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.

Secretin family (Class B) G protein-coupled receptors - from molecular to clinical perspectives

Family B G protein-coupled receptors represent an important but under-researched group of receptors. This edition of the British Journal of Pharmacology considers the roles and pharmacology of a number of these receptors. Whilst common themes emerge, it is clear that more work is needed to understand the details of each receptor in order to properly exploit them therapeutically.

Calcitonin and calcitonin receptor-like receptors:common themes with family B GPCRs?

The calcitonin receptor (CTR) and calcitonin receptor-like receptor (CLR) are two of the 15 human family B (or Secretin-like) GPCRs. CTR and CLR are of considerable biological interest as their pharmacology is moulded by interactions with receptor activity-modifying proteins. They also have therapeutic relevance for many conditions, such as osteoporosis, diabetes, obesity, lymphatic insufficiency, migraine and cardiovascular disease. In light of recent advances in understanding ligand docking and receptor activation in both the family as a whole and in CLR and CTR specifically, this review reflects how applicable general family B GPCR themes are to these two idiosyncratic receptors. We review the main functional domains of the receptors; the N-terminal extracellular domain, the juxtamembrane domain and ligand interface, the transmembrane domain and the intracellular C-terminal domain. Structural and functional findings from the CLR and CTR along with other family B GPCRs are critically appraised to gain insight into how these domains may function. The ability for CTR and CLR to interact with receptor activity-modifying proteins adds another level of sophistication to these receptor systems but means careful consideration is needed when trying to apply generic GPCR principles. This review encapsulates current thinking in the realm of family B GPCR research by highlighting both conflicting and recurring themes and how such findings relate to two unusual but important receptors, CTR and CLR.

Contract law concentrate

Contract Law Concentrate is a high quality revision guide which covers the main topics found on undergraduate courses. The clear, succinct coverage of key legal points within a specific topic area, including key cases, enables students to quickly grasp the fundamental principles of Contract law. Written by Jill Poole, an experienced teacher and examiner and author of Textbook on Contract Law and Casebook on Contract law. The book focuses on the needs of students to pass their exams with a number of pedagogical features which help with the preparation for exams and suggest ways to improve marks. Endorsed by students and lecturers for level of coverage, accuracy and exam advice. Online Resource Centre Interactive flashcards Glossary Exam and revision guidance.

'Family' ownership, tunnelling and earnings management:a review of the literature

In this review paper, we bring together a number of aspects of family firms that are ubiquitous in a number of institutional contexts, often as part of larger business groups. We pay particular attention to the mechanisms by which families retain control over firms, and the incentives of the families in control to expropriate other stakeholders by way of tunnelling. We examine the role of earnings management in facilitating tunnelling, and evidence about the incidence of earnings management in family firms. Our review suggests that while the literature on these aspects of family control is rich, the contexts in which the empirical exercises are undertaken are relatively few, and hence there is considerable opportunity to expand it to other contexts, in particular in the form of cross-country comparisons of the relative impact of agency conflicts and institutions on these issues.

Reputation and performance in large law firms

Reputation is a signalling device that serves as a proxy for the quality of a firm’s products, strategies and employees relative to its competitors, when communicating with clients and other stakeholders. It is especially important for professional service firms because of the complex and intangible nature of their service and because of the advantages it confers in the market for high-quality professional staff. This paper extends and refines existing research on reputation which shows positive returns to reputation for professional service firms. We use different rankings of the top 50 law firms in the UK to measure reputation and examine their relationship with financial performance as expressed in firm revenue and profits. We find positive but diminishing returns to reputation even within this group and we find a stronger relationship between reputation and profits than fee income. We conclude that reputation may be an important source of competitive advantage for leading firms but it seems to offer little leverage for others. If these results are generalizable across other professional sectors this raises the question of how the majority of firms can differentiate themselves.

Managing the human resource in Indian SMEs:The role of indigenous realities

This paper discusses how issues of people management are addressed in Indian small and medium enterprises (SMEs). It also highlights the indigenous approaches to human resource management (HRM) that have surfaced in the Indian SME context. The research formulation has been built on the mapping of people-management practices in two SME case studies, one of which is also a family-based organization. The analysis shows that indigenous realities in HRM in Indian SMEs relate mainly to the provision of financial, emotional and social support to the workforce; employee involvement (EI) practices; recruitment; skill development; managing employee relations; and managing vis-à-vis labor law framework. The paper argues that in the sphere of people management in SMEs, the willingness to innovate and formalize the HR systems is constrained by a kind of bounded rationality, i.e., the owners of SMEs mostly believe that they are already doing what is humanly possible in this regard. The analysis has an important message for concerned practitioners—in order to realize their full potential and to progress towards fulfilling their vision; SMEs eventually have to intertwine indigenization and formalization for their people management approaches.

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.

Impact of peanut allergy on quality of life, stress and anxiety in the family

Background: Peanut allergy (PA) is known to impact on quality of life (QoL) of the sufferer, but little research has focused on all family members. We therefore sought to establish the impact of PA on QoL and reported anxiety of children with clinically confirmed PA, their parents and older siblings. Methods: Forty-six families, who had a child with PA, completed QoL (PedsQLTM or WHOQOL-BREF), anxiety (SCAS or STAI) and perceived stress (PSS) scales. PA children completed a PA specific QoL questionnaire (Pediatr Allergy Immunol 2003;14:378). Parents and sibling also completed QoL proxy questionnaires for the PA child (PedsQLTM, Pediatr Allergy Immunol 2003;14:378). Results: Mothers rated their own psychological (P < 0.01) and physical (P < 0.05) QoL significantly worse than fathers rated theirs, and had higher scores than fathers for anxiety (P < 0.05) and stress (P < 0.001). Children with PA had significantly poorer physical health-related QoL (P < 0.05), QoL within school (P < 0.01) and general QoL (P < 0.05) than their siblings did, and greater separation anxiety (P < 0.05). The majority of differences were between girls with PA and female siblings. Mothers felt that there was a greater impact on QoL for their PA child, compared with that reported by siblings, fathers or the PA children themselves (P < 0.01). Conclusions: Mothers report that they have significantly poorer QoL and suffer more anxiety and stress than fathers do; this inter-parental difference may be an important feature of family stress caused by PA. Siblings have a similar view of how QoL affects the PA child as the PA child does, while mothers may possibly overestimate this impact.

Unraveling the role of forgiveness in family relationships

Testing the idea that the process of forgiveness is intrinsically different across diverse relationships, this study examined the role of forgiveness in different family relationships. In 2 laboratory sessions 1 year apart, 114 families (each including 2 parents and 1 child) completed a new measure of family forgiveness and many individual-level, relationship-level, and family-level variables that have been previously linked with forgiveness. After validating the measure of family forgiveness in cross-sectional analyses, investigators performed longitudinal analyses to examine the role of forgiveness in each family relationship over the 1-year interval. Results indicated many important positive consequences of forgiveness on individual traits, aspects of each family relationship, and general family environment. However, there were also important asymmetries in associates of forgiveness across parent-child and parent-parent relationships, demonstrating the relationship-bound nature of forgiveness.

'Only in the leap from the lion's head will he prove his worth':natural law and international relations

This article argues the benefits of including a theological interpretation of natural law morality within the normative discourses of international politics. It challenges the assumption of a Grotian secular natural law arguing that practical reason, in a Thomist interpretation, is better suited to the demands of international political theory. It engages with themes of agency, practical reason, and community in order to enhance the content of the post-territorial community evidenced in ethical cosmopolitan debates. Likewise, it envisions a simultaneously enhancing a rapprochement among cosmopolitan and communitarian discourses of international politics facilitated through an institutional design guided by the morality of natural law.