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David R Turner

Publications and source records attributed to David R Turner.

16 recordsLinked to original sources
PubMed2006

A conformationally flexible, urea-based tripodal anion receptor: solid-state, solution, and theoretical studies.

Tripodal tris(urea) cationic receptors 1 and 2 containing p-tolyl or octyl substituents, respectively, have been synthesized, and their association behavior with anionic guests has been studied via a variety of methods. The receptors are based around a hexasubstituted aryl core and contain both urea and pyridinium functionalities. For 1:1 complexes, anions reside within the central cavity of the host species, held by hydrogen bonds from both NH and CH donors. The following host-anion complexes have been characterized by X-ray crystallography: 1-(Br)3, 1-(PF6)3.2(CH3)2CO, and 1-(NO3)1.5(PF6)1.5. Each structure contains the receptor in a significantly different geometry, highlighting the anion-dependent conformational flexibility of 1. Solution 1H NMR spectroscopic titrations have shown the two host species to display significant affinity for both halides and hydrogen sulfate and strongly suggest the persistence of CH...X- interactions despite the presence of "stronger" NH donor groups. Variable-temperature 1H NMR studies on the more soluble octyl derivative 2 show that there is a distinct change in conformation associated with the formation of a 1:1 host/guest complex. Computations using density functional theory (with the B3LYP functional) have been employed to aid in understanding the geometry of the 1:1 host/chloride complexes of 1 and 2. These experiments suggest that the lowest energy conformation for 1-Cl is one in which the ureidopyridinium arms are orientated upward forming a cavity that is sealed by CH...pi interactions, effectively forming a unimolecular capsule, whereas for 2 a less symmetrical "2-up, 1-down" geometry is favored.

Journal Article↗
PubMed2006

Extremely low priming doses of X radiation induce an adaptive response for chromosomal inversions in pKZ1 mouse prostate.

An adaptive response is a response to a stress such as radiation exposure that results in a lower than expected biological response. We describe an adaptive response to X radiation in mouse prostate using the pKZ1 chromosomal inversion assay. pKZ1 mice were treated with a priming dose of 0.001, 0.01, 1 or 10 mGy followed 4 h later by a 1000-mGy challenge dose. All priming doses caused a similar reduction in inversions compared to the 1000-mGy group, supporting the hypothesis that the adaptive response is the result of an on/off mechanism. The adaptive response was induced by a priming dose of 0.001 mGy, which is three orders of magnitude lower than has been reported previously. The adaptive responses completely protected against the inversions that would have been induced by a single 1000-mGy dose as well as against a proportion of spontaneous background inversions. The distribution of inversions across prostate gland cross sections after priming plus challenge irradiation suggested that adaptive responses were predominantly due to reduced low-dose radiation-induced inversions rather than to reduced high-dose radiation-induced inversions. This study used radiation doses relevant to human exposure.

Adaptation, Physiological↗
PubMed2005

Cooperative hydrogen-bonding effects in a water square: a single-crystal neutron and partial atomic charges and hardness analysis study.

Four isomorphous complexes of formula [M(L)(4)(H(2)O)(2)]SO(4).2H(2)O (M = Co, 1a; Ni, 1b; Cu, 1c; Zn, 1d) have been isolated and characterized by single-crystal X-ray diffraction and neutron diffraction using the quasi-Laue diffractometer VIVALDI at the Institut Laue-Langevin as well as by thermogravimetric analysis. The structures contain a discrete, strongly hydrogen-bonded water tetramer which causes a significant distortion of the metal coordination sphere in each case. Partial atomic charges and hardness analysis (PACHA) calculations reveal that the shortest hydrogen bonds are not the strongest in this constrained, cyclic solid-state structure and show that the distortion at the metal center is caused by the drive to maintain the integrity of the water tetramer. The system undergoes a disorder-order transition on slow cooling that provides insight into the nature of communication between water squares.

Journal Article↗
PubMed2005

Achieving equal standards in medical student education: is a national exit examination the answer?

Although it is commonly assumed that the quality of medical school education in Australia is uniformly high, there is no national process for assessing its outcomes. There is substantial variability in the content of medical school curricula, and the process of curriculum change is becoming more challenging because of intense competition for time and space in the course. A national exit examination could provide a uniform standard of assessment for all medical school graduates in Australia, as well as foreign graduates applying to work in Australia. Such an examination could assess medical school outcomes, monitor the effects of curriculum change, and provide a benchmark for new medical schools that would help medical curricula evolve to better meet society's needs.

Australia↗
PubMed2004

Linear distortion of octahedral metal centres by multiple hydrogen bonds in modular ML(4) systems.

A series of compounds of the type [M(1)(4)(H(2)O)(2)]SO(4)[middle dot]2H(2)O containing a simple urea-based pyridyl ligand have been synthesised and characterised by X-ray crystallography. The enclathrated water exists within discrete linearly stacked cavities and causes significant distortions in the M-OH(2) bonds due to the presence of a strongly hydrogen bonded water square.

Journal Article↗
PubMed2004

A central role for the mast cell in early phase vasculitis in the Brown Norway rat model of vasculitis: a histological study.

Administration of mercuric chloride (HgCl(2)) to Brown Norway rats causes Th2-dominated autoimmunity with raised immunoglobulin E concentrations and gut vasculitis, both of which are T-cell dependent, peak at 14 days after starting HgCl(2) and then spontaneously resolve. If animals are re-challenged with HgCl(2) 6 weeks after initial exposure, they are resistant to autoimmunity, developing only attenuated disease. Recently, a separate phase of early caecal vasculitis was described beginning 24 h after initiating HgCl(2) and prior to caecal entry of T cells. Previous work suggested this early vasculitis was alpha beta T-cell independent and implied a role for mast cells. We further tested this hypothesis by performing a histological study during the first 93 h following HgCl(2) challenge defining the precise relationship between gut mast cell degranulation and appearing caecal vasculitis. We also studied whether early caecal vasculitis enters a resistant phase upon re-challenge with HgCl(2). We show a direct correlation between mast cell degranulation and early caecal vasculitis following initial HgCl(2) challenge. We demonstrate resistance to re-challenge in this phase of injury, with results at re-challenge also showing a correlation between mast cell degranulation and early caecal injury.

Animals↗
PubMed2003

Slow anion exchange, conformational equilibria, and fluorescent sensing in venus flytrap aminopyridinium-based anion hosts.

The synthesis, anion binding, and conformational properties of a series of 3-aminopyridinium-based, tripodal, tricationic hosts for anions are described. Slow anion and conformational exchange on the (1)H NMR time scale at low temperature, coupled with NMR titration, results in a high level of understanding of the anion-binding properties of the compounds, particularly with respect to significant conformational change resulting from induced fit complexation. Peak selectivity for halides, particularly Cl(-), is observed. The approach has been extended to dipodal and tripodal podands based on 3-aminopyridinium "arms" containing photoactive anthracenyl moieties. The 1,3,5-tripodal host shows a remarkable selectivity for acetate over other anions, in contrast to the analogous unsubstituted tris(3-aminopyridinium) analogue, despite the fact that low-temperature (1)H NMR experiments reveal a total of four acetate-binding conformations. Photodimerization of anthracene units results in the formation of potential fluorescent anion sensors.

Journal Article↗
PubMed2003

Mitotic recombination is an important mutational event following oxidative damage.

The mutagenic effects of hydrogen peroxide (H(2)O(2)), a source of reactive oxygen species (ROS) have been determined in human lymphocytes. T-lymphocytes mutated at the autosomal HLA-A locus on chromosome 6 have been clonally isolated (N = 2097 clones) and the molecular basis of each clonal mutation characterised as due to intragenic, deletion or mitotic recombination mutation. H(2)O(2) caused a dose dependent increase in mutation frequency. There was no significant increase in the frequency of intragenic mutations. Mitotic recombination (MR) was responsible for 87% of the increase in mutation frequency induced by H(2)O(2) and gene deletion was responsible for 13%. MR results in loss of heterozygosity (LOH) distal to the recombination site. It is known that LOH is important in the initiation and progression of cancer. These results suggest that the biologically important consequence of some ROS may be LOH as a by-product of recombination repair. They also suggest that if our observations apply to ROS generally, then many of the mutations which accumulate with ageing or which are observed in cancer may be due to factors other than ROS.

DNA Damage↗
PubMed2003

The determination of trace metals in estuarine and coastal waters using a voltammetric in situ profiling system.

This work presents the optimisation, validation and field deployment of a voltammetric in situ profiling (VIP) system for the simultaneous determinations of dynamic Cd(II), Cu(II) and Pb(II) in estuarine and coastal waters. Systematic studies in NaNO3 (as a supporting electrolyte) and seawater, indicated that variations in ionic strength, pH and dissolved oxygen did not affect the response of the instrument, whereas an Arrhenius type temperature response was observed. The VIP instrument allows the determination of 2-3 samples h(-1), and has a detection limit (defined as 3sigma) in seawater for Cd(II): 23 pM, Cu(II): 1.13 nM, and Pb(II): 23 pM. The VIP system accurately measured the total dissolved concentrations of Cd(II), Cu(II) and Pb(II) in two certified reference materials; SLRS-3, a river water, and SLEW-2, an estuarine water. Field evaluation of the instrumentation and analytical methods was achieved through a series of surveys in the Plym Estuary (Devon, UK), from which environmental data are presented.

Electrochemistry↗
PubMed2003

Linkage and association analysis of radiation damage repair genes XRCC3 and XRCC5 with nevus density in adolescent twins.

Previous studies have shown that a deficiency in DNA damage repair is associated with increased cancer risk, and exposure to UV radiation is a major risk factor for the development of malignant melanoma. High density of common nevi (moles) is a major risk factor for cutaneous melanoma. A nevus may result from a mutation in a single UV-exposed melanocyte which failed to repair DNA damage in one or more critical genes. XRCC3 and XRCC5 may have an effect on nevus count through their function as components of DNA repair processes that may be involved directly or indirectly in the repair of DNA damage due to UV radiation. This study aims to test the hypothesis that the frequency of flat or raised moles is associated with polymorphism at or near these DNA repair genes, and that certain alleles are associated with less efficient DNA repair, and greater nevus density. Twins were recruited from schools in south eastern Queensland and were examined close to their 12th birthday. Nurses examined each individual and counted all moles on the entire body surface. A 10cM genome scan of 274 families (642 individuals) was performed and microsatellite polymorphisms in XRCC3 and adjacent to XRCC5 were also typed. Linkage and association of nevus count to these loci were tested simultaneously using a structural-equation modeling approach implemented in MX. There is weak evidence for linkage of XRCC5 to a QTL influencing raised mole count, and also weak association. There is also weak evidence for association between flat mole count and XRCC3. No tests were significant after correction for testing multiple alleles, nor were any of the tests for total association significant. If variation in XRCC3 or XRCC5 influences UV sensitivity, and indirectly affects nevus density, then the effects are small.

Adolescent↗
PubMed2002

Cooperative anion binding and electrochemical sensing by modular podands.

A series of podands based on two or three hydrogen bonding "arms" situated in mutually ortho, meta, or para relationships about an aryl core have been prepared, and their affinities for simple inorganic anions were measured. Of the two-arm hosts the meta compound and to a lesser extent the ortho host exhibit a cooperative anion binding effect. The two arms function essentially independently in the para derivative. The mutually meta three-arm host shows dramatically enhanced cooperative binding. Conformational changes within the meta two-arm host result in significantly enhanced electrochemical anion sensing compared with the more conformationally rigid three-arm host.

Anions↗
PubMed2002

Antioxidants inhibit mercuric chloride-induced early vasculitis.

In the Brown Norway (BN) rat, mercuric chloride (HgCl(2)) induces a T(h)2-dominated autoimmune syndrome which includes an early phase of mast cell-dependent vasculitis. We have shown in vitro that oxidative stress up-regulates IL-4 in mast cells and predisposes to degranulation. The aim of this study was to determine whether administration of antioxidants inhibits HgCl(2)-induced early vasculitis in vivo, and, if so, to examine whether modulation of the oxidative/antioxidative balance influences IgE and IL-4 expression by mast cells in situ. Groups of rats were given HgCl(2) + saline, HgCl(2) + N-acetyl-L-cysteine (NAC), saline + saline or saline + NAC respectively and blood was taken and animals killed 48 h later. NAC significantly reduced both HgCl2-induced early vasculitis and HgCl(2)-enhanced IgE expression on mast cells with a trend to a decrease in HgCl(2)-enhanced IL-4 expression in these cells. In addition, there was an increased rat mast cell protease (RMCP) II concentration in the serum after HgCl(2) injection and the elevated levels of RMCP II stimulated by HgCl(2) were totally abolished by the administration NAC in the HgCl(2) + NAC group. However, there was no significant change in serum total IgE concentrations between the HgCl(2) + saline group and the HgCl(2) + NAC group. The non-sulphydryl-containing antioxidants desferrioxamine and pyruvate demonstrated a similar effect in inhibiting HgCl(2)-induced early vasculitis. Our data show that administration of an antioxidant to BN rats reduces HgCl(2)-induced early vasculitis, suggesting that oxidative stress plays a role in the pathogenesis of HgCl(2)-induced early vasculitis. This finding may have implications for the understanding of the initiation in this experimental model of T(h)2 cell-driven autoimmunity and possibly of analogous human diseases.

Acetylcysteine↗