A fission yeast homolog of Int-6, the mammalian oncoprotein and eIF3 subunit, induces drug resistance when overexpressed

Through a screen to identify genes that induce multi-drug resistance when overexpressed, we have identified a fission yeast homolog of Int-6, a component of the human translation initiation factor eIF3. Disruption of the murine Int-6 gene by mouse mammary tumor virus (MMTV) has been implicated previously in tumorigenesis, although the underlying mechanism is not yet understood. Fission yeast Int6 was shown to interact with other presumptive components of eIF3 in vivo, and was present in size fractions consistent with its incorporation into a 43S translation preinitiation complex. Drug resistance induced by Int6 overexpression was dependent on the AP-1 transcription factor Pap1, and was associated with increased abundance of Pap1-responsive mRNAs, but not with Pap1 relocalization. Fission yeast cells lacking the int6 gene grew slowly. This growth retardation could be corrected by the expression of full length Int6 of fission yeast or human origin, or by a C-terminal fragment of the fission yeast protein that also conferred drug resistance, but not by truncated human Int-6 proteins corresponding to the predicted products of MMTV-disrupted murine alleles. Studies in fission yeast may therefore help to explain the ways in which Int-6 function can be perturbed during MMTV-induced mammary tumorigenesis.

Proteasome inhibitors as anti-cancer agents

The ubiquitin (Ub)-proteasome pathway is the major nonlysosomal pathway of proteolysis in human cells and accounts for the degradation of most short-lived, misfolded or damaged proteins. This pathway is important in the regulation of a number of key biological regulatory mechanisms. Proteins are usually targeted for proteasome-mediated degradation by polyubiquitinylation, the covalent addition of multiple units of the 76 amino acid protein Ub, which are ligated to 1-amino groups of lysine residues in the substrate. Polyubiquitinylated proteins are degraded by the 26S proteasome, a large, ATP-dependent multicatalytic protease complex, which also regenerates monomeric Ub. The targets of this pathway include key regulators of cell proliferation and cell death. An alternative form of the proteasome, termed the immunoproteasome, also has important functions in the generation of peptides for presentation by MHC class I molecules. In recent years there has been a great deal of interest in the possibility that proteasome inhibitors, through elevation of the levels of proteasome targets, might prove useful as a novel class of anti-cancer drugs. Here we review the progress made to date in this area and highlight the potential advantages and weaknesses of this approach.

Frames of Anime: Culture and Image-Building

With the rising popularity of anime amongst animation students, audiences and scholars around the world, it has become increasingly important to critically analyse anime as being more than a ‘limited’ form of animation, and thematically as encompassing more than super robots and pocket monsters. Frames of Anime: Culture and Image-Building charts the development of Japanese animation from its indigenous roots within a native culture, through Japan’s experience of modernity and the impact of the Second World War. This text is the result of a rigorous study that recognises the heterogeneous and polymorphous background of anime. As such, Tze-Yue has adopted an ‘interdisciplinary and transnational’ (p. 7) approach to her enquiry, drawing upon face-to-face interviews, on-site visits and biographical writings of animators. Tze-Yue delineates anime from other forms of animation by linking its visual style to pre-modern Japanese art forms and demonstrating the connection it shares with an indigenous folk system of beliefs. Via the identification of traditional Japanese art forms and their visual connectedness to Japanese animation, Tze-Yue shows that the Japanese were already heavily engaged in what was destined to become anime once technology had enabled its production. Tze-Yue’s efforts to connect traditional Japanese art forms, and their artistic elements, to contemporary anime reveals that the Japanese already had a rich culture of visual storytelling that pre-dates modern animation. She identifies the Japanese form of the magic lantern at the turn of the 19th century, utsushi-e, as the pre-modern ancestor of Japanese animation, describing it as ‘Edo anime’ (p. 43). Along with utsushi-e, the Edo period also saw the woodblock print, ukiyo-e, being produced for the rising middle class (p. 32). Highlighting the ‘resurfacing’ of ‘realist’ approaches to Japanese art in ukiyo-e, Tze-Yue demonstrates the visual connection of ukiyo-e and anime in the …

A multilevel investigation of inequalities in clinical and psychosocial outcomes for women after breast cancer

Background In Australia, breast cancer is the most common cancer affecting Australian women. Inequalities in clinical and psychosocial outcomes have existed for some time, affecting particularly women from rural areas and from areas of disadvantage. We have a limited understanding of how individual and area-level factors are related to each other, and their associations with survival and other clinical and psychosocial outcomes. Methods/Design This study will examine associations between breast cancer recurrence, survival and psychosocial outcomes (e.g. distress, unmet supportive care needs, quality of life). The study will use an innovative multilevel approach using area-level factors simultaneously with detailed individual-level factors to assess the relative importance of remoteness, socioeconomic and demographic factors, diagnostic and treatment pathways and processes, and supportive care utilization to clinical and psychosocial outcomes. The study will use telephone and self-administered questionnaires to collect individual-level data from approximately 3, 300 women ascertained from the Queensland Cancer Registry diagnosed with invasive breast cancer residing in 478 Statistical Local Areas Queensland in 2011 and 2012. Area-level data will be sourced from the Australian Bureau of Statistics census data. Geo-coding and spatial technology will be used to calculate road travel distances from patients' residence to diagnostic and treatment centres. Data analysis will include a combination of standard empirical procedures and multilevel modelling. Discussion The study will address the critical question of: what are the individual- or area-level factors associated with inequalities in outcomes from breast cancer? The findings will provide health care providers and policy makers with targeted information to improve the management of women with breast cancer, and inform the development of strategies to improve psychosocial care for women with breast cancer.

Prevalence and prognostic significance of secondary lymphedema following breast cancer

Background The adverse consequences of lymphedema following breast cancer in relation to physical function and quality of life are clear; however, its potential relationship with survival has not been investigated. Our purpose was to determine the prevalence of lymphedema and associated upper-body symptoms at 6 years following breast cancer and to examine the prognostic significance of lymphedema with respect to overall 6-year survival (OS). Methods and Results A population-based sample of Australian women (n=287) diagnosed with invasive, unilateral breast cancer was followed for a median of 6.6 years and prospectively assessed for lymphedema (using bioimpedance spectroscopy [BIS], sum of arm circumferences [SOAC], and self-reported arm swelling), a range of upper-body symptoms, and vital status. OS was measured from date of diagnosis to date of death or last follow-up. Kaplan-Meier methods were used to calculate OS and Cox proportional hazards models quantified the risk associated with lymphedema. Approximately 45% of women had reported at least one moderate to extreme symptom at 6.6 years postdiagnosis, while 34% had shown clinical evidence of lymphedema, and 48% reported arm swelling at least once since baseline assessment. A total of 27 (9.4%) women died during the follow-up period, and lymphedema, diagnosed by BIS or SOAC between 6–18 months postdiagnosis, predicted mortality (BIS: HR=2.5; 95% CI: 0.9, 6.8, p=0.08; SOAC: 3.0; 95% CI: 1.1, 8.7, p=0.04). There was no association (HR=1.2; 95% CI: 0.5, 2.6, p=0.68) between self-reported arm swelling and OS. Conclusions These findings suggest that lymphedema may influence survival following breast cancer treatment and warrant further investigation in other cancer cohorts and explication of a potential underlying biology.

The implementation of sustainable housing through mutual benefits to key stakeholders

Among the Australian general public, there are increasing concerns about environmental issues. Accordingly, sustainability in the housing industry is also becoming a priority on the development agenda. However, putting the principles of ecological sustainability into practice within social and economic development requires intensive involvement of major stakeholders such as governments, developers, builders, consumers and a range of other professionals. Establishing a sustainable value entails asymmetric life-cycle returns, making it important for major stakeholders to appreciate the benefits of this new agenda not only for the individual businesses but also for other supply chain partners. This context warrants the study to promote collective benefits for key stakeholders by establishing a mutual-benefit framework for sustainable housing implementation. A research was carried out in the hope to establish a mutual-benefit framework by investigating challenges of achieving benefits (CABs) from sustainable housing development in a multi-stakeholder context. In the research work reported in this article, a comparative questionnaire study was first conducted among seven stakeholder groups in the Australian housing industry, to examine the importance and inter-relationships of CABs. In-depth interviews then furthered the survey findings with a focus on stakeholder diversity. The synthesized findings of the survey and interview study lead to the identification of 12 critical mutual-benefit factors and their mutual influence. Based on such a platform, a systematic framework is developed with the aid of Interpretive Structural Modelling (ISM), to identify the patterns of stakeholder benefit materialisation, suggest the priority of critical factors and provide related stakeholder-specific action guide for sustainable housing implementation.

Charitable bequests a specific case of gift giving

Over the last 5 years, charities have acknowledged that bequests are a source of income with the potential for enormous growth. As the population ages the number of possible bequest donors will increase. Charities are implementing bequest campaigns to target the older donors, and the need for research is evident...

Accounting Research Journal Editorial : "ARJ – The First 25 Years"

In this 25th year of publication of the Accounting Research Journal we pay tribute to the efforts of the dedicated Editors who have successfully guided and developed the journal since its inception in 1988. After the rapid growth in accounting and finance research in the 1970s and 1980s the absence of outlets in Asia-Pacific region to publish novel, timely and applied research became increasingly apparent. In response to this gap, ARJ’s first volume was published in 1988 by the School of Accountancy at the Queensland Institute of Technology (QIT), which became the Queensland University of Technology (QUT) in the following year. The founding Editor was Myles McGregor-Lowndes and his editorship continued for three years until Scott Holmes took over as Editor in 1991. In 1992, Robert Faff joined Scott Holmes as Joint Editor, and their joint editorship continued for six years until Robert Faff took the reins as Editor in 1998. At that time Scott remained as Associate Editor and the editorial team was joined by Roger Willett as Consulting Editor and Chris Lambert as Associate Editor. This arrangement continued until 2002 when Tim Brailsford was newly appointed as Managing Editor. The editorship returned to QUT in 2008 and was taken on by Chris Ryan with our support as Co-editors. Since 2011 we have been the Joint Editors. Table 1 lists the individuals who have been involved in editing ARJ over the 25-year period and their roles...

Will Queensland tort reform change valuation practice and valuers liability

It has been common practice over past property boom and bust cycles in Australia for financial institutions and property owners who have suffered a loss in the property downturn to sue valuers for negligence. Damages claimed are based on the price differential between the valuation at or nearing the peak of the market and the subsequent sale in the market downturn. However, the context of valuers liability has become increasingly complex as a result of statutory reforms introduced in response to the Review of the Law of Negligence Final Report 2002), in particular the introduction of Civil Liability Acts introducing proportionate liability provisions. Legislative reforms have had some positive outcomes for Valuers, however valuers need to continue to maintain high ethical standards, independence and professionalism in valuation practice.

Education on plant and machinery valuation for the real market : Malaysian practicality

The purpose of this paper is to determine and discuss on the plant and machinery valuation syllabus for higher learning education in Malaysia to ensure the practicality of the subject in the real market. There have been limited studies in plant and machinery area, either by scholars or practitioners. Most papers highlighted the methodologies but limited papers discussed on the plant and machinery valuation education. This paper will determine inputs for plant and machinery valuation guidance focussing on the syllabus set up and references for valuers interested in this area of expertise. A qualitative approach via content analysis is conducted to compare international and Malaysian plant and machinery valuation syllabus and suggest improvements for Malaysian syllabus. It is found that there are few higher education institutions in the world that provide plant and machinery valuation courses as part of their property studies syllabus. Further investigation revealed that on the job training is the preferable method for plant and machinery valuation education and based on the valuers experience. The significance of this paper is to increase the level of understanding of plant and machinery valuation criteria and provide suggestions to Malaysian stakeholders with the relevant elements in plant and machinery valuation education syllabus.

Residential property investment : assessing home ownership long term viability

Home purchase and ownership is seen by the majority of Australians as the basis for a sound investment strategy and to seciure their long term retirement goals. Although home ownership rates in Australia are in excess of 65% of the population, there have been doubts raised as to the effectiveness of purchasing a house as the main source of retirement income. The main issue with this approach is that the house has to be sold to gain access to these funds or the owners have to take out a reverse mortgage to access the capital tied up in their home, which can be more expensive than selling. This paper will carryout a detailed analysis of a number of investment options to determine the effectiveness of home purchase as a long term investment vehicle. This study has found that the long term investment in equities or managed superannuation funds can provide a greater retirement income than the purchase of a residential property for owner occupation

“They’re My Two Favourites” versus “The Bigger Scheme of Things” : pro-Am historians remember Australian television

This chapter reports on eleven interviews with Pro-Am archivists of Australian television which aimed to find out how they decide what materials are important enough to archive. Interviewees mostly choose to collect materials in which they have a personal interest. But they are also aware of the relationship between their own favourites and wider accounts of Australian television history, and negotiate between these two positions. Most interviewees acknowledged Australian television’s links with British and American programming, but also felt that Australian television is distinctive. They argued that Australian television history is ignored in a way that isn’t true for the UK or the US. Several also argued that Australian television has had a ‘naïve’ nature that has allowed it to be more experimental.

Exercise for health : a randomized, controlled trial evaluating impact of a pragmatic, translational exercise intervention on quality of life, function and treatment-related side effects following breast cancer

Purpose Exercise for Health was a randomized, controlled trial designed to evaluate two modes of delivering (face-to-face [FtF] and over-the-telephone [Tel]) an 8-month translational exercise intervention, commencing 6-weeks post-breast cancer surgery (PS). Methods Outcomes included quality of life (QoL), function (fitness and upper-body) and treatment-related side effects (fatigue, lymphoedema, body mass index, menopausal symptoms, anxiety, depression and pain). Generalised estimating equation modelling determined time (baseline [5-weeks PS], mid-intervention [6-months PS], post-intervention [12-months PS]), group (FtF, Tel, Usual Care [UC]) and time-by-group effects. 194 women representative of the breast cancer population were randomised to the FtF (n=67), Tel (n=67) and UC (n=60) groups. Results: There were significant (p<0.05) interaction effects on QoL, fitness and fatigue, with differences being observed between the treatment groups and the UC group. Trends observed for the treatment groups were similar. The treatment groups reported improved QoL, fitness and fatigue over time and changes observed between baseline and post-intervention were clinically relevant. In contrast, the UC group experienced no change, or worsening QoL, fitness and fatigue, mid-intervention. Although improvements in the UC group occurred by 12-months post-surgery, the change did not meet the clinically relevant threshold. There were no differences in other treatment-related side-effects between groups. Conclusion This translational intervention trial, delivered either face-to-face or over-the-telephone, supports exercise as a form of adjuvant breast cancer therapy that can prevent declines in fitness and function during treatment and optimise recovery post-treatment.