While current research perspectives on nicotine addiction emphasize the contribution of reward-related mesocorticolimbic dopamine (DA) systems, the role of the amygdala remains less well characterized, although it is crucially engaged in the emotional and motivational modulation of cognition and behavior. Consequently, we here review brain imaging studies reporting altered neural responses of the amygdala in nicotine addiction. A major focus is placed upon

resting-state and cue-induction studies documenting that nicotine addiction is associated with aberrant amygdala activity. Importantly, unprovoked abstinence-induced nicotine cravings have been shown to interfere with the amygdala’s ability to detect and adequately respond to harm signals. In light of this empirical evidence, we propose that impaired amygdala-guided harm avoidance and executive functions may be instrumental in maintaining selleck inhibitor nicotine addiction despite serious health consequences. (C) 2012 Elsevier Ltd. All rights reserved.”
“One of the many challenging tasks of protein design is the introduction of a completely new function into an existing protein scaffold. In this study, we introduce a new computational

SP600125 cost procedure OptGraft for placing a novel binding pocket onto a protein structure so as its geometry is minimally perturbed. This is accomplished by introducing a two-level procedure where we first identify where are the most appropriate locations to graft the new binding pocket into the protein fold by minimizing the departure from a set of geometric restraints using mixed-integer

linear optimization. On identifying the suitable locations that can accommodate the new binding pocket, CHARMM energy calculations are employed to identify what mutations in the neighboring residues, if any, are needed to ensure that the minimum energy conformation of the binding pocket conserves the desired geometry. This computational framework is benchmarked against the results available in the literature for engineering a copper binding site into thioredoxin protein. Subsequently, OptGraft is used to during guide the transfer of a calcium-binding pocket from thermitase protein (PDB: 1thm) into the first domain of CD2 protein (PDB:1hng). Experimental characterization of three de novo redesigned proteins with grafted calcium-binding centers demonstrated that they all exhibit high affinities for terbium (K(d) similar to 22, 38, and 55 mu M) and can selectively bind calcium over magnesium.”
“The systems-level neuronal mechanisms that coordinate temporally, anatomically and functionally distributed neuronal activity into coherent cognitive operations in the human brain have remained poorly understood. Synchronization of neuronal oscillations may regulate network communication and could thus serve as such a mechanism.