Ran is a potential therapeutic target for cancer cells with molecular changes associated with activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways

Purpose Cancer cells have been shown to be more susceptible to Ran knockdown than normal cells. We now investigate whether Ran is a potential therapeutic target of cancers with frequently found mutations that lead to higher Ras/MEK/ERK [mitogen-activated protein/extracellular signal-regulated kinase (ERK; MEK)] and phosphoinositide 3-kinase (PI3K)/Akt/mTORC1 activities. Experimental Design Apoptosis was measured by flow cytometry [propidium iodide (PI) and Annexin V staining] and MTT assay in cancer cells grown under different conditions after knockdown of Ran. The correlations between Ran expression and patient survival were examined in breast and lung cancers. Results Cancer cells with their PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways inhibited are less susceptible to Ran silencing-induced apoptosis. K-Ras-mutated, c-Met-amplified, and Pten-deleted cancer cells are also more susceptible to Ran silencing-induced apoptosis than their wild-type counterparts and this effect is reduced by inhibitors of the PI3K/Akt/mTORC1 and MEK/ERK pathways. Overexpression of Ran in clinical specimens is significantly associated with poor patient outcome in both breast and lung cancers. This association is dramatically enhanced in cancers with increased c-Met or osteopontin expression, or with oncogenic mutations of K-Ras or PIK3CA, all of which are mutations that potentially correlate with activation of the PI3K/Akt/mTORC1 and/or Ras/MEK/ERK pathways. Silencing Ran also results in dysregulation of nucleocytoplasmic transport of transcription factors and downregulation of Mcl-1 expression, at the transcriptional level, which are reversed by inhibitors of the PI3K/Akt/mTORC1 and MEK/ERK pathways. Conclusion Ran is a potential therapeutic target for treatment of cancers with mutations/changes of expression in protooncogenes that lead to activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways. ©2011 AACR.

Efficient silencing of endogenous microRNAs using artificial microRNAs in Arabidopsis thaliana

We report here that the expression of endogenous microRNAs (miRNAs) can be efficiently silenced in Arabidopsis thaliana (Arabidopsis) using artificial miRNA (amiRNA) technology. We demonstrate that an amiRNA designed to target a mature miRNA directs silencing against all miRNA family members, whereas an amiRNA designed to target the stem-loop region of a miRNA precursor transcript directs silencing against only the individual family member targeted. Furthermore, our results indicate that amiRNAs targeting both the mature miRNA and stem-loop sequence direct RNA silencing through cleavage of the miRNA precursor transcript, which presumably occurs in the nucleus of a plant cell during the initial stages of miRNA biogenesis. This suggests that small RNA (sRNA)-guided RNA cleavage in plants occurs not only in the cytoplasm, but also in the nucleus. Many plant miRNA gene families have been identified via sequencing and bioinformatic analysis, but, to date, only a small tranche of these have been functionally characterized due to a lack of effective forward or reverse genetic tools. Our findings therefore provide a new and powerful reverse-genetic tool for the analysis of miRNA function in plants. © The Author 2010. Published by the Molecular Plant Shanghai Editorial Office in association with Oxford University Press on behalf of CSPP and IPPE, SIBS, CAS.

Synthesis of complementary RNA by RNA-dependent RNA polymerases in plant extracts is independent of an RNA primer

RNA-dependent RNA polymerase (RDR) activities were readily detected in extracts from cauliflower and broccoli florets, Arabidopsis thaliana (L.) Heynh callus tissue and broccoli nuclei. The synthesis of complementary RNA (cRNA) was independent of a RNA primer, whether or not the primer contained a 3′ terminal 2′-O-methyl group or was phosphorylated at the 5′ terminus. cRNA synthesis in plant extracts was not affected by loss-of-function mutations in the DICER-LIKE (DCL) proteins DCL2, DCL3, and DCL4, indicating that RDRs function independently of these DCL proteins. A loss-of-function mutation in RDR1, RDR2 or RDR6 did not significantly reduce the amount of cRNA synthesis. This indicates that these RDRs did not account for the bulk RDR activities in plant extracts, and suggest that either the individual RDRs each contribute a fraction of polymerase activity or another RDR(s) is predominant in the plant extract. © CSIRO 2008.

Grand tours in the glare of the sun : harnessing digital media to develop cultural tourism in Queensland, Australia

It has been well established that highlighting the cultural attributes of a region through stories of place, local histories, and the creative arts boosts tourism income to a region. Cultural tourism also serves to promote the creative industries to visitors and residents alike and, by enhancing a region’s cultural identity, fosters new opportunities for the arts. It can therefore offer considerable potential benefit to the creative economy in Australia. However, in comparison with Europe, where cultural tourism can rely upon an established historical, artistic and literary cultural identity that stretches back to Grand Tours of the seventeenth century, in Queensland, Australia the relatively new enterprise of cultural tourism must compete with visitor expectations of sun, surf and the natural landscapes, which have become the mainstay of tourism advertising. Moreover, in Queensland, it is essential to connect vast distances, diverse communities and a variety of cultural experiences. We must also take account of the expectations of contemporary tourists, who anticipate a digitally mediated travel experience and increasingly seek to connect with local communities in authentic ways. In this paper we consider the unique considerations that must be taken into account in the Queensland context and propose approaches to developing an integrated identity that embraces both the ‘great outdoors’ and the region’s cultural attributes. We make recommendations for providing the types of digitally mediated ‘local’ experiences that cultural tourists now expect, and illustrate the design principles we propose through early, tentative approaches to smart phones, locative media and augmented reality applications for cultural tourism in the region. We conclude by proposing additional ways to formulate a digital strategy in line with the recommendations we make.

A theory of literacies for considering the role of adult and community education in postcolonial change

In this paper, I use a case study drawn from education in the Grenada revolution and afterwards to discuss lessons that postcolonial societies can learn from comparing two approaches to adult basic and popular education. I argue that some approaches to adult education provide subordinate literacies and catch-up schooling on the cheap, while others contribute to sociopolitical change by helping participants develop powerful literacies that challenge the structures of injustice, inefficiency, and dysfunctionality that are still entrenched in most societies. The paper puts forward the concept of epistemic, humanist and public ‘literacies’ as a tool for considering the role of adult education in national development.

Exposure to solar ultraviolet radiation is associated with a decreased folate status in women of childbearing age

In vitro studies indicate that folate in collected human blood is vulnerable to degradation after exposure to ultraviolet (UV) radiation. This has raised concerns about folate depletion in individuals with high sun exposure. Here, we investigate the association between personal solar UV radiation exposure and serum folate concentration, using a three-week prospective study that was undertaken in females aged 18–47 years in Brisbane, Australia (153 E, 27 S). Following two weeks of supplementation with 500 μg of folic acid daily, the change in serum folate status was assessed over a 7-day period of measured personal sun exposure. Compared to participants with personal UV exposures of <200 Joules per day, participants with personal UV exposures of 200–599 and >600 Joules per day had significantly higher depletion of serum folate (p = 0.015). Multivariable analysis revealed personal UV exposure as the strongest predictor accounting for 20% of the overall change in serum folate (Standardised B = −0.49; t = −3.75; p = <0.01). These data show that increasing solar UV radiation exposures reduces the effectiveness of folic acid supplementation. The consequences of this association may be most pronounced for vulnerable individuals, such as women who are pregnant or of childbearing age with high sun exposures.

Designing Assessment for Quality Learning

- Considers broad-scale assessment approaches and how they impact on educational opportunity and outcomes. - Brings together internationally recognised scholars providing new insights into assessment for learning improvement and accountability. - Presents different theoretical and methodological perspectives influential in the field of assessment, learning and social change. - Contributes to the theorising of assessment in contexts characterised by heightened accountability requirements and constant change. This book brings together internationally recognised scholars with an interest in how to use the power of assessment to improve student learning and to engage with accountability priorities at both national and global levels. It includes distinguished writers who have worked together for some two decades to shift the assessment paradigm from a dominant focus on assessment as measurement towards assessment as central to efforts to improve learning. These writers have worked with the teaching profession and, in so doing, have researched and generated key insights into different ways of understanding assessment and its relationship to learning. The volume contributes to the theorising of assessment in contexts characterised by heightened accountability requirements and constant change. The book’s structure and content reflect already significant and growing international interest in assessment as contextualised practice, as well as theories of learning and teaching that underpin and drive particular assessment approaches. Learning theories and practices, assessment literacies, teachers’ responsibilities in assessment, the role of leadership, and assessment futures are the organisers within the book’s structure and content. The contributors to this book have in common the view that quality assessment, and quality learning and teaching are integrally related. Another shared view is that the alignment of assessment with curriculum, teaching and learning is linchpin to efforts to improve both learning opportunities and outcomes for all. Essentially, the book presents new perspectives on the enabling power of assessment. In so doing, the writers recognise that validity and reliability - the traditional canons of assessment – remain foundational and therefore necessary. However, they are not of themselves sufficient for quality education. The book argues that assessment needs to be radically reconsidered in the context of unprecedented societal change. Increasingly, communities are segregating more by wealth, with clear signs of social, political, economic and environmental instability. These changes raise important issues relating to ethics and equity, taken to be core dimensions in enabling the power of assessment to contribute to quality learning for all. This book offers readers new knowledge about how assessment can be used to re/engage learners across all phases of education.

Dispensing doctor : an underutilise resource?

Introduction Multidisciplinary models of organising and providing care have been proposed to decrease the health services gap between urban and rural populations but health workforce shortages exist across most professions and are further exacerbated by maldistribution. Flexibility and expansion of the range of tasks that a health professional can undertake were proposed. Dispensing doctors (DDs) are such an example. As part of DDs’ routine medical practice, DDs are able to both prescribe and dispense medicines to their patients. The granting of a dispensing licence to a doctor is intended to improve rural community access to medicines where there is no pharmacy within a reasonable distance. Method An iterative, qualitative descriptive methodology was used to identify factors which influenced DDs’ practice. Qualitative data were collected by in-depth face-to-face and telephone interviews with DDs. A combination of processes: qualitative content analysis and constant comparison were used to analyse the interview transcripts thematically. Member checking and separate coding were utilised to ensure rigour. Result Thirty-one interviews were conducted. The respondents universally acknowledged that the main reason for dispensing were for the convenience and benefits of their patients and to ensure continuity of care. DDs’ communities were generally more isolated and smaller when compared to their non-dispensing counterparts. DD-respondents viewed their dispensary as a service to the community. Peer pressure on prescribing was a key factors in self-regulating prescribing and dispensing. Conclusion DDs fulfill an important area of unmet needs by providing continuity of pharmaceutical care but the practice is hindered by significant barriers

Mobility and out-of-home activities of older people living in suburban environments : ‘Because I'm a driver, I don't have a problem'

Governments are challenged by the need to ensure that ageing populations stay active and engaged as they age. Therefore, it is critical to investigate the role of mobility in older people's engagement in out-of-home activities, and to identify the experiences they have within their communities. This research investigates the use of transportation by older people and its implications for their out-of-home activities within suburban environments. The qualitative, mixed-method approach employs data collection methods which include a daily travel diary (including a questionnaire), Global Positioning System (GPS) tracking and semi-structured interviews with older people living in suburban environments in Brisbane, Australia. Results show that older people are mobile throughout the city, and their car provides them with that opportunity to access desired destinations. This ability to drive allows older people to live independently and to assist others who do not drive, particularly where transport alternatives are not as accessible. The ability to transport goods and other people is a significant advantage of the private car over other transport options. People with no access to private transportation who live in low-density environments are disadvantaged when it comes to participation within the community. Further research is needed to better understand the relationship between transportation and participation within the community environment, to assist policy makers and city and transportation planners to develop strategies for age-friendly environments within the community.