Epidermal growth factor-induced epithelio-mesenchymal transition in human breast carcinoma cells

PMC42-LA cells display an epithelial phenotype: the cells congregate into pavement epithelial sheets in which E-cadherin and β-catenin are localized at cell-cell borders. They abundantly express cytokeratins, although 5% to 10% of the cells also express the mesenchymal marker vimentin. Stimulation of PMC42-LA cells with epidermal growth factor (EGF) leads to epithelio-mesenchymal transition-like changes including up-regulation of vimentin and down-regulation of E-cadherin. Vimentin expression is seen in virtually all cells, and this increase is abrogated by treatment of cells with an EGF receptor antagonist. The expression of the mesenchyme-associated extracellular matrix molecules fibronectin and chondroitin sulfate proteoglycan also increase in the presence of EGF. PMC42-LA cells adhere rapidly to collagen I, collagen IV, and laminin-1 substrates and markedly more slowly to fibronectin and vitronectin. EGF increases the speed of cell adhesion to most of these extracellular matrix molecules without altering the order of adhesive preference. EGF also caused a time-dependent increase in the motility of PMC42-LA cells, commensurate with the degree of vimentin staining. The increase in motility was at least partly chemokinetic, because it was evident both with and without chemoattractive stimuli. Although E-cadherin staining at cell-cell junctions disappeared in response to EGF, β-catenin persisted at the cell periphery. Further analysis revealed that N-cadherin was present at the cell-cell junctions of untreated cells and that expression was increased after EGF treatment. N- and E-cadherin are not usually coexpressed in human carcinoma cell lines but can be coexpressed in embryonic tissues, and this may signify an epithelial cell population prone to epithelio-mesenchymal-like responses.

Promoting resilience in children with intellectual disability : a randomized controlled trial in Australian schools

Children with intellectual disability are more vulnerable to adverse developmental outcomes because of the lifelong risks associated with cognitive impairment. Difficulties with learning and adaptive behaviour inevitably produce considerable personal, social and economic disadvantage. Of concern is consistent evidence that psychiatric disorders affect a substantial proportion of people with intellectual disability. The estimated prevalence rate of between 35 and 49 % is three times that found in the general population (Wallander, Dekker, & Koot, 2006). Until recently, mental illness has been relatively neglected for people with intellectual disability, especially in relation to prevention or early detection (Kolaitis, 2008) and most research to date has been descriptive rather than focused on intervention (Bouras, 2013). Yet a considerable body of evidence demonstrates that efficacious interventions do exist for preventing psychopathology and enhancing resilience in typically developing children and adolescents (see Mallin, Walker, & Levin, 2013 for a review). In order to prevent the high comorbidity of intellectual disability and psychopathology, there is a compelling need for evidence-based practices that promote the resilience of individuals with intellectual disability (Matson, Terlonge, & Minshawi, 2008). In this chapter, we describe a randomized controlled trial of an intervention that was designed to enhance the resilience of a group of children with mild intellectual disability as they prepared to make the transition to high school. We report results from our evaluation of this intervention, and reflect on the difficulties of providing successful interventions for children whose lives are complicated not only by intellectual disability, but also by a range of contextual disadvantages.

Phosphoprotein pathway mapping: Akt/Mammalian target of rapamycin activation is negatively associated with childhood rhabdomyosarcoma survival

Mapping of protein signaling networks within tumors can identify new targets for therapy and provide a means to stratify patients for individualized therapy. Despite advances in combination chemotherapy, the overall survival for childhood rhabdomyosarcoma remains ∼60%. A critical goal is to identify functionally important protein signaling defects associated with treatment failure for the 40% nonresponder cohort. Here, we show, by phosphoproteomic network analysis of microdissected tumor cells, that interlinked components of the Akt/mammalian target of rapamycin (mTOR) pathway exhibited increased levels of phosphorylation for tumors of patients with short-term survival. Specimens (n = 59) were obtained from the Children's Oncology Group Intergroup Rhabdomyosarcoma Study (IRS) IV, D9502 and D9803, with 12-year follow-up. High phosphorylation levels were associated with poor overall and poor disease-free survival: Akt Ser473 (overall survival P < 0.001, recurrence-free survival P < 0.0009), 4EBP1 Thr37/46 (overall survival P < 0.0110, recurrence-free survival P < 0.0106), eIF4G Ser1108 (overall survival P < 0.0017, recurrence-free survival P < 0.0072), and p70S6 Thr389 (overall survival P < 0.0085, recurrence-free survival P < 0.0296). Moreover, the findings support an altered interrelationship between the insulin receptor substrate (IRS-1) and Akt/mTOR pathway proteins (P < 0.0027) for tumors from patients with poor survival. The functional significance of this pathway was tested using CCI-779 in a mouse xenograft model. CCI-779 suppressed phosphorylation of mTOR downstream proteins and greatly reduced the growth of two different rhabdomyosarcoma (RD embryonal P = 0.00008; Rh30 alveolar P = 0.0002) cell lines compared with controls. These results suggest that phosphoprotein mapping of the Akt/mTOR pathway should be studied further as a means to select patients to receive mTOR/IRS pathway inhibitors before administration of chemotherapy.

A linear-elastic model of anisotropic tumour growth

This paper examines the effect of anisotropic growth on the evolution of mechanical stresses in a linear-elastic model of a growing, avascular tumour. This represents an important improvement on previous linear-elastic models of tissue growth since it has been shown recently that spatially-varying isotropic growth of linear-elastic tissues does not afford the necessary stress-relaxation for a steady-state stress distribution upon reaching a nutrient-regulated equilibrium size. Time-dependent numerical solutions are developed using a Lax-Wendroff scheme, which show the evolution of the tissue stress distributions over a period of growth until a steady-state is reached. These results are compared with the steady-state solutions predicted by the model equations, and key parameters influencing these steady-state distributions are identified. Recommendations for further extensions and applications of this model are proposed.

Setting the research agenda in IHRM

Firstly, on behalf of the secretariat that has coordinated these meetings every two years since 1985, our thanks to the organising committee here at the University of Economics in Cracow, Poland, for hosting this conference. I was asked to offer comment on the research agenda. There are many famous names to refer to. Two Australian colleagues here today are Peter Dowling and Helen De Cieri, longtime stalwarts of the field of IHRM. I acknowledge their contributions over many years, along with Randy Schuler and Denise Welch, and Dennis Briscoe. Other names such as Rosalie Tung, Pawan Bhudwhar, Michael Morley, Paul Sparrow and Wayne Cascio are known to us all. Their books have become classics. One example is the 700 page benchmark 2012 work by Chris Brewster and Wolfgang Mayrhofer, Handbook of Research on Comparative Human Resource Management (Brewster & Mayrhofer, 2012). More recently, in a book published by Cambridge University press in 2014, Mustafa Özbilgin, Dimitria Groutsis and William Harvey offer students a very accessible overview of the basics in IHRM (Ozbilgin, Groutsis, & Harvey, 2014). As for a research agenda, there are excellent literature reviews to which I would refer you, such as those by people who over the years have been frequent participants at this conference (Tarique & Schuler, 2010), (Farndale, Scullion, & Sparrow, 2010), and (Scullion & Collings, 2011).

Keynote address : aligning HR with a changing business landscape

"Firstly, I thank you sincerely for your kind invitation and warm welcome to Sri Lanka and to this national HR conference, I particularly acknowledge the initiative of Chairman of the Technical Committee, Dr Asoka Jinadasa in making it possible for me to be here, and to offer this contribution to your conference. I congratulate you on assembling such an impressive array of talent to aid your discussions. I hope I can add usefully to your conversations. In particular I congratulate you on developing such a good definition of HRM: “A strategic and integrated approach in acquisition, development and engagement of talent using relevant tools, with proper policies, products and processes in creating a conducive climate towards achieving organizational excellence and societal well-being” To me, that means that HR has to add value to the organisation, through an integrated set of tools, competencies, and policies, which are all consistent with the business model..."

Wet hail and thunderstorm electrification

Hailstones in wet growth are commonly found in thunderclouds. While the ice-ice relative growth rate mechanism is generally accepted as the most likely cause of thunderstorm electrification, it is uncertain if this mechanism will operate under wet growth conditions because ice crystals are more likely to stick to the wet surface of a hailstone rather than bounce off it. Experiments were carried out in the laboratory to investigate if there was any charge separated when vapor-grown ice crystals bounced off a wet hailstone. A cloud of supercooled droplets, with and without ice crystals, was drawn past a simulated hailstone. In the dry growth regime, the hailstone charged strongly positive when droplets and crystals co-existed in the cloud. With only droplets in the cloud, there was no charging in the dry growth regime. However, as the hailstone attained wet growth, positive charging currents of about 0.5 and 3.5 pA were observed at 12 and 20 m s-1, respectively. We hypothesize that this observed charging was due to the evaporation of melt water. This so called Dinger-Gunn Effect is due to the ejection of negatively charged minute droplets produced by air bubbles bursting at the surface of the melt water. However the charge separated in wet growth was an order of magnitude smaller than that in dry growth and, therefore, we conclude that it is unlikely to play an important role in the electrification of thunderstorms.

Geographical distribution of human Schistosoma japonicum infection in the Philippines : tools to support disease control and further elimination

S. japonicum infection is believed to be endemic in 28 of the 80 provinces of the Philippines and the most recent data on schistosomiasis prevalence have shown considerable variability between provinces. In order to increase the efficient allocation of parasitic disease control resources in the country, we aimed to describe the small scale spatial variation in S. japonicum prevalence across the Philippines, quantify the role of the physical environment in driving the spatial variation of S. japonicum, and develop a predictive risk map of S. japonicum infection. Data on S. japonicum infection from 35,754 individuals across the country were geo-located at the barangay level and included in the analysis. The analysis was then stratified geographically for Luzon, the Visayas and Mindanao. Zero-inflated binomial Bayesian geostatistical models of S. japonicum prevalence were developed and diagnostic uncertainty was incorporated. Results of the analysis show that in the three regions, males and individuals aged ≥ 20 years had significantly higher prevalence of S. japonicum compared with females and children <5 years. The role of the environmental variables differed between regions of the Philippines. S. japonicum infection was widespread in the Visayas whereas it was much more focal in Luzon and Mindanao. This analysis revealed significant spatial variation in prevalence of S. japonicum infection in the Philippines. This suggests that a spatially targeted approach to schistosomiasis interventions, including mass drug administration, is warranted. When financially possible, additional schistosomiasis surveys should be prioritized to areas identified to be at high risk, but which were underrepresented in our dataset.

Health education and the control of intestinal worm infections in China : a new vision

Background: The transmission of soil-transmitted helminths (STHs) is associated with poverty, poor hygiene behaviour, lack of clean water and inadequate waste disposal and sanitation. Periodic administration of benzimidazole drugs is the mainstay for global STH control but it does not prevent re-infection, and is unlikely to interrupt transmission as a stand-alone intervention. Findings: We reported recently on the development and successful testing in Hunan province, PR China, of a health education package to prevent STH infections in Han Chinese primary school students. We have recently commenced a new trial of the package in the ethnically diverse Xishuangbanna autonomous prefecture in Yunnan province and the approach is also being tested in West Africa, with further expansion into the Philippines in 2015. Conclusions: The work in China illustrates well the direct impact that health education can have in improving knowledge and awareness, and in changing hygiene behaviour. Further, it can provide insight into the public health outcomes of a multi-component integrated control program, where health education prevents re-infection and periodic drug treatment reduces prevalence and morbidity.

Identification of theta-class glutathione S-transferase in liver cytosol of the marmoset monkey

The presence of theta-class glutathione S-transferase (GST) in marmoset monkey liver cytosol was investigated. An anti-peptide antibody targeted against the C-terminus of rGSTT1 reacted with a single band in marmoset liver cytosol that corresponded to a molecular weight of 28 kDa. The intensity of the immunoreactive band was not affected by treatment of marmoset monkeys with 2,3,7,8-tetrachlorodibenzo-p-dioxin, phenobarbitone, rifampicin or clofibric acid. Similarly, activity towards methyl chloride (MC) was unaffected by these treatments. However, GST activity towards 1,2-epoxy3-(p- nitrophenoxy)-propane (EPNP) was increased in marmosets treated with phenobarbitone (2.6-fold) and rifampicin (2.6-fold), activity towards dichloromethane (DCM) was increased by 50% after treatment of marmosets with clofibric acid, and activity towards 1-chloro-2,4-dinitrobenzene (CDNB) was raised slightly (30-42% increases) after treatment with phenobarbitone, rifampicin or clofibric acid. Compared with humans, marmoset liver cytosol GST activity towards DCM was 18-fold higher, activity towards MC was 7 times higher and activity towards CDNB was 4 times higher. Further, EPNP activity was clearly detectable in marmoset liver cytosol samples, but was undetectable in human samples. Immunoreactive marmoset GST was partially purified by affinity chromatography using hexylglutathione-Sepharose and Orange A resin. The interaction of immunoreactive marmoset GST was similar to that found previously for rat and human GSTT1, suggesting that this protein is also a theta class GST. However, unlike rat GSTT1, the marmoset enzyme was not the major catalyst of EPNP conjugation. Instead, immunoreactivity was closely associated with activity towards MC. In conclusion, these results provide evidence for the presence of theta-class GST in the marmoset monkey orthologous to rGSTT1 and hGSTT1.

Creating quality cross-media experiences

There are many ways to create a cross-media project, but there are approaches which facilitate a quality implementation. The crucial starting point with any creative project is a great story or game. However, because the cross-media artform is still emerging and many practitioners are new to the area, just how to produce a quality cross-media project is not well known. Based on my work on both small- and large-scale projects, I outline ten approaches that will aid in facilitating a quality cross-media project.

A transcriptome resource for the koala (Phascolarctos cinereus) : insights into koala retrovirus transcription and sequence diversity

Background The koala, Phascolarctos cinereus, is a biologically unique and evolutionarily distinct Australian arboreal marsupial. The goal of this study was to sequence the transcriptome from several tissues of two geographically separate koalas, and to create the first comprehensive catalog of annotated transcripts for this species, enabling detailed analysis of the unique attributes of this threatened native marsupial, including infection by the koala retrovirus. Results RNA-Seq data was generated from a range of tissues from one male and one female koala and assembled de novo into transcripts using Velvet-Oases. Transcript abundance in each tissue was estimated. Transcripts were searched for likely protein-coding regions and a non-redundant set of 117,563 putative protein sequences was produced. In similarity searches there were 84,907 (72%) sequences that aligned to at least one sequence in the NCBI nr protein database. The best alignments were to sequences from other marsupials. After applying a reciprocal best hit requirement of koala sequences to those from tammar wallaby, Tasmanian devil and the gray short-tailed opossum, we estimate that our transcriptome dataset represents approximately 15,000 koala genes. The marsupial alignment information was used to look for potential gene duplications and we report evidence for copy number expansion of the alpha amylase gene, and of an aldehyde reductase gene. Koala retrovirus (KoRV) transcripts were detected in the transcriptomes. These were analysed in detail and the structure of the spliced envelope gene transcript was determined. There was appreciable sequence diversity within KoRV, with 233 sites in the KoRV genome showing small insertions/deletions or single nucleotide polymorphisms. Both koalas had sequences from the KoRV-A subtype, but the male koala transcriptome has, in addition, sequences more closely related to the KoRV-B subtype. This is the first report of a KoRV-B-like sequence in a wild population. Conclusions This transcriptomic dataset is a useful resource for molecular genetic studies of the koala, for evolutionary genetic studies of marsupials, for validation and annotation of the koala genome sequence, and for investigation of koala retrovirus. Annotated transcripts can be browsed and queried at http://koalagenome.org

Comparing the effectiveness of education and technology in reducing wood smoke pollution: A field experiment

This study describes a field experiment assessing the effectiveness of education and technological innovation in reducing air pollution generated by domestic wood heaters. Two-hundred and twenty four households from a small regional center in Australia were randomly assigned to one of four experimental conditions: (1) Education only – households received a wood smoke reduction education pack containing information about the negative health impacts of wood smoke pollution, and advice about wood heater operation and firewood management; (2) SmartBurn only – households received a SmartBurn canister designed to improve combustion and help wood fires burn more efficiently, (3) Education and SmartBurn, and (4) neither Education nor SmartBurn (control). Analysis of covariance, controlling for pre-intervention household wood smoke emissions, wood moisture content, and wood heater age, revealed that education and SmartBurn were both associated with significant reduction in wood smoke emissions during the post-intervention period. Follow-up mediation analyses indicated that education reduced emissions by improving wood heater operation practices, but not by increasing health risk perceptions. As predicted, SmartBurn exerted a direct effect on emission levels, unmediated by wood heater operation practices or health risk perceptions.

“This is not a burning issue for me”: How citizens justify their use of wood heaters in a city with a severe air pollution problem

Although wood smoke pollution has been linked to health problems, wood burning remains a popular form of domestic heating in many countries across the world. In this paper, we describe the rhetoric of resistance to wood heater regulation amongst citizens in the regional Australian town of Armidale, where wood smoke levels regularly exceed national health advisory limits. We discuss how this is related to particular sources of resistance, such as affective attachment to wood heating and socio-cultural norms. The research draws on six focus groups with participants from households with and without wood heating. With reference to practice theory, we argue that citizen discourses favouring wood burning draw upon a rich suite of justifications and present this activity as a natural and traditional activity promoting comfort and cohesion. Such discourses also emphasise the identity of the town as a rural community and the supposed gemeinschaft qualities of such places. We show that, in this domain of energy policy, it is not enough to present ‘facts’ which have little emotional association or meaning for the populace. Rather, we need understand how social scripts, often localised, inform identity and practice.