The contribution of different androgen receptor domains to receptor dimerization and signaling

The androgen receptor (AR) is a ligand-activated transcription factor of the nuclear receptor superfamily that plays a critical role in male physiology and pathology. Activated by binding of the native androgens testosterone and 5-dihydrotestosterone, the AR regulates transcription of genes involved in the development and maintenance of male phenotype and male reproductive function as well as other tissues such as bone and muscle. Deregulation of AR signaling can cause a diverse range of clinical conditions, including the X-linked androgen insensitivity syndrome, a form of motor neuron disease known as Kennedy’s disease, and male infertility. In addition, there is now compelling evidence that the AR is involved in all stages of prostate tumorigenesis including initiation, progression, and treatment resistance. To better understand the role of AR signaling in the pathogenesis of these conditions, it is important to have a comprehensive understanding of the key determinants of AR structure and function. Binding of androgens to the AR induces receptor dimerization, facilitating DNA binding and the recruitment of cofactors and transcriptional machinery to regulate expression of target genes. Various models of dimerization have been described for the AR, the most well characterized interaction being DNA-binding domain- mediated dimerization, which is essential for the AR to bind DNA and regulate transcription. Additional AR interactions with potential to contribute to receptor dimerization include the intermolecular interaction between the AR amino terminal domain and ligand-binding domain known as the N-terminal/C-terminal interaction, and ligand-binding domain dimerization. In this review, we discuss each form of dimerization utilized by the AR to achieve transcriptional competence and highlight that dimerization through multiple domains is necessary for optimal AR signaling.

Joint consumer submission to the review of the code of banking practice

This submission has been prepared on behalf of Australian consumer advocates by Nicola Howell, Faculty of Law, Queensland University of Technology (‘the researcher’), under a consultancy arrangement with the Australian Securities and Investments Commission (ASIC). The researcher has been engaged by ASIC to consult with consumer advocates across Australia in order to prepare a detailed consumer submission to the Review of the Code of Banking Practice and the Review Issues Paper.

Oxygen consumption and muscle activation patterns during constant load exercise

The collective purpose of these two studies was to determine a link between the V02 slow component and the muscle activation patterns that occur during cycling. Six, male subjects performed an incremental cycle ergometer exercise test to determine asub-TvENT (i.e. 80% of TvENT) and supra-TvENT (TvENT + 0.75*(V02 max - TvENT) work load. These two constant work loads were subsequently performed on either three or four occasions for 8 mins each, with V02 captured on a breath-by-breath basis for every test, and EMO of eight major leg muscles collected on one occasion. EMG was collected for the first 10 s of every 30 s period, except for the very first 10 s period. The V02 data was interpolated, time aligned, averaged and smoothed for both intensities. Three models were then fitted to the V02 data to determine the kinetics responses. One of these models was mono-exponential, while the other two were biexponential. A second time delay parameter was the only difference between the two bi-exponential models. An F-test was used to determine significance between the biexponential models using the residual sum of squares term for each model. EMO was integrated to obtain one value for each 10 s period, per muscle. The EMG data was analysed by a two-way repeated measures ANOV A. A correlation was also used to determine significance between V02 and IEMG. The V02 data during the sub-TvENT intensity was best described by a mono-exponential response. In contrast, during supra-TvENT exercise the two bi-exponential models best described the V02 data. The resultant F-test revealed no significant difference between the two models and therefore demonstrated that the slow component was not delayed relative to the onset of the primary component. Furthermore, only two parameters were deemed to be significantly different based upon the two models. This is in contrast to other findings. The EMG data, for most muscles, appeared to follow the same pattern as V02 during both intensities of exercise. On most occasions, the correlation coefficient demonstrated significance. Although some muscles demonstrated the same relative increase in IEMO based upon increases in intensity and duration, it cannot be assumed that these muscles increase their contribution to V02 in a similar fashion. Larger muscles with a higher percentage of type II muscle fibres would have a larger increase in V02 over the same increase in intensity.

The differential impact of holocaust trauma across three generations

In the current thesis, the reasons for the differential impact of Holocaust trauma on Holocaust survivors, and the differential intergenerational transmission of this trauma to survivors’ children and grandchildren were explored. A model specifically related to Holocaust trauma and its transmission was developed based on trauma, family systems and attachment theories as well as theoretical and anecdotal conjecture in the Holocaust literature. The Model of the Differential Impact of Holocaust Trauma across Three Generations was tested firstly by extensive meta-analyses of the literature pertaining to the psychological health of Holocaust survivors and their descendants and secondly via analysis of empirical study data. The meta-analyses reported in this thesis represent the first conducted with research pertaining to Holocaust survivors and grandchildren of Holocaust survivors. The meta-analysis of research conducted with children of survivors is the first to include both published and unpublished research. Meta-analytic techniques such as meta-regression and sub-set meta-analyses provided new information regarding the influence of a number of unmeasured demographic variables on the psychological health of Holocaust survivors and descendants. Based on the results of the meta-analyses it was concluded that Holocaust survivors and their children and grandchildren suffer from a statistically significantly higher level or greater severity of psychological symptoms than the general population. However it was also concluded that there is statistically significant variation in psychological health within the Holocaust survivor and descendant populations. Demographic variables which may explain a substantial amount of this variation have been largely under-assessed in the literature and so an empirical study was needed to clarify the role of demographics in determining survivor and descendant mental health. A total of 124 participants took part in the empirical study conducted for this thesis with 27 Holocaust survivors, 69 children of survivors and 28 grandchildren of survivors. A worldwide recruitment process was used to obtain these participants. Among the demographic variables assessed in the empirical study, aspects of the survivors’ Holocaust trauma (namely the exact nature of their Holocaust experiences, the extent of family bereavement and their country of origin) were found to be particularly potent predictors of not only their own psychological health but continue to be strongly influential in determining the psychological health of their descendants. Further highlighting the continuing influence of the Holocaust was the finding that number of Holocaust affected ancestors was the strongest demographic predictor of grandchild of survivor psychological health. Apart from demographic variables, the current thesis considered family environment dimensions which have been hypothesised to play a role in the transmission of the traumatic impact of the Holocaust from survivors to their descendants. Within the empirical study, parent-child attachment was found to be a key determinant in the transmission of Holocaust trauma from survivors to their children and insecure parent-child attachment continues to reverberate through the generations. In addition, survivors’ communication about the Holocaust and their Holocaust experiences to their children was found to be more influential than general communication within the family. Ten case studies (derived from the empirical study data set) are also provided; five Holocaust survivors, three children of survivors and two grandchildren of survivors. These cases add further to the picture of heterogeneity of the survivor and descendant populations in both experiences and adaptations. It is concluded that the legacy of the Holocaust continues to leave its mark on both its direct survivors and their descendants. Even two generations removed, the direct and indirect effects of the Holocaust have yet to be completely nullified. Research with Holocaust survivor families serves to highlight the differential impacts of state-based trauma and the ways in which its effects continue to be felt for generations. The revised and empirically tested Model of the Differential Impact of Holocaust Trauma across Three Generations presented at the conclusion of this thesis represents a further clarification of existing trauma theories as well as the first attempt at determining the relative importance of both cognitive, interpersonal/interfamilial interaction processes and demographic variables in post-trauma psychological health and transmission of traumatic impact.

Relaxin stimulates leukocyte adhesion and migration through a relaxin receptor LGR7-dependent mechanism

Leukocytes are critical effectors of inflammation and tumor biology. Chemokine-like factors produced by such inflammatory sites are key mediators of tumor growth that activate leukocytic recruitment and tumor infiltration and suppress immune surveillance. Here we report that the endocrine peptide hormone, relaxin, is a regulator of leukocyte biology with properties important in recruitment to sites of inflammation. This study uses the human monocytic cell line THP-1 and normal human peripheral blood mononuclear cells to define a novel role for relaxin in regulation of leukocyte adhesion and migration. Our studies indicate that relaxin promotes adenylate cyclase activation, substrate adhesion, and migratory capacity of mononuclear leukocytes through a relaxin receptor LGR7-dependent mechanism. Relaxin-stimulated cAMP accumulation was observed to occur primarily in non-adherent cells. Relaxin stimulation results in increased substrate adhesion and increased migratory activity of leukocytes. In addition, relaxin-stimulated substrate adhesion resulted in enhanced chemotaxis to monocyte chemoattractant protein-1. These responses in THP-1 and peripheral blood mononuclear cells are relaxin dose-dependent and proportional to cAMP accumulation. We further demonstrate that LGR7 is critical for mediating these biological responses by use of RNA interference lentiviral short hairpin constructs. In summary, we provide evidence that relaxin is a novel leukocyte stimulatory agent with properties affecting adhesion and chemomigration

Marketing VM services to achieve competitive advantage in the Malaysian Construction Sector

Value Management (VM) has been proven to provide a structured framework, together with supporting tools and techniques that facilitate effective decision-making in many types of projects, thus achieving ‘best value’ for clients. It is identified at International level as a natural career progression for the construction service provider and as an opportunity in developing leading-edge skills. The services offered by contractors and consultants in the construction sector have been expanding. In an increasingly competitive and global marketplace, firms are seeking ways to differentiate their services to ever more knowledgeable and demanding clients. The traditional demarcations have given way, and the old definition of what contractors, designers, engineers and quantity surveyors can, and cannot do in terms of their market offering has changed. Project management, design and cost and safety consultancy services, are being delivered by a diverse range of suppliers. Value management services have been developing in various sectors in industry; from manufacturing to the military and now construction. Given the growing evidence that VM has been successful in delivering value-for-money to the client, VM would appear to be gaining some momentum as an essential management tool in the Malaysian construction sector. The recently issued VM Circular 3/2009 by the Economic Planning Unit Malaysia (EPU) possibly marks a new beginning in public sector client acceptance on the strength of VM in construction. This paper therefore attempts to study the prospects of marketing the benefits of VM by construction service providers, and how it may provide an edge in an increasingly competitive Malaysian construction industry.

A vision of the past : The Mill Albion

This paper examines The Mill Albion community history project, a diverse, multi-layered public history/art program that captures the social heritage of The Albion Flour Mill, as told through images produced as part of a research consultancy undertaken by QUT for FKP Property Group. The Albion Flour Mill was built in 1930 and continued operations for more than 72 years. After ceasing operation in 2005 the site was left to deteriorate. The FKP Property Group purchased the land to undertake a new urban redevelopment project. This paper reflects on the project and showcases some of the culturally creative ways this community’s history was told, using images.

Exercise and cancer rehabilitation : a systematic review

Introduction: Cancer is increasingly being viewed as a chronic illness requiring long-term management, and there is a growing need for evidence-based rehabilitation interventions for cancer survivors. Previous reviews have evaluated the benefits of exercise interventions for patients undergoing cancer treatment and long-term survivors, but none have investigated the role of exercise during cancer rehabilitation, the period immediately following cancer treatment completion. This systematic review summarises the literature on the health effects of exercise during cancer rehabilitation and evaluates the methodological rigour of studies in this area to date.----------- Methods: Relevant studies were identified through a systematic search of PubMed and Embase to April 2009. Data on study design, recruitment strategy, participants, exercise intervention, adherence rates, and outcomes were extracted. Methodological rigour was assessed using a structured rating system.---------- Results: Ten studies were included. Breast cancer patients were the predominate patient group represented. Most interventions were aerobic or resistance-training exercise programmes, and exercise type, frequency, duration and intensity varied across studies. Improvements in physical functioning, strength, physical activity levels, quality of life, fatigue, immune function, haemoglobin concentrations, potential markers of recurrence, and body composition were reported. However, all studies were limited by incomplete reporting and methodological limitations.---------- Conclusions: Although the methodological limitations of studies in this new field must be acknowledged, initial evidence indicates that exercise is feasible and may provide physiological and psychological benefits for cancer survivors during the rehabilitation period. Future studies with rigorous study designs are now required to advance the field.

Facilitating needs based cancer care for people with a chronic disease : evaluation of an intervention using a multi-centre interrupted time series design

Background: Palliative care should be provided according to the individual needs of the patient, caregiver and family, so that the type and level of care provided, as well as the setting in which it is delivered, are dependent on the complexity and severity of individual needs, rather than prognosis or diagnosis. This paper presents a study designed to assess the feasibility and efficacy of an intervention to assist in the allocation of palliative care resources according to need, within the context of a population of people with advanced cancer. ---------- Methods/design: People with advanced cancer and their caregivers completed bi-monthly telephone interviews over a period of up to 18 months to assess unmet needs, anxiety and depression, quality of life, satisfaction with care and service utilisation. The intervention, introduced after at least two baseline phone interviews, involved a) training medical, nursing and allied health professionals at each recruitment site on the use of the Palliative Care Needs Assessment Guidelines and the Needs Assessment Tool: Progressive Disease - Cancer (NAT: PD-C); b) health professionals completing the NAT: PD-C with participating patients approximately monthly for the rest of the study period. Changes in outcomes will be compared pre-and post-intervention.---------- Discussion: The study will determine whether the routine, systematic and regular use of the Guidelines and NAT: PD-C in a range of clinical settings is a feasible and effective strategy for facilitating the timely provision of needs based care.

Attraction and image for the Australian rail industry

Despite the global financial downturn, the Australian rail industry is in a period of expansion. Reports indicate that the industry is not attracting sufficient entry level and mid-career engineers and skilled technicians from within the Australian labour market and is facing widespread retirements from an ageing workforce. This paper reports on a completed qualitative study that explores the perceptions of engineering students, their lecturers, careers advisors and recruitment consultants regarding rail as a brand and of careers in the rail industry. Findings are presented about career knowledge, job characteristic preferences, branding and image and indicate that rail as a brand has a dated image, that young people and their influencers have little knowledge of rail careers and that rail could better focus its image and recruitment strategies. Conclusions include suggestions for more effective attraction and image strategies for the industry and for further research.

Defending the patch : a labour geography analysis of unions’ construction of and responses to the problem of declining union membership amongst youth

If the trade union movement is to remain an influential force in the industrial, economic and socio/political arenas of industrialised nations it is vital that its recruitment of young members improve dramatically. Australian union membership levels have declined markedly over the last three decades and youth union membership levels have decreased more than any age group. Currently around 10% of young workers aged between 16-24 years are members of unions in Australia compared to 26% of workers aged 45-58 (Oliver, 2008). This decline has occurred throughout the union movement, in all states and in almost all industries and occupations. This research, which consists of interviews with union organisers and union officials, draws on perspectives from the labour geography literature to explore how union personnel located in various places, spaces and scales construct the issue of declining youth union membership. It explores the scale of connections within the labour movement and the extent to which these connections are leveraged to address the problem of youth union membership decline. To offer the reader a sense of context and perspective, the thesis firstly outlines the historical development of the union movement. It also reviews the literature on youth membership decline. Labour geography offers a rich and apposite analytical tool for investigation of this area. The notion of ‘scale’ as a dynamic, interactive, constructed and reconstructed entity (Ellem, 2006) is an appropriate lens for viewing youth-union membership issues. In this non-linear view, scale is a relational element which interplays with space, place and the environment (Howett, in Marston, 2000) rather than being ‘sequential’ and hierarchical. Importantly, the thesis investigates the notion of unions as ‘spaces of dependence’ (Cox, 1998a, p.2), organisations whose space is centred upon realising essential interests. It also considers the quality of unions’ interactions with others – their ‘spaces of engagement‘(Cox, 1998a, p.2), and the impact that this has upon their ability to recruit youth. The findings reveal that most respondents across the spectrum of the union movement attribute the decline in youth membership levels to factors external to the movement itself, such as changes to industrial relations legislation and the impact of globalisation on employment markets. However, participants also attribute responsibility for declining membership levels to the union movement itself, citing factors such as a lack of resourcing and a need to change unions’ perceived identity and methods of operation. The research further determined that networks of connections across the union movement are tenuous and, to date, are not being fully utilised to assist unions to overcome the youth recruitment dilemma. The study concludes that potential connections between unions are hampered by poor resourcing, workload issues and some deeply entrenched attitudes related to unions ‘defending (and maintaining) their patch’.

The role of assisted self-help in services for alcohol-related disorders

Potentially harmful substance use is common, but many affected people do not receive treatment. Brief face-to-face treatments show impact, as do strategies to assist self-help remotely, by using bibliotherapies, computers or mobile phones. Remotely delivered treatments offer more sustained and multifaceted support than brief interventions, and they show a substantial cost advantage as users increase in number. They may also build skills, confidence and treatment fidelity in providers who use them in sessions. Engagement and retention remain challenges, but electronic treatments show promise in engaging younger populations. Recruitment may be assisted by integration with community campaigns or brief opportunistic interventions. However, routine use of assisted self-help by standard services faces significant challenges. Strategies to optimize adoption are discussed. ----- ----- Research Highlights: ► Many people with risky or problematic drinking do not currently receive treatment. ► Assisted self-help has a significant impact and can be delivered at low cost. ► Maximal effects from assisted self-help require engagement of potential users. ► Marketing campaigns and integration into existing service models may assist.