Unimolecular reaction chemistry of a charge-tagged beta-hydroxyperoxyl radical

β-Hydroxyperoxyl radicals are formed during atmospheric oxidation of unsaturated volatile organic compounds such as isoprene. They are intermediates in the combustion of alcohols. In these environments the unimolecular isomerization and decomposition of β-hydroxyperoxyl radicals may be of importance, either through chemical or thermal activation. We have used ion-trap mass spectrometry to generate the distonic charge-tagged β-hydroxyalkyl radical anion, ˙CH2C(OH)(CH3)CH2C(O)O−, and investigated its subsequent reaction with O2 in the gas phase under conditions that are devoid of complicating radical–radical reactions. Quantum chemical calculations and master equation/RRKM theory modeling are used to rationalize the results and discern a reaction mechanism. Reaction is found to proceed via initial hydrogen abstraction from the γ-methylene group and from the β-hydroxyl group, with both reaction channels eventually forming isobaric product ions due to loss of either ˙OH + HCHO or ˙OH + CO2. Isotope labeling studies confirm that a 1,5-hydrogen shift from the β-hydroxyl functionality results in a hydroperoxyalkoxyl radical intermediate that can undergo further unimolecular dissociations. Furthermore, this study confirms that the facile decomposition of β-hydroxyperoxyl radicals can yield ˙OH in the gas phase.

Spatial distribution of selected persistent organic pollutants (POPs) in Australia's atmosphere

A nation-wide passive air sampling campaign recorded concentrations of persistent organic pollutants in Australia's atmosphere in 2012. XAD-based passive air samplers were deployed for one year at 15 sampling sites located in remote/background, agricultural and semi-urban and urban areas across the continent. Concentrations of 47 polychlorinated biphenyls ranged from 0.73 to 72 pg m-3 (median of 8.9 pg m-3) and were consistently higher at urban sites. The toxic equivalent concentration for the sum of 12 dioxin-like PCBs was low, ranging from below detection limits to 0.24 fg m-3 (median of 0.0086 fg m-3). Overall, the levels of polychlorinated biphenyls in Australia were among the lowest reported globally to date. Among the organochlorine pesticides, hexachlorobenzene had the highest (median of 41 pg m-3) and most uniform concentration (with a ratio between highest and lowest value [similar]5). Bushfires may be responsible for atmospheric hexachlorobenzene levels in Australia that exceeded Southern Hemispheric baseline levels by a factor of [similar]4. Organochlorine pesticide concentrations generally increased from remote/background and agricultural sites to urban sites, except for high concentrations of [small alpha]-endosulfan and DDTs at specific agricultural sites. Concentrations of heptachlor (0.47-210 pg m-3), dieldrin (ND-160 pg m-3) and trans- and cis-chlordanes (0.83-180 pg m-3, sum of) in Australian air were among the highest reported globally to date, whereas those of DDT and its metabolites (ND-160 pg m-3, sum of), [small alpha]-, [small beta]-, [gamma]- and [small delta]-hexachlorocyclohexane (ND-6.7 pg m-3, sum of) and [small alpha]-endosulfan (ND-27 pg m-3) were among the lowest.

Changes in lycopene and beta carotene contents in aril and oil of gac fruit during storage

Gac fruits were physically measured and stored under ambient conditions for up to 2 weeks to observe changes in carotenoid contents (lycopene and beta carotene) in its aril. Initial concentrations in the aril of lycopene were from 2.378 mg/g fresh weight (FW) to 3.728 mg/g FW and those of beta carotene were from 0.257 to 0.379 mg/g FW. Carotenoid concentrations in the aril remained stable after 1 week but sharply declined after 2 weeks of storage. Gac oil, pressed from gac aril, has similar concentrations of lycopene and beta carotene (2.436 and 2.592 mg/g, respectively). Oil was treated with 0.02% of butylated hydroxytoluene, or with a stream of nitrogen or untreated then stored in the dark for up to 15 or 19 weeks under different temperatures (5 °C, ambient, 45 and 60 °C). Lycopene and beta carotene in control gac oil degraded following the first-order kinetic model. The degradation rate of lycopene and beta carotene in the treated oil samples were lower than that in the control oil but the first-order kinetic was not always followed. However, both lycopene and beta carotene degraded quickly in gac oil with the first-order kinetic under high temperature conditions (45 and 60 °C) regardless of the treatments used. © 2009 Elsevier Ltd. All rights reserved.

A new regulatory variant in the interleukin-6 receptor gene associates with asthma risk

The main genetic determinant of soluble interleukin 6 receptor (sIL-6R) levels is the missense variant rs2228145 that maps to the cleavage site of IL-6R. For each Ala allele, sIL-6R serum levels increase by ∼20 ng ml -1 and asthma risk by 1.09-fold. However, this variant does not explain the total heritability for sIL-6R levels. Additional independent variants in IL6R may therefore contribute to variation in sIL-6R levels and influence asthma risk. We imputed 471 variants in IL6R and tested these for association with sIL-6R serum levels in 360 individuals. An intronic variant (rs12083537) was associated with sIL-6R levels independently of rs4129267 (P=0.0005), a proxy single-nucleotide polymorphism for rs2228145. A significant and consistent association for rs12083537 was observed in a replication panel of 354 individuals (P=0.033). Each rs12083537:A allele increased sIL-6R serum levels by 2.4 ng ml -1. Analysis of mRNA levels in two cohorts did not identify significant associations between rs12083537 and IL6R transcription levels. On the other hand, results from 16 705 asthmatics and 30 809 controls showed that the rs12083537:A allele increased asthma risk by 1.04-fold (P=0.0419). Genetic risk scores based on IL6R regulatory variants may prove useful in explaining variation in clinical response to tocilizumab, an anti-IL-6R monoclonal antibody.

Immunopathogenesis of ankylosing spondylitis

Ankylosing spondylitis is a model immunogenetic disease with major common and rare genetic risk factors, likely environmental contributors to its pathogenesis and, to date, no treatment that has been shown to induce disease remission in long-term studies. The discovery of the association of HLA-B27 with the disease in the early 1970s triggered extensive efforts to elucidate the mechanism of this association. However, the precise role of HLA-B27 in ankylosing spondylitis pathogenesis remains unclear. In recent years, rapid progress made in the discovery of non-MHC genes involved in susceptibility to ankylosing spondylitis has combined with increasing ability to investigate the immune system to make rapid progress in unraveling the etiopathogenesis of the condition. © 2013 Future Medicine Ltd.

Editorial for Journal of Learning Design, 6(3) - "Special issue: Legal education and curriculum renewal"

Welcome to this special edition of the Journal of Learning Design which focuses on legal education and curriculum renewal in law. At the outset ,we would like to thank the editors of the Journal, Margaret Lloyd and Nan Bahr for agreeing to host this special edition. The special edition is timely as legal education in Australia is enjoying a lively period of renewal.

Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility

Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 × 10-8 in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 × 10-6 overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27-positive individuals. These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides.

Suggestive linkage of the parathyroid receptor type 1 to osteoporosis

We have investigated the role of 23 candidate genes in the control of bone mineral density (BMD) by linkage studies in families of probands with osteoporosis (lumbar spine [LS] or femoral neck [FN] BMD T score < -2.5) and low BMD relative to an age- and gender-matched cohort (Z score < -2.0). One hundred and fifteen probands (35 male, 80 female) and 499 of their first- or second-degree relatives (223 males and 276 females) were recruited for the study. BMD was measured at the LS and FN using dual-energy X-ray absorptiometry and expressed as age- and gender-matched Z scores corrected for body mass index. The candidate genes studied were the androgen receptor, type I collagen A1 (COLIA1), COLIA2, COLIIA1, vitamin D receptor (VDR), colony-stimulating factor 1, calcium-sensing receptor, epidermal growth factor (EGF), estrogen receptor 1 (ESR1), fibrillin type 1, insulin-like growth factor 1, interleukin-1 alpha (IL-1α), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-11 (IL-11), osteopontin, parathyroid hormone (PTH), PTH-related peptide, PTH receptor type 1 (PTHR1), transforming growth factor-beta 1, and tumor necrosis factors alpha and beta. Sixty-four microsatellites lying close to or within these genes were investigated for linkage with BMD. Using the program MapMaker/Sibs there was suggestive evidence of linkage between BMD and PTHR1 (maximum LOD score obtained [MLS] 2.7-3.5). Moderate evidence of linkage was also observed with EGF (MLS 1.8), COLIA1 (MLS 1.7), COLIIA1/VDR (MLS 1.7), ESR1 (MLS 1.4), IL-1α (MLS 1.4), IL-4 (MLS 1.2), and IL-6 (MLS 1.2). Variance components analysis using the program ACT, correcting for proband-wise ascertainment, also showed evidence of linkage (p ≤0.05) at markers close to or within the candidate genes IL- 1α, PTHR1, IL-6, and COLIIA1/VDR. Further studies will be required to confirm these findings, to refine the location of gene responsible for the observed linkage, and to screen the candidate genes targeted at these loci for mutations.

Evolution of multivariant microstructures with anisotropic misfit: A phase field study

We study, in two dimensions, the effect of misfit anisotropy on microstructural evolution during precipitation of an ordered beta phase from a disordered alpha matrix; these phases have, respectively, 2- and 6-fold rotation symmetries. Thus, precipitation produces three orientational variants of beta phase particles, and they have an anisotropic (and crystallographically equivalent) misfit strain with the matrix. The anisotropy in misfit is characterized using a parameter t = epsilon(yy)/epsilon(xx), where epsilon(xx) and epsilon(yy) are the principal components of the misfit strain tensor. Our phase field, simulations show that the morphology of beta phase particles is significantly influenced by 1, the level of misfit anisotropy. Particles are circular in systems with dilatational misfit (t = 1), elongated along the direction of lower principal misfit when 0 < t < 1 and elongated along the invariant direction when - 1 <= t <= 0. In the special case of a pure shear misfit strain (t = - 1), the microstructure exhibits star, wedge and checkerboard patterns; these microstructural features are in agreement with those in Ti-Al-Nb alloys.

Beta-Turn Conformations In Crystal-Structures Of Model Peptides Containing Alpha,Alpha-Di-N-Propylglycine And Alpha,Alpha-Di-N-Butylglycine

The crystal state conformations of three peptides containing the alpha, alpha-dialkylated residues, alpha,alpha-di-n-propylglycine (Dpg) and alpha,alpha-di-n-butylglycine (Dbg), have been established by x-ray diffraction. Boc-Ala-Dpg-Ala-OMe (I) and Boc-Ala-Dbg-Ala-OMe (III) adopt distorted type II beta-turn conformations with Ala (1) and Dpg/Dbg (2) as the corner residues. In both peptides the conformational angles at the Dxg residue (I: phi = 66.2 degrees, psi = 19.3 degrees; III: phi = 66.5 degrees, psi = 21.1 degrees) deviate appreciably from ideal values for the i + 2 residue in a type II beta-turn. In both peptides the observed (N...O) distances between the Boc CO and Ala(3) NH groups are far too long (I: 3.44 Angstrom; III: 3.63 Angstrom) for an intramolecular 4 --> 1 hydrogen bond. Boc-Ala-Dpg-Ala-NHMe (II) crystallizes with two independent molecules in the asymmetric unit. Both molecules IIA and IIB adopt consecutive beta-turn (type III-III in IIA and type III-I in IIB) or incipient 3(10)-helical structures, stabilized by two intramolecular 4 --> 1 hydrogen bonds. In all four molecules the bond angle N-C-alpha-C' (tau) at the Dxg residues are greater than or equal to 110 degrees. The observation of conformational angles in the helical region of phi,psi space at these residues is consistent with theoretical predictions.

Spectroscopic studies of the interactions of the pyrethroid insecticide fenvalerate with gramicidin

Fenvalerate is a pyrethroid insecticide which interacts with ionic channels. Using circular dichroism technique we have studied the interaction of fenvalerate with gramicidin, a model channel peptide which transports ions. In most organic solvents, gramicidin exists as a double helix except in trifluoroethanol where it exists as a channel forming single stranded beta(6.3) helical monomer. In model lipid membranes, under certain experimental conditions, gramicidin exists as a channel forming single stranded beta(6.3) helical dimer. Our results show that fenvalerate interacts more with the single stranded beta(6.3) helical monomer or dimer than with the double helical form of gramicidin. This was further confirmed by an increase in the rate of gramicidin mediated proton transport in liposomes by fenvalerate, using the pH sensitive fluorophore, pyranine.

A New Method For The Generation Of 5,6-Quinolinedione 5-Methide .5. Synthesis Of Polycyclic Heteroaromatics

Reaction of 6-acetoxy-5-bromomethylquinoline (1c) and 2-bromomethyl-4-(2'-pyridyl)phenyl acetate (2b) with tetrachlorocatechol in acetone in the presence of anhydrous potassium carbonate resulted in the formation of diastereomeric products 3c, 3d, 4e and 4f.

An asymmetric homodinuclear complex containing the mu-x-oxobis(mu-x-carboxylato)diruthenium(III) core: X-ray structure of [Ru20(o2ec6H4-p-OMe)3(en) (PPh3)2] (C104)" 3CHC13

Asymmetric tri-bridged diruthenium(III) complexes, [Ru2O(O(2)CR)(3)(en) (PPh(3))(2)](ClO4) (R = C6H4-p-X: X = OMe (1a), Me (1b); en=1,2-diaminoethane), were prepared and structurally characterized. Complex 1a 3CHCl(3), crystallizes in the triclinic space group P (1) over bar with a = 14.029(5), b = 14.205(5), c = 20.610(6) Angstrom, alpha= 107.26(3), beta = 101.84(3), gamma= 97.57(3)degrees, V= 3756(2) Angstrom(3) and Z = 2. The complex has an {Ru-2(mu-O)(mu-O(2)CR)(2)(2+)} core and exhibits [O4PRu(mu-O)RuPO2N2](+) coordination environments for the metal centers. The novel structural feature is the asymmetric arrangement of ligands at the terminal sites of the core which shows an Ru... Ru separation of 3.226(3) Angstrom and an Ru-O-Ru angle of 119.2(5)degrees. An intense visible band observed near 570 nm is assigned to a charge transfer transition involving the d pi-Ru(III) and p pi-mu-O Orbitals. Cyclic voltammetry of the complexes displays a reversible Ru-2(III,III) reversible arrow Ru-2(III,IV) couple near 0.8 V (versus SCE) in MeCN-0.1 M TBAP.

Homology between jacalin and artocarpin from jackfruit (Artocarpus integrifolia) seeds. Partial sequence and preliminary crystallographic studies of artocarpin

Jacalin and artocarpin, the two lectins from jackfruit (Artocarpus integrifolia) seeds, have different physicochemical properties and carbohydrate-binding specificities. However, comparison of the partial amino-acid sequence of artocarpin with the known sequence of jacalin indicates close to 50% sequence identity. Artocarpin crystallizes in two forms, both monoclinic P2(1), with one and two tetramic molecules, respectively, in the asymmetric units of form I (a = 69.9, b = 73.7, c = 60.6 Angstrom and beta = 95.1 degrees) and form II (a = 87.6, b = 72.2, c = 92.6 Angstrom and beta = 101.1 degrees). Both the crystal structures have been solved by the molecular replacement method using the known structure of jacalin as the search model and ope of them partially refined, confirming that the two lectins are indeed homologous.

Expression, Purification and Characterization of Peanut (Arachis hypogaea) Agglutinin (PNA) from Baculovirus Infected Insect Cells

Peanut (Arachis hypogaea) seed lectin, PNA is widely used to identify tumor specific antigen (T-antigen), Gal beta 1-3GalNAc on the eukaryotic cell surface. The functional amino acid coding region of a cDNA clone, pBSH-PN was PCR amplified and cloned downstream of the polyhedrin promoter in the Autographa californica nucleopolyhedrovirus (AcNPV) based transfer vector pVL1393. Co-transfection of Spodoptera frugiperda cells (Sf9) with the transfer vector, pAcPNA and AcRP6 (a recombinant AcNPV having B-gal downstream of the polyhedrin promoter) DNAs produced a recombinant virus, AcPNA which expresses PNA. Infection of suspension culture of Sf9 cells with plaque purified AcPNA produced as much as 9.8 mg PNA per liter (2.0 x 10(6) cells/ml) of serum-free medium. Intracellularly expressed protein (re-PNA) was purified to apparent homogeneity by affinity chromatography using ECD-Sepharose. Polyclonal antibodies against natural PNA (n-PNA) crossreacted with re-PNA. The subunit molecular weight (30 kDa), hemagglutination activity, and carbohydrate specificity of re-PNA were found to be identical to that of n-PNA, thus confirming the abundant production of a functionally active protein in the baculovirus expression system.