Transforming habitus: Changing self, changing school

Since 2004, Australian Indigenous (Aboriginal and Torres Strait Islander) students at a low socioeconomic area Australian urban secondary school have used participatory action research to investigate issues of disengagement and absenteeism among their peers. Their research revealed that Indigenous students, who made up about 8% to 10% of the school’s population lacked a sense of belonging to the school. The researchers also revealed an apparent official disregard of the academic or sporting achievements of Indigenous students and, more disturbingly, their presence within the school. The young researchers followed up their findings with action to address the issues. These actions have resulted in a positive change of culture across the whole school, with Indigenous students now able to express pride in their heritage and feel some degree of ownership of the school.

Project alliancing and information technology in building construction : the National Museum of Australia

The construction industry demands priority from all governments because it impacts economically and socially on all citizens. A number of recent studies have identified inefficiencies in the Australian construction industry by modelling the building process. A culture of reform supported by industry and government is now emerging in the industry – one in which alternate forms of project delivery are being trialed. The Australian Building and Construction Industry Action Agenda brought together industry and government to identify actions necessary to lift Australia’s innovative and knowledge creating capacity at the sector level. A central activity under this Action Agenda was dissemination of information relating to industry best practice initiatives in innovation, project delivery and the use of information technology. Government and industry identified project alliance contracting and more advanced information technology as means to increase efficiency in construction as part of a new innovative procurement environment.

PARP inhibition induces BAX/BAK-independent synthetic lethality of BRCA1-deficient non-small cell lung cancer

Evasion of apoptosis contributes to both tumourigenesis and drug resistance in non-small cell lung carcinoma (NSCLC). The pro-apoptotic BCL-2 family proteins BAX and BAK are critical regulators of mitochondrial apoptosis. New strategies for targeting NSCLC in a mitochondria-independent manner should bypass this common mechanism of apoptosis block. BRCA1 mutation frequency in lung cancer is low; however, decreased BRCA1 mRNA and protein expression levels have been reported in a significant proportion of lung adenocarcinomas. BRCA1 mutation/deficiency confers a defect in homologous recombination DNA repair that has been exploited by synthetic lethality through inhibition of PARP (PARPi) in breast and ovarian cells; however, it is not known whether this same synthetic lethal mechanism exists in NSCLC cells. Additionally, it is unknown whether the mitochondrial apoptotic pathway is required for BRCA1/PARPi-mediated synthetic lethality. Here we demonstrate that silencing of BRCA1 expression by RNA interference sensitizes NSCLC cells to PARP inhibition. Importantly, this sensitivity was not attenuated in cells harbouring mitochondrial apoptosis block induced by co-depletion of BAX and BAK. Furthermore, we demonstrate that BRCA1 inhibition cannot override platinum resistance, which is often mediated by loss of mitochondrial apoptosis signalling, but can still sensitize to PARP inhibition. Finally we demonstrate the existence of a BRCA1-deficient subgroup (11–19%) of NSCLC patients by analysing BRCA1 protein levels using immunohistochemistry in two independent primary NSCLC cohorts. Taken together, the existence of BRCA1-immunodeficient NSCLC suggests that this molecular subgroup could be effectively targeted by PARP inhibitors in the clinic and that PARP inhibitors could be used for the treatment of BRCA1-immunodeficient, platinum-resistant tumours.

Identifying engaging features of schooling : assessing the psychometric soundness of student generated research

In this article we report on data analysed from a student project about attitudes to school and student perception of engagement and disengagement. The data were collected by students in an Australian study that employed the Young People as Researchers Model. Middle years students devised and administered a questionnaire to students in grade eight, nine and ten at a secondary school in Australia. A total of 239 students completed the questionnaire. The students completed the initial analysis which was followed by a more detailed analysis by the authors of this paper. The findings support the work of American, British and Australian researchers about the factors that influence engagement and disengagement from schooling. The reported outcomes from the student work and the secondary analysis indicate that students do have the capacity to undertake valid and meaningful research and can make informed contributions to school improvement and student engagement.

Teachers as advocates for widening participation

In England and Australia, higher education institutions (HEIs) are expected to widen participation (WP) in higher education (HE) to enhance social justice and improve individual and national economic returns. Furthermore, HEIs are the major providers of initial and in-service teacher education. This article surveys international literature to explore ways in which teacher education programmes could and do contribute to preparing teachers to advocate for WP, including drawing on learning from WP research that demonstrates the value of current HE students engaging young people in schools and colleges to support them in seriously considering progressing to HE. We conclude that teachers and pre-service teachers are well placed to be advocates for WP. In the majority of higher education institutions, however, WP and teacher education functions are not working collaboratively to embed advocacy for WP into teacher education programmes.

Education in City and Suburban Communities

This chapter will discuss how environmental factors, specifically one’s backgrounds and where one lives, has an impact on teaching and learning. You have learned from previous chapters that inclusive education is underpinned by human rights and social justice issues. This chapter takes up that argument by identifying the diversity of students in city and suburban schools and how some are excluded, leading to disengagement with learning. We suggest possible pedagogy such as differentiated instruction and a ‘pedagogy of hope’ to counter student disengagement. Inclusive education, as an ‘act of imagination’ engages students in creative ways with the curriculum, where they can find meaning and purpose in what they are doing. Such engagement allows student to make connections between their school work and their own life worlds.

Human Kallikrein 4 signal peptide induces cytotoxic T cell responses in healthy donors and prostate cancer patients.

Immunotherapy is a promising new treatment for patients with advanced prostate and ovarian cancer, but its application is limited by the lack of suitable target antigens that are recognized by CD8+ cytotoxic T lymphocytes (CTL). Human kallikrein 4 (KLK4) is a member of the kallikrein family of serine proteases that is significantly overexpressed in malignant versus healthy prostate and ovarian tissue, making it an attractive target for immunotherapy. We identified a naturally processed, HLA-A*0201-restricted peptide epitope within the signal sequence region of KLK4 that induced CTL responses in vitro in most healthy donors and prostate cancer patients tested. These CTL lysed HLA-A*0201+ KLK4 + cell lines and KLK4 mRNA-transfected monocyte-derived dendritic cells. CTL specific for the HLA-A*0201-restricted KLK4 peptide were more readily expanded to a higher frequency in vitro compared to the known HLA-A*0201-restricted epitopes from prostate cancer antigens; prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA) and prostatic acid phosphatase (PAP). These data demonstrate that KLK4 is an immunogenic molecule capable of inducing CTL responses and identify it as an attractive target for prostate and ovarian cancer immunotherapy.

Analysing children’s drawings : applied imagination

This article centres on a research project in which freehand drawings provided a richly creative and colourful data source of children’s imagined, ideal learning environments. Issues concerning the analysis of the visual data are discussed, in particular how imaginative content was analysed and how the analytical process was dependent on an accompanying, secondary data source comprising brief, explanatory written texts.

Imagination in school children's choice of their learning environment: An Australian study

A visual research project addressed school children's concepts of ideal learning environments. Drawings and accompanying narratives were collected from Year 5 and Year 6 children in nine Queensland primary schools. The 133 submissions were analysed and coded to develop themes, identify key features and consider the uses of imagination. The children's imagined schools echo ideas promoted by progressive educators. The results of this study suggest benefits for school designers can emerge from the imaginative contributions of children in creating engaging environments, while educational policy makers can benefit from children's ideas in the promotion of engaging, student-centred pedagogies.

Krüppel-associated box (KRAB)-associated co-repressor (KAP-1) Ser-473 phosphorylation regulates heterochromatin protein 1 (HP1- ) mobilization and DNA repair in heterochromatin

The DNA damage response encompasses a complex series of signaling pathways that function to regulate and facilitate the repair of damaged DNA. Recent studies have shown that the repair of transcriptionally inactive chromatin, named heterochromatin, is dependent upon the phosphorylation of the co-repressor, Krüppel-associated box (KRAB) domain-associated protein (KAP-1), by the ataxia telangiectasia-mutated (ATM) kinase. Co-repressors, such as KAP-1, function to regulate the rigid structure of heterochromatin by recruiting histone-modifying enzymes, such HDAC1/2, SETDB1, and nucleosome-remodeling complexes such as CHD3. Here, we have characterized a phosphorylation site in the HP1-binding domain of KAP-1, Ser-473, which is phosphorylated by the cell cycle checkpoint kinase Chk2. Expression of a nonphosphorylatable S473A mutant conferred cellular sensitivity to DNA-damaging agents and led to defective repair of DNA double-strand breaks in heterochromatin. In addition, cells expressing S473A also displayed defective mobilization of the HP1-β chromodomain protein. The DNA repair defect observed in cells expressing S473A was alleviated by depletion of HP1-β, suggesting that phosphorylation of KAP-1 on Ser-473 promotes the mobilization of HP1-β from heterochromatin and subsequent DNA repair. These results suggest a novel mechanism of KAP-1-mediated chromatin restructuring via Chk2-regulated HP1-β exchange from heterochromatin, promoting DNA repair.

BRCA1 is an essential mediator of vinorelbine-induced apoptosis in mesothelioma

The rapeutic options for malignant pleural mesothelioma (MPM) are limited despite the increasing incidence globally. The vinca alkaloid vinorelbine exhibits clinical activity; however, to date, treatment optimization has not been achieved using biomarkers. BRCA1 regulates sensitivity to microtubule poisons; however, its role in regulating vinorelbine-induced apoptosis in mesothelioma is unknown. Here we demonstrate that BRCA1 plays an essential role in mediating vinorelbine-induced apoptosis, as evidenced by (1) the strong correlation between vinorelbine sensitivity and BRCA1 expression level; (2) induction of resistance to vinorelbine by BRCA1 using siRNA oligonucleotides; (3) dramatic down-regulation of BRCA1 following selection for vinorelbine resistance; and (4) the re-activation of vinorelbine-induced apoptosis following re-expression of BRCA1 in resistant cells. To determine whether loss of BRCA1 expression in mesothelioma was potentially relevant in vivo, BRCA1 immunohistochemistry was subsequently performed on 144 primary mesothelioma specimens. Loss of BRCA1 protein expression was identified in 38.9% of samples. Together, these data suggest that BRCA1 plays a critical role in mediating apoptosis by vinorelbine in mesothelioma, warranting its clinical evaluation as a predictive biomarker. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

INT6/EIF3E interacts with ATM and is required for proper execution of the DNA damage response in human cells

Altered expression of the INT6 gene, encoding the e subunit of the translational initiation factor eIF3, occurs in human breast cancers, but how INT6 relates to carcinogenesis remains unestablished. Here, we show that INT6 is involved in the DNA damage response. INT6 was required for cell survival following γ-irradiation and G(2)-M checkpoint control. RNA interference-mediated silencing of INT6 reduced phosphorylation of the checkpoint kinases CHK1 and CHK2 after DNA damage. In addition, INT6 silencing prevented sustained accumulation of ataxia telangiectasia mutated (ATM) at DNA damage sites in cells treated with γ-radiation or the radiomimetic drug neocarzinostatin. Mechanistically, this result could be explained by interaction of INT6 with ATM, which together with INT6 was recruited to the sites of DNA damage. Finally, INT6 silencing also reduced ubiquitylation events that promote retention of repair proteins at DNA lesions. Accordingly, accumulation of the repair factor BRCA1 was defective in the absence of INT6. Our findings reveal unexpected and striking connections of INT6 with ATM and BRCA1 and suggest that the protective action of INT6 in the onset of breast cancers relies on its involvement in the DNA damage response.