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Full-Text Articles in Social and Behavioral Sciences
Online Ozonolysis Methods For The Determination Of Double Bond Position In Unsaturated Lipids, Michael Thomas, Todd W. Mitchell, Stephen J. Blanksby
Online Ozonolysis Methods For The Determination Of Double Bond Position In Unsaturated Lipids, Michael Thomas, Todd W. Mitchell, Stephen J. Blanksby
Stephen Blanksby
Modern lipidomics relies heavily on mass spectrometry for the structural characterization and quantification of lipids of biological origins. Structural information is gained by tandem mass spectrometry (MS/MS) whereby lipid ions are fragmented to elucidate lipid class, fatty acid chain length, and degree of unsaturation. Unfortunately, however, in most cases double bond position cannot be assigned based on MS/MS data alone and thus significant structural diversity is hidden from such analyses. For this reason, we have developed two online methods for determining double bond position within unsaturated lipids; ozone electrospray ionization mass spectrometry (OzESI-MS) and ozone-induced dissociation (OzID). Both techniques utilize …
Identification Of Abundant Alkyl Ether Glycerophospholipids In The Human Lens By Tandem Mass Spectrometry Techniques, Roger J. Truscott, Jane Deeley, Todd W. Mitchell, Michael Thomas, Stephen J. Blanksby
Identification Of Abundant Alkyl Ether Glycerophospholipids In The Human Lens By Tandem Mass Spectrometry Techniques, Roger J. Truscott, Jane Deeley, Todd W. Mitchell, Michael Thomas, Stephen J. Blanksby
Stephen Blanksby
Previous studies have shown that the human lens contains glycerophospholipids with ether linkages. These lipids differ from conventional glycerophospholipids in that the sn-1 substituent is attached to the glycerol backbone via an 1-O-alkyl or an 1-O-alk-1'-enyl ether rather than an ester bond. The present investigation employed a combination of collision-induced dissociation (CID) and ozone-induced dissociation (OzID) to unambiguously distinguish such 1-O-alkyl and 1-O-alk-1'-enyl ethers. Using these methodologies the human lens was found to contain several abundant 1-O-alkyl glycerophos-phoethanolamines, including GPEtn(16:0e/9Z-18:1), GPEtn(11Z-18:1e/9Z-18:1), and GPEtn(18:0e/9Z-18:1), as well as a related series of unusual 1-O-alkyl glycerophosphoserines, including GPSer(16:0e/9Z-18:1), GPSer(11Z-18:1e/9Z-18:1), GPSer(18:0e/9Z-18:1) that to our …
Tandem Mass Spectrometry Of Deprotonated Iodothyronines, A. M. Couldwell, M. C. Thomas, Todd Mitchell, A. Hulbert, Stephen J. Blanksby
Tandem Mass Spectrometry Of Deprotonated Iodothyronines, A. M. Couldwell, M. C. Thomas, Todd Mitchell, A. Hulbert, Stephen J. Blanksby
Stephen Blanksby
In order to assist with the development of more selective and sensitive methods for thyroid hormone analysis the [M-H]– anions of the iodothyronines; T4, T3, rT3, (3,5)-T2 and the non-iodinated thyronine (T0) have been generated by negative ion electrospray mass spectrometry. Tandem mass spectra of these ions were recorded on a triple quadrupole mass spectrometer and show a strong analogy with the fragmentation pathways of the parent compound, tyrosine. All iodothyronines also show significant abundances of the iodide anion in their tandem mass spectra, which represents an attractive target for MRM analysis, given that iodothyronines are the only iodine bearing …
A Comparison Of The Gas Phase Acidities Of Phospholipid Headgroups:Experimental And Computational Studies, M. C. Thomas, Todd Mitchell, Stephen J. Blanksby
A Comparison Of The Gas Phase Acidities Of Phospholipid Headgroups:Experimental And Computational Studies, M. C. Thomas, Todd Mitchell, Stephen J. Blanksby
Stephen Blanksby
Proton-bound dimers consisting of two glycerophospholipids with different headgroups were prepared using negative ion electrospray ionization and dissociated in a triple quadrupole mass spectrometer. Analysis of the tandem mass spectra of the dimers using the kinetic method provides, for the first time, an order of acidity for the phospholipid classes in the gas phase of PE < PA << PG < PS < PI. Hybrid density functional calculations on model phospholipids were used to predict the absolute deprotonation enthalpies of the phospholipid classes from isodesmic proton transfer reactions with phosphoric acid. The computational data largely support the experimental acidity trend, with the exception of …
Synthesis And In Vitro Binding Of N,N-Dialkyl-2-Phenylindol-3-Ylglyoxylamides For The Peripheral Benzodiazepine Binding Sites, T. P. Homes, F. Mattner, Paul A. Keller, A. Katsifis
Synthesis And In Vitro Binding Of N,N-Dialkyl-2-Phenylindol-3-Ylglyoxylamides For The Peripheral Benzodiazepine Binding Sites, T. P. Homes, F. Mattner, Paul A. Keller, A. Katsifis
Paul Keller
A series of N,N-dialkyl-2-phenylindol-3-ylglyoxylamides bearing the halogens iodine and bromine were synthesised and their binding affinity for the peripheral benzodiazepine binding sites (PBBS) in rat kidney mitochondrial membranes were evaluated using [3H]-PK11195. Central benzodiazepine receptor (CBR) affinities were also evaluated in rat cortices using 3H-flumazenil to determine their selectivity for PBBS over CBR. The tested compounds had PBBS binding affinities (IC50) ranging from 7.86 nM to 618 nM, with all compounds showing high selectivity over the CBR (CBR IC50 > 5000 nM). Among the 12 compounds tested, those with a diethylamide group were the most potent. The highest affinity iodinated PBBS …
Synthesis Of Some Cyclic Indolic Peptoids As Potential Antibacterials, Vicki S. Au, John B. Bremner, Jonathan Coates, Paul A. Keller, Stephen G. Pyne
Synthesis Of Some Cyclic Indolic Peptoids As Potential Antibacterials, Vicki S. Au, John B. Bremner, Jonathan Coates, Paul A. Keller, Stephen G. Pyne
Paul Keller
The synthesis of cyclic peptoids containing an indole hydrophobic scaffold has been realised through the ring-closing metathesis of diallylated precursors. The precursors and their cyclic counterparts possessed poor antibacterial activity in contrast to previously reported cyclic peptoids containing hydrophobic scaffolds.
[60]Fullerene Amino Acids And Related Derivatives, Glenn A. Burley, Paul A. Keller, Stephen G. Pyne
[60]Fullerene Amino Acids And Related Derivatives, Glenn A. Burley, Paul A. Keller, Stephen G. Pyne
Paul Keller
This paper is a review of the literature concerning the preparation of [60]fullerene amino acid and peptide derivatives. The structure and applications of these derivatives to the biological and material sciences is also presented.
Reactions Of Iminoglycines With C60 Fullerene And Their Unambiguous Characterisation Using Nmr Spectroscopy, Paul A. Keller, Stephen G. Pyne, Bill C. Hawkins
Reactions Of Iminoglycines With C60 Fullerene And Their Unambiguous Characterisation Using Nmr Spectroscopy, Paul A. Keller, Stephen G. Pyne, Bill C. Hawkins
Paul Keller
This review examines the addition of iminoglycine derivatives to C60, yielding protected fullerenyl pyrroline derivatives. Subsequent reduction with sodium cyanoborohydride produces ring-opening adducts which are protected fullerenyl α-amino acids. Pyrroline bisadducts can be produced using tethers to link two iminoglycine units together, and variations include combining with malonate reactive groups this giving rise to interesting observations as to the regioselectivity of such reactions. All derivatives are fully characterised by NMR spectroscopy, and in the case of bis-adducts, the regioselectivity is determined from 1H/13C and 13C/13C connectivity patterns using HMBC and INADEQUATE experiments, respectively, thus eliminating the need for comparative techniques …
New Cyclic Peptides Via Ring-Closing Metathesis Reactions And Their Anti-Bacterial Activities, Timothy P. Boyle, John B. Bremner, Jonathan Coates, John Deadman, Paul A. Keller, Stephen G. Pyne, David I. Rhodes
New Cyclic Peptides Via Ring-Closing Metathesis Reactions And Their Anti-Bacterial Activities, Timothy P. Boyle, John B. Bremner, Jonathan Coates, John Deadman, Paul A. Keller, Stephen G. Pyne, David I. Rhodes
Paul Keller
As part of a program investigating cyclic peptides with an internal aromatic hydrophobic scaffold as potential novel anti-bacterial agents, we explored the synthesis of simple tyrosine-based systems. These were prepared via key intermediates containing internal allylglycine and allyltyrosine residues for subsequent ring closing metathesis reactions. Although the resulting anti-bacterial activity against Staphylococcus aureus was modest, this represents a novel and simple route to this class of compounds. One intermediate acyclic dipeptide precursor showed good activity against S. aureus with an MIC of 7.8 µg/mL.
Regioselective Synthesis Of Novel E-Edge-[60]Fullerenylmethanodihydropyrroles And 1,2-Dihydromethano[60]Fullerenes, Leila Chaker, Graham E. Ball, James R. Williams, Glenn A. Burley, Bill C. Hawkins, Paul A. Keller, Stephen G. Pyne
Regioselective Synthesis Of Novel E-Edge-[60]Fullerenylmethanodihydropyrroles And 1,2-Dihydromethano[60]Fullerenes, Leila Chaker, Graham E. Ball, James R. Williams, Glenn A. Burley, Bill C. Hawkins, Paul A. Keller, Stephen G. Pyne
Paul Keller
Treatment of a tethered N-(diphenylmethylene)glycinate-malonate derivative with [60]fullerene under Bingel conditions yielded an e-edge-[60]fullerenylmethanodihydropyrrole adduct in a regioselective manner. The regiochemical outcome was independent of the order of addition of either the N-(diphenylmethylene)glycinate or the malonate moieties. This new bis-adduct was also prepared in 13C enriched form allowing for its unequivocal structural characterization by 2D INADEQUATE NMR experiments. Ring-opening of the dihydropyrrole functionality of the bisadducts under reductive conditions gave exclusively novel dihydromethano[60]fullerene derivatives.
The Role Of The Hpa Axis In Psychiatric Disorders And Crf Antagonists As Potential Treatments, Paul A. Keller, A. Mccluskey, J. Morgan, S. M. O'Connor
The Role Of The Hpa Axis In Psychiatric Disorders And Crf Antagonists As Potential Treatments, Paul A. Keller, A. Mccluskey, J. Morgan, S. M. O'Connor
Paul Keller
An overview of the links between the Hypothalamic-Pituitary-Adrenal (HPA) axis and psychiatric disorders is presented. The current treatments are outlined, indicating that they are insufficient to meet the needs of those that suffer from these affective disorders. Therefore, there is an urgent need for the generation of new therapeutics, in particular, against new targets. The association of the corticotrophin releasing factor (CRF) and the HPA axis indicates that CRF antagonists should be beneficial as potential therapeutics.
A Convenient And Efficient Synthesis Of (S)-Lysine And (S)-Arginine Homologues Via Olefin Cross-Metathesis, Timothy P. Boyle, John B. Bremner, Jonathan A. Coates, Paul A. Keller, Stephen G. Pyne
A Convenient And Efficient Synthesis Of (S)-Lysine And (S)-Arginine Homologues Via Olefin Cross-Metathesis, Timothy P. Boyle, John B. Bremner, Jonathan A. Coates, Paul A. Keller, Stephen G. Pyne
Paul Keller
A convenient five step synthesis of (S)-homolysine, incorporating a key olefin cross-metathesis step in the chain extension methodology, has been developed, together with a six step related synthesis of a new homologue of arginine, (S)-bishomoarginine.
Antimalarial Activity Of 2,4-Diaminopyrimidines, J. Morgan, R. Haritakul, Paul A. Keller
Antimalarial Activity Of 2,4-Diaminopyrimidines, J. Morgan, R. Haritakul, Paul A. Keller
Paul Keller
A series of 2,4- and 4,6-diaminopyrimidines were prepared and evaluated for their in vitro antimalarial activity. Of the 12 compounds tested 7 showed reasonable activity with 1 having a sub-micromolar IC50.
Aryl Nitro Reduction With Iron Powder Or Stannous Chloride Under Ultrasonic Irradiation, A. B. Gamble, James A. Garner, Christopher Gordon, S. M. J. O'Conner, Paul A. Keller
Aryl Nitro Reduction With Iron Powder Or Stannous Chloride Under Ultrasonic Irradiation, A. B. Gamble, James A. Garner, Christopher Gordon, S. M. J. O'Conner, Paul A. Keller
Paul Keller
The selective reduction of aryl nitro compounds in the presence of sensitive functionalities, including halide, carbonyl, nitrile and ester substituents under ultrasonic irradiation at 35 kHz is reported in yields of 39-98%. Iron powder proved superior to stannous chloride with high tolerance of sensitive functional groups and high yields of the desired aryl amines in relatively short reaction times. Simple experimental procedure and purification also make the iron reduction of aryl nitro compounds advantageous over other methods of reduction.
Control Of Hiv Through The Inhibition Of Hiv-1 Integrase: A Medicinal Chemistry Perspective, Christopher Gordon, R. Griffith, Paul A. Keller
Control Of Hiv Through The Inhibition Of Hiv-1 Integrase: A Medicinal Chemistry Perspective, Christopher Gordon, R. Griffith, Paul A. Keller
Paul Keller
This article reviews the current status of classes of HIV-1 integrase enzyme inhibitors. These classes include peptide-based inhibitors, natural products, polyhydroxylated aromatics, diketo acids, naphthyridines, and sulfonated compounds including sulfonic acids. Discussions of structure activity relationships are presented and include the current overview of the structure-based model, suitable for the further design and development. To date, the advances in the medicinal chemistry of HIV-1 integrase inhibitors have relied mostly on ligand-based designs leading to most displaying similar binding interactions within the active site or at the dimer interface. This paves the way for single enzyme mutations rendering entire compound classes …
The Prevention Of Preterm Labour – Corticotropin Releasing Hormone Type 1 Receptors As A Target For Drug Design And Development, Paul A. Keller, K. Kirkwood, J. Morgan, S. Westcott, A. Mccluskey
The Prevention Of Preterm Labour – Corticotropin Releasing Hormone Type 1 Receptors As A Target For Drug Design And Development, Paul A. Keller, K. Kirkwood, J. Morgan, S. Westcott, A. Mccluskey
Paul Keller
The role of the corticotropin releasing hormone in the onset of labour and the subsequent medicinal chemistry implications of CRH antagonists for the prevention of premature birth, and identification of the CRH type 1 receptor as the target for this drug design, are reviewed here.
A New Methodology For The Simulation Of Flexible Protein – Ligand Interactions, James A. Garner, John Deadman, David I. Rhodes, Renate Griffith, Paul A. Keller
A New Methodology For The Simulation Of Flexible Protein – Ligand Interactions, James A. Garner, John Deadman, David I. Rhodes, Renate Griffith, Paul A. Keller
Paul Keller
A methodology has been developed for the simulation of induced fit between a ligand and its target protein. It utilizes constrained molecular dynamics where atoms determined to be immobile from difference distance matrix studies are fixed. Application of this methodology to HIV-1 reverse transcriptase (RT) as the example target protein has demonstrated its robustness. Short simulation times are sufficient to achieve good refinement of docking poses resulting from exchange of structurally dissimilar inhibitors between crystal structures.
Corticotropin Releasing Hormone - A Gpcr Drug Target, C. Hemley, A. Mccluskey, Paul A. Keller
Corticotropin Releasing Hormone - A Gpcr Drug Target, C. Hemley, A. Mccluskey, Paul A. Keller
Paul Keller
Corticotrophin Releasing Hormone (CRH) is a primary hormone in the fight or flight response targeting a membrane bound G-protein coupled receptor (GPCR). Many people worldwide stand to benefit by the development of CRH agonists and antagonists for the treatment of anxiety and depression, with additional therapeutic targets including Alzheimer’s, pain and the prevention of premature birth: so why the delay in development? In this review, we will discuss not only CRH, related proteins, receptors and ligands, but some of the obstacles that have arisen, as well as strategies being pursued to overcome these problems in the pursuit of this GPCR …
Identification Of Human Plasma Proteins As Major Clients For The Extracellular Chaperone Clusterin, Amy R. Wyatt, Mark R. Wilson
Identification Of Human Plasma Proteins As Major Clients For The Extracellular Chaperone Clusterin, Amy R. Wyatt, Mark R. Wilson
Faculty of Science - Papers (Archive)
Clusterin (CLU) is an extracellular chaperone that is likely to play an important role in protein folding quality control. This study identified three deposition disease-associated proteins as major plasma clients for clusterin by studying CLU-client complexes formed in response to physiologically relevant stress (shear stress, similar to 36 dynes/cm(2) at 37 degrees C). Analysis of plasma samples by size exclusion chromatography indicated that (i) relative to control plasma, stressed plasma contained proportionally more soluble protein species of high molecular weight, and (ii) high molecular weight species were far more abundant when proteins purified by anti-CLU immunoaffinity chromatography from stressed plasma …
The Two-Faced Nature Of Small Heat Shock Proteins: Amyloid Assembly And The Inhibition Of Fibril Formation. Relevance To Disease States, Heath W. Ecroyd, S Meehan, John A. Carver
The Two-Faced Nature Of Small Heat Shock Proteins: Amyloid Assembly And The Inhibition Of Fibril Formation. Relevance To Disease States, Heath W. Ecroyd, S Meehan, John A. Carver
Faculty of Science - Papers (Archive)
The ability of small heat-shock proteins (sHsps) such as alphaB-crystallin to inhibit the amorphous (disordered) aggregation of varied target proteins in a chaperone-like manner has been well described. The mechanistic details of this action are not understood. Amyloid fibril formation is an alternative off-folding pathway that leads to highly ordered beta-sheet-containing aggregates. Amyloid fibril formation is associated with a broad range of protein conformational diseases such as Alzhiemer's, Parkinson's and Huntington's and sHsp expression is elevated in the protein deposits that are characteristic of these disease states. The ability of sHsps to prevent fibril formation has been less well characterised. …
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.
Toxicity To Melita Plumulosa From Intermittent And Continuous Exposures To Dissolved Copper, Brad M. Angel, Stuart L. Simpson, Dianne F. Jolley
Toxicity To Melita Plumulosa From Intermittent And Continuous Exposures To Dissolved Copper, Brad M. Angel, Stuart L. Simpson, Dianne F. Jolley
Faculty of Science - Papers (Archive)
The concentrations of metal contaminants often fluctuate in estuarine waters; yet we have limited knowledge about the effects of intermittent exposures on estuarine organisms. Using 10-d lethality bioassays with the epibenthic amphipod Melita plumulosa, different combinations of intermittent (pulsed) dissolved Cu exposure were investigated, varying Cu concentration, pulse duration, and time between pulses. Negligible organism mortality was observed immediately after single 12- to 62-h duration pulsed exposures of 100 to 900 mg/L dissolved Cu. However, delayed mortality was observed in the subsequent 96-h nonexposure period, after which negligible additional mortality occurred during the remainder of the 240-h tests. For multiple …
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 …
Essential Biological Processes Of An Emerging Pathogen: Dna Replication, Transcription, And Cell Division In Acinetobacter Spp., Andrew Robinson, Anthony J. Brzoska, Kylie M. Turner, Ryan Withers, Elizabeth J. Harry, Peter J. Lewis, Nicholas E. Dixon
Essential Biological Processes Of An Emerging Pathogen: Dna Replication, Transcription, And Cell Division In Acinetobacter Spp., Andrew Robinson, Anthony J. Brzoska, Kylie M. Turner, Ryan Withers, Elizabeth J. Harry, Peter J. Lewis, Nicholas E. Dixon
Faculty of Science - Papers (Archive)
Species of the bacterial genus Acinetobacter are becoming increasingly important as a source of hospital-acquired infections (31, 185, 204). Acinetobacter spp. are ubiquitous nonmotile gammaproteobacteria, typified by metabolic versatility and a capacity for natural transformation (172, 204). The species of most clinical relevance is A. baumannii; however, pathogenic strains of A. lwoffi and A. baylyi have also been described (38, 185, 215).
The Quaternary Organization And Dynamics Of The Molecular Chaperone Hsp26 Are Thermally Regulated, J. L. Benesch, Andrew Aquilina, Andrew Baldwin, Agata Rekas, Florian Stengel, Robyn Lindner, Eman Basha, G. Devlin, J. Horwitz, Elizabeth Vierling, John Carver, C. V. Robinson
The Quaternary Organization And Dynamics Of The Molecular Chaperone Hsp26 Are Thermally Regulated, J. L. Benesch, Andrew Aquilina, Andrew Baldwin, Agata Rekas, Florian Stengel, Robyn Lindner, Eman Basha, G. Devlin, J. Horwitz, Elizabeth Vierling, John Carver, C. V. Robinson
Faculty of Science - Papers (Archive)
The function of ScHSP26 is thermally controlled: the heat shock that causes the destabilization of target proteins leads to its activation as a molecular chaperone. We investigate the structural and dynamical properties of ScHSP26 oligomers through a combination of multiangle light scattering, fluorescence spectroscopy, NMR spectroscopy, and mass spectrometry. We show that ScHSP26 exists as a heterogeneous oligomeric ensemble at room temperature. At heat-shock temperatures, two shifts in equilibria are observed: toward dissociation and to larger oligomers. We examine the quaternary dynamics of these oligomers by investigating the rate of exchange of subunits between them and find that this not …
Preclinical Evaluation Of Novel All-In-One Formulations Of 5-Fluorouracil And Folinic Acid With Reduced Toxicity Profiles - Supplementary Data, Tamantha K. Stutchbury, Kara L. Vine, Julie M. Locke, Jeremy S. Chrisp, J. B. Bremner, P Clingan, Marie Ranson
Preclinical Evaluation Of Novel All-In-One Formulations Of 5-Fluorouracil And Folinic Acid With Reduced Toxicity Profiles - Supplementary Data, Tamantha K. Stutchbury, Kara L. Vine, Julie M. Locke, Jeremy S. Chrisp, J. B. Bremner, P Clingan, Marie Ranson
Faculty of Science - Papers (Archive)
Objectives: 5-Fluorouracil (5-FU) in combination with its synergistic biomodulator folinic acid maintains a pivotal position in cancer chemotherapy. However, clinical limitations persist with the administration of these drugs in combination including phlebitis and catheter blockages, which are associated with reduced efficacy and/or quality of life for patients. We have previously reported novel all-in-one, pH neutral, parenteral 5-FU and folinic acid formulations (termed Fluorodex) incorporating beta-cyclodextrins. Fluorodex maintains potency while overcoming the accepted incompatibility of 5-FU and folinic acid.
Methods: We performed toxicological, pharmacokinetic and biodistribution, and efficacy evaluations of Fluorodex compared to 5-FU:folinic acid using several administration routes …
Elastic Scattering Studies Of Aligned Dmpc Multilayers On Different Hydrations, Marcus Trapp, Fanni Juranyi, Moeava Tehei, Lambert Van Eijck, Bruno Demé, Thomas Gutberlet, Judith Peters
Elastic Scattering Studies Of Aligned Dmpc Multilayers On Different Hydrations, Marcus Trapp, Fanni Juranyi, Moeava Tehei, Lambert Van Eijck, Bruno Demé, Thomas Gutberlet, Judith Peters
Faculty of Science - Papers (Archive)
Biological membranes, consisting mainly of phospholipids and proteins, are organized in a bilayered structure which exhibits dynamical behaviour within time regimes ranging from 10-12 s with the motion of alkyl chain defects and 1 s corresponding to collective excitations of the bilayer [1]. With the prominent role hydration plays on the structural phase behaviour of phospholipids membranes, it is essential for a better description of membranes to understand also the influence of hydration on the dynamics of membrane systems. In the present study we have performed neutron scattering investigations on highly oriented DMPC-d54 multilayers at two different relative humidity (rh) …