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Of the hollowing out of books there is, it seems, no end. When we raised the subject late last year (November 19), the phenomenon was not unknown to us. But [...]

Kv1.2 [alpha]-subunits are components of low-threshold, rapidly activating voltage-gated potassium (Kv) channels in mammalian neurons. Expression and localization of Kv channels is regulated by trafficking signals encoded in their primary structure. Kv1.2 is unique in lacking strong trafficking signals and in exhibiting dramatic cell-specific differences in trafficking, which is suggestive of conditional trafficking signals. Here we show that a cluster of cytoplasmic C-terminal phosphorylation sites regulates Kv1.2 trafficking. Using tandem MS to analyze Kv1.2 purified from rat, human, and mouse brain, we identified in each sample in vivo phosphoserine (pS) phosphorylation sites at pS434, pS440, and pS441, as well as doubly phosphorylated pS440/pS441. We also found these sites, as well as pS449, on recombinant Kv1.2 expressed in heterologous cells. We found that phosphorylation at pS440/pS441 is present only on the post-endoplasmic reticulum (ER)/cell surface pool of Kv1.2 and is not detectable on newly synthesized and ER-localized Kvl.2, on which we did observe pS449 phosphorylation. Elimination of PS440/PS441 phosphorylation by mutation reduces cell-surface expression efficiency and functional expression of homomeric Kv1.2 channels. Interestingly, mutation of $449 reduces phosphorylation at pS440/pS441 and also decreases Kv1.2 cell-surface expression efficiency and functional expression. These mutations also suppress trafficking of Kv1.2/ Kv1.4 heteromeric channels, suggesting that incorporation of Kv1.2 into heteromeric complexes confers conditional phosphorylation-dependent trafficking to diverse Kv channel complexes. These data support Kvl.2 phosphorylation at these clustered C-terminal sites as playing an important role in regulating trafficking of Kv1.2-containing Kv channels. ion channel | mass spectrometry | proteomics I brain | phosphospecific

Byline: Cornelius Friesendorf (1) Abstract: Drug policy scholars generally agree that coercive attempts by the United States to reduce drug supplies from abroad have negative side effects. This article confirms that US coercion has made a bad situation worse. However, it also argues against oversimplified statements about the creation of side effects. The empirical focus is on the Air Bridge Denial Program, a US-sponsored attempt from the late 1980s to 2001 to reduce aerial drug trafficking in South America. A causal mechanism is developed that helps to understand and explain how air interdiction contributed to the displacement of coca cultivation from Peru to Colombia, an increase in Peruvian and Bolivian cocaine production, and a diversification of trafficking routes and methods. The analysis also examines contingent conditions, empirical black boxes, and alternative explanations. A complex empirical picture means that the popular metaphor of a balloon whose air, when squeezed, simply moves elsewhere is misleading. Although US-sponsored air interdiction has contributed to displacement, other factors have played a role as well. Author Affiliation: (1) Geneva School of Diplomacy & International Relations and Center for Security Studies, ETH Zurich (Swiss Federal Institute of Technology) ETH Zentrum SEI, 8092, Zurich, Switzerland Article History: Registration Date: 11/01/2006 Received Date: 01/05/2005 Accepted Date: 11/01/2006 Online Date: 30/03/2006

Byline: Monica Massari (1) Abstract: How do 'new' drug markets develop and operate? Which are the characteristics of synthetic drug suppliers? How are they organized, owned and managed? This article summarizes the outcomes of a cross-national study which investigated three urban synthetic drug markets at a different stage of development: Amsterdam, Barcelona and Turin. The study -- the first of this type in Europe -- outlines a composite picture which clearly indicates the presence of rather flexible and dynamic actors and a quasi 'free' drug economy. Hence, the role played by more structured, mafia-type organizations, even in Italy, needs to be reconceived. The wide use of primary sources, altogether the adoption of qualitative interpretative tools, contributed to shed some light on a phenomenon which is still poorly investigated both at national and international levels. Author Affiliation: (1) Department of Sociology and Political Science, University of Calabria, Calabria, Italy Article History: Registration Date: 23/03/2006 Received Date: 16/06/2003 Accepted Date: 22/03/2006 Online Date: 13/05/2006