Social and Behavioral Sciences Commons^™

Activity And Molecular Dynamics Relationship Within The Family Of Human Cholinesterase, Judith Peters, Marie Trovaslet, Marcus Trapp, Florian Nachon, Flynn Hill, Etienne Royer, Frank Gabel, Lambert Van Eijck, Patrick Masson, Moeava Tehei

Faculty of Science - Papers (Archive)

The temperature dependence of the dynamics of recombinant human acetylcholinesterase (hAChE) and plasma human butyrylcholinesterase (hBChE) is examined using elastic incoherent neutron scattering. These two enzymes belong to the same family and present 50% amino acid sequence identity. However, significantly higher flexibility and catalytic activity of hAChE when compared to the ones of hBChE are measured. At the same time, the average height of the potential barrier to the motions is increased in the hBChE, e.g. more thermal energy is needed to cross it in the latter case, which might be the origin of the increase in activation energy and …

Emulsion-Coaxial Electrospinning: Designing Novel Architectures For Sustained Release Of Highly Soluble Low Molecular Weight Drugs, Lucie Viry, Simon E. Moulton, Tony Romeo, Courtney Suhr, Damia Mawad, Mark Cook, Gordon G. Wallace

Faculty of Science - Papers (Archive)

In drug therapy, most therapeutic drugs are of low molecular weight and could freely diffuse in the biological milieu depending on the administration route applied. The main reason for the development of polymeric drug carriers is to obtain desired effects such as sustained therapy, local and controlled release, prolonged activity and reduction of side effects. Alternatively, polymeric carriers can be made bioerodible in order to be eliminated by natural ways after a certain time of therapy. Core-shell fibres from coaxial spinneret or emulsion electrospinning are good candidates for the development of such devices; however difficulties remain especially in controlling the …

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, …

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 Characterization Of Escherichia Coli Strains That Cause Symptomatic And Asymptomatic Urinary Tract Infections, Sam Abraham, Toni A. Chapman, Ren Zhang, James Chin, Amanda N. Mabbett, Makrina Totsika, Mark A. Schembri

Faculty of Science - Papers (Archive)

The differences between Escherichia coli strains associated with symptomatic and asymptomatic urinary tract infections (UTIs) remain to be properly determined. Here we examined the prevalence of plasmid types and bacteriocins, as well as genetic relatedness, in a defined collection of E. coli strains that cause UTIs. Comparative analysis identified a subgroup of strains with a high number of virulence genes (VGs) and microcins M/H47. We also identified associations between microcin genes, VGs, and specific plasmid types.

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 …

Molecular Mechanisms Of K+ Selectivity In Na/K Pump, Haibo Yu, Ian Ratheal, Pablo Artigas, Benoit Roux

Faculty of Science - Papers (Archive)

The sodium–potassium (Na/K) pump plays an essential role in maintaining cell volume and secondary active transport of other solutes by establishing the Na⁺ and K⁺ concentration gradients across the plasma membrane of animal cells. The recently determined crystal structures of the Na/K pump to atomic resolution provide a new impetus to investigate molecular determinants governing the binding of Na⁺ and K⁺ ions and conformational transitions during the functional cycle. The pump cycle is generally described by the alternating access mechanism, in which the pump toggles between different conformational states, where ions can bind from either the …

Molecular Characterization Of Commensal Escherichia Coli Adapted To Different Compartments Of The Porcine Gastrointestinal Tract, Sam Abraham, David M. Gordon, James Chin, Huub J. M Brouwers, Peter Njuguna, Mitchell D. Groves, Ren Zhang, Toni A. Chapman

Faculty of Science - Papers (Archive)

The role of Escherichia coli as a pathogen has been the focus of considerable study, while much less is known about it as a commensal and how it adapts to and colonizes different environmental niches within the mammalian gut. In this study, we characterize Escherichia coli organisms (n=146) isolated from different regions of the intestinal tracts of eight pigs (dueodenum, ileum, colon, and feces). The isolates were typed using the method of random amplified polymorphic DNA (RAPD) and screened for the presence of bacteriocin genes and plasmid replicon types. Molecular analysis of variance using the RAPD data showed that E. …

Beyond Barcoding: A Mitochondrial Genomics Approach To Molecular Phylogenetics And Diagnostics Of Blowflies (Diptera: Calliphoridae), Leigh Nelson, Christine L. Lambkin, Philip Batterham, James F. Wallman, Mark P. Dowton, Michael F. Whiting, David K. Yeates, Stephen L. Cameron

Faculty of Science - Papers (Archive)

Members of the Calliphoridae (blowflies) are significant for medical and veterinary management, due to the ability of some species to consume living flesh as larvae, and for forensic investigations due to the ability of others to develop in corpses. Due to the difficulty of accurately identifying larval blowflies to species there is a need for DNA-based diagnostics for this family, however the widely used DNA-barcoding marker, cox1, has been shown to fail for several groups within this family. Additionally, many phylogenetic relationships within the Calliphoridae are still unresolved, particularly deeper level relationships. Sequencing whole mt genomes has been demonstrated both …

Binding Of The Molecular Chaperone Alphab-Crystallin To Abeta Amyloid Fibrils Inhibits Fibril Elongation, Sarah L. Shammas, Christopher A. Waudby, Shuyu Wang, Alexander K. Buell, Tuomas P. Knowles, Heath W. Ecroyd, Mark E. Welland, John A. Carver, Christopher M. Dobson, Sarah Meehan

Faculty of Science - Papers (Archive)

The molecular chaperone αB-crystallin is a small heat-shock protein that is upregulated in response to a multitude of stress stimuli, and is found colocalized with Aβ amyloid fibrils in the extracellular plaques that are characteristic of Alzheimer's disease. We investigated whether this archetypical small heat-shock protein has the ability to interact with Aβ fibrils in vitro. We find that αB-crystallin binds to wild-type Aβ₄₂ fibrils with micromolar affinity, and also binds to fibrils formed from the E22G Arctic mutation of Aβ₄₂. Immunoelectron microscopy confirms that binding occurs along the entire length …

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 …

Beads, Boats And Switches: Making Things Happen With Molecular Photoswitches, Robert P. Byrne, Silvia Scaramagnani, Michael J. Higgins, Gordon G. Wallace, Dermot Diamond

Faculty of Science - Papers (Archive)

In this paper we present recent results obtained with a stimulus-responsive materials based on the photo-switchable behaviour exhibited by spiro-cyclic derivatives. Our results suggest that these highly novel materials offer unique capabilities hitherto inaccessible using conventional materials. In particular, we will focus on photocontrolled guest binding and release, inherent signalling of status, photo-actuation and solvent driven motion of small structures as examples of the fascinating behaviour of these exceptional materials. Copyright 2009 IEEE NANO Organizers.

A Bio-Inspired Molecular Catalyst That Selectively Catalyzes Water Oxidation In Seawater, Without Significant Chlorine Formation, Robin Brimblecombe, G. Charles Dismukes, Gerhard F. Swiegers, Leone Spiccia

Faculty of Science - Papers (Archive)

Most transport fuels are derived from fossil fuels, generate greenhouse gases, and consume significant amounts of water in the extraction, purification, and/or burning processes. The generation of hydrogen using solar energy to split water, ideally from sea water or other non-potable sources, could potentially provide an unlimited, clean fuel for the future. Solar, electrochemical water splitting typically combines a photoanode at which water oxidation occurs, with a cathode for proton reduction to hydrogen. In recent work we have found that a bioinspired tetra-manganese cluster catalyzes water oxidation at relatively low overpotentials (0.38 V) when doped into a Nafion proton conduction …

Molecular Water Oxidation Catalysts For Photoelectrochemical Cells, Robin Brimblecombe, Charles Dismukes, Gerhard F. Swiegers, Leone Spiccia

Faculty of Science - Papers (Archive)

Photoelectrochemical cells that efficiently split water into oxygen and hydrogen, "the fuel of the future", need to combine robust water oxidation catalysts at the anode (2H(2)O -> O-2 + 4H(+) + 4e(-)) with hydrogen reduction catalysts at the cathode (2H(+) + 2e(-) -> H-2). Both sets of catalysts will, ideally, operate at low overpotentials and employ light-driven or light-assisted processes. In this Perspective article, we focus on significant efforts to develop solid state materials and molecular coordination complexes as catalyst for water oxidation. We briefly review the field with emphasis on the various molecular catalysts that have been developed and …

A Bio-Inspired Molecular Water Oxidation Catalyst For Renewable Hydrogen Generation: An Examination Of Salt Effects, Robin Brimblecombe, Miriam Rotstein, Annette Koo, G Charles Dismukes, Gerhard F. Swiegers, Leone Spiccia

Faculty of Science - Papers (Archive)

Most transport fuels are derived from fossil fuels, generate greenhouse gases, and consume significant amounts of water in the extraction, purification, and/or burning processes. The generation of hydrogen using solar energy to split water, ideally from abundant water sources such as sea water or other non-potable sources, could potentially provide an unlimited, clean fuel for the future. Solar, electrochemical water splitting typically combines a photoanode at which water oxidation occurs, with a cathode for proton reduction to hydrogen. In recent work, we have found that a bioinspired tetra-manganese cluster catalyzes water oxidation at relatively low overpotentials (0.38 V) when doped …

Molecular And Morphological Description Of A Hepatozoon Species In Reptiles And Their Ticks In The Northern Territory, Australia, Inger-Marie E. Vilcins, Beata Ujvari, Julie M. Old, Elizabeth Deane

Faculty of Science - Papers (Archive)

Ticks, representing 3 species of Amblyomma, were collected from the water python (Liasis fuscus) and 3 additional reptile species in the Northern Territory, Australia, and tested for the presence of Hepatozoon sp., the most common blood parasites of snakes. In addition, blood smears were collected from 5 reptiles, including the water python, and examined for the presence of the parasite. Hepatozoon sp. DNA was detected in all tick and reptile species, with 57.7% of tick samples (n = 187) and 35.6% of blood smears (n = 35) showing evidence of infection. Phylogenetic analysis of the 18S rRNA gene demonstrated that …

Nmr Study Of Complexes Between Low Molecular Mass Inhibitors And The West Nile Virus Ns2b-Ns3 Protease, X Su, Kiyoshi Ozawa, Hiromasa Yagi, S P. Lim, D Wen, D Ekonomiuk, D Huang, T Keller, S Sonntag, A Caflisch, S G. Vasudevan, G Otting

Faculty of Science - Papers (Archive)

The two-component NS2B-NS3 protease of West Nile virus is essential for its replication and presents an attractive target for drug development. Here, we describe protocols for the high-yield expression of stable isotope-labelled samples in vivo and in vitro. We also describe the use of NMR spectroscopy to determine the binding mode of new low molecular mass inhibitors of the West Nile virus NS2B-NS3 protease which were discovered using high-throughput in vitro screening. Binding to the substrate-binding sites S1 and S3 is confirmed by intermolecular NOEs and comparison with the binding mode of a previously identified low molecular mass inhibitor. Our …

Attachment Of Molecular Hydrogen To An Isolated Boron Cation: An Infrared And Ab Initio Study, Viktoras Dryza, Berwyck L. J Poad, Evan J. Bieske

Faculty of Science - Papers (Archive)

Structural properties of the B⁺−H₂ electrostatic complex are investigated through its rotationally resolved infrared spectrum in the H−H stretch region (3905−3975 cm⁻¹). The spectrum, which was obtained by monitoring B⁺ photofragments while the IR wavelength was scanned, is consistent with the complex having a T-shaped structure and a vibrationally averaged intermolecular separation of 2.26 Å, which decreases by 0.04 Å when the H₂ subunit is vibrationally excited. The H−H stretch transition of B⁺−H₂ is red-shifted by 220.6 ± 1.5 cm⁻¹ from that of the free H₂ molecule, much …

Anisotropic Atomic Motions In High-Resolution Protein Crystallography Molecular Dynamics Simulations, Conrad J. Burden, Aaron J. Oakley

Faculty of Science - Papers (Archive)

Molecular dynamics (MD) simulations using empirical force fields are popular for the study of proteins. In this work, we compare anisotropic atomic fluctuations in nanosecond-timescale MD simulations with those observed in an ultra-high-resolution crystal structure of crambin. In order to make our comparisons, we have developed a compact graphical technique for assessing agreement between spatial atomic distributions determined by MD simulations and observed anisotropic temperature factors.

The Epididymal Soluble Prion Protein Forms A High-Molecular-Mass Complex In Association With Hydrophobic Proteins, Heath W. Ecroyd, Maya Belghazi, Jean-Louis Dacheux, Jean-Luc Gatti

Faculty of Science - Papers (Archive)

We have shown previously that a 'soluble' form of PrP (prion protein), not associated with membranous vesicles, exists in the male reproductive fluid [Ecroyd, Sarradin, Dacheux and Gatti (2004) Biol. Reprod. 71, 993-1001]. Attempts to purify this 'soluble' PrP indicated that it behaves like a high-molecular-mass complex of more than 350 kDa and always co-purified with the same set of proteins. The main associated proteins were sequenced by MS and were found to match to clusterin (apolipoprotein J), BPI (bacterial permeability-increasing protein), carboxylesterase-like urinary excreted protein (cauxin), beta-mannosidase and beta-galactosidase. Immunoblotting and enzymatic assay confirmed the presence of clusterin and …

Molecular Dynamics Simulations Of Peptides Containing An Unnatural Amino Acid: Dimerization, Folding, And Protein Binding, Haibo Yu, Xavier Daura, Wilfred Van Gunsteren

Faculty of Science - Papers (Archive)

We have performed molecular dynamics (MD) simulations to study the dimerization, folding, and binding to a protein of peptides containing an unnatural amino acid. NMR studies have shown that the substitution of one residue in a tripeptide β-strand by the unnatural amino acid Hao (5-HO2CCONH-2-MeO-C6H3-CO-NHNH2) modifies the conformational flexibility of the β-strand and the hydrogen-bonding properties of its two edges: The number of hydrogen-bond donors and acceptors increases at one edge, whereas at the other, they are sterically hindered. In simulations in chloroform, the Hao-containing peptide 9 (i-PrCO-Phe-Hao-Val-NHBu) forms a β-sheet–like hydrogen-bonded dimer, in good agreement with the available experimental …

Molecular Dynamics Simulation Of Biomolecular Systems, Wilfred Van Gunsteren, Dirk Bakowies, Roland Buergi, Indira Chandrasekhar, Markus Christen, Xavier Daura, Peter Gee, Alice Glaettli, Tomas Hansson, Chris Oostenbrink, Christine Peter, Jed Pitera, Lukas Schuler, Thereza Soares, Haibo Yu

Faculty of Science - Papers (Archive)

The group for computer-aided chemistry at the ETH Zurich focuses its research on the development of methodology to simulate the behavior of biomolecular systems and the use of simulation techniques to analyze and understand biomolecular processes at the atomic level. Here, the current research directions are briefly reviewed and illustrated with a few examples.