Biomedical subjects

Frank Mueller

Publications and source records attributed to Frank Mueller.

3 recordsLinked to original sources

PubMed2006

Analysis assistant for single-molecule force spectroscopy data on membrane proteins--MPTV.

UNLABELLED: Force-distance (F-D) curves of single membrane proteins reveal information on inter- and intramolecular interactions occurring within a protein and between proteins. However, the analysis of single-molecule force spectroscopy data is a time consuming and complex process requiring objective criteria. In most cases the user requires additional information to interpret F-D curves. Therefore we developed a software assistant representing the force or molecular interaction pattern and the topology or the 3D structure of the membrane protein. This representation establishes a basis for detailed interpretation of the protein structure and its underlying molecular interactions. Various integrated bioinformatic features further assist in the interpretation of measured and assigned molecular interactions that determine membrane protein folding, structure, stability and function. Web queries and programs about the topology are directly linked. Motifs, helix types, representation of Venn diagrams and the complete functionality of the program Jmol belong to it. AVAILABILITY: The program MPTV is freely available from the website at http://www.bioforscher.de/mptv.htm/.

Algorithms↗

PubMed2006

Measurements of vocal fold elasticity using the linear skin rheometer.

OBJECTIVE: The linear skin rheometer (LSR), which measures skin visco-elasticity, was adapted for measurements of vocal fold properties. A series of studies was performed on animal and human excised larynges to determine if the LSR technique can be applied to the vocal fold. METHODS: In excised larynges, small patches of mucosa were driven sinusoidally at 0.3 Hz over distances of 1-2 mm using a small probe. Forces in the order of 1 g equivalent gave optimal measurements. Stiffness and viscosity values were derived from stress/strain data. RESULTS: The instrument was able to measure the visco-elasticity of the tissue in a repeatable manner and it could detect areas where the tissue was artificially stiffened. Two-dimensional maps of the mechanical properties of the laryngeal mucosa were obtained showing local variations in elasticity both parallel and perpendicular to the vocal fold edge. Initial studies were undertaken using animal tissue; more recently, the LSR has been successfully used to obtain similar data from human tissue. CONCLUSION: The LSR was been demonstrated to be capable of measuring the elastic properties of the vocal fold in a repeatable and reliable manner. Further studies will now be undertaken to obtain data from a larger sample of human tissue.

Animals↗

PubMed2005

Fibronectin-induced proliferation in thyroid cells is mediated by alphavbeta3 integrin through Ras/Raf-1/MEK/ERK and calcium/CaMKII signals.

We recently demonstrated in an immortalized thyroid cell line that integrin stimulation by fibronectin (FN) simultaneously activates two signaling pathways: Ras/Raf/MAPK kinase (Mek)/Erk and calcium Ca2+/calcium calmodulin-dependent kinase II (CaMKII). Both signals are necessary to stimulate Erk phosphorylation because CaMKII modulates Ras-induced Raf-1 activity. In this study we present evidence that extends these findings to normal human thyroid cells in primary culture, demonstrating its biological significance in a more physiological cell model. In normal thyroid cells, immobilized FN-induced activation of p21Ras and Erk phosphorylation. This pathway was responsible for FN-induced cell proliferation. Concurrent increase of intracellular Ca2+ concentration and CaMKII activation was observed. Both induction of p21Ras activity and increase of intracellular Ca2+ concentration were mediated by FN binding to alphavbeta3 integrin. Inhibition of the Ca2+/CaMKII signal pathway by calmodulin or CaMKII inhibitors completely abolished the FN-induced Erk phosphorylation. Binding to FN induced Raf-1 and CaMKII to form a protein complex, indicating that intersection between Ras/Raf/Mek/Erk and Ca2+/CaMKII signaling pathways occurred at Raf-1 level. Interruption of the Ca2+/CaMKII signal pathway arrested cell proliferation induced by FN. We also analyzed thyroid tumor cell lines that displayed concomitant aberrant integrin expression and signal transduction. These data confirm that integrin activation by FN in normal thyroid cells generates Ras/Raf/Mek/Erk and Ca2+/CaMKII signaling pathways and that both are necessary to stimulate cell proliferation, whereas in thyroid tumors integrin signaling is altered.

Calcium Signaling↗