Measurement of the vertical atmospheric density profile from the X-ray Earth occultation of the Crab Nebula with Insight-HXMT

In this paper, the X-ray Earth occultation (XEO) of the Crab Nebula is investigated by using the Hard X-ray Modulation Telescope (Insight-HXMT). The pointing observation data on the 30th September, 2018 recorded by the Low Energy X-ray telescope (LE) of Insight-HXMT are selected and analyzed. The extinction lightcurves and spectra during the X-ray Earth occultation process are extracted. A forward model for the XEO lightcurve is established and the theoretical observational signal for lightcurve is predicted. The atmospheric density model is built with a scale factor to the commonly used MSIS density profile within a certain altitude range. A Bayesian data analysis method is developed for the XEO lightcurve modeling and the atmospheric density retrieval. The posterior probability distribution of the model parameters is derived through the Markov Chain Monte Carlo (MCMC) algorithm with the NRLMSISE-00 model and the NRLMSIS 2.0 model as basis functions and the best-fit density profiles are retrieved respectively. It is found that in the altitude range of 105--200 km, the retrieved density profile is 88.8% of the density of NRLMSISE-00 and 109.7% of the density of NRLMSIS 2.0 by fitting the lightcurve in the energy range of 1.0--2.5 keV based on XEOS method. In the altitude range of 95--125 km, the retrieved density profile is 81.0% of the density of NRLMSISE-00 and 92.3% of the density of NRLMSIS 2.0 by fitting the lightcurve in the energy range of 2.5--6.0 keV based on XEOS method. In the altitude range of 85--110 km, the retrieved density profile is 87.7% of the density of NRLMSISE-00 and 101.4% of the density of NRLMSIS 2.0 by fitting the lightcurve in the energy range of 6.0--10.0 keV based on XEOS method. This study demonstrates that the XEOS from the X-ray astronomical satellite Insight-HXMT can provide an approach for the study of the upper atmosphere.Comment: 31 pages, 15 figures, 5 tables, accepted for publication in Atmospheric Measurement Technique

Alternative splicing and promoter usage generates an intracellular stromelysin 3 isoform directly translated as an active matrix metalloproteinase

International audienceHuman stromelysin 3 (ST3) is a matrix metalloproteinase (MMP) that has been implicated in cancer progression and in various tissue remodeling processes. Unlike most MMPs, ST3 is characterized by a distinct substrate specificity and a specific regulation and is not directly involved in extracellular matrix degradation. In the present study, we have identified an additional ST3 gene promoter that is accessible to nuclear factors such as C/EBP and retinoic acid receptors. This human specific promoter is inducible and controls the expression of a novel ST3 transcript called the beta-ST3 that is expressed in cultured cells and in placenta. This transcript encodes a 40-kDa ST3 isoform that lacks both the signal peptide common to all secreted MMPs and the prodomain that normally maintains enzyme latency. Consistent with the lack of a signal peptide, the beta-ST3 was found to be intracellular. The relative amount of the extracellular alpha-ST3 isoform was about 20-fold higher than that of the intracellular ST3 isoforms, as estimated by Western blot analysis. Furthermore, recombinant beta-ST3 produced in Escherichia coli exhibits a proteolytic activity against alpha1-proteinase inhibitor, a substrate previously shown to be inactivated by the alpha-ST3. Therefore, although it was thought that all MMPs were synthesized as inactive zymogens and functioned extracellularly, this is the first MMP isoform reported that is generated by alternative promoter usage and directly translated as an active enzyme. Although the intracellular function of the beta-ST3 remains to be investigated, these data support the idea that the functions of MMPs are not restricted to the extracellular space

Effect of calcium ionophore A23187 on prostaglandin synthase type 2 and 15-hydroxy-prostaglandin dehydrogenase expression in human chorion trophoblast cells.

Objective: Prostaglandins induce parturition in humans. Prostaglandin output is regulated by the synthetic and metabolic enzymes, prostaglandin synthase type 2 (PTGS2) and 15-hydroxyprostaglandin dehydrogenase (PGDH). The role of calcium in regulating PTGS2 and PGDH expression was investigated in chorion trophoblasts. Study Design: Cells were treated with calcium ionophore A23187 in the presence or absence of calcium chelators; changes in messenger ribonucleic acid expression were measured with real-time polymerase chain reaction and analyzed with analysis of variance. Protein expression was evaluated with Western blot and dual immunofluorescence. Results: A23187 stimulated PTGS2 and suppressed PGDH expression. Effects of A23187 were reversed by calcium chelators. PTGS2 had perinuclear and cytosolic distribution, whereas PGDH was cytosolic. Some cells expressed both enzymes, some neither enzyme, and some either PTGS2 or PGDH. Conclusion: Chorion cells showed heterogeneity in the expression of PTGS2 and PGDH. Calcium influx regulates PTGS2 and PGDH expression, thereby promoting coordinated increased prostaglandin output in circumstances such as term and preterm labor. © 2008 Mosby, Inc. All rights reserved

Reversal of Surfactant Protein B Deficiency in Patient Specific Human Induced Pluripotent Stem Cell Derived Lung Organoids by Gene Therapy

Surfactant protein B (SFTPB) deficiency is a fatal disease affecting newborn infants. Surfactant is produced by alveolar type II cells which can be differentiated in vitro from patient specific induced pluripotent stem cell (iPSC)-derived lung organoids. Here we show the differentiation of patient specific iPSCs derived from a patient with SFTPB deficiency into lung organoids with mesenchymal and epithelial cell populations from both the proximal and distal portions of the human lung. We alter the deficiency by infecting the SFTPB deficient iPSCs with a lentivirus carrying the wild type SFTPB gene. After differentiating the mutant and corrected cells into lung organoids, we show expression of SFTPB mRNA during endodermal and organoid differentiation but the protein product only after organoid differentiation. We also show the presence of normal lamellar bodies and the secretion of surfactant into the cell culture medium in the organoids of lentiviral infected cells. These findings suggest that a lethal lung disease can be targeted and corrected in a human lung organoid model in vitro

Hypoxia-inducible factor-1 stimulates postnatal lung development but does not prevent o2-induced alveolar injury

This study investigated whether hypoxia-inducible factor (HIF)-1 influences postnatal vascularization and alveologenesis in mice and whether stable (constitutive-active) HIF could prevent hyperoxia-induced lung injury. We assessed postnatal vessel and alveolar formation in transgenic mice, expressing a stable, constitutive-active, HIF1a-subunit (HIF-1aDODD) in the distal lung epithelium. In addition,we compared lung function, histology, and morphometry of neonatal transgenic and wild-type mice subjected to hyperoxia. We found that postnatal lungs of HIF-1aDODDmice had a greater peripheral vessel density and displayed advanced alveolarization compared with control lungs. Stable HIF-1a expression was associated with increased postnatal expression of angiogenic factors, including vascular endothelial growth factor, angiopoietins 1 and 2, Tie2, and Ephrin B2 and B4. Hyperoxiaexposed neonatal HIF-1aDODD mice exhibited worse lung function but had similar histological and surfactant abnormalities compared with hyperoxia-exposed wild-type controls. In conclusion, expression of constitutive-active HIF-1a in the lung epithelium was associated with increased postnatal vessel growth via up-regulation of angiogenic factors. The increase in postnatal vasculature was accompanied by enhanced alveolar formation. However, stable HIF-1a expression in the distal lung did not prevent hyperoxia-induced lung injury in neonates but instead worsened lung function