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Induced Pluripotent Stem Cells As Tools For Disease Modelling And Drug Discovery In Alzheimer's Disease, Lezanne Ooi, Kuldip Sidhu, Anne Poljak, Greg Sutherland, Michael D. O'Connor, Perminder Sachdev, Gerald Munch Jan 2013

Induced Pluripotent Stem Cells As Tools For Disease Modelling And Drug Discovery In Alzheimer's Disease, Lezanne Ooi, Kuldip Sidhu, Anne Poljak, Greg Sutherland, Michael D. O'Connor, Perminder Sachdev, Gerald Munch

Faculty of Science - Papers (Archive)

Alzheimer’s disease (AD) is a progressive neurodegenerative brain disorder that leads to a progressive decline in a person’s memory and ability to communicate and carry out daily activities. The brain pathology in AD is characterized by extensive neuronal loss, particularly of cholinergic neurons, intracellular neurofibrillary tangles composed of the tau protein (NFTs) and extracellular deposition of plaques composed of β-amyloid (Aβ), a cleavage product of the amyloid precursor protein (APP). These two insoluble protein aggregates are accompanied by a chronic inflammatory response and extensive oxidative damage. Whereas dys-regulation of APP expression or processing appears to be important for the familial, …


Short And Long Sleep Duration Are Associated With Prevalent Cardiovascular Disease In Australian Adults, Christopher A. Magee, Len Kritharides, John Attia, Patrick Mcelduff, Emily Banks Jan 2012

Short And Long Sleep Duration Are Associated With Prevalent Cardiovascular Disease In Australian Adults, Christopher A. Magee, Len Kritharides, John Attia, Patrick Mcelduff, Emily Banks

Faculty of Health and Behavioural Sciences - Papers (Archive)

A growing number of studies from a range of different countries have observed an association between sleep duration and cardiovascular disease. The objective of this paper was to examine the associations between sleep duration and prevalent cardiovascular disease in a large sample of Australian adults, and identify the sociodemographic and health-related factors moderating these associations. Participants included 218 155 Australian adults aged 45 years and over. The results indicated that 6 h versus 7 h sleep was associated with increased odds of heart disease [odds ratio (OR) = 1.11 (1.06–1.17)], diabetes [OR = 1.15 (1.09–1.22)], stroke [OR = 1.25 (1.14–1.38)] …


Selective Reduction Of Hydroperoxyeicosatetraenoic Acids To Their Hydroxy Derivatives By Apolipoprotein D: Implications For Lipid Antioxidant Activity And Alzheimer's Disease, Surabhi Bhatia, Bianca Knoch, Jenny Wong, Woojin Scott Kim, Paul Else, Aaron J. Oakley, Brett Garner Jan 2012

Selective Reduction Of Hydroperoxyeicosatetraenoic Acids To Their Hydroxy Derivatives By Apolipoprotein D: Implications For Lipid Antioxidant Activity And Alzheimer's Disease, Surabhi Bhatia, Bianca Knoch, Jenny Wong, Woojin Scott Kim, Paul Else, Aaron J. Oakley, Brett Garner

Faculty of Science - Papers (Archive)

ApoD (apolipoprotein D) is up-regulated in AD (Alzheimer's disease) and upon oxidative stress. ApoD inhibits brain lipid peroxidation in vivo, but the mechanism is unknown. Specific methionine residues may inhibit lipid peroxidation by reducing radical-propagating L-OOHs (lipid hydroperoxides) to non-reactive hydroxides via a reaction that generates MetSO (methionine sulfoxide). Since apoD has three conserved methionine residues (Met49, Met93 and Met157), we generated recombinant proteins with either one or all methionine residues replaced by alanine and assessed their capacity to reduce HpETEs (hydroperoxyeicosatetraenoic acids) to their HETE (hydroxyeicosatetraenoic acid) derivatives. ApoD, apoDM49-A and apoDM157-A all catalysed the reduction of HpETEs to …


Disease Awareness Advertising: Women's Intentions Following Exposure, Danika Hall, Sandra C. Jones, Donald C. Iverson Jan 2011

Disease Awareness Advertising: Women's Intentions Following Exposure, Danika Hall, Sandra C. Jones, Donald C. Iverson

Faculty of Health and Behavioural Sciences - Papers (Archive)

Background: In Australia, where direct to consumer advertising of prescription medicines is prohibited, pharmaceutical companies can sponsor disease awareness advertising targeting consumers. This study examined the impact of disease awareness advertising exposure on older women's reported behavioural intentions. Method: Women were approached in a shopping centre and randomly assigned mock advertisements for two health conditions. Disease information and sponsors were manipulated. Results: Two hundred and forty-one women responded to 466 advertisements. Almost half reported an intention to ask their doctor for a prescription or referral as a result of seeing the advertisement, but more reported they would talk to their …


Effects Of Dairy Products On Crohn's Disease Symptoms Are Influenced By Fat Content And Disease Location But Not Lactose Content Or Disease Activity Status In A New Zealand Population, Deborah Nolan, Linda C. Tapsell, Rong Hu, Dug Yeo Han, Lynnette Ferguson Jan 2011

Effects Of Dairy Products On Crohn's Disease Symptoms Are Influenced By Fat Content And Disease Location But Not Lactose Content Or Disease Activity Status In A New Zealand Population, Deborah Nolan, Linda C. Tapsell, Rong Hu, Dug Yeo Han, Lynnette Ferguson

Faculty of Health and Behavioural Sciences - Papers (Archive)

Background Dairy products have been perceived as having the potential to cause adverse effects in individuals with Crohn’s disease (CD) and are often avoided, potentially increasing the risk of osteoporosis and related morbidity associated with inadequate dietary calcium intake. Objective To evaluate the self-reported effects of dairy products on CD symptoms and to determine whether these effects differed between types of dairy products consumed and disease state or location. Design Secondary analysis of dietary survey and clinical data from participants in the Genes and Diet in Inflammatory Bowel Disease study based in Auckland, New Zealand. Subjects/setting One hundred and sixty-five …


Wild Type And Tangier Disease Abca1 Mutants Modulate Cellular Amyloid-Beta Production Independent Of Cholesterol Efflux Activity, Kim S. Woojin, Andrew F. Hill, Michael L. Fitzgerald, Mason W. Freeman, Genevieve Evin, Brett Garner Jan 2011

Wild Type And Tangier Disease Abca1 Mutants Modulate Cellular Amyloid-Beta Production Independent Of Cholesterol Efflux Activity, Kim S. Woojin, Andrew F. Hill, Michael L. Fitzgerald, Mason W. Freeman, Genevieve Evin, Brett Garner

Faculty of Science - Papers (Archive)

Cerebral amyloid-β (Aβ) deposition is a critical feature of Alzheimer’s disease. Aβ is derived from the amyloid-β protein precursor (AβPP) via two sequential cleavages that are mediated by β-secretase and the γ-secretase complex. Such amyloidogenic AβPP processing occurs in lipid raft microdomains of cell membranes and it is thought that modulating the distribution of lipids in rafts may regulate AβPP processing and Aβ production. Certain ATP-binding cassette (ABC) transporters regulate lipid transport across cell membranes and, as recent studies reveal, within membrane microdomains. ABCA1 also regulates Aβ metabolism in the brain although its direct impact on AβPP remains an open …


Lipid Pathway Alterations In Parkinson's Disease Primary Visual Cortex, Danni Cheng, Andrew M. Jenner, Guanghou Shui, Wei Fun Cheong, Todd W. Mitchell, Jessica Nealon, Woojin Scott Kim, H Mccann, Markus R. Wenk, Glenda Halliday, Brett Garner Jan 2011

Lipid Pathway Alterations In Parkinson's Disease Primary Visual Cortex, Danni Cheng, Andrew M. Jenner, Guanghou Shui, Wei Fun Cheong, Todd W. Mitchell, Jessica Nealon, Woojin Scott Kim, H Mccann, Markus R. Wenk, Glenda Halliday, Brett Garner

Faculty of Science - Papers (Archive)

Background: We present a lipidomics analysis of human Parkinson’s disease tissues. We have focused on the primary visual cortex, a region that is devoid of pathological changes and Lewy bodies; and two additional regions, the amygdala and anterior cingulate cortex which contain Lewy bodies at different disease stages but do not have as severe degeneration as the substantia nigra. Methodology/Principal Findings: Using liquid chromatography mass spectrometry lipidomics techniques for an initial screen of 200 lipid species, significant changes in 79 sphingolipid, glycerophospholipid and cholesterol species were detected in the visual cortex of Parkinson’s disease patients (n = 10) compared to …


Genetic Adult Lactase Persistence Is Associated With Risk Of Crohn's Disease In A New Zealand Population, Deborah Nolan, Dug Yeo Han, Wen Jiun Lam, Angharad R. Morgan, Alan G. Fraser, Linda C. Tapsell, Lynnette R. Ferguson Jan 2010

Genetic Adult Lactase Persistence Is Associated With Risk Of Crohn's Disease In A New Zealand Population, Deborah Nolan, Dug Yeo Han, Wen Jiun Lam, Angharad R. Morgan, Alan G. Fraser, Linda C. Tapsell, Lynnette R. Ferguson

Faculty of Health and Behavioural Sciences - Papers (Archive)

Background Mycobacterium avium subspecies paratuberculosis (MAP) is an infective agent found in ruminants and milk products, which has been suggested to increase the risk of gastrointestinal inflammation in genetically susceptible hosts. It is hypothesized that lactase persistence facilitates exposure to such milk products increasing the likelihood of adverse outcomes. Individuals either homozygous or heterozygous for the T allele of DNA variant, rs4988235, located 14kb upstream from the LCT locus, are associated with having lactase persistence. The aim of this study was to determine whether lactase persistence as evident by the T allele of rs4988235 is associated with Crohn’s Disease (CD) …


Short Term Effects Of Energy Restriction And Dietary Fat Sub-Type On Weight Loss And Disease Risk Factors, Linda C. Tapsell, Marijka Batterham, Xu-Feng Huang, Sze Yen Tan, Grigorijs Teuss, Karen E. Charlton, Jane E. O'Shea, Eva M. Warensjo Jan 2010

Short Term Effects Of Energy Restriction And Dietary Fat Sub-Type On Weight Loss And Disease Risk Factors, Linda C. Tapsell, Marijka Batterham, Xu-Feng Huang, Sze Yen Tan, Grigorijs Teuss, Karen E. Charlton, Jane E. O'Shea, Eva M. Warensjo

Faculty of Health and Behavioural Sciences - Papers (Archive)

Background and aims: Decreasing energy intake relative to energy expenditure is the indisputable tenet of weight loss. In addition to caloric restriction modification of the type of dietary fat may provide further benefits. The aim of the present study was to examine the effect of energy restriction alone and with dietary fat modification on weight loss and adiposity, as well as on risk factors for obesity related disease. Methods and results: One-hundred and fifty overweight men and women were randomized into a 3 month controlled trial with four low fat (30% energy) dietary arms: (1) isocaloric (LF); (2) isocaloric with …


Protein Chemistry Of Amyloid Fibrils And Chaperones: Implications For Amyloid Formation And Disease, Justin J. Yerbury, Janet R. Kumita Jan 2010

Protein Chemistry Of Amyloid Fibrils And Chaperones: Implications For Amyloid Formation And Disease, Justin J. Yerbury, Janet R. Kumita

Faculty of Science - Papers (Archive)

Understanding the mechanisms by which amyloid fibrils are formed, both in vivo and in vitro, is vital for developing methods to treat and prevent debilitating deposition diseases such as Alzheimer's disease, Parkinson's disease, type II diabetes and systemic amyloidoses. In recent years, computer modelling and biophysical studies have broadened our understanding of the biochemical mechanisms underpinning protein aggregation. As a result, it is now believed that the ability to form fibrils is an intrinsic property of polypeptide chains and not isolated to disease-related proteins or peptides. Molecular chaperones are a diverse group of functionally related proteins well known for their …


Parameters Governing Invasive Disease Propensity Of Non-M1 Serotype Group A Streptococci, Peter G. Maamary, Martina L. Sanderson-Smith, Ramy K. Aziz, Andrew Hollands, Jason N. Cole, Fiona C. Mckay, Jason D. Mcarthur, Joshua K. Kirk, Amanda J. Cork, Rachael J. Keefe, Rita G. Kansal, Hongmin Sun, William L. Taylor, Gursharan S. Chhatwal, David Ginsburg, Victor Nizet, Malak Kotb, Mark J. Walker Jan 2010

Parameters Governing Invasive Disease Propensity Of Non-M1 Serotype Group A Streptococci, Peter G. Maamary, Martina L. Sanderson-Smith, Ramy K. Aziz, Andrew Hollands, Jason N. Cole, Fiona C. Mckay, Jason D. Mcarthur, Joshua K. Kirk, Amanda J. Cork, Rachael J. Keefe, Rita G. Kansal, Hongmin Sun, William L. Taylor, Gursharan S. Chhatwal, David Ginsburg, Victor Nizet, Malak Kotb, Mark J. Walker

Faculty of Science - Papers (Archive)

Group A Streptococcus (GAS) causes rare but life-threatening syndromes of necrotizing fasciitis and toxic shock-like syndrome in humans. The GAS serotype M1T1 clone has globally disseminated, and mutations in the control of virulence regulatory sensor kinase (covRS) operon correlate with severe invasive disease. Here, a cohort of non-M1 GAS was screened to determine whether mutation in covRS triggers systemic dissemination in divergent M serotypes. A GAS disease model defining parameters governing invasive propensity of differing M types is proposed. The vast majority of GAS infection is benign. Nonetheless, many divergent M types possess limited capacity to cause invasive infection. Mill …


The Two-Faced Nature Of Small Heat Shock Proteins: Amyloid Assembly And The Inhibition Of Fibril Formation. Relevance To Disease States, Heath W. Ecroyd, S Meehan, John A. Carver Jan 2010

The Two-Faced Nature Of Small Heat Shock Proteins: Amyloid Assembly And The Inhibition Of Fibril Formation. Relevance To Disease States, Heath W. Ecroyd, S Meehan, John A. Carver

Faculty of Science - Papers (Archive)

The ability of small heat-shock proteins (sHsps) such as alphaB-crystallin to inhibit the amorphous (disordered) aggregation of varied target proteins in a chaperone-like manner has been well described. The mechanistic details of this action are not understood. Amyloid fibril formation is an alternative off-folding pathway that leads to highly ordered beta-sheet-containing aggregates. Amyloid fibril formation is associated with a broad range of protein conformational diseases such as Alzhiemer's, Parkinson's and Huntington's and sHsp expression is elevated in the protein deposits that are characteristic of these disease states. The ability of sHsps to prevent fibril formation has been less well characterised. …


Disease Awareness Advertisements In Australian Magazines: An Analysis Of Content And Compliance, Danika Hall, Sandra C. Jones, Donald C. Iverson Jan 2009

Disease Awareness Advertisements In Australian Magazines: An Analysis Of Content And Compliance, Danika Hall, Sandra C. Jones, Donald C. Iverson

Faculty of Health and Behavioural Sciences - Papers (Archive)

In Australia, Direct to Consumer Advertising (DTCA) of prescription medicine is prohibited; however pharmaceutical companies can communicate directly with consumers via Disease Awareness Advertising (DAA). DAA can contain information about a disease including treatment information, but cannot mention the name of a particular product or brand. DAA is currently regulated by the industry body Medicines Australia (MA). In the current study, content analysis methodology was used to determine the extent and nature of DAA in popular Australian women’s magazines which were monitored for 12 months. Findings relating to the use of visual appeals in the imagery and rational appeals in …


Industry Partnerships For Health Nonprofits And Disease Awareness Advertising, Danika Hall, Sandra C. Jones, Donald C. Iverson Jan 2009

Industry Partnerships For Health Nonprofits And Disease Awareness Advertising, Danika Hall, Sandra C. Jones, Donald C. Iverson

Faculty of Health and Behavioural Sciences - Papers (Archive)

Marketing partnerships between non-profit organisations (NPOs) and industry generally bring favourable results for both parties (Brønn and Vrioni 2001; Varadarajan and Menon 1988). However, there is some scepticism about corporate exploitation of such arrangements and growing concern in Australia and elsewhere about partnerships between the pharmaceutical industry and NPOs (Angell 2006; Moynihan and Cassels 2005) and the co-sponsorship of Disease Awareness Advertising (DAA). This paper reports the findings from a study of how Australian women respond to DAA with differing sponsors including their ability to identify, and their attitude toward, the sponsor. The results are of importance for health NPOs …


Content Analysis Of Disease Awareness Advertisements In Popular Australian Women's Magazines, Danika V. Hall, Sandra C. Jones, Donald C. Iverson Jan 2009

Content Analysis Of Disease Awareness Advertisements In Popular Australian Women's Magazines, Danika V. Hall, Sandra C. Jones, Donald C. Iverson

Faculty of Health and Behavioural Sciences - Papers (Archive)

Objective: To examine the nature of disease awareness advertising (DAA). Design: Therapeutic advertisements in six popular Australian women’s magazines were monitored between April 2006 and March 2007. A subset of advertisements was included in the study based on criteria derived from a definition of DAA. Unique advertisements were analysed by four independent coders. Main outcome measures: Types of advertisements and their sponsors, the types of disease information present, and the persuasive techniques utilised. Results: Of 711 advertisements identified, 60 met the inclusion criteria for DAA, and 30 of these were unique. Over one-third of the advertisements were classified as “unbranded …


Unrealistic Pessimism About Risk Of Coronary Heart Disease And Stroke In Patients With Type 2 Diabetes, Koula G. Asimakopoulou, Timothy Chas Skinner, Jennifer Spimpolo, Sally Marsh, Charles Fox Jan 2008

Unrealistic Pessimism About Risk Of Coronary Heart Disease And Stroke In Patients With Type 2 Diabetes, Koula G. Asimakopoulou, Timothy Chas Skinner, Jennifer Spimpolo, Sally Marsh, Charles Fox

Faculty of Health and Behavioural Sciences - Papers (Archive)

OBJECTIVE: We examined the accuracy of type 2 diabetes (T2D) patients risk estimates of developing Coronary Heart Disease (CHD)/ having a stroke as a consequence of diabetes and their mood about these risks. METHODS: Patients reported their perceived risks of developing CHD/ having a stroke and rated their mood about these risks using a self-report measure. Using an objective risk calculator, they were then told their actual risk of CHD and stroke and their mood was re-assessed. RESULTS: Patients estimates of their risk of CHD / stroke were grossly inflated. A negative relationship between disease risk and mood was also …


Widespread Disruption Of Repressor Element-1 Silencing Transcription Factor/Neuron-Restrictive Silencer Factor Occupancy At Its Target Genes In Huntington's Disease, Chiara Zuccato, Nikolai D. Belyaev, Paola Conforti, Lezanne Ooi, Marzia Tartari, Evangelia Papadimou, Marcy Macdonald, Elisa Fossale, Scott Zeitlin, Noel J. Buckley, Elena Cattaneo Jan 2007

Widespread Disruption Of Repressor Element-1 Silencing Transcription Factor/Neuron-Restrictive Silencer Factor Occupancy At Its Target Genes In Huntington's Disease, Chiara Zuccato, Nikolai D. Belyaev, Paola Conforti, Lezanne Ooi, Marzia Tartari, Evangelia Papadimou, Marcy Macdonald, Elisa Fossale, Scott Zeitlin, Noel J. Buckley, Elena Cattaneo

Faculty of Science - Papers (Archive)

Huntingtin is a protein that is mutated in Huntington's disease (HD), a dominant inherited neurodegenerative disorder. We previously proposed that, in addition to the gained toxic activity of the mutant protein, selective molecular dysfunctions in HD may represent the consequences of the loss of wild-type protein activity. We first reported that wild-type huntingtin positively affects the transcription of the brain-derived neurotrophic factor (BDNF) gene, a cortically derived survival factor for the striatal neurons that are mainly affected in the disease. Mutation in huntingtin decreases BDNF gene transcription. One mechanism involves the activation of repressor element 1/neuron-restrictive silencer element (RE1/NRSE) located …


Targeting C-Reactive Protein For The Treatment Of Cardiovascular Disease, Mark B. Pepys, Gideon M. Hirschfield, Glenys A. Tennent, J Ruth Gallimore, Melvyn C. Kahan, Vittorio Bellotti, Philip N. Hawkins, Rebecca M. Myers, Martin D. Smith, Alessandra Polara, Alexander J. A Cobb, Steven V. Ley, J. Andrew Aquilina, Carol V. Robinson, Isam Sharif, Gillian A. Gray, Caroline A. Sabin, Michelle C. Jenvey, Simon E. Kolstoe, Darren Thompson, Stephen P. Wood Jan 2006

Targeting C-Reactive Protein For The Treatment Of Cardiovascular Disease, Mark B. Pepys, Gideon M. Hirschfield, Glenys A. Tennent, J Ruth Gallimore, Melvyn C. Kahan, Vittorio Bellotti, Philip N. Hawkins, Rebecca M. Myers, Martin D. Smith, Alessandra Polara, Alexander J. A Cobb, Steven V. Ley, J. Andrew Aquilina, Carol V. Robinson, Isam Sharif, Gillian A. Gray, Caroline A. Sabin, Michelle C. Jenvey, Simon E. Kolstoe, Darren Thompson, Stephen P. Wood

Faculty of Science - Papers (Archive)

Complement-mediated inflammation exacerbates the tissue injury of ischaemic necrosis in heart attacks and strokes, the most common causes of death in developed countries. Large infarct size increases immediate morbidity and mortality and, in survivors of the acute event, larger non-functional scars adversely affect long-term prognosis. There is thus an important unmet medical need for new cardioprotective and neuroprotective treatments. We have previously shown that human C-reactive protein (CRP), the classical acute-phase protein that binds to ligands exposed in damaged tissue and then activates complement1, increases myocardial and cerebral infarct size in rats subjected to coronary or cerebral artery ligation, respectively2,3. …


Importance Of Soy Protein And Isoflavone Intake For Protection Against Heart Disease, A Thorp, J Buckley, A Coates, Trevor A Mori, Jo Hodgson, Jackie Mansour, Peter Howe, Barbara Meyer Jan 2006

Importance Of Soy Protein And Isoflavone Intake For Protection Against Heart Disease, A Thorp, J Buckley, A Coates, Trevor A Mori, Jo Hodgson, Jackie Mansour, Peter Howe, Barbara Meyer

Faculty of Health and Behavioural Sciences - Papers (Archive)

Abstract presented at The 2006 Annual Scientific Meeting of the Nutrition Society of Australia, 29 November - 2 December, Sydney, Australia


Dietary Fats And Membrane Function: Implications For Metabolism And Disease, Anthony J. Hulbert, Nigel Turner, Leonard H. Storlein, Paul Else Jan 2005

Dietary Fats And Membrane Function: Implications For Metabolism And Disease, Anthony J. Hulbert, Nigel Turner, Leonard H. Storlein, Paul Else

Faculty of Health and Behavioural Sciences - Papers (Archive)

Lipids play varied and critical roles in metabolism, with function dramatically modulated by the individual fatty acid moities in complex lipid entities. In particular, the fatty acid composition of membrane lipids greatly influences membrane function. Here we consider the role of dietary fatty acid profile on membrane composition and, in turn, its impact on prevalent disease clusters of the metabolic syndrome and mental illness. Applying the classical physiological conformer-regulator paradigm to quantify the influence of dietary fats on membrane lipid composition (i.e. where the membrane variable is plotted against the same variable in the environment - in this case dietary …