Tetraspanins as regulators of the tumour microenvironment : implications for metastasis and therapeutic strategies

One of the hallmarks of cancer is the ability to activate invasion and metastasis (Hanahan et al., 2011). Cancer morbidity and mortality are largely related to the spread of the primary, localised tumour to adjacent and distant sites (Pantel et al., 2004). Appropriate management and treatment decisions of predicting metastatic disease at the time of diagnosis is thus crucial, which supports better understanding of the metastatic process. There are common events that occur during metastasis: dissociation from the primary tumour mass, reorganisation/remodelling of extracellular matrix, cell migration, recognition and transversal of endothelial cells and the vascular circulation and lodgement and proliferation within ectopic stroma (Wells, 2006). One of the key and initial events is the increased capability of cancer cells to move, escaping the regulation of normal physiological control. The cellular cytoskeleton plays an important role in cancer cell motility and active cytoskeletal rearrangement can result in metastatic disease. This active change in cytoskeletal dynamics results in manipulation of plasma membrane and cellular balance between cellular adhesion and motility which in turn determines cancer cell movement. Members of the tetraspanins play important roles in regulation of cancer migration and cancer-endothelial cell interactions, which are critical for cancer invasion and metastasis. Their involvements in active cytoskeletal dynamics, cancer metastasis and potential clinical application will be discussed in this review. In particular, tetraspanin member, CD151, is highlighted for its major role in cancer invasion and metastasis

Three-dimensional geological modelling of the Galilee and central Eromanga basins, Australia: New insights into aquifer/aquitard geometry and potential influence of faults on inter-connectivity

Study region The Galilee and Eromanga basins are located in central Queensland, Australia. Both basins are components of the Great Artesian Basin which host some of the most significant groundwater resources in Australia. Study focus This study evaluates the influence of regional faults on groundwater flow in an aquifer/aquitard interbedded succession that form one of the largest Artesian Basins in the world. In order to assess the significance of regional faults as potential barriers or conduits to groundwater flow, vertical displacements of the major aquifers and aquitards were studied at each major fault and the general hydraulic relationship of units that are juxtaposed by the faults were considered. A three-dimensional (3D) geological model of the Galilee and Eromanga basins was developed based on integration of well log data, seismic surfaces, surface geology and elevation data. Geological structures were mapped in detail and major faults were characterised. New hydrological insights for the region Major faults that have been described in previous studies have been confirmed within the 3D geological model domain and a preliminary assessment of their hydraulic significance has been conducted. Previously unknown faults such as the Thomson River Fault (herein named) have also been identified in this study.

Emerging water treatment technologies for decentralised systems : an overview of selected systems suited for application in towns and settlements in remote and very remote regions of Australia and vulnerable and lagging rural regions in Sri Lanka

The primary purpose of this paper is to overview a selection of advanced water treatment technology systems that are suited for application in towns and settlements in remote and very remote regions of Australia and vulnerable and lagging rural regions in Sri Lanka. This recognises that sanitation and water treatment are inextricably linked and both are needed to reduce risks to environment and population health from contaminated water sources. For both Australia and Sri Lanka only a small fraction of the settlements in rural and remote regions are connected to water treatment facilities and town water supplies. In Australia’s remote/very remote regions raw water is drawn from underground sources and rainwater capture. Most settlements in rural Sri Lanka rely on rivers, reservoirs, wells, springs or carted water. Furthermore, Sri Lanka has more than 25,000 hand pumped tube wells which saved the communities during recent droughts. Decentralised water supply systems offer the opportunity to provide safe drinking water to these remote/very remote and rural regions where centralised systems are not feasible due to socio-cultural, economic, political, technological reasons. These systems reduce health risks from contaminated water supplies. In remote areas centralized systems fail due to low population density and less affordability. Globally, a new generation of advanced water treatment technologies are positioned to make a major impact on the provision of safe potable water in remote/very remote regions in Australia and rural regions in Sri Lanka. Some of these systems were developed for higher income countries. However, with careful selection and further research they can be tailored to match local socio-economic conditions and technical capacity. As such, they can equally be used to provide decentralised water supply in communities in developed and developing countries such as Australia and Sri Lanka.

Critical literacy finds a 'place': Writing and social action in a low-income Australian grad 2/3 classroom

In a study of socioeconomically disadvantaged children's acquisition of school literacies, a university research team investigated how a group of teachers negotiated critical literacies and explored notions of social power with elementary children in a suburban school located in an area of high poverty. Here we focus on a grade 2/3 classroom where the teacher and children became involved in a local urban renewal project and on how in the process the children wrote about place and power. Using the students' concerns about their neighborhood, the teacher engaged her class in a critical literacy project that not only involved a complex set of literate practices but also taught the children about power and the possibilities for local civic action. In particular, we discuss examples of children's drawing and writing about their neighborhoods and their lives. We explore how children's writing and drawing might be key elements in developing "critical literacies" in elementary school settings. We consider how such classroom writing can be a mediator of emotions, intellectual and academic learning, social practice, and political activism.

Hydrostratigraphic and hydrochemical characterisation of aquifers, aquitards and coal seams in the Galilee and Eromanga basins, Central Queensland, Australia

Inter-aquifer mixing studies are usually made carrying out hydrochemical and isotopic techniques only. In this thesis these techniques have been integrated with three-dimensional geological modelling proving to be a better approach for inter—aquifer mixing assessment in regional areas, and also highlighting the influence of faulting in the understanding of groundwater and gas migration, which could not be possible using the two fist techniques alone. The results are of particular interest for coal seam gas basins and can even be used as exploration tools as areas of higher permeability and gas migration were identified.

Priority threat management of non-native plants to maintain ecosystem integrity across heterogeneous landscapes

Invasive non-native plants have negatively impacted on biodiversity and ecosystem functions world-wide. Because of the large number of species, their wide distributions and varying degrees of impact, we need a more effective method for prioritizing control strategies for cost-effective investment across heterogeneous landscapes. Here, we develop a prioritization framework that synthesizes scientific data, elicits knowledge from experts and stakeholders to identify control strategies, and appraises the cost-effectiveness of strategies. Our objective was to identify the most cost-effective strategies for reducing the total area dominated by high-impact non-native plants in the Lake Eyre Basin (LEB). We use a case study of the ˜120 million ha Lake Eyre Basin that comprises some of the most distinctive Australian landscapes, including Uluru-Kata Tjuta National Park. More than 240 non-native plant species are recorded in the Lake Eyre Basin, with many predicted to spread, but there are insufficient resources to control all species. Lake Eyre Basin experts identified 12 strategies to control, contain or eradicate non-native species over the next 50 years. The total cost of the proposed Lake Eyre Basin strategies was estimated at AU$1·7 billion, an average of AU$34 million annually. Implementation of these strategies is estimated to reduce non-native plant dominance by 17 million ha – there would be a 32% reduction in the likely area dominated by non-native plants within 50 years if these strategies were implemented. The three most cost-effective strategies were controlling Parkinsonia aculeata, Ziziphus mauritiana and Prosopis spp. These three strategies combined were estimated to cost only 0·01% of total cost of all the strategies, but would provide 20% of the total benefits. Over 50 years, cost-effective spending of AU$2·3 million could eradicate all non-native plant species from the only threatened ecological community within the Lake Eyre Basin, the Great Artesian Basin discharge springs. Synthesis and applications. Our framework, based on a case study of the ˜120 million ha Lake Eyre Basin in Australia, provides a rationale for financially efficient investment in non-native plant management and reveals combinations of strategies that are optimal for different budgets. It also highlights knowledge gaps and incidental findings that could improve effective management of non-native plants, for example addressing the reliability of species distribution data and prevalence of information sharing across states and regions.

STEM: Challenges and opportunities for mathematics education

Climbing Mountains, Building Bridges is a rich theme for exploring some of the “challenges, obstacles, links, and connections” facing mathematics education within the current STEM climate (Science, Technology, Engineering and Mathematics). This paper first considers some of the issues and debates surrounding the nature of STEM education, including perspectives on its interdisciplinary nature. It is next argued that mathematics is in danger of being overshadowed, in particular by science, in the global urgency to advance STEM competencies in schools and the workforce. Some suggestions are offered for lifting the profile of mathematics education within an integrated STEM context, with examples drawn from modelling with data in the sixth grade.

Assessing a statistical inquiry

As statistical education becomes more firmly embedded in the school curriculum and its value across the curriculum is recognised, attention moves from knowing procedures, such as calculating a mean or drawing a graph, to understanding the purpose of a statistical investigation in decision making in many disciplines. As students learn to complete the stages of an investigation, the question of meaningful assessment of the process arises. This paper considers models for carrying out a statistical inquiry and, based on a four-phase model, creates a developmental squence that can be used for the assessment of outcomes from each of the four phases as well as for the complete inquiry. The developmental sequence is based on the SOLO model, focussing on the "observed" outcomes during the inquiry process.

Towards the pathogenesis of autoimmune liver disease

There have been recent improvements in the clinical understanding and definition of the major types of autoimmune liver disease. However, still lacking is knowledge of their prevalence and pathogenesis. Three areas of study are in progress in our laboratory. First, in type 1 autoimmune hepatitis, the search continues to identify a liver/disease-specific autoantigenic reactant. Using hepatocyte membrane preparations, immunoblotting has underlined the problem of distinguishing, among multiple reactants, those that may be causally rather than consequentially related to hepatocellular damage. Second, in primary biliary cirrhosis (PBC), the need for population screening to ascertain prevalence and detect preclinical cases can be met by a rapid automated procedure for detection, by specific enzyme inhibition in microtitre wells, of antibody (anti-M2) to the pyruvate dehydrogenase complex E2 subunit (PDC-E2). Third, the structure of the conformational epitope within the inner lipoyl domain of PDC-E2 is being investigated by screening random phage-displayed peptide libraries using PBC sera. This has yielded phage clones in which the sequence of the peptide insert portrays the structure of this epitope, as judged by clustering of PBC-derived sequences to particular branches of a guide-tree that shows relatedness of peptides, and by reactivity of selected phage clones with anti-PDC-E2. Thus phage display identifies a peptide 'mimotope' of the antibody epitope in the inner lipoyl domain of PDC-E2.

Life-course determinants of bone mass in young adults from a transitional rural community in India: The Andhra Pradesh Children and Parents Study (APCAPS)

Background: Undernutrition and physical inactivity are both associated with lower bone mass. Objective: This study aimed to investigate the combined effects of early-life undernutrition and urbanized lifestyles in later life on bone mass accrual in young adults from a rural community in India that is undergoing rapid socioeconomic development. Design: This was a prospective cohort study of participants of the Hyderabad Nutrition Trial (1987–1990), which offered balanced protein-calorie supplementation to pregnant women and preschool children younger than 6 y in the intervention villages. The 2009–2010 follow-up study collected data on current anthropometric measures, bone mineral density (BMD) measured by dual-energy X-ray absorptiometry, blood samples, diet, physical activity, and living standards of the trial participants (n = 1446, aged 18–23 y). Results: Participants were generally lean and had low BMD [mean hip BMD: 0.83 (women), 0.95 (men) g/cm2; lumbar spine: 0.86 (women), 0.93 (men) g/cm2]. In models adjusted for current risk factors, no strong evidence of a positive association was found between BMD and early-life supplementation. On the other hand, current lean mass and weight-bearing physical activity were positively associated with BMD. No strong evidence of an association was found between BMD and current serum 25-hydroxyvitamin D or dietary intake of calcium, protein, or calories. Conclusions: Current lean mass and weight-bearing physical activity were more important determinants of bone mass than was early-life undernutrition in this population. In transitional rural communities from low-income countries, promotion of physical activity may help to mitigate any potential adverse effects of early nutritional disadvantage.

Spatially explicit perceptions of ecosystem services and land cover change in forested regions of Borneo

Spatially explicit information on local perceptions of ecosystem services is needed to inform land use planning within rapidly changing landscapes. In this paper we spatially modelled local people's use and perceptions of benefits from forest ecosystem services in Borneo, from interviews of 1837 people in 185 villages. Questions related to provisioning, cultural/spiritual, regulating and supporting ecosystem services derived from forest, and attitudes towards forest conversion. We used boosted regression trees (BRTs) to combine interview data with social and environmental predictors to understand spatial variation of perceptions across Borneo. Our results show that people use a variety of products from intact and highly degraded forests. Perceptions of benefits from forests were strongest: in human-altered forest landscapes for cultural and spiritual benefits; in human-altered and intact forests landscapes for health benefits; intact forest for direct health benefits, such as medicinal plants; and in regions with little forest and extensive plantations, for environmental benefits, such as climatic impacts from deforestation. Forest clearing for small scale agriculture was predicted to be widely supported yet less so for large-scale agriculture. Understanding perceptions of rural communities in dynamic, multi-use landscapes is important where people are often directly affected by the decline in ecosystem services.

High incidence of contaminating maternal cell overgrowth in human placental mesenchymal stem/stromal cell cultures: A systematic review

Placenta is a readily accessible translationally advantageous source of mesenchymal stem/stromal cells (MSCs) currently used in cryobanking and clinical trials. MSCs cultured from human chorion have been widely assumed to be fetal in origin, despite evidence that placental MSCs may be contaminated with maternal cells, resulting in entirely maternally derived MSC cultures. To document the frequency and determinants of maternal cell contamination in chorionic MSCs, we undertook a PRISMA-compliant systematic review of publications in the PubMed, Medline, and Embase databases (January 2000 to July 2013) on placental and/or chorionic MSCs from uncomplicated pregnancies. Of 147 studies, only 26 (18%) investigated fetal and/or maternal cell origin. After excluding studies that did not satisfy minimal MSC criteria, 7 of 15 informative studies documented MSC cultures as entirely fetal, a further 7 studies reported cultured human chorionic MSC populations to be either maternal (n=6) or mixed (n=1), whereas 1 study separately cultured pure fetal and pure maternal MSC from the same placenta. Maternal cell contamination was associated with term and chorionic membrane samples and greater passage number but was still present in 30% of studies of chorionic villous MSCs. Although most studies assume fetal origin for MSCs sourced from chorion, this systematic review documents a high incidence of maternal-origin MSC populations in placental MSC cultures. Given that fetal MSCs have more primitive properties than adult MSCs, our findings have implications for clinical trials in which knowledge of donor and tissue source is pivotal. We recommend sensitive methods to quantitate the source and purity of placental MSCs.

Adjusting body cell mass for size in women of differing nutritional status

Background: Body cell mass (BCM) may be estimated in clinical practice to assess functional nutritional status, eg, in patients with anorexia nervosa. Interpretation of the data, especially in younger patients who are still growing, requires appropriate adjustment for size. Previous investigations of this general issue have addressed chemical rather than functional components of body composition and have not considered patients at the extremes of nutritional status, in whom the ability to make longitudinal comparisons is of particular importance. Objective: Our objective was to determine the power by which height should be raised to adjust BCM for height in women of differing nutritional status. Design: BCM was estimated by K-40 counting in 58 healthy women, 33 healthy female adolescents, and 75 female adolescents with anorexia nervosa. The relation between BCM and height was explored in each group by using log-log regression analysis. Results: The powers by which height should be raised to adjust BCM,A,ere 1.73. 1.73, and 2.07 in the women, healthy female adolescents, and anorexic female adolescents, respectively. A simplified version of the index, BCM/height(2), was appropriate for all 3 categories and was negligibly correlated with height. Conclusions: In normal-weight women, the relation between height and BCM is consistent with that reported previously between height and fat-free mass. Although the consistency of the relation between BCM and fat-free mass decreases with increasing weight loss, the relation between height and BCM is not significantly different between normal-weight and underweight women. The index BCM/height(2) is easy to calculate and applicable to both healthy and underweight women. This information may be helpful in interpreting body-composition data in clinical practice.

Centile reference charts for total energy expenditure in infants from 1 to 12 months

Background: A knowledge of energy expenditure in infancy is required for the estimation of recommended daily amounts of food energy, for designing artificial infant feeds, and as a reference standard for studies of energy metabolism in disease states. Objectives: The objectives of this study were to construct centile reference charts for total energy expenditure (TEE) in infants across the first year of life. Methods: Repeated measures of TEE using the doubly labeled water technique were made in 162 infants at 1.5, 3, 6, 9 and 12 months. In total, 322 TEE measurements were obtained. The LMS method with maximum penalized likelihood was used to construct the centile reference charts. Centiles were constructed for TEE expressed as MJ/day and also expressed relative to body weight (BW) and fat-free mass (FFM). Results: TEE increased with age and was 1.40,1.86, 2.64, 3.07 and 3.65 MJ/day at 1.5, 3, 6, 9 and 12 months, respectively. The standard deviations were 0.43, 0.47, 0.52,0.66 and 0.88, respectively. TEE in MJ/kg increased from 0.29 to 0.36 and in MJ/day/kg FFM from 0.36 to 0.48. Conclusions: We have presented centile reference charts for TEE expressed as MJ/day and expressed relative to BW and FFM in infants across the first year of life. There was a wide variation or biological scatter in TEE values seen at all ages. We suggest that these centile charts may be used to assess and possibly quantify abnormal energy metabolism in disease states in infants.

A continuum to characterise and support teacher interpretation of an innovative curriculum

A continuum for describing the degree to which teachers interpret the various features of a curriculum is presented. The continuum has been developed based upon the observation of classroom practices and discussions with a group of teachers who are using an innovative junior secondary mathematics curriculum. It is anticipated that the ongoing use of the continuum will lead to its improvement as well as the refinement of the curriculum, more focussed support for the teachers,improved student learning, and the building of explanatory theory regarding mathematics teaching and learning.