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.

Brain drain:inclination to stay abroad after studies

'Brain drain' is a phenomenon in which people of a high level of skills, qualifications, and competence, leave their countries and emigrate. One major case of the brain drain happens when students from developing countries studying in the developed countries decide not to return home after their studies. We examined the reasons for international students' inclination to stay in their host countries in a sample of 949 management students who came to study in the United Kingdom and the United States. The results support a three-fold model of factors that influenced this inclination. Students' perceptions of ethnic differences and labor markets, their adjustment process to the host country, and their family ties in host and home countries all affect their intention to stay. © 2006 Elsevier Inc. All rights reserved.

Family relocation: worse or just different?

Organisational relocation directly affects the family. It is thus often assumed that relocation is more difficult for individuals with families; however, few studies actually examine this premise. This paper investigates whether family status plays a role in relocation by comparing single individuals to married individuals. The paper uses qualitative and quantitative indicators to uncover subtle nuances between the groups and, on the basis of these, develops proposition for future research to test. Quantitative indicators highlight several important differences: Individuals with families report a greater number of moving tasks and difficulties; family relocation is viewed as more complex because of the impact of non-relocation related factors; and employees with families experience more negative and positive consequences of relocation. Qualitative techniques help to uncover subtle differences between groups and suggest that although relocation for families is different from individual relocation, it is not necessarily worse. RP0721.

Vapour-liquid equilibrium studies at atmospheric to moderate pressures

A study of vapour-liquid equilibria is presented together with current developments. The theory of vapour-liquid equilibria is discussed. Both experimental and prediction methods for obtaining vapour-liquid equilibria data are critically reviewed. The development of a new family of equilibrium stills to measure experimental VLE data from sub-atmosphere to 35 bar pressure is described. Existing experimental techniques are reviewed, to highlight the needs for these new apparati and their major attributes. Details are provided of how apparatus may be further improved and how computer control may be implemented. To provide a rigorous test of the apparatus the stills have been commissioned using acetic acid-water mixture at one atmosphere pressure. A Barker-type consistency test computer program, which allows for association in both phases has been applied to the data generated and clearly shows that the stills produce data of a very high quality. Two high quality data sets, for the mixture acetone-chloroform, have been generated at one atmosphere and 64.3oC. These data are used to investigate the ability of the new novel technique, based on molecular parameters, to predict VLE data for highly polar mixtures. Eight, vapour-liquid equilibrium data sets have been produced for the cyclohexane-ethanol mixture at one atmosphere, 2, 4, 6, 8 and 11 bar, 90.9oC and 132.8oC. These data sets have been tested for thermodynamic consistency using a Barker-type fitting package and shown to be of high quality. The data have been used to investigate the dependence of UNIQUAC parameters with temperature. The data have in addition been used to compare directly the performance of the predictive methods - Original UNIFAC, a modified version of UNIFAC, and the new novel technique, based on molecular parameters developed from generalised London's potential (GLP) theory.

The role of the extracellular loops of the CGRP receptor, a family B GPCR

The CGRP (calcitonin gene-related peptide) receptor is a family B GPCR (G-protein-coupled receptor). It consists of a GPCR, CLR (calcitonin receptor-like receptor) and an accessory protein, RAMP1 (receptor activity-modifying protein 1). RAMP1 is needed for CGRP binding and also cell-surface expression of CLR. There have been few systematic studies of the ECLs (extracellular loops) of family B GPCRs. However, they are likely to be especially important for the interaction of the N-termini of the peptide agonists that are the natural agonists for these receptors. We have carried out alanine scans on all three ECLs of CLR, as well as their associated juxtamembrane regions. Residues within all three loops influence CGRP binding and receptor activation. Mutation of Ala203 and Ala206 on ECL1 to leucine increased the affinity of CGRP. Residues at the top of TM (transmembrane) helices 2 and 3 influenced CGRP binding and receptor activation. L351A and E357A in TM6/ECL3 reduced receptor expression and may be needed for CLR association with RAMP1. ECL2 seems especially important for CLR function; of the 16 residues so far examined in this loop, eight residues reduce the potency of CGRP at stimulating cAMP production when mutated to alanine.

Teamwork for product innovation in Taiwanese family firms:an indigenous psychology perspective: An indigenous psychology

As the existing team literature mostly excludes context and culture, little is known about how these elements affect real-life team working (Engestrom, 2008; Salas & Wildman, 2009), and how teams work in non-Western settings, such as in Chinese firms (Phan, Zhou, & Abrahamson, 2010).This research addresses this issue by investigating how new product design (NPD) teams use team working to carry out product innovation in the context of Chinese family businesses (CFBs) via an indigenous psychology perspective. Unlike mainstream teamwork literature which mostly employs an etic design, an indigenous psychology perspective adopts an emic approach which places emphasis on understanding real-life phenomena in context through a cultural-insider perspective (Kim, 2000). Compatible with this theoretical position, a multiple qualitative case study approach was used as the research methodology. Three qualitative case studies were carried out in three longstanding family-run manufacturing firms in Taiwan, where family firms have been the pillars of high economic growth in the past five decades (W.-w. Chu, 2009). Two salient findings were established across the three case studies. First, the team processes identified across the three family firms are very similar with the exception of owners’ involvement and on-the-job training. All three family firms’ NPD teams are managed in a highly hierarchical manner, with considerable emphasis placed on hierarchical ranking, cost-effectiveness, efficiency, practicability, and interpersonal harmony. Second, new products developed by CFBNPD teams are mostly incremental innovation or copycat innovation, while radical or original products are rare. In many ways, CFBNPD teams may not be the ideal incubators for innovation. This is because several aspects of their unique context can cast constraints on how they work and innovate, and thus limit the ratio of radical innovation. A multi-level review into the facilitators and inhibitors of creativity or innovation in CFBNPD teams is provided. The theoretical and practical implications of the findings and the limitations of the study are also addressed.

Involving the family in higher education:do they really matter?

In an ever-changing higher education (HE) environment, institutions are seeing the involvement of parents in students' education increasing. This may partly be due to tuition fees and the introduction of deferred variable tuition fees ("top-up fees") from 2006, and also because of the increased number of students choosing to remain in the family home for the duration of their studies. Many students see their families as the most important source of motivation and advice right through from school age to when they make decisions about HE. In the light of this increase in involvement, institutions need to provide information about, and access to, university to ensure that families are fully prepared and able to support their children throughout the university experience. In recognition of the vital role parents play, the Involving the Family project focuses on parents or key family members from groups currently under-represented in HE in order to increase their awareness and understanding of HE. This article evaluates research undertaken to investigate the views, perceptions and key concerns held by minority ethnic parents with regards to their children and participation in HE. The article then details how these results were utilised in the development of the Involving the Family project.

Disabling a family? Emotional dilemmas experienced in becoming a parent of a child with learning disabilities

Becoming the parent of a child diagnosed with learning disabilities can have a dramatic impact. Chrissie Rogers, the author of this article, is both a lecturer in education studies at Keele University and the mother of a daughter who has learning disabilities. She argues here that the pressures on mothers to produce ‘perfect’ babies and to meet all their needs are immense. These pressures arise from both internalised norms and societal expectations and, in the face of these pressures, parents may feel shock, loss and disappointment. These feelings may lead, in turn, to denial, anxiety and conflict affecting both the parents and the professionals involved with the family. Drawing on a series of in-depth interviews and personal narratives, Chrissie Rogers makes a powerful case for the importance of support, whether that support is formal or informal. She suggests that, without the right levels of support and understanding, having a child with a diagnosis of learning disability can disable the whole family.

The application of counter immunoelectrophoresis (CIE) in ocular protein studies. Part II:kinin activity in the lens wearing eye

The kinin family are a group of bioactive peptides that are closely involved in the modulation of vascular inflammation and local injury. We have demonstrated here, for the first time, a link between kinin activity and contact lens wear. Protein extracts from daily and extended wear etafilcon A, Group IV, Acuvue lenses (Vistakon), were analysed by counter immunoelectrophoresis. In this way, kinin activity associated with contact lens wear was detected. High molecular weight kininogen was used as the marker protein. In contrast, no kinin activity was detected in the non-lens wearing normal eye. © 2002 British Contact Lens Association. Published by Elsevier Science Ltd. All rights reserved.

Medical students' personal experience of high-stakes failure:case studies using interpretative phenomenological analysis

Abstract (provisional): Background Failing a high-stakes assessment at medical school is a major event for those who go through the experience. Students who fail at medical school may be more likely to struggle in professional practice, therefore helping individuals overcome problems and respond appropriately is important. There is little understanding about what factors influence how individuals experience failure or make sense of the failing experience in remediation. The aim of this study was to investigate the complexity surrounding the failure experience from the student’s perspective using interpretative phenomenological analysis (IPA). Methods The accounts of 3 medical students who had failed final re-sit exams, were subjected to in-depth analysis using IPA methodology. IPA was used to analyse each transcript case-by-case allowing the researcher to make sense of the participant’s subjective world. The analysis process allowed the complexity surrounding the failure to be highlighted, alongside a narrative describing how students made sense of the experience. Results The circumstances surrounding students as they approached assessment and experienced failure at finals were a complex interaction between academic problems, personal problems (specifically finance and relationships), strained relationships with friends, family or faculty, and various mental health problems. Each student experienced multi-dimensional issues, each with their own individual combination of problems, but experienced remediation as a one-dimensional intervention with focus only on improving performance in written exams. What these students needed to be included was help with clinical skills, plus social and emotional support. Fear of termination of the their course was a barrier to open communication with staff. Conclusions These students’ experience of failure was complex. The experience of remediation is influenced by the way in which students make sense of failing. Generic remediation programmes may fail to meet the needs of students for whom personal, social and mental health issues are a part of the picture.

Help in finding the right balance:leadership, work-family balance and employee outcomes

Although much research has examined employees’ experience of the work-family interface, its conceptualization has been rather problematic, ranging from work and family as mutually constraining through to mutually enriching and, more recently, to work-family balance (WFB). Building on Greenhaus and Allen’s (2011) conceptualization of WFB as comprising satisfaction and effectiveness components, I proposed and tested a model of he antecedents and outcomes of WFB. Based on work-family border theory, I hypothesised that family-supportive supervisor behaviours (FSSB) facilitate WFB and hat the relationship is stronger when the organisation also offers formal support (availability of family-friendly practices (FFPs); enhancement effect). Furthermore, I integrated the leadership and work-family interface literatures by proposing authentic eadership as an antecedent of FSSB. Based on role accumulation theories, I proposed life satisfaction and health as outcomes of WFB satisfaction and WFB effectiveness and job performance as an outcome of only WFB effectiveness. I tested my hypotheses with individual-level data in Study 1 (two waves of data; employees from Germany and the UK) and nested data (individuals nested in teams; two waves of data; employee and supervisor ratings; Germany and the UK) in Study 2. The obtained findings largely supported the hypothesized model and showed that both authentic leadership (Study 1) and team authentic leadership (Study 2) predicted FSSB which, in turn, increased WFB satisfaction and WFB effectiveness. Contrary to my prediction, both studies revealed that FSSB and (team) availability of FFPs compensated for each other, only impacting WFB satisfaction/effectiveness if the other form of family support was not available. Furthermore, both components were positively related to life satisfaction and health, while WFB effectiveness was only related to self-rated performance (Study 1) and not supervisor-rated performance (Study 2). Lastly, the serial moderated mediation model hat tested the conditional indirect effect of (team) authentic leadership on the outcomes received mixed support.