A5029288248- Cardiomyopathy and Myosin Studies
- Muscle Physiology and Disorders
- Cellular Mechanics and Interactions
- Blood properties and coagulation
- Cardiovascular Effects of Exercise
- Skin and Cellular Biology Research
- Connective tissue disorders research
- Hemostasis and retained surgical items
- Platelet Disorders and Treatments
- Viral Infections and Immunology Research
- Muscle activation and electromyography studies
- Electromagnetic Fields and Biological Effects
- Transcranial Magnetic Stimulation Studies
- RNA and protein synthesis mechanisms
- Surface Modification and Superhydrophobicity
- Adhesion, Friction, and Surface Interactions
- Advanced Sensor and Energy Harvesting Materials
- Force Microscopy Techniques and Applications
- Wound Healing and Treatments
- Inflammatory Myopathies and Dermatomyositis
- Bone fractures and treatments
- Hearing, Cochlea, Tinnitus, Genetics
- Hemispheric Asymmetry in Neuroscience
- Neurogenetic and Muscular Disorders Research
- Periodontal Regeneration and Treatments
Semmelweis University
2014-2025
University of Arizona
2016-2022
University of Pecs
2006-2010
The contractile machinery of heart and skeletal muscles has as an essential component the thick filament, comprised molecular motor myosin. filament is a precisely controlled length, defining thereby force level that generate how this varies with muscle length. It been speculated mechanism by which length involves giant protein titin, but no conclusive support for hypothesis exists. Here we show in mouse model deleted two titin's C-zone super-repeats, reduced cardiac muscles. In addition,...
Titin, the largest protein known, forms an elastic myofilament in striated muscle sarcomere. To establish titin’s contribution to skeletal passive stiffness, relative that of extracellular matrix, a mouse model was created which molecular spring region shortened by deleting 47 exons, TtnΔ112-158 model. RNA sequencing and super-resolution microscopy predicts much stiffer titin molecule. Mechanical studies with this novel support is main determinant stiffness. Unexpectedly, vivo sarcomere...
Thin filament myopathies are among the most common nondystrophic congenital muscular disorders, and caused by mutations in genes encoding proteins that associated with skeletal muscle thin filament. Mechanisms underlying weakness poorly understood, but might involve length of filament, an important determinant force generation.We investigated sarcomere length-dependence force, a functional assay provides insights into contractile strength fibers as well filaments, from 51 patients myopathy...
A fundamental requirement of cells is their ability to transduce and interpret mechanical environment. This contributes regulation growth, differentiation adaptation in many cell types. The intermediate filament (IF) system not only provides passive structural support the cell, but recent evidence points IF involvement active biological processes such as signaling, mechanotransduction gene regulation. However, mechanisms that underlie these are well known. Skeletal muscle provide a...
Highlights•The layout of titin's C-zone in relation to MyBP-C is relevant cardiomyopathies but unknown.•Immuno-localization studies showed that cMyBP-C locates near the interface between titin super-repeats.•Interface domains belong two super-repeats are likely involved anchoring cMyBP-C.•Not all super-repeat interfaces equal: 1 and 2 does not localize cMyBP-C.•This study enhances insights molecular its cMyBP-C.AbstractTitin largely comprised serially-linked immunoglobulin (Ig) fibronectin...
Marfan syndrome (MFS) is an autosomal dominant disease caused by mutations in the gene (FBN1) of fibrillin-1, a major determinant extracellular matrix (ECM). Functional impairment cardiac left ventricle (LV) these patients usually consequence aortic valve disease. However, LV passive stiffness may also be affected chronic changes mechanical load and ECM dysfunction. Passive determined giant sarcomeric protein titin that has two main splice isoforms: shorter stiffer N2B longer more compliant...
Significance Nebulin is a giant actin-binding protein in skeletal muscle which localizes along most of the length thin filament. Genetic alterations or reduction expression level nebulin are accompanied by dramatic loss force, resulting weakness and severe myopathy. Using an inducible tissue-specific nebulin-knockout mouse model not expressed muscle, we investigated ultrastructure filaments passive contracting under physiological conditions using X-ray diffraction. Thin were found to be...
The mechanisms that modulate the kinetics of muscle relaxation are critically important for function. A prime example impact impaired is nemaline myopathy caused by mutations in KBTBD13 (NEM6). In addition to weakness, NEM6 patients have slow relaxation, compromising contractility and daily life activities. role unknown, pathomechanism underlying undetermined. combination transcranial magnetic stimulation-induced fiber- sarcomere-contractility assays, low-angle x-ray diffraction,...
Heterozygous (HET) truncating variant mutations in the TTN gene (TTNtvs), encoding giant titin protein, are most common genetic cause of dilated cardiomyopathy (DCM). However, molecular mechanisms by which TTNtv induce DCM controversial. Here, we studied 127 clinically identified human cardiac samples with next-generation sequencing (NGS), high-resolution gel electrophoresis, Western blot analysis, and super-resolution microscopy order to dissect structural functional consequences mutations....
Nebulin rules thin-filament length in fast skeletal muscle but collaborates with leiomodin-2 muscles optimized for efficiency.
Fibrin, the main scaffold of thrombi, is susceptible to citrullination by PAD (peptidyl arginine deiminase) 4, secreted from neutrophils during formation neutrophil extracellular traps. Citrullinated fibrinogen (citFg) has been detected in human plasma as well murine venous and it decreases lysability mechanical resistance fibrin clots.To investigate effect on structure clots.Fibrinogen was citrullinated with PAD4 clotted thrombin. Scanning electron microscopy (SEM) atomic force (AFM) were...
Abstract Nebulin is a giant protein that winds around the actin filaments in skeletal muscle sarcomere. Compound-heterozygous mutations nebulin gene ( NEB ) cause typical nemaline myopathy (NM), disorder characterized by weakness with limited treatment options. We created mouse model missense mutation p.Ser6366Ile and deletion of exon 55, Compound-Het resembles NM. show mice are growth-retarded have weakness. Muscles reduced myofibrillar fractional-area sarcomeres disorganized, contain rod...
Abstract Recent research demonstrated that exposure of mice to both inhomogeneous (3–477 mT) and homogeneous (145 static magnetic fields (SMF) generated an analgesic effect toward visceral pain elicited by the intraperitoneal injection 0.6% acetic acid. In present work, we investigated behavioral responses such as writhing, entry avoidance, site preference with help a specially designed cage partially protruded into either (ho) or (inh) SMF. Aversive effects, cognitive recognition analgesia,...
Abstract Background Frozen shoulder is a common medical condition, but the ideal therapeutic method yet to be determined. Our aim was analyze pain-relieving effect of different treatment options used for management this disease. Methods Medical records 59 patients (22 male, 37 female, average age: 55.5 years ±9.9) with early stage primary frozen were evaluated, their demographic data, physical examination, concomitant diseases and specific data registered. Life quality level pain assessed...
Desmin filaments form the intermediate filament system of muscle cells where they play important role in maintaining mechanical integrity and elasticity. Although importance desmin elasticity assembly–disassembly dynamics cellular mechanics is being increasingly recognized, molecular basis neither desmin's nor its disassembly pathway well understood. In present work, we explored topographical structure purified reconstituted by using scanning force microscopy. With addition divalent cation...
Titin's C-zone is an inextensible segment in titin, comprised of 11 super-repeats and located the cMyBP-C-containing region thick filament. Previously we showed that deletion titin's C1 C2 (TtnΔC1–2 model) results shorter filaments contractile dysfunction left ventricular (LV) chamber but unexpectedly LV diastolic stiffness normal. Here studied contraction-relaxation kinetics from time-varying elastance intact cardiomyocyte, cellular work loops cardiomyocytes, Ca2+ transients, cross-bridge...