Aggravation of ADAMTS and MMP production and ERK1/2 pathway in the interaction of osteoarthritic subchondral bone osteoblasts and articular cartilage chondrocytes : a possible pathogenic role in osteoarthritis

Introduction: Degradative enzymes, such as A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) and matrix metalloproteinases (MMPs), play key roles in osteoarthritis (OA) development. The aim of the present study was to investigate if cross-talk between subchondral bone osteoblasts (SBOs) and articular cartilage chondrocytes (ACCs) in OA alters the expression and regulation of ADAMTS5, ADAMTS4, MMP-1, MMP-2, MMP-3, MMP-8, MMP-9 and MMP-13, and also to test the possible involvement of mitogen activated protein kinase (MAPK) signaling pathway during this process. Methods: ACCs and SBOs were isolated from normal and OA patients. An in vitro co-culture model was developed to study the regulation of ADAMTS and MMPs under normal and OA joint cross-talk conditions. MAPK-ERK inhibitor, PD98059 was applied to delineate the involvement of specific pathway during this interaction process. Results: Indirect co-culture of OA SBOs with normal ACCs resulted in significantly increased expression of ADAMTS5, ADAMTS4, MMP-2, MMP-3 and MMP-9 in ACCs, whereas co-culture of OA ACCs led to increased MMP-1 and MMP-2 expression in normal SBOs. The upregulation of ADAMTS and MMPs under these conditions was correlated with activation of the MAPK-ERK1/2 signaling pathway and the addition of the MAPK-ERK inhibitor, PD98059, reversed the overexpression of ADAMTS and MMPs in co-cultures. Conclusion: In summary, we believe, these results add to the evidence that in human OA, altered bi-directional signals transmitted between SBOs and ACCs significantly impacts the critical features of both cartilage and bone by producing abnormal levels of ADAMTS and MMPs. Furthermore, we have demonstrated for the first time that this altered cross-talk was mediated by the phosphorylation of MAPK-ERK1/2 signaling pathway.

Competition and innovation : independent production in the Chinese TV industry

Independent television production is recognised for its capacity to generate new kinds of program content, as well as deliver innovation in formats. Globally, the television industry is entering into the post-broadcasting era where audiences are fragmented and content is distributed across multiple platforms. The effects of this convergence are now being felt in China, as it both challenges old statist models and presents new opportunities for content innovation. This thesis discusses the status of independent production in China, making relevant comparisons with independent production in other countries. Independent television production has become an important element in the reform of broadcasting in China in the past decade. The first independent TV production company was registered officially in 1994. While there are now over 4000 independent companies, the term „independent. does not necessarily constitute autonomy. The question the thesis addresses is: what is the status and nature of independence in China? Is it an appropriate term to use to describe the changing environment, or is it a misnomer? The thesis argues that Chinese independents operate alongside the mainstream state-owned system; they are „dependent. on the mainstream. Therefore independent television in China is a relative term. By looking at several companies in Beijing, mainly in entertainment, TV drama and animation, the thesis shows how the sector is injecting fresh ideas into the marketplace and how it plays an important role in improving innovation in many aspects of the television industry. The thesis shows how independent television companies in China are looking to protect their property rights. It demonstrates that far from being at the cutting edge, independents are reliant on a system that has many inbuilt structural problems. The thesis outlines many of the challenges facing 'independents'.

Analysis of productive performance of crop and animal production systems : an integrated analytical framework

This article presents a two-stage analytical framework that integrates ecological crop (animal) growth and economic frontier production models to analyse the productive efficiency of crop (animal) production systems. The ecological crop (animal) growth model estimates "potential" output levels given the genetic characteristics of crops (animals) and the physical conditions of locations where the crops (animals) are grown (reared). The economic frontier production model estimates "best practice" production levels, taking into account economic, institutional and social factors that cause farm and spatial heterogeneity. In the first stage, both ecological crop growth and economic frontier production models are estimated to calculate three measures of productive efficiency: (1) technical efficiency, as the ratio of actual to "best practice" output levels; (2) agronomic efficiency, as the ratio of actual to "potential" output levels; and (3) agro-economic efficiency, as the ratio of "best practice" to "potential" output levels. Also in the first stage, the economic frontier production model identifies factors that determine technical efficiency. In the second stage, agro-economic efficiency is analysed econometrically in relation to economic, institutional and social factors that cause farm and spatial heterogeneity. The proposed framework has several important advantages in comparison with existing proposals. Firstly, it allows the systematic incorporation of all physical, economic, institutional and social factors that cause farm and spatial heterogeneity in analysing the productive performance of crop and animal production systems. Secondly, the location-specific physical factors are not modelled symmetrically as other economic inputs of production. Thirdly, climate change and technological advancements in crop and animal sciences can be modelled in a "forward-looking" manner. Fourthly, knowledge in agronomy and data from experimental studies can be utilised for socio-economic policy analysis. The proposed framework can be easily applied in empirical studies due to the current availability of ecological crop (animal) growth models, farm or secondary data, and econometric software packages. The article highlights several directions of empirical studies that researchers may pursue in the future.

Power relations and small and medium-sized enterprise strategies for capturing value in global production networks: visual effects (VFX) service firm in the Hollywood film industry

Power relations and small and medium-sized enterprise strategies for capturing value in global production networks: visual effects (VFX) service firms in the Hollywood film industry, Regional Studies. This paper provides insights into the way in which non-lead firms manoeuvre in global value chains in the pursuit of a larger share of revenue and how power relations affect these manoeuvres. It examines the nature of value capture and power relations in the global supply of visual effects (VFX) services and the range of strategies VFX firms adopt to capture higher value in the global value chain. The analysis is based on a total of thirty-six interviews with informants in the industry in Australia, the United Kingdom and Canada, and a database of VFX credits for 3323 visual products for 640 VFX firms.

Microbial colonisation of human follicular fluid and adverse in vitro fertilisation outcomes

This study, investigating 263 women undergoing trans-vaginal oocyte retrieval for in vitro fertilisation (IVF) found that microorganisms colonising follicular fluid contributed to adverse IVF (pre-implantation) and pregnancy (post-implantation) outcomes including poor quality embryos, failed pregnancy and early pregnancy loss (< 37 weeks gestation). Some microorganisms also showed in vitro growth patterns in liquid media that appeared to be enhanced by the hormonal stimulation protocol used for oocyte retrieval. Elaborated cytokines within follicular fluid were also associated with adverse IVF outcomes. This study is imperative because infertility affects 16% of the human population and the numbers of couples needing assistance continues to increase. Despite significant improvements in the technical aspects of assisted reproductive technologies (ART), the live birth rate has not increased proportionally. Overt genital tract infection has been associated with both infertility and adverse pregnancy outcomes (including miscarriage and preterm birth) as a direct result of the infection or the host response to it. Importantly, once inflammation had become established, medical treatment often failed to prevent these significant adverse outcomes. Current evaluations of fertility focus on the ovary as a site of steroid hormone production and ovulation. However, infertility as a result of subclinical colonisation of the ovary has not been reported. Furthermore, identification of the microorganisms present in follicular fluid and the local cytokine profile may provide clinicians with an early indication of the prognosis for IVF treatment in infertile couples, thus allowing antimicrobial treatment and/or counselling about possible IVF failure. During an IVF cycle, multiple oocytes undergo maturation in vivo in response to hormonal hyperstimulation. Oocytes for in vitro insemination are collected trans-vaginally. The follicular fluid that bathes the maturing oocyte in vivo, usually is discarded as part of the IVF procedure, but provides a unique opportunity to investigate microbial causes of adverse IVF outcomes. Some previous studies have identified follicular fluid markers that predict IVF pregnancy outcomes. However, there have not been any detailed microbiological studies of follicular fluid. For this current study, paired follicular fluid and vaginal secretion samples were collected from women undergoing IVF cycles to determine whether microorganisms in follicular fluid were associated with adverse IVF outcomes. Microorganisms in follicular fluid were regarded as either "colonisers" or "contaminants"; colonisers, if they were unique to the follicular fluid sample, and contaminants if the same microorganisms were detected in the vaginal and follicular fluid samples indicating that the follicular fluid was merely contaminated during the oocyte retrieval process. Quite unexpectedly, by these criteria, we found that follicular fluid from approximately 30% of all subjects was colonised with bacteria. Fertile and infertile women with colonised follicular fluid had decreased embryo transfer rates and decreased pregnancy rates compared to women with contaminated follicular fluids. The observation that follicular fluid was not always sterile, but contained a diverse range of microorganisms, is novel. Many of the microorganisms we detected in follicular fluid are known opportunistic pathogens that have been detected in upper genital tract infections and are associated with adverse pregnancy outcomes. Bacteria were able to survive for at least 28 weeks in vitro, in cultures of follicular fluid. Within 10 days of establishing these in vitro cultures, several species (Lactobacillus spp., Bifidobacterium spp., Propionibacterium spp., Streptococcus spp. and Salmonella entericus) had formed biofilms. Biofilms play a major role in microbial pathogenicity and persistence. The propensity of microbial species to form biofilms in follicular fluid suggests that successful treatment of these infections with antimicrobials may be difficult. Bifidobacterium spp. grew, in liquid media, only if concentrations of oestradiol and progesterone were similar to those achieved in vivo during an IVF cycle. In contrast, the growth of Streptococcus agalactiae and Escherichia coli was inhibited or abolished by the addition of these hormones to culture medium. These data suggest that the likelihood of microorganisms colonising follicular fluid and the species of bacteria involved is influenced by the stage of the menstrual cycle and, in the case of IVF, the nature and dose of steroid hormones administered for the maturation of multiple oocytes in vivo. Our findings indicate that the elevated levels of steroid hormones during an IVF cycle may influence the microbial growth within follicular fluid, suggesting that the treatment itself will impact on the microflora present in the female upper genital tract during pre-conception and early post-conception phases of the cycle. The effect of the host immune response on colonising bacteria and on the outcomes of IVF also was investigated. White blood cells reportedly compose between 5% and 15% of the cell population in follicular fluid. The follicular membrane is semi-permeable and cells are actively recruited as part of the normal menstrual cycle and in response to microorganisms. A previous study investigated follicular fluid cytokines from infertile women and fertile oocyte donors undergoing IVF, and concluded that there were no significant differences in the cytokine concentrations between the two groups. However, other studies have reported differences in the follicular fluid cytokine levels associated with infertile women with endometriosis or polycystic ovary syndrome. In this study, elevated levels of interleukin (IL)-1 á, IL-1 â and vascular endothelial growth factor (VEGF) in vaginal fluid were associated with successful fertilisation, which may be useful marker for successful fertilisation outcomes for women trying to conceive naturally or prior to oocyte retrieval for IVF. Elevated levels of IL-6, IL-12p40, granulocyte colony stimulating factor (GCSF) and interferon-gamma (IFN ã) in follicular fluid were associated with successful embryo transfer. Elevated levels of pro-inflammatory IL-18 and decreased levels of anti-inflammatory IL-10 were identified in follicular fluid from women with idiopathic infertility. Successful fertilisation and implantation is dependent on a controlled pro-inflammatory environment, involving active recruitment of pro-inflammatory mediators to the genital tract as part of the menstrual cycle and early pregnancy. However, ongoing pregnancy requires an enhanced anti-inflammatory environment to ensure that the maternal immune system does not reject the semi-allergenic foetus. The pro-inflammatory skew in the follicular fluid of women with idiopathic infertility, correlates with normal rates of fertilisation, embryo discard and embryo transfer, observed for this cohort, which were similar to the outcomes observed for fertile women. However, their pregnancy rate was reduced compared to fertile women. An altered local immune response in follicular fluid may provide a means of explaining infertility in this cohort, previously defined as 'idiopathic'. This study has found that microorganisms colonising follicular fluid may have contributed to adverse IVF and pregnancy outcomes. Follicular fluid bathes the cumulus oocyte complex during the in vivo maturation process, and microorganisms in the fluid, their metabolic products or the local immune response to these microorganisms may result in damage to the oocytes, degradation of the cumulus or contamination of the IVF culture system. Previous studies that have discounted bacterial contamination of follicular fluid as a cause of adverse IVF outcomes failed to distinguish between bacteria that were introduced into the follicular fluid at the time of trans-vaginal oocyte retrieval and those that colonised the follicular fluid. Those bacteria that had colonised the fluid may have had time to form biofilms and to elicit a local immune response. Failure to draw this distinction has previously prevented consideration of bacterial colonisation of follicular fluid as a cause of adverse IVF outcomes. Several observations arising from this study are of significance to IVF programs. Follicular fluid is not always sterile and colonisation of follicular fluid is a cause of adverse IVF and pregnancy outcomes. Hormonal stimulation associated with IVF may influence whether follicular fluid is colonised and enhance the growth of specific species of bacteria within follicular fluid. Bacteria in follicular fluid may form biofilms and literature has reported that this may influence their susceptibility to antibiotics. Monitoring the levels of selected cytokines within vaginal secretions may inform fertilisation outcomes. This study has identified novel factors contributing to adverse IVF outcomes and that are most likely to affect also natural conception outcomes. Early intervention, possibly using antimicrobial or immunological therapies may reduce the need for ART and improve reproductive health outcomes for all women.

Re-engaging marginalized youth through digital music production: performance, audience and evaluation

This paper presents two case studies of marginalised youth experimenting with digital music production in flexible education settings. The cases were drawn from a three-year study of alternative assessment in flexible learning centres that enrol 650+ students who have left formal schooling in Queensland, Australia. The cases are framed in reference to the literature on cultural studies approaches to education and the digital arts. Each case describes the student’s histories, cultural background and experiences, music productions, evidence of learning and re-engagement with education. Findings document how digital music production can re-engage and extend participation among students who have left formal education. They do so by theorising the online judgements and blog comments about the digital music production as a social field of exchange. It also raises critical questions about the adequacy of current approaches to evaluating and accounting for the learning and development of such youth, especially where this has occurred through creative arts and digital production.

The film studio: film production in the global economy

The Film Studio sheds new light on the evolution of global film production, highlighting the role of film studios worldwide. The authors explore the contemporary international production environment, alleging that global competition is best understood as an unequal and unstable partnership between the 'design interest' of footloose producers and the 'location interest' of local actors. Ben Goldsmith and Tom O'Regan identify various types of film studios and investigate the consequences for Hollywood, international film production, and the studio locations.

Local Hollywood: global film production and the Gold Coast

Hollywood films and television programs are watched by a global audience. While many of these productions are still made in southern California, the last twenty years have seen new production centres emerge in the US, Canada and other locations worldwide. Global Hollywood has been made possible by this growing number of Local Hollywoods: locations equipped with the requisite facilities, resources and labour, as well as the political will and tax incentives, to attract and retain high-budget, Hollywood-standard projects. This new book gives an unprecedented insight into how the Gold Coast became the first outpost of Hollywood in Australia. When a combination of forces drove Hollywood studios and producers to work outside California, the Gold Coast's unique blend of government tax support, innovative entrepreneurs and diverse natural settings made it a perfect choice to host Hollywood productions. 'Local Hollywood' makes an essential contribution to the field of film and media studies, as well as giving film buffs a behind-the-scenes tour of the film industry.

Hydrothermal technologies for the production of fuels and chemicals from biomass

Biomass and non-food crop residues are seen as relatively low cost and abundant renewable sources capable of making a large contribution to the world’s future energy and chemicals supply. Signifi cant quantities of ethanol are currently produced from biomass via biochemical processes, but thermochemical conversion processes offer greater potential to utilize the entire biomass source to produce a range of products. This chapter will review thermochemical gasifi cation and pyrolysis methods with a focus on hydrothermal liquefaction processes. Hydrothermal liquefaction is the most energetically advantageous thermochemical biomass conversion process. If the target is to produce sustainable liquid fuels and chemicals and reduce the impact of global warming as a result of carbon dioxide, nitrous oxide, and methane emissions (i.e., protect the natural environment), the use of “green” solvents, biocatalysts and heterogeneous catalysts must be the main R&D initiatives. As the biocrude produced from hydrothermal liquefaction is a complex mixture which is relatively viscous, corrosive, and unstable to oxidation (due to the presence of water and oxygenated compounds), additional upgrading processes are required to produce suitable biofuels and chemicals.

In vitro breeding strategies in the development of Australian native plants

Plant tissue culture is a technique that exploits the ability of many plant cells to revert to a meristematic state. Although originally developed for botanical research, plant tissue culture has now evolved into important commercial practices and has become a significant research tool in agriculture, horticulture and in many other areas of plant sciences. Plant tissue culture is the sterile culture of plant cells, tissues, or organs under aseptic conditions leading to cell multiplication or regeneration or organs and whole plants. The steps required to develop reliable systems for plant regeneration and their application in plant biotechnology are reviewed in countless books. Some of the major landmarks in the evolution of in vitro techniques are summarised in Table 5.1. In this chapter the current applications of this technology to agriculture, horticulture, forestry and plant breeding are briefly described with specific examples from Australian plants when applicable.

Polarization dependent photorefractive amplitude modulation production in MgO:LiNbO 3 phase modulators

We present experimental and theoretical results of the intensity dependence of residual amplitude modulation (RAM) production in electro-optic phase modulators. By utilizing the anisotropy of the medium, we show that RAM has a photorefractive origin.