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Deciphering the function of the essential yeast Sec14p protein has revealed a regulatory interface between cargo secretion from Golgi and lipid homeostasis. Abrogation of the CDP-choline (CDP-Cho) pathway for phosphatidylcholine (PC) synthesis allows for life in the absence of the otherwise essential Sec14p. Nte1p, the product of open reading frame YML059c, is an integral membrane phospholipase against CDP-Cho-derived PC producing intracellular glycerophosphocholine (GPCho) and free fatty acids. We monitored Nte1p activity through in vivo PC turnover measurements and observed that intracellular GPCho accumulation is decreased in a sec14 ts strain shifted to 37°C in 10 mM choline (Cho)-containing medium compared with a Sec14p-proficient strain. Overexpression of two Sec14p homologs Sfh2p and Sfh4p in sec14 ts cells restored secretion and growth at the restrictive temperature but did not restore GPCho accumulation. Instead, newly synthesized PC was degraded by phospholipase D (Spo14p). Similar analysis performed in a sec14⌬ background confirmed these observations. These results imply that the ability of Sfh2p and Sfh4p to restore secretion and growth is not through a shared function with Sec14p in the regulation of PC turnover via Nte1p. Furthermore, our analyses revealed a profound alteration of PC metabolism triggered by the absence of Sec14p: Nte1p unresponsiveness, Spo14p activation, and deregulation of Pct1p. Sfh2p-and Sfh4p-overexpressing cells coped with the absence of Sec14p by controlling the rate of phosphocholine formation, limiting the amount of Cho available for this reaction, and actively excreting Cho from the cell. Increased Sfh4p also significantly reduced the uptake of exogenous Cho. Beyond the new PC metabolic control features we ascribe to Sfh2p and Sfh4p we also describe a second role for Sec14p in mediating PC homeostasis. Sec14p acts as a positive regulator of Nte1p-mediated PC deacylation with the functional consequence of increased Nte1p activity increasing the permissive temperature for the growth of sec14 ts cells.Lipid homeostasis is fulfilled through the coordinated synthesis, degradation, and trafficking of the lipid constituents of biological membranes. Many biological processes such as vesicle formation, protein trafficking, and lipid signaling are dependent on proper lipid content at particular membrane locations, and many cellular pathophysiological situations are associated with perturbations in lipid homeostasis (1).Deciphering the function of the Saccharomyces cerevisiae Sec14p protein has uncovered a regulatory interface between cargo secretion from the Golgi and lipid metabolism (2, 3). Sec14p is an essential soluble protein possessing in vitro phosphatidylinositol (PI) 1 /phosphatidylcholine (PC) transfer activity. Sec14p is located primarily in the cytoplasm, and it has been observed to associate with Golgi membranes presumably through its phospholipid binding ability (4). The lethality associated with Sec14p dysfunction or absence can be overcome by inactivating mutations ...

The Medical Humanities Program at Dalhousie University Faculty of Medicine in Nova Scotia, Canada, was initiated in 1992 to incorporate the medical humanities into the learning and experiences of medical students. The goal of the program was to gain acceptance as an integral part of the medical school. The program assumed a broad concept of the medical humanities that includes medical history, literature, music, art, multiculturalism, philosophy, epistemology, theology, anthropology, professionalism, history of alternative therapies, writing, storytelling, health law, international medicine, and ethics. Phase I of the program has provided the same elective and research opportunities in the medical humanities that are available to the students in clinical and basic sciences, and has encouraged and legitimized the involvement of the humanities in the life and learning of the medical student through a wide array of programs and activities. Phase II will focus on further incorporation of the humanities into the curriculum. Phase III will be the development of a graduate program in medical humanities to train more faculty who will incorporate the humanities into their teaching and into the development of education programs.

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