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Articles 31 - 60 of 64
Full-Text Articles in Physical Sciences and Mathematics
Architecture And Conservation Of The Bacterial Dna Replication Machinery, An Underexploited Drug Target, Andrew Robinson, Rebecca J. Causer, Nicholas E. Dixon
Architecture And Conservation Of The Bacterial Dna Replication Machinery, An Underexploited Drug Target, Andrew Robinson, Rebecca J. Causer, Nicholas E. Dixon
Professor Nick E Dixon
"New antibiotics with novel modes of action are required to combat the growing threat posed by multi-drug resistant bacteria. Over the last decade, genome sequencing and other high-throughput techniques have provided tremendous insight into the molecular processes underlying cellular functions in a wide range of bacterial species. We can now use these data to assess the degree of conservation of certain aspects of bacterial physiology, to help choose the best cellular targets for development of new broad-spectrum antibacterials. DNA replication is a conserved and essential process, and the large number of proteins that interact to replicate DNA in bacteria are …
Defining The Structural Basis Of Human Plasminogen Binding By Streptococcal Surface Enolase, Amanda J. Cork, Slobodan Jergic, Sven Hammerschmidt, Bostjan Kobe, Vijay Pancholi, Justin L.P. Benesch, Carol V, Robinson, Nicholas E. Dixon, J Andrew Aquilina, Mark J. Walker
Defining The Structural Basis Of Human Plasminogen Binding By Streptococcal Surface Enolase, Amanda J. Cork, Slobodan Jergic, Sven Hammerschmidt, Bostjan Kobe, Vijay Pancholi, Justin L.P. Benesch, Carol V, Robinson, Nicholas E. Dixon, J Andrew Aquilina, Mark J. Walker
Professor Nick E Dixon
The flesh-eating bacterium group A Streptococcus (GAS) binds and activates human plasminogen, promoting invasive disease. Streptococcal surface enolase (SEN), a glycolytic pathway enzyme, is an identified plasminogen receptor of GAS. Here we used mass spectrometry (MS) to confirm that GAS SEN is octameric, thereby validating in silico modeling based on the crystal structure of S. pneumoniae -enolase. Site-directed mutagenesis of surface-located lysine residues (SENK252+255A, SENK304A, SENK334A, SENK344E, SENK435L and SEN434-435) was used to examine their roles in maintaining structural integrity, enzymatic function and plasminogen binding. Structural integrity of the GAS SEN octamer was retained for all mutants except SENK344E, as …
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
Professor Nick E Dixon
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).
Incorporation Of Chlorinated Analogues Of Aliphatic Amino Acids During Cell-Free Protein Synthesis, Dannon J. Stigers, Zachary I. Watts, James E. Hennessy, Hye-Kyung Kim, Romeo Martini, Matthew C. Taylor, Kiyoshi Ozawa, Jeffrey W. Keillor, Nicholas E. Dixon, Christopher J. Easton
Incorporation Of Chlorinated Analogues Of Aliphatic Amino Acids During Cell-Free Protein Synthesis, Dannon J. Stigers, Zachary I. Watts, James E. Hennessy, Hye-Kyung Kim, Romeo Martini, Matthew C. Taylor, Kiyoshi Ozawa, Jeffrey W. Keillor, Nicholas E. Dixon, Christopher J. Easton
Professor Nick E Dixon
3-Chloro-Abu and 4-chloro-Nva are biosynthetically incorporated into E. coli peptidyl-Pro cis-trans isomerase B, as substitutes for Val and Leu, respectively. The extent of incorporation is up to 90%, and substituted protein is catalytically active. By contrast, 4-chloro-Val is not an effective replacement for Ile.
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
Professor Nick E Dixon
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. …
Proteomic Dissection Of Dna Polymerization, Jennifer L. Beck, Thitima Urathamakul, Stephen James Watt, Margaret Sheil, Patrick M. Schaeffer, Nicholas E. Dixon
Proteomic Dissection Of Dna Polymerization, Jennifer L. Beck, Thitima Urathamakul, Stephen James Watt, Margaret Sheil, Patrick M. Schaeffer, Nicholas E. Dixon
Professor Nick E Dixon
DNA polymerases replicate the genome by associating with a range of other proteins that enable rapid, high-fidelity copying of DNA. This complex of proteins and nucleic acids is called the replisome. Proteins of the replisome must interact with other networks of proteins, such as those involved in DNA repair. Many of the proteins involved in DNA polymerisation and the accessory proteins are known, but the array of proteins they interact with, and the spatial and temporal arrangement of these interactions is a current research topic. Mass spectrometry is a technique that can be used to identify the sites of these …
Helicase-Binding To Dnai Exposes A Cryptic Dna-Binding Site During Helicase Loading In Bacillus Subtilis, Charikleia Ioannou, Patrick M. Schaeffer, Nicholas E. Dixon, Panos Soultanas
Helicase-Binding To Dnai Exposes A Cryptic Dna-Binding Site During Helicase Loading In Bacillus Subtilis, Charikleia Ioannou, Patrick M. Schaeffer, Nicholas E. Dixon, Panos Soultanas
Professor Nick E Dixon
The Bacillus subtilis DnaI, DnaB and DnaD proteins load the replicative ring helicase DnaC onto DNA during priming of DNA replication. Here we show that DnaI consists of a C-terminal domain (Cd) with ATPase and DNA-binding activities and an N-terminal domain (Nd) that interacts with the replicative ring helicase. A Zn21-binding module mediates the interaction with the helicase and C67, C70 and H84 are involved in the coordination of the Zn21. DnaI binds ATP and exhibits ATPase activity that is not stimulated by ssDNA, because the DNAbinding site on Cd is masked by Nd. The ATPase activity resides on the …
Ultrasensitive Detection Of Antibodies Using A New Tus-Ter-Lock Immunopcr System, Isabelle Morin, Nicholas E. Dixon, Patrick M. Schaeffer
Ultrasensitive Detection Of Antibodies Using A New Tus-Ter-Lock Immunopcr System, Isabelle Morin, Nicholas E. Dixon, Patrick M. Schaeffer
Professor Nick E Dixon
A system consisting of a protein LG coated surface for the capture of mammalian antibodies (target), and an antigen fused to Tus and stoichiometrically linked to a DNA template via the Tus-Ter-lock sequence allowed the ultrasensitive detection of 5.5 attomol of target by real-time immunoPCR in complex media. © The Royal Society of Chemistry 2010.
The Unstructured C-Terminus Of The Tau Subunit Of Escherichia Coli Dna Polymerase Iii Holoenzyme Is The Site Of Interaction With The Alpha Subunit, Slobodan Jergic, Kiyoshi Ozawa, Neal K. Williams, Xun-Cheng Su, Daniel D. Scott, Samir M. Hamdan, Jeffrey A. Crowther, Gottfried Otting, Nicholas E. Dixon
The Unstructured C-Terminus Of The Tau Subunit Of Escherichia Coli Dna Polymerase Iii Holoenzyme Is The Site Of Interaction With The Alpha Subunit, Slobodan Jergic, Kiyoshi Ozawa, Neal K. Williams, Xun-Cheng Su, Daniel D. Scott, Samir M. Hamdan, Jeffrey A. Crowther, Gottfried Otting, Nicholas E. Dixon
Professor Nick E Dixon
The τ subunit of Escherichia coli DNA polymerase III holoenzyme interacts with the α subunit through its C-terminal Domain V, τC16. We show that the extreme C-terminal region of τC16 constitutes the site of interaction with α. The τC16 domain, but not a derivative of it with a C-terminal deletion of seven residues (τC16Δ7), forms an isolable complex with α. Surface plasmon resonance measurements were used to determine the dissociation constant (KD) of the α−τC16 complex to be ∼260 pM. Competition with immobilized τC16 by τC16 derivatives for binding to α gave values of KD of 7 μM for the …
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
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
Professor Nick E Dixon
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.
Synthesis And Applications Of Covalent Protein-Dna Conjugates, Patrick M. Schaeffer, Nicholas E. Dixon
Synthesis And Applications Of Covalent Protein-Dna Conjugates, Patrick M. Schaeffer, Nicholas E. Dixon
Professor Nick E Dixon
Synthetic protein-DNA conjugates are valuable tools with applications in fields including nanobiotechnology, bioanalytical chemistry, and molecular diagnostics, and various synthetic methods for their production have been developed during the past three decades. The present article reviews current methodologies for the synthesis of covalent protein-DNA conjugates with particular focus on the regiospecificity and stoichiometry of these reactions.
The Proofreading Exonuclease Subunit E Of Escherichia Coli Dna Polymerase Iii Is Tethered To The Polymerase Subunit A Via A Flexible Linker, Kiyoshi Ozawa, Slobodan Jergic, Ah-Young Park, Nicholas E. Dixon, Gottfried Otting
The Proofreading Exonuclease Subunit E Of Escherichia Coli Dna Polymerase Iii Is Tethered To The Polymerase Subunit A Via A Flexible Linker, Kiyoshi Ozawa, Slobodan Jergic, Ah-Young Park, Nicholas E. Dixon, Gottfried Otting
Professor Nick E Dixon
Escherichia coli DNA polymerase III holoenzyme is composed of 10 different subunits linked by noncovalent interactions. The polymerase activity resides in the α-subunit. The ε-subunit, which contains the proofreading exonuclease site within its N-terminal 185 residues, binds to α via a segment of 57 additional C-terminal residues, and also to θ, whose function is less well defined. The present study shows that θ greatly enhances the solubility of ε during cell-free synthesis. In addition, synthesis of ε in the presence of θ and α resulted in a soluble ternary complex that could readily be purified and analyzed by NMR spectroscopy. …
A Novel Zinc-Binding Fold In The Helicase Interaction Domain Of The Bacillus Subtilis Dnal Helicase Loader, Karin V. Loscha, Kristaps Jaudzems, Charikleia Ioannou, Xun-Cheng Su, Flynn R. Hill, Gottfried Otting, Nicholas E. Dixon, Edvards Liepinsh
A Novel Zinc-Binding Fold In The Helicase Interaction Domain Of The Bacillus Subtilis Dnal Helicase Loader, Karin V. Loscha, Kristaps Jaudzems, Charikleia Ioannou, Xun-Cheng Su, Flynn R. Hill, Gottfried Otting, Nicholas E. Dixon, Edvards Liepinsh
Professor Nick E Dixon
The helicase loader protein DnaI (the Bacillus subtilis homologue of Escherichia coli DnaC) is required to load the hexameric helicase DnaC (the B. subtilis homologue of E. coli DnaB) onto DNA at the start of replication. While the C-terminal domain of DnaI belongs to the structurally well-characterized AAA+ family of ATPases, the structure of the N-terminal domain, DnaI-N, has no homology to a known structure. Three-dimensional structure determination by nuclear magnetic resonance (NMR) spectroscopy shows that DnaI presents a novel fold containing a structurally important zinc ion. Surface plasmon resonance experiments indicate that DnaI-N is largely responsible for binding of …
Instant Insight: Think Outside The Cell, Mark R. Wilson, Justin J. Yerbury
Instant Insight: Think Outside The Cell, Mark R. Wilson, Justin J. Yerbury
Mark R Wilson
Proteins perform many different functions critical for life, from building our muscle structure to digesting our food. These large biological molecules each have a unique three-dimensional shape which they require to perform their function. In protein deposition diseases (PDDs), however, a disease-specific protein molecule unfolds from its normal shape and assembles together with like molecules into insoluble rod-shaped fibrils. These protein deposits can be found in the brain, skeletal tissue and various organs; in some cases they may become large enough to disrupt tissue structure and function.
Stress-Induced Retrotranslocation Of Clusterin/Apoj Into The Cytosol, P Nizard, Suzanne Tetley, Y Le Drean, T Watrin, P Le Goff, Mark R. Wilson, Denis Michel
Stress-Induced Retrotranslocation Of Clusterin/Apoj Into The Cytosol, P Nizard, Suzanne Tetley, Y Le Drean, T Watrin, P Le Goff, Mark R. Wilson, Denis Michel
Mark R Wilson
Clusterin is a usually secreted glycoprotein with chaperone properties. Recently, it has been suggested that clusterin isoforms reside in the nuclear and cytosolic compartments of human cell types, where they can influence various cellular programs including DNA repair, transcription and apoptosis. Several mechanisms have been proposed to explain this atypical location, including alternative transcription initiation and alternative splicing. However none of these have been unequivocally established as occurring in live cells. Here we provide direct experimental evidence that in live intact cells, under certain stress conditions, clusterin can evade the secretion pathway and reach the cytosol. This was demonstrated using …
Macroglobulin And Haptoglobin Suppress Amyloid Formation By Interacting With Prefibrillar Protein Species, Justin J. Yerbury, Janet R. Kumita, Sarah Meehan, Christopher M. Dobson, Mark R. Wilson
Macroglobulin And Haptoglobin Suppress Amyloid Formation By Interacting With Prefibrillar Protein Species, Justin J. Yerbury, Janet R. Kumita, Sarah Meehan, Christopher M. Dobson, Mark R. Wilson
Mark R Wilson
α2-Macroglobulin (α2M) and haptoglobin (Hp) are both abundant secreted glycoproteins that are best known for their protease trapping and hemoglobin binding activities, respectively. Like the small heat shock proteins, both these glycoproteins have in common the ability to protect a range of proteins from stress-induced amorphous aggregation and have been described as extracellular chaperones. Using an array of biophysical techniques, this study establishes that in vitro at substoichiometric levels and under physiological conditions α2M and Hp both inhibit the formation of amyloid fibrils from a range of proteins. We also provide evidence that both α2M and Hp interact with prefibrillar …
Clusterin Facilitates In Vivo Clearance Of Extracellular Misfolded Proteins, Amy R. Wyatt, Justin J. Yerbury, Paula Berghofer, I Greguric, Andrew Katsifis, Christopher Dobson, Mark R. Wilson
Clusterin Facilitates In Vivo Clearance Of Extracellular Misfolded Proteins, Amy R. Wyatt, Justin J. Yerbury, Paula Berghofer, I Greguric, Andrew Katsifis, Christopher Dobson, Mark R. Wilson
Mark R Wilson
The extracellular deposition of misfolded proteins is a characteristic of many debilitating age-related disorders. However, little is known about the specific mechanisms that act to suppress this process in vivo. Clusterin (CLU) is an extracellular chaperone that forms stable and soluble complexes with misfolded client proteins. Here we explore the fate of complexes formed between CLU and misfolded proteins both in vitro and in a living organism. We show that proteins injected into rats are cleared more rapidly from circulation when complexed with CLU as a result of their more efficient localisation to the liver and that this clearance is …
Potential Roles Of Abundant Extracellular Chaperones In The Control Of Amyloid Formation And Toxicity, Mark R. Wilson, Justin J. Yerbury, Stephen Poon
Potential Roles Of Abundant Extracellular Chaperones In The Control Of Amyloid Formation And Toxicity, Mark R. Wilson, Justin J. Yerbury, Stephen Poon
Mark R Wilson
The in vivo formation of fibrillar proteinaceous deposits called amyloid is associated with more than 40 serious human diseases, collectively referred to as protein deposition diseases. In many cases the amyloid deposits are extracellular and are found associated with newly identified abundant extracellular chaperones (ECs). Evidence is presented suggesting an important regulatory role for ECs in amyloid formation and disposal in the body. A model is presented which proposes that, under normal conditions, ECs stabilize extracellular misfolded proteins by binding to them, and then guide them to specific cell receptors for uptake and subsequent degradation. Thus ECs and their receptors …
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
Mark R Wilson
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 …
Extracellular Chaperones And Amyloids, Mark R. Wilson, Justin J. Yerbury, Stephen Poon
Extracellular Chaperones And Amyloids, Mark R. Wilson, Justin J. Yerbury, Stephen Poon
Mark R Wilson
The pathology of more than 40 human degenerative diseases is associated with fibrillar proteinaceous deposits called amyloid. Collectively referred to as protein deposition diseases, many of these affect the brain and the central nervous system. In many cases the amyloid deposits are extracellular and are found associated with newly identified abundant extracellular chaperones (ECs). Evidence is discussed which suggests an important regulatory role for ECs in amyloid formation and disposal in vivo. This is emerging as an exciting field. A model is presented in which it is proposed that, under normal conditions, ECs stabilize extracellular misfolded proteins by binding to …
Clusterin Is An Extracellular Chaperone That Specifically Interacts With Slowly Aggregating Proteins On Their Off-Folding Pathway, Stephen Poon, T. M. Treweek, Mark R. Wilson, Simon B. Easterbrook-Smith, John A. Carver
Clusterin Is An Extracellular Chaperone That Specifically Interacts With Slowly Aggregating Proteins On Their Off-Folding Pathway, Stephen Poon, T. M. Treweek, Mark R. Wilson, Simon B. Easterbrook-Smith, John A. Carver
Mark R Wilson
Clusterin is an extracellular mammalian chaperone protein which inhibits stress-induced precipitation of many different proteins. The conformational state(s) of proteins that interact with clusterin and the stage(s) along the folding and off-folding (precipitation-bound) pathways where this interaction occurs were previously unknown. We investigated this by examining the interactions of clusterin with different structural forms of α-lactalbumin, γ-crystallin and lysozyme. When assessed by ELISA and native gel electrophoresis, clusterin did not bind to various stable, intermediately folded states of α-lactalbumin nor to the native form of this protein, but did bind to and inhibit the slow precipitation of reduced α-lactalbumin. Reduction-induced …
Clusterin Interacts With Paclitaxel And Confer Paclitaxel Resistance In Ovarian Cancer, Dong Choon Park, Seung Geun Yeo, Mark R. Wilson, Justin J. Yerbury, Joseph Kwong, William R. Welch, Yang Kyu Choi, Michael J. Birrer, Samuel C. Mok, Kwong-Kwok Wong
Clusterin Interacts With Paclitaxel And Confer Paclitaxel Resistance In Ovarian Cancer, Dong Choon Park, Seung Geun Yeo, Mark R. Wilson, Justin J. Yerbury, Joseph Kwong, William R. Welch, Yang Kyu Choi, Michael J. Birrer, Samuel C. Mok, Kwong-Kwok Wong
Mark R Wilson
Optimal debulking followed by chemotherapy is the standard treatment of managing late-stage ovarian cancer, but chemoresistance is still a major problem. In this study, we compared expression profiles of primary tumor tissue from five long-term (>8 years) and five short-term (years) ovarian cancer survivors and identified clusterin as one of the genes that were significantly up-regulated in short-term survivors. We then evaluated the prognostic significance of clusterin and its possible correlation with chemoresistance in ovarian cancer by immunohistostaining of clusterin in 62 tumor samples from patients with stage III, high-grade serous ovarian cancer. After adjusting for debulking status and …
Apolipoprotein J And Leptin Levels In Patients With Coronary Heart Disease, Mark Wilson, Dimitri Mikhailidis, Maria Poulakou, Christos Tsigris, Despina Perrea, Kosmas Paraskevas, Dimitrios Iliopoulos
Apolipoprotein J And Leptin Levels In Patients With Coronary Heart Disease, Mark Wilson, Dimitri Mikhailidis, Maria Poulakou, Christos Tsigris, Despina Perrea, Kosmas Paraskevas, Dimitrios Iliopoulos
Mark R Wilson
No abstract provided.
Structural Characterization Of Clusterin-Chaperone Client Protein Complexes, Amy Wyatt, Justin Yerbury, Mark Wilson
Structural Characterization Of Clusterin-Chaperone Client Protein Complexes, Amy Wyatt, Justin Yerbury, Mark Wilson
Mark R Wilson
Clusterin (CLU) is a potent extracellular chaperone that inhibits protein aggregation and precipitation otherwise caused by physical or chemical stresses (e.g. heat, reduction). This action involves CLU forming soluble high molecular weight (HMW) complexes with the client protein. Other than their unquantified large size, the physical characteristics of these complexes were previously unknown. In this study, HMW CLU-citrate synthase (CS), HMW CLU-fibrinogen (FGN), and HMW CLU-glutathione S-transferase (GST) complexes were generated in vitro, and their structures studied using size exclusion chromatography (SEC), ELISA, SDS-PAGE, dynamic light scattering (DLS), bisANS fluorescence, and circular dichroism spectrophotometry (CD). Densitometry of …
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
Mark R Wilson
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 …
Therapeutic Targets In Extracellular Protein Deposition Diseases, Amy R. Wyatt, Justin J. Yerbury, Stephen Poon, Mark R. Wilson
Therapeutic Targets In Extracellular Protein Deposition Diseases, Amy R. Wyatt, Justin J. Yerbury, Stephen Poon, Mark R. Wilson
Mark R Wilson
Many litres of fluids are found outside cells in the human body. These fluids are rich in dissolved proteins that each have a characteristic three dimensional shape, necessary for normal function, which has been attained by the correct folding of their polypeptide chain(s). The structure of these extracellular proteins can be damaged by a variety of environmental stresses (e. g. heat and oxidation) leading to their partial unfolding and aggregation. This in turn can produce toxic soluble aggregates and/or large insoluble protein deposits, either of which can disrupt normal body function (e. g. in Alzheimer's disease and the systemic amyloidoses). …
Roles Of Extracellular Chaperones In Amyloidosis, Amy R. Wyatt, Justin J. Yerbury, Rebecca A. Dabbs, Mark R. Wilson
Roles Of Extracellular Chaperones In Amyloidosis, Amy R. Wyatt, Justin J. Yerbury, Rebecca A. Dabbs, Mark R. Wilson
Mark R Wilson
Extracellular protein misfolding and aggregation underlie many of the most serious amyloidoses including Alzheimer's disease, spongiform encephalopathies and type II diabetes. Despite this, protein homeostasis (proteostasis) research has largely focussed on characterising systems that function to monitor protein conformation and concentration within cells. We are now starting to identify elements of corresponding systems, including an expanding family of secreted chaperones, which exist in the extracellular space. Like their intracellular counterparts, extracellular chaperones are likely to play a central role in systems that maintain proteostasis; however, the precise details of how they participate are only just emerging. It is proposed that …
Ozone-Induced Dissociation On A Modified Tandem Linear Ion-Trap: Observations Of Different Reactivity For Isomeric Lipids, Berwyck Poad, Huong Pham, Michael Thomas, Jessica Hughes, J Campbell, Todd Mitchell, Stephen Blanksby
Ozone-Induced Dissociation On A Modified Tandem Linear Ion-Trap: Observations Of Different Reactivity For Isomeric Lipids, Berwyck Poad, Huong Pham, Michael Thomas, Jessica Hughes, J Campbell, Todd Mitchell, Stephen Blanksby
Berwyck L. J. Poad
Ozone-induced dissociation (OzID) exploits the gas-phase reaction between mass-selected lipid ions and ozone vapor to determine the position(s) of unsaturation. In this contribution, we describe the modification of a tandem linear ion-trap mass spectrometer specifically for OzID analyses wherein ozone vapor is supplied to the collision cell. This instrumental configuration provides spatial separation between mass-selection, the ozonolysis reaction, and mass-analysis steps in the OzID process and thus delivers significant enhancements in speed and sensitivity (ca. 30-fold). These improvements allow spectra revealing the double-bond position(s) within unsaturated lipids to be acquired within 1 s: significantly enhancing the utility of OzID in …
On The Electrodeposition Of Titanium In Ionic Liquids, William E. Price, Gordon G. Wallace, Douglas Macfarlane, S Z. El Abedin, A Y. Saad, F Endres, E M. Moustafa, P J. Newman, A Bund, N Borissenko
On The Electrodeposition Of Titanium In Ionic Liquids, William E. Price, Gordon G. Wallace, Douglas Macfarlane, S Z. El Abedin, A Y. Saad, F Endres, E M. Moustafa, P J. Newman, A Bund, N Borissenko
Gordon Wallace
The ability to electrodeposit titanium at low temperatures would be an important breakthrough for making corrosion resistant layers on a variety of technically important materials. Ionic liquids have often been considered as suitable solvents for the electrodeposition of titanium. In the present paper we have extensively investigated whether titanium can be electrodeposited from its halides (TiCl4, TiF4, TiI4) in different ionic liquids, namely1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide ([EMIm]Tf2N), 1-butyl-1-methylpyrrolidinium bis(trifluoromethyl-sulfonyl)amide ([BMP]Tf2N), and trihexyltetradecyl-phosphonium bis(trifluoromethylsulfonyl)amide ([P14,6,6,6]Tf2N). Cyclic voltammetry and EQCM measurements show that, instead of elemental Ti, only non-stoichiometric halides are formed, for example with average stoichiometries of TiCl0.2, TiCl0.5 and TiCl1.1. In situ …
Autopolymerization Of Pyrrole In The Presence Of A Host/Guest Calixarene, David A. Reece, Jennifer M. Pringle, Stephen F. Ralph, Gordon G. Wallace
Autopolymerization Of Pyrrole In The Presence Of A Host/Guest Calixarene, David A. Reece, Jennifer M. Pringle, Stephen F. Ralph, Gordon G. Wallace
Gordon Wallace
Aqueous solutions containing pyrrole and calix-6-arenehexasulfonic acid were found to undergo polymerization in the absence of either a chemical oxidant or electrochemical oxidation. The product was an unstable colloidal suspension consisting of spherical polypyrrole particles measuring ≥500 nm in diameter. Conductivity measurements showed the material to be insulating, while cyclic voltammetry studies demonstrated that it was electroactive. Infrared spectroscopy and microanalysis confirmed that the polypyrrole produced was doped with calix-6-arenehexasulfonic acid. When the reaction was repeated using solutions containing stabilizing agents, stable colloidal dispersions were obtained. These were shown by both particle size analysis and transmission electron microscopy to contain …