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Serum Apob Levels In Depressive Patients: Associated With Cognitive Deficits, Li Hui, Mei Han, Xiang Dong Du, Bao Hua J. Zhang, Shu Chang He, Tian Nan Shao, Guang Zhong Yin Jan 2017

Serum Apob Levels In Depressive Patients: Associated With Cognitive Deficits, Li Hui, Mei Han, Xiang Dong Du, Bao Hua J. Zhang, Shu Chang He, Tian Nan Shao, Guang Zhong Yin

Illawarra Health and Medical Research Institute

Cognitive deficits have been regarded as one of the most significant clinical symptoms of depressive disorder. Accumulating evidence has shown that apolipoprotein B (ApoB) levels, which are responsible for inducing neurodegeneration, may be involved in cognitive deficits. This study examines cognitive deficits, and the correlation of serum ApoB levels with cognitive deficits of depressive disorder. 90 depressive patients and 90 healthy controls with matched age and gender were recruited. Cognition was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Serum ApoB levels in depressive patients were measured by immunoturbidimetric method. Our results showed that depressive patients …


Accessing Hospital Packaged Foods And Beverages: The Importance Of A Seated Posture When Eating, Alison F. Bell, Linda C. Tapsell, Karen L. Walton, Alaster Yoxall Jan 2017

Accessing Hospital Packaged Foods And Beverages: The Importance Of A Seated Posture When Eating, Alison F. Bell, Linda C. Tapsell, Karen L. Walton, Alaster Yoxall

Illawarra Health and Medical Research Institute

Background Hospitalised and community dwelling older people (aged 65 years and over) have difficulties opening certain food and beverage items (e.g. cheese portions and tetra packs) served in public hospitals. Previously, the role of hand strength on successful pack opening has been explored in a seated position. However, because many people in hospital eat in bed, the present laboratory study examined the differences between participants opening a selection of products in a hospital bed and a chair.

Methods The present study used a qualitative method (satisfaction) and quantitative methods (grip and pinch strength, dexterity, time and attempts) in two conditions …


Prevalence And Correlates Of Psychological Distress Among Diabetes Mellitus Adults In The Jilin Province In China: A Cross-Sectional Study, Shuang Qiu, Xuan Hong Sun, Wen Ya Liu, Joseph Sam Kanu, Ri Li, Qin Ya Yu, Xu-Feng Huang, Bo Li, Yang Xiang Zhang Jan 2017

Prevalence And Correlates Of Psychological Distress Among Diabetes Mellitus Adults In The Jilin Province In China: A Cross-Sectional Study, Shuang Qiu, Xuan Hong Sun, Wen Ya Liu, Joseph Sam Kanu, Ri Li, Qin Ya Yu, Xu-Feng Huang, Bo Li, Yang Xiang Zhang

Illawarra Health and Medical Research Institute

Background: Psychological disorders are common in diabetes mellitus (DM) patients, and the aim of this study was to estimate the prevalence of psychological distress and to determine the influence factors associated with psychological distress among DM patients in the Jilin province of China.

Methods and Materials: Multistage, stratified cluster sampling was used in this cross-sectional study. The 12-item General Health Questionnaire (GHQ-12) was used to assess psychological status with the total score of ≥4 as the threshold for psychological distress.

Results: A total of 1,956 subjects with DM were included in the study. Out of this total diabetic …


A Systematic Review Of The Effect Of Cannabidiol On Cognitive Function: Relevance To Schizophrenia, Ashleigh L. Osborne, Nadia Solowij, Katrina Weston-Green Jan 2017

A Systematic Review Of The Effect Of Cannabidiol On Cognitive Function: Relevance To Schizophrenia, Ashleigh L. Osborne, Nadia Solowij, Katrina Weston-Green

Illawarra Health and Medical Research Institute

Background and objectives Cognitive impairment is a core symptom domain of schizophrenia, neurological disorders and substance abuse. It is characterised by deficits in learning, memory, attention and executive functioning and can severely impact daily living. Antipsychotic drugs prescribed to treat schizophrenia provide limited cognitive benefits and novel therapeutic targets are required. Cannabidiol (CBD), a component of the cannabis plant, has anti-inflammatory and antipsychotic-like properties; however, its ability to improve cognitive impairment has not been thoroughly explored. The aim of this systematic review was to evaluate preclinical and clinical literature on the effects of CBD in cognitive domains relevant to schizophrenia. …


Improved Social Interaction, Recognition And Working Memory With Cannabidiol Treatment In A Prenatal Infection (Poly I:C) Rat Model, Ashleigh L. Osborne, Nadia Solowij, Ilijana Babic, Xu-Feng Huang, Katrina Weston-Green Jan 2017

Improved Social Interaction, Recognition And Working Memory With Cannabidiol Treatment In A Prenatal Infection (Poly I:C) Rat Model, Ashleigh L. Osborne, Nadia Solowij, Ilijana Babic, Xu-Feng Huang, Katrina Weston-Green

Illawarra Health and Medical Research Institute

Neuropsychiatric disorders such as schizophrenia are associated with cognitive impairment, including learning, memory and attention deficits. Antipsychotic drugs are limited in their efficacy to improve cognition; therefore, new therapeutic agents are required. Cannabidiol (CBD), the non-intoxicating component of cannabis, has anti-inflammatory, neuroprotective and antipsychotic-like properties; however, its ability to improve the cognitive deficits of schizophrenia remains unclear. Using a prenatal infection model, we examined the effect of chronic CBD treatment on cognition and social interaction. Time-mated pregnant Sprague-Dawley rats (n=16) were administered polyinosinic-polycytidilic acid (poly I:C) (POLY; 4 mg/kg) or saline (CONT) at gestation day 15. Male offspring …


Outcomes Of Multisite Antimicrobial Stewardship Programme Implementation With A Shared Clinical Decision Support System, Stuart Bond, Adriana J. Chubaty, Suman Adhikari, Spiros Miyakis, Craig S. Boutlis, Wilfred W. Yeo, Marijka Batterham, Cara Dickson, Brendan J. Mcmullan, Mona Mostaghim Jan 2017

Outcomes Of Multisite Antimicrobial Stewardship Programme Implementation With A Shared Clinical Decision Support System, Stuart Bond, Adriana J. Chubaty, Suman Adhikari, Spiros Miyakis, Craig S. Boutlis, Wilfred W. Yeo, Marijka Batterham, Cara Dickson, Brendan J. Mcmullan, Mona Mostaghim

Illawarra Health and Medical Research Institute

Background: Studies evaluating antimicrobial stewardship programmes (ASPs) supported by computerized clinical decision support systems (CDSSs) have predominantly been conducted in single site metropolitan hospitals.

Objectives: To examine outcomes of multisite ASP implementation supported by a centrally deployed CDSS.

Methods: An interrupted time series study was conducted across five hospitals in New South Wales, Australia, from 2010 to 2014. Outcomes analysed were: effect of the intervention on targeted antimicrobial use, antimicrobial costs and healthcare-associated Clostridium difficile infection (HCA-CDI) rates. Infection-related length of stay (LOS) and standardized mortality ratios (SMRs) were also assessed.

Results: Post-intervention, antimicrobials targeted for …


Increased Levels Of C1q In The Prefrontal Cortex Of Adult Offspring After Maternal Immune Activation: Prevention By 7,8-Dihydroxyflavone, Mei Han, Ji-Chun Zhang, Kenji Hashimoto Jan 2017

Increased Levels Of C1q In The Prefrontal Cortex Of Adult Offspring After Maternal Immune Activation: Prevention By 7,8-Dihydroxyflavone, Mei Han, Ji-Chun Zhang, Kenji Hashimoto

Illawarra Health and Medical Research Institute

Objective: Prenatal infection is implicated in the etiology of schizophrenia. The objective of this paper is to study the role of complement protein C1q in the psychosis of adult offspring after maternal immune activation (MIA). In addition, effect of 7,8-dihydroxyflavone (7,8-DHF: A tropomyosin receptor kinase B [TrkB] agonist) was also examined.

Methods: Western blot analysis of C1q in the brain regions from adult offspring after prenatal poly(I:C) (5.0 mg/kg/day from E12 to E17) exposure was performed. 7,8-DHF or vehicle was given from 4 to 8-weeks old.

Results: Expression of C1q in the prefrontal cortex (PFC) of adult …


Cannabis-Related Hippocampal Volumetric Abnormalities Specific To Subregions In Dependent Users, Yann Chye, Chao Suo, Murat Yucel, Lauren Den Ouden, Nadia Solowij, Valentina Lorenzetti Jan 2017

Cannabis-Related Hippocampal Volumetric Abnormalities Specific To Subregions In Dependent Users, Yann Chye, Chao Suo, Murat Yucel, Lauren Den Ouden, Nadia Solowij, Valentina Lorenzetti

Illawarra Health and Medical Research Institute

Rationale - Cannabis use is associated with neuroanatomical alterations in the hippocampus. While the hippocampus is composed of multiple subregions, their differential vulnerability to cannabis dependence remains unknown.

Objectives - The objective of the study is to investigate gray matter alteration in each of the hippocampal subregions (presubiculum, subiculum, cornu ammonis (CA) subfields CA1-4, and dentate gyrus (DG)) as associated with cannabis use and dependence.

Methods - A total of 35 healthy controls (HC), 22 non-dependent (CB-nondep), and 39 dependent (CB-dep) cannabis users were recruited. We investigated group differences in hippocampal subregion volumes between HC, CB-nondep, and CB-dep users. We …


Time-Dependent Changes And Potential Mechanisms Of Glucose-Lipid Metabolic Disorders Associated With Chronic Clozapine Or Olanzapine Treatment In Rats, Xuemei Liu, Zhixiang Wu, Jiamei Lian, Chang-Hua Hu, Xu-Feng Huang, Chao Deng Jan 2017

Time-Dependent Changes And Potential Mechanisms Of Glucose-Lipid Metabolic Disorders Associated With Chronic Clozapine Or Olanzapine Treatment In Rats, Xuemei Liu, Zhixiang Wu, Jiamei Lian, Chang-Hua Hu, Xu-Feng Huang, Chao Deng

Illawarra Health and Medical Research Institute

Chronic treatment with second-generation antipsychotic drugs (SGAs) has been associated with an increased risk of metabolic syndrome. To evaluate the longitudinal changes in glucose-lipid homeostasis after SGA use, we studied the time-dependent effects of olanzapine (OLZ) (3 mg/kg, b.i.d.) or clozapine (CLZ) (20 mg/kg, b.i.d.) treatment on metabolic profiles for 9 weeks in rats. Although only OLZ significantly increased body weight in rats, both OLZ and CLZ elevated blood lipid levels. Chronic OLZ treatment induced significant weight gain leading to a higher fasting insulin level and impaired glucose tolerance, whereas CLZ lowered fasting insulin levels and impaired glucose tolerance independent …


Single-Molecule Visualization Of Fast Polymerase Turnover In The Bacterial Replisome, Jacob S. Lewis, Lisanne Spenkelink, Slobodan Jergic, Elizabeth A. Wood, Enrico Monachino, Nicholas Horan, Karl E. Duderstadt, Michael M. Cox, Andrew Robinson, Nicholas E. Dixon, Antoine M. Van Oijen Jan 2017

Single-Molecule Visualization Of Fast Polymerase Turnover In The Bacterial Replisome, Jacob S. Lewis, Lisanne Spenkelink, Slobodan Jergic, Elizabeth A. Wood, Enrico Monachino, Nicholas Horan, Karl E. Duderstadt, Michael M. Cox, Andrew Robinson, Nicholas E. Dixon, Antoine M. Van Oijen

Illawarra Health and Medical Research Institute

The Escherichia coli DNA replication machinery has been used as a road map to uncover design rules that enable DNA duplication with high efficiency and fidelity. Although the enzymatic activities of the replicative DNA Pol III are well understood, its dynamics within the replisome are not. Here, we test the accepted view that the Pol III holoenzyme remains stably associated within the replisome. We use in vitro single-molecule assays with fluorescently labeled polymerases to demonstrate that the Pol III* complex (holoenzyme lacking the β2 sliding clamp), is rapidly exchanged during processive DNA replication. Nevertheless, the replisome is highly resistant …


A Novel Lid-Covering Peptide Inhibitor Of Nicotinic Acetylcholine Receptors Derived From Αd-Conotoxin Gexxa, Longjin Yang, Han Shen Tae, Zhou Fan, Xiaoxia Shao, Shaoqiong Xu, Suwen Zhao, David J. Adams, Chunguang Wang Jan 2017

A Novel Lid-Covering Peptide Inhibitor Of Nicotinic Acetylcholine Receptors Derived From Αd-Conotoxin Gexxa, Longjin Yang, Han Shen Tae, Zhou Fan, Xiaoxia Shao, Shaoqiong Xu, Suwen Zhao, David J. Adams, Chunguang Wang

Illawarra Health and Medical Research Institute

Nicotinic acetylcholine receptors (nAChRs) play a fundamental role in nervous signal transmission, therefore various antagonists and agonists are highly desired to explore the structure and function of nAChRs. Recently, a novel dimeric αD-conotoxin GeXXA was identified to inhibit nAChRs by binding at the top surface of the receptors, and the monomeric C-terminal domain (CTD) of αD-GeXXA retains some inhibitory activity. In this study, the internal dimeric N-terminal domain (NTD) of this conopeptide was further investigated. We first developed a regio-selective protection strategy to chemically prepare the anti-parallel dimeric NTD, and found that the isolated NTD part of GeXXA possesses the …


The Effect Of A High Frequency Electromagnetic Field In The Microwave Range On Red Blood Cells, The Hong Phong Nguyen, Vy T. Pham, Vladimir Baulin, Rodney J. Croft, Russell Crawford, Elena Ivanova Jan 2017

The Effect Of A High Frequency Electromagnetic Field In The Microwave Range On Red Blood Cells, The Hong Phong Nguyen, Vy T. Pham, Vladimir Baulin, Rodney J. Croft, Russell Crawford, Elena Ivanova

Illawarra Health and Medical Research Institute

The effect of red blood cells (RBC) exposed to an 18 GHz electromagnetic field (EMF) was studied. The results of this study demonstrated for the first time that exposure of RBCs to 18 GHz EMF has the capacity to induce nanospheres uptake in RBCs. The uptake of nanospheres (loading efficiency 96% and 46% for 23.5 and 46.3 nm nanospheres respectively), their presence and locality were confirmed using three independent techniques, namely scanning electron microscopy, confocal laser scanning microscopy and transmission electron microscopy. It appeared that 23.5 nm nanospheres were translocated through the membrane into the cytosol, while the 46.3 nm-nanospheres …


Exploring The Relationship Between Nicotinic Acetylcholine Receptor Ligand Size, Efficiency, Efficacy, And C-Loop Opening, Qianyun Ma, Han Shen Tae, Guanzhao Wu, Tao Jiang, Rilei Yu Jan 2017

Exploring The Relationship Between Nicotinic Acetylcholine Receptor Ligand Size, Efficiency, Efficacy, And C-Loop Opening, Qianyun Ma, Han Shen Tae, Guanzhao Wu, Tao Jiang, Rilei Yu

Illawarra Health and Medical Research Institute

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels mediating fundamental physiological activities in the nervous system and have become important targets for drug design. For a long time, the acetylcholine binding protein (AChBP) has been used as a surrogate to study the nAChR structure-function. Taking advantage of more than 100 AChBP crystal structures in the Protein DataBank (PDB), we explored the relationship between the size, efficiency, and efficacy of nAChR ligands and the C-loop movement. We found that the size of the ligand is correlated with the opening of the C-loop, which can be used in selecting AChBP crystal structures …


The Relevance Of Contact-Independent Cell-To-Cell Transfer Of Tdp-43 And Sod1 In Amyotrophic Lateral Sclerosis, Maya Hanspal, Christopher M. Dobson, Justin J. Yerbury, Janet R. Kumita Jan 2017

The Relevance Of Contact-Independent Cell-To-Cell Transfer Of Tdp-43 And Sod1 In Amyotrophic Lateral Sclerosis, Maya Hanspal, Christopher M. Dobson, Justin J. Yerbury, Janet R. Kumita

Illawarra Health and Medical Research Institute

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease involving the formation of cytoplasmic aggregates by proteins including TDP-43 and SOD1, in affected cells in the central nervous system (CNS). Pathology spreads from an initial site of onset to contiguous anatomical regions. There is evidence that for disease-associated proteins, including TDP-43 and SOD1, non-native protein conformers can promote misfolding of the natively folded counterparts, and cell-to-cell transfer of pathological aggregates may underlie the spread of the disease throughout the CNS. A variety of studies have demonstrated that SOD1 is released by neuron-like cells into the surrounding culture medium, either in their …


Correlates Of Tummy Time In Infants Aged 0-12 Months Old: A Systematic Review, Lyndel Hewitt, Rebecca M. Stanley, Anthony D. Okely Jan 2017

Correlates Of Tummy Time In Infants Aged 0-12 Months Old: A Systematic Review, Lyndel Hewitt, Rebecca M. Stanley, Anthony D. Okely

Illawarra Health and Medical Research Institute

Background: Tummy time, defined as an infant being placed on their stomach whilst they are awake and supervised, has been shown to have a positive effect on infant development and head shape. Tummy time can be influenced by a number of factors. Using a social ecological model, categories of potential variables can be examined to determine their influence on behaviours such as tummy time. The purpose of this systematic review was to examine potential correlates of tummy time in infants from birth to 12 months old.

Methods: Electronic databases were originally searched between March to December 2016. Included …


Effects Of Neuropeptide Y On Stem Cells And Their Potential Applications In Disease Therapy, Song Peng, You-Li Zhou, Zhi-Yuan Song, Shu Lin Jan 2017

Effects Of Neuropeptide Y On Stem Cells And Their Potential Applications In Disease Therapy, Song Peng, You-Li Zhou, Zhi-Yuan Song, Shu Lin

Illawarra Health and Medical Research Institute

Neuropeptide Y (NPY), a 36-amino acid peptide, is widely distributed in the central and peripheral nervous systems and other peripheral tissues. It takes part in regulating various biological processes including food intake, circadian rhythm, energy metabolism, and neuroendocrine secretion. Increasing evidence indicates that NPY exerts multiple regulatory effects on stem cells. As a kind of primitive and undifferentiated cells, stem cells have the therapeutic potential to replace damaged cells, secret paracrine molecules, promote angiogenesis, and modulate immunity. Stem cell-based therapy has been demonstrated effective and considered as one of the most promising treatments for specific diseases. However, several limitations still …


Luteolin, A Natural Flavonoid, Inhibits Methylglyoxal Induced Apoptosis Via The Mtor/4e-Bp1 Signaling Pathway, Yi Liu, Jie Huang, Xian Zheng, Xia Yang, Yan Ding, Tongyong Fang, Yuyun Zhang, Shuaishuai Wang, Xiaofei Zhang, Xuan Luo, Anlei Guo, Kelly A. Newell, Yinghua Yu, Xu-Feng Huang Jan 2017

Luteolin, A Natural Flavonoid, Inhibits Methylglyoxal Induced Apoptosis Via The Mtor/4e-Bp1 Signaling Pathway, Yi Liu, Jie Huang, Xian Zheng, Xia Yang, Yan Ding, Tongyong Fang, Yuyun Zhang, Shuaishuai Wang, Xiaofei Zhang, Xuan Luo, Anlei Guo, Kelly A. Newell, Yinghua Yu, Xu-Feng Huang

Illawarra Health and Medical Research Institute

Methylglyoxal (MG) accumulation has been observed in human cerebrospinal fluid and body tissues under hyperglycaemic conditions. Recent research has demonstrated that MG-induces neuronal cell apoptosis, which promotes the development of diabetic encephalopathy. Our previous animal study has shown that luteolin, a natural flavonoid, attenuates diabetes-associated cognitive dysfunction. To further explore the neuroprotective properties of luteolin, we investigated the inhibitive effect of luteolin on MG-induced apoptosis in PC12 neuronal cells. We found that MG inhibited cell viability in a dose-dependent manner and induced apoptosis in PC12 cells. Pretreatment with Luteolin significantly elevated cell viability, reduced MG-induced apoptosis, inhibited the activation of …


No Preliminary Evidence Of Differences In Astrocyte Density Within The White Matter Of The Dorsolateral Prefrontal Cortex In Autism, Ting Ting Lee, Efstratios Skafidas, Mirella Dottori, Daniela Zantomio, Christos Pantelis, Ian Everall, Gursharan Chana Jan 2017

No Preliminary Evidence Of Differences In Astrocyte Density Within The White Matter Of The Dorsolateral Prefrontal Cortex In Autism, Ting Ting Lee, Efstratios Skafidas, Mirella Dottori, Daniela Zantomio, Christos Pantelis, Ian Everall, Gursharan Chana

Illawarra Health and Medical Research Institute

Background: While evidence for white matter and astrocytic abnormalities exist in autism, a detailed investigation of astrocytes has not been conducted. Such an investigation is further warranted by an increasing role for neuroinflammation in autism pathogenesis, with astrocytes being key players in this process. We present the first study of astrocyte density and morphology within the white matter of the dorsolateral prefrontal cortex (DLPFC) in individuals with autism.

Methods: DLPFC formalin-fixed sections containing white matter from individuals with autism (n = 8, age = 4-51 years) and age-matched controls (n = 7, age = 4-46 years) were immunostained …


Advances And Unresolved Challenges In The Structural Characterization Of Isomeric Lipids, Sarah Hancock, Berwyck L. J Poad, Amani M. Batarseh, Sarah K. Abbott, Todd W. Mitchell Jan 2017

Advances And Unresolved Challenges In The Structural Characterization Of Isomeric Lipids, Sarah Hancock, Berwyck L. J Poad, Amani M. Batarseh, Sarah K. Abbott, Todd W. Mitchell

Illawarra Health and Medical Research Institute

As the field of lipidomics grows and its application becomes wide and varied it is important that we don't forget its foundation, i.e. the identification and measurement of molecular lipids.Advances in liquid chromatography and the emergence of ion mobility as a useful tool in lipid analysis are allowing greater separation of lipid isomers than ever before. At the same time, novel ion activation techniques, such as ozone-induced dissociation, are pushing lipid structural characterization by mass spectrometry to new levels. Nevertheless, the quantitative capacity of these techniques is yet to be proven and further refinements are required to unravel the high …


The Tarantula Toxin Β/Δ-Trtx-Pre1a Highlights The Importance Of The S1-S2 Voltage-Sensor Region For Sodium Channel Subtype Selectivity, Joshua Wingerd, Christine A. Mozar, Christine Ussing, Swetha Murali, Yanni K.-Y Chin, Ben Cristofori-Armstrong, Thomas Durek, John Gilchrist, Christopher W. Vaughan, Frank Bosmans, David J. Adams, Richard J. Lewis, Paul F. Alewood, Mehdi Mobli, Macdonald J. Christie, Lachlan D. Rash Jan 2017

The Tarantula Toxin Β/Δ-Trtx-Pre1a Highlights The Importance Of The S1-S2 Voltage-Sensor Region For Sodium Channel Subtype Selectivity, Joshua Wingerd, Christine A. Mozar, Christine Ussing, Swetha Murali, Yanni K.-Y Chin, Ben Cristofori-Armstrong, Thomas Durek, John Gilchrist, Christopher W. Vaughan, Frank Bosmans, David J. Adams, Richard J. Lewis, Paul F. Alewood, Mehdi Mobli, Macdonald J. Christie, Lachlan D. Rash

Illawarra Health and Medical Research Institute

Voltage-gated sodium (NaV) channels are essential for the transmission of pain signals in humans making them prime targets for the development of new analgesics. Spider venoms are a rich source of peptide modulators useful to study ion channel structure and function. Here we describe β/δ-TRTX-Pre1a, a 35-residue tarantula peptide that selectively interacts with neuronal NaV channels inhibiting peak current of hNaV1.1, rNaV1.2, hNaV1.6, and hNaV1.7 while concurrently inhibiting fast inactivation of hNaV1.1 and rNaV1.3. The DII and DIV S3-S4 loops of NaV channel voltage …


Addition Of Exogenous Sod1 Aggregates Causes Tdp-43 Mislocalisation And Aggregation, Rafaa Zeineddine, Natalie E. Farrawell, Isabella Lambert-Smith, Justin J. Yerbury Jan 2017

Addition Of Exogenous Sod1 Aggregates Causes Tdp-43 Mislocalisation And Aggregation, Rafaa Zeineddine, Natalie E. Farrawell, Isabella Lambert-Smith, Justin J. Yerbury

Illawarra Health and Medical Research Institute

ALS is characterised by a focal onset of motor neuron loss, followed by contiguous outward spreading of pathology throughout the nervous system, resulting in paralysis and death generally within a few years after diagnosis. The aberrant release and uptake of toxic proteins including SOD1 and TDP-43 and their subsequent propagation, accumulation and deposition in motor neurons may explain such a pattern of pathology. Previous work has suggested that the internalization of aggregates triggers stress granule formation. Given the close association of stress granules and TDP-43, we wondered whether internalisation of SOD1 aggregates stimulated TDP-43 cytosolic aggregate structures. Addition of recombinant …


Improving The Delivery Of Sod1 Antisense Oligonucleotides To Motor Neurons Using Calcium Phosphate-Lipid Nanoparticles, Liyu Chen, Clare A. Watson, Marco Morsch, Nicholas Cole, Roger Chung, Darren N. Saunders, Justin J. Yerbury, Kara L. Vine Jan 2017

Improving The Delivery Of Sod1 Antisense Oligonucleotides To Motor Neurons Using Calcium Phosphate-Lipid Nanoparticles, Liyu Chen, Clare A. Watson, Marco Morsch, Nicholas Cole, Roger Chung, Darren N. Saunders, Justin J. Yerbury, Kara L. Vine

Illawarra Health and Medical Research Institute

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease affecting the upper and lower motor neurons in the motor cortex and spinal cord. Abnormal accumulation of mutant superoxide dismutase I (SOD1) in motor neurons is a pathological hallmark of some forms of the disease. We have shown that the orderly progression of the disease may be explained by misfolded SOD1 cell-to-cell propagation, which is reliant upon its active endogenous synthesis. Reducing the levels of SOD1 is therefore a promising therapeutic approach. Antisense oligonucleotides (ASOs) can efficiently silence proteins with gain-of-function mutations. However, naked ASOs have a short circulation half-life and …


Proceedings Of 3rd Australian Lipid Meeting, Simon H. J Brown, Thusitha W. T Rupasinghe Jan 2017

Proceedings Of 3rd Australian Lipid Meeting, Simon H. J Brown, Thusitha W. T Rupasinghe

Illawarra Health and Medical Research Institute

More than 100 lipid researchers from across Australia participated in the 3rd Australian Lipid Meeting (ALM3), held on the 21st and 22nd of November 2016 in Melbourne, Australia.


Transition State-Based St6gal I Inhibitors: Mimicking The Phosphodiester Linkage With A Triazole Or Carbamate Through An Enthalpy-Entropy Compensation, Andrew Montgomery, Danielle Skropeta, Haibo Yu Jan 2017

Transition State-Based St6gal I Inhibitors: Mimicking The Phosphodiester Linkage With A Triazole Or Carbamate Through An Enthalpy-Entropy Compensation, Andrew Montgomery, Danielle Skropeta, Haibo Yu

Illawarra Health and Medical Research Institute

Human β-galactoside α-2,6-sialyltransferase I (ST6Gal I) catalyses the synthesis of sialylated glycoconjugates. Overexpression of ST6Gal I is observed in many cancers, where it promotes metastasis through altered cell surface sialylation. A wide range of sialyltransferase inhibitors have been developed, with analogues structurally similar to the transition state exhibiting the highest inhibitory activity. To improve synthetic accessibility and pharmacokinetics of previously reported inhibitors, the replacement of the charged phosphodiester linker with a potential neutral isostere such as a carbamate or a 1,2,3-triazole has been investigated. Extensive molecular dynamics simulations have demonstrated that compounds with the alternate linkers could maintain key interactions …


Unexpected Synthesis Of 3-Imino-2-(Pyrrol-2-Yl) Isatogen Derivatives Affords Facile Access To A 2-Pyrrolyl Isatogen, Nicholas Kirk, Geraud Sansom, Pichit Sudta, Sunit Suksamrarn, Anthony C. Willis, John B. Bremner, Michael J. Kelso Jan 2017

Unexpected Synthesis Of 3-Imino-2-(Pyrrol-2-Yl) Isatogen Derivatives Affords Facile Access To A 2-Pyrrolyl Isatogen, Nicholas Kirk, Geraud Sansom, Pichit Sudta, Sunit Suksamrarn, Anthony C. Willis, John B. Bremner, Michael J. Kelso

Illawarra Health and Medical Research Institute

2-Aryl isatogens and their 3-imino derivatives have been extensively studied but to date there have been no reported variants carrying pyrrolyl substituents at the 2-position. This study describes the unexpected synthesis of two novel 3-imino-2-(pyrrol-2-yl) isatogen derivatives upon attempted amide couplings with (E)- or (Z)-3-(3,5-dimethyl-1H-pyrrol-2-yl)-2-(2-nitrophenyl)acrylic acids and p-phenylenediamines in the presence of uronium-based coupling reagents. Imine hydrolysis of one derivative under mild acid conditions afforded a 2-pyrrolyl isatogen in high yield. The compound showed potent in vitro antiplasmodial activity against Plasmodium falciparum.


Α-Conotoxin Vc1.1 Inhibits Human Dorsal Root Ganglion Neuroexcitability And Mouse Colonic Nociception Via GabaB Receptors, Joel Castro, Andrea M. Harrington, Sonia Garcia-Caraballo, Jessica Maddern, Luke Grundy, Jingming Zhang, Guy Page, Paul E. Miller, David J. Craik, David J. Adams, Stuart Brierley Jan 2017

Α-Conotoxin Vc1.1 Inhibits Human Dorsal Root Ganglion Neuroexcitability And Mouse Colonic Nociception Via GabaB Receptors, Joel Castro, Andrea M. Harrington, Sonia Garcia-Caraballo, Jessica Maddern, Luke Grundy, Jingming Zhang, Guy Page, Paul E. Miller, David J. Craik, David J. Adams, Stuart Brierley

Illawarra Health and Medical Research Institute

Objective α-Conotoxin Vc1.1 is a small disulfidebonded peptide from the venom of the marine cone snail Conus victoriae. Vc1.1 has antinociceptive actions in animal models of neuropathic pain, but its applicability to inhibiting human dorsal root ganglion (DRG) neuroexcitability and reducing chronic visceral pain (CVP) is unknown.

Design We determined the inhibitory actions of Vc1.1 on human DRG neurons and on mouse colonic sensory afferents in healthy and chronic visceral hypersensitivity (CVH) states. In mice, visceral nociception was assessed by neuronal activation within the spinal cord in response to noxious colorectal distension (CRD). Quantitativereverse- transcription-PCR, single-cell-reversetranscription- PCR and immunohistochemistry …


Watching Cellular Machinery In Action, One Molecule At A Time, Enrico Monachino, Lisanne Spenkelink, Antoine M. Van Oijen Jan 2017

Watching Cellular Machinery In Action, One Molecule At A Time, Enrico Monachino, Lisanne Spenkelink, Antoine M. Van Oijen

Illawarra Health and Medical Research Institute

Single-molecule manipulation and imaging techniques have become important elements of the biologist's toolkit to gain mechanistic insights into cellular processes. By removing ensemble averaging, single-molecule methods provide unique access to the dynamic behavior of biomolecules. Recently, the use of these approaches has expanded to the study of complex multiprotein systems and has enabled detailed characterization of the behavior of individual molecules inside living cells. In this review, we provide an overview of the various force-and fluorescence-based single-molecule methods with applications both in vitro and in vivo, highlighting these advances by describing their applications in studies on cytoskeletal motors and DNA …


Forward Osmosis As A Platform For Resource Recovery From Municipal Wastewater - A Critical Assessment Of The Literature, Ashley Ansari, Faisal I. Hai, William E. Price, Jörg E. Drewes, Long D. Nghiem Jan 2017

Forward Osmosis As A Platform For Resource Recovery From Municipal Wastewater - A Critical Assessment Of The Literature, Ashley Ansari, Faisal I. Hai, William E. Price, Jörg E. Drewes, Long D. Nghiem

Illawarra Health and Medical Research Institute

Forward osmosis (FO) is an emerging membrane separation technology that has the potential to serve as a game changer in wastewater treatment. FO-based processes can simultaneously produce high quality effluent and pre-concentrated wastewater for anaerobic treatment to facilitate the recovery of energy and nutrients. Complex wastewaters can be directly pre-treated by FO and fresh water can be produced when coupled with a draw solute recovery process (i.e. reverse osmosis or membrane distillation). By enriching organic carbon and nutrients for subsequent biogas production, FO extends the resource recovery potential of current wastewater treatment processes. Here, we critically review recent applications of …


Longitudinal Assessment Of Metal Concentrations And Copper Isotope Ratios In The G93a Sod1 Mouse Model Of Amyotrophic Lateral Sclerosis, T. Gabriel Enge, Heath Ecroyd, Dianne F. Jolley, Justin J. Yerbury, Anthony Dosseto Jan 2017

Longitudinal Assessment Of Metal Concentrations And Copper Isotope Ratios In The G93a Sod1 Mouse Model Of Amyotrophic Lateral Sclerosis, T. Gabriel Enge, Heath Ecroyd, Dianne F. Jolley, Justin J. Yerbury, Anthony Dosseto

Illawarra Health and Medical Research Institute

Amyotrophic lateral sclerosis (ALS) is a motor neuron disease, which involves progressive motor neuron degeneration in the central nervous system (CNS). The G93A SOD1 mouse model simulates one of the most common causes of familial ALS through the overexpression of a mutated form of the human gene encoding copper/zinc superoxide dismutase (SOD1). Transition metals, particularly Cu and Zn, have been shown to behave abnormally in the disease context and have been hypothesized to contribute to and potentially trigger the disease. In this study, concentrations of Cu, Zn and Fe, as well as Cu isotope ratios were assessed in keystone tissues …


A Diet Enriched With Red Sorghum Flaked Biscuits, Compared To A Diet Containing White Wheat Flaked Biscuits, Does Not Enhance The Effectiveness Of An Energy-Restricted Meal Plan In Overweight And Mildly Obese Adults, Anita Stefoska-Needham, Eleanor J. Beck, Stuart K. Johnson, Marijka Batterham, Ross Grant, John F. Ashton, Linda C. Tapsell Jan 2017

A Diet Enriched With Red Sorghum Flaked Biscuits, Compared To A Diet Containing White Wheat Flaked Biscuits, Does Not Enhance The Effectiveness Of An Energy-Restricted Meal Plan In Overweight And Mildly Obese Adults, Anita Stefoska-Needham, Eleanor J. Beck, Stuart K. Johnson, Marijka Batterham, Ross Grant, John F. Ashton, Linda C. Tapsell

Illawarra Health and Medical Research Institute

Objectives: Whole grain sorghum is a promising ingredient in foods, especially those targeting satiety and weight control. This study aimed to test weight loss effects of a whole grain red sorghum product incorporated into an energy-restricted diet.

Methods: Sixty subjects (46 females) were randomized to either a sorghum (intervention) or white wheat (control) group, receiving 45 g of flaked cereal biscuits to include daily in their prescribed diets for 12 weeks. Primary outcome was weight loss. Secondary outcomes included plasma glucose, glycosylated hemoglobin (HbA1c), insulin, total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triacylglycerides (TAG), interleukin (IL)-1β, …