A metabolomic, geographic, and seasonal analysis of the contribution of pollen-derived adenosine to allergic sensitization

Background Studies on ragweed and birch pollen extracts suggested that the adenosine content is an important factor in allergic sensitization. However, exposure levels from other pollens and considerations of geographic and seasonal factors have not been evaluated. Objective This study compared the metabolite profile of pollen species important for allergic disease, specifically measured the adenosine content, and evaluated exposure to pollen-derived adenosine. Methods An NMR metabolomics approach was used to measure metabolite concentrations in twenty-six pollen extracts. Pollen count data was analyzed from five cities to model exposure. Results A principal component analysis of the various metabolites identified by NMR showed that pollen extracts could be differentiated primarily by sugar content: glucose, fructose, sucrose, and myo-inositol. In extracts of 10 mg of pollen/ml, the adenosine was highest for grasses (45 μM) followed by trees (23 μM) and weeds (19 μM). Pollen count data showed that tree pollen was typically 5–10 times the amount of other pollens. At the daily peaks of tree, grass, and weed season the pollen-derived adenosine exposure per day is likely to only be 1.1, 0.11, and 0.12 μg, respectively. Seasonal models of pollen exposure and respiration suggest that it would be a rare event limited to tree pollen season for concentrations of pollen-derived adenosine to approach physiological levels. Conclusions Sugar content and other metabolites may be useful in classifying pollens. Unless other factors create localized exposures that are very different from these models, pollen-derived adenosine is unlikely to be a major factor in allergic sensitization

The Quark-Photon Vertex and the Pion Charge Radius

The rainbow truncation of the quark Dyson-Schwinger equation is combined with the ladder Bethe-Salpeter equation for the dressed quark-photon vertex to study the low-momentum behavior of the pion electromagnetic form factor. With model gluon parameters previously fixed by the pion mass and decay constant, the pion charge radius $r_\pi$ is found to be in excellent agreement with the data. When the often-used Ball-Chiu Ansatz is used to construct the quark-photon vertex directly from the quark propagator, less than half of $r_\pi^2$ is generated. The remainder of $r^2_\pi$ is seen to be attributable to the presence of the $\rho$-pole in the solution of the ladder Bethe-Salpeter equation.Comment: 21 pages, 9 figure

Adiabatic Pair Creation

We give here the proof that pair creation in a time dependent potentials is possible. It happens with probability one if the potential changes adiabatically in time and becomes overcritical, that is when an eigenvalue enters the upper spectral continuum. The potential may be assumed to be zero at large negative and positive times. The rigorous treatment of this effect has been lacking since the pioneering work of Beck, Steinwedel and Suessmann in 1963 and Gershtein and Zeldovich in 1970.Comment: 53 pages, 1 figure. Editorial changes on page 22 f

Synthesis of Organosilicon Ligands for Europium (III) and Gadolinium (III) as Potential Imaging Agents

The relaxivity of MRI contrast agents can be increased by increasing the size of the contrast agent and by increasing concentration of the bound gadolinium. Large multi-site ligands able to coordinate several metal centres show increased relaxivity as a result. In this paper, an “aza-type Michael” reaction is used to prepare cyclen derivatives that can be attached to organosilicon frameworks via hydrosilylation reactions. A range of organosilicon frameworks were tested including silsesquioxane cages and dimethylsilylbenzene derivatives. Michael donors with strong electron withdrawing groups could be used to alkylate cyclen on three amine centres in a single step. Hydrosilylation successfully attached these to mono-, di-, and tri-dimethylsilyl-substituted benzene derivatives. The europium and gadolinium complexes were formed and studied using luminescence spectroscopy and relaxometry. This showed the complexes to contain two bound water moles per lanthanide centre and T1 relaxation time measurements demonstrated an increase in relaxivity had been achieved, in particular for the trisubstituted scaffold 1,3,5-tris((pentane-sDO3A)dimethylsilyl)benzene-Gd3. This showed a marked increase in the relaxivity (13.1 r1p/mM−1s−1)

miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice

Excessive or inappropriate activation of the immune system can be deleterious to the organism, warranting multiple molecular mechanisms to control and properly terminate immune responses. MicroRNAs (miRNAs), ~22-nt-long noncoding RNAs, have recently emerged as key posttranscriptional regulators, controlling diverse biological processes, including responses to non-self. In this study, we examine the biological role of miR-146a using genetically engineered mice and show that targeted deletion of this gene, whose expression is strongly up-regulated after immune cell maturation and/or activation, results in several immune defects. Collectively, our findings suggest that miR-146a plays a key role as a molecular brake on inflammation, myeloid cell proliferation, and oncogenic transformation

The Angular Correlation Function of Galaxies from Early SDSS Data

The Sloan Digital Sky Survey is one of the first multicolor photometric and spectroscopic surveys designed to measure the statistical properties of galaxies within the local Universe. In this Letter we present some of the initial results on the angular 2-point correlation function measured from the early SDSS galaxy data. The form of the correlation function, over the magnitude interval 18<r*<22, is shown to be consistent with results from existing wide-field, photographic-based surveys and narrower CCD galaxy surveys. On scales between 1 arcminute and 1 degree the correlation function is well described by a power-law with an exponent of ~ -0.7. The amplitude of the correlation function, within this angular interval, decreases with fainter magnitudes in good agreement with analyses from existing galaxy surveys. There is a characteristic break in the correlation function on scales of approximately 1-2 degrees. On small scales, < 1', the SDSS correlation function does not appear to be consistent with the power-law form fitted to the 1'< theta <0.5 deg data. With a data set that is less than 2% of the full SDSS survey area, we have obtained high precision measurements of the power-law angular correlation function on angular scales 1' < theta < 1 deg, which are robust to systematic uncertainties. Because of the limited area and the highly correlated nature of the error covariance matrix, these initial results do not yet provide a definitive characterization of departures from the power-law form at smaller and larger angles. In the near future, however, the area of the SDSS imaging survey will be sufficient to allow detailed analysis of the small and large scale regimes, measurements of higher-order correlations, and studies of angular clustering as a function of redshift and galaxy type

What is the economic cost of providing an all Wales postpartum haemorrhage quality improvement initiative (OBS Cymru)? A cost-consequences comparison with standard care

Background and Objective: A postpartum haemorrhage quality improvement initiative (the Obstetric Bleeding Strategy for Wales [OBS Cymru]), including about 60,000 maternities, was adopted across Wales (2017–2018). We performed a cost-consequences analysis to inform ongoing provision and wider uptake. Methods: Analysis was based on primary data from the All Wales postpartum haemorrhage database, with a UK National Health Services perspective, a time horizon from delivery until hospital discharge and no discounting. Costs were based on UK published sources with viscoelastic haemostatic assay costs provided by the OBS Cymru national team. Mean costs per eligible patient (postpartum haemorrhage > 1000 mL) were calculated for OBS Cymru, using the early implementation period as a comparator. Modelling allowed comparisons of three scenarios (two predefined and one post hoc) and implementation in different sizes of maternity unit. Results: All analyses demonstrated consistent savings in blood products, critical care and haematology time, and also a reduced occurrence of massive postpartum haemorrhage (> 2500 mL). Incremental postnatal length of stay varied between scenarios, substantially impacting on total costs. Mean incremental cost of OBS Cymru, compared with standard care, across Wales was £18.41 per patient (postpartum haemorrhage > 1000 mL) or − £10.66 if the length of stay was excluded. Modelling a maternity unit of 5000 births per annum, OBS Cymru incurred an incremental cost of £9.53 per patient with postpartum haemorrhage > 1000 mL. Conclusions: OBS Cymru reduces the occurrence of massive postpartum haemorrhage, need for transfusions, quantity of blood products and intensive care. In medium-to-large maternity units (>3000 maternities per annum), the OBS Cymru intervention approaches cost neutrality compared to standard care

Prostaglandin E2 stimulates Fas ligand expression via the EP1 receptor in colon cancer cells

Fas ligand (FasL/CD95L) is a member of the tumour necrosis factor superfamily that triggers apoptosis following crosslinking of the Fas receptor. Despite studies strongly implicating tumour-expressed FasL as a major inhibitor of the anti-tumour immune response, little is known about the mechanisms that regulate FasL expression in tumours. In this study, we show that the cyclooxygenase (COX) signalling pathway, and in particular prostaglandin E2 (PGE2), plays a role in the upregulation of FasL expression in colon cancer. Suppression of either COX-2 or COX-1 by RNA interference in HCA-7 and HT29 colon tumour cells reduced FasL expression at both the mRNA and protein level. Conversely, stimulation with PGE2 increased FasL expression and these cells showed increased cytotoxicity against Fas-sensitive Jurkat T cells. Prostaglandin E2-induced FasL expression was mediated by signalling via the EP1 receptor. Moreover, immunohistochemical analysis using serial sections of human colon adenocarcinomas revealed a strong positive correlation between COX-2 and FasL (r=0.722; P<0.0001) expression, and between EP1 receptor and FasL (r=0.740; P<0.0001) expression, in the tumour cells. Thus, these findings indicate that PGE2 positively regulates FasL expression in colon tumour cells, adding another pro-neoplastic activity to PGE2