Medicine and Health Sciences Commons^™

Heme Consumption Reduces Hepatic Triglyceride And Fatty Acid Accumulation In A Rat Model Of Nafld Fed Westernized Diet, Soon Yew Tang, Irwin Kee M. Cheah, Pei Ern Ng, Aina Hoi, Andrew M. Jenner

Illawarra Health and Medical Research Institute

Studies have identified that serum-free hemoglobin subunits correlate positively with the severity of nonalcoholic fatty liver disease (NAFLD). However, the role of hemoglobin in the development of NAFLD remains unclear. In the present study, a rat model of NAFLD was developed, using a westernized diet high in saturated fat and refined sugar. Since a "westernized" diet is also high in red meat, we tested the effect of hemoglobin as a dietary source of heme in our model. Sprague-Dawley rats were fed ad libitum for 4 weeks either control diet (7% fat), westernized diet (WD, 18% fat + 1% cholesterol), hemoglobin …

Expression And Purification Of Chaperone-Active Recombinant Clusterin, Rebecca Dabbs, Mark R. Wilson

Illawarra Health and Medical Research Institute

Clusterin was the first described secreted mammalian chaperone and is implicated as being a key player in both intra- and extracellular proteostasis. Its unique combination of structural features and biological chaperone activity has, however, previously made it very challenging to express and purify the protein in a correctly processed and chaperone-active form. While there are multiple reports in the literature describing the use of recombinant clusterin, all of these reports suffer from one or more of the following shortcomings: details of the methods used to produce the protein are poorly described, the product is incompletely (if at all) characterised, and …

Plasmin(Ogen) Acquisition By Group A Streptococcus Protects Against C3b-Mediated Neutrophil Killing, Diane Ly, Jude Taylor, James A. Tsatsaronis, Mercedes M. Monteleone, Amanda Skora, Cortny A. Donald, Tracy A. Maddocks, Victor Nizet, Nicholas P. West, Marie Ranson, Mark J. Walker, Jason D. Mcarthur, Martina L. Sanderson-Smith

Illawarra Health and Medical Research Institute

The globally significant human pathogen group A Streptococcus (GAS) sequesters the host protease plasmin to the cell surface during invasive disease initiation. Recent evidence has shown that localized plasmin activity prevents opsonization of several bacterial species by key components of the innate immune system in vitro. Here we demonstrate that plasmin at the GAS cell surface resulted in degradation of complement factor C3b, and that plasminogen acquisition is associated with a decrease in C3b opsonization and neutrophil-mediated killing in vitro. Furthermore, the ability to acquire cell surface plasmin(ogen) correlates directly with a decrease in C3b opsonization, neutrophil phagocytosis, and increased …

Altered Ceramide Acyl Chain Length And Ceramide Synthase Gene Expression In Parkinson's Disease, Sarah Abbott, Hongyun Li, Sonia Sanz Munoz, Bianca Knoch, Marijka Batterham, Karen E. Murphy, Glenda M. Halliday, Brett Garner

Illawarra Health and Medical Research Institute

Genetic studies have provided increasing evidence that ceramide homeostasis plays a role in neurodegenerative diseases including Parkinson's disease (PD). It is known that the relative amounts of different ceramide molecular species, as defined by their fatty acyl chain length, regulate ceramide function in lipid membranes and in signaling pathways. In the present study we used a comprehensive sphingolipidomic case-control approach to determine the effects of PD on ceramide composition in postmortem brain tissue from the anterior cingulate cortex (a region with significant PD pathology) and the occipital cortex (spared in PD), also assessing mRNA expression of the major ceramide synthase …

Foods And Food Components In The Mediterranean Diet: Supporting Overall Effects, Linda Tapsell

Illawarra Health and Medical Research Institute

The recent publication of the PREDIMED trial provided definitive evidence that a Mediterranean diet provides protection against cardiovascular disease. Two articles published in BMC Medicine provide further understanding of why this may be the case, by considering contributory effects of olive oil, a core food in the diet, and polyphenols, a class of identifiable protective compounds. Using a number of statistical models, analyses were conducted to show around a 35% cardiovascular disease risk reduction in the highest consumers of olive oil and a similar degree of risk reduction for all-cause mortality comparing highest to lowest quintiles of polyphenol intake. The …

Trust, Continuity And Agency: Keys To Understanding Older Patients' Attitudes To General Practice Trainees, Andrew Bonney, Sandra C. Jones, Donald C. Iverson, Christopher Magee

Illawarra Health and Medical Research Institute

Background: Populations are ageing and therefore non-communicable diseases are becoming leading causes of global morbidity, which need to be the focus of primary care services and training. Some older patients are uncomfortable with general practitioner (GP) trainees managing their chronic conditions, reducing clinical experience opportunities for trainees. This Australian cross-sectional study explored the factors underlying patients' attitudes to trainees in an agency theory framework. Methods: Fifty patients aged 60 and over from each of 38 training practices were offered a questionnaire after their consultation. Principal component analysis of the results was undertaken. Factor scores were calculated. Binary logistic modelling was …

Validating The Western Neuro Sensory Stimulation Profile For Patients With Severe Traumatic Brain Injury Who Are Slow-To-Recover, Anne Cusick, Natasha Lannin, Robyn Hanssen, Jeanine Allaous

Illawarra Health and Medical Research Institute

Background/aim The Western Neuro Sensory Stimulation Profile (WNSSP) is designed to measure disorders of consciousness in people with severe traumatic brain injury who are slow-to-recover. This study explores internal consistency reliability and concurrent validity of the WNSSP with function and two other consciousness measures. Method Retrospective chart audit of all severe traumatic brain injury patients admitted to a specialist neurological rehabilitation centre from January 2001 to December 2006 in a vegetative or minimally conscious state. Medical record of demographical, clinical and Glasgow Coma Scale (GCS) data were recorded. To be included in the study, patients needed admission and discharge WNSSP …

The Molecular Mechanisms Underpinning The Therapeutic Properties Of Oleanolic Acid, Its Isomer And Derivatives For Type 2 Diabetes And Associated Complications, Danielle Camer, Yinghua Yu, Alexander Szabo, Xu-Feng Huang

Illawarra Health and Medical Research Institute

Recent research has uncovered the molecular mechanisms responsible for the therapeutic properties of oleanolic acid (OA), its isomer ursolic acid (UA), and derivatives. In particular, recent reports have highlighted the benefits of these compounds in the prevention and treatment of type 2 diabetes and associated life-threatening complications, such as nonalcoholic fatty liver disease, nephropathy, retinopathy, and atherosclerosis. The prevalence of type 2 diabetes is of major concern since it is reaching global epidemic levels. Treatments targeting the signaling pathways altered in type 2 diabetes are being actively investigated, and OA and UA in natural and derivative forms are potential candidates …

The Common Acid Sphingomyelinase Polymorphism P.G508r Is Associated With Self-Reported Allergy, Martin Reichel, Tanja Richter-Schmidinger, Christiane Muhle, Cosima Rhein, Panagiotis Alexopoulos, Sibylle G. Schwab, Erich Gulbins, Johannes Kornhuber

Illawarra Health and Medical Research Institute

Background: Acid sphingomyelinase (ASM) is a key regulator of ceramide-dependent signalling pathways. Among others, activation of ASM can be induced by CD95 or cytokine signalling and by cellular stress resulting from inflammation or infection. Increased ASM activity was observed in a variety of human diseases including inflammatory and neuropsychiatric disorders. We hypothesized that basal ASM activity might influence the susceptibility for common human diseases. Methods: The general health condition of 100 young people was assessed using a questionnaire. The ASM polymorphism rs1050239 (c.1522G>A; encoding p.G508R) was determined from genomic DNA. Activities of secretory (S-) and lysosomal (L-) ASM were …

Comment On: Oleanolic Acid Co-Administration Alleviates Ethanol-Induced Hepatic Injury Via Nrf-2 And Ethanol-Metabolizing Modulation (Sic) In Rats, Danielle Camer, Xu-Feng Huang

Illawarra Health and Medical Research Institute

To the Editor: Alcohol induced hepatic oxidative stress and inflammation is known to cause liver injury. An increase in reactive oxidative species (ROS) from alcohol consumption leads to oxidative stress [1]. This can activate the inflammatory cytokines, IL-6 and TNF-α which promote liver injury. Both IL-6 and TNF-α are activated and transcribed by the inflammatory molecule, NFκB [2]. We read the interesting paper by Liu et al., entitled, “Oleanolic acid co-administration alleviates ethanol-induced hepatic injury via Nrf-2 and ethanol-metabolizing modulating in rats”, published in your journal recently [3]. The authors demonstrated that oleanolic acid can reduce hepatic injury by elevating …

The Endothelin Pathway: A Protective Or Detrimental Target Of Bardoxolone Methyl On Cardiac Function In Patients With Advanced Chronic Kidney Disease?, Danielle Camer, Xu-Feng Huang

Illawarra Health and Medical Research Institute

Bardoxolone methyl has been reported to cause detrimental cardiovascular events in the terminated BEACON Phase III human clinical trial via modulation of the renal endothelin pathway. However, the effects of bardoxolone methyl administration on the endothelin pathway in the heart are unknown. Our purpose in this perspective is to highlight the distinctive opposing roles of the renal and heart endothelin pathway in cardiac function. Furthermore, we address the need for further investigation in order to determine if bardoxolone methyl has a protective role in cardiac function through the suppression of the endothelin pathway in the heart.

Regulation Of A Trkb Alternative Transcript By Micrornas, Jenny Wong

Illawarra Health and Medical Research Institute

Background/Aims: Tropomyosin-related kinase B receptor (TrkB)-mediated signaling is vital for neuronal differentiation, survival, plasticity, and cognition. In this study, the focus was placed on TrkB-Shc, a neuron-specific transcript, to determine if microRNAs (miRNAs) play a role in TrkB-Shc regulation. Methods: A combination of bioinformatics and molecular gene expression analysis techniques was used to assess the effect of miR-409-3p and miR-216b on TrkB-Shc expression. Results: miR-409-3p and miR-216b were found to regulate the TrkB-Shc 3′UTR through the identified putative binding sites. When the effect of the miRNAs on TrkB was assessed using SHSY5Y neuronal cells, differential effects were observed between mRNA …

Loss Of The Neuroprotective Factor Sphingosine 1-Phosphate Early In Alzheimer's Disease Pathogenesis, Timothy A. Couttas, Nupur Kain, Benjamin Daniels, Xin Ying Lim, Claire E. Shepherd, Jillian Kril, Russell Pickford, Hongyun Li, Brett Garner, Anthony Don

Illawarra Health and Medical Research Institute

Background The greatest genetic risk factor for late-onset Alzheimer's disease (AD) is the ϵ4 allele of Apolipoprotein E (ApoE). ApoE regulates secretion of the potent neuroprotective signaling lipid Sphingosine 1-phosphate (S1P). S1P is derived by phosphorylation of sphingosine, catalysed by sphingosine kinases 1 and 2 (SphK1 and 2), and SphK1 positively regulates glutamate secretion and synaptic strength in hippocampal neurons. S1P and its receptor family have been subject to intense pharmacological interest in recent years, following approval of the immunomodulatory drug Fingolimod, an S1P mimetic, for relapsing multiple sclerosis. Results We quantified S1P levels in six brain regions that are …

Dyslipidemia Awareness, Treatment, Control And Influence Factors Among Adults In The Jilin Province In China: A Cross-Sectional Study, Huan He, Yaqin Yu, Yong Li, Chang Gui Kou, Bo Li, Yuchun Tao, Qing Zhen, Chang Wang, Joseph Sam Kanu, Xu-Feng Huang, Mei Han, Yawen Liu

Illawarra Health and Medical Research Institute

Background In China, even though the prevalence of dyslipidemia among adults increased yearly and dyslipidemia being an important risk factor for cardiovascular diseases among the Chinese population, however, the awareness, treatment and control of dyslipidemia are at low levels, and only limited studies on the influence factors associated with the awareness, treatment and control dyslipidemia in China have been carried out. Methods The analysis was based on a representative sample of 7138 adult subjects aged 18 ~ 79 years recruited from a cross-sectional study of chronic disease and risk factors among adults in the Jilin province in 2012. Chi-square test …

Hypothermia Protects Human Neurons, Ana Antonic, Mirella Dottori, Jessie Leung, Kate Sidon, Peter Batchelor, William J. Wilson, Malcolm R. Macleod, David W. Howells

Illawarra Health and Medical Research Institute

Background and Aims: Hypothermia provides neuroprotection after cardiac arrest, hypoxic-ischemic encephalopathy, and in animal models of ischemic stroke. However, as drug development for stroke has been beset by translational failure, we sought additional evidence that hypothermia protects human neurons against ischemic injury.

Methods: Human embryonic stem cells were cultured and differentiated to provide a source of neurons expressing β III tubulin, microtubule-associated protein 2, and the Neuronal Nuclei antigen. Oxygen deprivation, oxygen-glucose deprivation, and H₂O₂ -induced oxidative stress were used to induce relevant injury.

Results: Hypothermia to 33°C protected these human neurons against H …

Directing Human Induced Pluripotent Stem Cells Into A Neurosensory Lineage For Auditory Neuron Replacement, Niliksha Gunewardene, Nicole Van Bergen, Duncan E. Crombie, Karina Needham, Mirella Dottori, Bryony A. Nayagam

Illawarra Health and Medical Research Institute

Emerging therapies for sensorineural hearing loss include replacing damaged auditory neurons (ANs) using stem cells. Ultimately, it is important that these replacement cells can be patient-matched to avoid immunorejection. As human induced pluripotent stem cells (hiPSCs) can be obtained directly from the patient, they offer an opportunity to generate patient-matched neurons for transplantation. Here, we used an established neural induction protocol to differentiate two hiPSC lines (iPS1 and iPS2) and one human embryonic stem cell line (hESC; H9) toward a neurosensory lineage in vitro. Immunocytochemistry and qRT-PCR were used to analyze the expression of key markers involved in AN development …

A Reduction In Npas4 Expression Results In Delayed Neural Differentiation Of Mouse Embryonic Stem Cells, Thomas S. Klaric, Paul Q. Thomas, Mirella Dottori, Wai Khay Leong, Simon A. Koblar, Martin D. Lewis

Illawarra Health and Medical Research Institute

Introduction: Npas4 is a calcium-dependent transcription factor expressed within neurons of the brain where it regulates the expression of several genes that are important for neuronal survival and synaptic plasticity. It is known that in the adult brain Npas4 plays an important role in several key aspects of neurobiology including inhibitory synapse formation, neuroprotection and memory, yet very little is known about the role of Npas4 during neurodevelopment. The aim of this study was to examine the expression and function of Npas4 during nervous system development by using a combination of in vivo experiments in the developing mouse embryo …

Electrophysiological Properties Of Neurosensory Progenitors Derived From Human Embryonic Stem Cells, Karina Needham, Tomoko Hyakumura, Niliksha Gunewardene, Mirella Dottori, Bryony A. Nayagam

Illawarra Health and Medical Research Institute

In severe cases of sensorineural hearing loss where the numbers of auditory neurons are significantly depleted, stem cell-derived neurons may provide a potential source of replacement cells. The success of such a therapy relies upon producing a population of functional neurons from stem cells, to enable precise encoding of sound information to the brainstem. Using our established differentiation assay to produce sensory neurons from human stem cells, patch-clamp recordings indicated that all neurons examined generated action potentials and displayed both transient sodium and sustained potassium currents. Stem cell-derived neurons reliably entrained to stimuli up to 20 pulses per second (pps), …

Functional Characterization Of Friedreich Ataxia Ips-Derived Neuronal Progenitors And Their Integration In The Adult Brain, Matthew J. Bird, Karina Needham, Ann E. Frazier, Jorien Van Rooijen, Jessie Leung, Shelley Hough, Mark Denham, Matthew E. Thornton, Clare L. Parish, Bryony A. Nayagam, Martin F. Pera, David R. Thorburn, Lachlan H. Thompson, Mirella Dottori

Illawarra Health and Medical Research Institute

Friedreich ataxia (FRDA) is an autosomal recessive disease characterised by neurodegeneration and cardiomyopathy that is caused by an insufficiency of the mitochondrial protein, frataxin. Our previous studies described the generation of FRDA induced pluripotent stem cell lines (FA3 and FA4 iPS) that retained genetic characteristics of this disease. Here we extend these studies, showing that neural derivatives of FA iPS cells are able to differentiate into functional neurons, which don't show altered susceptibility to cell death, and have normal mitochondrial function. Furthermore, FA iPS-derived neural progenitors are able to differentiate into functional neurons and integrate in the nervous system when …

Perturbation Of Neuronal Cobalamin Transport By Lysosomal Enzyme Inhibition, Hua Zhao, Kalani Ruberu, Hongyun Li, Brett Garner

Illawarra Health and Medical Research Institute

Cobalamin (Cbl) utilization as an enzyme cofactor is dependent on its efficient transit through lysosomes to the cytosol and mitochondria. We have previously proposed that pathophysiological perturbations in lysosomal function may inhibit intracellular Cbl transport with consequences for down-stream metabolic pathways. In the current study we used both HT1080 fibroblasts and SH-SY5Y neurons to assess the impact that protease inhibitors, chloroquine and leupeptin, have on the distribution of [57Co] Cbl in lysosomes, mitochondria and cytosol. Under standard cell culture conditions the distribution of [57Co] Cbl in both neurons and fibroblasts was approximately 5% in lysosomes, 14% in mitochondria, and 81% …

Determination Of Anti-Inflammatory Activities Of Standardised Preparations Of Plant- And Mushroom-Based Foods, Dhanushka Gunawardena, Kirubakaran Shanmugam, Suresh Govindaraghavan, Mitchell Low, Louise Bennett, Richard Head, Lezanne Ooi, Gerald Münch

Illawarra Health and Medical Research Institute

Purpose: Chronic inflammatory processes contribute to the pathogenesis of many age-related diseases. In search of anti-inflammatory foods, we have systematically screened a variety of common dietary plants and mushrooms for their anti-inflammatory activity.

Methods: A selection of 115 samples was prepared by a generic food-compatible processing method involving heating. These products were tested for their anti-inflammatory activity in murine N11 microglia and RAW 264.7 macrophages, using nitric oxide (NO) and tumour necrosis factor-α (TNF-α) as pro-inflammatory readouts.

Results: Ten food samples including lime zest, English breakfast tea, honey-brown mushroom, button mushroom, oyster mushroom, cinnamon and cloves inhibited NO production in …

Hypothalamic Ghrelin Signalling Mediates Olanzapine-Induced Hyperphagia And Weight Gain In Female Rats, Qingsheng Zhang, Meng He, Chao Deng, Hongqin Wang, Jiamei Lian, Xu-Feng Huang

Illawarra Health and Medical Research Institute

Excessive weight gain is a major metabolic side effect of second-generation antipsychotics (SGAs) in the treatment of schizophrenia. Ghrelin is an orexigenic hormone secreted mainly from the stomach, which can induce weight gain and hyperphagia through regulating neuropeptides at the hypothalamus. Accumulating evidence implicates a relationship between ghrelin signalling and SGA-induced hyperphagia and weight gain. We report that olanzapine (a SGA with high weight gain liability) potently and time-dependently up-regulate ghrelin and ghrelin signalling, leading to hyperphagia and weight gain in female Sprague-Dawley rats, an action reversed by i.c.v. injection of a ghrelin receptor (GHS-R1a) antagonist. These findings indicate a …

Hypothalamic Histamine H1 Receptor-Ampk Signaling Time-Dependently Mediates Olanzapine-Induced Hyperphagia And Weight Gain In Female Rats, Meng He, Qingsheng Zhang, Chao Deng, Hongqin Wang, Jiamei Lian, Xu-Feng Huang

Illawarra Health and Medical Research Institute

Although second-generation antipsychotics induce severe weight gain and obesity, there is a lack of detailed knowledge about the progressive development of antipsychotic-induced obesity. This study examined the hypothalamic histamine H1 receptor and AMP-activated protein kinase (H1R-AMPK) signaling at three distinctive stages of olanzapine-induced weight gain (day 1-12: early acceleration, day 13-28: middle new equilibrium, and day 29-36: late heavy weight maintenance). At the early acceleration stage, the rats were hyperphagic with an underlying mechanism of olanzapine-increased H1R mRNA expression and AMPK phosphorylation (pAMPK), in which pAMPK levels positively correlated with H1R mRNA expression and food intake. At the middle stage, …

Insulin Induces Drug Resistance In Melanoma Through Activation Of The Pi3k/Akt Pathway, Mengna Chi, Yan Ye, Xu Dong Zhang, Jiezhong Chen

Illawarra Health and Medical Research Institute

Introduction: There is currently no curative treatment for melanoma once the disease spreads beyond the original site. Although activation of the PI3K/Akt pathway resulting from genetic mutations and epigenetic deregulation of its major regulators is known to cause resistance of melanoma to therapeutic agents, including the conventional chemotherapeutic drug dacarbazine and the Food and Drug Administration-approved mutant BRAF inhibitors vemurafenib and dabrafenib, the role of extracellular stimuli of the pathway, such as insulin, in drug resistance of melanoma remains less understood. Objective: To investigate the effect of insulin on the response of melanoma cells to dacarbazine, and in particular, the …

Probenecid Blocks Human P2x7 Receptor-Induced Dye Uptake Via A Pannexin-1 Independent Mechanism, Archana Bhaskaracharya, Phuong Dao-Ung, Iman Jalilian, Mari Spildrejorde, Kristen K. Skarratt, Stephen Fuller, Ronald Sluyter, Leanne Stokes

Illawarra Health and Medical Research Institute

P2X7 is a ligand-gated ion channel which is activated by ATP and displays secondary permeability characteristics. The mechanism of development of the secondary permeability pathway is currently unclear, although a role for the hemichannel protein pannexin-1 has been suggested. In this study we investigated the role of pannexin-1 in P2X7-induced dye uptake and ATP-induced IL-1β secretion from human monocytes. We found no pharmacological evidence for involvement of pannexin-1 in P2X7-mediated dye uptake in transfected HEK-293 cells with no inhibition seen for carbenoxolone and the pannexin-1 mimetic inhibitory peptide, 10Panx1. However, we found that probenecid inhibited P2X7-induced cationic and anionic dye …

Informal Mining In Livelihood Diversification: Mineral Dependence And Rural Communities In Lao Pdr, Kuntala Lahiri-Dutt, Kim Alexander, Chansouk Insouvanh

Illawarra Health and Medical Research Institute

In the context of mineral extraction in South East Asia, the rural poor are generally portrayed as victims of large, invading corporatized mining enterprises. However, this paper argues that local villagers have also shown considerable agency in taking advantage of the mineral resource boom by diversifying their livelihoods to include informal mining. In South East Asia, the growth of informal mining has occurred within the overall process of agrarian transition. This paper focuses on a mineral-rich valley in southern Laos to highlight the location-specific nature of such transitions. The valley's environmental transformation has both caused and accompanied a modification in …

Negativity Towards Negative Results: A Discussion Of The Disconnect Between Scientific Worth And Scientific Culture, Natalie Matosin, Elisabeth Frank, Martin Engel, Jeremy S. Lum, Kelly Newell

Illawarra Health and Medical Research Institute

Science is often romanticised as a flawless system of knowledge building, where scientists work together to systematically find answers. In reality, this is not always the case. Dissemination of results are straightforward when the findings are positive, but what happens when you obtain results that support the null hypothesis, or do not fit with the current scientific thinking? In this Editorial, we discuss the issues surrounding publication bias and the difficulty in communicating negative results. Negative findings are a valuable component of the scientific literature because they force us to critically evaluate and validate our current thinking, and fundamentally move …

Human Protein Aging: Modification And Crosslinking Through Dehydroalanine And Dehydrobutyrine Intermediates, Zhen Wang, Brian Lyons, Roger J. W Truscott, Kevin L. Schey

Illawarra Health and Medical Research Institute

Nonenzymatic post-translational modification (PTM) of proteins is a fundamental molecular process of aging. The combination of various modifications and their accumulation with age not only affects function, but leads to crosslinking and protein aggregation. In this study, aged human lens proteins were examined using HPLC–tandem mass spectrometry and a blind PTM search strategy. Multiple thioether modifications of Ser and Thr residues by glutathione (GSH) and its metabolites were unambiguously identified. Thirty-four of 36 sites identified on 15 proteins were found on known phosphorylation sites, supporting a mechanism involving dehydroalanine (DHA) and dehydrobutyrine (DHB) formation through β-elimination of phosphoric acid from …

Intercellular Propagated Misfolding Of Wild-Type Cu/Zn Superoxide Dismutase Occurs Via Exosome-Dependent And -Independent Mechanisms, Leslie I. Grad, Justin J. Yerbury, Bradley J. Turner, William C. Guest, Edward Pokrishevsky, Megan A. O'Neill, Anat Yanai, Judith M. Silverman, Rafaa Zeineddine, Lisa Corcoran, Janet Kumita, Leila Luheshi, Masoud Yousefi, Bradley M. Coleman, Andrew Hill, Steven S. Plotkin, Ian R. Mackenzie, Neil R. Cashman

Illawarra Health and Medical Research Institute

Amyotrophic lateral sclerosis (ALS) is predominantly sporadic, but associated with heritable genetic mutations in 5-10% of cases, including those in Cu/Zn superoxide dismutase (SOD1). We previously showed that misfolding of SOD1 can be transmitted to endogenous human wild-type SOD1 (HuWtSOD1) in an intracellular compartment. Using NSC-34 motor neuron-like cells, we now demonstrate that misfolded mutant and HuWtSOD1 can traverse between cells via two nonexclusive mechanisms: protein aggregates released from dying cells and taken up by macropinocytosis, and exosomes secreted from living cells. Furthermore, once HuWtSOD1 propagation has been established, misfolding of HuWtSOD1 can be efficiently and repeatedly propagated between HEK293 …

A Novel Population Health Data Source To Inform Local Planning: The Simlr Study, Darren J. Mayne, Andrew Bonney, Bryan Jones, Lawrence Bott, Stephen Andersen, Peter Caputi, Donald C. Iverson

Illawarra Health and Medical Research Institute

Abstract of a paper that was presented at 2014 Primary Health Care Research Conference, Canberra, Australia, 23-25 July.