
Upasana Tayal, Sanjay Prasad, Stuart A Cook
Heart failure is a major health burden, affecting 40 million people globally. One of the main causes of systolic heart failure is dilated cardiomyopathy (DCM), the leading global indication for heart transplantation. Our understanding of the genetic basis of both DCM and systolic heart failure has improved in recent years with the application of next-generation sequencing and genome-wide association studies (GWAS). This has enabled rapid sequencing at scale, leading to the discovery of many novel rare variants in DCM and of common variants in both systolic heart failure and DCM...
February 22, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28214268/219th-enmc-international-workshop-titinopathies-international-database-of-titin-mutations-and-phenotypes-heemskerk-the-netherlands-29-april-1-may-2016
#10
Peter Hackman, Bjarne Udd, Carsten G Bönnemann, Ana Ferreiro
No abstract text is available yet for this article.
January 16, 2017: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/28213770/myosin-heavy-chain-and-cardiac-troponin-t-damage-is-associated-with-impaired-myofibrillar-atpase-activity-contributing-to-sarcomeric-dysfunction-in-ca-2-paradox-rat-hearts
#11
Árpád Kovács, Judit Kalász, Enikő T Pásztor, Attila Tóth, Zoltán Papp, Naranjan S Dhalla, Judit Barta
This study aimed to explore the potential contribution of myofibrils to contractile dysfunction in Ca(2+)-paradox hearts. Isolated rat hearts were perfused with Krebs-Henseleit solution (Control), followed by Ca(2+)-depletion, and then Ca(2+)-repletion after Ca(2+)-depletion (Ca(2+)-paradox) by Langendorff method. During heart perfusion left ventricular developed pressure (LVDP), end-diastolic pressure (LVEDP), rate of pressure development (+ dP/dt), and pressure decay (-dP/dt) were registered. Control LVDP (127...
February 17, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28173117/exploiting-the-crispr-cas9-system-to-study-alternative-splicing-in-vivo-application-to-titin
#12
Karine Charton, Laurence Suel, Sara F Henriques, Jean-Paul Moussu, Matteo Bovolenta, Miguel Taillepierre, Céline Becker, Karelia Lipson, Isabelle Richard
No abstract text is available yet for this article.
October 15, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28151760/titin-truncating-mutations-in-dilated-cardiomyopathy-the-long-and-short-of-it
#13
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/28101866/titin-and-nebulin-in-thick-and-thin-filament-length-regulation
#14
Larissa Tskhovrebova, John Trinick
In this review we discuss the history and the current state of ideas related to the mechanism of size regulation of the thick (myosin) and thin (actin) filaments in vertebrate striated muscles. Various hypotheses have been considered during of more than half century of research, recently mostly involving titin and nebulin acting as templates or 'molecular rulers', terminating exact assembly. These two giant, single-polypeptide, filamentous proteins are bound in situ along the thick and thin filaments, respectively, with an almost perfect match in the respective lengths and structural periodicities...
2017: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/28097712/force-generation-by-titin-folding
#15
Zsolt Mártonfalvi, Pasquale Bianco, Katalin Naftz, György G Ferenczy, Miklós Kellermayer
Titin is a giant protein that provides elasticity to muscle. As the sarcomere is stretched, titin extends hierarchically according to the mechanics of its segments. Whether titin's globular domains unfold during this process and how such unfolded domains might contribute to muscle contractility are strongly debated. To explore the force-dependent folding mechanisms, here we manipulated skeletal-muscle titin molecules with high-resolution optical tweezers. In force-clamp mode, after quenching the force (<10 pN), extension fluctuated without resolvable discrete events...
January 18, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28096424/%C3%AE-actinin-titin-interaction-a-dynamic-and-mechanically-stable-cluster-of-bonds-in-the-muscle-z-disk
#16
Marco Grison, Ulrich Merkel, Julius Kostan, Kristina Djinović-Carugo, Matthias Rief
Stable anchoring of titin within the muscle Z-disk is essential for preserving muscle integrity during passive stretching. One of the main candidates for anchoring titin in the Z-disk is the actin cross-linker α-actinin. The calmodulin-like domain of α-actinin binds to the Z-repeats of titin. However, the mechanical and kinetic properties of this important interaction are still unknown. Here, we use a dual-beam optical tweezers assay to study the mechanics of this interaction at the single-molecule level...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28092128/biomimetic-supramolecular-polymer-networks-exhibiting-both-toughness-and-self-recovery
#17
Ji Liu, Cindy Soo Yun Tan, Ziyi Yu, Yang Lan, Chris Abell, Oren A Scherman
Biomimetic supramolecular dual networks: By mimicking the structure/function model of titin, integration of dynamic cucurbit[8]uril mediated host-guest interactions with a trace amount of covalent cross-linking leads to hierarchical dual networks with intriguing toughness, strength, elasticity, and energy dissipation properties. Dynamic host-guest interactions can be dissociated as sacrificial bonds and their facile reformation results in self-recovery of the dual network structure as well as its mechanical properties...
January 16, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28074486/introduction-of-steered-molecular-dynamics-into-unres-coarse-grained-simulations-package
#18
Adam K Sieradzan, Rafał Jakubowski
In this article, an implementation of steered molecular dynamics (SMD) in coarse-grain UNited RESidue (UNRES) simulations package is presented. Two variants of SMD have been implemented: with a constant force and a constant velocity. The huge advantage of SMD implementation in the UNRES force field is that it allows to pull with the speed significantly lower than the accessible pulling speed in simulations with all-atom representation of a system, with respect to a reasonable computational time. Therefore, obtaining pulling speed closer to those which appear in the atomic force spectroscopy is possible...
January 11, 2017: Journal of Computational Chemistry
https://www.readbyqxmd.com/read/28065693/inhibition-of-mir-208b-improves-cardiac-function-in-titin-based-dilated-cardiomyopathy
#19
Qifeng Zhou, Sonja Schötterl, Daniel Backes, Eva Brunner, Julia Kelley Hahn, Elena Ionesi, Parwez Aidery, Carsten Sticht, Siegfried Labeit, Reinhard Kandolf, Meinrad Gawaz, Michael Gramlich
BACKGROUND: Dilated cardiomyopathy (DCM) is the result of maladaptive cardiac remodeling, which involves microRNA regulation. In turn, microRNAs can contribute to the remodeling process by post-transcriptional modulation of gene expression networks. The exact role of microRNAs in the pathogenesis of DCM is largely unknown. Here, we used an inducible DCM mouse model that carries a human truncation mutation in the sarcomeric protein titin to dissect microRNA pathways in DCM development...
March 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28059474/csa-promotes-xist-expression-to-regulate-human-trophoblast-cells-proliferation-and-invasion-through-mir-144-titin-axis
#20
Nanhui Yu, Ying Liang, Hong Zhu, Hongying Mo, Haiping Pei
In our previous study, we revealed that Cyclosporin A (CsA) could inhibit miR-144 expression to regulate proliferation and invasion of human trophoblast (HT) cells through miR-144 targeting titin. This partially demonstrated the mechanism by which CsA promotes titin expression to increase the vitality of HT cells. However, the mechanism by which CsA inhibits miR-144 expression remains to be investigated. Recently, the interaction between lncRNA and miRNA has been frequently reported to play major role in several biological processes...
January 6, 2017: Journal of Cellular Biochemistry
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