Calcineurin is a conserved Ca2؉ -calmodulin-activated, serine/threonine-specific protein phosphatase that regulates a variety of physiological processes, e.g., cell cycle progression, polarized growth, and adaptation to salt and alkaline pH stresses. In the pathogenic yeast Cryptococcus neoformans, calcineurin is also essential for growth at 37°C and virulence. To investigate whether calcineurin plays a role in the virulence of Candida albicans, the major fungal pathogen of humans, we constructed C. albicans mutants in which both alleles of the CMP1 gene, encoding the calcineurin catalytic subunit, were deleted. The C. albicans ⌬cmp1 mutants displayed hypersensitivity to elevated Na ؉ , Li ؉ , and Mn 2؉ concentrations and to alkaline pH, phenotypes that have been described after calcineurin inactivation in the related yeast Saccharomyces cerevisiae. Unlike S. cerevisiae calcineurin mutants, which exhibit reduced susceptibility to high Ca 2؉ concentrations, growth of C. albicans was inhibited in the presence of 300 mM CaCl 2 after the deletion of CMP1, demonstrating that there are also differences in calcineurin-mediated cellular responses between these two yeast species. In contrast to C. neoformans, inactivation of calcineurin did not cause temperature sensitivity in C. albicans. In addition, hyphal growth, an important virulence attribute of C. albicans, was not impaired in the ⌬cmp1 mutants under a variety of inducing conditions. Nevertheless, the virulence of the mutants was strongly attenuated in a mouse model of systemic candidiasis, demonstrating that calcineurin signaling is essential for virulence in C. albicans.
By generating a calcineurin mutant of the Candida albicans wild-type strain SC5314 with the help of a new recyclable dominant selection marker, we confirmed that calcineurin mediates tolerance to a variety of stress conditions but is not required for the ability of C. albicans to switch to filamentous growth in response to hypha-inducing environmental signals. While calcineurin was essential for virulence of C. albicans in a mouse model of disseminated candidiasis, deletion of CMP1 did not significantly affect virulence during vaginal or pulmonary infection, demonstrating that the requirement for calcineurin for a successful infection depends on the host niche.
In order to assist surgeons during surgery on moving organs, e.g. minimally invasive beating heart bypass surgery, a master-slave system which synchronizes surgical instruments with the organ's motion is desired. This synchronization requires reliable estimation of the organ's motion. In this paper, we present a new approach to motion estimation based on a state motion model for a partition of the heart's surface. Its motion behavior is described by a partial differential equation whose input function is assumed to be periodic. An estimator is used on one hand to predict future model states based on reconstruction of the input function and on the other hand to incorporate noisy spatially discrete measurements in order to improve state estimation. The model-based motion estimation is evaluated using a simple heart simulator. Measurements are obtained by reconstructing 3D position of markers on a pulsating membrane by means of a stereo camera system.
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