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Full-Text Articles in Social and Behavioral Sciences
What You Need To Know About Selenium, Terry Young, Keith Finley, William Adams, John Besser, William D. Hopkins, Dianne F. Jolley, Eugenia Mcnaughton, Theresa S. Presser, D. Patrick Shaw, Jason Unrine
What You Need To Know About Selenium, Terry Young, Keith Finley, William Adams, John Besser, William D. Hopkins, Dianne F. Jolley, Eugenia Mcnaughton, Theresa S. Presser, D. Patrick Shaw, Jason Unrine
Faculty of Science - Papers (Archive)
No abstract provided.
Synthesis Of Polyhydroxylated Pyrrolizidine And Indolizidine Compounds And Their Glycosidase Inhibitory Activities, Thunwadee Ritthiwigrom, Robert J. Nash, Stephen G. Pyne
Synthesis Of Polyhydroxylated Pyrrolizidine And Indolizidine Compounds And Their Glycosidase Inhibitory Activities, Thunwadee Ritthiwigrom, Robert J. Nash, Stephen G. Pyne
Faculty of Science - Papers (Archive)
The synthesis of the natural product 3-epi-casuarine and two tricyclic ether bridged analogues, plus 7-deoxy-3,6-diepi-casuarine, 7-epi-australine, 1-epi-castanospermine and 1,6-diepi-castanospermine is described. The glycosidase inhibitory activities of these compounds, along with that of uniflorine A and other polyhydroxylated pyrrolizidines and indolizidines that we have published before, are reported.
Synthesis Of 2′-Aminoalkyl-1-Benzylisoquinoline Derivatives And Medium Sized Ring Analogues With Mu Opiod Receptor Binding Activities, Uta Mbere-Nguyen, Alison T. Ung, Stephen G. Pyne
Synthesis Of 2′-Aminoalkyl-1-Benzylisoquinoline Derivatives And Medium Sized Ring Analogues With Mu Opiod Receptor Binding Activities, Uta Mbere-Nguyen, Alison T. Ung, Stephen G. Pyne
Faculty of Science - Papers (Archive)
Novel 2′-aminoalkyl-1-benzylisoquinoline compounds and medium size ring analogues have been prepared using reductive alkylation methods. Four of these analogues were tested for biological activity across 48 different CNS receptors and were showed to have binding activities at the mu opiod receptor.
The Acute Nociceptive Signals Induced By Bradykinin In Rat Sensory Neurons Are Mediated By Inhibition Of M-Type K+ Channels And Activation Of Ca2+-Activated Cl- Channels, Boyi Liu, John E. Linley, Xiaona Du, Xuan Zhang, Lezanne Ooi, Hailin Zhang, Nikita Gamper
The Acute Nociceptive Signals Induced By Bradykinin In Rat Sensory Neurons Are Mediated By Inhibition Of M-Type K+ Channels And Activation Of Ca2+-Activated Cl- Channels, Boyi Liu, John E. Linley, Xiaona Du, Xuan Zhang, Lezanne Ooi, Hailin Zhang, Nikita Gamper
Faculty of Science - Papers (Archive)
Bradykinin (BK) is an inflammatory mediator and one of the most potent endogenous pain-inducing substances. When released at sites of tissue damage or inflammation, or applied exogenously, BK produces acute spontaneous pain and causes hyperalgesia (increased sensitivity to potentially painful stimuli). The mechanisms underlying spontaneous pain induced by BK are poorly understood. Here we report that in small nociceptive neurons from rat dorsal root ganglia, BK, acting through its B2 receptors, PLC, and release of calcium from intracellular stores, robustly inhibits M-type K+ channels and opens Ca2+-activated Cl- channels (CaCCs) encoded by Tmem16a (also known as Ano1). Summation of these …
Transcriptional Control Of Kcnq Channel Genes And The Regulation Of Neuronal Excitability, Mariusz Mucha, Lezanne Ooi, John Linley, Pawel Mordaka, Carine Dalle, Brian Robertson, Nikita Gamper, Ian C. Wood
Transcriptional Control Of Kcnq Channel Genes And The Regulation Of Neuronal Excitability, Mariusz Mucha, Lezanne Ooi, John Linley, Pawel Mordaka, Carine Dalle, Brian Robertson, Nikita Gamper, Ian C. Wood
Faculty of Science - Papers (Archive)
Regulation of the resting membrane potential and the repolarization of neurons are important in regulating neuronal excitability. The potassium channel subunits Kv7.2 and Kv7.3 play a key role in stabilizing neuronal activity. Mutations in KCNQ2 and KCNQ3, the genes encoding Kv7.2 and Kv7.3, cause a neonatal form of epilepsy, and activators of these channels have been identified as novel antiepileptics and analgesics. Despite the observations that regulation of these subunits has profound effects on neuronal function, almost nothing is known about the mechanisms responsible for controlling appropriate expression levels. Here we identify two mechanisms responsible for regulating KCNQ2 and …
Localization Of Low Molecular Weight Crystallin Peptides In The Aging Human Lens Using A Maldi Mass Spectrometry Imaging Approach, S. P. Su, Jason D. Mcarthur, J. A. Aquilina
Localization Of Low Molecular Weight Crystallin Peptides In The Aging Human Lens Using A Maldi Mass Spectrometry Imaging Approach, S. P. Su, Jason D. Mcarthur, J. A. Aquilina
Faculty of Science - Papers (Archive)
Low molecular weight (LMW) peptides, derived from the breakdown of the major eye lens proteins, the crystallins, accumulate in the human lens with age. These LMW peptides are associated with age-related lens opacity and cataract, with some shown to inhibit the chaperone activity of α-crystallin. However, the mechanism(s) giving rise to the production of these peptides, as well as their distribution within the lens, are not well understood. In this study, we have mapped the distribution of these crystallin-derived peptides present in human lenses of different ages using matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS). Our data showed that most of …
Synthesis Of Hyacinthacine B-3 And Purported Hyacinthacine B-7, Christopher W.G. Au, Robert J. Nash, Stephen G. Pyne
Synthesis Of Hyacinthacine B-3 And Purported Hyacinthacine B-7, Christopher W.G. Au, Robert J. Nash, Stephen G. Pyne
Faculty of Science - Papers (Archive)
The synthesis of hyacinthacines B-3 and B-7 has confirmed the structure of the former alkaloid and shown that the structure of the latter is incorrect.
Dipyridyl Beta-Diketonate Complexes: Versatile Polydentate Metalloligands For Metal-Organic Frameworks And Hydrogen-Bonded Networks, Andrew D. Burrows, Christopher G. Frost, Mary F. Mahon, Paul R. Raithby, Catherine L. Renouf, Christopher Richardson, Anna J. Stevenson
Dipyridyl Beta-Diketonate Complexes: Versatile Polydentate Metalloligands For Metal-Organic Frameworks And Hydrogen-Bonded Networks, Andrew D. Burrows, Christopher G. Frost, Mary F. Mahon, Paul R. Raithby, Catherine L. Renouf, Christopher Richardson, Anna J. Stevenson
Faculty of Science - Papers (Archive)
The Group 13 metal complexes [M(L-2)(3)], where M is Al or Ga and L-2 is 1,3-di(4-pyridyl)-1,3-propanedionato, are hexatopic metalloligands that have been used to prepare mixed-metalorganic frameworks containing interpenetrated primitive cubic networks. In contrast, the europium complex [Eu(HL2)(3)-(H2L2)]Cl-4 center dot EtOH forms a hydrogen-bonded network following partial protonation of the pyridyl groups.
Esi-Ms And Thermal Melting Studies Of Nanoscale Platinum(Ii) Metallomacrocycles With Dna, Margaret M. Harding, Louis M. Rendina, David Schilter, Thitima Urathamakul, Jennifer L. Beck
Esi-Ms And Thermal Melting Studies Of Nanoscale Platinum(Ii) Metallomacrocycles With Dna, Margaret M. Harding, Louis M. Rendina, David Schilter, Thitima Urathamakul, Jennifer L. Beck
Faculty of Science - Papers (Archive)
The hydrophilic, long-chain diamine PEGda (O,O′-bis(2-aminoethyl)octadeca(ethylene glycol)), when complexed with cis-protected Pt(II) ions afforded water-soluble complexes of the type [Pt(N,N)(PEGda)](NO3)2 (N,N = N,N,N′,N′-tetramethyl-1,2-diaminoethane (tmeda), 1,2-diaminoethane (en), and 2,2′-bipyridine (2,2′-bipy)) featuring unusual 62-membered chelate rings. Equimolar mixtures containing either the 16-mer duplex DNA D2 or the single-stranded D2a and [Pt(N,N)(PEGda)]2+ were analyzed by negative-ion ESI-MS. Analysis of D2-Pt(II) mixtures showed the formation of 1:1 adducts of [Pt(en)(PEGda)]2+, [Pt(tmeda)(PEGda)]2+ and the previously-described metallomacrocycle [Pt2(2,2′-bipy)2{4,4′-bipy(CH2)44,4′-bipy}2]8+ with D2; the dinuclear species bound to D2 most strongly, consistent with its greater charge and aromatic surface area. D2 formed 1:2 complexes with the acyclic species [Pt(2,2′-bipy)(Mebipy)2]4+ …
Novel Technique Shows Different Hydrophobic Chemical Signatures Of Exotic And Indigenous Plant Soils With Similar Effects Of Extracts On Indigenous Species Seedling Growth, Emilie-Jane Ens, Kristine O. French, John B. Bremner, Jurgen Korth
Novel Technique Shows Different Hydrophobic Chemical Signatures Of Exotic And Indigenous Plant Soils With Similar Effects Of Extracts On Indigenous Species Seedling Growth, Emilie-Jane Ens, Kristine O. French, John B. Bremner, Jurgen Korth
Faculty of Science - Papers (Archive)
Changes to ecosystem abiotic parameters are regarded as possible mechanisms facilitating plant invasion and community composition shifts. This study compared the hydrophobic chemical signatures of soil from exotic bitou bush (Chrysanthemoides monilifera spp. rotundata) invaded, indigenous acacia (Acacia longifolia var. sophorae) dominated and bare sand (unvegetated) habitats using a novel, rapid, capturing technique which utilised AmberliteA (R) XAD4 resin filled bags that were placed in situ. The hydrophobic chemical signature of the bitou bush soil extract was significantly different to the acacia soil and bare sand extracts. High concentrations of 18 sesquiterpenes dominated the hydrophobic signature of the bitou bush …
Extracellular Chaperones Modulate The Effects Of Alzheimer's Patient Cerebrospinal Fluid On A Beta(1-42) Toxicity And Uptake , Justin J. Yerbury, Mark R. Wilson
Extracellular Chaperones Modulate The Effects Of Alzheimer's Patient Cerebrospinal Fluid On A Beta(1-42) Toxicity And Uptake , Justin J. Yerbury, Mark R. Wilson
Faculty of Science - Papers (Archive)
Alzheimer's disease is characterised by the inappropriate death of brain cells and accumulation of the A beta peptide in the brain. Thus, it is possible that there are fundamental differences between Alzheimer's disease patients and healthy individuals in their abilities to clear A beta from brain fluid and to protect neurons from A beta toxicity. In the present study, we examined (1) the cytotoxicity of Alzheimer's disease cerebrospinal fluid (CSF) compared to control CSF, (2) the ability of Alzheimer's disease and control CSF to protect cells from A beta toxicity and to promote cell-mediated clearance of A beta and lastly …
Differential Endocytosis Of Tissue Plasminogen Activator By Serpins Pai-1 And Pai-2 On Human Peripheral Blood Monocytes, Jodi A. Lee, David Croucher, Marie Ranson
Differential Endocytosis Of Tissue Plasminogen Activator By Serpins Pai-1 And Pai-2 On Human Peripheral Blood Monocytes, Jodi A. Lee, David Croucher, Marie Ranson
Faculty of Science - Papers (Archive)
Generation of the broad spectrum protease plasmin is facilitated by the tissue (t-PA) and urokinase (u-PA) plasminogen activators, within multiple physiological and disease states. Finely tuned control of this proteolytic cascade is exerted by the plasminogen activator inhibitors type-1 (PAI-1/SERPINE1) and 2 (PAI-2/SERPINB2). Expression of this network of activators and inhibitors by cells of myeloid lineage appears to be highly interchangeable between physiological environments, and whilst the role of PAI-1 and PAI-2 in regulating u-PA-dependent functions is well established, the interaction between t-PA and PAI-2 on these cell types is poorly characterised. To this end, we used freshly isolated peripheral …
The Interaction Of Alphab-Crystallin With Mature Alpha-Synuclein Amyloid Fibrils Inhibits Their Elongation, Christopher A. Waudby, Tuomas P. J Knowles, Glyn L. Devlin, Jeremy N. Skepper, Heath Ecroyd, John A. Carver, Mark E. Welland, John Christodoulou, Christopher M. Dobson, Sarah Meehan
The Interaction Of Alphab-Crystallin With Mature Alpha-Synuclein Amyloid Fibrils Inhibits Their Elongation, Christopher A. Waudby, Tuomas P. J Knowles, Glyn L. Devlin, Jeremy N. Skepper, Heath Ecroyd, John A. Carver, Mark E. Welland, John Christodoulou, Christopher M. Dobson, Sarah Meehan
Faculty of Science - Papers (Archive)
alphaB-Crystallin is a small heat-shock protein (sHsp) that is colocalized with alpha-synuclein (alphaSyn) in Lewy bodies—the pathological hallmarks of Parkinson's disease—and is an inhibitor of alphaSyn amyloid fibril formation in an ATP-independent manner in vitro. We have investigated the mechanism underlying the inhibitory action of sHsps, and here we establish, by means of a variety of biophysical techniques including immunogold labeling and nuclear magnetic resonance spectroscopy, that alphaB-crystallin interacts with alphaSyn, binding along the length of mature amyloid fibrils. By measurement of seeded fibril elongation kinetics, both in solution and on a surface using a quartz crystal microbalance, this binding …
Alphab-Crystallin Inhibits The Cell Toxicity Associated With Amyloid Fibril Formation By Kappa-Casein And The Amyloid-Beta Peptide, Francis C. Dehle, Heath Ecroyd, Ian F. Musgrave, John A. Carver
Alphab-Crystallin Inhibits The Cell Toxicity Associated With Amyloid Fibril Formation By Kappa-Casein And The Amyloid-Beta Peptide, Francis C. Dehle, Heath Ecroyd, Ian F. Musgrave, John A. Carver
Faculty of Science - Papers (Archive)
Amyloid fibril formation is associated with diseases such as Alzheimer’s, Parkinson’s, and prion diseases. Inhibition of amyloid fibril formation by molecular chaperone proteins, such as the small heat-shock protein αB-crystallin, may play a protective role in preventing the toxicity associated with this form of protein misfolding. Reduced and carboxymethylated κ-casein (RCMκ-CN), a protein derived from milk, readily and reproducibly forms fibrils at physiological temperature and pH. We investigated the toxicity of fibril formation by RCMκ-CN using neuronal model PC12 cells and determined whether the inhibition of fibril formation altered its cell toxicity. To resolve ambiguities in the literature, we also …
Modulation Of Amyloid Precursor Protein Processing By Synthetic Ceramide Analogues, Hongyun Li, Woojin Scott Kim, Gilles Guillemin, Andrew F. Hill, Genevieve Evin, Brett Garner
Modulation Of Amyloid Precursor Protein Processing By Synthetic Ceramide Analogues, Hongyun Li, Woojin Scott Kim, Gilles Guillemin, Andrew F. Hill, Genevieve Evin, Brett Garner
Faculty of Science - Papers (Archive)
Previous studies suggest that membrane lipids may regulate proteolytic processing of the amyloid precursor protein (APP) to generate amyloid-beta peptide (Abeta). In the present study, we have assessed the capacity for a series of structurally related synthetic ceramide analogues to modulate APP processing in vitro. The compounds tested are established glucosylceramide synthase (GS) inhibitors based on the D-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) structure. PDMP and related compounds PPMP and EtDO-P4 inhibited Abeta secretion from Chinese hamster ovary cells expressing human APP (CHO-APP) with approximate IC50 values of 15, 5, and 1 mu M, respectively. A trend for reduced secretion of the APP alpha-secretase …
Sensitivity Of The Female Rat To Olanzapine-Induced Weight Gain - Far From The Clinic?, Katrina Weston-Green, Xu-Feng Huang, Chao Deng
Sensitivity Of The Female Rat To Olanzapine-Induced Weight Gain - Far From The Clinic?, Katrina Weston-Green, Xu-Feng Huang, Chao Deng
Faculty of Science, Medicine and Health - Papers: part A
Dear Editor, The recent paper by Chintoh and colleagues (2008) reporting olanzapine-induced dysfunction in glucose metabolism, enhanced visceral fat and reduced locomotor activity in female rats was highly interesting as it illustrated olanzapine’s ability to replicate aspects of metabolic dysfunction in the rodent model in a similar manner to the human scenario. However, contrary to previous reports in the rat and the clinic, the authors reported no change in body weight or food intake following olanzapine treatment, questioning the validity of the rat model.................
What Is The Mechanism For Aripiprazole's Effect On Reducing Olanzapine-Associated Obesity?, Chao Deng, J-Z Chen, Changhua Hu, Xu-Feng Huang
What Is The Mechanism For Aripiprazole's Effect On Reducing Olanzapine-Associated Obesity?, Chao Deng, J-Z Chen, Changhua Hu, Xu-Feng Huang
Faculty of Science, Medicine and Health - Papers: part A
We read with great interest Henderson and colleagues’ paper in your journal (2009; 29:165–169), which reported that aripiprazole reduced olanzapine-induced overweight/obesity and hyperlipidemia in a 10-week placebo-controlled double-blind crossover study. This and their previous studies, provide a new way for controlling olanzapine- and clozapine-induced weight gain/obesity using another atypical antipsychotic, even without reducing the original olanzapine and clozapine doses, which is important particularly for treatment of refractory schizophrenia patients. ....
Berberine-Inf55 (5-Nitro-2-Phenylindole) Hybrid Antimicrobials: Effects Of Varying The Relative Orientation Of The Berberine And Inf55 Components, Danuta Tomkiewicz, Gabriele Casadei, Jonah Larkins-Ford, Terence I. Moy, James A. Garner, John B. Bremner, Frederik M. Ausubel, Kim Lewis, Michael J. Kelso
Berberine-Inf55 (5-Nitro-2-Phenylindole) Hybrid Antimicrobials: Effects Of Varying The Relative Orientation Of The Berberine And Inf55 Components, Danuta Tomkiewicz, Gabriele Casadei, Jonah Larkins-Ford, Terence I. Moy, James A. Garner, John B. Bremner, Frederik M. Ausubel, Kim Lewis, Michael J. Kelso
Faculty of Science - Papers (Archive)
Hybrid antimicrobials containing an antibacterial linked to a multidrug resistance (MDR) pump inhibitor make up a promising new class of agents for countering efflux-mediated bacterial drug resistance. This study explores the effects of varying the relative orientation of the antibacterial and efflux pump inhibitor components in three isomeric hybrids (SS14, SS14-M, and SS14-P) which link the antibacterial alkaloid and known substrate for the NorA MDR pump berberine to different positions on INF55 (5-nitro-2-phenylindole), an inhibitor of NorA. The MICs for all three hybrids against wild-type, NorA-knockout, and NorA-overexpressing Staphylococcus aureus cells were found to be similar (9.4 to 40.2 mu …
Nanometer-Scale Distance Measurements In Proteins Using Gd3+ Spin Labeling, Alexey Potapov, Hiromasa Yagi, Thomas Huber, Slobodan Jergic, Nicholas E. Dixon, Gottfried Otting, Daniella Goldfarb
Nanometer-Scale Distance Measurements In Proteins Using Gd3+ Spin Labeling, Alexey Potapov, Hiromasa Yagi, Thomas Huber, Slobodan Jergic, Nicholas E. Dixon, Gottfried Otting, Daniella Goldfarb
Faculty of Science - Papers (Archive)
Methods for measuring nanometer-scale distances between specific sites in proteins are essential for analysis of their structure and function. In this work we introduce Gd3+ spin labeling for nanometer-range distance measurements in proteins by high-field pulse electron paramagnetic resonance (EPR). To evaluate the performance of such measurements, we carried out four-pulse double-electron electron resonance (DEER) measurements on two proteins, p75ICD and τC14, labeled at strategically selected sites with either two nitroxides or two Gd3+ spin labels. In analogy to conventional site-directed spin labeling using nitroxides, Gd3+ tags that are derivatives of dipicolinic acid were covalently attached to cysteine thiol groups. …
Synthesis Of Reaction-Ready 6,6 '-Biindole And 6,6 '-Biisatin Via Palladium(Ii)-Catalysed Intramolecular C-H Functionalisation, Allan B. Gamble, Paul A. Keller
Synthesis Of Reaction-Ready 6,6 '-Biindole And 6,6 '-Biisatin Via Palladium(Ii)-Catalysed Intramolecular C-H Functionalisation, Allan B. Gamble, Paul A. Keller
Faculty of Science - Papers (Archive)
The first synthesis of a 6,6'-biindole and 6,6'-biisatin scaffold is reported with the penultimate step being the formation of the di-heterocyclic ring by Pd(II)-catalysed intramolecular C-H functionalisation and Sandmeyer cyclisation, respectively.
Distribution Of Class 1 Integrons With Is26-Mediated Deletions In Their 3'-Conserved Segments In Escherichia Coli Of Human And Animal Origin., Fay E. Dawes, Alexander Kuzevski, Karl A Bettelheim, Michael A Hornitzky, Steven P Djordjevic, Mark J. Walker
Distribution Of Class 1 Integrons With Is26-Mediated Deletions In Their 3'-Conserved Segments In Escherichia Coli Of Human And Animal Origin., Fay E. Dawes, Alexander Kuzevski, Karl A Bettelheim, Michael A Hornitzky, Steven P Djordjevic, Mark J. Walker
Faculty of Science - Papers (Archive)
Class 1 integrons play a role in the emergence of multi-resistant bacteria by facilitating the recruitment of gene cassettes encoding antibiotic resistance genes. 512 E. coli strains sourced from humans (n = 202), animals (n = 304) and the environment (n = 6) were screened for the presence of the intI1 gene. In 31/79 integron positive E. coli strains, the gene cassette regions could not be PCR amplified using standard primers. DNA sequence analysis of 6 serologically diverse strains revealed atypical integrons harboured the dfrA5 cassette gene and only 24 bp of the integron 3'-conserved segment (CS) remained, due to …
Semisynthesis And Acetylcholinesterase Inhibitory Activity Of Stemofoline Alkaloids And Analogues, Kwankamol Sastraruji, Thanapat Sastraruji, Stephen G. Pyne, Alison T. Ung, Araya Jatisatienr, Wilford Lie
Semisynthesis And Acetylcholinesterase Inhibitory Activity Of Stemofoline Alkaloids And Analogues, Kwankamol Sastraruji, Thanapat Sastraruji, Stephen G. Pyne, Alison T. Ung, Araya Jatisatienr, Wilford Lie
Faculty of Science - Papers (Archive)
Semisynthesis of the known Stemona alkaloids oxystemofoline (7) and methoxystemofoline (8) has been achieved starting from (11Z)-1′,2′-didehydrostemofoline (6), which confirmed their structures and absolute configurations. The synthesis of (1′R)-hydroxystemofoline (9) helped establish this compound as a natural product from Stemona aphylla. (1′S)- Hydroxystemofoline (10) and a number of related analogues were also prepared. In a TLC bioautographic assay, 9 was found to be the most active acetylcholinesterase inhibitor, but it was not as active as galanthamine.
Potential Control Of Antipsychotic-Induced Hyperprolactinemia And Obesity In Children And Adolescents By Aripiprazole, J Lian, Xu-Feng Huang, Nagesh Pai, Chao Deng
Potential Control Of Antipsychotic-Induced Hyperprolactinemia And Obesity In Children And Adolescents By Aripiprazole, J Lian, Xu-Feng Huang, Nagesh Pai, Chao Deng
Faculty of Science, Medicine and Health - Papers: part A
The paper published in your journal by Migiliardi et al. (2009) reported that increased hyperprolactinemia is a major side-effect of risperidone and olanzapine treatment in children and adolescents. They showed that risperidone could cause 10 times higher prolactin levels than olanzapine treatment in children and adolescents. This was a well-designed study that controlled for dose, gender, and individual differences, as well as response differences to treatment duration (Migliardi et al. 2009). However, another important issue that should be considered, but was not reported in this study, is antipsychotic-induced weight gain/obesity. Clinical data have demonstrated that weight gain is a major …
Lipids And Alzheimer's Disease, Brett Garner
Lipids And Alzheimer's Disease, Brett Garner
Faculty of Science, Medicine and Health - Papers: part A
According to the World Health Organisation (WHO), the number of people suffering from Alzheimer's disease (AD) worldwide is around 18 million. The prevalence of AD doubles every five years between 65 and 85 years of age and it is estimated that due to the ageing population, 34 million people will suffer from AD by 2025. The WHO has also stated that if AD onset were delayed by 5 years, the number of cases worldwide could be halved. Currently there are no curative or disease-stalling treatments for AD and a major research effort is underway in order to better understand the …
Carboxymethylated-K-Casein: A Convenient Tool For The Identification Of Polyphenolic Inhibitors Of Amyloid Fibril Formation, John A. Carver, Peter J. Duggan, Heath Ecroyd, Yanqin Liu, Adam G. Meyer, C E. Tranberg
Carboxymethylated-K-Casein: A Convenient Tool For The Identification Of Polyphenolic Inhibitors Of Amyloid Fibril Formation, John A. Carver, Peter J. Duggan, Heath Ecroyd, Yanqin Liu, Adam G. Meyer, C E. Tranberg
Faculty of Science - Papers (Archive)
Reduced and carboxymethylated-κ-casein (RCM-κ-CN) is a milk-derived amyloidogenic protein that readily undergoes nucleation-dependent aggregation and amyloid fibril formation via a similar pathway to disease-specific amyloidogenic peptides like amyloid beta (Aβ), which is associated with Alzheimer’s disease. In this study, a series of flavonoids, many known to be inhibitors of Aβ fibril formation, were screened for their ability to inhibit RCM-κ-CN fibrilisation, and the results were compared with literature data on Aβ inhibition. Flavonoids that had a high degree of hydroxylation and molecular planarity gave good inhibition of RCM-κ-CN fibril formation. IC50 values were between 10- and 200-fold higher with RCM-κ-CN …
The Interaction Of Unfolding Α-Lactalbumin And Malate Dehydrogenase With The Molecular Chaperone Αb-Crystallin: A Light And X-Ray Scattering Investigation, J W. Regini, Heath Ecroyd, Sarah Meehan, Kristen Bremmell, Matthew J. Clarke, Donna Lammie, Tim Wess, John A. Carver
The Interaction Of Unfolding Α-Lactalbumin And Malate Dehydrogenase With The Molecular Chaperone Αb-Crystallin: A Light And X-Ray Scattering Investigation, J W. Regini, Heath Ecroyd, Sarah Meehan, Kristen Bremmell, Matthew J. Clarke, Donna Lammie, Tim Wess, John A. Carver
Faculty of Science - Papers (Archive)
Purpose: The molecular chaperone αB-crystallin is found in high concentrations in the lens and is present in all major body tissues. Its structure and the mechanism by which it protects its target protein from aggregating and precipitating are not known. Methods: Dynamic light scattering and X-ray solution scattering techniques were used to investigate structural features of the αB-crystallin oligomer when complexed with target proteins under mild stress conditions, i.e., reduction of α- lactalbumin at 37 °C and malate dehydrogenase when heated at 42 °C. In this investigation, the size, shape and particle distribution of the complexes were determined in real-time …
Protein Chemistry Of Amyloid Fibrils And Chaperones: Implications For Amyloid Formation And Disease, Justin J. Yerbury, Janet R. Kumita
Protein Chemistry Of Amyloid Fibrils And Chaperones: Implications For Amyloid Formation And Disease, Justin J. Yerbury, Janet R. Kumita
Faculty of Science - Papers (Archive)
Understanding the mechanisms by which amyloid fibrils are formed, both in vivo and in vitro, is vital for developing methods to treat and prevent debilitating deposition diseases such as Alzheimer's disease, Parkinson's disease, type II diabetes and systemic amyloidoses. In recent years, computer modelling and biophysical studies have broadened our understanding of the biochemical mechanisms underpinning protein aggregation. As a result, it is now believed that the ability to form fibrils is an intrinsic property of polypeptide chains and not isolated to disease-related proteins or peptides. Molecular chaperones are a diverse group of functionally related proteins well known for their …
Detection And Quantification Of Tear Phospholipids And Cholesterol In Contact Lens Deposits: The Effect Of Contact Lens Material And Lens Care Solution, Jennifer Saville, Zhenjun Zhao, Mark D.P. Willcox, Stephen J. Blanksby, Todd W. Mitchell
Detection And Quantification Of Tear Phospholipids And Cholesterol In Contact Lens Deposits: The Effect Of Contact Lens Material And Lens Care Solution, Jennifer Saville, Zhenjun Zhao, Mark D.P. Willcox, Stephen J. Blanksby, Todd W. Mitchell
Faculty of Science - Papers (Archive)
PURPOSE. To examine the deposition of tear phospholipids and cholesterol onto worn contact lenses and the effect of lens material and lens care solution. METHODS. Lipids were extracted from tears and worn contact lenses using 2: 1 chloroform: methanol and the extract washed with aqueous ammonium acetate, before analysis by electrospray ionization tandem mass spectrometry (ESI-MS/MS). RESULTS. Twenty-three molecular lipids from the sphingomyelin (SM) and phosphatidylcholine (PC) classes were detected in tears, with total concentrations of each class determined to be 5 +/- 1 pmol/mu L (similar to 3.8 mu g/mL) and 6 +/- 1 pmol/mu L (similar to 4.6 …
A Mass Spectrometric Investigation Of Novel Quadruplex Dna-Selective Berberine Derivatives, Karina Gornall, Siritron Samosorn, Bongkot Tanwirat, Apichart Suksamrarn, John B. Bremner, Michael J. Kelso, Jennifer L. Beck
A Mass Spectrometric Investigation Of Novel Quadruplex Dna-Selective Berberine Derivatives, Karina Gornall, Siritron Samosorn, Bongkot Tanwirat, Apichart Suksamrarn, John B. Bremner, Michael J. Kelso, Jennifer L. Beck
Faculty of Science - Papers (Archive)
ESI mass spectrometry was used to assess the binding of 13-substituted, 5-nitro-2-phenylindolyl- and 2-naphthalenyl-based berberine derivatives to inter- and intramolecular G-quadruplex DNA molecules. In contrast with the parent berberine, the compounds showed selectivity for quadruplex over duplex DNA and stabilised the quadruplex structure. They represent a new class of quadruplex DNA-selective ligands. © 2010 The Royal Society of Chemistry.
Copper-Mediated Cyclization-Halogenation And Cyclization-Cyanation Reactions Of Β-Hydroxyalkynes And O-Alkynylphenols And Anilines, Nalivela K. Swamy, Arife Yazici, Stephen G. Pyne
Copper-Mediated Cyclization-Halogenation And Cyclization-Cyanation Reactions Of Β-Hydroxyalkynes And O-Alkynylphenols And Anilines, Nalivela K. Swamy, Arife Yazici, Stephen G. Pyne
Faculty of Science - Papers (Archive)
The CuX (X = I, Br, Cl, CN)-mediated cyclization-halogenation and cyclization-cyanation reactions of β-hydroxyalkynes and o-alkynylphenol and -aniline derivatives give rise to 3-halo- and 3-cyanofuro[3,2-b]pyrroles, 3-iodo-, 3-bromo-, and 3-cyanobenzofurans, and 3-cyanoindoles, respectively. © 2010 American Chemical Society.