Activation of matrix metalloproteinase-2 (MMP-2) by membrane type 1 matrix metalloproteinase through an artificial receptor for ProMMP-2 generates active MMP-2

The suggested model for pro-matrix metalloproteinase-2 (proMMP-2) activation by membrane type 1 MMP (MT1-MMP) implicates the complex between MT1-MMP and tissue inhibitor of MMP-2 (TIMP-2) as a receptor for proMMP-2. To dissect this model and assess the pathologic significance of MMP-2 activation, an artificial receptor for proMMP-2 was created by replacing the signal sequence of TIMP-2 with cytoplasmic/transmembrane domain of type II transmembrane mosaic serine protease (MSP-T2). Unlike TIMP-2, MSP-T2 served as a receptor for proMMP-2 without inhibiting MT1-MMP, and generated TIMP-2-free active MMP-2 even at a low level of MT1-MMP. Thus, MSP-T2 did not affect direct cleavage of the substrate testican-1 by MT1-MMP, whereas TIMP-2 inhibited it even at the level that stimulates proMMP-2 processing. Expression of MSP-T2 in HT1080 cells enhanced MMP-2 activation by endogenous MT1-MMP and caused intensive hydrolysis of collagen gel. Expression of MSP-T2 in U87 glioma cells, which express a trace level of endogenous MT1-MMP, induced MMP-2 activation and enhanced cell-associated protease activity, activation of extracellular signal-regulated kinase, and metastatic ability into chick embryonic liver and lung. MT1-MMP can exert both maximum MMP-2 activation and direct cleavage of substrates with MSP-T2, which cannot be achieved with TIMP-2. These results suggest that MMP-2 activation by MT1-MMP potentially amplifies protease activity, and combination with direct cleavage of substrate causes effective tissue degradation and enhances tumor invasion and metastasis, which highlights the complex role of TIMP-2. MSP-T2 is a unique tool to analyze physiologic and pathologic roles of MMP-2 and MT1-MMP in comparison with TIMP-2.

Epidermal growth factor promotes MDA-MB-231 breast cancer cell migration through a phosphatidylinositol 3'-kinase and phospholipase C-dependent mechanism

Epidermal growth factor receptor (EGFR) levels predict a poor outcome in human breast cancer and are most commonly associated with proliferative effects of epidermal growth factor (EGF), with little emphasis placed on motogenic responses to EGF. We found that MDA-MB-231 human breast cancer cells elicited a potent chemotactic response despite their complete lack of a proliferative response to EGF. Antagonists of EGFR ligation, the EGFR kinase, phosphatidylinositol 3'-kinase, and phospholipase C, but not the mitogen- activated protein kinases (extracellular signal-regulated protein kinase 1 and 2), blocked MDA-MB-231 chemotaxis. These findings suggest that EGF may influence human breast cancer progression via migratory pathways, the signaling for which appears to be dissociated, at least in part, from the proliferative pathways.

Exploring the scope of gene patents through new levels of transparency

As the global intellectual property (IP) system grows and now impacts virtually all citizens, it is crucial that the means to understand these rights and their teachings, as well as their implications and scope become global public goods. To do so requires not only that the primary data is available freely and openly in a standardized and re-useable form, but that tools to visualize, analyse and model that data are similarly open and free public goods, adaptable to diverse needs and uses; this we call ‘transparency’.

Improvements to bauxite residue neutralisation efficiency through the use of alternative feed sources

Currently, open circuit Bayer refineries pump seawater directly into their operations to neutralise the caustic fraction of the Bayer residue. The resulting supernatant has a reduced pH and is pumped back to the marine environment. This investigation has assessed modified seawater sources generated from different ion filtration processes to compare their relative capacities to neutralise bauxite residues. An assessment of the chemical stability of the neutralisation products, neutralisation efficiency, discharge water quality, bauxite residue composition, and associated economic benefits have been considered to determine the most preferable seawater filtration process based on implementation costs, savings to operations and environmental benefits. The mechanism of neutralisation for each technology was determined to be predominately due to the formation of Bayer hydrotalcite and calcium carbonate, however variations in neutralisation capacity and efficiencies have been observed. The neutralisation efficiency of each feed source has been found to be dependent on the concentration of magnesium, aluminium, calcium and carbonate. These studies have revealed that multiple neutralisation steps occur throughout the process. Environmental, economic and social advantages and disadvantages of the different filtration technologies have been explored to determine the most sustainable method for the neutralisation of bauxite residues. The relative degree of “green” associated with nanofiltered seawater and reverse osmosis filtered seawater are discussed.

Building capacity for 21st century engineering through curriculum renewal

At the 2012 CDIO conference, it was clear to all that engineering for 21st Century challenges and opportunities will be critical to the success of society over the next 2-3 decades, in dealing with pressures including climate change, resource depletion and urban densification. Within this context there is a growing imperative for rapid curriculum renewal towards education for sustainable development across all types and disciplines of engineering education, around the world. Building on a paper presented by these authors at the 2012 CDIO conference, this 2013 roundtable will draw on participants’ experiences to discuss how sustainability knowledge and skills can be embedded within a CDIO-based program using a holistic approach to curriculum renewal. The highly interactive and dynamic session will include two parts: 1) a short presentation from the chairs of the roundtable on an emergent model for rapid curriculum renewal; and 2) a facilitated discussion with participants about challenges and opportunities for action. Session notes will be recorded for distribution among participants following the conference.

Transformation in educational practices through STEM

The need for strong science, technology and innovation linkages between Higher Education Institutions (HEIs) and industries is a pivotal point for middle-income countries in their endeavor to enhance human capital in socioeconomic development. Currently, the University-Industry partnerships are at an infant stage in Sri Lankan higher education context. Technological maturity and effective communication skills are contributing factors for an efficient graduate profile. Also, expanding internship programs in particular for STEM disciplines provide work experience to students that would strengthen the relevance of higher education programs. This study reports historical overviews and current trends in STEM education in Sri Lanka. Emphasis will be drawn to recent technological and higher education curricular reforms. Data from the last 10 years were extracted from the higher education sector and Ministry of Higher Education Policy portfolios. Associations and trend analysis of the sector growth were compared with STEM existence, merger and predicted augmentations. Results were depicted and summarised based on STEM streams and disciplines. It was observed that the trend of STEM augmentation in the Sri Lankan Higher Education context is growing at a slow but steady pace. Further analysis with other sectors in particular, Industry information, would be useful and a worthwhile exercise.

Bone sialoprotein supports breast cancer cell adhesion proliferation and migration through differential usage of the αvβ3 and αvβ5 integrins

Bone sialoprotein (BSP), a secreted glycoprotein found in bone matrix, has been implicated in the formation of mammary microcalcifications and osteotropic metastasis of human breast cancer (HBC). BSP possesses an integrin-binding RGD (Arg-Gly-Asp) domain, which may promote interactions between HBC cells and bone extracellular matrix. Purified BSP, recombinant human BSP fragments and BSP-derived RGD peptides are shown to elicit migratory, adhesive, and proliferative responses in the MDA-MB-231 HBC cell line. Recombinant BSP fragment analysis localized a significant component of these activities to the RGD domain of the protein, and synthetic RGD peptides with BSP flanking sequences (BSPRGD) also conferred these responses. The fibronectin-derived RGD counterpart, GRGDSP (Gly-Arg-Gly-Asp-Ser-Pro), could not support these cellular responses, emphasizing specificity of the BSP configuration. Although most of the proliferative and adhesive responses could be attributed to RGD interactions, these interactions were only partly responsible for the migrational responses. Experiments with integrin-blocking antibodies demonstrated that BSP-RGD-induced migration utilizes the αvβ3 vitronectin receptor, whereas adhesion and proliferation responses were αvβ5-mediated. Using fluorescence activated cell sorting, we selected two separate subpopulations of MDA-MB-231 cells enriched for αvβ3 or αvβ5 respectively. Although some expression of the alternate αv integrin was still retained, the αvβ5-enriched MDA-MB-231 cells showed enhanced proliferative and adhesive responses, whereas the αvβ3-enriched subpopulation was suppressed for proliferation and adhesion, but showed enhanced migratory responses to BSP-RGD. In addition, similar analysis of two other HBC cell lines showed less marked, but similar RGD-dependent trends in adhesion and proliferation to the BSP fragments. Collectively, these data demonstrate BSP effects on proliferative, migratory, and adhesive functions in HBC cells and that the RGD-mediated component differentially employs αvβ3 and αvβ5 integrin receptors.

MTI-MMP expression promotes tumor growth and angiogenesis through an up-regulation of vascular endothelial growth factor expression

Membrane type 1 metalloprotease (MT1-MMP) is a transmembrane metalloprotease that plays a major role in the extracellular matrix remodeling, directly by degrading several of its components and indirectly by activating pro-MMP2. We investigated the effects of MT1-MMP overexpression on in vitro and in vivo properties of human breast adenocarcinoma MCF7 cells, which do not express MT1-MMP or MMP-2. MT1-MMP and MMP-2 cDNAs were either transfected alone or cotransfected. All clones overexpressing MT1-MMP 1) were able to activate endogenous or exogenous pro-MMP-2, 2) displayed an enhanced in vitro invasiveness through matrigel-coated filters independent of MMP-2 transfection, 3) induced the rapid development of highly vascularized tumors when injected subcutanously in nude mice, and 4) promoted blood vessels sprouting in the rat aortic ring assay. These effects were observed in all clones overexpressing MT1-MMP regardless of MMP-2 expression levels, suggesting that the production of MMP-2 by tumor cells themselves does not play a critical role in these events. The angiogenic phenotype of MT1-MMP-producing cells was associated with an up-regulation of VEGF expression. These results emphasize the importance of MT1-MMP during tumor angiogenesis and open new opportunities for the development of antiangiogenic strategies combining inhibitors of MT1-MMP and VEGF antagonists. - Sounni, N. E., Devy, L., Hajitou, A., Frankenne, F., Munaut, C., Gilles, C., Deroanne, C., Thompson, E. W., Foidart, J. M., Noel, A. MT1-MMP expression promotes tumor growth and angiogenesis through an up-regulation of vascular endothelial growth factor expression.

Promoting physical activity to older adults through general practice

This study aimed to assess the efficacy of a general practice based intervention to increase physical activity (PA) levels among 50-70 year old adults. One hundred and thirty-six inactive patients (50-70 years) were randomised into three groups. All participants received brief advice and a written prescription from a GP. Group one received this 'usual care' only (GP, n=46); group two received individualised counselling and follow-up contact from an Exercise Scientist (ES, n=45); group three received a pedometer to supplement the ES counselling (PED, n=45). The Active Australia Survey was administered at baseline, after the 12- week intervention and at a 24-week follow-up. One-way ANOVA showed no significant group differences at baseline in self-reported PA. Average time spent walking increased in all three groups at the 24-week follow-up (GP, 68158min/wk, p=0.006; ES, 83160min/wk, p=0.001; PED, 87132min/wk, p<0.001). Total time in PA (weighted min/wk) also increased significantly in all three groups (GP, 98 213min/wk, p=0.003; ES, 108 182min/wk, p<0.001; PED, 158 229min/wk, p<0.001 ). The proportion of participants who initially did not meet National PA Guidelines (150 minutes and 5 sessions/week) but who met the Guidelines at the 12 and 24-week follow-up was 15% (12 weeks) and 20% (24 weeks) in the GP group compared with 36% and 24% in the ES group and 20% and 42% in the PED group. All three intervention strategies were effective in increasing PA, but the ES intervention resulted in a higher proportion of active participants after 12 weeks and the PED group resulted in a higher proportion of active participants after 24 weeks.

Connecting people to their resource consumption through real-time data visualisations

Combining human-computer interaction and urban informatics, this design research developed and tested novel interfaces offering users real-time feedback on their paper and energy consumption. Findings from deploying these interfaces in both domestic and office environments in Australia, the UK, and Ireland, will innovate future generations of resource monitoring technologies. The study draws conclusions with implications for government policy, the energy industry, and sustainability researchers.

Removal of methyl orange from aqueous solutions through adsorption by calcium aluminate hydrates

Methyl orange (MO) is a kind of anionic dye and widely used in industry. In this study, tricalcium aluminate hydrates (Ca-Al-LDHs) are used as an adsorbent to remove methyl orange (MO) from aqueous solutions. The resulting products were studied by X-ray diffraction (XRD), infrared spectroscopy (MIR), thermal analysis (TG-DTA) and scanning electron microscope (SEM). The XRD results indicated that the MO molecules were successfully intercalated into the tricalcium aluminate hydrates, with the basal spacing of Ca-Al-LDH expanding to 2.48 nm. The MIR spectrum for CaAl-MO-LDH shows obvious bands assigned to the N@N, N@H stretching vibrations and S@O, SO_ 3 group respectively, which are considered as marks to assess MO_ ion intercalation into the interlayers of LDH. The overall morphology of CaAl-MOLDH displayed a ‘‘honey-comb’’ like structure, with the adjacent layers expanded.

Improving US airport taxicab services through governance arrangements

Most airports internationally have implemented customer satisfaction programs into their operations to increase non-aeronautical revenues. In the US, taxicabs are an essential airport transport mode given the limited public transport options available. Effective airport taxicab planning can increase airport customer satisfaction levels, as well as facilitate handling increased airport passenger volumes. However, little is known on how US airports have adapted their governance practices from a traditional hierarchical to a network approach in their efforts to undertake airport taxicab planning initiatives since the deregulation of the transportation industry. Data acquired from 51 US hub airports is used to examine their existing taxicab planning practices. The findings offer how US airports can modify governance processes in their airport taxicab planning processes to better support increases in the customer satisfaction levels of airport taxicab patrons.

Differential effects of aging on spatial learning through exploratory navigation and map reading

It has been shown that abilities in spatial learning and memory are adversely affected by aging. The present study was conducted to investigate whether increasing age has equal consequences for all types of spatial learning or impacts certain types of spatial learning selectively. Specifically, two major types of spatial learning, exploratory navigation and map reading, were contrasted. By combining a neuroimaging finding that the medial temporal lobe (MTL) is especially important for exploratory navigation and a neurological finding that the MTL is susceptible to age-related atrophy, it was hypothesized that spatial learning through exploratory navigation would exhibit a greater decline in later life than spatial learning through map reading. In an experiment, young and senior participants learned locations of landmarks in virtual environments either by navigating in them in the first-person perspective or by seeing aerial views of the environments. Results showed that senior participants acquired less accurate memories of the layouts of landmarks than young participants when they navigated in the environments, but the two groups did not differ in spatial learning performance when they viewed the environments from the aerial perspective. These results suggest that spatial learning through exploratory navigation is particularly vulnerable to adverse effects of aging, whereas elderly adults may be able to maintain their map reading skills relatively well.

Audiencing through social media : a brief overview

Notwithstanding the problems with identifying audiences (c.f. Hartley, 1987), nor with sampling them (c.f. Turner, 2005), we contend that by using social media, it is at least possible to gain an understanding of the habits of those who chose to engage with content through social media. In this chapter, we will broadly outline the ways in which networks such as Twitter and Facebook can stand as proxies for audiences in a number of scenarios, and enable content creators, networks and researchers to understand the ways in which audiences come into existence, change over time, and engage with content. Beginning with the classic audience – television – we will consider the evolution of metrics from baseline volume metrics to the more sophisticated ‘telemetrics’ that are the focus of our current work. We discuss the evolution of these metrics, from principles developed in the field of ‘sabermetrics’, and highlight their effectiveness as both a predictor and a baseline for producers and networks to measure the success of their social media campaigns. Moving beyond the evaluation of the audiences engagement, we then move to consider the ‘audiences’ themselves. Building on Hartley’s argument that audiences are “imagined” constructs (1987, p. 125), we demonstrate the continual shift of Australian television audiences, from episode to episode and series to series, demonstrating through our map of the Australian Twittersphere (Bruns, Burgess & Highfield, 2014) both the variation amongst those who directly engage with television content, and those who are exposed to it through their social media networks. Finally, by exploring overlaps between sporting events (such as the NRL and AFL Grand Finals), reality TV (such as Big Brother, My Kitchen Rules & Biggest Loser), soaps (e.g. Bold & The Beautiful, Home & Away), and current affairs programming (e.g. Morning Television & A Current Affair), we discuss to what extent it is possible to profile and categorize Australian television audiences. Finally, we move beyond television audiences to consider audiences around social media platforms themselves. Building on our map of the Australian Twittersphere (Bruns, Burgess & Highfield, 2014), and a pool of 5000 active Australian accounts, we discuss the interconnectedness of audiences around particular subjects, and how specific topics spread throughout the Twitter Userbase. Also, by using Twitter as a proxy, we consider the career of a number of popular YouTuber’s, utilizing a method we refer to as Twitter Accession charts (Bruns & Woodford, 2014) to identify the growth curves, and relate them to specific events in the YouTubers career, be that ‘viral’ videos or collaborations, to discuss how audiences form around specific content creators.

Everyone’s watching it : the role of hype in television engagement through social media

Social media is playing an ever-increasing role in both viewers engagement with television and in the television industries evaluation of programming, in Australia – which is the focus of our study - and beyond. Twitter hashtags and viewer comments are increasingly incorporated into broadcasts, while Facebook fan pages provide a means of marketing upcoming shows and television personalities directly into the social media feed of millions of users. Additionally, bespoke applications such as FanGo and ZeeBox, which interact with the mainstream social networks, are increasingly being utilized by broadcasters for interactive elements of programming (c.f. Harrington, Highfield and Bruns, 2012). However, both the academic and industry study of these platforms has focused on the measure of content during the specific broadcast of the show, or a period surrounding it (e.g. 3 hours before until 3 am the next day, in the case of 2013 Nielsen SocialGuide reports). In this paper, we argue that this focus ignores a significant period for both television producers and advertisers; the lead-up to the program. If, as we argue elsewhere (Bruns, Woodford, Highfield & Prowd, forthcoming), users are persuaded to engage with content both by advertising of the Twitter hash-tag or Facebook page and by observing their network connections engaging with such content, the period before and between shows may have a significant impact on a viewers likelihood to watch a show. The significance of this period for broadcasters is clearly highlighted by the efforts they afford to advertising forthcoming shows through several channels, including television and social media, but also more widely. Biltereyst (2004, p.123) has argued that reality television generates controversy to receive media attention, and our previous small-scale work on reality shows during 2013 and 2014 supports the theory that promoting controversial behavior is likely to lead to increased viewing (Woodford & Prowd, 2014a). It remains unclear, however, to what extent this applies to other television genres. Similarly, while networks use of social media has been increasing, best practices remain unclear. Thus, by applying our telemetrics, that is social media metrics for television based on sabermetric approaches (Woodford, Prowd & Bruns, forthcoming; c.f. Woodford & Prowd, 2014b), to the period between shows, we are able to better understand the period when key viewing decisions may be made, to establish the significance of observing discussions within your network during the period between shows, and identify best practice examples of promoting a show using social media.