Off-Target Effects of Psychoactive Drugs Revealed by Genome-Wide Assays in Yeast

To better understand off-target effects of widely prescribed psychoactive drugs, we performed a comprehensive series of chemogenomic screens using the budding yeast Saccharomyces cerevisiae as a model system. Because the known human targets of these drugs do not exist in yeast, we could employ the yeast gene deletion collections and parallel fitness profiling to explore potential off-target effects in a genome-wide manner. Among 214 tested, documented psychoactive drugs, we identified 81 compounds that inhibited wild-type yeast growth and were thus selected for genome-wide fitness profiling. Many of these drugs had a propensity to affect multiple cellular functions. The sensitivity profiles of half of the analyzed drugs were enriched for core cellular processes such as secretion, protein folding, RNA processing, and chromatin structure. Interestingly, fluoxetine (Prozac) interfered with establishment of cell polarity, cyproheptadine (Periactin) targeted essential genes with chromatin-remodeling roles, while paroxetine (Paxil) interfered with essential RNA metabolism genes, suggesting potential secondary drug targets. We also found that the more recently developed atypical antipsychotic clozapine (Clozaril) had no fewer off-target effects in yeast than the typical antipsychotics haloperidol (Haldol) and pimozide (Orap). Our results suggest that model organism pharmacogenetic studies provide a rational foundation for understanding the off-target effects of clinically important psychoactive agents and suggest a rational means both for devising compound derivatives with fewer side effects and for tailoring drug treatment to individual patient genotypes

What determines cell size?

AbstractFirst paragraph (this article has no abstract) For well over 100 years, cell biologists have been wondering what determines the size of cells. In modern times, we know all of the molecules that control the cell cycle and cell division, but we still do not understand how cell size is determined. To check whether modern cell biology has made any inroads on this age-old question, BMC Biology asked several heavyweights in the field to tell us how they think cell size is controlled, drawing on a range of different cell types. The essays in this collection address two related questions - why does cell size matter, and how do cells control it

Re-examining policies for food security in Asia

In the wake of recent food price spikes, plus growing demands for food in emerging Asia and for biofuels in Europe and the United States, governments are re-examining their strategies for dealing with both short-term and long-term food security concerns. This paper argues that long-run trends in real agricultural prices have policy implications for food security that are at least as important as those related to short-lived spikes around trend prices. The paper therefore summarizes recent projections of markets to 2030 under various scenarios, and then reviews evidence on how trade policy restrictions typically are altered to insulate domestic markets from short-run fluctuations in international prices around their long-run trends. That provides a firm empirical basis for re-examining the effectiveness and efficiency of various policy options for ensuring food security in Asia and elsewhere. Those options include boosting agricultural productivity growth rates to deal with long-run concerns, and using more-appropriate domestic policy measures rather than trade policies to cope with price volatility.Kym Anderson & Shikha Jha & Signe Nelgen & Anna Strut