Functional and biophysical analysis of the C-terminus of the CGRP-receptor; a family B GPCR

G-protein coupled receptors (GPCRs) typically have a functionally important C-terminus which, in the largest subfamily (family A), includes a membrane-parallel eighth helix. Mutations of this region are associated with several diseases. There are few C-terminal studies on the family B GPCRs and no data supporting the existence of a similar eighth helix in this second major subfamily, which has little or no sequence homology to family A GPCRs. Here we show that the C-terminus of a family B GPCR (CLR) has a disparate region from N400 to C436 required for CGRP-mediated internalization, and a proximal region of twelve residues (from G388 to W399), in a similar position to the family A eighth helix, required for receptor localization at the cell surface. A combination of circular and linear dichroism, fluorescence and modified waterLOGSY NMR spectroscopy (SALMON) demonstrated that a peptide mimetic of this domain readily forms a membrane-parallel helix anchored to the liposome by an interfacial tryptophan residue. The study reveals two key functions held within the C-terminus of a family B GPCR and presents support for an eighth helical region with striking topological similarity to the nonhomologous family A receptor. This helix structure appears to be found in most other family B GPCRs.

Structural properties of a family of hydrogen-bonded co-crystals formed between gemfibrozil and hydroxy derivatives of t-butylamine, determined directly from powder X-ray diffraction data

We report the formation and structural properties of co-crystals containing gemfibrozil and hydroxy derivatives of t-butylamine H2NC(CH3)3-n(CH2OH)n, with n=0, 1, 2 and 3. In each case, a 1:1 co-crystal is formed, with transfer of a proton from the carboxylic acid group of gemfibrozil to the amino group of the t-butylamine derivative. All of the co-crystal materials prepared are polycrystalline powders, and do not contain single crystals of suitable size and/or quality for single crystal X-ray diffraction studies. Structure determination of these materials has been carried out directly from powder X-ray diffraction data, using the direct-space Genetic Algorithm technique for structure solution followed by Rietveld refinement. The structural chemistry of this series of co-crystal materials reveals well-defined structural trends within the first three members of the family (n=0, 1, 2), but significantly contrasting structural properties for the member with n=3. © 2007 Elsevier Inc. All rights reserved.

Effect of support and cultural intelligence on the adjustment and performance of expatriates and their family members in Malaysia

Theory suggests that people fear the unknown and no matter how experienced one is, the feelings of anxiety and uncertainty, if not managed well would affect how we view ourselves and how others view us. Hence, it is in human nature to engage in activities to help decipher behaviours that seem contrary to their beliefs and hinder the smooth-flowing of their work and daily activities. Building on these arguments, this research investigates the two types of support that are provided by multinational corporations (MNCs) and host country nationals (HCNs) to the expatriates and their family members whilst on international assignments in Malaysia as antecedents to their adjustment and performance in the host country. To complement the support provided, cultural intelligence (CQ) is investigated to explain the influence of cultural elements in facilitating adjustment and performance of the relocating families, especially to socially integrate into the host country. This research aims to investigate the influence of support and CQ on the adjustment and performance of expatriates in Malaysia. Path analyses are used to test the hypothesised relationships. The findings substantiate the pivotal roles that MNCs and HCNs play in helping the expatriates and their families acclimatise to the host country. This corroborates the norm of reciprocity where assistance or support rendered especially at the times when they were crucially needed would be reciprocated with positive behaviour deemed of equal value. Additionally, CQ is significantly positive in enhancing adjustment to the host country, which highlights the vital role that cultural awareness and knowledge play in enhancing effective intercultural communication and better execution of contextual performance. The research highlights the interdependence of the expatriates? multiple stakeholders (i.e. MNCs, HCNs, family members) in supporting the expatriates whilst on assignments. Finally, the findings reveal that the expatriate families do influence how the locals view the families and would be a great asset in initiating future communication between the expatriates and HCNs. The research contributes to the fields of intercultural adjustment and communication and also has key messages for policy makers.

Families 'at risk' and the family nurse partnership:the intrusion of risk into social exclusion policy

This article considers why the family nurse partnership (FNP) has been promoted as a means of tackling social exclusion in the UK. The FNP consists in a programme of visits by nurses to low-income first-time mothers, both while the mothers are pregnant and for the first two years following birth. The FNP is focused on both teaching parenthood and encouraging mothers back into education and/or into employment. Although the FNP marks a considerable discontinuity with previous approaches to family health, it is congruent with an emerging new approach to social exclusion. This new approach maintains that the most important task of social policy is to identify quickly the most 'at-risk' households, individuals and children so that interventions can be targeted more effectively at those 'at risk', either to themselves or to others. The article illustrates this new approach by analysing a succession of reports by the Social Exclusion Unit. It indicates that there is a considerable amount of ambiguity about the relationship between specific risk-factors and being 'at risk of social exclusion'. Nonetheless, this new approach helps to explain why British policy-makers may have chosen to promote the new FNP now. © 2009 Cambridge University Press.

The dark side of the internet:protecting yourself and your family from online criminals

In less than a decade, personal computers have become part of our daily lives. Many of us come into contact with computers every day, whether at work, school or home. As useful as the new technologies are, they also have a darker side. By making computers part of our daily lives, we run the risk of allowing thieves, swindlers, and all kinds of deviants directly into our homes. Armed with a personal computer, a modem and just a little knowledge, a thief can easily access confidential information, such as details of bank accounts and credit cards. This book helps people avoid harm at the hands of Internet criminals. It offers a tour of the more dangerous parts of the Internet, as the author explains who the predators are, their motivations, how they operate and how to protect against them. In less than a decade, personal computers have become part of our daily lives. Many of us come into contact with computers every day, whether at work, school or home. As useful as the new technologies are, they also have a darker side. By making computers part of our daily lives, we run the risk of allowing thieves, swindlers, and all kinds of deviants directly into our homes. Armed with a personal computer, a modem and just a little knowledge, a thief can easily access confidential information, such as details of bank accounts and credit cards. This book is intended to help people avoid harm at the hands of Internet criminals. It offers a tour of the more dangerous parts of the Internet, as the author explains who the predators are, their motivations, how they operate and how to protect against them. Behind the doors of our own homes, we assume we are safe from predators, con artists, and other criminals wishing us harm. But the proliferation of personal computers and the growth of the Internet have invited these unsavory types right into our family rooms. With a little psychological knowledge a con man can start to manipulate us in different ways. A terrorist can recruit new members and raise money over the Internet. Identity thieves can gather personal information and exploit it for criminal purposes. Spammers can wreak havoc on businesses and individuals. Here, an expert helps readers recognize the signs of a would-be criminal in their midst. Focusing on the perpetrators, the author provides information about how they operate, why they do it, what they hope to do, and how to protect yourself from becoming a victim.

Encoding order and developmental dyslexia:a family of skills predicting different orthographic components

We investigated order encoding in developmental dyslexia using a task that presented nonalphanumeric visual characters either simultaneously or sequentially—to tap spatial and temporal order encoding, respectively—and asked participants to reproduce their order. Dyslexic participants performed poorly in the sequential condition, but normally in the simultaneous condition, except for positions most susceptible to interference. These results are novel in demonstrating a selective difficulty with temporal order encoding in a dyslexic group. We also tested the associations between our order reconstruction tasks and: (a) lexical learning and phonological tasks; and (b) different reading and spelling tasks. Correlations were extensive when the whole group of participants was considered together. When dyslexics and controls were considered separately, different patterns of association emerged between orthographic tasks on the one side and tasks tapping order encoding, phonological processing, and written learning on the other. These results indicate that different skills support different aspects of orthographic processing and are impaired to different degrees in individuals with dyslexia. Therefore, developmental dyslexia is not caused by a single impairment, but by a family of deficits loosely related to difficulties with order. Understanding the contribution of these different deficits will be crucial to deepen our understanding of this disorder.