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Full-Text Articles in Social and Behavioral Sciences

Automated Surface Sampling Of Lipids From Worn Contact Lenses Coupled With Tandem Mass Spectrometry, Simon H. Brown, Liam H. Huxtable, Mark D. P Willcox, Stephen J. Blanksby, Todd W. Mitchell Nov 2012

Automated Surface Sampling Of Lipids From Worn Contact Lenses Coupled With Tandem Mass Spectrometry, Simon H. Brown, Liam H. Huxtable, Mark D. P Willcox, Stephen J. Blanksby, Todd W. Mitchell

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

The deposition of biological material (biofouling) onto polymeric contact lenses is thought to be a major contributor to lens discomfort and hence discontinuation of wear. We describe a method to characterize lipid deposits directly from worn contact lenses utilizing liquid extraction surface analysis coupled to tandem mass spectrometry (LESA-MS/MS). This technique effected facile and reproducible extraction of lipids from the contact lens surfaces and identified lipid molecular species representing all major classes present in human tear film. Our data show that LESA-MS/MS is a rapid and comprehensive technique for the characterization of lipid-related biofouling on polymer surfaces.


The Small Heat-Shock Protein Αb-Crystallin Uses Different Mechanisms Of Chaperone Action To Prevent The Amorphous Versus Fibrillar Aggregation Of Α-Lactalbumin, Melissa Kulig, Heath Ecroyd Sep 2012

The Small Heat-Shock Protein Αb-Crystallin Uses Different Mechanisms Of Chaperone Action To Prevent The Amorphous Versus Fibrillar Aggregation Of Α-Lactalbumin, Melissa Kulig, Heath Ecroyd

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

Stress conditions can destabilize proteins, promoting them to unfold and adopt intermediately folded states. Partially folded protein intermediates are unstable and prone to aggregation down off-folding pathways leading to the formation of either amorphous or amyloid fibril aggregates. The sHsp (small heat-shock protein) αB-crystallin acts as a molecular chaperone to prevent both amorphous and fibrillar protein aggregation; however, the precise molecular mechanisms behind its chaperone action are incompletely understood. To investigate whether the chaperone activity of αB-crystallin is dependent upon the form of aggregation (amorphous compared with fibrillar), bovine α-lactalbumin was developed as a model target protein that could be …


Simulation Study Of Ion Pairing In Concentrated Aqueous Salt Solutions With A Polarizable Force Field, Yun Luo, Wei Jiang, Haibo Yu, Alexander D. Mackerrell, Benoit Roux May 2012

Simulation Study Of Ion Pairing In Concentrated Aqueous Salt Solutions With A Polarizable Force Field, Yun Luo, Wei Jiang, Haibo Yu, Alexander D. Mackerrell, Benoit Roux

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

The accuracy of empirical force fields is critical for meaningful molecular dynamics simulations of concentrated ionic solutions. Current models are typically developed on the basis of single ion properties such as the monohydrate energy in the gas phase, or the absolute hydration free energy at infinite dilution. However, the failure of these models to represent accurately the properties of concentrated solutions cannot be excluded. Here, these issues are illustrated for a polarizable potential based on classical Drude oscillators. To model accurately concentrated ionic solutions, the parameters of the potential functions are optimized to reproduce osmotic pressure data. The sodium-chloride potential …


The Role Of Streptokinase As A Virulence Determinant Of Streptococcus Pyogenes - Potential For Therapeutic Targeting, Jason D. Mcarthur, Simon M. Cook, Carola Venturini, Mark J. Walker Mar 2012

The Role Of Streptokinase As A Virulence Determinant Of Streptococcus Pyogenes - Potential For Therapeutic Targeting, Jason D. Mcarthur, Simon M. Cook, Carola Venturini, Mark J. Walker

Faculty of Science - Papers (Archive)

Streptococcus pyogenes is a major human pathogen responsible for numerous diseases ranging from uncomplicated skin and throat infections to severe, life threatening invasive disease such as necrotising fasciitis and streptococcal toxic shock syndrome. These severe invasive infections progress rapidly and produce high rates of morbidity and mortality despite the implementation of aggressive treatment plans. The activation of plasminogen and the acquisition of plasmin activity at the bacterial cell surface is critical for the invasive pathogenesis of this organism. To facilitate this process, S. pyogenes secrete streptokinase, a potent plasminogen activating protein. Here, we describe the role of streptokinase in invasive …


Polymorphic Male Color Morphs Visualized With Steroids In Monomorphic Females: A Tool For Designing Analysis Of Sex-Limited Trait Inheritance, Mats M. Olsson, Mo Healey, Mark Wilson, Michael Tobler Feb 2012

Polymorphic Male Color Morphs Visualized With Steroids In Monomorphic Females: A Tool For Designing Analysis Of Sex-Limited Trait Inheritance, Mats M. Olsson, Mo Healey, Mark Wilson, Michael Tobler

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

In diploid animals, males and females share most of the genome (except sex-specific elements, such as sex chromosome genes), yet despite sharing the underlying genes that hard-wire traits, males and females may differ in their phenotypes when traits are controlled by proximate mechanisms, such as hormones. In color polymorphic species where coloration is only expressed in one sex, the design of studies of the inheritance of color and coevolved morph-specific traits (e.g. territorial vs sneaker strategies, skewed energetic investment in territorial defense vs sperm production, etc.) is compromised as the expression of morph-coding genes is only visualized in one sex. …


Inorganic Arsenic And Iron(Ii) Distributions In Sediment Porewaters Investigated By A Combined Dgt - Colourimetric Det Technique, William Bennett, Peter R. Teasdale, David T. Welsh, Jarad Panther, Ryan R. Stewart, Helen L. Price, Dianne F. Jolley Jan 2012

Inorganic Arsenic And Iron(Ii) Distributions In Sediment Porewaters Investigated By A Combined Dgt - Colourimetric Det Technique, William Bennett, Peter R. Teasdale, David T. Welsh, Jarad Panther, Ryan R. Stewart, Helen L. Price, Dianne F. Jolley

Faculty of Science - Papers (Archive)

No abstract provided.


Does Cytotoxicity Of Metallointercalators Correlate With Cellular Uptake Or Dna Affinity?, Kimberley J. Davis, Judith A. Carrall, Barry Lai, Janice R. Aldrich-Wright, Stephen F. Ralph, Carolyn T. Dillon Jan 2012

Does Cytotoxicity Of Metallointercalators Correlate With Cellular Uptake Or Dna Affinity?, Kimberley J. Davis, Judith A. Carrall, Barry Lai, Janice R. Aldrich-Wright, Stephen F. Ralph, Carolyn T. Dillon

Faculty of Science - Papers (Archive)

The cytotoxicity of the metallointercalators, [Pt(5,6-dimethyl-1,10-phenanthroline)(trans-1R,2Rdiaminocyclohexane)] 2+ ([56MERR]) and [Pt(5,6-dimethyl-1,10-phenanthroline)(trans-1S,2Sdiaminocyclohexane)] 2+ ([56MESS]), towards A549 human lung cancer cells was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The IC50 value obtained following exposure of A549 cells to [56MESS] for 4 h was approximately three times smaller than that obtained when [56MERR] was administered under the same conditions, indicating that the former complex displayed greater cytotoxicity. Both IC50 values were greater than that obtained after exposure of A549 cells to cisplatin, demonstrating that the latter compound was the most cytotoxic of the three examined. Microprobe synchrotron radiation X-ray fluorescence (SR-XRF) analyses of …


High-Yield Cell-Free Protein Synthesis For Site-Specific Incorporation Of Unnatural Amino Acids At Two Sites, Kiyoshi Ozawa, Karin V. Loscha, Kekini V. Kuppan, Choy Theng Loh, Nicholas E. Dixon, Gottfried Otting Jan 2012

High-Yield Cell-Free Protein Synthesis For Site-Specific Incorporation Of Unnatural Amino Acids At Two Sites, Kiyoshi Ozawa, Karin V. Loscha, Kekini V. Kuppan, Choy Theng Loh, Nicholas E. Dixon, Gottfried Otting

Faculty of Science - Papers (Archive)

Using aminoacyl-tRNA synthetase/suppressor tRNA pairs derived from Methanocaldococcus jannaschii, an Escherichia coli cell-free protein production system affords proteins with site-specifically incorporated unnatural amino acids (UAAs) in high yields through the use of optimized amber suppressor tRNACUA opt and optimization of reagent concentrations. The efficiency of the cell-free system allows the incorporation of trifluoromethyl-phenylalanine using a polyspecific synthetase evolved previously for p-cyanophenylalanine, and the incorporation of UAAs at two different sites of the same protein without any re-engineering of the E. coli cells used to make the cell-free extract.


Dgt-Induced Copper Flux Predicts Bioaccumulation And Toxicity To Bivalves In Sediments With Varying Properties, Stuart L. Simpson, Heloise Yverneau, Anne Cremazy, Chad V. Jarolimek, Helen Price, Dianne F. Jolley Jan 2012

Dgt-Induced Copper Flux Predicts Bioaccumulation And Toxicity To Bivalves In Sediments With Varying Properties, Stuart L. Simpson, Heloise Yverneau, Anne Cremazy, Chad V. Jarolimek, Helen Price, Dianne F. Jolley

Faculty of Science - Papers (Archive)

Many regulatory frameworks for sediment quality assessment include consideration of contaminant bioavailability. However, the “snap-shots” of metal bioavailability provided by analyses of porewaters or acid-volatile sulfidesimultaneously extractable metal (AVS-SEM) relationships do not always contribute sufficient information. The use of inappropriate or inadequate information for assessing metal bioavailability in sediments may result in incorrect assessment decisions. The technique of diffusive gradients in thin films (DGT) enables the in situ measurement of metal concentrations in waters and fluxes from sediment porewaters. We utilized the DGT technique to interpret the bioavailability of copper to the benthic bivalve Tellina deltoidalis in sediments of varying …


Molecular Characterization Of A 21.4 Kilobase Antibiotic Resistance Plasmid From An Hemolytic Escherichia Coli O108:H-Human Clinical Isolate, Fay E. Dawes, Dieter M. Bulach, Alexander Kuzevski, Karl A. Bettelheim, Carola Venturini, Steven P. Djordjevic, Mark J. Walker Jan 2012

Molecular Characterization Of A 21.4 Kilobase Antibiotic Resistance Plasmid From An Hemolytic Escherichia Coli O108:H-Human Clinical Isolate, Fay E. Dawes, Dieter M. Bulach, Alexander Kuzevski, Karl A. Bettelheim, Carola Venturini, Steven P. Djordjevic, Mark J. Walker

Faculty of Science - Papers (Archive)

This study characterizes the 21.4 kilobase plasmid pECTm80 isolated from Escherichia coli strain 80, an α hemolytic human clinical diarrhoeal isolate (serotype O108:H-). DNA sequence analysis of pECTm80 revealed it belonged to incompatibility group X1, and contained plasmid partition and toxin-antitoxin systems, an R6K-like triple origin (ori) replication system, genes required for replication regulation, insertion sequences IS1R, ISEc37 and a truncated transposase gene (Tn3-like ΔtnpA) of the Tn3 family, and carried a class 2 integron. The class 2 integron of pECTm80 contains an intact cassette array dfrA1-sat2, encoding resistance to trimethoprim and streptothricin, …


Isolation Of Tuberospironine A, A Novel Croomine Derivative From Stemona Tuberosa Lour., Pratiwi Pudjiastuti, Stephen G. Pyne, S Sugiyanto, Wilford Lie Jan 2012

Isolation Of Tuberospironine A, A Novel Croomine Derivative From Stemona Tuberosa Lour., Pratiwi Pudjiastuti, Stephen G. Pyne, S Sugiyanto, Wilford Lie

Faculty of Science - Papers (Archive)

A novel croomine derivative, tuberospironine A (3-epi-tuberospironine) was isolated from the root extracts of Stemona tuberosa Lour. found growing on Seram Island, Moluccas Province, Indonesia. The structure of this novel alkaloid, with unprecedented configuration at C-3 for a croomine derivative, was determined from interpretation of its NMR spectroscopic data.


Activation Of The Damage-Associated Molecular Pattern Receptor P2x7 Induces Interleukin-1b Release From Canine Monocytes, Iman Jalilian, Michelle Peranec, Belinda L. Curtis, Aine Seavers, Mari Spildrejorde, Vanessa Sluyter, Ronald Sluyter Jan 2012

Activation Of The Damage-Associated Molecular Pattern Receptor P2x7 Induces Interleukin-1b Release From Canine Monocytes, Iman Jalilian, Michelle Peranec, Belinda L. Curtis, Aine Seavers, Mari Spildrejorde, Vanessa Sluyter, Ronald Sluyter

Faculty of Science - Papers (Archive)

P2X7, a damage-associated molecular pattern receptor and adenosine 5'-triphosphate (ATP)-gated cation channel, plays an important role in the activation of the NALP3 inflammasome and subsequent release of interleukin (IL)-1β from human monocytes; however its role in monocytes from other species including the dog remains poorly defined. This study investigated the role of P2X7 in canine monocytes, including its role in IL-1β release. A fixed-time flow cytometric assay demonstrated that activation of P2X7 by extracellular ATP induces the uptake of the organic cation, YO-PRO-12+, into peripheral blood monocytes from various dog breeds, a process impaired by the specific P2X7 …


Molecular Dynamics Analysis Of Apolipoprotein-D - Lipid Hydroperoxide Interactions: Mechanism For Selective Oxidation Of Met-93, Aaron J. Oakley, Surabhi Bhatia, Heath Ecroyd, Brett Garner Jan 2012

Molecular Dynamics Analysis Of Apolipoprotein-D - Lipid Hydroperoxide Interactions: Mechanism For Selective Oxidation Of Met-93, Aaron J. Oakley, Surabhi Bhatia, Heath Ecroyd, Brett Garner

Faculty of Science - Papers (Archive)

Background: Recent studies suggest reduction of radical-propagating fatty acid hydroperoxides to inert hydroxides by interaction with apolipoprotein-D (apoD) Met93 may represent an antioxidant function for apoD. The nature and structural consequences of this selective interaction are unknown.

Methodology/Principal Findings: Herein we used molecular dynamics (MD) analysis to address these issues. Longtimescale simulations of apoD suggest lipid molecules are bound flexibly, with the molecules free to explore multiple conformations in a binding site at the entrance to the classical lipocalin ligand-binding pocket. Models of 5s- 12s- and 15s hydroperoxyeicosatetraenoic acids were created and the lipids found to wrap around Met93 thus …


Fragment-Based Screening By Protein Crystallography: Successes And Pitfalls, Zorik Chilingaryan, Zhou Yin, Aaron J. Oakley Jan 2012

Fragment-Based Screening By Protein Crystallography: Successes And Pitfalls, Zorik Chilingaryan, Zhou Yin, Aaron J. Oakley

Faculty of Science - Papers (Archive)

Fragment-based drug discovery (FBDD) concerns the screening of low-molecular weight compounds against macromolecular targets of clinical relevance. These compounds act as starting points for the development of drugs. FBDD has evolved and grown in popularity over the past 15 years. In this paper, the rationale and technology behind the use of X-ray crystallography in fragment based screening (FBS) will be described, including fragment library design and use of synchrotron radiation and robotics for high-throughput X-ray data collection. Some recent uses of crystallography in FBS will be described in detail, including interrogation of the drug targets β-secretase, phenylethanolamine N-methyltransferase, phosphodiesterase …


Dissociation Of Erk Signalling Inhibition From The Anti-Amyloidogenic Action Of Synthetic Ceramide Analogues, Hongyun Li, Genevieve Evin, Andrew F. Hill, Ya Hui Hung, Ashley I. Bush, Brett Garner Jan 2012

Dissociation Of Erk Signalling Inhibition From The Anti-Amyloidogenic Action Of Synthetic Ceramide Analogues, Hongyun Li, Genevieve Evin, Andrew F. Hill, Ya Hui Hung, Ashley I. Bush, Brett Garner

Faculty of Science - Papers (Archive)

Inhibition of GSL (glycosphingolipid) synthesis reduces Aβ (amyloid β-peptide) production in vitro. Previous studies indicate that GCS (glucosylceramide synthase) inhibitors modulate phosphorylation of ERK1/2 (extracellular-signal-regulated kinase 1/2) and that the ERK pathway may regulate some aspects of Aβ production. It is not clear whether there is a causative relationship linking GSL synthesis inhibition, ERK phosphorylation and Aβ production. In the present study, we treated CHO cells (Chinese-hamster ovary cells) and SH-SY5Y neuroblastoma cells, that both constitutively express human wild-type APP (amyloid precursor protein) and process this to produce Aβ, with GSL-modulating agents to explore this relationship. We found that three …


Phytochemical And Biological Activity Studies Of The Bhutanese Medicinal Plant Corydalis Crispa, Phurpa Wangchuk, Paul A. Keller, Stephen G. Pyne, Thanapat Sastraruji, Malai Taweechotipatr, Roonglawan Rattanajak, Aunchalee Tonsomboon, Sumalee Kamchonwongpaisan Jan 2012

Phytochemical And Biological Activity Studies Of The Bhutanese Medicinal Plant Corydalis Crispa, Phurpa Wangchuk, Paul A. Keller, Stephen G. Pyne, Thanapat Sastraruji, Malai Taweechotipatr, Roonglawan Rattanajak, Aunchalee Tonsomboon, Sumalee Kamchonwongpaisan

Faculty of Science - Papers (Archive)

The chemical constituents and biological activities of Corydalis crispa (Fumariaceae) were investigated for the first time. The phytochemical study resulted in the isolation of nine known isoquinoline alkaloids: protopine (1), 13-oxoprotopine (2), 13-oxocryptopine (3), stylopine (4), coreximine (5), rheagenine (6), ochrobirine (7), sibiricine (8) and bicuculline (9), with complete NMR data for 2 and 3 provided here for the first time. Crude extracts exhibitedsignificant anti-inflammatory (p < 0.01) activity against TNF-alpha production in LPS activated THP-1 cells. The acetylcholinesterase inhibitory activity of compounds 2, 4 and 7 and the antiplasmodial activity of compound 5 against P. falciparum strains TM4/8.2 and K1CB1 (multidrug resistant strain) are reported here for the first time. Stylopine (4) did not show antimalarial activity against the K1CB1 strain in contrast to a previous report. This study generated a scientific basis for the use of this plant in Bhutanese traditional medicine, either individually or in combination with other medicinal ingredients to treat a broad range of disorders. This study also identified compound 5 as potential new antimalarial lead compound.


Synthesis Of Stemofoline Analogues As Acetylcholinesterase Inhibitors, Kwankamol Sastraruji, Thanapat Sastraruji, Alison T. Ung, Renate Griffith, Araya Jatisatienr, Stephen G. Pyne Jan 2012

Synthesis Of Stemofoline Analogues As Acetylcholinesterase Inhibitors, Kwankamol Sastraruji, Thanapat Sastraruji, Alison T. Ung, Renate Griffith, Araya Jatisatienr, Stephen G. Pyne

Faculty of Science - Papers (Archive)

Thirty two new stemofoline analogues were prepared from didehydrostemofoline for studies as AChE inhibitors. C-3 side-chain modified amino, carbamate, triazole and oxazole stemofoline derivatives were prepared. In general the amine derivatives were found to be stronger inhibitors of AChE than their alcohol analogues that we previously reported. Compounds 5 and 26, with small C-3 side chain substituents, were two of the most active inhibitors. Preliminary molecular docking studies suggested that these compounds may inhibit AChE by binding horizontally along the passage of the active-site gorge and block access to acetylcholine.


Influence Of Plantlet Age And Different Soilless Culture On Acclimatization Of Stemona Curtisii Hook.F., Jiraporn Palee, Srisulak Dheeranupattana, Araya Jatisatienr, Sunanta Wangkarn, Pitchaya Mungkornasawakul, Stephen Pyne, Alison Ung, Thanapat Sastraruji Jan 2012

Influence Of Plantlet Age And Different Soilless Culture On Acclimatization Of Stemona Curtisii Hook.F., Jiraporn Palee, Srisulak Dheeranupattana, Araya Jatisatienr, Sunanta Wangkarn, Pitchaya Mungkornasawakul, Stephen Pyne, Alison Ung, Thanapat Sastraruji

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

The aim of this experiment was to study the optimal age of Stemona curtisii plantlets for acclimatization. The in vitro shoots of S. curtisii were cultured on Murashige and Skoog solid medium supplemented with 1 mg L-1 naphthalene acetic acid to induce roots. Then, the plantlets from in vitro culture of 4, 8 and 12 week-old were transferred into the soil and their survival rate during the acclimatization process in the greenhouse was investigated. It was found that the 8 week-old plantlets had the highest survival rate of 80%. However, to enhance the survival rate of these plantlets, a soilless …


Gender Differences In Cognitive Function Of Patients With Chronic Schizophrenia, Mei Han, Xu-Feng Huang, Da Chun Chen, Mei Hong Xiu, Li Hui, Haibo Liu, Thomas R. Kosten, Xiang Yang Zhang Jan 2012

Gender Differences In Cognitive Function Of Patients With Chronic Schizophrenia, Mei Han, Xu-Feng Huang, Da Chun Chen, Mei Hong Xiu, Li Hui, Haibo Liu, Thomas R. Kosten, Xiang Yang Zhang

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

Schizophrenic patients have cognitive impairments, but gender differences in these cognitive deficits have had limited study. This study assessed cognitive functioning in 471 subjects including 122 male and 78 female schizophrenic patients and 141 male and 130 female healthy controls. We found that immediate memory, language, delayed memory and total RBANS scores were significantly decreased in schizophrenia compared with healthy controls for both genders. Male patients had significant lower immediate memory, delayed memory and total RBANS scores than female patients, and healthy controls showed a similar gender difference. The RBANS showed modest correlations with PANSS scores, duration of illness and …


Characterization Of Cleavage Events In The Multifunctional Cilium Adhesin Mhp684 (P146) Reveals A Mechanism By Which Mycoplasma Hyopneumoniae Regulates Surface Topography, Daniel Bogema, Ania T. Deutscher, Lauren K. Woolley, Lisa M. Seymour, Benjamin B. A Raymond, Jessica L. Tacchi, Matthew P. Padula, Nicholas E. Dixon, F Chris Minion, Cheryl Jenkins, Mark J. Walker, Steven P. Djordjevic Jan 2012

Characterization Of Cleavage Events In The Multifunctional Cilium Adhesin Mhp684 (P146) Reveals A Mechanism By Which Mycoplasma Hyopneumoniae Regulates Surface Topography, Daniel Bogema, Ania T. Deutscher, Lauren K. Woolley, Lisa M. Seymour, Benjamin B. A Raymond, Jessica L. Tacchi, Matthew P. Padula, Nicholas E. Dixon, F Chris Minion, Cheryl Jenkins, Mark J. Walker, Steven P. Djordjevic

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

Mycoplasma hyopneumoniae causes enormous economic losses to swine production worldwide by colonizing the ciliated epithelium in the porcine respiratory tract, resulting in widespread damage to the mucociliary escalator, prolonged inflammation, reduced weight gain, and secondary infections. Protein Mhp684 (P146) comprises 1,317 amino acids, and while the N-terminal 400 residues display significant sequence identity to the archetype cilium adhesin P97, the remainder of the molecule is novel and displays unusual motifs. Proteome analysis shows that P146 preprotein is endogenously cleaved into three major fragments identified here as P50P146, P40P146, and P85P146 that reside on the cell surface. Liquid chromatography with tandem …


Membrane Lipids In Human Lenses And Age, J R. Hughes, J M. Deeley, J -A Seng, S R. Ellis, Stephen J. Blanksby, F Leisch, Roger J. W Truscott, T W. Mitchell Jan 2012

Membrane Lipids In Human Lenses And Age, J R. Hughes, J M. Deeley, J -A Seng, S R. Ellis, Stephen J. Blanksby, F Leisch, Roger J. W Truscott, T W. Mitchell

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

Abstract of paper that presented at the XX Biennial Meeting of the International society for Eye Research, 21-25 July, Berlin.


Model Studies Towards The Total Synthesis Of The Stemona Alkaloid 1-Hydroxyprotostemonine: Synthesis Of Ent-1-Hydroxystemoamide, Nalivela Kumara Swamy, Stephen G. Pyne Jan 2012

Model Studies Towards The Total Synthesis Of The Stemona Alkaloid 1-Hydroxyprotostemonine: Synthesis Of Ent-1-Hydroxystemoamide, Nalivela Kumara Swamy, Stephen G. Pyne

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

As part of a model study towards the total synthesis of Stemona alkaloid 1-hydroxyprotostemonine 1, we have achieved the synthesis an A-B-C ring precursor, ent-1-hydroxystemoamide. Key steps involve an ene-yne RCM reaction and a diastereoselective dihydroxylation-lactonization reaction.


Is Seladin-1 Really A Selective Alzheimer's Disease Indicator?, Laura J. Sharpe, Jenny Wong, Brett Garner, Glenda M. Halliday, Andrew J. Brown Jan 2012

Is Seladin-1 Really A Selective Alzheimer's Disease Indicator?, Laura J. Sharpe, Jenny Wong, Brett Garner, Glenda M. Halliday, Andrew J. Brown

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

Selective Alzheimer's Disease Indicator-1 (Seladin-1) was originally identified by its down-regulation in the brains of Alzheimer's disease (AD) patients. Here, we re-examine existing data and present new gene expression data that refutes its role as a selective AD indicator. Furthermore, we caution against the use of the name “Seladin-1” and instead recommend adoption of the approved nomenclature, 3β-hydroxysterol Δ24-reductase (or DHCR24), which describes its catalytic function in cholesterol synthesis. Further work is required to determine what link, if any, exists between DHCR24 and AD.


Novel Olanzapine Analogues Presenting A Reduced H1 Receptor Affinity And Retained 5ht2a/D2 Binding Affinity Ratio, Somayeh Jafari, Marc E. Bouillon, Xu-Feng Huang, Stephen G. Pyne, Francesca Fernandez-Enright Jan 2012

Novel Olanzapine Analogues Presenting A Reduced H1 Receptor Affinity And Retained 5ht2a/D2 Binding Affinity Ratio, Somayeh Jafari, Marc E. Bouillon, Xu-Feng Huang, Stephen G. Pyne, Francesca Fernandez-Enright

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

Background Olanzapine is an atypical antipsychotic drug with high clinical efficacy, but which can cause severe weight gain and metabolic disorders in treated patients. Blockade of the histamine 1 (H1) receptors is believed to play a crucial role in olanzapine induced weight gain, whereas the therapeutic effects of this drug are mainly attributed to its favourable serotoninergic 2A and dopamine 2 (5HT2A/D2) receptor binding affinity ratios. Results We have synthesized novel olanzapine analogues 8a and 8b together with the already known derivative 8c and we have examined their respective in vitro affinities for the 5HT2A, D2, and H1 receptors. Conclusions …


Sensitivity To Lysosome-Dependent Cell Death Is Directly Regulated By Lysosomal Cholesterol Content, Hanna Appelqvist, Linnea Sandin, Karin Bjornstrom, Paul Saftig, Brett Garner, Karin Ollinger, Katarina Kagedal Jan 2012

Sensitivity To Lysosome-Dependent Cell Death Is Directly Regulated By Lysosomal Cholesterol Content, Hanna Appelqvist, Linnea Sandin, Karin Bjornstrom, Paul Saftig, Brett Garner, Karin Ollinger, Katarina Kagedal

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

Alterations in lipid homeostasis are implicated in several neurodegenerative diseases, although the mechanisms responsible are poorly understood. We evaluated the impact of cholesterol accumulation, induced by U18666A, quinacrine or mutations in the cholesterol transporting Niemann-Pick disease type C1 (NPC1) protein, on lysosomal stability and sensitivity to lysosome-mediated cell death. We found that neurons with lysosomal cholesterol accumulation were protected from oxidative stress-induced apoptosis. In addition, human fibroblasts with cholesterol-loaded lysosomes showed higher lysosomal membrane stability than controls. Previous studies have shown that cholesterol accumulation is accompanied by the storage of lipids such as sphingomyelin, glycosphingolipids and sphingosine and an up …


Synthesis Of Spirocyclic Azacycles From The Cyclization Of Furan Tethered N-Acyliminium Ions, Sudhir R. Shengule, Anthony Willis, Stephen G. Pyne Jan 2012

Synthesis Of Spirocyclic Azacycles From The Cyclization Of Furan Tethered N-Acyliminium Ions, Sudhir R. Shengule, Anthony Willis, Stephen G. Pyne

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

The protic and Lewis acid promoted cyclization reactions of tethered furan-4,5-dihydroxypiperid-2-ones, furan-4,5-diacetoxypiperid-2-ones and furan-3,4-diacetoxypyrrolid-2-ones, via their corresponding N-acyliminium ion intermediates, have been studied. In the case of the furan-4,5-dihydroxypiperid-2-one 2a and its diacetate derivative 2b, macrocyclic products were formed from an initial intermolecular reaction between 2a or 2b, via the nucleophilic C5 furan carbon, and their corresponding N-acyliminium ion intermediates. When the furan C5 position of 2b was blocked by substitution with bromine then TFA or Sc(OTf)3 catalysed cyclization reactions gave a spirotricyclic product (a 5-6-6-tricycle) in a highly diastereoselective manner. Cyclization of the analogous C5-Br-furan-pyrrolidone 29 with TFA resulted …


Streptokinase Variants From Streptococcus Pyogenes Isolates Display Altered Plasminogen Activation Characteristics - Implications For Pathogenesis, Simon M. Cook, Amanda Skora, Christine M. Gillen, Mark J. Walker, Jason D. Mcarthur Jan 2012

Streptokinase Variants From Streptococcus Pyogenes Isolates Display Altered Plasminogen Activation Characteristics - Implications For Pathogenesis, Simon M. Cook, Amanda Skora, Christine M. Gillen, Mark J. Walker, Jason D. Mcarthur

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

Streptococcus pyogenes (group A streptococcus, GAS) secretes streptokinase, a potent plasminogen activating protein. Among GAS isolates, streptokinase gene sequences (ska) are polymorphic and can be grouped into two distinct sequence clusters (termed cluster type-1 and cluster type-2) with cluster type-2 being further divided into sub-clusters type-2a and type-2b. In this study, far-UV circular dichroism spectroscopy indicated that purified streptokinase variants of each type displayed similar secondary structure. Type-2b streptokinase variants could not generate an active site in Glu-plasminogen through non-proteolytic mechanisms while all other variants had this capability. Furthermore, when compared with other streptokinase variants, type-2b variants displayed a 29- …


Antioxidant And Anticancer Activities From Aerial Parts Of Acalypha Indica Linn, Duangsuree Sanseera, Wirat Niwatananun, Boonsom Liawruangrath, Saisunee Liawruangrath, Apiwat Baramee, Kongkiat Trisuwan, Stephen G. Pyne Jan 2012

Antioxidant And Anticancer Activities From Aerial Parts Of Acalypha Indica Linn, Duangsuree Sanseera, Wirat Niwatananun, Boonsom Liawruangrath, Saisunee Liawruangrath, Apiwat Baramee, Kongkiat Trisuwan, Stephen G. Pyne

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

Extracts of Acalypha indica Linn. (aerial parts) were investigated for antioxidant activity, anticancer activity, and cytotoxicity. The extracts showed a non-cytotoxic response against Vero cells (African green monkey kidney). The anticancer activity of the extracts was tested using the Resazurin Microplate Assay (REMA). The methanol extract showed anticancer activity against NCIH187-Small Cell Lung Cancer with an IC50 of 25.00 μgmL-1. In addition, the hexane, chloroform, and methanol extracts also showed significant antioxidant activities with an IC50 of 6.19, 5.70, and 7.79 mg/mL, respectively, by means of the DPPH radical scavenging assay. The hexane, chloroform, and methanol extracts also showed significant …


Chemical Composition And Biological Activities Of The Essential Oil From Leaves Of Cleidion Javanicum Bl, Duangsuree Sanseera, Wirat Niwatananun, Boonsom Liawruangrath, Saisunee Liawruangrath, Apiwat Baramee, Stephen G. Pyne Jan 2012

Chemical Composition And Biological Activities Of The Essential Oil From Leaves Of Cleidion Javanicum Bl, Duangsuree Sanseera, Wirat Niwatananun, Boonsom Liawruangrath, Saisunee Liawruangrath, Apiwat Baramee, Stephen G. Pyne

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

The essential oil from the leaves of Cleidion javanicum Bl. was isolated by hydrodistillation with the percentage yield of 0.003 % as a pale yellow liquid. The composition of the essential oil was analysed by means of GC-(FID) and GC-MS. Ten constituents accounting for 92.60% total oil were identified. The major components were ethyl linoleolate (32.12 %), hexadecanoic acid (26.77 %), trans-phytol (24.64 %) and iso-phytol (4.80 %). The antimicrobial, anticancer, antioxidant activities and cytotoxicity test of this essential oil were investigated. The oil showed non-cytotoxic effects against Vero cells (African green monky kidney) because it inhibited more than 50 …


Isolation, Biological Activities, And Synthesis Of The Natural Casuarines, Thunwadee Ritthiwigrom, Stephen G. Pyne Jan 2012

Isolation, Biological Activities, And Synthesis Of The Natural Casuarines, Thunwadee Ritthiwigrom, Stephen G. Pyne

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

This chapter describes the isolation, structure elucidation, glycosidase inhibitory activities, and the synthesis of the four naturally occurring casuarines. These are casuarine, casuarine-6-O-α-d-glucoside, 6-epi-casuarine (uniflorine A), and 3-epi-casuarine.