Identification of Keratinocyte Growth Factor as a Target of microRNA-155 in Lung Fibroblasts: Implication in Epithelial-Mesenchymal Interactions

International audienceBACKGROUND: Epithelial-mesenchymal interactions are critical in regulating many aspects of vertebrate embryo development, and for the maintenance of homeostatic equilibrium in adult tissues. The interactions between epithelium and mesenchyme are believed to be mediated by paracrine signals such as cytokines and extracellular matrix components secreted from fibroblasts that affect adjacent epithelia. In this study, we sought to identify the repertoire of microRNAs (miRNAs) in normal lung human fibroblasts and their potential regulation by the cytokines TNF-alpha, IL-1beta and TGF-beta. METHODOLOGY/PRINCIPAL FINDINGS: MiR-155 was significantly induced by inflammatory cytokines TNF-alpha and IL-1beta while it was down-regulated by TGF-beta. Ectopic expression of miR-155 in human fibroblasts induced modulation of a large set of genes related to "cell to cell signalling", "cell morphology" and "cellular movement". This was consistent with an induction of caspase-3 activity and with an increase in cell migration in fibroblasts tranfected with miR-155. Using different miRNA bioinformatic target prediction tools, we found a specific enrichment for miR-155 predicted targets among the population of down-regulated transcripts. Among fibroblast-selective targets, one interesting hit was keratinocyte growth factor (KGF, FGF-7), a member of the fibroblast growth factor (FGF) family, which owns two potential binding sites for miR-155 in its 3'-UTR. Luciferase assays experimentally validated that miR-155 can efficiently target KGF 3'-UTR. Site-directed mutagenesis revealed that only one out of the 2 potential sites was truly functional. Functional in vitro assays experimentally validated that miR-155 can efficiently target KGF 3'-UTR. Furthermore, in vivo experiments using a mouse model of lung fibrosis showed that miR-155 expression level was correlated with the degree of lung fibrosis. CONCLUSIONS/SIGNIFICANCE: Our results strongly suggest a physiological function of miR-155 in lung fibroblasts. Altogether, this study implicates this miRNA in the regulation by mesenchymal cells of surrounding lung epithelium, making it a potential key player during tissue injury

Synthesis of oxygenated compounds from methane, carbon dioxide and liquid water using non-thermal plasma

Oxygenated compounds were obtained from methane and carbon dioxide using the unconventional activation by dielectric barrier discharge plasma. The process was performed using a multiphase feed composed of methane, liquid water and carbon dioxide as oxidizing agent. The effect of the CH4/CO2 ratio as well as the flow of liquid water were investigated. The results show that the presence of liquid water in the reactor favors the formation of oxygenated compounds. A direct proportional relation between the flow of water, concentration of methane in the gaseous feed (in the presence of water) and the amount of the produced oxygenates was observed. The highest value of selectivity towards oxygenated compounds was 21.2%, with methanol and formic acid being the main products formed

Unrecognized misplacement of endotracheal tubes in a mixed urban to rural emergency medical services setting

OBJECTIVE: To determine the rate of unrecognized endotracheal tube misplacement when performed by emergency medical services (EMS) personnel in a mixed urban and rural setting. METHODS: The authors conducted a prospective, observational analysis of out-of-hospital endotracheal intubations (EIs) performed by EMS personnel serving a mixed urban, suburban, and rural population. From July 1, 1998, to August 30, 1999, emergency physicians assessed and recorded the position of out-of-hospital EIs using auscultation, direct laryngoscopy, infrared CO(2) detectors, esophageal detector devices, and chest x-ray. The state EMS database also was reviewed to determine the number of EIs involving patients transported to the authors' medical center and paramedic assessment of success for these encounters. RESULTS: A total of 167 out-of-hospital EIs were recorded, of which 136 (81%) were deemed successful by EMS personnel. Observational forms were completed for 109 of the 136 patients who arrived intubated to the emergency department. Of the studied patients, 12% (13 of 109) were found to have misplaced endotracheal tubes. For the patients with unrecognized improperly placed tubes, 9% (10 of 109) were in the esophagus, 2% (2 of 109) were in the right main stem, and 1% (1 of 109) were above the cords. Paramedics serving urban and suburban areas did not perform significantly better (p < 0.05) than intermediate-level providers serving areas that are more rural. CONCLUSIONS: The incidence of unrecognized misplacement of endotracheal tubes by EMS personnel may be higher than most previous studies, making regular EMS evaluation and the out-of-hospital use of devices to confirm placement imperative. The authors were unable to show a difference in misplacement rates based on provider experience or level of training

Insights into the Mechanisms of Isopropanol Conversion on ?-Al2O3 by Dielectric Barrier Discharge

International audienceMechanisms of isopropanol (IPA) conversion on ?-Al2O3 by dielectric barrier discharge plasma are elucidated by the means of operando Fourier transformed infrared spectroscopy. In that case, it is shown that the IPA conversion proceeds by successive steps. Firstly, via the oxidation of IPA into acetone by atomic oxygen and ozone produced in the plasma composed of dry air. Secondly, after aldolization of acetone into mesityl oxide at the surface of the ?-Al2O3 catalyst. Thirdly, after fragmentation of mesityl oxide into acetaldehyde and isobutene. Such cascade reactions are only possible when a catalyst is placed in the discharge zone (in-plasma catalysis). It initially supports the IPA molecules and then allows products condensation before their fragmentation

Measurement of the French national tritiated-water standard by helium-3 mass spectrometry

International audienceThe (3)He ingrowth technique is based on the detection of the tritium radioactive daughter, (3)He, by mass spectrometry. Over the last three decades it has been used extensively in oceanography and groundwater studies for measurements of very low to ultra-low levels of tritium. To compare it with the best available methods of radioactive counting, we applied this method to measure the massic activity of a tritiated-water primary standard prepared by the French Laboratoire National Henri Becquerel (LNHB). One liter of a low-level tritium solution was prepared from a small aliquot of the LNHB standard by two-step gravimetric dilution with tritium-free groundwater. Sixteen samples of this solution were analyzed at the LSCE-Saclay noble gas facility, using the (3)He ingrowth method. The massic activity of the prepared solution was also measured by Liquid Scintillation Counting using the Quantulus LNHB counter and an internal calibration method with the LNHB tritiated water standard. All results agree within their standard uncertainty

Temporally integrated estimate of the Indonesian throughflow using tritium

Because of the high interannual and seasonal variability, transports from the various methods used to estimate the Indonesian throughflow encompass a large range of values. Here, we estimate a temporally integrated transport for the throughflow from comparison of the tritium water column inventory on both sides of the throughflow. Our approach is based on the simple idea that tritium, with a radioactive decay half-life of 12.32 yr, is well suited to infer the transit time ( and consequently the mass flow) of the waters through the Indonesian archipelago. We show that the tritium budget implies a flow of 8.6 +/- 4 Sv, corresponding to a transit time of 10.5 yr. This result, which represents an average over seasons and several ENSO and non-ENSO periods, shows that repeated tritium measurements on both sides of the Indonesian Seas could provide a useful method for monitoring the long-term evolution of the throughflow

The surface structure of BaO on Pt(111): (2x2)-reconstructed BaO(111)

The surface structure of BaO(111) has been determined using STM and computer modelling. The BaO(111) surface was prepared in thin film form on Pt(111) and presents a surface with twice the lattice parameter expected for that of the bulk termination, i.e. a (2 x 2) reconstruction. Computer modelling indicates that the bulk termination is unstable, but that the (2 x 2) reconstructed BaO(111) surface has a low surface energy and is hence a stable surface reconstruction. The (2 x 2) reconstruction consists of small, three-sided pyramids with (100) oriented sides and either oxygen or barium ions at the apices. Less regular surface reconstructions containing the same pyramids are almost equally stable, indicating that we may also expect less regular regions to appear with a fairly random distribution of these surface species. The simulations further suggest that a regular (4 x 4) reconstruction built up of bigger pyramids is even more energetically favourable, and some evidence is found for such a structure in the STM. (c) 2006 Elsevier B.V. All rights reserved