Intimal smooth muscle cells are a source but not a sensor of anti-inflammatory CYP450 derived oxylipins

AbstractVascular pathologies are associated with changes in the presence and expression of morphologically distinct vascular smooth muscle cells. In particular, in complex human vascular lesions and models of disease in pigs and rodents, an intimal smooth muscle cell (iSMC) which exhibits a stable epithelioid or rhomboid phenotype in culture is often found to be present in high numbers, and may represent the reemergence of a distinct developmental vascular smooth muscle cell phenotype. The CYP450-oxylipin - soluble epoxide hydrolase (sEH) pathway is currently of great interest in targeting for cardiovascular disease. sEH inhibitors limit the development of hypertension, diabetes, atherosclerosis and aneurysm formation in animal models. We have investigated the expression of CYP450-oxylipin-sEH pathway enzymes and their metabolites in paired intimal (iSMC) and medial (mSMC) cells isolated from rat aorta. iSMC basally released significantly larger amounts of epoxy-oxylipin CYP450 products from eicosapentaenoic acid > docosahexaenoic acid > arachidonic acid > linoleic acid, and expressed higher levels of CYP2C12, CYP2B1, but not CYP2J mRNA compared to mSMC. When stimulated with the pro-inflammatory TLR4 ligand LPS, epoxy-oxylipin production did not change greatly in iSMC. In contrast, LPS induced epoxy-oxylipin products in mSMC and induced CYP2J4. iSMC and mSMC express sEH which metabolizes primary epoxy-oxylipins to their dihydroxy-counterparts. The sEH inhibitors TPPU or AUDA inhibited LPS-induced NFκB activation and iNOS induction in mSMC, but had no effect on NFκB nuclear localization or inducible nitric oxide synthase in iSMC; effects which were recapitulated in part by addition of authentic epoxy-oxylipins. iSMCs are a rich source but not a sensor of anti-inflammatory epoxy-oxylipins. Complex lesions that contain high levels of iSMCs may be more resistant to the protective effects of sEH inhibitors

Vacuum ultraviolet instrumentation for solar irradiance and thermospheric airglow

A NASA sounding rocket experiment was developed to study the solar extreme ultraviolet (EUV) spectral irradiance and its effect on the upper atmosphere. Both the solar flux and the terrestrial molecular nitrogen via the Lyman-Birge-Hopfield bands in the far ultraviolet (FUV) were measured remotely from a sounding rocket on October 27, 1992. The rocket experiment also includes EUV instruments from Boston University (Supriya Chakrabarti), but only the National Center for Atmospheric Research (NCAR)/University of Colorado (CU) four solar instruments and one airglow instrument are discussed here. The primary solar EUV instrument is a 1/4 meter Rowland circle EUV spectrograph which has flown on three rockets since 1988 measuring the solar spectral irradiance from 30 to 110 nm with 0.2 nm resolution. Another solar irradiance instrument is an array of six silicon XUV photodiodes, each having different metallic filters coated directly on the photodiodes. This photodiode system provides a spectral coverage from 0.1 to 80 nm with about 15 nm resolution. The other solar irradiance instrument is a silicon avalanche photodiode coupled with pulse height analyzer electronics. This avalanche photodiode package measures the XUV photon energy providing a solar spectrum from 50 to 12,400 eV (25 to 0.1 nm) with an energy resolution of about 50 eV. The fourth solar instrument is an XUV imager that images the sun at 17.5 nm with a spatial resolution of 20 arc-seconds. The airglow spectrograph measures the terrestrial FUV airglow emissions along the horizon from 125 to 160 nm with 0.2 nm spectral resolution. The photon-counting CODACON detectors are used for three of these instruments and consist of coded arrays of anodes behind microchannel plates. The one-dimensional and two-dimensional CODACON detectors were developed at CU by Dr. George Lawrence. The pre-flight and post-flight photometric calibrations were performed at our calibration laboratory and at the Synchrotron Ultraviolet Radiation Facility (SURF) at the National Institute of Standards and Technology (NIST) in Gaithersburg, Maryland

The phase diagrams of KCaF3 and NaMgF3 by ab initio simulations

ABF3 compounds have been found to make valuable low-pressure analogues for high-pressure silicate phases that are present in the Earth’s deep interior and that may also occur in the interiors of exoplanets. The phase diagrams of two of these materials, KCaF3 and NaMgF3, have been investigated in detail by static ab initio computer simulations based on density functional theory. Six ABF3 polymorphs were considered, as follows: the orthorhombic perovskite structure (GdFeO3-type; space group Pbnm); the orthorhombic CaIrO3 structure (Cmcm; commonly referred to as the “post-perovskite” structure); the orthorhombic Sb2S3 and La2S3 structures (both Pmcn); the hexagonal structure previously suggested in computer simulations of NaMgF3 (P63/mmc); the monoclinic structure found to be intermediate between the perovskite and CaIrO3 structures in CaRhO3 (P21/m). Volumetric and axial equations of state of all phases considered are presented. For KCaF3, as expected, the perovskite phase is shown to be the most thermodynamically stable at atmospheric pressure. With increasing pressure, the relative stability of the KCaF3 phases then follows the sequence: perovskite → La2S3 structure → Sb2S3 structure → P63/mmc structure; the CaIrO3 structure is never the most stable form. Above about 2.6 GPa, however, none of the KCaF3 polymorphs are stable with respect to dissociation into KF and CaF2. The possibility that high-pressure KCaF3 polymorphs might exist metastably at 300 K, or might be stabilised by chemical substitution so as to occur within the standard operating range of a multi-anvil press, is briefly discussed. For NaMgF3, the transitions to the high-pressure phases occur at pressures outside the normal range of a multi-anvil press. Two different sequences of transitions had previously been suggested from computer simulations. With increasing pressure, we find that the relative stability of the NaMgF3 phases follows the sequence: perovskite → CaIrO3 structure → Sb2S3 structure → P63/mmc structure. However, only the perovskite and CaIrO3 structures are stable with respect to dissociation into NaF and MgF2

Basal and inducible anti-inflammatory epoxygenase activity in endothelial cells

The roles of CYP lipid-metabolizing pathways in endothelial cells are poorly understood. Human endothelial cells expressed CYP2J2 and soluble epoxide hydrolase (sEH) mRNA and protein. The TLR-4 agonist LPS (1 μg/ml; 24 h) induced CYP2J2 but not sEH mRNA and protein. LC–MS/MS analysis of the stable commonly used human endothelial cell line EA.Hy926 showed active epoxygenase and epoxide hydrolase activity: with arachidonic acid (stable epoxide products 5,6-DHET, and 14,15-DHET), linoleic acid (9,10-EPOME and 12,13-EPOME and their stable epoxide hydrolase products 9,10-DHOME and 12,13-DHOME), docosahexaenoic acid (stable epoxide hydrolase product 19,20-DiHDPA) and eicosapentaenoic acid (stable epoxide hydrolase product 17,18-DHET) being formed. Inhibition of epoxygenases using either SKF525A or MS-PPOH induced TNFα release, but did not affect LPS, IL-1β, or phorbol-12-myristate-13-acetate (PMA)-induced TNFα release. In contrast, inhibition of soluble epoxide hydrolase by AUDA or TPPU inhibited basal, LPS, IL-1β and PMA induced TNFα release, and LPS-induced NFκB p65 nuclear translocation. In conclusion, human endothelial cells contain a TLR-4 regulated epoxygenase CYP2J2 and metabolize linoleic acid > eicosapentaenoic acid > arachidonic acid > docosahexaenoic acid to products with anti-inflammatory activity

Description and Status of the DC Lightning Mapping Array

The DC Lightning Mapping Array (DC LMA) centered on the Washington, DC metro region has been in operation since 2006. During that time the DC LMA has provided real time data to regional National Weather Service (NSF) Sterling, VA forecast office for operations support and the NOAA Meteorological Development Laboratory (MDL) for new product development and assessment. Data from this network (as well as other from other LMA systems) are now being used to create proxy Geostationary Lightning Mapper (GLM) data sets for GOES-R risk reduction and algorithm development activities. In addition, since spring 2009 data are provided to the Storm Prediction Center in support of Hazardous Weather Testbed and GOES-R Proving Ground activities during the Spring Program. Description, status and plans will be discussed

Improving the efficacy of selenium fertilizers for wheat biofortification

© 2019, The Author(s). Increasing the selenium (Se) concentration of staple crops by fertilization is a valuable pathway to increase Se in the human diet, thus preventing Se deficiency. A pot trial was set up to investigate whether the application of 3.33 µg kg−1 of Se (equivalent to 10 g ha−1) to wheat can be made more efficient by its co-application with macronutrient carriers, either to the soil or to the leaves. In the soil, Se was applied either on its own (selenate only) or as a granular, Se-enriched macronutrient fertilizer supplying nitrogen, phosphorus, potassium or sulfur. Selenium was also applied to leaves at head emergence with, or without, 2% w/v N fertilizers. With grain Se concentrations varying from 0.13–0.84 mg kg−1, soil application of selenate-only was 2–15 times more effective than granular Se-enriched macronutrient fertilizers in raising grain Se concentrations. Co-application of foliar Se with an N carrier doubled the Se concentration in wheat grains compared to the application of foliar Se on its own, the majority of which was in the highly bioavailable selenomethionine fraction. Results from this study demonstrate the possibility of improving the efficacy of Se fertilizers, which could enrich crops with Se without additional application costs in the field