Prediction of transcriptional regulatory interactions in bacteria : a comparative genomics approach

Exponential growth of genomic data in the last two decades has made manual analyses impractical for all but trial studies. As genomic analyses have become more sophisticated, and move toward comparisons across large datasets, computational approaches have become essential. One of the most important biological questions is to understand the mechanisms underlying gene regulation. Genetic regulation is commonly investigated and modelled through the use of transcriptional regulatory network (TRN) structures. These model the regulatory interactions between two key components: transcription factors (TFs) and the target genes (TGs) they regulate. Transcriptional regulatory networks have proven to be invaluable scientific tools in Bioinformatics. When used in conjunction with comparative genomics, they have provided substantial insights into the evolution of regulatory interactions. Current approaches to regulatory network inference, however, omit two additional key entities: promoters and transcription factor binding sites (TFBSs). In this study, we attempted to explore the relationships among these regulatory components in bacteria. Our primary goal was to identify relationships that can assist in reducing the high false positive rates associated with transcription factor binding site predictions and thereupon enhance the reliability of the inferred transcription regulatory networks. In our preliminary exploration of relationships between the key regulatory components in Escherichia coli transcription, we discovered a number of potentially useful features. The combination of location score and sequence dissimilarity scores increased de novo binding site prediction accuracy by 13.6%. Another important observation made was with regards to the relationship between transcription factors grouped by their regulatory role and corresponding promoter strength. Our study of E.coli ��70 promoters, found support at the 0.1 significance level for our hypothesis | that weak promoters are preferentially associated with activator binding sites to enhance gene expression, whilst strong promoters have more repressor binding sites to repress or inhibit gene transcription. Although the observations were specific to �70, they nevertheless strongly encourage additional investigations when more experimentally confirmed data are available. In our preliminary exploration of relationships between the key regulatory components in E.coli transcription, we discovered a number of potentially useful features { some of which proved successful in reducing the number of false positives when applied to re-evaluate binding site predictions. Of chief interest was the relationship observed between promoter strength and TFs with respect to their regulatory role. Based on the common assumption, where promoter homology positively correlates with transcription rate, we hypothesised that weak promoters would have more transcription factors that enhance gene expression, whilst strong promoters would have more repressor binding sites. The t-tests assessed for E.coli �70 promoters returned a p-value of 0.072, which at 0.1 significance level suggested support for our (alternative) hypothesis; albeit this trend may only be present for promoters where corresponding TFBSs are either all repressors or all activators. Nevertheless, such suggestive results strongly encourage additional investigations when more experimentally confirmed data will become available. Much of the remainder of the thesis concerns a machine learning study of binding site prediction, using the SVM and kernel methods, principally the spectrum kernel. Spectrum kernels have been successfully applied in previous studies of protein classification [91, 92], as well as the related problem of promoter predictions [59], and we have here successfully applied the technique to refining TFBS predictions. The advantages provided by the SVM classifier were best seen in `moderately'-conserved transcription factor binding sites as represented by our E.coli CRP case study. Inclusion of additional position feature attributes further increased accuracy by 9.1% but more notable was the considerable decrease in false positive rate from 0.8 to 0.5 while retaining 0.9 sensitivity. Improved prediction of transcription factor binding sites is in turn extremely valuable in improving inference of regulatory relationships, a problem notoriously prone to false positive predictions. Here, the number of false regulatory interactions inferred using the conventional two-component model was substantially reduced when we integrated de novo transcription factor binding site predictions as an additional criterion for acceptance in a case study of inference in the Fur regulon. This initial work was extended to a comparative study of the iron regulatory system across 20 Yersinia strains. This work revealed interesting, strain-specific difierences, especially between pathogenic and non-pathogenic strains. Such difierences were made clear through interactive visualisations using the TRNDifi software developed as part of this work, and would have remained undetected using conventional methods. This approach led to the nomination of the Yfe iron-uptake system as a candidate for further wet-lab experimentation due to its potential active functionality in non-pathogens and its known participation in full virulence of the bubonic plague strain. Building on this work, we introduced novel structures we have labelled as `regulatory trees', inspired by the phylogenetic tree concept. Instead of using gene or protein sequence similarity, the regulatory trees were constructed based on the number of similar regulatory interactions. While the common phylogentic trees convey information regarding changes in gene repertoire, which we might regard being analogous to `hardware', the regulatory tree informs us of the changes in regulatory circuitry, in some respects analogous to `software'. In this context, we explored the `pan-regulatory network' for the Fur system, the entire set of regulatory interactions found for the Fur transcription factor across a group of genomes. In the pan-regulatory network, emphasis is placed on how the regulatory network for each target genome is inferred from multiple sources instead of a single source, as is the common approach. The benefit of using multiple reference networks, is a more comprehensive survey of the relationships, and increased confidence in the regulatory interactions predicted. In the present study, we distinguish between relationships found across the full set of genomes as the `core-regulatory-set', and interactions found only in a subset of genomes explored as the `sub-regulatory-set'. We found nine Fur target gene clusters present across the four genomes studied, this core set potentially identifying basic regulatory processes essential for survival. Species level difierences are seen at the sub-regulatory-set level; for example the known virulence factors, YbtA and PchR were found in Y.pestis and P.aerguinosa respectively, but were not present in both E.coli and B.subtilis. Such factors and the iron-uptake systems they regulate, are ideal candidates for wet-lab investigation to determine whether or not they are pathogenic specific. In this study, we employed a broad range of approaches to address our goals and assessed these methods using the Fur regulon as our initial case study. We identified a set of promising feature attributes; demonstrated their success in increasing transcription factor binding site prediction specificity while retaining sensitivity, and showed the importance of binding site predictions in enhancing the reliability of regulatory interaction inferences. Most importantly, these outcomes led to the introduction of a range of visualisations and techniques, which are applicable across the entire bacterial spectrum and can be utilised in studies beyond the understanding of transcriptional regulatory networks.

Experience of overseas-trained health professionals in rural and remote areas of destination countries: A literature review

This study aimed to review and synthesise existing literature that investigated the experience of overseastrained health professionals (OTHPs) in rural and remote areas of destination countries. A systematic literature review was conducted using electronic databases and manual search of studies published from January 2004 to February 2011. Data were analysed from the final 17 original report articles that met the inclusion criteria. The reviewed research studies were conducted in Australia, Canada, New Zealand, the UK and the USA. Overseas-trained medical practitioners were the most frequently researched (n = 14); two studies involved nurses and one study included several health professionals. Three main themes emerged from the review and these were: (i) expectations; (ii) cultural diversity; and (iii) orientation and integration to rural and remote health work environment. The OTHPs were expected to possess the appropriate professional and cultural skills while they themselves expected recognition of their previous experiences and adequate organisational orientation and support. A welcoming and accepting community coupled with a relaxed rural lifestyle and the joy of continued patient care resulted in successful integration and contributed to increased staff retention rates. Recognition of expectations and cultural diversity by all parties and comprehensive orientation with sufficient organisational support are important elements in the integration of OTHPs and subsequent delivery of quality health care to people living in rural and remote areas.

Family-based programmes for preventing smoking by children and adolescents

BACKGROUND: There is evidence that children's decisions to smoke are influenced by family and friends. OBJECTIVES: To assess the effectiveness of interventions to help family members to strengthen non-smoking attitudes and promote non-smoking by children and other family members. SEARCH STRATEGY: We searched 14 electronic bibliographic databases, including the Cochrane Tobacco Addiction Group specialized register, MEDLINE, EMBASE, PsycINFO and CINAHL. We also searched unpublished material, and the reference lists of key articles. We performed both free-text Internet searches and targeted searches of appropriate websites, and we hand-searched key journals not available electronically. We also consulted authors and experts in the field. The most recent search was performed in July 2006. SELECTION CRITERIA: Randomized controlled trials (RCTs) of interventions with children (aged 5-12) or adolescents (aged 13-18) and family members to deter the use of tobacco. The primary outcome was the effect of the intervention on the smoking status of children who reported no use of tobacco at baseline. Included trials had to report outcomes measured at least six months from the start of the intervention. DATA COLLECTION AND ANALYSIS: We reviewed all potentially relevant citations and retrieved the full text to determine whether the study was an RCT and matched our inclusion criteria. Two authors independently extracted study data and assessed them for methodological quality. The studies were too limited in number and quality to undertake a formal meta-analysis, and we present a narrative synthesis. MAIN RESULTS: We identified 19 RCTs of family interventions to prevent smoking. We identified five RCTs in Category 1 (minimal risk of bias on all counts); nine in Category 2 (a risk of bias in one or more areas); and five in Category 3 (risks of bias in design and execution such that reliable conclusions cannot be drawn from the study).Considering the fourteen Category 1 and 2 studies together: (1) four of the nine that tested a family intervention against a control group had significant positive effects, but one showed significant negative effects; (2) one of the five RCTs that tested a family intervention against a school intervention had significant positive effects; (3) none of the six that compared the incremental effects of a family plus a school programme to a school programme alone had significant positive effects; (4) the one RCT that tested a family tobacco intervention against a family non-tobacco safety intervention showed no effects; and (5) the one trial that used general risk reduction interventions found the group which received the parent and teen interventions had less smoking than the one that received only the teen intervention (there was no tobacco intervention but tobacco outcomes were measured). For the included trials the amount of implementer training and the fidelity of implementation are related to positive outcomes, but the number of sessions is not. AUTHORS' CONCLUSIONS: Some well-executed RCTs show family interventions may prevent adolescent smoking, but RCTs which were less well executed had mostly neutral or negative results. There is thus a need for well-designed and executed RCTs in this area.

Educational accountability tests, social and legal inclusion approaches to discrimination for students with disability : a national case study from Australia

The UN Convention on the Rights of Persons with Disability (CRPD) promotes equal and full participation by children in education. Equity of educational access for all students, including students with disability, free from discrimination, is the first stated national goal of Australian education (MCEETYA 2008). Australian federal disability discrimination law, the Disability Discrimination Act 1992 (DDA), follows the Convention, with the federal Disability Standards for Education 2005 (DSE) enacting specific requirements for education. This article discusses equity of processes for inclusion of students with disability in Australian educational accountability testing, including international tests in which many countries participate. The conclusion drawn is that equitable inclusion of students with disability in current Australian educational accountability testing in not occurring from a social perspective and is not in principle compliant with law. However, given the reluctance of courts to intervene in education matters and the uncertainty of an outcome in any court consideration, the discussion shows that equitable inclusion in accountability systems is available through policy change rather than expensive, and possibly unsuccessful, legal challenges.

The Chemistry Discipline Network: One Year On

The Chemistry Discipline Network was funded in mid-2011, with the aim of improving communication between chemistry academics in Australia. In our first year of operation, we have grown to over 100 members, established a web presence, and produced substantial mapping reports on chemistry teaching in Australia. We are now working on the definition of standards for a chemistry degree based on the Threshold Learning Outcomes published by the Learning and Teaching Academic Standards Project.

Does the social inclusion discourse add value?

The election of a national Labor Government in 2007 saw ‘social inclusion’ emerge as Australia’s overarching social policy agenda. Being ‘included’ has since been defined as being able to ‘have the resources, opportunities and capabilities needed to learn, work, engage and have a voice’. Various researchers have adopted the social inclusion concept to construct a multi-dimensional framework for measuring disadvantage, beyond poverty alleviation. This research program has enabled various forms of statistical modelling based on some agreement about what it means to be ‘included’ in society. At the same time it is acknowledged that social inclusion remains open and contestable and can be used in the name of both progressive and more punitive programs and policies. This ambiguity raises questions about whether the social inclusion framework, as it is presently defined, has the potential to be a progressive and transformative discourse. In this paper we examine whether the Australian social inclusion agenda has the capacity to address social inequality in a meaningful way, concluding with a discussion about the need to understand social inequality and social disadvantage in relational terms.

Building intercultural competence one “Patch” at a time

This paper describes a program called Patches that was implemented to assist a group of Australian and Malaysian pre-service teachers to enhance their intercultural competence through their involvement in a series of reciprocal learning activities. Each learning experience was considered a “patch” that eventually created a “quilt of intercultural learning.” The purpose of this study was to enhance the intercultural competence of domestic and international students through organized intercultural activities, through a series of reflective writing sessions, and mutual engagement on a common project. The effectiveness of the Patches program was analysed in accordance with Deardorff’s elements of intercultural competence. The qualitative findings indicate that both cohorts of preservice teachers showed elements of intercultural competence through participation in the program, with both groups reporting a deeper appreciation and understanding of how to communicate more effectively in intercultural contexts.

Weight stigma in maternity care : women's experiences and care providers' attitudes

Background: Weight stigma is pervasive in Western society and in healthcare settings, and has a negative impact on victims’ psychological and physical health. In the context of an increasing focus on the management of overweight and obese women during and after pregnancy in research and clinical practice, the current studies aimed to examine the presence of weight stigma in maternity care. Addressing previous limitations in the weight stigma literature, this paper quantitatively explores the presence of weight stigma from both patient and care provider perspectives. Methods: Study One investigated associations between pre-pregnancy body mass index (BMI) and experiences of maternity care from a state-wide, self-reported survey of 627 Australian women who gave birth in 2009. Study Two involved administration of an online survey to 248 Australian pre-service medical and maternity care providers, to investigate their perceptions of, and attitudes towards, providing care for pregnant patients of differing body sizes. Both studies used linear regression analyses. Results: Women with a higher BMI were more likely to report negative experiences of care during pregnancy and after birth, compared to lower weight women. Pre-service maternity care providers perceived overweight and obese women as having poorer self-management behaviours, and reported less positive attitudes towards caring for overweight or obese pregnant women, than normal weight pregnant women. Even care providers who reported few weight-stigmatising attitudes responded less positively to overweight and obese pregnant women. Conclusions: Overall, these results provide preliminary evidence that weight stigma is present in maternity care settings in Australia. They suggest a need for further research into the nature and consequences of weight stigma in maternity care, and for the inclusion of strategies to recognise and combat weight stigma in maternity care professionals’ training.

Effects of type 2 diabetes behavioural telehealth interventions on glycaemic control and adherence : a systematic review

We reviewed the effect of behavioural telehealth interventions on glycaemic control and diabetes self-management in patients with type 2 diabetes. The databases CINAHL, Medline and psychINFO were searched in August 2012. Journal articles were selected that had been published in English with a randomized controlled trial design using a usual care comparison group, and in which the primary intervention component was delivered by telehealth. Relevant outcome measures were glycaemic control and one or more of the following diabetes self-care areas: diet, physical activity, blood glucose self-monitoring (BGSM) or medication adherence. Interventions were excluded if they were primarily based on telemonitoring. The search retrieved 1027 articles, from which 49 were selected based on their title and abstract. Fourteen articles (reporting 13 studies) met the eligibility criteria for inclusion. Four studies reported significant improvements in glycaemic control. Five of eight studies on dietary adherence reported significant treatment effects, as did five of eight on physical activity, four of nine on blood glucose self-monitoring, and three of eight on medication adherence. Overall, behavioural telehealth interventions show promise in improving the diabetes self-care and glycaemic control of people with type 2 diabetes.

The emerging framework of cross-border insolvency in and around Australia : Saad Investments, Japan Airlines and Lehman Brothers – part one

Recent decades have witnessed a global acceleration of legislative and private sector initiatives to deal with Cross-Border insolvency. Legislative institutions include the various national implementations of the Model Law on Cross-Border Insolvency (Model Law) published by the United Nations Commission on International Trade (UNCITRAL).3 Private mechanisms include Cross-Border protocols developed and utilised by insolvency professionals and their advisers (often with the imprimatur of the judiciary), on both general and ad hoc bases. The Asia Pacific region has not escaped the effect of those developments, and the economic turmoil of the past few years has provided an early test for some of the emerging initiatives in that region. This two-part article explores the operation of those institutions through the medium of three recent cases.

Preservice teachers’ perceptions of their middle schooling teacher preparation : a sample of the Australian context

Reviews into teacher education and reform measures, such as implementing professional standards for teachers, are designed to raise the quality of education. Such reviews and reforms also target preservice teachers; hence universities examine their teacher education programs to address these issues, including developing programs that are current with the literature. Over the past fifteen years, concerns have arisen about Australian early adolescents and their disengagement from the schooling system, their “at risk” behaviour and their need for social, emotional and academic support. These concerns have prompted a middle schooling movement in Australia with the literature recognising a need for specialised middle school teachers. As a result, various universities have responded by developing courses specifically designed to graduate teachers who possess the theoretical and pedagogical knowledge for engaging early adolescent learners. This mixed-method study analysed the responses of preservice teachers from three universities across two states in Australia near the completion of their middle years teacher preparation program. The three aims of the study were to: (1) investigate final-year preservice teachers’ perceptions of their confidence to teach in the middle years of schooling; (2) analyse the experiences included in their teacher preparation course that made them feel confident; and (3) describe strategies for enhancing middle schooling teacher education preparation. Data were gathered from final-year preservice teachers (n=142) using a survey that was developed in response to middle schooling literature and the Professional Standards for Queensland Teachers (Queensland College of Teachers, 2006). A questionnaire collected extended information about the participants’ (n=142) experiences that made them feel confident. It also gathered information about strategies for enhancing middle years teacher preparation. One-to-one, 45-minute interviews (n=10) were conducted to elicit in-depth responses aligned with the research aims. Quantitative results indicated that the majority of preservice teachers (n=142) claimed confidence associated with survey items relating to creating a positive classroom environment (range: 70-97%), developing positive relationships for teaching (71-98%), pedagogical knowledge for teaching (72-95%), and implementation of teaching (70-91%). Qualitative findings suggested that the experiences that assisted them to be confident for teaching were practicum and associated field studies coursework, a positive mentor teacher, specifically designed middle years subjects, the pedagogical approaches of university staff, and other real-world experiences such as volunteering in schools and participating in professional development alongside their mentors. This study demonstrated that universities presenting middle years teacher preparation need to consider: the quality of the practicum experience; the suitability of mentor teachers; the significance and practicalities of middle years subjects; university lecturers’ modelling of pedagogical practices; and the inclusion of real-world learning experiences. Although the findings of this study provided evidence as to how preservice teacher confidence for teaching has been influenced by their middle schooling teacher preparation, further research is required to investigate how confidence translates into practice within their first years of teaching.

Media Literacy through Arts Education in Australia

Media arts has been included as one of five Arts subjects for the new Australian Curriculum and will become mandatory learning for all Australian children from pre-school to year six, and elective for children in years seven to twelve. While media education has historically been associated with English curriculum in Australia, it has also occurred through the Arts since at least the 1960s and creative practice has almost always been included as an aspect of official media curricula. This chapter investigates the possibilities for creative and critical learning enabled through media arts by discussing the media learning of one primary school student. This chapter investigates the possibilities for creative and critical learning enabled through the inclusion of media arts in the curriculum. Media arts has been included as one of five Arts subjects for the new Australian Curriculum and will become mandatory learning for all Australian children from pre-school to year six, and elective for children in years seven to twelve. Media education has historically been associated with English curriculum in Australia due to its development through the critical reading tradition. However, media literacy education in secondary schools has also occurred through the Arts since at least the 1960s and creative practice has almost always been included as an aspect of official media curricula. This chapter investigates the media learning of one primary school student, to consider the nature of creative learning and how this relates to the ‘critical’ aspects of media arts curriculum. We undertook this work as part of a large research project that has been investigating the relationship between digital media and traditional literacy outcomes in a primary school.

Asian representations in films for the Australian Curriculum : an annotated guide

In this annotated guide we offer a reference list, with brief synposes, of possible films for inclusion in schools and linked to the Australian Curriculum: English (AC:E). These films meet one of the three cross curriculum priorities in the Australian Curriculum, which is Studies of Asia, specifically Australia’s contribution to Asia and Asia’s impact on Australia. This priority was recently introduced to curriculum policy in the 2008 Melbourne Declaration (Ministerial Council for Education Early Childhood Development and Youth Affairs, 2008). In this guide we include Australians films made by Asian Australian filmmakers, as well as films about people from Asian countries in Australia, where representations of Asia are a significant part of the film’s content.

Justice and social inclusion policies

Since 2008 the social policy of Australia’s Labor government (in office since 2007) has been framed by a commitment to ‘social inclusion’. In this respect Australia belatedly aligned itself with policy imaginaries already widely, if variably, adopted in Europe (Atkinson & Davoudi 2000; Levitas et al 2007; Buckmaster & Thomas 2009). This framework has been self-consciously identified as what Labor governments are equipped to do. Framed by the post-2007 global financial crisis and agreeing with claims that ‘excessive greed’ and irresponsibility on the part of financial markets sponsored that calamity, the Labor government vigorously promoted its ‘social democratic’ credentials. Former Prime Minister Rudd has explained this meant that Australia would no longer adopt a neo-liberal orientation promoting unrestrained capitalism (Rudd 2009).

Wherefore art thou, inclusion? Analysing the development of inclusive education in New South Wales, Finland and Alberta

Over the last two decades, moves toward “inclusion” have prompted change in the formation of education policies, schooling structures and pedagogical practice. Yet, exclusion through the categorisation and segregation of students with diverse abilities has grown; particularly for students with challenging behaviour. This paper considers what has happened to inclusive education by focusing on three educational jurisdictions known to be experiencing different rates of growth in the identification of special educational needs: New South Wales (Australia), Alberta (Canada) and Finland (Europe). In our analysis, we consider the effects of competing policy forces that appear to thwart the development of inclusive schools in two of our case-study regions.