The authors thank R. Frackowiak and C. Lopez for their critical comments on an earlier version of the manuscript. This work was supported by the Stoicescu Foundation, the Swiss Science Foundation (Sinergia grant Balancing Body and Self), the Centre d’Imagerie BioMédicale (CIBM) of the University of Lausanne (UNIL), the Swiss Federal Institute of Technology Lausanne (EPFL), the University of Geneva (UniGe), the Centre Hospitalier Universitaire Vaudois (CHUV), the Hôpitaux Universitaires de Genève (HUG), and the Leenaards and the Jeantet Foundations. LH is supported by the Swiss National Science Foundation (SNSF, grant

323530-123718). The authors are supported by the Swiss National Foundation (SINERGIA CRSII1-125135/1). “
“(Neuron 70, 141–152; April 14, 2011) Because of an error during production, the first sentence

of Dabrafenib molecular weight the abstract mistakenly used “attend” instead of “attended”: Neurons in the primate dorsolateral prefrontal cortex (dlPFC) filter attend targets distinctly from distracters through their response rates. The journal regrets this error, and the online version of the manuscript now correctly reads “attended. “
“Endoplasmic SCH 900776 ic50 reticulum (ER) homeostasis, protein synthesis, and protein quality control processes are tightly coordinated events that together ensure a smooth and adequate flow of proteins through cellular compartments, without build-up of misfolded or unfolded proteins. In mammalian cells, disturbances in ER homeostasis trigger three distinct adaptive signaling pathways (Figure 1). First, the accumulation of unfolded proteins activates the ER-resident kinase PERK, whose major substrate is the translation initiation factor eiF2a. Upon phosphorylation of eiF2a, translation is inhibited, thus reducing the load on the folding machinery. In parallel, eiF2a phosphorylation Cell press stimulates

the translation of a specific subset of mRNAs, including that encoding the transcription factor ATF4. In turn, ATF4 drives the transcription of several critical genes including CHOP, the transcription factor that can trigger the expression of pro-apoptotic genes. A second pathway relies on the bifunctional transmembrane kinase-endonuclease IRE1. Upon detecting unfolded proteins in the ER lumen, IRE1 undergoes multimerization and autophosphorylation, which activates its ribonuclease domain. Active IRE1 is responsible for the unconventional splicing of the mRNA coding for XBP1: when activated, IRE1 ribonuclease removes the intron in XBP1 mRNA, allowing the mRNA to properly code for XBP1, a transcription factor that upregulates ER membrane biosynthesis, ER chaperones, and ER-associated degradation complexes. A third system is based on the cleavage of the transmembrane domain of the transcription factor ATF6.