A5024267673- Force Microscopy Techniques and Applications
- Molecular Junctions and Nanostructures
- Cardiomyopathy and Myosin Studies
- Cardiovascular Effects of Exercise
- DNA and Nucleic Acid Chemistry
- Mechanical and Optical Resonators
- Skin and Cellular Biology Research
- Cellular Mechanics and Interactions
- Near-Field Optical Microscopy
- Polysaccharides and Plant Cell Walls
- Advanced biosensing and bioanalysis techniques
- Polysaccharides Composition and Applications
- Muscle Physiology and Disorders
- RNA Interference and Gene Delivery
- Nuclear Structure and Function
- Lipid Membrane Structure and Behavior
- Viral Infections and Immunology Research
- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Polymer Surface Interaction Studies
- Sports injuries and prevention
- Virus-based gene therapy research
- Advanced Fluorescence Microscopy Techniques
- Cardiac Arrhythmias and Treatments
Bielefeld University
2014-2024
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease, frequently accompanied by sudden cardiac death and terminal failure. Genotyping of ARVC patients might be used for palliative treatment the affected family. We genotyped a cohort 22 referred to molecular genetic screening in our center mutations desmosomal candidate genes JUP, DSG2, DSC2, DSP PKP2 known associated with ARVC. In 43% cohort, we found disease-associated sequence variants. addition,...
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare genetic condition caused predominantly by mutations within desmosomal genes. The mutation leading to ARVC-5 was recently identified on the island of Newfoundland and fully penetrant missense p.S358L in TMEM43. Although TMEM43-p.S358L carriers were also found USA, Germany, Denmark, relationship between North American European patients disease mechanism this remained be clarified. We screened 22 unrelated ARVC without genes...
Mutations in the DES gene coding for intermediate filament protein desmin may cause skeletal and cardiac myopathies, which are frequently characterized by cytoplasmic aggregates of associated proteins at cellular level. By atomic force microscopy, we demonstrated formation defects mutants, with arrhythmogenic right ventricular cardiomyopathy. To understand pathogenesis this disease, it is essential to analyze structures under conditions both healthy mutant expressed equimolar levels...
The intermediate filament protein desmin is encoded by the gene DES and contributes to mechanical stabilization of striated muscle sarcomere cell contacts within cardiac intercalated disk. mutations cause severe skeletal diseases with heterogeneous phenotypes. Recently, were also found in patients arrhythmogenic right ventricular cardiomyopathy. Currently, cellular molecular pathomechanisms leading this disease are not exactly known.We identified 2 novel variants DES-p.A120D (c.359C>A)...
BACKGROUND: Nonischemic cardiomyopathies are frequently caused by genetic mutations in about 100 different genes. The cardiomyopathy-associated gene DES encodes the intermediate filament protein desmin, which is important for structural integrity of cardiomyocytes. METHODS: Using a next-generation sequencing approach, we performed cascade screening previously identified heterozygous missense mutation (c.380G>C, p.R127P) segregating large 6-generation Kuwaiti family, where several members...
In biological adhesion, the biophysical mechanism of specific biomolecular interaction can be divided in slip and catch bonds, respectively. Conceptually, bonds exhibit a reduced bond lifetime under increased external force contrast, an (for certain interval). Since 2003, handful systems have been identified to display properties. Upon investigating between unique hydrophilic domain (HD) human cell-surface sulfatase Sulf1 against its physiological glycosaminoglycan (GAG) target heparan...
Fluorescent DNA dyes are broadly used in many biotechnological applications for detecting and imaging cells gels. Their binding alters the structural nanomechanical properties of affects biological processes that associated with it. Although interaction modes like intercalation minor groove already have been identified, mechanic effects local elongation, unwinding, softening often remain question. We magnetic tweezers to quantitatively investigate impact three DNA-binding (YOYO-1, DAPI,...
Abstract Cadherins are calcium dependent adhesion proteins that establish the intercellular mechanical contact by bridging gap to adjacent cells. Desmoglein-2 (Dsg2) is a specific cadherin of cell-cell in cardiac desmosomes. Mutations DSG2 -gene regarded cause arrhythmogenic (right ventricular) cardiomyopathy (ARVC) which rare but severe heart muscle disease. The molecular pathomechanisms vast majority mutations, however, unknown. Here, we investigated homophilic binding wildtype Dsg2 and...
Abstract Background DES mutations cause different cardiac and skeletal myopathies. Most of them are missense mutations. Methods Using a next‐generation sequencing 174 gene panel, we identified novel heterozygous in‐frame indel mutation ( ‐c.493_520del28insGCGT, p.Q165_A174delinsAS) in Caucasian patient with cardiomyopathy combination atrioventricular block myopathy. This is located the coding region first exon. Family anamnesis revealed history sudden death. We performed cell transfection...
Abstract The cardiac muscle consists of individual cardiomyocytes that are mechanically linked by desmosomes. Desmosomal adhesion is mediated densely packed and organized cadherins which, in presence Ca 2+ , stretch out their extracellular domains (EC) dimerize with opposing binding partners exchanging an N-terminal tryptophan. strand-swap motif like desmocollin 2 (Dsc2) (and desmoglein2 alike) highly specific but low affinity average bond lifetimes the range approximately 0.3 s. Notably,...
A new means of switching the fluorescence emission a single nanocrystal by intervention gold-modified AFM tip, and luminescence properties (see TIRFM image) as function distance between quantum dot are presented. Significant enhancement due to exciton–plasmon coupling was detected. This is important in controlling molecular individuals with applications ranging from microarrays manipulation reporter molecules. TIRFM: Total-internal-reflection microscopy.
The great interest for naked plasmid DNA in gene therapy studies is reflected by the fact that it currently used 18% of all trials. Therefore, validation topology and functionality resulting from its long-term stability an essential requirement safe effective transfer. To this aim, we analyzed good manufacturing practice-grade pCMVβ reporter capillary gel electrophoresis, agarose atomic force microscopy. was produced a clinical transfer study started 2005 stored meanwhile 7 years under...
In fluorescence microscopy and spectroscopy, energy transfer processes between single fluorophores fluorophore quencher pairs play an important role in the investigation of molecular distances or orientations. At larger than about 3 nm these effects originate predominantly from dipolar coupling. As experiments are commonly performed homogenous media, at interface boundaries can be neglected. Nevertheless, combination such assays with single-molecule manipulation techniques as atomic force...
Xanthomonas campestris strains are used world-wide for the production of industrially important exopolysaccharide xanthan. The high industrial relevance xanthan can be explained by its extraordinary qualities as rheological control agent in aqueous systems and stabilizing properties suspensions emulsions. phytopathogen is a motile bacterium with one polar flagellum. flagellum cost intensive structure, terms energy building block consumption. Based on assumption that inhibition flagellar...
The specific interaction of a supramolecular binding motif was quantitatively evaluated by dynamic single-molecule force spectroscopy (SMFS) using an atomic microscope (AFM). capsule forms two different cavitands stitched together four hydrogen bonds between carboxylic acid and pyridyl groups. tetra(carboxyl)cavitand is monofunctionalized at the lower rim with flexible poly(ethylene glycol) linker attached to AFM sensor tip. Single-molecule association experiments are accomplished diluted...
Fluorescent dyes are widely used for detecting and visualizing DNA molecules in many biotechnological applications. However, their binding to alters the structural nanomechanical properties of thus affects also associated biological processes. In this work, we employed magnetic tweezers investigate influence four fluorescent (YOYO-1, DAPI, DRAQ5 PicoGreen) on a concentration dependent manner. Via extending overwinding single, torsionally constrained, nick-free λ dsDNA molecules, measured...
Xanthan gum is a polysaccharide that widely used as thickening agent in numerous food, cosmetic, and technical applications. Therefore, the knowledge of molecular interplay builds up stabilizes water-binding networks crucial for optimization xanthan performance. Using atomic force microscopy, rheometry, inductively coupled plasma optical emission spectroscopy, we show clear correlation between properties ability to form characteristic secondary structures well valence amount cations...
A combined approach based on isothermal titration calorimetry (ITC), fluorescence resonance energy transfer (FRET) experiments, circular dichroism spectroscopy (CD), atomic force microscopy (AFM) dynamic (DFS), and surface plasmon (SPR) was applied to elucidate the mechanism of protein-DNA complex formation impact protein dimerization DNA-binding domain PhoB (PhoB(DBD)). These insights can be translated related members family winged helix-turn-helix proteins. One central question assembly...