University General - Research Publications
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ItemMacronuclear genome sequence of the ciliate Tetrahymena thermophila, a model eukaryote.(Public Library of Science (PLoS), 2006-09)The ciliate Tetrahymena thermophila is a model organism for molecular and cellular biology. Like other ciliates, this species has separate germline and soma functions that are embodied by distinct nuclei within a single cell. The germline-like micronucleus (MIC) has its genome held in reserve for sexual reproduction. The soma-like macronucleus (MAC), which possesses a genome processed from that of the MIC, is the center of gene expression and does not directly contribute DNA to sexual progeny. We report here the shotgun sequencing, assembly, and analysis of the MAC genome of T. thermophila, which is approximately 104 Mb in length and composed of approximately 225 chromosomes. Overall, the gene set is robust, with more than 27,000 predicted protein-coding genes, 15,000 of which have strong matches to genes in other organisms. The functional diversity encoded by these genes is substantial and reflects the complexity of processes required for a free-living, predatory, single-celled organism. This is highlighted by the abundance of lineage-specific duplications of genes with predicted roles in sensing and responding to environmental conditions (e.g., kinases), using diverse resources (e.g., proteases and transporters), and generating structural complexity (e.g., kinesins and dyneins). In contrast to the other lineages of alveolates (apicomplexans and dinoflagellates), no compelling evidence could be found for plastid-derived genes in the genome. UGA, the only T. thermophila stop codon, is used in some genes to encode selenocysteine, thus making this organism the first known with the potential to translate all 64 codons in nuclear genes into amino acids. We present genomic evidence supporting the hypothesis that the excision of DNA from the MIC to generate the MAC specifically targets foreign DNA as a form of genome self-defense. The combination of the genome sequence, the functional diversity encoded therein, and the presence of some pathways missing from other model organisms makes T. thermophila an ideal model for functional genomic studies to address biological, biomedical, and biotechnological questions of fundamental importance.
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ItemNo Preview AvailableThe design of a valid and reliable questionnaire to measure osteoporosis knowledge in women: the Osteoporosis Knowledge Assessment Tool (OKAT)(BMC, 2003-07-24)BACKGROUND: Osteoporosis knowledge is an important contributor to improving exercise and calcium intake behaviour. However, there are few validated instruments for measuring osteoporosis knowledge levels. The aim of this study was to design a valid and reliable instrument to measure osteoporosis knowledge in Australian women. METHODS: A 20 item instrument with true, false and don't know responses was drafted, based on the Osteoporosis Australia Osteoporosis Prevention and Self-management course and the information leaflet "Understanding Osteoporosis". The scoring range was 1 to 20. This was administered to a 467 randomly-selected, healthy women aged 25-44 years. Questionnaire performance was assessed by Flesch reading ease, index of difficulty, Ferguson's sigma, inter-item and item-total correlations, Cronbach's alpha and principal component factor analysis. RESULTS: Flesch reading ease was higher than desirable at 45, but this was due to the use of the word osteoporosis in many items. Of the individual items 17 had an index of difficulty less than 0.75. The questionnaire had a Ferguson's sigma of 0.96, a Cronbach's alpha of 0.70 and factor analysis consistent with only one factor (osteoporosis knowledge) being measured. Levels of osteoporosis knowledge were low with a mean score of 8.8 out of 20 which suggests the OKAT may be sensitive to change. CONCLUSIONS: The OKAT for measuring osteoporosis knowledge has good psychometric properties in Australian 25-44 year old females. While it should be applicable to other Caucasian populations, this will require confirmation by further research.
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ItemEscherichia coli and community-acquired gastroenteritis, Melbourne, Australia(CENTERS DISEASE CONTROL, 2004-10)As part of a study to determine the effects of water filtration on the incidence of community-acquired gastroenteritis in Melbourne, Australia, we examined fecal samples from patients with gastroenteritis and asymptomatic persons for diarrheagenic strains of Escherichia coli. Atypical strains of enteropathogenic E. coli (EPEC) were the most frequently identified pathogens of all bacterial, viral, and parasitic agents in patients with gastroenteritis. Moreover, atypical EPEC were more common in patients with gastroenteritis (89 [12.8%] of 696) than in asymptomatic persons (11 [2.3%] of 489, p < 0.0001). Twenty-two random isolates of atypical EPEC that were characterized further showed marked heterogeneity in terms of serotype, genetic subtype, and carriage of virulence-associated determinants. Apart from the surface protein, intimin, no virulence determinant or phenotype was uniformly present in atypical EPEC strains. This study shows that atypical EPEC are an important cause of gastroenteritis in Melbourne.
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ItemNo Preview AvailableThe postural effects of load carriage on young people - a systematic review(BIOMED CENTRAL LTD, 2003-06-17)BACKGROUND: Spinal pain in young people is a significant source of morbidity in industrialised countries. The carriage of posterior loads by young people has been linked with spinal pain, and the amount of postural change produced by load carriage has been used as a measure of the potential to cause tissue damage. The purpose of this review was to identify, appraise and collate the research evidence regarding load-carriage related postural changes in young people. METHODS: A systematic literature review sought published literature on the postural effects of load carriage in young people. Sixteen databases were searched, which covered the domains of allied health, childcare, engineering, health, health-research, health-science, medicine and medical sciences. Two independent reviewers graded the papers according to Lloyd-Smith's hierarchy of evidence scale. Papers graded between 1a (meta-analysis of randomised controlled trials) and 2b (well-designed quasi-experimental study) were eligible for inclusion in this review. These papers were quality appraised using a modified Crombie tool. The results informed the collation of research evidence from the papers sourced. RESULTS: Seven papers were identified for inclusion in this review. Methodological differences limited our ability to collate evidence. CONCLUSIONS: Evidence based recommendations for load carriage in young people could not be made based on the results of this systematic review, therefore constraining the use of published literature to inform good load carriage practice for young people.
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ItemAustralian health policy on access to medical care for refugees and asylum seekers.(Springer Science and Business Media LLC, 2005-10-09)Since the tightening of Australian policy for protection visa applicants began in the 1990s, access to health care has been increasingly restricted to asylum seekers on a range of different visa types. This paper summarises those legislative changes and discusses their implications for health policy relating to refugees and asylum seekers in Australia. Of particular concern are asylum seekers on Bridging Visas with no work rights and no access to Medicare. The paper examines several key questions: What is the current state of play, in terms of health screening and medical care policies, for asylum seekers and refugees? Relatedly, how has current policy changed from that of the past? How does Australia compare with other countries in relation to health policy for asylum seekers and refugees? These questions are addressed with the aim of providing a clear description of the current situation concerning Australian health policy on access to medical care for asylum seekers and refugees. Issues concerning lack of access to appropriate health care and related services are raised, ethical and practical issues are explored, and current policy gaps are investigated.
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ItemA novel duplication polymorphism in the FANCA promoter and its association with breast and ovarian cancer -: art. no. 43(BMC, 2005-04-29)UNLABELLED: The FANCA gene is one of the genes in which mutations lead to Fanconi anaemia, a rare autosomal recessive disorder characterised by congenital abnormalities, bone marrow failure, and predisposition to malignancy. FANCA is also a potential breast and ovarian cancer susceptibility gene. A novel allele was identified which has a tandem duplication of a 13 base pair sequence in the promoter region. METHODS: We screened germline DNA from 352 breast cancer patients, 390 ovarian cancer patients and 256 normal controls to determine if the presence of either of these two alleles was associated with an increased risk of breast or ovarian cancer. RESULTS: The duplication allele had a frequency of 0.34 in the normal controls. There was a non-significant decrease in the frequency of the duplication allele in breast cancer patients. The frequency of the duplication allele was significantly decreased in ovarian cancer patients. However, when malignant and benign tumours were considered separately, the decrease was only significant in benign tumours. CONCLUSION: The allele with the tandem duplication does not appear to modify breast cancer risk but may act as a low penetrance protective allele for ovarian cancer.
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ItemInterventions for increasing chlamydia screening in primary care: a review(BMC, 2007-06-04)BACKGROUND: Despite guidelines recommending opportunistic chlamydia screening of younger women, screening rates in some countries remain low. Our aim was to review the evidence for specific interventions aimed at increasing chlamydia screening rates in primary care. METHODS: A Medline search was conducted for controlled trials that assessed the effectiveness of interventions aimed at improving chlamydia screening rates in primary health care settings. The Medline search was done for studies in English published prior to December 2005 using the following key words: chlamydia, screening, intervention, primary care and GPs. In addition, the references cited in the articles were reviewed. Studies in English published prior to December 2005 were reviewed. RESULTS: Four controlled studies met the inclusion criteria--3 were randomized studies and one was not. Strategies to increase screening rates included the use of educational packages targeting primary care physicians and the correction of barriers to screening within clinic systems. In 3 studies, the intervention was associated with an increase in screening rates of between 100% and 276% (p < 0.04). In the fourth study, the intervention was associated with a significant attenuation in declining screening rates over time (4% versus 34% decline, p = 0.04). CONCLUSION: There are only a limited number of randomized or controlled studies that demonstrate improved chlamydia screening of younger women in primary care.
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ItemExploring the feasibility of a community-based strength training program for older people with depressive symptoms and its impact on depressive symptoms.(Springer Science and Business Media LLC, 2006-11-30)BACKGROUND: Depression is a disabling, prevalent condition. Physical activity programs may assist depression management in older people, ameliorate co-morbid conditions and reduce the need for antidepressants. The UPLIFT pilot study assessed the feasibility of older depressed people attending a community-based progressive resistance training (PRT) program. The study also aimed to determine whether PRT improves depressive status in older depressed patients. METHODS: A randomised controlled trial was conducted. People aged > or = 65 years with depressive symptoms were recruited via general practices. Following baseline assessment, subjects were randomly allocated to attend a local PRT program three times per week for 10 weeks or a brief advice control group. Follow-up assessment of depressive status, physical and psychological health, functional and quality of life status occurred post intervention and at six months. RESULTS: Three hundred and forty six people responded to the study invitation, of whom 22% had depressive symptoms (Geriatric Depression Scale, GDS-30 score > or = 11). Thirty two people entered the trial. There were no significant group differences on the GDS at follow-up. At six months there was a trend for the PRT intervention group to have lower GDS scores than the comparison group, but this finding did not reach significance (p = 0.08). More of the PRT group (57%) had a reduction in depressive symptoms post program, compared to 44% of the control group. It was not possible to discern which specific components of the program influenced its impact, but in post hoc analyses, improvement in depressive status appeared to be associated with the number of exercise sessions completed (r = -0.8, p < 0.01). CONCLUSION: The UPLIFT pilot study confirmed that older people with depression can be successfully recruited to a community based PRT program. The program can be offered by existing community-based facilities, enabling its ongoing implementation for the potential benefit of other older people.
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ItemApaf-1 and caspase-9 accelerate apoptosis, but do not determine whether factor-deprived or drug-treated cells die(ROCKEFELLER UNIV PRESS, 2004-06-21)Apoptosis after growth factor withdrawal or drug treatment is associated with mitochondrial cytochrome c release and activation of Apaf-1 and caspase-9. To determine whether loss of Apaf-1, caspase-2, and caspase-9 prevented death of factor-starved cells, allowing them to proliferate when growth factor was returned, we generated IL-3-dependent myeloid lines from gene-deleted mice. Long after growth factor removal, cells lacking Apaf-1, caspase-9 or both caspase-9 and caspase-2 appeared healthy, retained intact plasma membranes, and did not expose phosphatidylserine. However, release of cytochrome c still occurred, and they failed to form clones when IL-3 was restored. Cells lacking caspase-2 alone had no survival advantage. Therefore, Apaf-1, caspase-2, and caspase-9 are not required for programmed cell death of factor-dependent cells, but merely affect its rate. In contrast, transfection with Bcl-2 provided long-term, clonogenic protection, and could act independently of the apoptosome. Unlike expression of Bcl-2, loss of Apaf-1, caspase-2, or caspase-9 would therefore be unlikely to enhance the survival of cancer cells.
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ItemBroad genomic and transcriptional analysis reveals a highly derived genome in dinoflagellate mitochondria(BIOMED CENTRAL LTD, 2007-09-27)BACKGROUND: Dinoflagellates comprise an ecologically significant and diverse eukaryotic phylum that is sister to the phylum containing apicomplexan endoparasites. The mitochondrial genome of apicomplexans is uniquely reduced in gene content and size, encoding only three proteins and two ribosomal RNAs (rRNAs) within a highly compacted 6 kb DNA. Dinoflagellate mitochondrial genomes have been comparatively poorly studied: limited available data suggest some similarities with apicomplexan mitochondrial genomes but an even more radical type of genomic organization. Here, we investigate structure, content and expression of dinoflagellate mitochondrial genomes. RESULTS: From two dinoflagellates, Crypthecodinium cohnii and Karlodinium micrum, we generated over 42 kb of mitochondrial genomic data that indicate a reduced gene content paralleling that of mitochondrial genomes in apicomplexans, i.e., only three protein-encoding genes and at least eight conserved components of the highly fragmented large and small subunit rRNAs. Unlike in apicomplexans, dinoflagellate mitochondrial genes occur in multiple copies, often as gene fragments, and in numerous genomic contexts. Analysis of cDNAs suggests several novel aspects of dinoflagellate mitochondrial gene expression. Polycistronic transcripts were found, standard start codons are absent, and oligoadenylation occurs upstream of stop codons, resulting in the absence of termination codons. Transcripts of at least one gene, cox3, are apparently trans-spliced to generate full-length mRNAs. RNA substitutional editing, a process previously identified for mRNAs in dinoflagellate mitochondria, is also implicated in rRNA expression. CONCLUSION: The dinoflagellate mitochondrial genome shares the same gene complement and fragmentation of rRNA genes with its apicomplexan counterpart. However, it also exhibits several unique characteristics. Most notable are the expansion of gene copy numbers and their arrangements within the genome, RNA editing, loss of stop codons, and use of trans-splicing.