0000000000075923
AUTHOR
Rolf Müller
Evidence for heterogeneous chlorine activation in the tropical UTLS
Airborne in-situ observations of ClO in the tropics were made during the TROCCINOX (Aracatuba, Brazil, February 2005) and SCOUT-O<sub>3</sub> (Darwin, Australia, November/December 2005) field campaigns. While during most flights significant amounts of ClO (≈10–20 parts per trillion, ppt) were present only in aged stratospheric air, instances of enhanced ClO mixing ratios of up to 40 ppt – significantly exceeding those expected from gas phase chemistry – were observed in air masses of a more tropospheric character. Most of these observations are associated with low temperatures or with the presence of cirrus clouds (often both), suggesting that cirrus ice particles and/or liquid …
In situ observations of CH2Cl2 and CHCl3 show efficient transport pathways for very short-lived species into the lower stratosphere via the Asian and the North American summer monsoon
Efficient transport pathways for ozone-depleting very short-lived substances (VSLSs) from their source regions into the stratosphere are a matter of current scientific debate; however they have yet to be fully identified on an observational basis. Understanding the increasing impact of chlorine-containing VSLSs (Cl-VSLSs) on stratospheric ozone depletion is important in order to validate and improve model simulations and future predictions. We report on a transport study using airborne in situ measurements of the Cl-VSLSs dichloromethane (CH2Cl2) and trichloromethane (chloroform, CHCl3) to derive a detailed description of two transport pathways from (sub)tropical source regions into the ext…
Tropical troposphere to stratosphere transport of carbon monoxide and long-lived trace species in the Chemical Lagrangian Model of the Stratosphere (CLaMS)
Variations in the mixing ratio of trace gases of tropospheric origin entering the stratosphere in the tropics are of interest for assessing both troposphere to stratosphere transport fluxes in the tropics and the impact of these transport fluxes on the composition of the tropical lower stratosphere. Anomaly patterns of carbon monoxide (CO) and long-lived tracers in the lower tropical stratosphere allow conclusions about the rate and the variability of tropical upwelling to be drawn. Here, we present a simplified chemistry scheme for the Chemical Lagrangian Model of the Stratosphere (CLaMS) for the simulation, at comparatively low numerical cost, of CO, ozone, and long-lived trace substances…
Ribosome-Targeting Antibiotics Impair T Cell Effector Function and Ameliorate Autoimmunity by Blocking Mitochondrial Protein Synthesis
Summary While antibiotics are intended to specifically target bacteria, most are known to affect host cell physiology. In addition, some antibiotic classes are reported as immunosuppressive for reasons that remain unclear. Here, we show that Linezolid, a ribosomal-targeting antibiotic (RAbo), effectively blocked the course of a T cell-mediated autoimmune disease. Linezolid and other RAbos were strong inhibitors of T helper-17 cell effector function in vitro, showing that this effect was independent of their antibiotic activity. Perturbing mitochondrial translation in differentiating T cells, either with RAbos or through the inhibition of mitochondrial elongation factor G1 (mEF-G1) progressi…
Targeting cellular fatty acid synthesis limits T helper and innate lymphoid cell function during intestinal inflammation and infection
CD4+ T cells contribute critically to a protective immune response during intestinal infections, but have also been implicated in the aggravation of intestinal inflammatory pathology. Previous studies suggested that T helper type (Th)1 and Th17 cells depend on de novo fatty acid (FA) synthesis for their development and effector function. Here, we report that T-cell-specific targeting of the enzyme acetyl-CoA carboxylase 1 (ACC1), a major checkpoint controlling FA synthesis, impaired intestinal Th1 and Th17 responses by limiting CD4+ T-cell expansion and infiltration into the lamina propria in murine models of colitis and infection-associated intestinal inflammation. Importantly, pharmacolog…
Fast transport from Southeast Asia boundary layer sources to northern Europe: rapid uplift in typhoons and eastward eddy shedding of the Asian monsoon anticyclone
Abstract. Enhanced tropospheric trace gases such as CO, CH4 and H2O and reduced stratospheric O3 were measured in situ in the lowermost stratosphere over northern Europe on 26 September 2012 during the TACTS aircraft campaign. The measurements indicate that these air masses clearly differ from the stratospheric background. The calculation of 40-day backward trajectories with the trajectory module of the CLaMS model shows that these air masses are affected by the Asian monsoon anticyclone. Some air masses originate from the boundary layer in Southeast Asia/West Pacific and are rapidly lifted (1–2 days) within a typhoon up to the outer edge of the Asian monsoon anticyclone. Afterwards, the ai…
Induction of cholesterol biosynthesis by archazolid B in T24 bladder cancer cells.
Abstract Background Resistance of cancer cells towards chemotherapeutics represents a major cause of therapy failure. The objective of our study was to evaluate cellular defense strategies in response to the novel vacuolar H+-ATPase inhibitor, archazolid B. Experimental approach: The effects of archazolid B on T24 bladder carcinoma cells were investigated by combining “omics” technologies (transcriptomics (mRNA and miRNA) and proteomics). Free cholesterol distribution was determined by filipin staining using flow cytometry and fluorescence microscopy. Flow cytometry was performed for LDLR surface expression studies. Uptake of LDL cholesterol was visualized by confocal microscopy. SREBP acti…
In situ observations of CH&lt;sub&gt;2&lt;/sub&gt;Cl&lt;sub&gt;2&lt;/sub&gt; and CHCl&lt;sub&gt;3&lt;/sub&gt; show efficient transport pathways for very short-lived species into the lower stratosphere via the Asian and the North American summer monsoon
Abstract. Efficient transport pathways for ozone-depleting very short-lived substances (VSLSs) from their source regions into the stratosphere are a matter of current scientific debate; however they have yet to be fully identified on an observational basis. Understanding the increasing impact of chlorine-containing VSLSs (Cl-VSLSs) on stratospheric ozone depletion is important in order to validate and improve model simulations and future predictions. We report on a transport study using airborne in situ measurements of the Cl-VSLSs dichloromethane (CH2Cl2) and trichloromethane (chloroform, CHCl3) to derive a detailed description of two transport pathways from (sub)tropical source regions in…
Targeting V-ATPase in primary human monocytes by archazolid potently represses the classical secretion of cytokines due to accumulation at the endoplasmic reticulum
The macrolide archazolid inhibits vacuolar-type H(+)-ATPase (V-ATPase), a proton-translocating enzyme involved in protein transport and pH regulation of cell organelles, and potently suppresses cancer cell growth at low nanomolar concentrations. In view of the growing link between inflammation and cancer, we investigated whether inhibition of V-ATPase by archazolid may affect primary human monocytes that can promote cancer by sustaining inflammation through the release of tumor-promoting cytokines. Human primary monocytes express V-ATPase, and archazolid (10-100nM) increases the vesicular pH in these cells. Archazolid (10nM) markedly reduced the release of pro-inflammatory (TNF-α, interleuk…
Water vapor increase in the northern lower stratosphere by the Asian monsoon anticyclone observed during TACTS/ESMVal campaigns
Abstract. The impact of air masses from Asia influenced by the Asian monsoon anticyclone on the northern hemispheric stratosphere is investigated based on in-situ measurements. An statistical significant increase in water vapor of about 0.5 ppmv (11 %) and methane up to 20 ppbv (1.2 %) in the extra-tropical stratosphere above a potential temperature of 380 K was detected between August and September 2012 by in-situ instrumentation in the northern hemisphere during the HALO aircraft mission TACTS and ESMVal. We investigate the origin of this water vapor and methane increase with the help of the three-dimensional Lagrangian chemistry transport model CLaMS. We assign the source of the moist ai…