Acute and Chronic Effects of Smoking on Inflammation Markers in Exhaled Breath Condensate in Current Smokers

Background: Long-term cigarette smoking is associated with pulmonary inflammation, but the acute effects of smoking have been less well studied. Analysis of the exhaled breath condensate (EBC) can provide noninvasive markers that might be indicative of inflammation. Objectives: The aim of the study was to determine whether the pH, electrical conductivity and the levels of ammonium and interleukin 8 (IL-8) of EBC were altered in smokers and whether they changed after smoking a single cigarette. Methods: We included 19 healthy nonsmokers (controls), 29 asymptomatic smokers, 10 patients with stable chronic obstructive pulmonary disease (COPD) {[}Global Initiative for Chronic Obstructive Lung Disease stages (GOLD) stages II-III], and 10 patients with exacerbated COPD. In 13 smokers, EBC was also analyzed before and after smoking. EBC was obtained during 10 min tidal breathing with a cooled RTube (TM). pH was determined after deaeration with argon. Results: Acute smoking did not alter the pH or ammonium and IL-8 levels, but raised conductivity. As in COPD patients, the pH was significantly decreased in chronic smokers with a history of at least 10 pack-years compared to controls. Conclusions: EBC can be used to detect the acute and chronic effects of smoking. The increased conductivity of EBC after smoking suggests acute inflammatory effects. The reduced pH in chronic smokers shows cigarette-induced inflammation. Copyright (C) 2009 S. Karger AG, Base

Titan Atmospheric Chemistry Revealed by Low-temperature N2-CH4 Plasma Discharge Experiments

Chemistry in Titan's N2-CH4 atmosphere produces complex organic aerosols. The chemical processes and the resulting organic compounds are still far from understood, although extensive observations, laboratory, and theoretical simulations have greatly improved physical and chemical constraints on Titan's atmosphere. Here, we conduct a series of Titan atmosphere simulation experiments with N2-CH4 gas mixtures and investigate the effect of initial CH4 ratio, pressure, and flow rate on the production rates and composition of the gas and solid products at a Titan relevant temperature (100 K) for the first time. We find that the production rate of the gas and solid products increases with increasing CH4 ratio. The nitrogen-containing species have much higher yield than hydrocarbons in the gas products, and the N-to-C ratio of the solid products appears to be the highest compared to previous plasma simulations with the same CH4 ratio. The greater degree of nitrogen incorporation in the low temperature simulation experiments suggests temperature may play an important role in nitrogen incorporation in Titan's cold atmosphere. We also find that H2 is the dominant gas product and serves as an indicator of the production rate of new organic molecules in the experiment, and that CH2NH may greatly contribute to the incorporation of both carbon and nitrogen into the solid particles. The pressure and flow rate affect the amount of time of the gas mixture exposed to the energy source and therefore impact the N2-CH4 chemistry initiated by the plasma discharge, emphasizing the influence of the energy flux in Titan atmospheric chemistry.Comment: Accepted in ACS Earth and Space Chemistry, 6 figure

Localization of the succinate receptor in the distal nephron and its signaling in polarized MDCK cells

When the succinate receptor (SUCNR1) is activated in the afferent arterioles of the glomerulus it increases renin release and induces hypertension. To study its location in other nephron segments and its role in kidney function, we performed immunohistochemical analysis and found that SUCNR1 is located in the luminal membrane of macula densa cells of the juxtaglomerular apparatus in close proximity to renin-producing granular cells, the cortical thick ascending limb, and cortical and inner medullary collecting duct cells. In order to study its signaling, SUCNR1 was stably expressed in Madin-Darby Canine Kidney (MDCK) cells, where it localized to the apical membrane. Activation of the cells by succinate caused Gq and Gi-mediated intracellular calcium mobilization, transient phosphorylation of extracellular regulated kinase (ERK)1/2 and the release of arachidonic acid along with prostaglandins E2 and I2. Signaling was desensitized without receptor internalization but rapidly resensitized upon succinate removal. Immunohistochemical evidence of phosphorylated ERK1/2 was found in cortical collecting duct cells of wild type but not SUCNR1 knockout streptozotocin-induced diabetic mice, indicating in vivo relevance. Since urinary succinate concentrations in health and disease are in the activation range of the SUCNR1, this receptor can sense succinate in the luminal fluid. Our study suggests that changes in the luminal succinate concentration may regulate several aspects of renal function

Optical Properties of Organic Haze Analogues in Water-rich Exoplanet Atmospheres Observable with JWST

JWST has begun its scientific mission, which includes the atmospheric characterization of transiting exoplanets. Some of the first exoplanets to be observed by JWST have equilibrium temperatures below 1000 K, which is a regime where photochemical hazes are expected to form. The optical properties of these hazes, which controls how they interact with light, are critical for interpreting exoplanet observations, but relevant experimental data are not available. Here we measure the density and optical properties of organic haze analogues generated in water-rich exoplanet atmosphere experiments. We report optical constants (0.4 to 28.6 {\mu}m) of organic haze analogues for current and future observational and modeling efforts covering the entire wavelength range of JWST instrumentation and a large part of Hubble. We use these optical constants to generate hazy model atmospheric spectra. The synthetic spectra show that differences in haze optical constants have a detectable effect on the spectra, impacting our interpretation of exoplanet observations. This study emphasizes the need to investigate the optical properties of hazes formed in different exoplanet atmospheres, and establishes a practical procedure to determine such properties.Comment: 4 figures, 1 Table, Published in Nature Astronom

Laboratory Simulations of Haze Formation in the Atmospheres of super-Earths and mini-Neptunes: Particle Color and Size Distribution

Super-Earths and mini-Neptunes are the most abundant types of planets among the ~3500 confirmed exoplanets, and are expected to exhibit a wide variety of atmospheric compositions. Recent transmission spectra of super-Earths and mini-Neptunes have demonstrated the possibility that exoplanets have haze/cloud layers at high altitudes in their atmospheres. However, the compositions, size distributions, and optical properties of these particles in exoplanet atmospheres are poorly understood. Here, we present the results of experimental laboratory investigations of photochemical haze formation within a range of planetary atmospheric conditions, as well as observations of the color and size of produced haze particles. We find that atmospheric temperature and metallicity strongly affect particle color and size, thus altering the particles' optical properties (e.g., absorptivity, scattering, etc.); on a larger scale, this affects the atmospheric and surface temperature of the exoplanets, and their potential habitability. Our results provide constraints on haze formation and particle properties that can serve as critical inputs for exoplanet atmosphere modeling, and guide future observations of super-Earths and mini-Neptunes with the Transiting Exoplanet Survey Satellite (TESS), the James Webb Space Telescope (JWST), and the Wide-Field Infrared Survey Telescope (WFIRST).Comment: 19 pages, 4 figures and 1 tabl

Wearable devices can predict the outcome of standardized 6-minute walk tests in heart disease

Wrist-worn devices with heart rate monitoring have become increasingly popular. Although current guidelines advise to consider clinical symptoms and exercise tolerance during decision-making in heart disease, it remains unknown to which extent wearables can help to determine such functional capacity measures. In clinical settings, the 6-minute walk test has become a standardized diagnostic and prognostic marker. We aimed to explore, whether 6-minute walk distances can be predicted by wrist-worn devices in patients with different stages of mitral and aortic valve disease. A total of n = 107 sensor datasets with 1,019,748 min of recordings were analysed. Based on heart rate recordings and literature information, activity levels were determined and compared to results from a 6-minute walk test. The percentage of time spent in moderate activity was a predictor for the achievement of gender, age and body mass index-specific 6-minute walk distances (p < 0.001; R2 = 0.48). The uncertainty of these predictions is demonstrated

Exome Sequencing Identifies a Recurrent De Novo ZSWIM6 Mutation Associated with Acromelic Frontonasal Dysostosis

Acromelic frontonasal dysostosis (AFND) is a rare disorder characterized by distinct craniofacial, brain, and limb malformations, including frontonasal dysplasia, interhemispheric lipoma, agenesis of the corpus callosum, tibial hemimelia, preaxial polydactyly of the feet, and intellectual disability. Exome sequencing of one trio and two unrelated probands revealed the same heterozygous variant (c.3487C>T [p. Arg1163Trp]) in a highly conserved protein domain of ZSWIM6; this variant has not been seen in the 1000 Genomes data, dbSNP, or the Exome Sequencing Project. Sanger validation of the three trios confirmed that the variant was de novo and was also present in a fourth isolated proband. In situ hybridization of early zebrafish embryos at 24 hr postfertilization (hpf) demonstrated telencephalic expression of zswim6 and onset of midbrain, hindbrain, and retinal expression at 48 hpf. Immunohistochemistry of later-stage mouse embryos demonstrated tissue-specific expression in the derivatives of all three germ layers. qRT-PCR expression analysis of osteoblast and fibroblast cell lines available from two probands was suggestive of Hedgehog pathway activation, indicating that the ZSWIM6 mutation associated with AFND may lead to the craniofacial, brain and limb malformations through the disruption of Hedgehog signaling