670 research outputs found
El análisis de formas libres en arquitectura a partir de la generación digital de superficies. La cubierta de Ronchamp
No full text[ES] Sin resumenDe Mesa Gisbert, A.; Regot Marimón, J. (2005). El análisis de formas libres en arquitectura a partir de la generación digital de superficies. La cubierta de Ronchamp. EGA. Revista de Expresión Gráfica Arquitectónica. (10):86-93. https://doi.org/10.4995/ega.2005.10334SWORD869310STOLLER, Ezra. The Chapel at Ronchamp. Building blocks. Princeton Architectural Press. New York, 1999.PETIT, Jean. Le Livre de Ronchamp Le Corbusier Les Cahiers Forces Vives. 1961.SCHNEIDER. Philip J. NURB Curves: A Guide Oevelop far the Uninitiated. The Apple Technical Journal. lssue 25, 1996.PIEGL, Les A. & TILLER Wayne. The Nurbs Book (Monographs in Visual Communications) Springer Verlag. Berlín, 1997.FARIN. Gerald E. Curves and Surfaces far Computer-aided Geometric Design. Margan Kaufmann Publishers. San Francisco, 1996
Calcium binding protects E-cadherin from cleavage by Helicobacter pylori HtrA
Get PDFBackground: The cell adhesion and tumor suppressor protein E-cadherin is an important factor in the establishment and maintenance of epithelial integrity. E-cadherin is a single transmembrane protein, which consists of an intracellular domain (IC), a transmembrane domain (TD), and five extracellular domains (EC). EC domains form homophilic interactions in cis and trans that require calcium binding to the linker region between the EC domains. In our previous studies, we identified the serine protease high temperature requirement A (HtrA) from the human pathogen and class-I carcinogen Helicobacter pylori (H. pylori) as a bacterial E-cadherin-cleaving protease that targets the linker region of the EC domains, thereby disrupting gastric epithelial integrity. However, it remains unclear how calcium binding to the E-cadherin linker regions affects HtrA-mediated cleavage.
Results: Investigating the influence of calcium on the HtrA-mediated cleavage of recombinant E-cadherin (rCdh1) in vitro, we tested different concentrations of calcium ions and the calcium chelator ethylenediaminetetraacetic acid (EDTA). Calcium efficiently reduced HtrA-mediated E-cadherin fragmentation. Conversely, the addition of EDTA strongly increased cleavage, resulting in a ladder of defined E-cadherin fragments. However, calcium ions did not affect HtrA oligomerization and protease activity as monitored by degradation of the universal protease substrate casein. Finally, addition of ethyleneglycol-bis-tetraacetic acid (EGTA) slightly enhanced E-cadherin cleavage during H. pylori infection of gastric epithelial cells.
Conclusions: Our results suggest that calcium blocks HtrA-mediated cleavage by interfering with the accessibility of calcium-binding regions between the individual EC domains, which have been identified as cleavage sites of HtrA.Thomas P. Schmidt, Camilla Goetz, Markus Huemer, Gisbert Schneider and Silja Wessle
Prediction of type III secretion signals in genomes of gram-negative bacteria
No full textBackground: Pathogenic bacteria infecting both animals as well as plants use various mechanisms to transport virulence factors across their cell membranes and channel these proteins into the infected host cell. The type III secretion system represents such a mechanism. Proteins transported via this pathway (‘‘effector proteins’’) have to be distinguished from all other proteins that are not exported from the bacterial cell. Although a special targeting signal at the N-terminal end of effector proteins has been proposed in literature its exact characteristics remain unknown. Methodology/Principal Findings: In this study, we demonstrate that the signals encoded in the sequences of type III secretion system effectors can be consistently recognized and predicted by machine learning techniques. Known protein effectors were compiled from the literature and sequence databases, and served as training data for artificial neural networks and support vector machine classifiers. Common sequence features were most pronounced in the first 30 amino acids of the effector sequences. Classification accuracy yielded a cross-validated Matthews correlation of 0.63 and allowed for genome-wide prediction of potential type III secretion system effectors in 705 proteobacterial genomes (12% predicted candidates protein), their chromosomes (11%) and plasmids (13%), as well as 213 Firmicute genomes (7%). Conclusions/Significance: We present a signal prediction method together with comprehensive survey of potential type III secretion system effectors extracted from 918 published bacterial genomes. Our study demonstrates that the analyzed signal features are common across a wide range of species, and provides a substantial basis for the identification of exported pathogenic proteins as targets for future therapeutic intervention. The prediction software is publicly accessible from our web server ( www.modlab.org )
Curiosity-driven drug discovery: from pharmacophore profiling to active machine learning
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