MT1-MMP correlates with MMP-2 activation potential seen after epithelial to mesenchymal transition in human breast carcinoma cells

We have previously reported that human breast carcinoma (HBC) cell lines expressing the mesenchymal intermediate filament protein vimentin (VIM+) are highly invasive in vitro, and highly metastatic in nude mice when compared to their VIM- counterparts. Since only VIM+ cell lines can be induced to activate matrix metalloproteinase-2 (MMP-2) upon stimulation with Concanavalin A (Con A), we have examined here membrane type 1 MMP (MT1-MMP), a cell surface activator of MMP-2. Northern analysis reveals baseline expression of MT1-MMP in five of the six VIM+ cell lines studied (MDA-MB-231, MDA-MB-435, BT-549, Hs578T, MCF-7(ADR)), each of which showed variable activation of exogenous MMP-2 after treatment with Con A. In contrast, the four VIM-, poorly invasive HBC cell lines studied (MCF-7, T47D, MDA-MB 468, ZR-75-1) lacked baseline MT1-MMP mRNA expression, and showed no induction of either MT1-MMP expression or MMP-2-activation with Con A. Such differential MT1-MMP expression was confirmed in vivo using in situ hybridization analysis of nude mouse tumor xenografts of representative cell lines. Western analysis of the MDA-MB-231 cells revealed baseline membrane expression of a 60 kDa species, which was strongly induced by Con A treatment along with a weaker band co-migrating with that from MT1-MMP-transfected COS-1 cells (63 kDa), presumably representing latent MT1-MMP. MT1-MMP immunofluorescence strongly decorated Con A-stimulated MDA-MB-231 cells in a manner consistent with membranous staining, but did not decorate the unstimulated MDA-MB-231 cells or MCF-7 cells under either condition. Collectively, the results suggest the constitutive production of active MT1-MMP which is unavailable for either MMP-2 activation or immuno-decoration until Con A treatment. Since VIM expression arises by virtue of the so-called epithelial to mesenchymal transition (EMT) in invasive embryonic epithelia, we propose that this represents a major metastasis mechanism in breast carcinomas. MT1-MMP on the surface of such 'fibroblastoid' carcinoma cells may mediate a paracrine loop for the utilization of stromally produced MMP-2, and contribute to the poorer survival associated with VIM+ breast carcinomas.

Induction of tumorigenicity by galectin-3 in a nontumorigenic human breast-carcinoma cell-line

The human galectin-3 is a galactoside-binding protein of 31 kDa which functions as a receptor for glycoproteins containing poly N-acetyllactosamine side chains and as a substrate for matrix metalloproteinases-2 and -9. We studied its expression by flow cytofluorimetry, Western, Northern and Southern analyses, in five cultured human breast carcinoma cell lines previously characterized as non-tumorigenic, poorly metastatic or metastatic in nude mice. The expression of galectin-3 correlated with the reported tumorigenicity of the cells. The introduction of recombinant galectin-3 into the null expressing non-tumorigenic BT-549 cells resulted in the acquisition of anchorage-independent growth properties in alland tumorigenicity in 3/4 sense transfected cell crones. The data indicate a relationship between galectin-3 expression and malignancy of human breast carcinoma cell lines.

The type I collagen induction of MT1-MMP-mediated MMP-2 activation is repressed by αVβ3 integrin in human breast cancer cells

The influence of αVβ3 integrin on MT1-MMP functionality was studied in human breast cancer cells of differing β3 integrin status. Overexpression of β3 integrin caused increased cell surface expression of αV integrin and increased cellular adhesion to extracellular matrix (ECM) substrates in BT-549, MDA-MB-231 and MCF-7 cells. β3 integrin expression also enhanced the migration of breast cancer cells on ECM substrates and enhanced collagen gel contraction. In vivo, αVβ3 cooperated with MT1-MMP to increase the growth of MCF-7 cells after orthotopic inoculation in immunocompromised mice, but had no influence on in vitro proliferation. Despite these stimulatory effects, overexpression of β3 integrin suppressed the type I collagen (Col I) induced MMP-2 activation in all breast cancer cell lines analyzed. This was also evident in extracts from the MCF-7 tumors in vivo, where MMP-2 activation was stimulated by MT1-MMP transfection, but attenuated with β3 integrin expression. Although our studies confirm important biological effects of αVβ3 integrin on enhancing cell adhesion and migration, ECM remodeling and tumor growth, β3 integrin caused reduced MMP-2 activation in response to Col I in vitro, which appears to be physiologically relevant, as it was also seen in tumor xenografts in vivo. The reduction of MMP-2 activation (and thus MT1-MMP activity) by αVβ3 in response to Col I may be important in scenarios where cells which are activated for matrix degradation need to preserve some pericellular collagen, perhaps as a substrate for cell adhesion and migration, thus maintaining a balanced level of proteolysis required for efficient tumor growth.

Social support, self-efficacy, trauma and well-being in emergency medical dispatchers

Emergency Medical Dispatchers (EMDs) respond to crisis calls for ambulance; they dispatch paramedics and provide emotional and medical assistance to callers. Despite the stressful nature and exposure to potentially traumatising events in this role, there has been no published research specifically investigating well-being or posttraumatic growth among EMDs. Extrapolating from research conducted among other emergency services workers (e. g., paramedics, police), literature attests to the importance of self efficacy and social support in promoting mental health in emergency service workers. Therefore, this study assessed the impact of self efficacy, and giving and receiving social support on psychological well-being, posttraumatic growth (PTG), and symptoms of posttraumatic stress disorder (PTSD). Sixty EMDs (50% response rate) completed an online questionnaire. Three hierarchical multiple regression analyses were conducted to ascertain predictors of well-being, PTG and PTSD. Receiving social support emerged as a significant positive predictor of well-being and PTG, and a significant negative predictor of PTSD. Self efficacy was found to significantly and positively predict well-being, and shift-work was found to significantly and negatively predict PTSD. These results highlight that self efficacy and receiving social support are likely to be important for enhancing well-being within this population, and that receiving social support is also likely to facilitate positive post-trauma responses. Such findings have implications for the way emergency service personnel are educated with reference to aspects of mental health and how best to support personnel in order to achieve optimal mental health outcomes for all.

Kumarina and bidders voting in transfer schemes

Transfer schemes are an alternative means of acquiring control of a company to making a takeover bid under the provisions in Ch 6 of the Corporations Act 2001 (Cth). The recent decision Re Kumarina Resources Ltd [2013] FCA 549 overturned long-standing practice in relation to a certain type of transfer scheme. If followed, the decision would allow a “bidder” to vote at scheme meetings where the scheme consideration for the acquisition of the target shares are shares in another company, and the scheme results in a merger. But the bidder is not allowed to vote where the scheme consideration is cash. The article points out the difficulties arising from this decision and argues that it should not be followed. In providing a “no objection” statement, the Australian Securities and Investments Commission (ASIC) has created uncertainty as to the approach it will take towards the bidders being allowed to vote at scheme meetings where the scheme consideration for the acquisition of target shares are shares in another company. The article also points out that in providing the no objection statement in Kumarina, ASIC appears to have ignored breaches of s 606(1) of the Corporations Act. There is a pressing need for ASIC to clarify its position and, in particular, whether or not it will provide a no objection statement in respect of future transfer schemes where a bidder (or its parent company) votes at the scheme meeting.

Raewyn Connell: Hegemonic Masculinities and Men’s Health

This handbook offers a new perspective on the sociology of health, illness and medicine by stressing the importance of social theory, and giving due attention to theorists often overlooked in the healthcare field including Harriet Martineau and Raewyn Connell, as well as more widely known theorists such as Michel Foucault and Max Weber. This is a compendium of both male and female social theorists from the turn of the 19th century to the present day. Leading international sociologists from Europe, America, Britain, Australia, New Zealand and Canada investigate the key concepts and theories of a single theorist, looking at the way their ideas such as medicalisation, reflexivity, capitalism, hegemonic masculinity, the biomedical model and social stigma can be used to understand specific health issues including men's health, Indigenous health, disability, the health professions and chronic illness.

A holistic model for blended learning

While the studio environment has been promoted as an ideal educational setting for project-based disciplines, few qualitative studies have been undertaken in a comprehensive way (Bose, 2007). This study responds to this need by adopting Grounded Theory methodology in a qualitative comparative approach. The research aims to explore the limitations and benefits of a face-to-face (f2f) design studio as well as a virtual design studio (VDS) as experienced by architecture students and educators at an Australian university in order to find the optimal combination for a blended environment to maximize learning. The main outcome is a holistic multidimensional blended model being sufficiently flexible to adapt to various setting, in the process, facilitating constructivist learning through self-determination, self-management, and personalization of the learning environment.

Member perceptions of ESG investing through superannuation

Purpose Environmental, social and governance (ESG) risks have the potential to negatively impact financial returns, yet few superannuation funds integrate these considerations into their investment selection. The Cooper Review (2010) identified a lack of member demand as a key impediment to ESG investing by superannuation funds. Given this problem, the aim of this study is to explore superannuation fund members’ perceptions of ESG investing by their funds in order to identify reasons for the lack of demand. Design/methodology/approach An on-line survey was developed and distributed to assess possible reasons why members do not select ESG investment options. In total, 549 Australian superannuation fund members responded to the survey. Findings Results indicate that the majority of superannuation fund members are interested in ESG investing. Members lack awareness of their fund’s approach to ESG investing, and they do not perceive there to be a financial penalty from ESG investing. Finally, members show a preference for consideration of governance issues over both social and environmental issues. Research limitations Respondents are well educated and the majority did not choose their superannuation fund. There was no measure of financial literacy included in the research instrument. There is also a general limitation in surveying superannuation fund members when they lack knowledge about superannuation. Practical implications The results indicate that superannuation members are interested in both superannuation and ESG investing. Given the low take-up of ESG investment options, this finding raises the question of how effectively funds are engaging their members. Social implications The results should be of interest to superannuation funds and may lead to renewed interest in promoting ESG products. Originality/value This is the first study to examine superannuation members’ attitudes and behaviours towards ESG investing in the context of superannuation. The study also adds to our understanding of member decision making in the $1.8 trillion superannuation industry.

Global, regional, and national age–sex specifi c all-cause and cause-specifi c mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specific all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specific causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65·3 years (UI 65·0–65·6) in 1990, to 71·5 years (UI 71·0–71·9) in 2013, while the number of deaths increased from 47·5 million (UI 46·8–48·2) to 54·9 million (UI 53·6–56·3) over the same interval. Global progress masked variation by age and sex: for children, average absolute differences between countries decreased but relative differences increased. For women aged 25–39 years and older than 75 years and for men aged 20–49 years and 65 years and older, both absolute and relative differences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10·7%, from 4·3 million deaths in 1990 to 4·8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specific mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.

Perspectives on Australian bankruptcy law through the prism of the World Bank report on the treatment of the insolvency of natural persons

The insolvency of natural persons raises questions not only for a nation’s economy but also for its concern for equity. The World Bank has recently released a Report on the Treatment of the Insolvency of Natural Persons to guide nations in addressing the issues raised by an individual debtor’s insolvency. A brief review of Australia’s personal insolvency laws shows that it addresses many of the issues raised by the Report. However two areas are identified as worthy of further investigation by policy-makers and scholars to better address a concern for equity.

Can GRI light up the future of mankind?

There is strong evidence across the media that humanity has finally come to recognize the certainty and imminence of a global environmental crisis due to man-triggered ecological alterations. This widespread recognition of what is happening around us has matured even further as studies acknowledging that everything on Earth is interconnected begin to mount across various branches of learning. The appreciation of this simple linear and two-dimensional relationship implies enormous consequences for economic and management studies, as alternative business models will eventually have to supersede the old practices that still govern major industry sectors (e.g. energy, cement, agriculture, automotive, pharmaceutical, etc.). This paper argues that traditional knowledge found in developing countries can sometimes harness the potential of sparking genuine alternatives to established business practices. With a focus on the most fundamental geochemical cycles on Earth − nitrogen, water, and carbon − and the primary resources they govern (soil, water, and air), three case studies are presented to illustrate how traditional knowledge in the context of GRI (Grassroots Innovation) projects can lead to challenge the dominant logic, when allowed to thrive in terms of adoption and scalability.

Inertial sensor real-time feedback enhances the learning of cervical spine manipulation: A prospective study

Background Cervical Spinal Manipulation (CSM) is considered a high-level skill of the central nervous system because it requires bimanual coordinated rhythmical movements therefore necessitating training to achieve proficiency. The objective of the present study was to investigate the effect of real-time feedback on the performance of CSM. Methods Six postgraduate physiotherapy students attending a training workshop on Cervical Spine Manipulation Technique (CSMT) using inertial sensor derived real-time feedback participated in this study. The key variables were pre-manipulative position, angular displacement of the thrust and angular velocity of the thrust. Differences between variables before and after training were investigated using t-tests. Results There were no significant differences after training for the pre-manipulative position (rotation p = 0.549; side bending p = 0.312) or for thrust displacement (rotation p = 0.247; side bending p = 0.314). Thrust angular velocity demonstrated a significant difference following training for rotation (pre-training mean (sd) 48.9°/s (35.1); post-training mean (sd) 96.9°/s (53.9); p = 0.027) but not for side bending (p = 0.521). Conclusion Real-time feedback using an inertial sensor may be valuable in the development of specific manipulative skill. Future studies investigating manipulation could consider a randomized controlled trial using inertial sensor real time feedback compared to traditional training.

Attainment of early feeding milestones in preterm neonates

Objective: This study aimed to document the ages at which preterm neonates commence suckle-feeds and attain exclusive suckle-feeding, as well as the time taken to transition from commencement of suckle-feeds to exclusive suckle-feeding. It was hypothesized that gestational age (GA) at birth and degree of neonatal morbidity would influence the timing of these early feeding milestones. Study Design: A chart review was conducted for all neonates born <37;0 weeks GA admitted to a tertiary level perinatal facility over a 12-month period (n=735). Complete data relating to attainment of feeding milestones were available on 472 neonates. Results: Correlation analysis indicated that both a low GA at birth and a high neonatal morbidity rating were statistically significantly correlated with an increased transition time from commencement of suckle-feeds to exclusive suckle-feeding. Cox regression indicated that both of these variables were statistically significant risk factors for a delayed GA at attainment of exclusive suckle-feeding. Conclusion: Preterm neonates who were less mature at birth and/or who displayed a greater degree of neonatal morbidity took longer to transition from starting suckle-feeds to achieving independent suckle-feeding, and were more mature at attainment of independent suckle-feeding.

Consultation with Aboriginal and Torres Strait Islander people in early childhood education: The impact of colonial discourses

In Australian early years education, consultation and partnerships with Aboriginal and Torres Strait Islander people are central to embedding Indigenous perspectives. Building sustained and reciprocal partnerships with Aboriginal and Torres Strait Islander people supports access to local knowledges and perspectives to inform curriculum planning, as well as protocols and community processes, and contemporary responses to colonisation. Drawing on data from a doctoral study about embedding Aboriginal and Torres Strait Islander perspectives in early childhood education curricula, this paper examines interactional patterns in consultations between non-Indigenous early childhood educators and Indigenous people in real and supposed form. Data is read through whiteness studies literature and related critiques to identify how the educators positioned Indigenous people in interactional patterns and how the mobilisation of colonial discourses impacted the potential for reciprocity and sustained partnerships, despite the best of intentions. Colonial traces of positioning Indigenous people as informants, targeted resources or knowledge commissioners were shown to be most salient in interactional patterns. While these findings are contextualised within Australia, I suggest they have applicability in examining approaches to embedding Indigenous perspectives in education curricula in other colonising contexts such as Canada and New Zealand.

Species-area and species-individual relationships for tropical trees: A comparison of three 50-ha plots

1 Species-accumulation curves for woody plants were calculated in three tropical forests, based on fully mapped 50-ha plots in wet, old-growth forest in Peninsular Malaysia, in moist, old-growth forest in central Panama, and in dry, previously logged forest in southern India. A total of 610 000 stems were identified to species and mapped to < Im accuracy. Mean species number and stem number were calculated in quadrats as small as 5 m x 5 m to as large as 1000 m x 500 m, for a variety of stem sizes above 10 mm in diameter. Species-area curves were generated by plotting species number as a function of quadrat size; species-individual curves were generated from the same data, but using stem number as the independent variable rather than area. 2 Species-area curves had different forms for stems of different diameters, but species-individual curves were nearly independent of diameter class. With < 10(4) stems, species-individual curves were concave downward on log-log plots, with curves from different forests diverging, but beyond about 104 stems, the log-log curves became nearly linear, with all three sites having a similar slope. This indicates an asymptotic difference in richness between forests: the Malaysian site had 2.7 times as many species as Panama, which in turn was 3.3 times as rich as India. 3 Other details of the species-accumulation relationship were remarkably similar between the three sites. Rectangular quadrats had 5-27% more species than square quadrats of the same area, with longer and narrower quadrats increasingly diverse. Random samples of stems drawn from the entire 50 ha had 10-30% more species than square quadrats with the same number of stems. At both Pasoh and BCI, but not Mudumalai. species richness was slightly higher among intermediate-sized stems (50-100mm in diameter) than in either smaller or larger sizes, These patterns reflect aggregated distributions of individual species, plus weak density-dependent forces that tend to smooth the species abundance distribution and 'loosen' aggregations as stems grow. 4 The results provide support for the view that within each tree community, many species have their abundance and distribution guided more by random drift than deterministic interactions. The drift model predicts that the species-accumulation curve will have a declining slope on a log-log plot, reaching a slope of O.1 in about 50 ha. No other model of community structure can make such a precise prediction. 5 The results demonstrate that diversity studies based on different stem diameters can be compared by sampling identical numbers of stems. Moreover, they indicate that stem counts < 1000 in tropical forests will underestimate the percentage difference in species richness between two diverse sites. Fortunately, standard diversity indices (Fisher's sc, Shannon-Wiener) captured diversity differences in small stem samples more effectively than raw species richness, but both were sample size dependent. Two nonparametric richness estimators (Chao. jackknife) performed poorly, greatly underestimating true species richness.