Social and Behavioral Sciences Commons^™

Rapid Cascade Synthesis Of Poly-Heterocyclic Architectures From Indigo, Alireza Shakoori Ghasabi, John Bremner, Anthony C. Willis, Rachada Haritakun, Paul A. Keller

Faculty of Science, Medicine and Health - Papers: part A

The base-induced propargylation of the dye indigo results in the rapid and unprecedented one-pot synthesis of highly functionalized representatives of the pyrazino[1,2-a:4,3-a′]diindole, pyrido[1,2-a:3,4-b′]diindole and benzo[b]indolo[1,2-h]naphthyridine heterocyclic systems, with the last two reflecting the core skeleton of the anticancer/antiplasmodial marine natural products fascaplysin and homofascaplysins and a ring B-homologue, respectively. The polycyclic compounds 6–8, whose structures were confirmed through single-crystal X-ray crystallographic analysis, arise from sequential inter/intramolecular substitution–addition reactions, and in some cases, ring rearrangement reactions. Preliminary studies on controlling the reaction path selectivity, and the potential reaction mechanisms, are also described. Initial biological activity studies with these new heterocyclic derivatives …

Concise Synthesis Of (-)-Steviamine And Analogues And Their Glycosidase Inhibitory Activities, Nadechanok Jiangseubchatveera, Marc E. Bouillon, Boonsom Liawruangrath, Saisunee Liawruangrath, Robert J. Nash, Stephen G. Pyne

Faculty of Science, Medicine and Health - Papers: part A

A concise synthesis of (−)-steviamine is reported along with the synthesis of its analogues 10-nor-steviamine, 10-nor-ent-steviamine and 5-epi-ent-steviamine. These compounds were tested against twelve glycosidases (at 143 μg mL−1 concentrations) and were found to have in general poor inhibitory activity against most enzymes. The 10-nor analogues however, showed 50–54% inhibition of α-L-rhamnosidase from Penicillium decumbens while one of these, 10-nor-steviamine, showed 51% inhibition of N-acetyl-β-D-glucosaminidase (from Jack bean) at the same concentration (760 μM).

Single Molecule Characterization Of The Interactions Between Amyloid-Β Peptides And The Membranes Of Hippocampal Cells, Priyanka Narayan, Kristina A. Ganzinger, James Mccoll, Laura Weimann, Sarah Meehan, Seema Qamar, John A. Carver, Mark R. Wilson, Peter St George-Hyslop, Christopher M. Dobson, David Klenerman

Faculty of Science, Medicine and Health - Papers: part A

Oligomers of the 40 and 42 residue amyloid-β peptides (Aβ40 and Aβ42) have been implicated in the neuronal damage and impaired cognitive function associated with Alzheimer’s disease. However, little is known about the specific mechanisms by which these misfolded species induce such detrimental effects on cells. In this work, we use single-molecule imaging techniques to examine the initial interactions between Aβ monomers and oligomers and the membranes of live cells. This highly sensitive method enables the visualization of individual Aβ species on the cell surface and characterization of their oligomerization state, all at biologically relevant, nanomolar concentrations. The results indicate …

Concise Synthesis Of Α-Substituted 2-Benzofuranmethamines And Other 2-Subsituted Benzofurans Via Α-Substituted 2-Benzofuranmethyl Carbocation Intermediates, Nikhom Wongsa, Ubonta Sommart, Thunwadee Ritthiwigrom, Arife Yazici, Somdej Kanokmedhakul, Kwanjai Kanokmedhakul, Anthony C. Willis, Stephen G. Pyne

Faculty of Science, Medicine and Health - Papers: part A

Propargyl amines 4, where R3 is aryl, undergo 5-exo-dig cyclization reactions under relatively mild conditions (AgNO3, DMF, 60 °C, 1 h) to give 3-amino-2,3-dihydro-2-arylmethylidenebenzofurans 5 (R3 = aryl). In contrast, substrates where R3 is alkyl undergo competing 6-endo-dig and 5-exo-dig cyclization processes. The hydroxymethyl substrate 4 (R3 = CH2OH), however, was smoothly converted to its corresponding 5-exo-dig cyclization product 5, likely due to the assistance of the primary hydroxyl group in the 5-exo-dig cyclization process by silver cation coordination. Under more enforcing conditions (AgNO3, DMF, 100 °C, 18 h), the initially formed products 5 undergo a 1,3-allylic rearrangement to their …

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

Faculty of Science - Papers (Archive)

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

Dna Barcoding Identifies All Immature Life Stages Of A Forensically Important Flesh Fly (Diptera: Sarcophagidae), Kelly A. Meiklejohn, James F. Wallman, Mark Dowton

Faculty of Science, Medicine and Health - Papers: part A

Carrion-breeding insects, such as flesh flies (Diptera: Sarcophagidae), can be used as evidence in forensic investigations. Despite their considerable forensic potential, their use has been limited because morphological species identification, at any life stage, is very challenging. This study investigated whether DNA could be extracted and cytochrome oxidase subunit I (COI) barcode sequences obtained for molecular identification of each immature life stage of the forensically important Australian flesh fly, Sarcophaga (Sarcorohdendorfia) impatiens (Walker). Genomic DNA extracts were prepared from all larval instars and puparia. Amplification of the barcoding region was successful from all extracts, but puparia amplicons were weak. All …

Ozone-Induced Dissociation Of Conjugated Lipids Reveals Significant Reaction Rate Enhancements And Characteristic Odd-Electron Product Ions, Huong T. Pham, Alan T. Maccarone, J Larry Campbell, Todd W. Mitchell, Stephen J. Blanksby

Faculty of Science, Medicine and Health - Papers: part A

Ozone-induced dissociation (OzID) is an alternative ion activation method that relies on the gas phase ion-molecule reaction between a mass-selected target ion and ozone in an ion trap mass spectrometer. Herein, we evaluated the performance of OzID for both the structural elucidation and selective detection of conjugated carbon-carbon double bond motifs within lipids. The relative reactivity trends for [M + X]+ ions (where X = Li, Na, K) formed via electrospray ionization (ESI) of conjugated versus nonconjugated fatty acid methyl esters (FAMEs) were examined using two different OzID-enabled linear ion-trap mass spectrometers. Compared with nonconjugated analogues, FAMEs derived from conjugated …

Structure Based Design Towards The Identification Of Novel Binding Sites And Inhibitors For The Chikungunya Virus Envelope Proteins, Adel A. Rashad, Paul A. Keller

Faculty of Science, Medicine and Health - Papers: part A

Chikungunya virus is an emerging arbovirus that is widespread in tropical regions and is spreading quickly to temperate climates with recent epidemics in Africa, Asia, Europe and the Americas. It is having an increasingly major impact on humans with potentially life-threatening and debilitating arthritis. Thus far, neither vaccines nor medications are available to treat or control the virus and therefore, the development of medicinal chemistry is a vital and immediate issue that needs to be addressed. The viral envelope proteins play a major role during infection through mediation of binding and fusion with the infected cell surfaces. The possible binding …

A New Protoberberine Alkaloid From Meconopsis Simplicifolia (D. Don) Walpers With Potent Antimalarial Activity Against A Multidrug Resistant Plasmodium Falciparum Strain, Phurpa Wangchuk, Paul A. Keller, Stephen G. Pyne, Wilford Lie, Anthony C. Willis, Roonglawan Rattanajak, Sumalee Kamchonwongpaisan

Faculty of Science, Medicine and Health - Papers: part A

Ethnopharmacological relevance The aerial components of Meconopsis simplicifolia (D. Don) Walpers are indicated in Bhutanese traditional medicine for treating malaria, coughs and colds, and the infections of the liver, lung and blood. This study is to validate the ethnopharmacological uses of this plant and also identify potent antimalarial drug leads through bioassays of its crude extracts and phytochemical constituents.

Materials and methods Meconopsis simplicifolia (D. Don) Walpers was collected from Bhutan and its crude MeOH extract was subjected to acid-base fractionation. Through repeated extractions, separations and spectroscopic analysis, the alkaloids obtained were identified and tested for their antimalarial and cytotoxicity …

Daedalic Dna Vaccination Against Self Antigens As A Treatment For Chronic Kidney Disease, Yuan Min Wang, Jimmy Jianheng Zhou, Ya Wang, Debbie Watson, Geoff Yu Zhang, Min Hu, Huiling Wu, Guoping Zheng, Yiping Wang, Anne M. Durkan, David Ch Harris, Stephen I. Alexander

Faculty of Science, Medicine and Health - Papers: part A

Chronic kidney disease (CKD) is a major cause of death and morbidity in Australia and worldwide. DNA vaccination has been used for targeting foreign antigens to induce immune responses and prevent autoimmune disease, viral infection and cancer. However, the use of DNA vaccination has been restricted by a limited ability to induce strong immune responses, especially against self-antigens which are limited by mechanisms of self-tolerance. Furthermore, there have been few studies on the potential of DNA vaccination in chronic inflammatory diseases, including CKD. We have established strategies of DNA vaccination targeting specific self-antigens in the immune system including co-stimulatory pathways, …

Short-Term Effects Of Fish And Fish Oil Consumption On Total And High Molecular Weight Adiponectin Levels In Overweight And Obese Adults, Elizabeth P. Neale, Beverly Muhlhausler, Yasmine C. Probst, Marijka J. Batterham, Francesca Fernandez, Linda C. Tapsell

Faculty of Science, Medicine and Health - Papers: part A

Objective: Fish or fish oil consumption may increase levels of total and high molecular weight (HMW) adiponectin, a hormone associated with anti-inflammatory and insulin-sensitising effects, however it is not known if the effects of the food and supplement are the same. The aim of this study was to compare the effect of consuming fish and fish oil supplements on plasma total and HMW adiponectin concentrations in overweight human participants.

Materials/Methods: 29 overweight and obese participants underwent a two week run-in period, followed by a four week isocaloric dietary intervention which provided 1.8g of long chain omega-3 polyunsaturated fatty acids (LC …

Surface Analysis Of Lipids By Mass Spectrometry: More Than Just Imaging, Shane R. Ellis, Simon H. Brown, Marc In Het Panhuis, Stephen J. Blanksby, Todd W. Mitchell

Faculty of Science, Medicine and Health - Papers: part A

Mass spectrometry is now an indispensable tool for lipid analysis and is arguably the driving force in the renaissance of lipid research. In its various forms, mass spectrometry is uniquely capable of resolving the extensive compositional and structural diversity of lipids in biological systems. Furthermore, it provides the ability to accurately quantify molecular-level changes in lipid populations associated with changes in metabolism and environment; bringing lipid science to the "omics" age. The recent explosion of mass spectrometry-based surface analysis techniques is fuelling further expansion of the lipidomics field. This is evidenced by the numerous papers published on the subject of …

Slow Avoidance Response To Contaminated Sediments Elicits Sublethal Toxicity To Benthic Invertebrates, Daniel J. Ward, Stuart L. Simpson, Dianne F. Jolley

Faculty of Science, Medicine and Health - Papers: part A

Advanced analytical techniques have identified the heterogeneity of sediments in aquatic environments which may impact the exposure of benthic organisms to contaminants. Acute and chronic toxicity associated with short, intermittent exposure to four field-collected contaminated sediments were assessed for the epi-benthic amphipod Melita plumulosa and the harpacticoid copepod Nitocra spinipes. Increasing the duration of exposure caused a decrease in survival of M. plumulosa and N. spinipes during 10-d bioassays. Increasing the frequency of exposure to a total exposure time >96-h resulted in a significant toxicity to M. plumulosa. Reproduction decreased for both species from exposure to contaminated sediment. For M. …

An Assessment Of The Bhutanese Traditional Medicine For Its Ethnopharmacology, Ethnobotany And Ethnoquality: Textual Understanding And The Current Practices, Phurpa Wangchuk, Stephen G. Pyne, Paul A. Keller

Faculty of Science, Medicine and Health - Papers: part A

Ethnopharmacological relevance : This study involves the assessment of the Bhutanese traditional medicine (BTM) which was integrated with the mainstream biomedicine in 1967 to provide primary health care services in the country. It caters to 20-30% of the daily out-patients within 49 traditional medicine units attached to 20 district modern hospitals and 29 Basic Health Units in the country. Aim of the study : This study presents the ethnopharmacological, ethnobotanical and the ethnoquality concepts in relation to mainstream Tibetan medicine and describes the current practices of BTM. Materials and methods : Experienced BTM practitioners (Drung-tshos and Smen-pas) were selected using …

Diabetes And Cognitive Deficits In Chronic Schizophrenia: A Case-Control Study, Mei Han, Xu-Feng Huang, Da Chun Chen, Meihong Xiu, Thomas R. Kosten, Xiang Yang Zhang

Faculty of Science, Medicine and Health - Papers: part A

Cognitive impairment occurs in both schizophrenia and diabetes. There is currently limited understanding whether schizophrenia with diabetes has more serious cognitive deficits than schizophrenia without diabetes or diabetes only. This study assessed cognitive performance in 190 healthy controls, 106 diabetes only, 127 schizophrenia without diabetes and 55 schizophrenia with diabetes. This study was conducted from January 2008 to December 2010. Compared to healthy controls, all patient groups had significantly decreased total and five index RBANS scores (all p<0.01-p

The Boronic Acid Mannich Reaction In Alkaloid Synthesis, Stephen G. Pyne, Andrew S. Davis, Thunwadee Ritthiwigrom, Christopher W. G Au, Kongdech Savaspun, Matthew Wotherspoon

Faculty of Science, Medicine and Health - Papers: part A

Our work on the application of the boronic acid Mannich reaction to the synthesis of pyrrolizidine alkaloids is described.

The Role Of Hypothalamic H1 Receptor Antagonism In Antipsychotic-Induced Weight Gain, Meng He, Chao Deng, Xu-Feng Huang

Faculty of Science, Medicine and Health - Papers: part A

Treatment with second generation antipsychotics (SGAs), notably olanzapine and clozapine, causes severe obesity side effects. Antagonism of histamine H1 receptors has been identified as a main cause of SGA-induced obesity, but the molecular mechanisms associated with this antagonism in different stages of SGA-induced weight gain remain unclear. This review aims to explore the potential role of hypothalamic histamine H1 receptors in different stages of SGA-induced weight gain/obesity and the molecular pathways related to SGA-induced antagonism of these receptors. Initial data have demonstrated the importance of hypothalamic H1 receptors in both short- and long-term SGA-induced obesity. Blocking hypothalamic H1 receptors by …

Extracellular Chaperones And Proteostasis, Amy R. Wyatt, Justin J. Yerbury, Heath Ecroyd, Mark R. Wilson

Faculty of Science, Medicine and Health - Papers: part A

There is a family of currently untreatable serious human diseases that arise from the inappropriate misfolding and aggregation of extracellular proteins. At present our understanding of mechanisms that operate to maintain proteostasis in extracellular body fluids is limited but has significantly advanced with the discovery of a small but growing family of constitutively secreted extracellular chaperones (ECs). The available evidence strongly suggests that these chaperones act as both sensors and disposal-mediators of misfolded proteins in extracellular fluids, thereby normally protecting us from disease pathologies. It is critically important to further increase our understanding of the mechanisms that operate to effect …

The Antiangiogenic Properties Of Sulfated Β-Cyclodextrins In Anticancer Formulations Incorporating 5-Fluorouracil, Clare A. Watson, Kara L. Vine, Julie M. Locke, Anna Bezos, Christopher R. Parish, Marie Ranson

Faculty of Science, Medicine and Health - Papers: part A

Sulfated β-cyclodextrins (S-β-CDs) are useful excipients for improving the solubility of drugs. One such formulation incorporating 5-fluorouracil (5-FU), termed FD(S), showed improved efficacy over 5-FU alone in orthotopic carcinoma xenograft models. S-β-CDs have heparin-like anticoagulant properties, which may have contributed toward the improved antitumor effect of FD(S). S-β-CDs have also been reported to modify a number of processes involved in angiogenesis. Although the anticoagulant nature of S-β-CDs was established, the antiangiogenic properties of S-β-CDs within FD(S) were unknown. The effect of S-β-CD and FD(S) on the proliferation and migration of endothelial cells in live-cell kinetic assays, and the reorganization of …

Developing Galleria Mellonella As A Model Host For Human Pathogens, Simon M. Cook, Jason D. Mcarthur

Faculty of Science, Medicine and Health - Papers: part A

The larvae of Galleria mellonella (also known colloquially as the wax worm) is increasingly being used as an infection model to study virulence factors and pathogenesis of many prominent bacterial and fungal human pathogens. When compared with traditional mammalian model hosts, invertebrate infection models are cheaper to establish and maintain, are more amenable to high-throughput studies and are not subjected to the same ethical constraints as vertebrates. In addition to these benefits, G. mellonella larvae possess a number of other characteristics which make these organisms particularly useful for the study of human pathogens. Larvae are relatively large in size (12- …

Utility Of Coi, Cad And Morphological Data For Resolving Relationships Within The Genus Sarcophaga (Sensu Lato) (Diptera: Sarcophagidae): A Preliminary Study, Kelly A. Meiklejohn, James F. Wallman, Thomas Pape, Stephen L. Cameron, Mark Dowton

Faculty of Science, Medicine and Health - Papers: part A

Currently there are ∼3000 known species of Sarcophagidae (Diptera), which are classified into 173 genera in three subfamilies. Almost 25% of sarcophagids belong to the genus Sarcophaga (sensu lato) however little is known about the validity of, and relationships between the ∼150 (or more) subgenera of Sarcophaga s.l. In this preliminary study, we evaluated the usefulness of three sources of data for resolving relationships between 35 species from 14 Sarcophaga s.l. subgenera: the mitochondrial COI barcode region, ∼800 bp of the nuclear gene CAD, and 110 morphological characters. Bayesian, maximum likelihood (ML) and maximum parsimony (MP) analyses were performed on …

Generation Of Hydrogen Peroxide-Resistant Murine Neuroblastoma Cells: A Target Discovery Platform For Novel Neuroprotective Genes, Annette E. Maczurek, Rebekka Wild, Daunia Laurenti, Megan L. Steele, Lezanne Ooi, Gerald Munch

Faculty of Science, Medicine and Health - Papers: part A

Oxidative stress has been suggested to play an important role in the pathogenesis of various neurodegenerative diseases including Alzheimer’s disease (AD). Hydrogen peroxide (H2O2), one of the main reactive oxygen species, is converted into the highly toxic ·OH radical in the presence of redox-active transition metals, which then oxidises nucleic acids, lipids and proteins, leading to neurodegeneration and cell death. There is an urgent need to gain more knowledge about relevant therapeutic targets to combat oxidative stress and it neurotoxic effects, and how this knowledge can be utilized to develop novel neuroprotective therapies for AD. One way to identify new …

Mechanism For The Synergistic Effect Of Rapamycin And Resveratrol On Hyperinsulinemia May Involve The Activation Of Protein Kinase B, J Chen, Xu-Feng Huang

Faculty of Science, Medicine and Health - Papers: part A

Dear Editor, We read with great interest Leontiev et al.'s paper entitled 'Resveratrol potentiates rapamycin to prevent hyperinsulinemia and obesity in male mice on high-fat diet' recently published in Cell Death & Disease.1 Their finding that rapamycin and resveratrol have a synergistic effect is important for treating insulin resistance. They showed that rapamycin inhibited mammalian target of rapamycin (mTOR) activity, while resveratrol inhibited S6 kinase (S6K). We think that these compounds may exert their effects through activating protein kinase B (Akt), a key regulator of insulin sensitivity. Both the inhibition of mTOR by rapamycin and of S6K by resveratrol could …

Allosteric Activation Transitions In Enzymes And Biomolecular Motors: Insights From Atomistic And Coarse-Grained Simulations, Michael D. Daily, Haibo Yu, George N. Phillips, Qiang Cui

Faculty of Science, Medicine and Health - Papers: part A

The chemical step in enzymes is usually preceded by a kinetically distinct activation step that involves large-scale conformational transitions. In "simple" enzymes this step corresponds to the closure of the active site; in more complex enzymes, such as biomolecular motors, the activation step is more complex and may involve interactions with other biomolecules. These activation transitions are essential to the function of enzymes and perturbations in the scale and/or rate of these transitions are implicated in various serious human diseases; incorporating key flexibilities into engineered enzymes is also considered a major remaining challenge in rational enzyme design. Therefore it is …

Effect Of Nrf2 Activators On Release Of Glutathione, Cysteinylglycine And Homocysteine By Human U373 Astroglial Cells, Megan L. Steele, Stacey Fuller, Mili Patel, Cindy Kersaitis, Lezanne Ooi, Gerald Munch

Faculty of Science, Medicine and Health - Papers: part A

Neurons rely on the release and subsequent cleavage of GSH to cysteinylglycine (CysGly) by astrocytes in order to maintain optimal intracellular GSH levels. In neurodegenerative diseases characterised by oxidative stress, neurons need an optimal GSH supply to defend themselves against free radicals released from activated microglia and astroglia. The rate of GSH synthesis is controlled largely by the activity of γ-glutamyl cysteine ligase. Expression of γ-glutamyl cysteine ligase and of the Xc- system, which facilitates cystine uptake, is regulated by the redox-sensitive transcription factor, nuclear factor erythroid-2-related factor 2 (Nrf2). Compounds that can activate the Nrf2-ARE pathway, referred to as …

Extracellular Wildtype And Mutant Sod1 Induces Er-Golgi Pathology Characteristic Of Amyotrophic Lateral Sclerosis In Neuronal Cells, Vinod Sundaramoorthy, Adam K. Walker, Justin J. Yerbury, Kai Ying Soo, Manal A. Farg, Vy Hoang, Rafaa Zeineddine, Damian Spencer, Julie D. Atkin

Faculty of Science, Medicine and Health - Papers: part A

Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly progressing neurodegenerative disorder and the majority of ALS is sporadic, where misfolding and aggregation of Cu/Zn-superoxide dismutase (SOD1) is a feature shared with familial mutant-SOD1 cases. ALS is characterized by progressive neurospatial spread of pathology among motor neurons, and recently the transfer of extracellular, aggregated mutant SOD1 between cells was demonstrated in culture. However, there is currently no evidence that uptake of SOD1 into cells initiates neurodegenerative pathways reminiscent of ALS pathology. Similarly, whilst dysfunction to the ER-Golgi compartments is increasingly implicated in the pathogenesis of both sporadic and familial ALS, …

Molecular Evidence Of N-Methyl-D-Aspartate Receptor Hypofunction In Schizophrenia, C S. Weickert, S J. Fung, V S. Catts, P R. Schofield, K M. Allen, L T. Moore, Kelly A. Newell, D Pellen, Xu-Feng Huang, S V. Catts, T W Weickert

Faculty of Science, Medicine and Health - Papers: part A

Blockade of N-methyl-D-aspartate receptors (NMDARs) produces behavior in healthy people that is similar to the psychotic symptoms and cognitive deficits of schizophrenia and can exacerbate symptoms in people with schizophrenia. However, an endogenous brain disruption of NMDARs has not been clearly established in schizophrenia. We measured mRNA transcripts for five NMDAR subunit mRNAs and protein for the NR1 subunit in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia and control (n=74) brains. Five NMDAR single-nucleotide polymorphisms (SNPs) previously associated with schizophrenia were tested for association with NMDAR mRNAs in postmortem brain and for association with cognitive ability in an antemortem cohort …

Sequential 1,4- And 1,2-Addition Reactions To Α,Β-Unsaturated N-Acyliminium Ions: A New Strategy For The Synthesis Of Spiro And Bridged Heterocycles, Arife Yazici, Stephen G. Pyne

Faculty of Science, Medicine and Health - Papers: part A

Novel bicyclic and tetracyclic spirocycles and tricyclic bridged heterocyclic systems can be readily prepared from sequential 1,4- and 1,2-addition reactions of latent bis-nucleophiles to α,β-unsaturated N-acyliminium ions.

Glutathionylation Potentiates Benign Superoxide Dismutase 1 Variants To The Toxic Forms Associated With Amyotrophic Lateral Sclerosis, Luke Mcalary, Justin J. Yerbury, J. Andrew Aquilina

Faculty of Science, Medicine and Health - Papers: part A

Dissociation of superoxide dismutase 1 dimers is enhanced by glutathionylation, although the dissociation constants reported to date are imprecise. We have quantified the discreet dissociation constants for wild-type superoxide dismutase 1 and six naturally occurring sequence variants, in their unmodified and glutathionylated forms, at the ratios expressed. Unmodified superoxide dismutase 1 variants that shared similar dissociation constants with SOD1WT had disproportionately increased dissociation constants when glutathionylated. This defines a key role for glutathionylation in superoxide dismutase 1 associated familial amyotrophic lateral sclerosis.

Antimicrobial, Antimalarial And Cytoxicity Activities Of Constituents Of A Bhutanese Variety Of Ajania Nubigena, Phurpa Wangchuk, Paul A. Keller, Stephen G. Pyne, Jurgen Korth, - Samten, Malai Taweechotipatr, Roonglawan Rattanajak, Sumalee Kamchonwongpaisan

Faculty of Science, Medicine and Health - Papers: part A

An investigation of the essential oil (EO) and the crude MeOH extract of a Bhutanese variety of Ajania nubigena using GC/GC-MS and NMR found the following: a) one kg of the dried plant material contained 0.7% w/w EO; b) 44 of the 53 GC-FID peaks of the EO were identified with (3R,6R)-linalool oxide acetate (75.8 %) as the major constituent (chemotype II) and chamazulene as a new sub-chemotype; c) purification of the EO furnished (3R,6R)-linalool oxide acetate (1), chamazulene (2), (E)-2-(2,4-hexadiynylidene)-1,6-dioxaspiro[4,4]non-3-ene (3), and (Z)-2-(2,4-hexadinylidene)-1,6-dioxaspiro[4,4]non-3-ene (4); d) from the crude MeOH extract, four flavonoid compounds: 1-(4-hydroxyphenyl)propan-1-one (5), oxyanin B (6), luteolin …