Combination of MEK-ERK inhibitor and hyaluronic acid has a synergistic effect on anti-hypertrophic and pro-chondrogenic activities in osteoarthritis treatment

We hypothesised that a potentially disease-modifying osteoarthritis (OA) drug such as hyaluronic acid (HA) given in combination with anti-inflammatory signalling agents such as mitogen-activated protein kinase kinase–extracellular signal-regulated kinase (MEK-ERK) signalling inhibitor (U0126) could result in additive or synergistic effects on preventing the degeneration of articular cartilage. Chondrocyte differentiation and hypertrophy were evaluated using human OA primary cells treated with either HA or U0126, or the combination of HA + U0126. Cartilage degeneration in menisectomy (MSX) induced rat OA model was investigated by intra-articular delivery of either HA or U0126, or the combination of HA + U0126. Histology, immunostaining, RT-qPCR, Western blotting and zymography were performed to assess the expression of cartilage matrix proteins and hypertrophic markers. Phosphorylated ERK (pERK)1/2-positive chondrocytes were significantly higher in OA samples compared with those in healthy control suggesting the pathological role of that pathway in OA. It was noted that HA + U0126 significantly reduced the levels of pERK, chondrocyte hypertrophic markers (COL10 and RUNX2) and degenerative markers (ADAMTs5 and MMP-13), however, increased the levels of chondrogenic markers (COL2) compared to untreated or the application of HA or U0126 alone. In agreement with the results in vitro, intra-articular delivery of HA + U0126 showed significant therapeutic improvement of cartilage in rat MSX OA model compared with untreated or the application of HA or U0126 alone. Our study suggests that the combination of HA and MEK-ERK inhibition has a synergistic effect on preventing cartilage degeneration.

First international workshop on theory and applications of process visualization

The representation of business process models has been a continuing research topic for many years now. However, many process model representations have not developed beyond minimally interactive 2D icon-based representations of directed graphs and networks, with little or no annotation for information over- lays. With the rise of desktop computers and commodity mobile devices capable of supporting rich interactive 3D environments, we believe that much of the research performed in computer human interaction, virtual reality, games and interactive entertainment has much potential in areas of BPM; to engage, pro- vide insight, and to promote collaboration amongst analysts and stakeholders alike. This initial visualization workshop seeks to initiate the development of a high quality international forum to present and discuss research in this field. Via this workshop, we intend to create a community to unify and nurture the development of process visualization topics as a continuing research area.

“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.

Exploring the Pro-Am interface between production and produsage

This conference celebrates the passing of 40 years since the establishment of the Internet (dating this, presumably, to the first connection between two nodes on ARPANET in October 1969). For a gathering of media scholars such as this, however, it may be just as important not only to mark the first testing of the core technologies upon which much of our present-day Net continues to build, but also to reflect on another recent milestone: the 20th anniversary of what is today arguably the chief interface through which billions around the world access and experience the Internet – the World Wide Web, launched by Tim Berners-Lee in 1989.

Volunteering, pro-environmental attitudes and norms

In the spirit of previous work in the compliance literature (e.g., tax, littering), we investigate whether environmental social norms affect volunteering in environmental organizations. Using two ‘environmental morale’ variables as indirect measures, we analyze the impact of social norms on the incidence of unpaid work in environmental organizations. In addition, we test whether violation of a specific environmental norm initiates a conditional cooperation response. We explore a large individual data set covering 32 countries from both Western and Eastern Europe, and extend the number of countries investigated to test the robustness of the relationship at the macro level. Our results indicate a strong positive relationship between the proxies for environmental social norms and volunteering in environmental organizations. The relationship persists despite our various robustness checks.

Pro-Am curators of Australian television history : how is their practice different from that of professional television historians?

Eleven Pro-Am curators of Australian television history were interviewed about their practice. The data helps us to understand the relationship between professional and Pro-Am approaches to Australian television history. There is no simple binary – the lines are blurred – but there are some differences. Pro-Am curators of Australian television history are not paid for their work and present other motivations for practice – particularly being that ‘weird child’ who was obsessed with gathering information and objects related to television. They have freedom to curate only programs and genres that interest them, and they tend to collect merchandise as much as program texts themselves. And they have less interest in formally cataloguing their material than do professional curators of Australian television history.

An interpretative phenomenological analysis of participation in a pro-anorexia Internet site and its relationship to disordered eating

Pro-anorexia Internet sites aim to promote, support and discuss anorexia nervosa. Media coverage has raised concerns that sites may increase the level of eating disorders. This research examines the meaning of participation in a pro-anorexia Internet site and its relationship with disordered eating by using an interpretative phenomenological analysis of fifteen separate message ‘threads’ followed over a six-week period. Four themes were identified: (1) tips and techniques; (2) ‘ana’ v. anorexia nervosa; (3) social support; and (4) need for anorexia. Findings suggest participation was multi-purpose, providing a coping function in relation to weight loss, and the contribution of sites to increased levels of eating disorders is not inevitable.

Pro-inflammatory growth factors reduce secondary degeneration after traumatic spinal cord injury

The role of inflammatory response after spinal cord injury remains unclear. This thesis was a step forward in studying how promoting the inflammation, by delivery pro-inflammatory growth factors, affects the outcomes of spinal cord injury. A significant functional improvement was observed after treatment and these results suggest an interesting avenue for future clinical treatments and may provide a platform to improve the efficacy of other treatments.

PEGylation of lysine residues reduces the pro-migratory activity of IGF-I

Background: The insulin-like growth factor (IGF) system is composed of ligands and receptors which regulate cell proliferation, survival, differentiation and migration. Some functions are regulated via intracellular signaling cascades, others by involvement of the extracellular milieu, including binding proteins and other extracellular matrix proteins. However, understanding of their functions and the exact nature of these interactions remains incomplete. Methods: IGF-I was PEGylated at its lysine sites - K27, K65 and K68. Binding of PEG-IGF-I to the IGFBPs was analyzed using BIAcore and its ability to activate the IGF-IR was assessed using IGF-IR phosphorylation assay. Furthermore, functional consequences of PEGylating the lysine residues of IGF-I was investigated using cell viability and cell migration assays. In addition, particular downstream signaling pathways regularly implicated in these mechanisms were also dissected using phospho-AKT and phospho-ERK1/2 assays. Results: In this study, IGF-I specifically PEGylated at lysine 27 (PEG-K27), 65 (PEG-K65) or 68 (PEG-K68) were employed. Receptor phosphorylation was only reduced by 2-fold with PEG-K65 and PEG-K68 over all the time points tested, and as observed in two cell types, 3T3 fibroblasts and MCF-7 breast cancer cells. PEGylation at K27 resulted in a much larger effect, with more than 10-fold lower activation for 3T3 fibroblasts and a ~3 fold reduced IGF-IR activation for MCF-7 breast cancer cells over 15 minutes. In addition, all PEG-IGF-I variants demonstrated a ten-fold reduction in the association rate to IGF binding proteins (IGFBPs). Functionally, all PEG variants completely lost their ability to induce cell migration in the presence of IGFBP-3/vitronectin (VN) complexes as compared to IGF-I; in contrast, cell viability was fully preserved. Further investigations into the downstream signaling pathways revealed that the PI3-K/AKT pathway was preferentially affected upon treatment with the PEG-IGF-I variants compared to the MAPK/ERK pathway. Conclusion: PEGylation of IGF-I has an impact on cell migration but not cell viability. General significance: PEG-IGF-I may differentially modulate IGF-I mediated functions that are dependent on its interaction with its receptor as well as key extracellular proteins such as VN and IGFBPs.

Pro Bono partnerships : community lawyering to promote environmental justice

Rural communities across Australia are increasingly being asked to shoulder the environmental and social impacts of intensive mining and gas projects. Escalating demand for coal seam gas (CSG) is raising significant environmental justice issues for rural communities. Chief amongst environmental concerns are risks of contamination or depletion of vital underground aquifers as well as treatment and disposal of high-saline water close to high quality agricultural soils. Associated infrastructure such as pipelines, electricity lines, gas processing and port facilities can also adversely affect communities and ecosystems great distances from where the gas is originally extracted. Whilst community submission (and appeal) rights do exist, accessing expert independent information is challenging, legal terminology is complex and submission periods are short, leading ultimately to a lack of procedural justice for landholders and their communities. Since August 2012, Queensland University of Technology (QUT) has worked in partnership with not-for-profit legal centre - Queensland’s Environmental Defenders Office (EDO) - to help better educate communities about mining and CSG assessment processes. The project, now entering its third semester, aims to empower communities to access relevant information and actively engage in legal processes on their own behalf. Students involved in the project so far have helped to research chapters of a comprehensive community guide to mining and CSG law as well as organising multidisciplinary community forums and preparing information on land access and compensation rights for landholders. While environmental justice issues still exist without significant law reform, the project has led to greater awareness amongst the community of the laws relating the CSG. At the same time, it has led to a greater understanding by students and academics of real life environmental justice issues currently faced by rural communities.

IL-23 is pro-proliferative, epigenetically regulated and modulated by chemotherapy in non-small cell lung cancer

Background IL-23 is a member of the IL-6 super-family and plays key roles in cancer. Very little is currently known about the role of IL-23 in non-small cell lung cancer (NSCLC). Methods RT-PCR and chromatin immunopreciptiation (ChIP) were used to examine the levels, epigenetic regulation and effects of various drugs (DNA methyltransferase inhibitors, Histone Deacetylase inhibitors and Gemcitabine) on IL-23 expression in NSCLC cells and macrophages. The effects of recombinant IL-23 protein on cellular proliferation were examined by MTT assay. Statistical analysis consisted of Student's t-test or one way analysis of variance (ANOVA) where groups in the experiment were three or more. Results In a cohort of primary non-small cell lung cancer (NSCLC) tumours, IL-23A expression was significantly elevated in patient tumour samples (p<0.05). IL-23A expression is epigenetically regulated through histone post-translational modifications and DNA CpG methylation. Gemcitabine, a chemotherapy drug indicated for first-line treatment of NSCLC also induced IL-23A expression. Recombinant IL-23 significantly increased cellular proliferation in NSCLC cell lines. Conclusions These results may therefore have important implications for treating NSCLC patients with either epigenetic targeted therapies or Gemcitabine. © 2012 Elsevier Ireland Ltd.