Connections between Sphingosine Kinase and Phospholipase D in the Abscisic Acid Signaling Pathway in \u3ci\u3eArabidopsis\u3c/i\u3e

Background: Sphingosine kinase (SPHK) and phospholipaseD(PLD) produce different lipid mediators involved in abscisic acid (ABA) response. Results: Ablation of SPHKs and PLDα1 attenuates ABA-induced production of LCBPs and PA. Phyto-S1P closes stomata in sphk1, sphk2, but not in pldα1, whereas PA closes stomata in all mutants. Conclusion: SPHK acts upstream of PLDα1, whereas PLDα1 promotes SPHK. Significance: The roles of lipid messengers in the ABA signaling pathway are clarified

Synergistic HNO3-H2SO4-NH3 upper tropospheric particle formation

New particle formation in the upper free troposphere is a major global source of cloud condensation nuclei (CCN)(1-4). However, the precursorvapoursthat drive the process are not well understood. With experiments performed under upper tropospheric conditions in the CERN CLOUD chamber, we showthat nitric acid, sulfuric acid and ammonia form particles synergistically, at ratesthat are orders of magnitude faster than those from any two ofthe three components. The importance ofthis mechanism depends on the availability of ammonia, which was previously thought to be efficiently scavenged by cloud droplets during convection. However, surprisingly high concentrations of ammonia and ammonium nitrate have recently been observed in the uppertroposphere overthe Asian monsoon region(5,6). Once particles have formed, co-condensation of ammonia and abundant nitric acid alone is sufficient to drive rapid growth to CCN sizes with only trace sulfate. Moreover, our measurements showthat these CCN are also highly efficient ice nucleating particles-comparable to desert dust. Our model simulations confirm that ammonia is efficiently convected aloft during the Asian monsoon, driving rapid, multi-acid HNO3-H2SO4-NH3 nucleation in the uppertroposphere and producing ice nucleating particles that spread acrossthe mid-latitude Northern Hemisphere.Peer reviewe

Preclinical Evidence That Trametinib Enhances the Response to Antiangiogenic Tyrosine Kinase Inhibitors in Renal Cell Carcinoma.

Sunitinib and pazopanib are antiangiogenic tyrosine kinase inhibitors (TKI) used to treat metastatic renal cell carcinoma (RCC). However, the ability of these drugs to extend progression-free and overall survival in this patient population is limited by drug resistance. It is possible that treatment outcomes in RCC patients could be improved by rationally combining TKIs with other agents. Here, we address whether inhibition of the Ras-Raf-MEK-ERK1/2 pathway is a rational means to improve the response to TKIs in RCC. Using a xenograft model of RCC, we found that tumors that are resistant to sunitinib have a significantly increased angiogenic response compared with tumors that are sensitive to sunitinib in vivo. We also observed significantly increased levels of phosphorylated ERK1/2 in the vasculature of resistant tumors, when compared with sensitive tumors. These data suggested that the Ras-Raf-MEK-ERK1/2 pathway, an important driver of angiogenesis in endothelial cells, remains active in the vasculature of TKI-resistant tumors. Using an in vitro angiogenesis assay, we identified that the MEK inhibitor (MEKI) trametinib has potent antiangiogenic activity. We then show that, when trametinib is combined with a TKI in vivo, more effective suppression of tumor growth and tumor angiogenesis is achieved than when either drug is utilized alone. In conclusion, we provide preclinical evidence that combining a TKI, such as sunitinib or pazopanib, with a MEKI, such as trametinib, is a rational and efficacious treatment regimen for RCC

An intercomparison study of four different techniques for measuring the chemical composition of nanoparticles

Currently, the complete chemical characterization of nanoparticles (< 100 nm) represents an analytical challenge, since these particles are abundant in number but have negligible mass. Several methods for particle-phase characterization have been recently developed to better detect and infer more accurately the sources and fates of sub-100 nm particles, but a detailed comparison of different approaches is missing. Here we report on the chemical composition of secondary organic aerosol (SOA) nanoparticles from experimental studies of α-pinene ozonolysis at −50, −30, and −10 ∘C and intercompare the results measured by different techniques. The experiments were performed at the Cosmics Leaving OUtdoor Droplets (CLOUD) chamber at the European Organization for Nuclear Research (CERN). The chemical composition was measured simultaneously by four different techniques: (1) thermal desorption–differential mobility analyzer (TD–DMA) coupled to a NO$^-_3$ chemical ionization–atmospheric-pressure-interface–time-of-flight (CI–APi–TOF) mass spectrometer, (2) filter inlet for gases and aerosols (FIGAERO) coupled to an I$^−$ high-resolution time-of-flight chemical ionization mass spectrometer (HRToF-CIMS), (3) extractive electrospray Na$^+$ ionization time-of-flight mass spectrometer (EESI-TOF), and (4) offline analysis of filters (FILTER) using ultra-high-performance liquid chromatography (UHPLC) and heated electrospray ionization (HESI) coupled to an Orbitrap high-resolution mass spectrometer (HRMS). Intercomparison was performed by contrasting the observed chemical composition as a function of oxidation state and carbon number, by estimating the volatility and comparing the fraction of volatility classes, and by comparing the thermal desorption behavior (for the thermal desorption techniques: TD–DMA and FIGAERO) and performing positive matrix factorization (PMF) analysis for the thermograms. We found that the methods generally agree on the most important compounds that are found in the nanoparticles. However, they do see different parts of the organic spectrum. We suggest potential explanations for these differences: thermal decomposition, aging, sampling artifacts, etc. We applied PMF analysis and found insights of thermal decomposition in the TD–DMA and the FIGAERO

High Gas-Phase Methanesulfonic Acid Production in the OH-Initiated Oxidation of Dimethyl Sulfide at Low Temperatures

Dimethyl sulfide (DMS) influences climate via cloud condensation nuclei (CCN) formation resulting from its oxidation products (mainly methanesulfonic acid, MSA, and sulfuric acid, H2SO4). Despite their importance, accurate prediction of MSA and H2SO4from DMS oxidation remains challenging. With comprehensive experiments carried out in the Cosmics Leaving Outdoor Droplets (CLOUD) chamber at CERN, we show that decreasing the temperature from +25 to -10 °C enhances the gas-phase MSA production by an order of magnitude from OH-initiated DMS oxidation, while H2SO4production is modestly affected. This leads to a gas-phase H2SO4-to-MSA ratio (H2SO4/MSA) smaller than one at low temperatures, consistent with field observations in polar regions. With an updated DMS oxidation mechanism, we find that methanesulfinic acid, CH3S(O)OH, MSIA, forms large amounts of MSA. Overall, our results reveal that MSA yields are a factor of 2-10 higher than those predicted by the widely used Master Chemical Mechanism (MCMv3.3.1), and the NOxeffect is less significant than that of temperature. Our updated mechanism explains the high MSA production rates observed in field observations, especially at low temperatures, thus, substantiating the greater importance of MSA in the natural sulfur cycle and natural CCN formation. Our mechanism will improve the interpretation of present-day and historical gas-phase H2SO4/MSA measurements

High Gas-Phase Methanesulfonic Acid Production in the OH-Initiated Oxidation of Dimethyl Sulfide at Low Temperatures

Dimethyl sulfide (DMS) influences climate via cloud condensation nuclei (CCN) formation resulting from its oxidation products (mainly methanesulfonic acid, MSA, and sulfuric acid, H$_{2}$SO$_{4}$). Despite their importance, accurate prediction of MSA and H$_{2}$SO$_{4}$ from DMS oxidation remains challenging. With comprehensive experiments carried out in the Cosmics Leaving Outdoor Droplets (CLOUD) chamber at CERN, we show that decreasing the temperature from +25 to −10 °C enhances the gas-phase MSA production by an order of magnitude from OH-initiated DMS oxidation, while H$_{2}$SO$_{4}$ production is modestly affected. This leads to a gas-phase H$_{2}$SO$_{4}$-to-MSA ratio (H$_{2}$SO$_{4}$/MSA) smaller than one at low temperatures, consistent with field observations in polar regions. With an updated DMS oxidation mechanism, we find that methanesulfinic acid, CH$_{3}$S(O)OH, MSIA, forms large amounts of MSA. Overall, our results reveal that MSA yields are a factor of 2–10 higher than those predicted by the widely used Master Chemical Mechanism (MCMv3.3.1), and the NO$_{x}$ effect is less significant than that of temperature. Our updated mechanism explains the high MSA production rates observed in field observations, especially at low temperatures, thus, substantiating the greater importance of MSA in the natural sulfur cycle and natural CCN formation. Our mechanism will improve the interpretation of present-day and historical gas-phase H$_{2}$SO$_{4}$/MSA measurements

Synergistic HNO3_{3}–H2_{2}SO4_{4}–NH3_{3} upper tropospheric particle formation

New particle formation in the upper free troposphere is a major global source of cloud condensation nuclei (CCN)$^{1,2,3,4}$. However, the precursor vapours that drive the process are not well understood. With experiments performed under upper tropospheric conditions in the CERN CLOUD chamber, we show that nitric acid, sulfuric acid and ammonia form particles synergistically, at rates that are orders of magnitude faster than those from any two of the three components. The importance of this mechanism depends on the availability of ammonia, which was previously thought to be efficiently scavenged by cloud droplets during convection. However, surprisingly high concentrations of ammonia and ammonium nitrate have recently been observed in the upper troposphere over the Asian monsoon region5,6. Once particles have formed, co-condensation of ammonia and abundant nitric acid alone is sufficient to drive rapid growth to CCN sizes with only trace sulfate. Moreover, our measurements show that these CCN are also highly efficient ice nucleating particles—comparable to desert dust. Our model simulations confirm that ammonia is efficiently convected aloft during the Asian monsoon, driving rapid, multi-acid HNO$_{3}$–H$_{2}$SO$_{4}$–NH$_{3}$ nucleation in the upper troposphere and producing ice nucleating particles that spread across the mid-latitude Northern Hemisphere

Instrumentation and measurement strategy for the NOAA SENEX aircraft campaign as part of the Southeast Atmosphere Study 2013

Natural emissions of ozone-and-aerosol-precursor gases such as isoprene and monoterpenes are high in the southeastern US. In addition, anthropogenic emissions are significant in the southeastern US and summertime photochemistry is rapid. The NOAA-led SENEX (Southeast Nexus) aircraft campaign was one of the major components of the Southeast Atmosphere Study (SAS) and was focused on studying the interactions between biogenic and anthropogenic emissions to form secondary pollutants. During SENEX, the NOAA WP-3D aircraft conducted 20 research flights between 27 May and 10 July 2013 based out of Smyrna, TN. Here we describe the experimental approach, the science goals and early results of the NOAA SENEX campaign. The aircraft, its capabilities and standard measurements are described. The instrument payload is summarized including detection limits, accuracy, precision and time resolutions for all gas-and-aerosol phase instruments. The inter-comparisons of compounds measured with multiple instruments on the NOAA WP-3D are presented and were all within the stated uncertainties, except two of the three NO2 measurements. The SENEX flights included day- and nighttime flights in the southeastern US as well as flights over areas with intense shale gas extraction (Marcellus, Fayetteville and Haynesville shale). We present one example flight on 16 June 2013, which was a daytime flight over the Atlanta region, where several crosswind transects of plumes from the city and nearby point sources, such as power plants, paper mills and landfills, were flown. The area around Atlanta has large biogenic isoprene emissions, which provided an excellent case for studying the interactions between biogenic and anthropogenic emissions. In this example flight, chemistry in and outside the Atlanta plumes was observed for several hours after emission. The analysis of this flight showcases the strategies implemented to answer some of the main SENEX science questions.</p

High Gas-Phase Methanesulfonic Acid Production in the OH-Initiated Oxidation of Dimethyl Sulfide at Low Temperatures

Dimethyl sulfide (DMS) influences climate via cloud condensation nuclei (CCN) formation resulting from its oxidation products (mainly methanesulfonic acid, MSA, and sulfuric acid, H2SO4). Despite their importance, accurate prediction of MSA and H2SO4from DMS oxidation remains challenging. With comprehensive experiments carried out in the Cosmics Leaving Outdoor Droplets (CLOUD) chamber at CERN, we show that decreasing the temperature from +25 to -10 °C enhances the gas-phase MSA production by an order of magnitude from OH-initiated DMS oxidation, while H2SO4production is modestly affected. This leads to a gas-phase H2SO4-to-MSA ratio (H2SO4/MSA) smaller than one at low temperatures, consistent with field observations in polar regions. With an updated DMS oxidation mechanism, we find that methanesulfinic acid, CH3S(O)OH, MSIA, forms large amounts of MSA. Overall, our results reveal that MSA yields are a factor of 2-10 higher than those predicted by the widely used Master Chemical Mechanism (MCMv3.3.1), and the NOxeffect is less significant than that of temperature. Our updated mechanism explains the high MSA production rates observed in field observations, especially at low temperatures, thus, substantiating the greater importance of MSA in the natural sulfur cycle and natural CCN formation. Our mechanism will improve the interpretation of present-day and historical gas-phase H2SO4/MSA measurements.publishedVersionPeer reviewe

High Gas-Phase Methanesulfonic Acid Production in the OH-Initiated Oxidation of Dimethyl Sulfide at Low Temperatures

Dimethyl sulfide (DMS) influences climate via cloud condensation nuclei (CCN) formation resulting from its oxidation products (mainly methanesulfonic acid, MSA, and sulfuric acid, H2SO4). Despite their importance, accurate prediction of MSA and H2SO4from DMS oxidation remains challenging. With comprehensive experiments carried out in the Cosmics Leaving Outdoor Droplets (CLOUD) chamber at CERN, we show that decreasing the temperature from +25 to -10 °C enhances the gas-phase MSA production by an order of magnitude from OH-initiated DMS oxidation, while H2SO4production is modestly affected. This leads to a gas-phase H2SO4-to-MSA ratio (H2SO4/MSA) smaller than one at low temperatures, consistent with field observations in polar regions. With an updated DMS oxidation mechanism, we find that methanesulfinic acid, CH3S(O)OH, MSIA, forms large amounts of MSA. Overall, our results reveal that MSA yields are a factor of 2-10 higher than those predicted by the widely used Master Chemical Mechanism (MCMv3.3.1), and the NOxeffect is less significant than that of temperature. Our updated mechanism explains the high MSA production rates observed in field observations, especially at low temperatures, thus, substantiating the greater importance of MSA in the natural sulfur cycle and natural CCN formation. Our mechanism will improve the interpretation of present-day and historical gas-phase H2SO4/MSA measurements.Peer reviewe