RESUMO
Endoscopy simulators get more and more common for the training of physicians. It is important to make simulation as realistic as possible by providing optical, acoustical and haptical feedback. The haptic display of our simulator EndoSim allows applying active forces to all degrees of freedom and moving to defined positions. This positioning is used for our automatic guiding system. If the user asks for help, an algorithm calculates how to get over the next barrier, factoring forces and distances. The system is able to decide if it is wise to choose a longer way in order to reduce the force. The user gets either an optical help shown by signs or is guided directly by the automatically moved endoscope. This guiding system is a new possibility for teaching physicians to increase their examination capabilities.
Assuntos
Simulação por Computador , Endoscopia , Interface Usuário-Computador , AlemanhaRESUMO
The centromere binding factor 1 (Cbf1) is necessary for proper chromosome segregation and transcriptional activation of methionine biosynthesis genes in the yeast Saccharomyces cerevisiae and is essential for viability in the related yeasts Kluyveromyces lactis and Candida glabrata. To study the function of Cbf1p in Candida albicans, the major human fungal pathogen, we constructed strains in which both alleles of the CaCBF1 gene were deleted. The Deltacbf1 mutants exhibited a slow growth phenotype and were temperature-sensitive at 42 degrees C. In addition, the mutants were auxotrophic for sulfur amino acids and could grow on minimal medium only when it was supplemented with either methionine or cysteine, suggesting that CaCBF1 is necessary for the expression of genes involved in assimilation of inorganic sulfate. Deletion of CaCBF1 also resulted in morphological abnormalities, many cells being unusually large. All mutant phenotypes were complemented by reintroduction of a functional CaCBF1 copy. The Deltacbf1 mutants neither showed enhanced sensitivity to the microtubule destabilizing agent thiabendazole nor did they exhibit an increased frequency of chromosome loss. These results suggest that Cbf1p is not necessary for efficient chromosome segregation in C. albicans.
Assuntos
Candida albicans/genética , Proteínas de Ligação a DNA/genética , Proteínas Fúngicas/genética , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Divisão Celular/efeitos dos fármacos , Divisão Celular/genética , Instabilidade Cromossômica , Deleção Cromossômica , Segregação de Cromossomos/genética , Cromossomos Fúngicos/genética , Cisteína/farmacologia , Deleção de Genes , Metionina/farmacologia , Mutação , Fenótipo , Temperatura , Tiabendazol/farmacologiaRESUMO
The formation of the Mtr2-Mex67 heterodimer is essential for yeast mRNA export as it constitutes a key nuclear component for shuttling mRNA between the nuclear and cytoplasm compartments through the nuclear pore complex. We report the crystal structures of apo-Mtr2 from the human pathogen Candida albicans and of its complex with the Mex67 NTF2-like domain. Compared with other members of the NTF2 fold family, Mtr2 displays novel structural features involved in the nuclear export of the large ribosomal subunit and consistent with a dual functional role of Mtr2 during yeast nuclear export events. The structure of the Mtr2-Mex67 NTF2-like domain complex, which overall is similar to those of the human and Saccharomyces cerevisiae homologs, unveils three putative Phe-Gly repeat binding sites, of which one contributes to the heterodimer interface. These structures exemplify an unrecognized adaptability of the NTF2 building block in evolution, identify novel structural determinants associated with key biological functions at the molecular surface of the yeast Mtr2-Mex67 complex, and suggest that the yeast and human mRNA export machineries may differ.
Assuntos
Núcleo Celular/metabolismo , Proteínas de Membrana Transportadoras/química , Proteínas Nucleares/química , Proteínas de Transporte Nucleocitoplasmático/química , Proteínas de Ligação a RNA/química , Proteínas de Saccharomyces cerevisiae/química , Transporte Ativo do Núcleo Celular , Sequência de Aminoácidos , Sítios de Ligação , Candida albicans/metabolismo , Cromatografia em Gel , Cristalografia por Raios X , Citoplasma/metabolismo , Dimerização , Proteínas Fúngicas/química , Humanos , Proteínas de Membrana Transportadoras/metabolismo , Modelos Biológicos , Modelos Moleculares , Dados de Sequência Molecular , Proteínas Nucleares/metabolismo , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Ligação Proteica , Dobramento de Proteína , Estrutura Terciária de Proteína , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Homologia de Sequência de Aminoácidos , Especificidade da EspécieRESUMO
The RAP1 gene (repressor/activator protein 1) encodes a transcription factor and telomere binding protein that is essential for viability in the budding yeast Saccharomyces cerevisiae. The genome sequence of the opportunistic fungal pathogen Candida albicans contains a RAP1 homologue. We generated C. albicans mutants in which both RAP1 alleles were deleted. The Deltarap1 mutants grew as well as the wild-type parental strain and formed normal germ tubes and hyphae in response to a variety of inducing conditions. However, under conditions that promote budding yeast growth in the wild-type strain, the Deltarap1 mutants formed both yeast and pseudohyphal cells. This phenotype was reverted upon reintroduction of a functional RAP1 copy. Our results demonstrate that RAP1 is a non-essential gene in C. albicans which is required to repress the formation of pseudohyphae under conditions favouring growth as budding yeast.
