Role of the N-terminal region in G protein-coupled receptor functions : negative modulation revealed by 5-HT2B receptor polymorphisms

The putative role of the N-terminal region of rhodopsin-like 7 transmembrane biogenic amine receptors in agonist-induced signaling has not yet been clarified despite recent advances in 7 transmembrane receptor structural biology. Given the existence of N-terminal nonsynonymous polymorphisms (R6G;E42G) within the HTR2B gene in a drug-abusing population, we assessed whether these polymorphisms affect 5-hydroxytryptamine 2B (5-HT2B) receptor in vitro pharmacologic and coupling properties in transfected COS-7 cells. Modification of the 5-HT2B receptor N terminus by the R6G;E42G polymorphisms increases such agonist signaling pathways as inositol phosphate accumulation as assessed by either classic or operational models. The N-terminal R6G;E42G mutations of the 5-HT2B receptor also increase cell proliferation and slow its desensitization kinetics compared with the wild-type receptor, further supporting a role for the N terminus in transduction efficacy. Furthermore, by coexpressing a tethered wild-type 5-HT2B receptor N terminus with a 5-HT2B receptor bearing a N-terminal deletion, we were able to restore original coupling. This reversion to normal activity of a truncated 5-HT2B receptor by coexpression of the membrane-tethered wild-type 5-HT2B receptor N terminus was not observed using a membrane-tethered 5-HT2B receptor R6G;E42G N terminus. These data suggest that the N terminus exerts a negative control over basal as well as agonist-stimulated receptor activity that is lost in the R6G;E42G mutant. Our findings reveal a new and unanticipated role of the 5-HT2B receptor N terminus as a negative modulator, affecting both constitutive and agonist-stimulated activity. Moreover, our data caution against excluding the N terminus and extracellular loops in structural studies of this 7 transmembrane receptor family

Do children and adolescents with Down syndrome have deficits in motivation?

There appears to be a general acceptance that individuals with intellectual disability (ID) have deficits in motivation. Yet research with infants and young children has usually identified few differences in motivation for children with ID compared with those of the same mental age who are developing typically. Studies of motivation in children with ID in the middle years of childhood or adolescence are almost non-existent. However, research conducted more than 30 years ago (Harter & Zigler, 1974) continues to be cited as evidence of motivational deficits in those with ID even though the life experiences of people with ID have changed dramatically since that time.

Powering a curriculum for all : a critical ethnographic study of inclusive education

This project makes a contribution to knowledge about the successful leadership practices that enhance education for young people with a disability in a Queensland Secondary School. The project used a critical ethnographic approach with a variety of data collection methods and analysis. For example, the use of work diaries, semi-structured interviews, document analysis and observation. These leadership practices were found to be relevant to the development of inclusive schools for all learners.The most powerful leadership practices found were those used by the leader to challenge, interupt and replace exsisting discourse and processes that led to exclusion of students with a disability.

A critical success factors model for enterprise resource planning implementation

Enterprise Resource Planning (ERP) systems are integrated enterprise-wide standard information systems that automate all aspects of an organisations’ business processes. The ERP philosophy is that business systems incorporating sales, marketing, manufacturing, distribution, personnel and finance modules can be supported by a single integrated system with all of the company’s data captured in a central database. The ERP packages of vendors such as SAP, Baan, J.D. Edwards and Intentia represent more than a common systems platform for a business. They prescribe information blueprints of how organisation’s business processes should operate. In this paper, the scale and strategic importance of ERP systems is identified and the problem of ERP implementation is defined. Five company examples are analysed using a Critical Success Factors (CSFs) theoretical framework. The paper offers a framework for managers which provides the basis for developing an ERP implementation strategy. The case analysis identifies different approaches to ERP implementation, highlights the critical role of legacy systems in influencing the implementation process, and identifies the importance of business process change and software configuration in addition to factors already cited in the literature such as top management support and communication. The implications of the results and future research opportunities are outlined.

Knowledge Transfer in Transnational Programmes : Opportunities and Challenges for the Pacific Region

The globalised world: The current higher education community The last decade has seen rapid changes in the landscape of higher education (HE) throughout the world, largely as a product of globalisation. A major effect has been to propel the interconnectedness between nations and people across the globe (Scholte, 2005). The use of information and communication technology (ICT) has diminished the distance between countries. The world’s economies are becoming more integrated and interrelated through neoliberal economic policies, free trade agreements and open access of goods and services beyond national borders, policies promulgated by organisations such as the World Trade Organization and The World Bank (Marginson & Ordorika, 2011; Mok, 2011). As a consequence, universities are operating at global, national and local levels simultaneously. In the Pacific region, new universities are emerging. For example, Fiji now has one regional and two national universities; Samoa has a national university and Solomon Islands has an institute of higher education. These new players add to regional competition as they open opportunities for global partnerships and transnational programmes. Thus, participating at these multiple levels is inevitable, and no university is immune to these changes (Marginson, Kaur & Sawir, 2011a). Universities are now part of the global HE community that cannot be confined within a nation’s borders. Transitional HE programmes are perhaps one of the most evident demonstrations of the interconnectedness of universities across countries in this global era.

Sing fox to me : an investigation into the "use" of Down Syndrome in both the Down Syndrome and Gothic novel

This project investigates the current borders around and within, what I have in this exegesis termed, "the Down Syndrome novel", using a close reading analysis of literary texts containing characters with Down syndrome and contextualised by theoretical works drawn from both disability and literary theory. This practice-led thesis introduces and discusses select fictional characters with Down syndrome from numerous genres, revealing them as highly contained, or "boundaried", spoken for, and generally used for narrative conflict rather than included as individuals with agency and a legitimate, autonomous voice and narrative point of view. In reframing the Australian landscape as "disabled" this exegesis illustrates that the Australian Gothic novel can shift, and sometimes even remove, the boundary around characters with intellectual disabilities, allowing a space where the stories of characters with Down syndrome can emerge.

Examining the critical interplay of knowledge acquisition and integration capabilities in service innovation-based competitive advantage in project oriented service firms

While past knowledge-based approaches to service innovation have emphasized the role of knowledge integration in the delivery of customer-focused solutions, these approaches do not adequately address the complexities inherent in knowledge acquisition and integration in project-oriented firms. Adopting a dynamic capability framework and building on knowledge-based approaches to innovation, the current study examines how the interplay of learning capabilities and knowledge integration capability impacts service innovation and sustained competitive advantage. This two-stage multi-sample study finds that entrepreneurial project-oriented service firms in their quest for competitive advantage through greater innovation invest in knowledge acquisition and integration capabilities. Implications for theory and practice are discussed and directions for future research provided.

New reaction paths for metal diborides at low temperature and pressure

Attention has recently focussed on MgB2 superconductors (Tc~39K) which can be formed into wires with high material density and viable critical current densities (Jc)1. However, broader utilisation of this diboride and many others is likely to occur when facile synthesis for bulk applications is developed. To date, common synthesis methods include high temperature sintering of mixed elemental powders2, combustion synthesis3, mechano-chemical mixing with high temperature sintering4 and high pressure (~GPa region) with high temperature. In this work, we report on a lower temperature, moderate (<4MPa) pressure method to synthesise metal diborides.

Co-occurring anger in young people with Asperger's syndrome

Objectives: The co-occurrence of anger in young people with Asperger's syndrome (AS) has received little attention despite aggression, agitation, and tantrums frequently being identified as issues of concern in this population. The present study investigated the occurrence of anger in young people with AS and explores its relationship with anxiety and depression. Method: Sixty-two young people (12-23 years old) diagnosed with AS were assessed using the Beck Anger Inventory for Youth, Spence Children's Anxiety Scale, and Reynolds Adolescent Depression Scale. Results: Among young people with AS who participated in this study, 41% of participants reported clinically significant levels of anger (17%), anxiety (25.8%) and/or depression (11.5%). Anger, anxiety, and depression were positively correlated with each other. Depression, however, was the only significant predictor of anger. Conclusion: Anger is commonly experienced by young people with AS and is correlated with anxiety and depression. These findings suggest that the emotional and behavioral presentation of anger could serve as a cue for further assessment, and facilitate earlier identification and intervention for anger, as well as other mental health problems.

Marx as a Critical Discourse Analyst : The Genesis of a Critical Method and its Relevance to the Critique of Global Capital (with Phil Graham)

In this paper we identify elements in Marx’s economic and political writings that are relevant to contemporary critical discourse analysis (CDA). We argue that Marx can be seen to be engaging in a form of discourse analysis. We identify the elements in Marx’s historical materialist method that support such a perspective, and exemplify these in longitudinal comparison of Marx’s texts.