Characterizing the molecular phenotype of an Atp7a(T985I) conditional knock in mouse model for X-linked distal hereditary motor neuropathy (dHMNX)

ATP7A is a P-type ATPase essential for cellular copper (Cu) transport and homeostasis. Loss-of-function ATP7A mutations causing systemic Cu deficiency are associated with severe Menkes disease or its milder allelic variant, occipital horn syndrome. We previously identified two rare ATP7A missense mutations (P1386S and T994I) leading to a non-fatal form of motor neuron disorder, X-linked distal hereditary motor neuropathy (dHMNX), without overt signs of systemic Cu deficiency. Recent investigations using a tissue specific Atp7a knock out model have demonstrated that Cu plays an essential role in motor neuron maintenance and function, however the underlying pathogenic mechanisms of ATP7A mutations causing axonal degeneration remain unknown. We have generated an Atp7a conditional knock in mouse model of dHMNX expressing Atp7a(T985I), the orthologue of the human ATP7A(T994I) identified in dHMNX patients. Although a degenerative motor phenotype is not observed, the knock in Atp7a(T985I/Y) mice show altered Cu levels within the peripheral and central nervous systems, an increased diameter of the muscle fibres and altered myogenin and myostatin gene expression. Atp7a(T985I/Y) mice have reduced Atp7a protein levels and recapitulate the defective trafficking and altered post-translational regulatory mechanisms observed in the human ATP7A(T994I) patient fibroblasts. Our model provides a unique opportunity to characterise the molecular phenotype of dHMNX and the time course of cellular events leading to the process of axonal degeneration in this disease.

Evidence for a common role for the serine-type Plasmodium falciparum serine repeat antigen proteases : implications for vaccine and drug design

Serine repeat antigens (SERAs) are a family of secreted “cysteine-like” proteases of Plasmodium parasites. Several SERAs possess an atypical active-site serine residue in place of the canonical cysteine. The human malaria parasite Plasmodium falciparum possesses six “serine-type” (SERA1 to SERA5 and SERA9) and three “cysteine-type” (SERA6 to SERA8) SERAs. Here, we investigate the importance of the serine-type SERAs to blood-stage parasite development and examine the extent of functional redundancy among this group. We attempted to knock out the four P. falciparum serine-type SERA genes that have not been disrupted previously. SERA1, SERA4, and SERA9 knockout lines were generated, while only SERA5, the most strongly expressed member of the SERA family, remained refractory to genetic deletion. Interestingly, we discovered that while SERA4-null parasites completed the blood-stage cycle normally, they exhibited a twofold increase in the level of SERA5 mRNA. The inability to disrupt SERA5 and the apparent compensatory increase in SERA5 expression in response to the deletion of SERA4 provides evidence for an important blood-stage function for the serine-type SERAs and supports the notion of functional redundancy among this group. Such redundancy is consistent with our phylogenetic analysis, which reveals a monophyletic grouping of the serine-type SERAs across the genus Plasmodium and a predominance of postspeciation expansion. While SERA5 is to some extent further validated as a target for vaccine and drug development, our data suggest that the expression level of other serine-type SERAs is the only barrier to escape from anti-SERA5-specific interventions.

When our children come out : how to support gay, lesbian, bisexual and transgendered young people

Powerful and moving accounts from young people, parents and teachers on the important support that families, schools and communities can provide when children come out.

Working out intimacy: young people and friendship in an age of reflexivity

Drawing upon a longitudinal, interview-based study of Australian secondary school students, this article explores young people's friendship experiences and attitudes to intimacy and the interpersonal. The discussion develops in relation to the work of Anthony Giddens on detraditionalisation and reflexivity, and Nikolas Rose on modernity and the self. First, I argue that feminism and psychotherapeutic ways of constituting and knowing the self are reconfiguring the cultural meanings of intimacy. Second, I suggest that this reworking of intimacy has differential and uneven effects and has particular consequences for the production of gendered subjectivities. Third, I raise some critical questions about the extent to which either Giddens's or Rose's account can properly capture the gendered and situated experiences of intimacy. I offer examples in which gender is being rearticulated in new yet familiar ways and note some persistent tensions in desires for connection and community versus autonomy and freedom. Carol Gilligan's work on gender differences in orientations to autonomy and connection is briefly revisited. Overall, it is argued that we need to take more account of how class, location and schooling differences influence dispositions to friendship and the interpersonal, and this is elaborated through a discussion of the 'relationship orientations' of two white Australian young men.

Still plucking figures out of the air? Markarian and the affirmation of the instinctive synthesis

The High Court of Australia recently had the opportunity to reconsider the appropriate sentencing methodology to be adopted in the sentencing of offenders under Australian criminal law in the case of Markarian v The Queen. The High Court had to decide whether to continue with the instinctive synthesis approach to sentencing or a process that exposed in greater clarity the basis upon which sentencing was to occur. Ultimately, a majority of the Court favoured the continuance of the instinctive synthesis approach to sentencing in criminal cases. The article will consider the decision in Markarian and the implications that it will have for the sentencing of offenders in the States and Territories of Australia.

Bringing shared values out of the shadows

As part of its wider promotion of a world that is peaceful and tolerant, the United Nations declared 2005 the International Year of Sport and Physical Education. At the fore of the UN's proclamation was recognition of the important role sport and PE play in nurturing the health and harmony of society. Sport and PE, the UN declared, provide important nodes for social connection around which shared values and understandings can be formed. In the wake of the UN's endorsement of the role that sport and PE can play in fostering social and emotional development, it is more important that ever that we reflect on and refine our practices towards this end. This paper draws on two research narratives to illustrate how easily this potential can be undermined. Indeed, behind some of the wonderful opportunities for connection that exist through a participation in PE and sport exists a dark shadow of alienation and oppression. The challenge raised through this paper centres on the need for PE teachers and coaches to work deliberately and strategically towards the cultivation of inclusive, tolerant and responsible forms of participation, and not leave their development to chance.

Reconstituting the invisible out of structure and repetition: a walk through diary V3.2.

This presentation will discuss the production of an interactive personal diary constructed in digital form as an interactive CD-Rom: Diary V 3.2. This diary was conceived as a digital version of the family photo album of the artist's nuclear family, which unfortunately disintegrated during 4 years of the diary's making. As a result Diary V 3.2 became more a documentation of the mood and state of mind of the maker than the family it began to focus on. It acted more as a trace or a remnant of mood, an artifact of loss. This was communicated not so much through narrative but ideas of loss and erasure. Another layer to this work concerns the migration of images, technique from the old analogue technology to the new digital technology which can act as a replay of the migrant experience.

The square from inside out: Federation Square, Melbourne

This XXlst Annual Conference of SAHANZ offers a timely opportunity for celebrating and critically reflecting on Federation Square, Melbourne - a project that continually crosses the line between the purely experimental and the built form (A Benjamin, 2003) and offers an opportunity to identify and investigate the different, often competing, limits within the discipline of architecture. Here in this project, considered by the city of Melbourne to point to its future aspirations; and by the RAIA as demonstrating 'the strength of design and the leap into the unknown which is where good design always comes from' (I McDougall, 2003), different approaches to the possibilities of 'limit' as a contemporary concern can be fruitfully explored. Architectural masterpieces are daringly imaginative and each in their own way challenges architects, engineers, builders and technologists - those who are to realise the dream - and makes administrators, politicians and governments put their credibility on the line. So how does Federation Square contribute to contemporary architectural debate, specifically to Melbourne architecture? How has it dealt with thresholds? Where has It approached, crossed and/or exceeded boundaries? This paper will deal with design aesthetics in the realisation of the Lab architects 'vision' in the context of historical, urban and political realities. Analysis will provide insights into the limitations imposed upon this architectural project and the limitations it now, in turn, imposes on the city. Two aspects will be dealt with: understanding Lab's overall vision, and juxtaposing the vision with the reality of Federation Square. The author's interview with Don Bates, principal Lab architecture studio, forms the frame argument about Federation Square in this paper.

Casing out teaching and learning online: enhancing fidelity into the mainstream

In this paper we present the rationale and outcome of a University strategically funded project aimed at developing a broad range of cases illuminating good practices in the development and use of digital media and online technologies at Deakin University. The project is aimed at supporting the ongoing implementation of the University’s suite of e-learning technologies, Deakin Studies Online (DSO). It was seen as a significant strategic academic professional development initiative by the University in bringing together perspectives on effective teaching and learning in the context of various disciplines and professional fields of practice, with DSO possibilities for enhanced teaching/learning quality, efficiency, accessibility and satisfaction. The ‘case’ as a useful means of developing practice is outlined, along with the various project processes involving case selection, development, production and promotion. Finally, reflections on the outcomes of the project are considered. A number of positive though largely unintended consequences are identified

Reaching out to promote physical activity in Australia: a statewide randomized controlled trial of a stage-targeted intervention

Purpose. This study examined the broader use of a print-media intervention, which was previously shown to be effective at promoting physical activity to participants recruited from a regional Australian community, as a strategy suitable for a more diverse statewide population sample.
Methods. Participants were randomly selected adults who responded to a telephone interview conducted by the New South Wales Health Department and consented to Participate in a randomized controlled trial. Consenters were allocated to either intervention (n = 361) or control (n = 358) conditions. The intervention, a personalized letter plus stage-targeted booklets, was sent 1 week postbaseline. Data were collected via telephone interview at baseline and 2 and 8 months and were analyzed using repeated measures analysis of variance (ANOVA) and mean squared statistics.
Results. The groups were similar at baseline (mean age 43 +/- 3 years; 64 % women). Process evaluation showed high intervention recall (76 % at 2 months) and high follow-up response rates (> 85 % at 8 months) were achieved. Nonsignificant increases in physical activity were observed (Fl,719 = 2.18, p = .14).
Discussion. A single mailing of stage-targeted print materials was not effective in promoting increases in physical activity among participants selected from the statewide population. Future research could examine how the effectiveness of print media might be enhanced, possibly by using supplementary media, community-based prompts, or other incentives.

Getting out of deficit: pedagogies of reconnection

The fact that children growing up in poverty are likely to be in the lower ranges of achievement on standardised literacy tests is not a new phenomenon. Internationally there are a myriad of intervention and remedial programmes designed to address this problem with a range of effects. Frequently, sustainable reforms are curtailed by deficit views of families and children growing up in poverty. This article describes an ongoing research study entitled "Teachers Investigate Unequal Literacy Outcomes: Cross-Generational Perspectives", which made teacher researchers central in examining this long-standing dilemma. It outlines the research design and rationale, and analyses how two early career teachers worked their ways out of deficit analyses of two children they were most worried about. It argues that disrupting deficit discourses and re-designing new pedagogical repertoires to reconnect with children's lifeworlds is a long-term project that can best be achieved in reciprocal research relationships with teachers.

Jurisdictional differences in contracting out GBE audits : the impact on audit pricing

This paper examines audit costs for government business enterprises in various Australian jurisdictions, focusing on whether contracting private-sector suppliers induces competitive pricing and hence lower-priced audits. One jurisdiction (New South Wales) is shown to have low levels of contracting-out. It is argued that this lowers price competition and therefore, we predict, audit costs in NSW will be higher than elsewhere in Australia. An empirical comparison shows that, controlling for other factors, NSW is statistically significantly more expensive than other Australian jurisdictions. Alternative explanations relating to variation in audit quality, jurisdiction differences and relative cost are also discussed.

Drop out from behavioral management training programs for ADHD: a prospective study

To investigate dropout from parenting programs for disruptive behavior disorders, we followed 18 clients prospectively from the beginning of a manualized treatment program to three month follow-up. Using qualitative and quantitative methods, we then compared those who dropped out of the program with those who completed it. We found that in general, those participants who dropped out of the program were parents of children with more disturbed behavior, who perceived their children to be more difficult than others, and who experienced more subjective parenting stress. Those who dropped out were also not convinced that the strategies proposed in the program to help manage their children were useful. On the other hand, those who completed the program reported a determination to persevere with the strategies which they saw as assisting them to re-establish positive relationships with their adolescent children. The findings are discussed in the context of how manualized programs might be modified to increase retention.

Understanding women's breast screening behaviour: a study carried out in South East London, with women aged 50-64 years

Objective To understand low uptake of breast cancer screening through exploring the personal reasoning underlying women's attendance or non-attendance, and identifying differences between those who attend and those who decline.

Design Cross-sectional survey.

Setting Community and home environments of women eligible for breast screening aged 50—64 years, living in South East London. Method Structured, self-completed or assisted-completion questionnaires.

Results The decision to attend or decline screening is rational and personally justifiable, engaging factors linked to emotions and attitude. Attitudes about breast screening and perceived personal importance of breast screening are the strongest predictors of attendance and non-attendance. There are differences between ethnic groups in perceptions of breast screening. Regular attendance at screening is associated with ethnicity, although consistent avoidance of mammography is not. Inconvenience is an important factor in missing appointments, and tends to be prolonged rather than specific to the time or day of the pre-booked invitation. GP and health worker advice are good persuaders towards attendance. Pain and anxiety during mammography are notable dissuaders against re-attending.

Conclusion Appropriate service provision requires consideration of local factors, as well as the medical needs of the population eligible for breast screening. Lay perceptions of potential personal costs of attending or not attending breast screening are important for guiding health promotion. Information providers should consider the language needs of a culturally and educationally mixed community. Health care professionals are well placed to encourage uptake of breast screening through disseminating information that promotes attendance, both within and outside the breast screening service.

Reaching out to employees using B2E : the trials and tribulations

This paper is an extension of e-business models discussing business to employee (B2E) e- model. It describes the model, the technologies that support the model and benefits to the organisation identified from literature. To further understand the B2E issues a case study in a large organisation that manages its employees with the B2E model is included. Challenges, success factors and an analysis of the case study addressing a wide range of organisational benefits are included in the paper.