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https://www.readbyqxmd.com/read/28516329/screening-for-lipoprotein-receptor-related-protein-4-agrin-and-titin-antibodies-and-exploring-the-autoimmune-spectrum-in-myasthenia-gravis
#1
Isabell Cordts, Nicolas Bodart, Kathi Hartmann, Katerina Karagiorgou, John S Tzartos, Lin Mei, Jens Reimann, Philip Van Damme, Michael H Rivner, Alain Vigneron, Joachim Weis, Jörg B Schulz, Socrates J Tzartos, Kristl G Claeys
In autoimmune myasthenia gravis (MG), the identification of antibodies and characterization of serological subgroups is of great importance for diagnosis and management of the disease. Our aims were to study the frequency of antibodies against lipoprotein-related protein 4 (LRP4), agrin, and titin using the most recent techniques, and to characterize corresponding clinical features and autoimmune diseases (AID) in 100 MG-patients. The antibody frequencies in the 55 AChR-antibody positive patients were 7% LRP4, 5% agrin, 53% titin, and in the 45 AChR-antibody negative patients 2% MuSK, 2% LRP4, 2% agrin, and 27% titin...
May 17, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28510120/obscurin-variants-and-inherited-cardiomyopathies
#2
REVIEW
Steven Marston
The inherited cardiomyopathies, hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and left ventricular non-compaction (LVNC), have been frequently associated with mutations in sarcomeric proteins. In recent years, advances in DNA sequencing technology has allowed the study of the giant proteins of the sarcomere, such as titin and nebulin. Obscurin has been somewhat neglected in these studies, largely because its functional role is far from clear, although there was an isolated report in 2007 of obscurin mutations associated with HCM...
May 5, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28510119/genetic-epidemiology-of-titin-truncating-variants-in-the-etiology-of-dilated-cardiomyopathy
#3
REVIEW
Ali M Tabish, Valerio Azzimato, Aris Alexiadis, Byambajav Buyandelger, Ralph Knöll
Heart failure (HF) is a complex clinical syndrome defined by the inability of the heart to pump enough blood to meet the body's metabolic demands. Major causes of HF are cardiomyopathies (diseases of the myocardium associated with mechanical and/or electrical dysfunction), among which the most common form is dilated cardiomyopathy (DCM). DCM is defined by ventricular chamber enlargement and systolic dysfunction with normal left ventricular wall thickness, which leads to progressive HF. Over 60 genes are linked to the etiology of DCM...
May 5, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28510118/tampering-with-springs-phosphorylation-of-titin-affecting-the-mechanical-function-of-cardiomyocytes
#4
REVIEW
Nazha Hamdani, Melissa Herwig, Wolfgang A Linke
Reversible post-translational modifications of various cardiac proteins regulate the mechanical properties of the cardiomyocytes and thus modulate the contractile performance of the heart. The giant protein titin forms a continuous filament network in the sarcomeres of striated muscle cells, where it determines passive tension development and modulates active contraction. These mechanical properties of titin are altered through post-translational modifications, particularly phosphorylation. Titin contains hundreds of potential phosphorylation sites, the functional relevance of which is only beginning to emerge...
April 10, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28510117/novex-3-the-tiny-titin-of-muscle
#5
REVIEW
Dalma Kellermayer, John E Smith, Henk Granzier
The giant multi-functional striated muscle protein titin is the third most abundant muscle protein after myosin and actin. Titin plays a pivotal role in myocardial passive stiffness, structural integrity and stress-initiated signaling pathways. The complete sequence of the human titin gene contains three isoform-specific mutually exclusive exons [termed novel exons (novex)] coding for the I-band sequence, named novex-1 (exon 45), novex-2 (exon 46) and novex-3 (exon 48). Transcripts containing either the novex-1 or novex-2 exons code for the novex-1 and novex-2 titin isoforms...
April 7, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28476659/effect-of-exercise-on-passive-myocardial-stiffness-in-mice-with-diastolic-dysfunction
#6
Rebecca E Slater, Joshua G Strom, Henk Granzier
Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome, characterized by increased diastolic stiffness and a preserved ejection fraction, with no effective treatment options. Here we studied the therapeutic potential of exercise for improving diastolic function in a mouse model with HFpEF-like symptoms, the TtnΔIAjxn mouse model. TtnΔIAjxn mice have increased diastolic stiffness and reduced exercise tolerance, mimicking aspects of HFpEF observed in patients. We investigated the effect of free-wheel running exercise on diastolic function...
May 3, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28474792/molecular-stretching-modulates-mechanosensing-pathways
#7
REVIEW
Xian Hu, Felix Margadant, Mingxi Yao, Michael Sheetz
For individual cells in tissues to create the diverse forms of biological organisms, it is necessary that they must reliably sense and generate the correct forces over the correct distances and directions. There is considerable evidence that the mechanical aspects of the cellular microenvironment provide critical physical parameters to be sensed. How proteins sense forces and cellular geometry to create the correct morphology is not understood in detail but protein unfolding appears to be a major component in force and displacement sensing...
May 5, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28472418/increased-passive-stiffness-promotes-diastolic-dysfunction-despite-improved-ca2-handling-during-left-ventricular-concentric-hypertrophy
#8
Åsmund T Røe, Jan Magnus Aronsen, Kristine Skårdal, Nazha Hamdani, Wolfgang A Linke, Håvard E Danielsen, Ole M Sejersted, Ivar Sjaastad, William E Louch
Aims: Concentric hypertrophy following pressure-overload is linked to preserved systolic function but impaired diastolic function, and is an important substrate for heart failure with preserved ejection fraction. While increased passive stiffness of the myocardium is a suggested mechanism underlying diastolic dysfunction in these hearts, the contribution of a ctive diastolic Ca 2+ cycling in cardiomyocytes remains unclear. In this study, we sought to dissect contributions of passive and active mechanisms to diastolic dysfunction in the concentrically hypertrophied heart following pressure-overload...
May 4, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28470860/multiple-antibody-detection-in-seronegative-myasthenia-gravis-patients
#9
Y Hong, P Zisimopoulou, N Trakas, K Karagiorgou, C Stergiou, G O Skeie, H-J Hao, X Gao, J F Owe, X Zhang, Y-X Yue, F Romi, Q Wang, H-F Li, N E Gilhus, S J Tzartos
BACKGROUND AND PURPOSE: Myasthenia gravis (MG) is an autoimmune disease caused by antibody mediated impairment in the neuromuscular junction. Seronegative MG (SNMG) without antibodies against acetylcholine receptor (AChR) and muscle-specific kinase (MuSK) by routine assays accounts for about 20% of all MG patients. METHODS: Plasma from 81 Chinese MG patients previously found to be seronegative was tested by routine assays for AChR and MuSK antibodies. These samples were screened by (i) a novel, highly sensitive radioimmunoassay for AChR antibodies; (ii) cell-based assays for clustered AChR, MuSK and lipoprotein receptor-related protein 4 (LRP4) antibodies; (iii) a radioimmunoassay for titin antibodies...
May 4, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28469023/the-active-force-length-relationship-is-invisible-during-extensive-eccentric-contractions-in-skinned-skeletal-muscle-fibres
#10
André Tomalka, Christian Rode, Jens Schumacher, Tobias Siebert
In contrast to experimentally observed progressive forces in eccentric contractions, cross-bridge and sliding-filament theories of muscle contraction predict that varying myofilament overlap will lead to increases and decreases in active force during eccentric contractions. Non-cross-bridge contributions potentially explain the progressive total forces. However, it is not clear whether underlying abrupt changes in the slope of the nonlinear force-length relationship are visible in long isokinetic stretches, and in which proportion cross-bridges and non-cross-bridges contribute to muscle force...
May 17, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/28464408/intramolecular-cross-linking-addressing-mechanochemistry-with-a-bioinspired-approach
#11
Avishai Levy, Feng Wang, Arad Lang, Or Galant, Charles E Diesendruck
Many of the attractive properties in polymers are a consequence of their high molecular weight and therefore, scission of chains due to mechanochemistry leads to deterioration in properties and performance. Intramolecular cross-links are systematically added to linear chains, slowing down mechanochemical degradation to the point where the chains become virtually invincible to shear in solution. Our approach mimics the immunoglobulin-like domains of Titin, whose structure directs mechanical force towards the scission of sacrificial intramolecular hydrogen bonds, absorbing mechanical energy while unfolding...
May 2, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28464104/postmortem-protein-degradation-is-a-key-contributor-to-fresh-pork-loin-tenderness
#12
K B Carlson, K J Prusa, C A Fedler, E M Steadham, A C Outhouse, D A King, E Huff-Lonergan, S M Lonergan
The objective of this study was to determine factors that influence tenderness independent of variation in pH, color, or marbling. To achieve the objective, 2 sample groups were chosen from a population of 159 pork loins aged 11 to 16 d. Predetermined ranges (ultimate pH, 5.54 to 5.86; marbling score, 1.0 to 3.0; percent total lipid, 1.61 to 3.37%) were defined for inclusion of individual loins in the study. The pork loins with the greatest ( = 12) and least ( = 12) Instron star probe values were assigned to 2 classification groups...
April 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28460973/the-structural-basis-of-cooking-loss-in-beef-variations-with-temperature-and-ageing
#13
P P Purslow, S Oiseth, J Hughes, R D Warner
Meat loses fluid during cooking, resulting in textural changes and loss in cook yield. To understand the structural basis of cooking losses, this work used 10 bovine semitendinosus muscles and two ageing periods (1 vs 14days) to examine micro- and macro-level dimensional changes in muscle during heating. Muscle blocks, muscle fibre fragments and myofibrils all showed similar maximum shrinkage in cross sectional area (20-24%) but maximum length shrinkage was less in myofibrils (15%) than muscle blocks and fibre fragments (25%)...
November 2016: Food Research International
https://www.readbyqxmd.com/read/28436080/genotype-specific-pathogenic-effects-in-human-dilated-cardiomyopathy
#14
Ilse Ae Bollen, Maike Schuldt, Magdalena Harakalova, Aryan Vink, Folkert W Asselbergs, Jose R Pinto, Martina Krüger, Diederik Wd Kuster, Jolanda van der Velden
BACKGROUND: Dilated cardiomyopathy (DCM) can be caused by mutations in sarcomeric and non-sarcomeric genes. In this study we defined the pathogenic effects of three DCM causing mutations: the sarcomeric mutations in genes encoding cardiac troponin I (TNNI3p.98truncation ) and cardiac troponin T (TNNT2p.K217deletion ; also known as the K210del) and the non-sarcomeric gene mutation encoding lamin A/C (LMNAp.R331Q ). METHODS: We assessed sarcomeric protein expression and phosphorylation and contractile behaviour in single membrane-permeabilized cardiomyocytes in human left ventricular heart tissue...
April 24, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28433557/early-changes-of-left-ventricular-filling-pattern-after-reperfused-st-elevation-myocardial-infarction-and-doxycycline-therapy-insights-from-the-tiptop-trial
#15
Giampaolo Cerisano, Piergiovanni Buonamici, Guido Parodi, Alberto Santini, Guia Moschi, Renato Valenti, Angela Migliorini, Paolo Colonna, Benedetta Bellandi, Anna Maria Gori, David Antoniucci
AIM: Metalloproteinases inhibition by doxycycline reduces cardiac protein degradation at extracellular and intracellular level in the experimental model ischemia/reperfusion injury. Since both extracellular cardiac matrix and titin filaments inside the cardiomyocyte are responsible for the myocardial stiffness, we hypothesized that doxycycline could favorably act on left ventricular (LV) filling pressures in patients after reperfused acute ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: Seventy-three of 110 patients of the TIPTOP trial underwent a 2D-Echo-Doppler on admission, and at pre-discharge and at 6-month after a primary PCI for STEMI and LV dysfunction...
April 7, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28423146/recovery-in-patients-with-dilated-cardiomyopathy-with-loss-of-function-mutations-in-the-titin-gene
#16
Kevin Luk, Abeer Bakhsh, Nadia Giannetti, Eleanor Elstein, Mark Lathrop, George Thanassoulis, James C Engert
No abstract text is available yet for this article.
April 19, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28394039/elasticity-of-the-transition-state-leading-to-an-unexpected-mechanical-stabilization-of-titin-immunoglobulin-domains
#17
Guohua Yuan, Shimin Le, Mingxi Yao, Hui Qian, Xin Zhou, Jie Yan, Hu Chen
The giant protein titin plays a critical role in regulating the passive elasticity of muscles, mainly through the stochastic unfolding and refolding of its numerous immunoglobulin domains in the I-band of sarcomeres. The unfolding dynamics of titin immunoglobulin domains at a force range greater than 100 pN has been studied by atomic force microscopy, while that at smaller physiological forces has not been measured before. By using magnetic tweezers, it is found that the titin I27 domain unfolds in a surprising non-monotonic force-dependent manner at forces smaller than 100 pN, with the slowest unfolding rate occurring around 22 pN...
May 8, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28391696/muscle-protein-profiles-used-for-prediction-of-texture-of-farmed-salmon-salmo-salar-l
#18
Gine Ørnholt-Johansson, Stina Frosch, María Gudjónsdóttir, Tune Wulff, Flemming Jessen
A soft texture is undesired in Atlantic salmon as it leads to downgrading and reduced yield, yet it is a factor for which the cause is not fully understood. This lack of understanding highlights the need for identifying the cause of the soft texture and developing solutions by which the processing industry can improve the yield. Changes in muscle protein profiles can occur both pre- and postharvest and constitute an overall characterization of the muscle properties including texture. The aim of this study was to investigate this relationship between specific muscle proteins and the texture of the salmon fillet...
April 18, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28364296/juvenile-onset-myasthenia-gravis-autoantibody-status-clinical-characteristics-and-genetic-polymorphisms
#19
Yu Hong, Geir Olve Skeie, Paraskevi Zisimopoulou, Katerina Karagiorgou, Socrates J Tzartos, Xiang Gao, Yao-Xian Yue, Fredrik Romi, Xu Zhang, Hai-Feng Li, Nils Erik Gilhus
Myasthenia gravis (MG) is an autoimmune disorder mediated by antibodies against proteins at the neuromuscular junction. Juvenile-onset MG (JMG) has been reported to have special characteristics. It is still unclear whether there are any pathogenic and genetic differences between juvenile and adult MG. In this study, we evaluated the clinical characteristics, autoantibody status (antibodies against AChR, MuSK, LRP4, titin and RyR) and genetic susceptibility (CHRNA1, CTLA4 and AIRE) in 114 Chinese JMG patients, and compared with 207 young adult MG patients (onset age 18-40 years)...
May 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28353642/dysregulated-ier3-expression-is-associated-with-enhanced-apoptosis-in-titin-based-dilated-cardiomyopathy
#20
Qifeng Zhou, Julia Kelley Hahn, Balram Neupane, Parwez Aidery, Siegfried Labeit, Meinrad Gawaz, Michael Gramlich
Apoptosis (type I programmed cell death) of cardiomyocytes is a major process that plays a role in the progression of heart failure. The early response gene IER3 regulates apoptosis in a wide variety of cells and organs. However, its role in heart failure is largely unknown. Here, we investigate the role of IER3 in an inducible heart failure mouse model. Heart failure was induced in a mouse model that imitates a human titin truncation mutation we found in a patient with dilated cardiomyopathy (DCM). Transferase dUTP nick end labeling (TUNEL) and ssDNA stainings showed induction of apoptosis in titin-deficient cardiomyocytes during heart failure development, while IER3 response was dysregulated...
March 29, 2017: International Journal of Molecular Sciences
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