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1.
PLoS One ; 11(3): e0149106, 2016.
Article in English | MEDLINE | ID: mdl-27007410

ABSTRACT

The keratin intermediate filament cytoskeleton protects epithelial cells against various types of stress and is involved in fundamental cellular processes such as signaling, differentiation and organelle trafficking. These functions rely on the cell type-specific arrangement and plasticity of the keratin system. It has been suggested that these properties are regulated by a complex cycle of assembly and disassembly. The exact mechanisms responsible for the underlying molecular processes, however, have not been clarified. Accumulating evidence implicates the cytolinker plectin in various aspects of the keratin cycle, i.e., by acting as a stabilizing anchor at hemidesmosomal adhesion sites and the nucleus, by affecting keratin bundling and branching and by linkage of keratins to actin filament and microtubule dynamics. In the present study we tested these hypotheses. To this end, plectin was downregulated by shRNA in vulvar carcinoma-derived A431 cells. As expected, integrin ß4- and BPAG-1-positive hemidesmosomal structures were strongly reduced and cytosolic actin stress fibers were increased. In addition, integrins α3 and ß1 were reduced. The experiments furthermore showed that loss of plectin led to a reduction in keratin filament branch length but did not alter overall mechanical properties as assessed by indentation analyses using atomic force microscopy and by displacement analyses of cytoplasmic superparamagnetic beads using magnetic tweezers. An increase in keratin movement was observed in plectin-depleted cells as was the case in control cells lacking hemidesmosome-like structures. Yet, keratin turnover was not significantly affected. We conclude that plectin alone is not needed for keratin assembly and disassembly and that other mechanisms exist to guarantee proper keratin cycling under steady state conditions in cultured single cells.


Subject(s)
Keratins/metabolism , Plectin/metabolism , Actin Cytoskeleton/metabolism , Actins/metabolism , Carrier Proteins/metabolism , Cell Line, Tumor , Cell Movement/physiology , Cytoskeletal Proteins/metabolism , Cytoskeleton/metabolism , Dystonin , Epithelial Cells/metabolism , Hemidesmosomes/metabolism , Humans , Integrin beta4/metabolism , Intermediate Filament Proteins/metabolism , Intermediate Filaments/metabolism , Keratinocytes/metabolism , Nerve Tissue Proteins/metabolism , Protein Binding/physiology
2.
Methods Inf Med ; 46(3): 324-31, 2007.
Article in English | MEDLINE | ID: mdl-17492119

ABSTRACT

OBJECTIVES: Pleural thickenings as biomarker of exposure to asbestos may evolve into malignant pleural mesothelioma. For its early stage, pleurectomy with perioperative treatment can reduce morbidity and mortality. The diagnosis is based on a visual investigation of CT images, which is a time-consuming and subjective procedure. Our aim is to develop an automatic image processing approach to detect and quantitatively assess pleural thickenings. METHODS: We first segment the lung areas, and identify the pleural contours. A convexity model is then used together with a Hounsfield unit threshold to detect pleural thickenings. The assessment of the detected pleural thickenings is based on a spline-based model of the healthy pleura. RESULTS: Tests were carried out on 14 data sets from three patients. In all cases, pleural contours were reliably identified, and pleural thickenings detected. PC-based Computation times were 85 min for a data set of 716 slices, 35 min for 401 slices, and 4 min for 75 slices, resulting in an average computation time of about 5.2 s per slice. Visualizations of pleurae and detected thickenings were provided. CONCLUSION: Results obtained so far indicate that our approach is able to assist physicians in the tedious task of finding and quantifying pleural thickenings in CT data. In the next step, our system will undergo an evaluation in a clinical test setting using routine CT data to quantify its performance.


Subject(s)
Diagnosis, Computer-Assisted/methods , Image Processing, Computer-Assisted/methods , Pleural Neoplasms/diagnostic imaging , Pleural Neoplasms/diagnosis , Tomography, X-Ray Computed , Early Diagnosis , Germany , Humans , Radiography, Thoracic
3.
J Cardiovasc Electrophysiol ; 14(10 Suppl): S210-8, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14760926

ABSTRACT

INTRODUCTION: Myocytes from normal and failing myocardium show significant differences in electromechanical behavior. Mathematical modeling of the behavior provides insights into the underlying physiologic and pathophysiologic mechanisms. Electromechanical models of cardiomyocytes exist for various species, but models of human myocytes are lacking. METHODS AND RESULTS: A mathematical model of electromechanics in normal and failing cardiac myocytes in humans was created by assembly and adaptation of parameters of an electrophysiologic model at the level of single cells and a force development model at the level of the sarcomere. The adaptation was performed using data from recent studies of ventricular myocytes and myocardium. The model was applied to quantitatively reconstruct measurement data from different experimental studies of normal and failing myocardium. Several simulations were performed to quantify the transmembrane voltage Vm, intracellular concentration of calcium[Ca2+]i, the [Ca2+]i-force relationship, and force transients. Furthermore, frequency dependencies and restitution of action voltage duration to 90% recovery APD90, peak [Ca2+]i, duration to 50% force recovery FD50, and peak force were determined. CONCLUSION: The presented mathematical model was capable of quantitatively reconstructing data obtained from different studies of electrophysiology and force development in normal and failing myocardium of humans. In future work, the model can serve as a component for studying macroscopic mechanisms of excitation propagation, metabolism, and electromechanics in human myocardium.


Subject(s)
Heart Failure/physiopathology , Heart/physiology , Heart/physiopathology , Myocardial Contraction/physiology , Algorithms , Biomechanical Phenomena , Calcium/physiology , Calcium Signaling/physiology , Computer Simulation , Electrophysiology , Humans , Kinetics , Membrane Potentials/physiology , Models, Biological , Models, Statistical , Myocardium/cytology , Myocytes, Cardiac/physiology , Sarcomeres/physiology , Troponin C/physiology
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