Academic Services and Registrar - Research Publications
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ItemStyling Against Absolute Knowledge in Derrida's 'Glas'(Open Humanities Press, 2015)
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ItemNo Preview AvailableExperiences in developing an online teaching tool in support of evidence(Health Libraries Inc, 2015-01-01)
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ItemConstitutive and Inflammatory Immunopeptidome of Pancreatic β-Cells(AMER DIABETES ASSOC, 2012-11)Type 1 diabetes is characterized by the autoimmune destruction of pancreatic β-cells. Recognition of major histocompatibility complex (MHC)-bound peptides is critical for both the initiation and progression of disease. In this study, MHC peptide complexes were purified from NIT-1 β-cells, interferon-γ (IFN-γ)-treated NIT-1 cells, splenic and thymic tissue of 12-week-old NOD mice, and peptides identified by mass spectrometry. In addition to global liquid chromatography-tandem mass spectrometry analysis, the targeted approach of multiple-reaction monitoring was used to quantitate the immunodominant K(d)-restricted T-cell epitope islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)₂₀₆₋₂₁₄. We identified >2,000 MHC-bound peptides; 1,100 of these presented by β-cells grown under normal conditions or after exposure to IFN-γ. These include sequences from a number of known autoantigens. Quantitation of IGRP₂₀₆₋₂₁₄ revealed low-level presentation by K(d) (~25 complexes/cell) on NIT-1 cells after IFN-γ treatment compared with the simultaneous presentation of the endogenously processed K(d)-restricted peptide Janus kinase-1₃₅₅₋₃₆₃ (~15,000 copies/cell). We have successfully sequenced peptides from NIT-1 β-cells under basal and inflammatory conditions. We have shown the feasibility of quantitating disease-associated peptides and provide the first direct demonstration of the disparity between presentation of a known autoantigenic epitope and a common endogenously presented peptide.
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ItemPhysical and Linkage Maps for Drosophila serrata, a Model Species for Studies of Clinal Adaptation and Sexual Selection(GENETICS SOCIETY AMERICA, 2012-02-01)Drosophila serrata is a member of the montium group, which contains more than 98 species and until recently was considered a subgroup within the melanogaster group. This Drosophila species is an emerging model system for evolutionary quantitative genetics and has been used in studies of species borders, clinal variation and sexual selection. Despite the importance of D. serrata as a model for evolutionary research, our poor understanding of its genome remains a significant limitation. Here, we provide a first-generation gene-based linkage map and a physical map for this species. Consistent with previous studies of other drosophilids we observed strong conservation of genes within chromosome arms homologous with D. melanogaster but major differences in within-arm synteny. These resources will be a useful complement to ongoing genome sequencing efforts and QTL mapping studies in this species.
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ItemA Family of Helminth Molecules that Modulate Innate Cell Responses via Molecular Mimicry of Host Antimicrobial Peptides(PUBLIC LIBRARY SCIENCE, 2011-05)Over the last decade a significant number of studies have highlighted the central role of host antimicrobial (or defence) peptides in modulating the response of innate immune cells to pathogen-associated ligands. In humans, the most widely studied antimicrobial peptide is LL-37, a 37-residue peptide containing an amphipathic helix that is released via proteolytic cleavage of the precursor protein CAP18. Owing to its ability to protect against lethal endotoxaemia and clinically-relevant bacterial infections, LL-37 and its derivatives are seen as attractive candidates for anti-sepsis therapies. We have identified a novel family of molecules secreted by parasitic helminths (helminth defence molecules; HDMs) that exhibit similar biochemical and functional characteristics to human defence peptides, particularly CAP18. The HDM secreted by Fasciola hepatica (FhHDM-1) adopts a predominantly α-helical structure in solution. Processing of FhHDM-1 by F. hepatica cathepsin L1 releases a 34-residue C-terminal fragment containing a conserved amphipathic helix. This is analogous to the proteolytic processing of CAP18 to release LL-37, which modulates innate cell activation by classical toll-like receptor (TLR) ligands such as lipopolysaccharide (LPS). We show that full-length recombinant FhHDM-1 and a peptide analogue of the amphipathic C-terminus bind directly to LPS in a concentration-dependent manner, reducing its interaction with both LPS-binding protein (LBP) and the surface of macrophages. Furthermore, FhHDM-1 and the amphipathic C-terminal peptide protect mice against LPS-induced inflammation by significantly reducing the release of inflammatory mediators from macrophages. We propose that HDMs, by mimicking the function of host defence peptides, represent a novel family of innate cell modulators with therapeutic potential in anti-sepsis treatments and prevention of inflammation.
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ItemWomen's evaluation of abuse and violence care in general practice: a cluster randomised controlled trial (weave)(BMC, 2010-01-02)BACKGROUND: Intimate partner abuse (IPA) is a major public health problem with serious implications for the physical and psychosocial wellbeing of women, particularly women of child-bearing age. It is a common, hidden problem in general practice and has been under-researched in this setting. Opportunities for early intervention and support in primary care need to be investigated given the frequency of contact women have with general practice. Despite the high prevalence and health consequences of abuse, there is insufficient evidence for screening in primary care settings. Furthermore, there is little rigorous evidence to guide general practitioners (GPs) in responding to women identified as experiencing partner abuse. This paper describes the design of a trial of a general practice-based intervention consisting of screening for fear of partner with feedback to GPs, training for GPs, brief counselling for women and minimal practice organisational change. It examines the effect on women's quality of life, mental health and safety behaviours. METHODS/DESIGN: weave is a cluster randomised controlled trial involving 40 general practices in Victoria, Australia. Approximately 500 women (16-50 years) seen by the GP in the previous year are mailed a short lifestyle survey containing an item to screen for IPA. Women who indicate that they were afraid of a partner/ex-partner in the last year and provide contact details are invited to participate. Once baseline data are collected, GPs are randomly assigned to either a group involving healthy relationship and responding to IPA training plus inviting women for up to 6 sessions of counselling or to a group involving basic education and usual care for women. Outcomes will be evaluated by postal survey at 6 and 12 months following delivery of the intervention. There will be an economic evaluation, and process evaluation involving interviews with women and GPs, to inform understanding about implementation and outcomes. DISCUSSION: The weave trial responds to an urgent need for more evidence on what can be achieved in primary care with regard to responding to women who experience IPA. It will provide important knowledge about the effectiveness of a brief method of screening, professional IPA training program and brief counselling for women. TRIAL REGISTRATION: [ACTRN12608000032358].
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ItemMeasuring use of research evidence in public health policy: a policy content analysis.(Springer Science and Business Media LLC, 2014-05-23)BACKGROUND: There are few Australian studies showing how research evidence is used to inform the development of public health policy. International research has shown that compensation for injury rehabilitation can have negative impacts on health outcomes. This study examined transport injury compensation policy in the Australian state of Victoria to: determine type and purpose of reference to information sources; and to identify the extent of reference to academic research evidence in transport related injury rehabilitation compensation policy. METHODS: Quantitative content analysis of injury rehabilitation compensation policies (N = 128) from the Victorian state government transport accident compensation authority. RESULTS: The most commonly referenced types of information were Internal Policy (median = 6 references per policy), Clinical/Medical (2.5), and Internal Legislation (1). Academic Research Evidence was the least often referenced source of information. The main purpose of reference to information was to support injury treatment and rehabilitation compensation claims decision-making. CONCLUSIONS: Transport injury compensation policy development is complex; with multiple sources of information cited including legislation, internal policy, external policy and clinical/medical evidence. There is limited use of academic research evidence in Victorian state government injury treatment and rehabilitation compensation policies. Decisions regarding compensation for injury treatment and rehabilitation services could benefit from greater use of academic research evidence. This study is one of the first to examine the use of research evidence in existing Australian public health policy decision-making using rigorous quantitative methods. It provides a practical example of how use of research evidence in public health policy can be objectively measured.
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ItemStructural and functional characterization of TesB from Yersinia pestis reveals a unique octameric arrangement of hotdog domains(INT UNION CRYSTALLOGRAPHY, 2015-04)Acyl-CoA thioesterases catalyse the hydrolysis of the thioester bonds present within a wide range of acyl-CoA substrates, releasing free CoASH and the corresponding fatty-acyl conjugate. The TesB-type thioesterases are members of the TE4 thioesterase family, one of 25 thioesterase enzyme families characterized to date, and contain two fused hotdog domains in both prokaryote and eukaryote homologues. Only two structures have been elucidated within this enzyme family, and much of the current understanding of the TesB thioesterases has been based on the Escherichia coli structure. Yersinia pestis, a highly virulent bacterium, encodes only one TesB-type thioesterase in its genome; here, the structural and functional characterization of this enzyme are reported, revealing unique elements both within the protomer and quaternary arrangements of the hotdog domains which have not been reported previously in any thioesterase family. The quaternary structure, confirmed using a range of structural and biophysical techniques including crystallography, small-angle X-ray scattering, analytical ultracentrifugation and size-exclusion chromatography, exhibits a unique octameric arrangement of hotdog domains. Interestingly, the same biological unit appears to be present in both TesB structures solved to date, and is likely to be a conserved and distinguishing feature of TesB-type thioesterases. Analysis of the Y. pestis TesB thioesterase activity revealed a strong preference for octanoyl-CoA and this is supported by structural analysis of the active site. Overall, the results provide novel insights into the structure of TesB thioesterases which are likely to be conserved and distinguishing features of the TE4 thioesterase family.
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ItemPredicting research use in a public health policy environment: results of a logistic regression analysis(BMC, 2014-10-09)BACKGROUND: Use of research evidence in public health policy decision-making is affected by a range of contextual factors operating at the individual, organisational and external levels. Context-specific research is needed to target and tailor research translation intervention design and implementation to ensure that factors affecting research in a specific context are addressed. Whilst such research is increasing, there remain relatively few studies that have quantitatively assessed the factors that predict research use in specific public health policy environments. METHOD: A quantitative survey was designed and implemented within two public health policy agencies in the Australian state of Victoria. Binary logistic regression analyses were conducted on survey data provided by 372 participants. Univariate logistic regression analyses of 49 factors revealed 26 factors that significantly predicted research use independently. The 26 factors were then tested in a single model and five factors emerged as significant predictors of research over and above all other factors. RESULTS: The five key factors that significantly predicted research use were the following: relevance of research to day-to-day decision-making, skills for research use, internal prompts for use of research, intention to use research within the next 12 months and the agency for which the individual worked. CONCLUSIONS: These findings suggest that individual- and organisational-level factors are the critical factors to target in the design of interventions aiming to increase research use in this context. In particular, relevance of research and skills for research use would be necessary to target. The likelihood for research use increased 11- and 4-fold for those who rated highly on these factors. This study builds on previous research and contributes to the currently limited number of quantitative studies that examine use of research evidence in a large sample of public health policy and program decision-makers within a specific context. The survey used in this study is likely to be relevant for use in other public health policy contexts.
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ItemQuality standards for DNA sequence variation databases to improve clinical management under development in Australia(ELSEVIER SCIENCE BV, 2014-09-01)Despite the routine nature of comparing sequence variations identified during clinical testing to database records, few databases meet quality requirements for clinical diagnostics. To address this issue, The Royal College of Pathologists of Australasia (RCPA) in collaboration with the Human Genetics Society of Australasia (HGSA), and the Human Variome Project (HVP) is developing standards for DNA sequence variation databases intended for use in the Australian clinical environment. The outputs of this project will be promoted to other health systems and accreditation bodies by the Human Variome Project to support the development of similar frameworks in other jurisdictions.