Irradiation, cisplatin, and 5-azacytidine upregulate cytomegalovirus promoter in tumors and muscles: Implementation of non-invasive fluorescence imaging

Purpose: The cytomegalovirus (CMV) promoter is one of the most commonly used promoters for expression of transgenes in mammalian cells. The aim of our study was to evaluate the role of methylation and upregulation of the CMV promoter by irradiation and the chemotherapeutic agent cisplatin in vivo using non-invasive fluorescence in vivo imaging. Procedures: Murine fibrosarcoma LPB and mammary carcinoma TS/A cells were stably transfected with plasmids encoding CMV and p21 promoter-driven green fluorescent protein (GFP) gene. Solid TS/A tumors were induced by subcutaneous injection of fluorescent tumor cells, while leg muscles were transiently transfected with plasmid encoding GFP under the control of the CMV promoter. Cells, tumors, and legs were treated either by DNA methylation inhibitor 5-azacytidine, irradiation, or cisplatin. GFP expression was determined using a fluorescence microplate reader in vitro and by non-invasive fluorescence imaging in vivo. Results: Treatment of cells, tumors, and legs with 5-azacytidine (re)activated the CMV promoter. Furthermore, treatment with irradiation or cisplatin resulted in significant upregulation of GFP expression both in vitro and in vivo. Conclusions: Observed alterations in the activity of the CMV promoter limit the usefulness of this widely used promoter as a constitutive promoter. On the other hand, inducibility of CMV promoters can be beneficially used in gene therapy when combined with standard cancer treatment, such as radiotherapy and chemotherapy. © 2010 The Author(s).

Shaping development through mechanical strain: The transcriptional basis of diet-induced phenotypic plasticity in a cichlid fish

Adaptive phenotypic plasticity, the ability of an organism to change its phenotype to match local environments, is increasingly recognized for its contribution to evolution. However, few empirical studies have explored the molecular basis of plastic traits. The East African cichlid fish Astatoreochromis alluaudi displays adaptive phenotypic plasticity in its pharyngeal jaw apparatus, a structure that is widely seen as an evolutionary key innovation that has contributed to the remarkable diversity of cichlid fishes. It has previously been shown that in response to different diets, the pharyngeal jaws change their size, shape and dentition: hard diets induce an adaptive robust molariform tooth phenotype with short jaws and strong internal bone structures, while soft diets induce a gracile papilliform tooth phenotype with elongated jaws and slender internal bone structures. To gain insight into the molecular underpinnings of these adaptations and enable future investigations of the role that phenotypic plasticity plays during the formation of adaptive radiations, the transcriptomes of the two divergent jaw phenotypes were examined. Our study identified a total of 187 genes whose expression differs in response to hard and soft diets, including immediate early genes, extracellular matrix genes and inflammatory factors. Transcriptome results are interpreted in light of expression of candidate genesmarkers for tooth size and shape, bone cells and mechanically sensitive pathways. This study opens up new avenues of research at new levels of biological organization into the roles of phenotypic plasticity during speciation and radiation of cichlid fishes.

Early Intervention Program Final Evaluation Report

The Early Intervention Program aims to facilitate contact between children and their non-residential parent as soon as practicable after breakdown and separation of the immediate family unit. The Program is auspiced by the Sunshine Coast Family Contact Centre Association. The Program has been offered since late 2007 following receipt of a grant from the National Community Crime Prevention Program [NCCP] for Domestic Violence Prevention. This external evaluator report summarised main achievements with respect to meeting program objectives and also makes recommentations in view the of the continuation of this innovative program.

Producing and maintaining professional identities in early childhood

This study is an inquiry into early childhood teacher professional identities. In Australia, workforce reforms in early childhood include major shifts in qualification requirements that call for a university four-year degree-qualified teacher to be employed in child care. This marks a shift in the early years workforce, where previously there was no such requirement. At the same time as these reforms to quality measures are being implemented, and requiring a substantive up skilling of the workforce, there is a growing body of evidence through recent studies that suggests these same four-year degree-qualified early childhood teachers have an aversion to working in child care. Their preferred employment option is to work in the early years of more formal schooling, not in before-school contexts. This collision of agendas warrants investigation. This inquiry is designed to investigate the site at which advocacy for higher qualification requirements meets early childhood teachers who are reluctant to choose child care as a possible career pathway. The key research question for this study is: How are early childhood teachers’ professional identities currently produced? The work of this thesis is to problematise the early childhood teacher in child care through a particular method of discourse analysis. There are two sets of data. The first was a key early childhood political document that read as a "moment of arising" (Foucault, 1984a, p. 83). It is a political document which was selected for its current influence on the early childhood field, and in particular, workforce reforms that call for four-year degree-qualified teachers to work in before-school contexts, including child care. The second data set was generated through four focus group discussions conducted with preservice early childhood teachers. The document and transcripts of the focus groups were both analysed as text, as conceptualised by Foucault (1981). Foucault’s work spans a number of years and a range of philosophical matters. This thesis draws particularly on Foucault’s writings on discourse, power/knowledge, regimes of truth and resistance. In order to consider the production of early childhood teachers’ professional identities, the study is also informed by identity theorists, who have worked on gender, performativity and investment (Davies, 2004/2006; McNay, 1992; Osgood, 2012; Walkerdine, 1990; Weedon, 1997). The ways in which discourses intersect, compete and collide produce the subject (Foucault, 1981) and, in the case of this inquiry, there are a number of competing discourses at play, which produce the early childhood teacher. These particular theories turn particular lenses on the question of professional identities in early childhood, and such a study calls for the application of particular methodologies. Discourse analysis was used as the methodological framework, and the analysis was informed by Foucauldian concepts of discourse. While Foucault did not prescribe a form of discourse analysis as a method, his writings nonetheless provide a valuable framework for illuminating discursive practices and, in turn, how people are affected, through the shifts and distribution of power (Foucault, 1980a). The treatment used with both data sets involved redescription. For the policy document, a technique for reading document-as-text applied a genealogical approach (Foucault, 1984a). For the focus groups, the process of redescription (Rorty, 1989) involved reading talk-as-text. As a method, redescription involves describing "lots and lots of things in new ways until you have created a pattern of linguistic behaviour which will tempt the new generation to adopt it" (Rorty, 1989, p. 9). The development and application of categories (Davies, 2004/2006) built on a poststructuralist theoretical framework and the literature review informed the data analysis method of discourse analysis. Irony provided a rhetorical and playful tool (Haraway, 1991; Rorty, 1989), to look to how seemingly opposing discourses are held together. This opens a space to collapse binary thinking and consider seemingly contradictory terms in a way in which both terms are possible and both are true. Irony resists the choice of one or the other being right, and holds the opposites together in tension. The thesis concludes with proposals for new, ironic categories, which work to bring together seemingly opposing terms, located at sites in the field of early childhood where discourses compete, collide and intersect to produce and maintain early childhood teacher professional identities. The process of mapping these discourses goes some way to investigating the complexities about identities and career choices of early childhood teachers. The category of "the cost of loving" captures the collision between care/love, inherent in child care, and new discourses of investment/economics. Investment/economics has not completely replaced care/love, and these apparent opposites were not read as a binary because both are necessary and both are true (Haraway, 1991). They are held together in tension to produce early childhood teacher professional identities. The policy document under scrutiny was New Directions, released in 2007 by the then opposition ALP leader, Kevin Rudd. The claim was made strongly that the "economic prosperity" of Australia relies on investment in early childhood. The arguments to invest are compelling and the neuroscience/brain research/child development together with economic/investment discourses demand that early childhood is funding is increased. The intersection of these discourses produces professional identities of early childhood teachers as a necessary part of the country’s economy, and thus, worthy of high status. The child care sector and work in child care settings are necessary, with children and the early childhood teacher playing key roles in the economy of the nation. Through New Directions it becomes sayable (Foucault, 1972/1989) that the work the early childhood teacher performs is legitimated and valued. The children are produced as "economic units". A focus on what children are able to contribute to the future economy of the nation re-positions children and produces these "smart productive citizens", making future economic contribution. The early childhood teacher is produced through this image of a child and "the cost of loving" is emphasised. A number of these categories were produced through the readings of the document-as text and the talk-as-text. Two ironic categories were read in the analysis of the transcripts of the focus group discussions, when treated as talk-as-text data: the early childhood teacher as a "heroic victim"; and the early childhood teacher as a "glorified babysitter". This thesis raises new questions about professional identities in early childhood. These new questions might go some way to prompt re-thinking of some government policy, as well as some aspects of early childhood teacher education course design. The images of children and images of child care provide provocations to consider preservice teacher education course design. In particular, how child care, as one of the early childhood contexts, is located, conceptualised and spoken throughout the course. Consideration by course designers and teacher educators of what discourses are privileged in course content —what discourses are diminished or silenced—would go some way to reconceptualising child care within preservice teacher education and challenging dominant ways of speaking child care, and work in child care. This inquiry into early childhood teachers’ professional identities has gone some way to exploring the complexities around the early childhood teacher in child care. It is anticipated that the significance of this study will thus have immediate applicably and relevance for the Australian early childhood policy landscape. The early childhood field is in a state of rapid change, and this inquiry has examined some of the disconnects between policy and practice. Awareness of the discourses that are in play in the field will continue to allow space for conversations that challenge dominant assumptions about child care, work in child care and ways of being an early childhood teacher in child care.

Cost-effectiveness of a telephone-delivered education programme to prevent early childhood caries in a disadvantaged area : a cohort study

Objectives Early childhood caries is a highly destructive dental disease which is compounded by the need for young children to be treated under general anaesthesia. In Australia, there are long waiting periods for treatment at public hospitals. In this paper, we examined the costs and patient outcomes of a prevention programme for early childhood caries to assess its value for government services. Design Cost-effectiveness analysis using a Markov model. Setting Public dental patients in a low socioeconomic, socially disadvantaged area in the State of Queensland, Australia. Participants Children aged 6 months to 6 years received either a telephone prevention programme or usual care. Primary and secondary outcome measures A mathematical model was used to assess caries incidence and public dental treatment costs for a cohort of children. Healthcare costs, treatment probabilities and caries incidence were modelled from 6 months to 6 years of age based on trial data from mothers and their children who received either a telephone prevention programme or usual care. Sensitivity analyses were used to assess the robustness of the findings to uncertainty in the model estimates. Results By age 6 years, the telephone intervention programme had prevented an estimated 43 carious teeth and saved £69 984 in healthcare costs per 100 children. The results were sensitive to the cost of general anaesthesia (cost-savings range £36 043–£97 298) and the incidence of caries in the prevention group (cost-savings range £59 496–£83 368) and usual care (cost-savings range £46 833–£93 328), but there were cost savings in all scenarios. Conclusions A telephone intervention that aims to prevent early childhood caries is likely to generate considerable and immediate patient benefits and cost savings to the public dental health service in disadvantaged communities.

Treatment with the vascular disruptive agent OXi4503 induces an immediate and widespread epithelial to mesenchymal transition in the surviving tumor

Epithelial to mesenchymal transition (EMT) is considered an important mechanism in tumor resistance to drug treatments; however, in vivo observation of this process has been limited. In this study we demonstrated an immediate and widespread EMT involving all surviving tumor cells following treatment of a mouse model of colorectal liver metastases with the vascular disruptive agent OXi4503. EMT was characterized by significant downregulation of E-cadherin, relocation and nuclear accumulation of b-catenin as well as significant upregulation of ZEB1 and vimentin. Concomitantly, significant temporal upregulation in hypoxia and the pro-angiogenic growth factors hypoxia-inducible factor 1-alpha, hepatocyte growth factor, vascular endothelial growth factor and transforming growth factor-beta were seen within the surviving tumor. The process of EMT was transient and by 5 days after treatment tumor cell reversion to epithelial morphology was evident. This reversal, termed mesenchymal to epithelial transition (MET) is a process implicated in the development of new metastases but has not been observed in vivo histologically. Similar EMT changes were observed in response to other antitumor treatments including chemotherapy, thermal ablation, and antiangiogenic treatments in our mouse colorectal metastasis model and in a murine orthotopic breast cancer model after OXi4503 treatment. These results suggest that EMT may be an early mechanism adopted by tumors in response to injury and hypoxic stress, such that inhibition of EMT in combination with other therapies could play a significant role in future cancer therapy.

Lady Nugent and Tom Cringle on the veranda : early nineteenth century observations on a Caribbean architectural feature

This study of the veranda as seen through the eyes of Lady Maria Nugent and Michael Scott, alias Tom Cringle, clearly demonstrates the important role that the piazza, as it was then more commonly known, played in the life of early nineteenth century Caribbean colonial society. The popularity of the veranda throughout the region, in places influenced by different European as well as African cultures, and among all classes of people, suggests that the appeal of this typical feature was based on something more than architectural fashion. A place of relative comfort in hot weather, the veranda is also a space at the interface of indoors and outdoors which allows for a wide variety of uses, for solitary or small or large group activities, many of which were noted by Nugent and Scott. Quintessentially, the veranda is a place in which to relax and take pleasure, not least of which is the enjoyment of the prospect, be it a panoramic view, a peaceful garden or a lively street scene. Despite the great changes in the nature of society, in the Caribbean and in many other parts of the world, the veranda and related structures such as the balcony continue to play at least as important a role in daily life as they did two centuries ago. The veranda of today’s Californian or Australian bungalow, and the balcony of the apartment block in the residential area of the modern city are among the contemporary equivalents of the lower and upper piazzas of Lady Nugent’s and Tom Cringle’s day.