Loss of breast epithelial marker hCLCA2 promotes epithelial to mesenchymal transition and indicates higher risk of metastasis

Transition between epithelial and mesenchymal states is a feature of both normal development and tumor progression. We report that expression of chloride channel accessory protein hCLCA2 is a characteristic of epithelial differentiation in the immortalized MCF10A and HMLE models, while induction of epithelial-to-mesenchymal transition by cell dilution, TGFβ or mesenchymal transcription factors sharply reduces hCLCA2 levels. Attenuation of hCLCA2 expression by lentiviral small hairpin RNA caused cell overgrowth and focus formation, enhanced migration and invasion, and increased mammosphere formation in methylcellulose. These changes were accompanied by downregulation of E-cadherin and upregulation of mesenchymal markers such as vimentin and fibronectin. Moreover, hCLCA2 expression is greatly downregulated in breast cancer cells with a mesenchymal or claudin-low profile. These observations suggest that loss of hCLCA2 may promote metastasis. We find that higher-than-median expression of hCLCA2 is associated with a one-third lower rate of metastasis over an 18-year period among breast cancer patients compared with lower-than-median (n=344, unfiltered for subtype). Thus, hCLCA2 is required for epithelial differentiation, and its loss during tumor progression contributes to metastasis. Overexpression of hCLCA2 has been reported to inhibit cell proliferation and is accompanied by increases in chloride current at the plasma membrane and reduced intracellular pH (pHi). We found that knockdown cells have sharply reduced chloride current and higher pHi, both characteristics of tumor cells. These results suggest a mechanism for the effects on differentiation. Loss of hCLCA2 may allow escape from pHi homeostatic mechanisms, permitting the higher intracellular and lower extracellular pH that are characteristic of aggressive tumor cells.

Establishing virtual production as a research and teaching activity at QUT

Located within the Creative Industries Faculty, the Animation team at the Queensland University of Technology (QUT) recently acquired a full-body inertial motion capture system. Our research to date has been predominantly concerned with interdisciplinary practice and the benefits this could bring to undergraduate teaching. From early experimental tests it was identified that there was a need to develop a framework for best practice and an efficient production workflow to ensure the system was being used to its full potential. Through our ongoing investigation we have identified at least three areas that stand to have long-term benefits from universities engaging in motion capture related research activity. This includes interdisciplinary collaborative research, undergraduate teaching and improved production processes. The following paper reports the early stages of our research, which explores the use of a full-body inertial motion capture (MoCap) solution in collaboration with performing artists.

Objectifying the Subjective : Assessment and Feedback in Creative Arts Studio Learning and Teaching

This paper examines the Assessment and Feedback aspects of Studio Teaching as Creative Arts pedagogy. Prompted by USQ’s newly offered Bachelor of Creative Arts (BCA), the author has developed an Assessment Matrix specifically designed to satisfy a number of imperatives, including: • ‘objectifying’ the subjective aspects of creative practice as assessable coursework/research • providing the means by which accurate, detailed, personalised and confidential feedback may be provided to students individually • providing consistent, accurate, meaningful assessment records for student, lecturer, and institution • ensuring consistency, continuity, and transparency of assessment processes and records to satisfy quality audits • minimising marking and assessment time, whilst maximising assessment integrity and depth • requiring only basic level skills and knowledge of a computer application already in common use (Microsoft Excel) • adaptability to a range of creative courses ‐ across disciplines This Assessment Matrix has been in development (and trialled) since January 2009.

The subject and architecture

Invited Presentation on my book Architecture for a Free Subjectivity. In March of 1982, Skyline, the Institute for Architecture and Urban Studies serial, published the landmark interview between Paul Rabinow, an American anthropologist, and Michel Foucault, which would only appear two years later under the title “Space, Knowledge, and Power,” in Rabinow’s edited book The Foucault Reader. Foucault said that in the spatialization of knowledge and power beginning in the 18th century, architecture is not a signifier or metaphor for power, it is rather the “technique for practising social organization.” The role of the IAUS in the architectural dissemination of Foucault’s ideas on the subject and space in the North American academy – such as the concept “heterotopia,” and Foucault’s writing on surveillance and Jeremy Bentham’s Panopticon, subsequently analysed by Georges Teyssot, who was teaching at the Venice School – is well known. Teyssot’s work is part of the historical canalization of Foucauldianism, and French subjectivity more broadly, along its dizzying path, via Italy, to American architecture schools, where it solidified in the 1980s paradigm that would come to be known as American architecture theory. Foucault was already writing on incarceration and prisons, from the 1970s. (In the 1975 lectures he said “architecture was responsible for the invention of madness.”) But this work was not properly incorporated into architectural discussion until the early ’80s. What is not immediately apparent, what this history suggests to me is that subjectivity was not a marginal topic within “theory”, but was perhaps a platform and entry point for architecture theory. One of the ideas that I’m working on is that “theory” can be viewed, historically, as the making of architectural subjectivity, something that can be traced back to the Frankfurt School critique which begins with the modern subject...

Learning and teaching epidemiology with audience response technology

Background The learning and teaching of epidemiology is core to many public health programs. Many students find the content of epidemiology, and specifically risk of bias assessment, challenging to learn. Howbeit, learning is enhanced when knowledge is able to be acquired from an active-learning, hands-on experience. Methods The innovative use of wireless audience response technology “clickers” was incorporated into the lectures of the university’s post-graduate epidemiology units and the tailored epidemiological modules delivered for professional disciplines (e.g. optometry). Clickers were used to apply several pedagogical approaches of active learning including peer-instruction and real-world simulation. Students were also assessed for their gain in knowledge within the lecture (pre-post) and their perceptions of how the use of clickers helped them learn. The routine university-wide end of semester Insight Survey provided further information of the student’s satisfaction with the approach. Results The technology was useful in identifying deficits of knowledge of key concepts either before or after instruction. Where key concepts were re-tested post-lecture, as expected, knowledge increased significantly and provided immediate feed-back to students. Across the lecture series, typically 85% of students identified the technology helped them learn, increased their opportunity to interact with the lecturer, and recommend their use for future classes. The Insight Survey report identified 93% of respondents identified the unit in which clickers were consistently used provided good learning opportunities. Numerous student comments supported the teaching method. Conclusions Epidemiological subject matter lends itself to incorporation of audience response technology. The use of the technology to facilitate interactive voting provides an instant response and participation of everyone to enhance the classroom experience. The pedagogical approach increases students’ knowledge and increases their satisfaction with the unit.

The Australian prehospital pandemic risk perception study and an examination of new public health roles in pandemic response for ambulance services

This report is one of a series of products resulting from a National Health and Medical Research Council (NHMRC) Urgent Research Grant – Pandemic Influenza [No 409973]. The research targeted two key aspects of planning and preparedness for a human influenza pandemic, namely:

Robots, the internet and teaching history in the age of the NBN and the Australian curriculum

Have you ever wished you were Doctor Who and could pop yourself and your students into a Tardis and teleport them to an historical event or to meet a historical figure? We all know that unfortunately time travel is not (yet) possible, but maybe student and teacher teleportation just might be – sort of. Over the past few centuries and in lieu of time travel our communities have developed museums as a means of experiencing some of our history...

Rediscovering law students as citizens: Critical thinking and the public value of legal education

In a series of publications over the last decade, Australian National University Professor Margaret Thornton has documented a disturbing change in the nature of legal education. This body of work culminates in a recently published book based on interviews with 145 legal academics in Australia, the United Kingdom, New Zealand and Canada. In it, Thornton describes a feeling of widespread unease among legal academics that society, government, university administrators and students themselves are moving away from viewing legal education as a public good which benefits both students and society. Instead, legal education is increasingly being viewed as a purely private good, for consumption by the student in the quest for individual career enhancement.

Association between the interleukin 23 receptor and ankylosing spondylitis is confirmed by a new UK case-control study and meta-analysis of published series

Objectives. It has been shown previously that IL-23R variants are associated with AS. We conducted an extended analysis in the UK population and a meta-analysis with the previously published studies, in order to refine these IL-23R associations with AS. Methods. The UK case-control study included 730 new cases and 1331 healthy controls. In the extended study, the 730 cases were combined with 1088 published cases. Allelic associations were analysed using contingency tables. In the meta-analysis, 3482 cases and 3150 controls from four different published studies and the new UK cases were combined. DerSimonian-Laird test was used to calculate random effects pooled odds ratios (ORs). Results. In the UK case-control study with new cases, four of the eight SNPs showed significant associations, whereas in the extended UK study, seven of the eight IL-23R SNPs showed significant associations (P < 0.05) with AS, maximal with rs11209032 (P < 10-5, OR 1.3), when cases with IBD and/or psoriasis were excluded. The meta-analysis showed significant associations with all eight SNPs; the strongest associations were again seen not only with rs11209032 (P = 4.06 × 10-9, OR ∼1.2) but also with rs11209026 (P < 10-10, OR ∼0.6). Conclusions. IL-23R polymorphisms are clearly associated with AS, but the primary causal association(s) is(are) still not established. These polymorphisms could contribute either increased or decreased susceptibility to AS; functional studies will be required for their full evaluation. Additionally, observed stronger associations with SNPs rs11209026 and rs11465804 upon exclusion of IBD and/or psoriasis cases may represent an independent association with AS. © The Author 2009. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.