Sustainability of water transfer projects: A systematic review.

Inter-basin water transfer projects (IBTs) have significantly increased in number in recent decades due to the unremitting need to solve the problem of global water imbalance. However, given the complex challenges inherent in implementing and maintaining IBTs, there is a need to characterize the multi-faceted aspects of sustainability (or unsustainability) that result from these megaprojects. Through a systematic review of the literature, we sought to identify and characterize the positive and negative impacts that most often influence the sustainability of IBTs, focusing on impacts within the environmental, social, and economic pillars of sustainability.

Role of the Cys Loop and Transmembrane Domain in the Allosteric Modulation of α4β2 Nicotinic Acetylcholine Receptors.

Allosteric modulators of pentameric ligand-gated ion channels are thought to act on elements of the pathways that couple agonist binding to channel gating. Using α4β2 nicotinic acetylcholine receptors and the α4β2-selective positive modulators 17β-estradiol (βEST) and desformylflustrabromine (dFBr), we have identified pathways that link the binding sites for these modulators to the Cys loop, a region that is critical for channel gating in all pentameric ligand-gated ion channels. Previous studies have shown that the binding site for potentiating βEST is in the C-terminal (post-M4) region of the α4 subunit.

Non-equivalent ligand selectivity of agonist sites in (α4β2)2α4 nicotinic acetylcholine receptors: a key determinant of agonist efficacy.

The α4β2 nicotinic acetylcholine receptor (nAChR) is the most abundant nAChR type in the brain, and this receptor type exists in alternate (α4β2)2α4 and (α4β2)2β2 forms, which are activated by agonists with strikingly differing efficacies. Recent breakthroughs have identified an additional operational agonist binding site in the (α4β2)2α4 nAChR that is responsible for the signature sensitivity of this receptor to activation by agonists, yet the structural mechanisms determining agonist efficacy at this receptor type are not yet fully understood. In this study, we characterized the ligand selectivity of the individual agonist sites of the (α4β2)2α4 nAChR to determine whether differences in agonist selectivity influence agonist efficacy.