Interleukin-4 (IL-4), but not IL-10, regulates the synthesis of IL-6, IL-8 and leukemia inhibitory factor by human bone marrow stromal cells

AbstractLeukemia inhibitory factor (LIF), interleukin 6 (IL-6) and IL-8 are important regulators of inflammation and hematopoiesis. Human bone marrow stromal cells regulate marrow hematopoiesis by secreting cytokines. By using reverse-transcriptase polymerase chain reaction (RT-PCR), we demonstrate that human bone marrow stromal cells constitutively express LIF, IL-6 and IL-8 transcripts. By using specific ELISAs, we found that their spontaneous productions of LIF, IL-6 and IL-8 are elevated in response to serum and after stimulation with the pro-inflammatory cytokines IL-1α and TNF-α. The anti-inflammatory cytokine IL-4 reduces their serum- and cytokine-induced LIF secretion. By contrast, IL-4 stimulates their serum- and IL-1α-induced IL-6 synthesis. IL-4 has no effect on the serum-induced IL-8 synthesis by marrow stromal cells, but stimulates their cytokine-induced IL-8 production. The anti-inflammatory cytokine IL-10 has no effect on the serum- and cytokine-induced LIF, IL-6 and IL-8 synthesis by bone marrow stromal cells. RT-PCR experiments reveal the presence of IL-4 receptor α-chain mRNA and IL-10 receptor mRNA in cultured bone marrow stromal cells. The differential regulation by IL-4 of two related cytokines, such as LIF and IL-6, and the enhanced effect of this ‘anti-inflammatory’ cytokine on IL-6 and IL-8 synthesis highlight the tightly controlled regulation and the complexity of the cytokine production within the human bone marrow

A milestone toward understanding PDR properties in the extreme environment of LMC-30Dor

More complete knowledge of galaxy evolution requires understanding the process of star formation and interaction between the interstellar radiation field and the interstellar medium in galactic environments traversing a wide range of physical parameter space. Here we focus on the impact of massive star formation on the surrounding low metallicity ISM in 30 Doradus in the Large Magellanic Cloud. A low metal abundance, as is the case of some galaxies of the early universe, results in less ultra-violet shielding for the formation of the molecular gas necessary for star formation to proceed. The half-solar metallicity gas in this region is strongly irradiated by the super star cluster R136, making it an ideal laboratory to study the structure of the ISM in an extreme environment. Our spatially resolved study investigates the gas heating and cooling mechanisms, particularly in the photo-dissociation regions where the chemistry and thermal balance are regulated by far-ultraviolet photons (6 eV< h\nu <13.6 eV). We present Herschel observations of far-infrared fine-structure lines obtained with PACS and SPIRE/FTS. We have combined atomic fine-structure lines from Herschel and Spitzer observations with ground-based CO data to provide diagnostics on the properties and the structure of the gas by modeling it with the Meudon PDR code. We derive the spatial distribution of the radiation field, the pressure, the size, and the filling factor of the photodissociated gas and molecular clouds. We find a range of pressure of ~ 10^5 - 1.7x10^6 cm^{-3} K and a range of incident radiation field G_UV ~ 10^2 - 2.5x10^4 through PDR modeling. Assuming a plane-parallel geometry and a uniform medium, we find a total extinction of 1-3 mag , which correspond to a PDR cloud size of 0.2 to 3pc, with small CO depth scale of 0.06 to 0.5pc. We also determine the three dimensional structure of the gas. (Abridged)Comment: 20 pages, 23 figures, accepted in A&

The new vertebrate CYP1C family : cloning of new subfamily members and phylogenetic analysis

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Elsevier B. V. for personal use, not for redistribution. The definitive version was published in Biochemical and Biophysical Research Communications 331 (2005): 1016-1024, doi:10.1016/j.bbrc.2005.03.231.Two novel CYP1 genes from teleost fish constituting a new subfamily have been cloned. These paralogous sequences are designated CYP1C1 and CYP1C2. Both genes were initially obtained from untreated scup Stenotomus chrysops tissues by RT-PCR and RACE. Scup CYP1C1 and CYP1C2 code for 524 and 525 amino acids, respectively, and share 80-81% identity at the nucleotide and amino acid levels. Orthologues of CYP1C1 and CYP1C2 were identified in genome databases for other fish species, and both CYP1B1 and CYP1C1 were cloned from zebrafish (Danio rerio). Phylogenetic analysis shows that CYP1Cs and CYP1Bs constitute a sister clade to the CYP1As. Analysis of sequence domains likely to have functional significance suggests the two CYP1Cs in scup may have catalytic functions and/or substrate specificity that differ from each other and from those of mammalian CYP1Bs or CYP1As. RT-PCR results indicate that CYP1C1 and CYP1C2 are variously expressed in several scup organs.This work was supported by EPA grant R 827102-01-0 and NIH grants 5 P42-ES07381 and ES04696. JVG is supported by a Ruth L. Kirschstein NRSA Fellowship (F32 ES012794)

CalFUSE v3: A Data-Reduction Pipeline for the Far Ultraviolet Spectroscopic Explorer

Since its launch in 1999, the Far Ultraviolet Spectroscopic Explorer (FUSE) has made over 4600 observations of some 2500 individual targets. The data are reduced by the Principal Investigator team at the Johns Hopkins University and archived at the Multimission Archive at Space Telescope (MAST). The data-reduction software package, called CalFUSE, has evolved considerably over the lifetime of the mission. The entire FUSE data set has recently been reprocessed with CalFUSE v3.2, the latest version of this software. This paper describes CalFUSE v3.2, the instrument calibrations upon which it is based, and the format of the resulting calibrated data files.Comment: To appear in PASP; 29 pages, 13 figures, uses aastex, emulateap

Closed-loop separation control over a sharp edge ramp using Genetic Programming

We experimentally perform open and closed-loop control of a separating turbulent boundary layer downstream from a sharp edge ramp. The turbulent boundary layer just above the separation point has a Reynolds number $Re_{\theta}\approx 3\,500$ based on momentum thickness. The goal of the control is to mitigate separation and early re-attachment. The forcing employs a spanwise array of active vortex generators. The flow state is monitored with skin-friction sensors downstream of the actuators. The feedback control law is obtained using model-free genetic programming control (GPC) (Gautier et al. 2015). The resulting flow is assessed using the momentum coefficient, pressure distribution and skin friction over the ramp and stereo PIV. The PIV yields vector field statistics, e.g. shear layer growth, the backflow area and vortex region. GPC is benchmarked against the best periodic forcing. While open-loop control achieves separation reduction by locking-on the shedding mode, GPC gives rise to similar benefits by accelerating the shear layer growth. Moreover, GPC uses less actuation energy.Comment: 24 pages, 24 figures, submitted to Experiments in Fluid

Airway remodelling assessed by sputum and high resolution computed tomography in asthma and COPD

It is not known whether sputum elastase, metalloproteinase (MMP)-9 and tissue-inhibitor metalloproteinase (TIMP)-1 are related to structural changes of the airways, as assessed by high-resolution computed tomography (HRCT) scan. The relationships between these markers and the magnitude of structural changes of the airways in asthma and chronic obstructive pulmonary disease (COPD) were assessed. Induced sputum and HRCT scan were performed in 30 asthmatics (14 mild and 16 severe) and in 12 patients with COPD. A greater extent of HRCT scan abnormalities was found in COPD than in severe and mild asthmatics. HRCT scan abnormalities correlated with the degree of airway obstruction in COPD and in severe asthma. HRCT scan abnormalities also correlated with the levels of sputum elastase both in COPD and in severe asthma. HRCT scan abnormalities were associated with sputum MMP-9/TIMP-1 ratio in mild asthma, severe asthma and COPD. In conclusion, this study demonstrates that sputum elastase and the metalloproteinase-9/tissue-inhibitor metalloproteinase-1 ratio are associated with the magnitude of high-resolution computed tomography scan abnormalities of the airways in asthma and chronic obstructive pulmonary disease, and suggests that the levels of these markers reflect the extent of structural changes of the airway

Herschel Survey of Galactic OH+, H2O+, and H3O+: Probing the Molecular Hydrogen Fraction and Cosmic-Ray Ionization Rate

In diffuse interstellar clouds the chemistry that leads to the formation of the oxygen bearing ions OH+, H2O+, and H3O+ begins with the ionization of atomic hydrogen by cosmic rays, and continues through subsequent hydrogen abstraction reactions involving H2. Given these reaction pathways, the observed abundances of these molecules are useful in constraining both the total cosmic-ray ionization rate of atomic hydrogen (zeta_H) and molecular hydrogen fraction, f(H2). We present observations targeting transitions of OH+, H2O+, and H3O+ made with the Herschel Space Observatory along 20 Galactic sight lines toward bright submillimeter continuum sources. Both OH+ and H2O+ are detected in absorption in multiple velocity components along every sight line, but H3O+ is only detected along 7 sight lines. From the molecular abundances we compute f(H2) in multiple distinct components along each line of sight, and find a Gaussian distribution with mean and standard deviation 0.042+-0.018. This confirms previous findings that OH+ and H2O+ primarily reside in gas with low H2 fractions. We also infer zeta_H throughout our sample, and find a log-normal distribution with mean log(zeta_H)=-15.75, (zeta_H=1.78x10^-16 s^-1), and standard deviation 0.29 for gas within the Galactic disk, but outside of the Galactic center. This is in good agreement with the mean and distribution of cosmic-ray ionization rates previously inferred from H3+ observations. Ionization rates in the Galactic center tend to be 10--100 times larger than found in the Galactic disk, also in accord with prior studies.Comment: 76 pages, 25 figures, 6 tables; accepted for publication in Ap

Inversion of provenance data and sediment load into spatially varying erosion rates

Sediment fingerprinting methods aim to determine the relative contribution of different source areas in detrital sediments based on natural properties – fingerprints – of the source areas. Here, we use U/Th–Pb age signatures as fingerprints, assuming that the age signal is not altered during erosion–transportation–deposition events, and given that recent technological advances enable precise dating of large amounts of grains. We introduce a formal inversion method that allows to disentangle the amalgamation of source contributions in detrital zircon data and enables to convert this information into an erosion rate map starting from the spatial distribution of zircon age signatures. Relying on the least‐squares method and using prior and covariance information to deal with non‐uniqueness, we show, using synthetic and natural examples, that we are able to retrieve erosion rate patterns of a catchment when the age distribution and zircon fertility for each source area are well known. Moreover, we show that not only zircon age fingerprints but also other tracers such as mineral content can be used. Furthermore, we found that adding data from samples taken at the outlet of tributaries improves the estimation of erosion rate patterns. We conclude that the least squares inverse model applied to detrital data has great potential for investigating erosion rates