Apelin reduces left ventricular preload and afterload and increases contractile reserve without evidence of hypertrophy. These results associate apelin with a positive hemodynamic profile and suggest it as an attractive target for pharmacotherapy in the setting of heart failure.

In general, distributed practice with the task station resulted in improvement in the ability to perform an anastomosis, as assessed by times to completion and performance ratings, not only with the task station but also with the beating-heart model. Not all residents improved, which is consistent with a "ceiling effect" with the simulator and a "plateau effect" with the trainee. Simulation can be useful in preparing residents for coronary anastomosis and can provide an opportunity to identify the need and methods for remediation.

Abstract. Aminopeptidase I (API) is a soluble leucine aminopeptidase resident in the yeast vacuole (Frey, J., and K.H. Rohm. 1978. Biochim. Biophys. Acta. 527:31-41). The precursor form of API contains an amino-terminal 45-amino acid propeptide, which is removed by proteinase B (PrB) upon entry into the vacuole. The propeptide of API lacks a consensus signal sequence and it has been demonstrated that vacuolar localization of API is independent of the secretory pathway (Klionsky, D.J., R. Cueva, and D.S. Yaver. 1992. J. Cell Biol. 119:287-299). The predicted secondary structure for the API propeptide is composed of an amphipathic a-helix followed by a [3-turn and another a-helix, forming a helix-turn-helix structure. With the use of mutational analysis, we determined that the API propeptide is essential for proper transport into the vacuole. Deletion of the entire propeptide from the API molecule resuited in accumulation of a mature-sized protein in the cytosol. A more detailed examination using random mutagenesis and a series of smaller deletions throughout the propeptide revealed that API localization is severely affected by alterations within the predicted first a-helix. In vitro studies indicate that mutations in this predicted helix prevent productive binding interactions from taking place. In contrast, vacuolar import is relatively insensitive to alterations in the second predicted helix of the propeptide. Examination of API folding revealed that mutations that affect entry into the vacuole did not affect the structure of API. These data indicate that the API propeptide serves as a vacuolar targeting determinant at a critical step along the cytoplasm to vacuole targeting pathway.I n the yeast Saccharomyces cerevisiae soluble proteins enter the vacuole through one of four mechanisms: autophagy (Hirsch et al., 1992;Tsukada and Ohsumi, 1993;Thumm et al., 1994; reviewed in Seglen and Bohley, 1992), endocytosis (reviewed in Nothwehr and Stevens, 1994;Raths et al., 1993;Riezman, 1993), the secretory pathway (reviewed in Pryer et al., 1992), and the cytoplasm to vacuole targeting pathway (Cvt; Klionsky et al., 1992;Harding et al., 1995). In both autophagy and endocytosis there is bulk flow of soluble proteins into the vacuole but to date no soluble resident vacuolar protein has been shown to enter the yeast vacuole by these means.The majority of resident yeast vacuolar proteins enter this organelle through the secretory pathway (reviewed in Stack and Emr, 1993). Contrary to autophagy and endocytosis, proteins that transit through the secretory pathway are not engulfed by membranes but are translocated across the endoplasmic reticulum (ER) membrane. In a series of vesicle-mediated transport steps, the proteins are carried from the ER through the subcompartments of the Golgi before being directed to the vacuole (reviewed in Pryer et al., 1992 secretory pathway has been carefully documented for a number of vacuolar hydrolases (reviewed in Klionsky et al., 1990). These proteins translocate across the ER membrane via...

Simulation-based learning with formative feedback results in overall improved performance of simulated mitral annuloplasty. In complex surgical procedures, simulation may provide necessary early graduated training and practice. Importantly, a "passing" grade can be established for proficiency-based advancement.