Social and Behavioral Sciences Commons^™

Extracellular Adenosine 5'-Triphosphate And Lipopolysaccharide Induce Interleukin-1Β Release In Canine Blood, Mari Spildrejorde, Stephen J. Curtis, Belinda L. Curtis, Ronald Sluyter

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

Binding of extracellular adenosine 5′-triphosphate (ATP) or lipopolysaccharide (LPS) to the damage-associated molecular pattern receptor P2X7 or the pathogen-associated molecular pattern receptor Toll-like receptor (TLR)4, respectively, can induce the release of the pleiotropic cytokine interleukin (IL)-1β in humans and mice. However, the release of IL-1β in dogs remains poorly defined. Using a canine IL-1β enzyme-linked immunosorbent assay, this study investigated whether ATP or LPS could induce IL-1β release in a canine blood-based assay. Short-term incubations (30 min) with ATP induced IL-1β release in LPS-primed canine blood, and this process could be near-completely impaired by the P2X7 antagonist, A438079. In contrast, …

Sequential 1,4- And 1,2-Addition Reactions To Α,Β-Unsaturated N-Acyliminium Ions: A New Strategy For The Synthesis Of Spiro And Bridged Heterocycles, Arife Yazici, Stephen G. Pyne

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

Novel bicyclic and tetracyclic spirocycles and tricyclic bridged heterocyclic systems can be readily prepared from sequential 1,4- and 1,2-addition reactions of latent bis-nucleophiles to α,β-unsaturated N-acyliminium ions.

Glutathionylation Potentiates Benign Superoxide Dismutase 1 Variants To The Toxic Forms Associated With Amyotrophic Lateral Sclerosis, Luke Mcalary, Justin J. Yerbury, J. Andrew Aquilina

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

Dissociation of superoxide dismutase 1 dimers is enhanced by glutathionylation, although the dissociation constants reported to date are imprecise. We have quantified the discreet dissociation constants for wild-type superoxide dismutase 1 and six naturally occurring sequence variants, in their unmodified and glutathionylated forms, at the ratios expressed. Unmodified superoxide dismutase 1 variants that shared similar dissociation constants with SOD1WT had disproportionately increased dissociation constants when glutathionylated. This defines a key role for glutathionylation in superoxide dismutase 1 associated familial amyotrophic lateral sclerosis.

Improved Water Vapour Spectroscopy In The 4174-4300 Cm(-1) Region And Its Impact On Sciamachy Hdo/H2o Measurements, R A. Scheepmaker, C Frankenberg, A Galli, A Butz, H Schrijver, N M. Deutscher, D Wunch, T Warneke, S Fally, I Aben

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

The relative abundance of the heavy water isotopologue HDO provides a deeper insight into the atmospheric hydrological cycle. The SCanning Imaging Absorption spectroMeter for Atmospheric CartograpHY (SCIAMACHY) allows for global retrievals of the ratio HDO/H2O in the 2.3 micron wavelength range. However, the spectroscopy of water lines in this region remains a large source of uncertainty for these retrievals. We therefore evaluate and improve the water spectroscopy in the range 4174-4300 cm(-1) and test if this reduces systematic uncertainties in the SCIAMACHY retrievals of HDO/H2O. We use a laboratory spectrum of water vapour to fit line intensity, air broadening and …

Inhibition Of Tnf-Α Production In Lps-Activated Thp-1 Monocytic Cells By The Crude Extracts Of Seven Bhutanese Medicinal Plants, Phurpa Wangchuk, Paul A. Keller, Stephen G. Pyne, Malai Taweechotipatr

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

Ethnopharmacological relevance Seven studied medicinal plants; Aconitum laciniatum, Ajania nubigena, Codonopsis bhutanica, Corydalis crispa, Corydalis dubia, Meconopsis simplicifolia and Pleurospermum amabile, are currently used in the Bhutanese Traditional Medicine (BTM) for the management of different types of disorders including the diseases that bore relevance to various inflammatory conditions.

Aims of the study This study aimed to evaluate the inhibition of TNF-α production in LPS-activated THP-1 monocytic cells by the crude extracts of seven selected Bhutanese medicinal plants. It is expected to; (a) generate a scientific basis for their use in the BTM and (b) form a basis for prioritization of …

Non-Invasive Detection Of Microvascular Changes In A Paediatric And Adolescent Population With Type 1 Diabetes: A Pilot Cross-Sectional Study, Sarah P. M Hosking, Rani Bhatia, Patricia A. Crock, Ian M. R Wright, Marline L. Squance, Glenn Reeves

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

Background: The detection of microvascular damage in type 1 diabetes is difficult and traditional investigations do not detect changes until they are well established. The purpose of this study was to investigate the combined ability of nailfold capillaroscopy, laser Doppler flowmetry, retinal vessel analysis and 24-hr ambulatory blood pressure monitoring to detect early microvascular changes in a paediatric and adolescent population with type 1 diabetes.

Methods: Patients aged between 8 – 18 years with type I diabetes and no other autoimmune conditions were studied. The participants underwent the above cardiac and vascular investigations in a single three-hour session. Standard parameters …

Neuregulin-1 Signalling And Antipsychotic Treatment: Potential Therapeutic Targets In A Schizophrenia Candidate Signalling Pathway, Chao Deng, Bo Pan, Martin Engel, Xu-Feng Huang

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

Identifying the signalling pathways underlying the pathophysiology of schizophrenia is an essential step in the rational development of new antipsychotic drugs for this devastating disease. Evidence from genetic, transgenic and post-mortem studies have strongly supported neuregulin-1 (NRG1)-ErbB4 signalling as a schizophrenia susceptibility pathway. NRG1-ErbB4 signalling plays crucial roles in regulating neurodevelopment and neurotransmission, with implications for the pathophysiology of schizophrenia. Post-mortem studies have demonstrated altered NRG1-ErbB4 signalling in the brain of schizophrenia patients. Antipsychotic drugs have different effects on NRG1-ErbB4 signalling depending on treatment duration. Abnormal behaviours relevant to certain features of schizophrenia are displayed in NRG1/ErbB4 knockout mice or …

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

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

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

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

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

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

Polymorphisms Of Cx3cr1 And Cxcr6 Receptors In Relation To Haart Therapy Of Hiv Type 1 Patients, Andreas M. Passam, George Sourvinos, Elias Krambovitis, Spyridon Miyakis, Nikolaos G. Stavrianeas, Ioannis Zagoreos, Demetrios A. Spandidos

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

The chemokine polymorphisms CXCR6-3E/K, In1.1T/C, H7 haplotype, CX3CR1-V249I, and CX3CR1-T280M have been shown to affect the course of HIV infection. We studied their influence on immunologic and virologic response to HAART in a group of 143 HIV-1 patients. We performed Kaplan-Meier analysis using the following end-point criteria: (1) time from HAART initiation to undetectable viral load (VL < 50 copies/ml), (2) maximum duration of viral suppression, (3) time from HAART administration until CD4 elevation above 200 cells/ul for patients with baseline CD4 below 200 cells/ul and above 500 cells/ul for patients with baseline CD4 between 200 and 500 cells/ul, respectively, and (4) time from HAART initiation until CD4 reduction below baseline values. Our results revealed an improved immunologic response to HAART in patients with the CX3CR1-249I or CX3CR1-280M allele. On the contrary, patients with initial VL suppression due to HAART showed a faster virologic failure in the presence of the CXCR6-3K allele. The In1.1T/C polymorphism and H7 haplotype did not reveal any specific effect on HAART response.

Immune Responses Of A Liposome/Iscom Vaccine Adjuvant Against Streptococcal Fibronectin Binding Protein 1 (Sfb1) In Mice, Jason D. Mcarthur, K Schulze, James Chin, B J. Currie, K S. Sriprakash, S R. Talay, G S. Chhatwal, C A. Guzman, Mark J. Walker

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

BACKGROUND & OBJECTIVES: The fibronectin binding protein Sfb1 of Streptococcus pyogenes is a well characterised antigen which induces protection against lethal challenge with group A streptococcus (GAS) when adjuvanted with cholera toxin B-subunit (CTB). As an alternative to CTB adjuvanted intranasal immunisations we investigated the immune responses generated in mice using Sfb1 incorporated in to the skin and mucosal adjuvant SAMA4. METHODS: Mice (BALB/c) were vaccinated intradermally with 100 microl of either SAMA4 (adjuvant only group) or SAMA4/Sfb1 and were boosted 7 days later. Mice vaccinated with CTB based vaccines were immunised by intranasal inoculation with a mixture containing 30 …

Stx1c Is The Most Common Shiga Toxin 1 Subtype Among Shiga Toxin-Producing Escherichia Coli Isolates From Sheep But Not Among Isolates From Cattle, Kim Brett, Vidiya Ramachandran, Michael A Hornitzky, Karl A Bettelheim, Mark J. Walker, Steven P. Djordjevic

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

Unlike Shiga toxin 2 (stx₂) genes, most nucleotide sequences of Shiga toxin 1 (stx₁) genes from Shiga toxin-producing Escherichia coli (STEC), Shigella dysenteriae, and several bacteriophages (H19B, 933J, and H30) are highly conserved. Consequently, there has been little incentive to investigate variants of stx₁ among STEC isolates derived from human or animal sources. However stx_1OX3, originally identified in an OX3:H8 isolate from a healthy sheep in Germany, differs from other stx₁ subtypes by 43 nucleotides, resulting in changes to 12 amino acid residues, and has been renamed stx_{1c …}

Flexibility Revealed By The 1.85 Å Crystal Structure Of The Β Sliding-Clamp Subunit Of Escherichia Coli Dna Polymerase Iii, Aaron J. Oakley, Pavel Prosselkov, Gene Wijffels, Jennifer L. Beck, Matthew Cj Wilce, Nicholas E. Dixon

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

The subunit of the Escherichia coli replicative DNA polymerase III holoenzyme is the sliding clamp that interacts with the (polymerase) subunit to maintain the high processivity of the enzyme. The protein is a ring-shaped dimer of 40.6 kDa subunits whose structure has previously been determined at a resolution of 2.5 Å [Kong et al. (1992), Cell, 69, 425-437]. Here, the construction of a new plasmid that directs overproduction of to very high levels and a simple procedure for large-scale purification of the protein are described. Crystals grown under slightly modified conditions diffracted to beyond 1.9 Å at 100 …

Revised Age For Mojokerto 1, An Early Homo Erectus Cranium From East Java, Indonesia, Michael Morwood, P O'Sullivan, E E. Susanto, F Aziz

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

Dates of around 1.8 Ma have been claimed for a hominin cranial vault excavated near Mojokerto City in East Java, Indonesia. Such an early date for presumed Homo erectus in East Asia would require a major revision of the general model for timing of initial hominin dispersal 'Out of Africa'. Instead, our field study and redating of two pumice horizons at the site indicate that the age of the Mojokerto cranial vault is less than 1.49 Ma. Furthermore, we argue that a basic understanding of site and regional depositional processes is fundamental for assessing the significance of any radiometric date.