Identification and molecular mechanisms of the rapid tonicity-induced relocalization of the aquaporin 4 channel

The aquaporin family of integral membrane proteins is comprised of channels that mediate cellular water flow. Aquaporin 4 (AQP4) is highly expressed in the glial cells of the central nervous system and facilitates the osmotically-driven pathological brain swelling associated with stroke and traumatic brain injury. Here we show that AQP4 cell surface expression can be rapidly and reversibly regulated in response to changes of tonicity in primary cortical rat astrocytes and in transfected HEK293 cells. The translocation mechanism involves protein kinase A (PKA) activation, influx of extracellular calcium and activation of calmodulin. We identify five putative PKA phosphorylation sites and use site-directed mutagenesis to show that only phosphorylation at one of these sites, serine- 276, is necessary for the translocation response. We discuss our findings in the context of the identification of new therapeutic approaches to treating brain oedema

The structure of the hantavirus zinc finger domain is conserved and represents the only natively folded region of the Gn cytoplasmic tail

Hantaviruses, of the family Bunyaviridae, are present throughout the world and cause a variety of infections ranging from the asymptomatic to mild and severe hemorrhagic fevers. Hantaviruses are enveloped anti-sense RNA viruses that contain three genomic segments that encode for a nucleocapsid protein, two membrane glycoproteins (Gn and Gc), and an RNA polymerase. Recently, the pathogenicity of hantaviruses has been mapped to the carboxyl end of the 150 residue Gn cytoplasmic tail. The Gn tail has also been shown to play a role in binding the ribonucleoprotein (RNP), a step critical for virus assembly. In this study, we use NMR spectroscopy to compare the structure of a Gn tail zinc finger domain of both a pathogenic (Andes) and a non-pathogenic (Prospect Hill) hantavirus. We demonstrate that despite a stark difference in the virulence of both of these viruses, the structure of the Gn core zinc finger domain is largely conserved in both strains. We also use NMR backbone relaxation studies to demonstrate that the regions of the Andes virus Gn tail immediately outside the zinc finger domain, sites known to bind the RNP, are disordered and flexible, thus intimating that the zinc finger domain is the only structured region of the Gn tail. These structural observations provide further insight into the role of the Gn tail during viral assembly as well as its role in pathogenesis

'Feeling' risk and seeing solutions: Predicting vaccination intention against Hepatitis B infection among men who have sex with men

This study assessed cognitive and affective predictors of intention to obtain vaccination against the hepatitis B virus (HBV) among men who have sex with men (MSM), based on leading social cognitive models of health behavior. The key predictors of vaccination intention were perceived risk of contracting HBV, expectancies regarding the outcome of vaccination, and the interaction between risk perception and outcome expectancies. Negative affect increased risk perceptions, which, in turn, positively affected vaccination intention. It is concluded that MSM should feel they are at risk for HBV, and see solutions to this risk. Copyright © 2008 SAGE Publications

The experience of long-term opiate maintenance treatment and reported barriers to recovery: A qualitative systematic review

Background/Aim: To inform understanding of the experience of long-term opiate maintenance and identify barriers to recovery. Methods: A qualitative systematic review. Results: 14 studies in 17 papers, mainly from the USA (65%), met inclusion criteria, involving 1,088 participants. Studies focused on methadone prescribing. Participants reported stability; however, many disliked methadone. Barriers to full recovery were primarily ‘inward focused'. Conclusion: This is the first review of qualitative literature on long-term maintenance, finding that universal service improvements could be made to address reported barriers to recovery, including involving ex-users as positive role models, and increasing access to psychological support. Treatment policies combining harm minimisation and abstinence-orientated approaches may best support individualised recovery

Why It Is Important to Understand Animal Behavior

Although people have long been fascinated by the behavior of animals, the formal discipline of animal behavior--ethology--is actually relatively new, dating to the work of Konrad Lorenz in Austria in the 1930s. Application of ethological principles and methods to the study of animal welfare is an even newer endeavor, of course, and one that has generated a great deal of stimulating discussion and controversy during its short history. In this paper, I provide an overview of the development of behavioral approaches to the study of animal welfare. I then discuss some reasons that behaviors are important to animals and describe how an understanding of behavior can be useful when designing housing environments for laboratory animals

Energy Harvesting with a Liquid-Metal Microfluidic Influence Machine

We describe and demonstrate a new energy harvesting technology based on a microfluidic realization of a Wimshurst influence machine. The prototype device converts the mechanical energy of a pressure-driven flow into electrical energy, using a multiphase system composed of droplets of liquid mercury surrounded by insulating oil. Electrostatic induction between adjacent metal droplets drives charge through external electrode paths, resulting in continuous charge amplification and collection. We demonstrate a power output of 4 nW from the initial prototype and present calculations suggesting that straightforward device optimization could increase the power output by more than 3 orders of magnitude. At that level the power efficiency of this energy harvesting mechanism, limited by viscous dissipation, could exceed 90%. The microfluidic context enables straightforward scaling and parallelization, as well as hydraulic matching to a variety of ambient mechanical energy sources such as human locomotion.Comment: 7 pages, 7 figure

The second intracellular loop of the calcitonin gene-related peptide receptor provides molecular determinants for signal transduction and cell surface expression

The calcitonin gene-related peptide (CGRP) receptor is a heterodimer of a family B G-protein-coupled receptor, calcitonin receptor-like receptor (CLR), and the accessory protein receptor activity modifying protein 1. It couples to Gs, but it is not known which intracellular loops mediate this. We have identified the boundaries of this loop based on the relative position and length of the juxtamembrane transmembrane regions 3 and 4. The loop has been analyzed by systematic mutagenesis of all residues to alanine, measuring cAMP accumulation, CGRP affinity, and receptor expression. Unlike rhodopsin, ICL2 of the CGRP receptor plays a part in the conformational switch after agonist interaction. His-216 and Lys-227 were essential for a functional CGRP-induced cAMP response. The effect of (H216A)CLR is due to a disruption to the cell surface transport or surface stability of the mutant receptor. In contrast, (K227A)CLR had wild-type expression and agonist affinity, suggesting a direct disruption to the downstream signal transduction mechanism of the CGRP receptor. Modeling suggests that the loop undergoes a significant shift in position during receptor activation, exposing a potential G-protein binding pocket. Lys-227 changes position to point into the pocket, potentially allowing it to interact with bound G-proteins. His-216 occupies a position similar to that of Tyr-136 in bovine rhodopsin, part of the DRY motif of the latter receptor. This is the first comprehensive analysis of an entire intracellular loop within the calcitonin family of G-protein-coupled receptor. These data help to define the structural and functional characteristics of the CGRP-receptor and of family B G-protein-coupled receptors in general. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc

Why do people fail to turn good intentions into action? : The role of executive control processes in the translation of healthy eating intentions into action in young Scottish adults

Non peer reviewedPublisher PD

The Intention–Behavior Gap

© 2016 John Wiley & Sons LtdBitter personal experience and meta-analysis converge on the conclusion that people do not always do the things that they intend to do. This paper synthesizes research on intention–behavior relations to address questions such as: How big is the intention–behavior gap? When are intentions more or less likely to get translated into action? What kinds of problems prevent people from realizing their intentions? And what strategies show promise in closing the intention–behavior gap and helping people do the things that they intend to do?