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Olanzapine Prevents The Pcp-Induced Reduction In The Neurite Outgrowth Of Prefrontal Cortical Neurons Via Nrg1, Qingsheng Zhang, Yinghua Yu, Xu-Feng Huang Jan 2016

Olanzapine Prevents The Pcp-Induced Reduction In The Neurite Outgrowth Of Prefrontal Cortical Neurons Via Nrg1, Qingsheng Zhang, Yinghua Yu, Xu-Feng Huang

Illawarra Health and Medical Research Institute

Accumulating evidence suggests that reducing neurite outgrowth and synaptic plasticity plays a critical role in the pathology of cognitive deficits in schizophrenia. The N-methyl-D-aspartate receptor antagonist phencyclidine (PCP) can induce symptoms of schizophrenia as well as reduce dendritic spine density and neurite growth. The antipsychotic drug olanzapine may improve these deficits. This study aimed to investigate: (1) if olanzapine prevents PCP-induced suppression of neurite outgrowth and synaptic protein expression; (2) if olanzapine affects the Akt-GSK3 signaling pathway; and (3) the role of neuregulin 1 (NRG1) in this process. Immunofluorescence revealed that PCP treatment for 24 hours reduces both neurite length …


Exchange Between Escherichia Coli Polymerases Ii And Iii On A Processivity Clamp, James E. Kath, Seungwoo Chang, Michelle K. Scotland, Johannes H. Wilbertz, Slobodan Jergic, Nicholas E. Dixon, Mark D. Sutton, Joseph J. Loparo Jan 2016

Exchange Between Escherichia Coli Polymerases Ii And Iii On A Processivity Clamp, James E. Kath, Seungwoo Chang, Michelle K. Scotland, Johannes H. Wilbertz, Slobodan Jergic, Nicholas E. Dixon, Mark D. Sutton, Joseph J. Loparo

Illawarra Health and Medical Research Institute

Escherichia coli has three DNA polymerases implicated in the bypass of DNA damage, a process called translesion synthesis (TLS) that alleviates replication stalling. Although these polymerases are specialized for different DNA lesions, it is unclear if they interact differently with the replication machinery. Of the three, DNA polymerase (Pol) II remains the most enigmatic. Here we report a stable ternary complex of Pol II, the replicative polymerase Pol III core complex and the dimeric processivity clamp, β. Single-molecule experiments reveal that the interactions of Pol II and Pol III with β allow for rapid exchange during DNA synthesis. As with …


Spontaneous Cleavage Of Proteins At Serine And Threonine Is Facilitated By Zinc, Brian Lyons, Ann H. Kwan, Roger J. W Truscott Jan 2016

Spontaneous Cleavage Of Proteins At Serine And Threonine Is Facilitated By Zinc, Brian Lyons, Ann H. Kwan, Roger J. W Truscott

Illawarra Health and Medical Research Institute

Old proteins are widely distributed in the body. Over time, they deteriorate and many spontaneous reactions, for example isomerisation of Asp and Asn, can be replicated by incubation of peptides under physiological conditions. One of the signatures of long-lived proteins that has proven to be difficult to replicate in vitro is cleavage on the N-terminal side of Ser residues, and this is important since cleavage at Ser, and also Thr, has been observed in a number of human proteins. In this study, the autolysis of Ser- and Thr-containing peptides was investigated with particular reference to discovering factors that promote cleavage …


Cerebral Apolipoprotein-D Is Hypoglycosylated Compared To Peripheral Tissues And Is Variably Expressed In Mouse And Human Brain Regions, Hongyun Li, Kalani R. Ruberu, Tim Karl, Brett Garner Jan 2016

Cerebral Apolipoprotein-D Is Hypoglycosylated Compared To Peripheral Tissues And Is Variably Expressed In Mouse And Human Brain Regions, Hongyun Li, Kalani R. Ruberu, Tim Karl, Brett Garner

Illawarra Health and Medical Research Institute

Recent studies have shown that cerebral apoD levels increase with age and in Alzheimer's disease (AD). In addition, loss of cerebral apoD in the mouse increases sensitivity to lipid peroxidation and accelerates AD pathology. Very little data are available, however, regarding the expression of apoD protein levels in different brain regions. This is important as both brain lipid peroxidation and neurodegeneration occur in a region-specific manner. Here we addressed this using western blotting of seven different regions (olfactory bulb, hippocampus, frontal cortex, striatum, cerebellum, thalamus and brain stem) of the mouse brain. Our data indicate that compared to most brain …


Abca7 Deletion Does Not Affect Adult Neurogenesis In The Mouse, Hongyun Li, Tim Karl, Brett Garner Jan 2016

Abca7 Deletion Does Not Affect Adult Neurogenesis In The Mouse, Hongyun Li, Tim Karl, Brett Garner

Illawarra Health and Medical Research Institute

ATP-binding cassette transporter A7 (ABCA7) is highly expressed in the brain. Recent genome-wide association studies (GWAS) have identified ABCA7 single nucleotide polymorphisms (SNPs) that increase Alzheimer's disease (AD) risk, however, the mechanisms by which ABCA7 may control AD risk remain to be fully elucidated. Based on previous research suggesting that certain ABC transporters may play a role in the regulation of neurogenesis, we conducted a study of cell proliferation and neurogenic potential using cellular bromodeoxyuridine (BrdU) incorporation and doublecortin (DCX) immunostaining in adult Abca7 deficient mice and wild-type-like (WT) littermates. In the present study counting of BrdU-positive and DCX-positive cells …


Synthesis And Preliminary Evaluation Of 5,7-Dimethyl-2-Aryl-3h-Pyrrolizin-3-Ones As Angiogenesis Inhibitors, Nicholas Kirk, Anna Bezos, Anthony C. Willis, Pichit Sudta, Sunit Suksamrarn, Christopher R. Parish, Marie Ranson, Michael J. Kelso Jan 2016

Synthesis And Preliminary Evaluation Of 5,7-Dimethyl-2-Aryl-3h-Pyrrolizin-3-Ones As Angiogenesis Inhibitors, Nicholas Kirk, Anna Bezos, Anthony C. Willis, Pichit Sudta, Sunit Suksamrarn, Christopher R. Parish, Marie Ranson, Michael J. Kelso

Illawarra Health and Medical Research Institute

Sunitinib (Sutent®) is a receptor tyrosine kinase (RTK) and angiogenesis inhibitor approved for the treatment of renal cell carcinomas, gastrointestinal stromal tumours and pancreatic neuroendocrine tumours. A key structural motif retained throughout medicinal chemistry efforts during sunitinib's development was the indoline-2-one group. In the search for new anti-angiogenic scaffolds, we previously reported that non-indoline-2-one-based derivatives of semaxanib (SU5416, a structurally simpler sunitinib predecessor that underwent Phase III trials) are active as angiogenesis inhibitors, indicating that the group is not essential for activity. This Letter describes the synthesis and structure-activity relationships of another class of non-indoline-2-one angiogenesis inhibitors related to sunitinib/semaxanib; …


Ccnf Mutations In Amyotrophic Lateral Sclerosis And Frontotemporal Dementia, Kelly L. Williams, Simom Topp, Shu Yang, Bradley Smith, Jennifer A. Fifita, Sadaf T. Warraich, Katharine Y. Zhang, Natalie E. Farrawell, Caroline Vance, Xun Hu, Justin J. Yerbury Jan 2016

Ccnf Mutations In Amyotrophic Lateral Sclerosis And Frontotemporal Dementia, Kelly L. Williams, Simom Topp, Shu Yang, Bradley Smith, Jennifer A. Fifita, Sadaf T. Warraich, Katharine Y. Zhang, Natalie E. Farrawell, Caroline Vance, Xun Hu, Justin J. Yerbury

Illawarra Health and Medical Research Institute

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are overlapping, fatal neurodegenerative disorders in which the molecular and pathogenic basis remains poorly understood. Ubiquitinated protein aggregates, of which TDP-43 is a major component, are a characteristic pathological feature of most ALS and FTD patients. Here we use genome-wide linkage analysis in a large ALS/FTD kindred to identify a novel disease locus on chromosome 16p13.3. Whole-exome sequencing identified a CCNF missense mutation at this locus. Interrogation of international cohorts identified additional novel CCNF variants in familial and sporadic ALS and FTD. Enrichment of rare protein-altering CCNF variants was evident in a …


Aripiprazole Increases The Pka Signalling And Expression Of The GabaA Receptor And Creb1 In The Nucleus Accumbens Of Rats, Bo Pan, Jiamei Lian, Xu-Feng Huang, Chao Deng Jan 2016

Aripiprazole Increases The Pka Signalling And Expression Of The GabaA Receptor And Creb1 In The Nucleus Accumbens Of Rats, Bo Pan, Jiamei Lian, Xu-Feng Huang, Chao Deng

Illawarra Health and Medical Research Institute

The GABAA receptor is implicated in the pathophysiology of schizophrenia and regulated by PKA signalling. Current antipsychotics bind with D2-like receptors, but not the GABAA receptor. The cAMP-responsive element-binding protein 1 (CREB1) is also associated with PKA signalling and may be related to the positive symptoms of schizophrenia. This study investigated the effects of antipsychotics in modulating D2-mediated PKA signalling and its downstream GABAA receptors and CREB1. Rats were treated orally with aripiprazole (0.75 mg/kg, ter in die (t.i.d.)), bifeprunox (0.8 mg/kg, t.i.d.), haloperidol (0.1 mg/kg, t.i.d.) or vehicle for 1 week. The levels of PKA-Cα and p-PKA in the …


Validation Of An Automated Colony Counting System For Group A Streptococcus, H R. Frost, S K. Tsoi, C A. Baker, D Laho, Martina L. Sanderson-Smith, Andrew C. Steer, Pierre R. Smeesters Jan 2016

Validation Of An Automated Colony Counting System For Group A Streptococcus, H R. Frost, S K. Tsoi, C A. Baker, D Laho, Martina L. Sanderson-Smith, Andrew C. Steer, Pierre R. Smeesters

Illawarra Health and Medical Research Institute

Background The practice of counting bacterial colony forming units on agar plates has long been used as a method to estimate the concentration of live bacteria in culture. However, due to the laborious and potentially error prone nature of this measurement technique, an alternative method is desirable. Recent technologic advancements have facilitated the development of automated colony counting systems, which reduce errors introduced during the manual counting process and recording of information. An additional benefit is the significant reduction in time taken to analyse colony counting data. Whilst automated counting procedures have been validated for a number of microorganisms, the …


A Label-Free And High-Throughput Separation Of Neuron And Glial Cells Using An Inertial Microfluidic Platform, Tiantian Jin, Sheng Yan, Jun Zhang, Dan Yuan, Xu-Feng Huang, Weihua Li Jan 2016

A Label-Free And High-Throughput Separation Of Neuron And Glial Cells Using An Inertial Microfluidic Platform, Tiantian Jin, Sheng Yan, Jun Zhang, Dan Yuan, Xu-Feng Huang, Weihua Li

Illawarra Health and Medical Research Institute

While neurons and glial cells both play significant roles in the development and therapy of schizophrenia, their specific contributions are difficult to differentiate because the methods used to separate neurons and glial cells are ineffective and inefficient. In this study, we reported a high-throughput microfluidic platform based on the inertial microfluidic technique to rapidly and continuously separate neurons and glial cells from dissected brain tissues. The optimal working condition for an inertial biochip was investigated and evaluated by measuring its separation under different flow rates. Purified and enriched neurons in a primary neuron culture were verified by confocal immunofluorescence imaging, …


Common Pitfalls Of Stem Cell Differentiation: A Guide To Improving Protocols For Neurodegenerative Disease Models And Research, Martin Engel, Phuong Dzung Do-Ha, Sonia Sanz Munoz, Lezanne Ooi Jan 2016

Common Pitfalls Of Stem Cell Differentiation: A Guide To Improving Protocols For Neurodegenerative Disease Models And Research, Martin Engel, Phuong Dzung Do-Ha, Sonia Sanz Munoz, Lezanne Ooi

Illawarra Health and Medical Research Institute

Induced pluripotent stem cells and embryonic stem cells have revolutionized cellular neuroscience, providing the opportunity to model neurological diseases and test potential therapeutics in a pre-clinical setting. The power of these models has been widely discussed, but the potential pitfalls of stem cell differentiation in this research are less well described. We have analyzed the literature that describes differentiation of human pluripotent stem cells into three neural cell types that are commonly used to study diseases, including forebrain cholinergic neurons for Alzheimer's disease, midbrain dopaminergic neurons for Parkinson's disease and cortical astrocytes for neurodegenerative and psychiatric disorders. Published protocols for …


Chlorogenic Acid Protects D-Galactose-Induced Liver And Kidney Injury Via Antioxidation And Anti-Inflammation Effects In Mice, Yan Feng, Yinghua Yu, Shu-Ting Wang, Jing Ren, Danielle Camer, Yu-Zhou Hua, Qian Zhang, Jie Huang, Dan-Lu Xue, Xiaofei Zhang, Xu-Feng Huang, Yi Liu Jan 2016

Chlorogenic Acid Protects D-Galactose-Induced Liver And Kidney Injury Via Antioxidation And Anti-Inflammation Effects In Mice, Yan Feng, Yinghua Yu, Shu-Ting Wang, Jing Ren, Danielle Camer, Yu-Zhou Hua, Qian Zhang, Jie Huang, Dan-Lu Xue, Xiaofei Zhang, Xu-Feng Huang, Yi Liu

Illawarra Health and Medical Research Institute

Context Oxidative stress and inflammation are implicated in the aging process and its related hepatic and renal function decline. Chlorogenic acid (CGA) is one of the most abundant polyphenol compounds in the human diet. Recently, CGA has shown in vivo and in vitro antioxidant properties. Objective The current study investigates the effects of protective effects of chlorogenic acid (CGA) on d-galactose-induced liver and kidney injury. Materials and methods Hepatic and renal injuries were induced in a mouse model by subcutaneously injection of d-galactose (d-gal; 100 mg/kg) once a day for 8 consecutive weeks and orally administered simultaneously with CGA included …


An Mri Study Of White Matter Tract Integrity In Regular Cannabis Users: Effects Of Cannabis Use And Age, David D. Jakabek, Murat Yücel, Valentina Lorenzetti, Nadia Solowij Jan 2016

An Mri Study Of White Matter Tract Integrity In Regular Cannabis Users: Effects Of Cannabis Use And Age, David D. Jakabek, Murat Yücel, Valentina Lorenzetti, Nadia Solowij

Illawarra Health and Medical Research Institute

Rationale Conflicting evidence exists on the effects of cannabis use on brain white matter integrity. The extant literature has exclusively focused on younger cannabis users, with no studies sampling older cannabis users. Objectives We recruited a sample with a broad age range to examine the integrity of major white matter tracts in association with cannabis use parameters and neurodevelopmental stage. Methods Regular cannabis users (n = 56) and non-users (n = 20) with a mean age of 32 (range 18-55 years) underwent structural and diffusion MRI scans. White matter was examined using voxel-based statistics and via probabilistic tract reconstruction. The …


A School-Based Health Promotion Programme To Increase Help-Seeking For Substance Use And Mental Health Problems: Study Protocol For A Randomised Controlled Trial, Daniel Lubman, Bonita J. Berridge, Fiona Blee, Anthony F. Jorm, Coralie J. Wilson, Nicholas B. Allen, Lisa Mckay-Brown, Jenny Proimos, Ali Cheetham, Rory Wolfe Jan 2016

A School-Based Health Promotion Programme To Increase Help-Seeking For Substance Use And Mental Health Problems: Study Protocol For A Randomised Controlled Trial, Daniel Lubman, Bonita J. Berridge, Fiona Blee, Anthony F. Jorm, Coralie J. Wilson, Nicholas B. Allen, Lisa Mckay-Brown, Jenny Proimos, Ali Cheetham, Rory Wolfe

Illawarra Health and Medical Research Institute

Background Adolescence is a high-risk time for the development of mental health and substance use problems. However, fewer than one in four 16-24 year-olds with a current disorder access health services, with those experiencing a substance use disorder being the least likely to seek professional help. Research indicates that young people are keeping their problems to themselves or alternatively, turning to peers or trusted adults in their lives for help. These help-seeking preferences highlight the need to build the mental health literacy of adolescents, to ensure that they know when and how to assist themselves and their peers to access …


Beneficial Effects Of Increased Lysozyme Levels In Alzheimer's Disease Modelled In Drosophila Melanogaster, Linnea Sandin, Liza Bergkvist, Sangeeta Nath, Claudia Kielkopf, Camilla Janefjord, Linda Helmfors, Henrik Zetterberg, Kaj Blennow, Hongyun Li, Camilla Nilsberth, Brett Garner, Ann-Christin Brorsson, Katarina Kagedal Jan 2016

Beneficial Effects Of Increased Lysozyme Levels In Alzheimer's Disease Modelled In Drosophila Melanogaster, Linnea Sandin, Liza Bergkvist, Sangeeta Nath, Claudia Kielkopf, Camilla Janefjord, Linda Helmfors, Henrik Zetterberg, Kaj Blennow, Hongyun Li, Camilla Nilsberth, Brett Garner, Ann-Christin Brorsson, Katarina Kagedal

Illawarra Health and Medical Research Institute

Genetic polymorphisms of immune genes that associate with higher risk to develop Alzheimer's disease (AD) have led to an increased research interest on the involvement of the immune system in AD pathogenesis. A link between amyloid pathology and immune gene expression was suggested in a genome-wide gene expression study of transgenic amyloid mouse models. In this study, the gene expression of lysozyme, a major player in the innate immune system, was found to be increased in a comparable pattern as the amyloid pathology developed in transgenic mouse models of AD. A similar pattern was seen at protein levels of lysozyme …


Efficacy Of The Herpes Zoster Subunit Vaccine In Adults 70 Years Of Age Or Older, A L Cunningham, Himal Lal, Martina Kovac, Roman Chlibek, Shinn-Jang Hwang, Javier Diez-Domingo, Olivier Godeaux, Myron J. Levin, Janet E. Mcelhaney, Joan Puig-Barbera, Wilfred W. Yeo Jan 2016

Efficacy Of The Herpes Zoster Subunit Vaccine In Adults 70 Years Of Age Or Older, A L Cunningham, Himal Lal, Martina Kovac, Roman Chlibek, Shinn-Jang Hwang, Javier Diez-Domingo, Olivier Godeaux, Myron J. Levin, Janet E. Mcelhaney, Joan Puig-Barbera, Wilfred W. Yeo

Illawarra Health and Medical Research Institute

BACKGROUND A trial involving adults 50 years of age or older (ZOE-50) showed that the herpes zoster subunit vaccine (HZ/su) containing recombinant varicella-zoster virus glycoprotein E and the AS01B adjuvant system was associated with a risk of herpes zoster that was 97.2% lower than that associated with placebo. A second trial was performed concurrently at the same sites and examined the safety and efficacy of HZ/su in adults 70 years of age or older (ZOE-70). METHODS This randomized, placebo-controlled, phase 3 trial was conducted in 18 countries and involved adults 70 years of age or older. Participants received two doses …


Videomicroscopy As A Tool For Investigation Of The Microcirculation In The Newborn, Ian M. R Wright, Joanna L. Latter, Rebecca M. Dyson, Christopher (Chris) Levi, Vicki L. Clifton Jan 2016

Videomicroscopy As A Tool For Investigation Of The Microcirculation In The Newborn, Ian M. R Wright, Joanna L. Latter, Rebecca M. Dyson, Christopher (Chris) Levi, Vicki L. Clifton

Illawarra Health and Medical Research Institute

The perinatal period remains a time of significant risk of death or disability. Increasing evidence suggests that this depends on microcirculatory behavior. Sidestream dark-field orthogonal polarized light videomicroscopy (OPS) has emerged as a useful assessment of adult microcirculation but the values derived are not delineated for the newborn. We aimed to define these parameters in well term newborn infants. Demographic details were collected prospectively on 42 healthy term neonates (n = 20 females, n = 22 males). OPS videomicroscopy (Microscan) was used to view ear conch skin microcirculation at 6, 24, and 72 h of age. Stored video was analyzed …


Small Heat-Shock Proteins Prevent A-Synuclein Aggregation Via Transient Interactions And Their Efficacy Is Affected By The Rate Of Aggregation, Dezerae Cox, Emily Selig, Michael D. W Griffin, John A. Carver, Heath Ecroyd Jan 2016

Small Heat-Shock Proteins Prevent A-Synuclein Aggregation Via Transient Interactions And Their Efficacy Is Affected By The Rate Of Aggregation, Dezerae Cox, Emily Selig, Michael D. W Griffin, John A. Carver, Heath Ecroyd

Illawarra Health and Medical Research Institute

The aggregation of a-synuclein (a-syn) into amyloid fibrils is associated with neurodegenerative diseases, collectively referred to as the a-synucleinopathies. In vivo, molecular chaperones, such as the small heat-shock proteins (sHsps), normally act to prevent protein aggregation; however, it remains to be determined how aggregation-prone a-syn evades sHsp chaperone action leading to its disease-associated deposition. This work examines the molecular mechanism by which two canonical sHsps, aB-crystallin (aB-c) and Hsp27, interact with aggregation-prone a-syn to prevent its aggregation in vitro. Both sHsps are very effective inhibitors of ¿-syn aggregation, but no stable complex between the sHsps and a-syn was detected, indicating …


Intake Of 7,8-Dihydroxyflavone During Juvenile And Adolescent Stages Prevents Onset Of Psychosis In Adult Offspring After Maternal Immune Activation, Mei Han, Ji-Chun Zhang, Wei Yao, Chun Yang, Tamaki Ishima, Qian Ren, Min Ma, Chao Dong, Xu-Feng Huang, Kenji Hashimoto Jan 2016

Intake Of 7,8-Dihydroxyflavone During Juvenile And Adolescent Stages Prevents Onset Of Psychosis In Adult Offspring After Maternal Immune Activation, Mei Han, Ji-Chun Zhang, Wei Yao, Chun Yang, Tamaki Ishima, Qian Ren, Min Ma, Chao Dong, Xu-Feng Huang, Kenji Hashimoto

Illawarra Health and Medical Research Institute

Prenatal infection and subsequent abnormal neurodevelopment of offspring is involved in the etiology of schizophrenia. Brain-derived neurotrophic factor (BDNF) and its high affinity receptor, tropomyosin receptor kinase B (TrkB) signaling plays a key role in the neurodevelopment. Pregnant mice exposed to polyriboinosinic-polyribocytidylic acid [poly(I:C)] causes schizophrenia-like behavioral abnormalities in their offspring at adulthood. Here we found that the juvenile offspring of poly(I:C)-treated mice showed cognitive deficits, as well as reduced BDNF-TrkB signaling in the prefrontal cortex (PFC). Furthermore, the adult offspring of poly(I:C)-treated mice showed cognitive deficits, prepulse inhibition (PPI) deficits, reduced BDNF-TrkB signaling, immunoreactivity of parvalbumin (PV) and peroxisome …


Neurodevelopmental Expression Profile Of Dimeric And Monomeric Group 1 Mglurs: Relevance To Schizophrenia Pathogenesis And Treatment, Jeremy Lum, Francesca Fernandez-Enright, Natalie Matosin, Jessica L. Andrews, Xu-Feng Huang, Lezanne Ooi, Kelly A. Newell Jan 2016

Neurodevelopmental Expression Profile Of Dimeric And Monomeric Group 1 Mglurs: Relevance To Schizophrenia Pathogenesis And Treatment, Jeremy Lum, Francesca Fernandez-Enright, Natalie Matosin, Jessica L. Andrews, Xu-Feng Huang, Lezanne Ooi, Kelly A. Newell

Illawarra Health and Medical Research Institute

Group 1 metabotropic glutamate receptors (mGluR1/mGluR5) play an integral role in neurodevelopment and are implicated in psychiatric disorders, such as schizophrenia. mGluR1 and mGluR5 are expressed as homodimers, which is important for their functionality and pharmacology. We examined the protein expression of dimeric and monomeric mGluR1α and mGluR5 in the prefrontal cortex (PFC) and hippocampus throughout development (juvenile/adolescence/adulthood) and in the perinatal phencyclidine (PCP) model of schizophrenia. Under control conditions, mGluR1α dimer expression increased between juvenile and adolescence (209-328%), while monomeric levels remained consistent. Dimeric mGluR5 was steadily expressed across all time points; monomeric mGluR5 was present in juveniles, dramatically …


Cell Type-Specific Modulation Of Cobalamin Uptake By Bovine Serum, Hua Zhao, Kalani R. Ruberu, Hongyun Li, Brett Garner Jan 2016

Cell Type-Specific Modulation Of Cobalamin Uptake By Bovine Serum, Hua Zhao, Kalani R. Ruberu, Hongyun Li, Brett Garner

Illawarra Health and Medical Research Institute

Tracking cellular 57Co-labelled cobalamin (57Co-Cbl) uptake is a well-established method for studying Cbl homeostasis. Previous studies established that bovine serum is not generally permissive for cellular Cbl uptake when used as a supplement in cell culture medium, whereas supplementation with human serum promotes cellular Cbl uptake. The underlying reasons for these differences are not fully defined. In the current study we address this question. We extend earlier observations by showing that fetal calf serum inhibits cellular 57Co-Cbl uptake by HT1080 cells (a fibrosarcoma-derived fibroblast cell line). Furthermore, we discovered that a simple heat-treatment protocol (95o …


Scorpine-Like Peptides, Karen S. Luna Ramirez, Juana María Jimenez-Vargas, Lourival D. Possani Jan 2016

Scorpine-Like Peptides, Karen S. Luna Ramirez, Juana María Jimenez-Vargas, Lourival D. Possani

Illawarra Health and Medical Research Institute

Scorpine-like peptides are intriguing and unique compounds of scorpion venom. They possess two well-defined regions that confers them bi-functionality. The N-terminal region is similar to scorpion antimicrobial peptides lacking disulfide bridges, whereas the C-terminal region contains six cysteines forming three disulfide bridges that tightly bind the peptide. Scorpine-like peptides have shown activity against bacteria (i.e. B. subtilis, K. pneumoniae, P. aeruginosa), fungi and also as potassium channel blockers. Additionally, they have been successful in controlling malaria and some types of viruses.


Efficacy Of A Progressive Resistance Exercise Program To Increase Toe Flexor Strength In Older People, Karen J. Mickle, Peter Caputi, Jan M. Potter, Julie R. Steele Jan 2016

Efficacy Of A Progressive Resistance Exercise Program To Increase Toe Flexor Strength In Older People, Karen J. Mickle, Peter Caputi, Jan M. Potter, Julie R. Steele

Illawarra Health and Medical Research Institute

Background: Reduced toe flexor strength is an independent predictor of falls in older people. However it is unknown whether strengthening programs can restore toe flexor strength in older individuals. The aim of this study was to investigate whether a progressive resistance training program, focused specifically on the foot muscles, could improve toe flexor strength in community-dwelling older people. Methods After baseline testing, 85 men and women (age range 60¿90 years) were randomized to either a supervised, progressive resistance training (n = 43) or a home-based exercise (n = 42) group for 12 weeks. A further 32 participants were recruited for …


Reconceptualizing Involuntary Outpatient Psychiatric Treatment From "Capacity" To "Capability", Edwina M. Light, Michael D. Robertson, Ian Kerridge, Philip Boyce, Terry Carney, Alan Rosen, Michelle Cleary, Glenn E. Hunt, Nick O'Connor Jan 2016

Reconceptualizing Involuntary Outpatient Psychiatric Treatment From "Capacity" To "Capability", Edwina M. Light, Michael D. Robertson, Ian Kerridge, Philip Boyce, Terry Carney, Alan Rosen, Michelle Cleary, Glenn E. Hunt, Nick O'Connor

Illawarra Health and Medical Research Institute

Justifying involuntary psychiatric treatment on the basis of a judgment that a person lacks capacity is controversial because there are questions about the meaning and utility of the concept in this context. There are complexities to using capacity in this way, which are further amplified in the community outpatient setting compared with acute inpatient care. A richer account of capacity, its meanings, and practical applications in context, is required. This qualitative study sought to build inductively a model of capacity in the context of involuntary outpatient psychiatric treatment, based on 38 interviews with stakeholders from New South Wales, Australia. The …


Key Structural Determinants In The Agonist Binding Loops Of Human Β2 And Β4 Nicotinic Acetylcholine Receptor Subunits Contribute To Α3Β4 Subtype Selectivity Of Α-Conotoxins, Hartmut Cuny, Shiva N. Kompella, Han Shen Tae, Rilei Yu, David J. Adams Jan 2016

Key Structural Determinants In The Agonist Binding Loops Of Human Β2 And Β4 Nicotinic Acetylcholine Receptor Subunits Contribute To Α3Β4 Subtype Selectivity Of Α-Conotoxins, Hartmut Cuny, Shiva N. Kompella, Han Shen Tae, Rilei Yu, David J. Adams

Illawarra Health and Medical Research Institute

α-Conotoxins represent a large group of pharmacologically active peptides that antagonize nicotinic acetylcholine receptors (nAChRs). The α3β4 nAChR, a predominant subtype in the peripheral nervous system, has been implicated in various pathophysiological conditions. As many α-conotoxins have multiple pharmacological targets, compounds specifically targeting individual nAChR subtypes are needed. In this study, we performed mutational analyses to evaluate the key structural components of human β2 and β4 nAChR subunits that determine α-conotoxin selectivity for α3β4 nAChR. α-Conotoxin RegIIA was used to evaluate the impact of non-conserved human β2 and β4 residues on peptide affinity. Two mutations, α3β2[T59K] and α3β2[S113R], strongly enhanced …


Early Antipsychotic Treatment In Juvenile Rats Elicits Long-Term Alterations To The Dopamine Neurotransmitter System, Michael De Santis, Jiamei Lian, Xu-Feng Huang, Chao Deng Jan 2016

Early Antipsychotic Treatment In Juvenile Rats Elicits Long-Term Alterations To The Dopamine Neurotransmitter System, Michael De Santis, Jiamei Lian, Xu-Feng Huang, Chao Deng

Illawarra Health and Medical Research Institute

Prescription of antipsychotic drugs (APDs) to children has substantially increased in recent years. Whilst current investigations into potential long-term effects have uncovered some alterations to adult behaviours, further investigations into potential changes to neurotransmitter systems are required. The current study investigated potential long-term changes to the adult dopamine (DA) system following aripiprazole, olanzapine and risperidone treatment in female and male juvenile rats. Levels of tyrosine hydroxylase (TH), phosphorylated-TH (p-TH), dopamine active transporter (DAT), and D1 and D2 receptors were measured via Western blot and/or receptor autoradiography. Aripiprazole decreased TH and D1 receptor levels in the ventral tegmental …


Dietary Iodine Intake Of The Australian Population After Introduction Of A Mandatory Iodine Fortification Programme, Karen E. Charlton, Yasmine Probst, Gabriella Kiene Jan 2016

Dietary Iodine Intake Of The Australian Population After Introduction Of A Mandatory Iodine Fortification Programme, Karen E. Charlton, Yasmine Probst, Gabriella Kiene

Illawarra Health and Medical Research Institute

To address mild iodine deficiency in Australia, a mandatory fortification program of iodised salt in bread was implemented in 2009. This study aimed to determine factors associated with achieving an adequate dietary iodine intake in the Australian population post-fortification, and to assess whether bread consumption patterns affect iodine intake in high-risk groups. Using nationally representative data of repeated 24-h dietary recalls from the 2011-2012 Australian National Nutrition and Physical Activity Survey, dietary iodine intakes and food group contributions were compared by age, socioeconomic status (SES), and geographical remoteness (N = 7735). The association between fortified bread intake and adequacy …


Perspective: The Path To Confirming And Exploiting Potential Satiety-Enhancing Effects Of Sorghum-Based Foods For Human Diets, Anita Stefoska-Needham, Eleanor J. Beck, Linda C. Tapsell Jan 2016

Perspective: The Path To Confirming And Exploiting Potential Satiety-Enhancing Effects Of Sorghum-Based Foods For Human Diets, Anita Stefoska-Needham, Eleanor J. Beck, Linda C. Tapsell

Illawarra Health and Medical Research Institute

Consumer trends, particularly in populations burdened with high rates of obesity and overweight, indicate a growing demand for food products with specific satiety-enhancing effects to assist with appetite regulation and longer-term weight management. Sorghum whole grain, containing dietary fibre, slowly digestible starches and polyphenolic compounds, has been identified as a potential ingredient in the formulation of novel food products targeted for appetite control. Rigorous human clinical trials are necessary to build evidence for these purported effects, including studies that examine the underlying satiety-enhancing mechanisms. This paper provides perspectives on the path to confirming and exploiting potential satiety attributes of sorghum-based …


A Lipidomic Analysis Of Placenta In Preeclampsia: Evidence For Lipid Storage, Simon H. J Brown, Samuel Eather, Dilys J. Freeman, Barbara J. Meyer, Todd W. Mitchell Jan 2016

A Lipidomic Analysis Of Placenta In Preeclampsia: Evidence For Lipid Storage, Simon H. J Brown, Samuel Eather, Dilys J. Freeman, Barbara J. Meyer, Todd W. Mitchell

Illawarra Health and Medical Research Institute

In preeclampsia, maternal insulin resistance leads to defective expansion of adipocytes, enhanced adipocyte lipolysis, up-regulation of very low density lipoprotein synthesis, maternal hypertriglyceridaemia and the potential for ectopic fat storage. Our aim was to quantitate and compare the total amount and type of lipid in placenta from pregnancies complicated with preeclampsia and healthy pregnancies. Quantitative lipid analysis of lipid extracts from full thickness placental biopsies was carried out by shotgun lipidomics. Placental lipid profiles from pregnancies complicated by preeclampsia (n = 23) were compared to healthy pregnancies (n = 68), and placenta from intrauterine growth restriction pregnancies (n = 10) …


An Automated Chromatography Procedure Optimized For Analysis Of Stable Cu Isotopes From Biological Materials, T. Gabriel Enge, M P. Field, Dianne F. Jolley, Heath Ecroyd, M H. Kim, Anthony Dosseto Jan 2016

An Automated Chromatography Procedure Optimized For Analysis Of Stable Cu Isotopes From Biological Materials, T. Gabriel Enge, M P. Field, Dianne F. Jolley, Heath Ecroyd, M H. Kim, Anthony Dosseto

Illawarra Health and Medical Research Institute

An automated ion-exchange chromatography method is developed for the separation of copper (Cu) from biological samples prior to stable, naturally occurring, isotope analysis. The technique does not require Cu to be fully oxidized/reduced into either Cu+ or Cu2+. Distribution coefficients of Cu and other cations to the Cu-specific anion exchange resin enable the effective purification and separation of Cu from complex matrixes using a single, reusable chromatographic column, with the potential to be modified for varying sample types. The automated chromatography system (prepFAST-MC™) can process up to 60 samples per run at a rate of 36 samples per day on …