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Huntingtin-like proteins make yeast sick (bottom). eriin et al., reporting on page 997, have developed the first yeast model for studying Huntington's disease. Yeast cannot undergo neurodegeneration, of course, but the simplicity and genetic manipulability of the system are already providing important mechanistic insights. The authors report that aggregation of a polypeptide with an expanded poly-glutamine domain, mediated by a prion-like protein, is responsible for cell death in their system, suggesting revisions to earlier models of neurodegeneration. In Huntington's disease, expansion of the huntingtin polyglutamine domain leads to protein aggregation in inclusion bodies and neuronal cell death. In some systems, however, long polyglutamine peptides are toxic without aggregating, suggesting that aggregation of mutant huntingtin might not determine toxicity. Meriin and colleagues found, however, that aggregation of long polyglutamine peptides in yeast correlated with toxicity. Mutations in certain chaperone M genes, or curing the cells of the prion form of the Rnq1 protein, suppressed both aggregation and toxicity. The results directly link polyglutamine peptide aggregation with cell death, and demonstrate that prion proteins are required for this process, at least in yeast. The evolutionary conservation of these mechanisms suggests that prion-like proteins might also be involved in mammalian polyglutamine expansion diseases. ᭿ or years, epidemiologists and nutritionists have known that a diet high in the v-3 fatty acids found in fish oil correlates with a decreased risk of colon cancer. On page 915, Murray et al. explain why. As colon carcinogenesis is accompanied by an increase in the expression of the lipid-dependent protein kinase C ␤ II (PKC ␤ II), the authors reasoned that ␻-3 fatty acids might inhibit PKC ␤ II signaling. Analysis of rat colonic epithelia and PKC ␤ II transgenic mice demonstrated that ␻-3 fatty acids block F ␻-3 (right), but not ␻-6 (left), fatty acids restore TGF␤RII expression. PKC ␤ II activation and reduce the pro-carcinogenic effects of PKC ␤ II in vitro and in vivo. PKC ␤ II appears to repress the expression of transforming growth factor ␤ receptor II (TGF ␤ RII), desensitizing cells to the growth-inhibiting effects of TGF ␤. The results suggest that ␻-3 fatty acids inhibit PKC ␤ II, thus relieving the inhibition of TGF ␤ RII expression. This renders colon epithelial cells sensitive to TGF ␤ , and prevents or reverses the hyperproliferative state that leads to colon cancer. Dietary ␻-3 fatty acids are also associated with preventing prostate and breast …