Localization and production of peptide endocannabinoids in the rodent CNS and adrenal medulla.

The endocannabinoid system (ECS) comprises the cannabinoid receptors CB1 and CB2 and their endogenous arachidonic acid-derived agonists 2-arachidonoyl glycerol and anandamide, which play important neuromodulatory roles. Recently, a novel class of negative allosteric CB1 receptor peptide ligands, hemopressin-like peptides derived from alpha hemoglobin, has been described, with yet unknown origin and function in the CNS. Using monoclonal antibodies we now identified the localization of RVD-hemopressin (pepcan-12) and N-terminally extended peptide endocannabinoids (pepcans) in the CNS and determined their neuronal origin. Immunohistochemical analyses in rodents revealed distinctive and specific staining in major groups of noradrenergic neurons, including the locus coeruleus (LC), A1, A5 and A7 neurons, which appear to be major sites of production/release in the CNS. No staining was detected in dopaminergic neurons. Peptidergic axons were seen throughout the brain (notably hippocampus and cerebral cortex) and spinal cord, indicative of anterograde axonal transport of pepcans. Intriguingly, the chromaffin cells in the adrenal medulla were also strongly stained for pepcans. We found specific co-expression of pepcans with galanin, both in the LC and adrenal gland. Using LC-MS/MS, pepcan-12 was only detected in non-perfused brain (∼40 pmol/g), suggesting that in the CNS it is secreted and present in extracellular compartments. In adrenal glands, significantly more pepcan-12 (400-700 pmol/g) was measured in both non-perfused and perfused tissue. Thus, chromaffin cells may be a major production site of pepcan-12 found in blood. These data uncover important areas of peptide endocannabinoid occurrence with exclusive noradrenergic immunohistochemical staining, opening new doors to investigate their potential physiological function in the ECS. This article is part of a Special Issue entitled 'Fluorescent Neuro-Ligands'.

Search for pair and single production of new heavy quarks that decay to a ℤ boson and a third-generation quark in pp collisions at √ s=8 TeV with the ATLAS detector

A search is presented for the production of new heavy quarks that decay to a Z boson and a third-generation Standard Model quark. In the case of a new charge +2/3 quark (T), the decay targeted is T → Zt, while the decay targeted for a new charge −1/3 quark (B) is B → Zb. The search is performed with a dataset corresponding to 20.3 fb−1 of pp collisions at √ s = 8TeV recorded in 2012 with the ATLAS detector at the CERN Large Hadron Collider. Selected events contain a high transverse momentum Z boson candidate reconstructed from a pair of oppositely charged same-flavor leptons (electrons or muons), and are analyzed in two channels defined by the absence or presence of a third lepton. Hadronic jets, in particular those with properties consistent with the decay of a b-hadron, are also required to be present in selected events. Different requirements are made on the jet activity in the event in order to enhance the sensitivity to either heavy quark pair production mediated by the strong interaction, or single production mediated by the electroweak interaction. No significant excess of events above the Standard Model expectation is observed, and lower limits are derived on the mass of vector-like T and B quarks under various branching ratio hypotheses, as well as upper limits on the agnitude of electroweak coupling parameters.

Search for strong production of supersymmetric particles in final states with missing transverse momentum and at least three b-jets at √s= 8 TeV proton-proton collisions with the ATLAS detector

This paper reports the results of a search for strong production of supersymmetric particles in 20.1 fb−1 of proton-proton collisions at a centre-of-mass energy of 8TeV using the ATLAS detector at the LHC. The search is performed separately in events with either zero or at least one high-pT lepton (electron or muon), large missing transverse momentum, high jet multiplicity and at least three jets identified as originated from the fragmentation of a b-quark. No excess is observed with respect to the Standard Model predictions. The results are interpreted in the context of several supersymmetric models involving gluinos and scalar top and bottom quarks, as well as a mSUGRA/CMSSM model. Gluino masses up to 1340 GeV are excluded, depending on the model, significantly extending the previous ATLAS limits.

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at √s=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton-proton collision data at s√=8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t~→tχ~01 or t~→bχ~±1→bW(∗)χ~01, where χ~01 (χ~±1) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t~→tχ~01. For a branching fraction of 100%, top squark masses in the range 270-645 GeV are excluded for χ~01 masses below 30 GeV. For a branching fraction of 50% to either t~→tχ~01 or t~→bχ~±1, and assuming the χ~±1 mass to be twice the χ~01 mass, top squark masses in the range 250-550 GeV are excluded for χ~01 masses below 60 GeV.

Evidence for Electroweak Production of W±W±jj in pp Collisions at √s=8 TeV with the ATLAS Detector

This Letter presents the first study of W ± W ± jj , same-electric-charge diboson production in association with two jets, using 20.3  fb −1 of proton-proton collision data at s √ =8  TeV recorded by the ATLAS detector at the Large Hadron Collider. Events with two reconstructed same-charge leptons (e ± e ± , e ± μ ± , and μ ± μ ± ) and two or more jets are analyzed. Production cross sections are measured in two fiducial regions, with different sensitivities to the electroweak and strong production mechanisms. First evidence for W ± W ± jj production and electroweak-only W ± W ± jj production is observed with a significance of 4.5 and 3.6 standard deviations, respectively. The measured production cross sections are in agreement with standard model predictions. Limits at 95% confidence level are set on anomalous quartic gauge couplings

Search for direct production of charginos, neutralinos and sleptons in final states with two leptons and missing transverse momentum in pp collisions at √s = 8 TeV with the ATLAS detector

Searches for the electroweak production of charginos, neutralinos and sleptons in final states characterized by the presence of two leptons (electrons and muons) and missing transverse momentum are performed using 20.3 fb−1 of proton-proton collision data at ps = 8TeV recorded with the ATLAS experiment at the Large Hadron Collider. No significant excess beyond Standard Model expectations is observed. Limits are set on the masses of the lightest chargino, next-to-lightest neutralino and sleptons for different lightest-neutralino mass hypotheses in simplified models. Results are also interpreted in various scenarios of the phenomenological Minimal Supersymmetric Standard Model.

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in sqrts = 8TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three leptons and missing transverse momentum is presented. The analysis is based on 20.3 fb−1 of √s = 8TeV proton-proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with the Standard Model expectations and limits are set in R-parity-conserving phenomenological Minimal Supersymmetric Standard Models and in simplified supersymmetric models, significantly extending previous results. For simplified supersymmetric models of direct chargino (˜χ±1 ) and next-to-lightest neutralino (˜χ02) production with decays to lightest neutralino(˜χ01) via either all three generations of sleptons, staus only, gauge bosons, or Higgs bosons, ˜χ±1 and ˜χ02 masses are excluded up to 700GeV, 380GeV, 345GeV, or 148GeV respectively, for a massless ˜χ01.

Measurement of the production of a W boson in association with a charm quark in pp collisions at sqrts = 7 TeV with the ATLAS detector

The production of a W boson in association with a single charm quark is studied using 4.6 fb−1 of pp collision data at ps = 7TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a W boson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be 0.96+0.26−0.30 at Q2 = 1.9 GeV2, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally, the cross-section ratio ơ(W++c)/ơ(W−+c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about the s–s quark asymmetry.

Measurement of the electroweak production of dijets in association with a Z-boson and distributions sensitive to vector boson fusion in proton-proton collisions at √s = 8 TeV using the ATLAS detector

Measurements of fiducial cross sections for the electroweak production of two jets in association with a Z-boson are presented. The measurements are performed using 20.3 fb−1 of proton-proton collision data collected at a centre-of-mass energy of p s = 8TeV by the ATLAS experiment at the Large Hadron Collider. The electroweak component is extracted by a fit to the dijet invariant mass distribution in a fiducial region chosen to enhance the electroweak contribution over the dominant background in which the jets are produced via the strong interaction. The electroweak cross sections measured in two fiducial regions are in good agreement with the Standard Model expectations and the background-only hypothesis is rejected with significance above the 5ơ level. The electroweak process includes the vector boson fusion production of a Z-boson and the data are used to place limits on anomalous triple gauge boson couplings. In addition, measurements of cross sections and differential distributions for inclusive Z-boson-plus-dijet production are performed in five fiducial regions, each with different sensitivity to the electroweak contribution. The results are corrected for detector effects and compared to predictions from the Sherpa and Powheg event generators.

Refugee Settlement in Australia: Policy, Scholarship and the Production of Knowledge, 1952 − 2013

Since 1947, Australia has formally resettled more than 750,000 refugees. During that time, researchers have successfully completed more than 150 Masters and doctoral theses and published more than 900 articles, books and reports about issues of refugee settlement in Australia, with about half of them being published in the past 10 years. In this paper, we discuss the development of the production of knowledge about refugee resettlement. We identify trends in the literature, such as the emergence of an ethno-specific focus, and the concern with settlement's psychological and emotional impact, and relate them to policy changes. We suggest that scholars need critically to take stock of the knowledge produced so far and be more cognisant of the international scholarly debate.

L-mimosine increases the production of vascular endothelial growth factor in human tooth slice organ culture model.

AIM To assess the pro-angiogenic and pro-inflammatory capacity of the dentine-pulp complex in response to the prolyl hydroxylase inhibitor L-mimosine in a tooth slice organ culture model. METHODOLOGY Human teeth were sectioned transversely into 600-μm-thick slices and cultured in medium supplemented with serum and antibiotics. Then, pulps were stimulated for 48 h with L-mimosine. Pulps were subjected to viability measurements based on formazan formation in MTT assays. In addition, histological evaluation of pulps was performed based on haematoxylin and eosin staining. Culture supernatants were subjected to immunoassays for vascular endothelial growth factor (VEGF) to determine the pro-angiogenic capacity and to immunoassays for interleukin (IL)-6 and IL-8 to assess the pro-inflammatory response. Interleukin-1 served as pro-inflammatory control. Echinomycin was used to inhibit hypoxia-inducible factor-1 (HIF-1) alpha activity. Data were analysed using Student's t-test and Mann-Whitney U test. RESULTS Pulps within tooth slices remained vital upon L-mimosine stimulation as indicated by formazan formation and histological evaluation. L-mimosine increased VEGF production when normalized to formazan formation in the pulp tissue of the tooth slices (P < 0.05). This effect on VEGF was reduced by echinomycin (P < 0.01). Changes in normalized IL-6 and IL-8 levels upon treatment with L-mimosine did not reach the level of significance (P > 0.05), whilst treatment with IL-1, which served as positive control, increased IL-6 (P < 0.05) and IL-8 levels (P < 0.05). CONCLUSIONS The prolyl hydroxylase inhibitor L-mimosine increased VEGF production via HIF-1 alpha in the tooth slice organ culture model whilst inducing no prominent increase in IL-6 and IL-8. Pre-clinical studies will reveal if these in vitro effects translate into dental pulp regeneration.

Belowground ABA boosts aboveground production of DIMBOA and primes induction of chlorogenic acid in maize

Plants are important mediators between above- and belowground herbivores. Consequently, interactions between root and shoot defences can have far-reaching impacts on entire food webs. We recently reported that infestation of maize roots by the root feeding larvae of the beetle Diabrotica virgifera virgifera boosts shoot resistance against herbivores and pathogens. Root herbivory also induced DIMBOA levels and primed for enhanced induction of chlorogenic acid, two secondary metabolites that have been associated with biotic stress resistance. Interestingly, ABA emerged as a putative long-distance signal, possibly responsible for this effect. In this addendum, we investigate the role of root-derived ABA in the systemic regulation of aboveground DIMBOA, and the phenolic compounds chlorogenic acid, caffeic and ferulic acid. We discuss the relevance of the plant hormone in relation to defence against the leaf herbivore Spodoptera littoralis. Soil-drench treatment with ABA mimicked root herbivore-induced accumulation of DIMBOA in the leaves. Similarly, ABA mimicked aboveground priming of chlorogenic acid production, resulting in augmented accumulation of this compound upon subsequent shoot attack by S. littoralis. These findings confirm our notion that ABA acts as an important signal in the regulation of aboveground defence upon belowground herbivory. However, based on our previous finding that ABA alone is not sufficient to trigger aboveground resistance against S. littoralis caterpillars, the results suggest that the ABA-inducible effects on DIMBOA and chlorogenic acid are not solely responsible for root herbivore-induced resistance against S. littoralis. Full text HTML PDF