Interleukin-6 Gene-Deficient Mice Show Impaired Defense against Pneumococcal Pneumonia

Induction of pneumonia in C57Bl/6 mice by intranasal inoculation with 106 cfu of Streptococcus pneumoniae resulted in sustained expression of interleukin (IL)-6 mRNA in lungs and increases in lung and plasma IL-6 concentrations. In IL-6-deficient (IL-6−/−) mice, pneumonia was associated with higher lung levels of the proinflammatory cytokines tumor necrosis factor-α, IL-1β, and interferon-γ and of the antiinflammatory cytokine IL-10 than in wild type (IL-6+/+) mice (all P < .05). Also, the plasma concentrations of soluble tumor necrosis factor receptors were higher in IL-6−/− mice (P < .05), while the acute-phase protein response was strongly attenuated (P < .01). Lungs harvested from IL-6−/− mice 40 h after inoculation contained more S. pneumoniae colonies (P < .05). IL-6−/− mice died significantly earlier from pneumococcal pneumonia than did IL-6+/+ mice (P < .05). During pneumococcal pneumonia, IL-6 down-regulates the activation of the cytokine network in the lung and contributes to host defens

Determination of the light curve of the Rosetta target asteroid (2867) Steins by the OSIRIS cameras onboard Rosetta

7 pp.-- Article published by EDP Sciences and available at http://www.aanda.org or http://dx.doi.org/10.1051/0004-6361:20066694.-- Table 2 is only available in electronic form at http://www.aanda.org.[Context] In 2004 asteroid (2867) Steins has been selected as a flyby target for the Rosetta mission. Determination of its spin period and the orientation of its rotation axis are essential for optimization of the flyby planning.[Aims] Measurement of the rotation period and light curve of asteroid (2867) Steins at a phase angle larger than achievable from ground based observations, providing a high quality data set to contribute to the determination of the orientation of the spin axis and of the pole direction.[Methods] On March 11, 2006, asteroid (2867) Steins was observed continuously for 24 h with the scientific camera system OSIRIS onboard Rosetta. The phase angle was 41.7 degrees, larger than the maximum phase angle of 30 degrees when Steins is observed from Earth. A total of 238 images, covering four rotation periods without interruption, were acquired.[Results] The light curve of (2867) Steins is double peaked with an amplitude of ≈0.23 mag. The rotation period is 6.052 ± 0.007 h. The continuous observations over four rotation periods exclude the possibility of period ambiguities. There is no indication of deviation from a principal axis rotation state. Assuming a slope parameter of G = 0.15, the absolute visual magnitude of Steins is 13.05 ± 0.03.The OSIRIS imaging system on board Rosetta is managed by the Max-Planck-Intitute for Solar System Research in Katlenburg-Lindau (Germany), thanks to an International collaboration between Germany, France, Italy, Spain, and Sweden. The support of the national funding agencies DLR, CNES, ASI, MEC, and SNSB is gratefully acknowledged. We acknowledge the work of the Rosetta Science Operations Centre at ESA/ESTEC and of the Rosetta Mission Operations Centre at ESA/ESOC who made these observations possible on short notation and operated the spacecraft. S.C.L. acknowledges support from the Leverhulme Trust. This research made use of JPL’s online ephemeris generator (HORIZONS).Peer reviewe

Pretreatment with a 55-kDa Tumor Necrosis Factor Receptor-Immunoglobulin Fusion Protein Attenuates Activation of Coagulation, but not of Fibrinolysis, during Lethal Bacteremia in Baboons

Baboons (Papio anubis) receiving a lethal intravenous infusion with live Escherichia coli were pretreated with either a 55-kDa tumor necrosis factor (TNF) receptor-IgG fusion protein (TNFR55:IgG) (n = 4, 4.6 mg/kg) or placebo (n = 4). Neutralization of TNF activity in TNFR55:IgG-treated animals was associated with a complete prevention of mortality and a strong attenuation of coagulation activation as reflected by the plasma concentrations of thrombin-antithrombin III complexes (P < .05). Activation of fibrinolysis was not influenced by TNFR55:IgG (plasma tissue-type plasminogen activator and plasmin-a2-antiplasmin complexes), whereas TNFR55:IgG did inhibit the release of plasminogen activator inhibitor type I (P < .05). Furthermore, TNFR55:IgG inhibited neutrophil degranulation (plasma levels of elastase-α1-antitrypsin complexes, P < .05) and modestly reduced release of secretory phospholipase A2. These data suggest that endogenous TNF contributes to activation of coagulation, but not to stimulation of fibrinolysis, during severe bacteremi

Epinephrine inhibits tumor necrosis factor-a and potentiates interleukin-10 production during human endotoxemia.

Abstract Short-term preexposure of mononuclear cells to epinephrine inhibits LPS-induced production of TNF, whereas preexposure for 24 h results in increased TNF production. To assess the effects of epinephrine infusions of varying duration on in vivo responses to LPS, the following experiments were performed: ( a ) Blood obtained from eight subjects at 4-24 h after the start of a 24-h infusion of epinephrine (30 ng/kg per min) produced less TNF after ex vivo stimulation with LPS compared with blood drawn before the start of the infusion, and ( b ) 17 healthy men who were receiving a continuous infusion of epinephrine (30 ng/kg per min) started either 3 h (EPI-3; n ϭ 5) or 24 h (EPI-24; n ϭ 6) before LPS injection or an infusion of normal saline (LPS; n ϭ 6) were studied after intravenous injection of LPS (2 ng/kg, lot EC-5). EPI-3 inhibited LPS-induced in vivo TNF appearance and also increased IL-10 release (both P Ͻ 0.005 versus LPS), whereas EPI-24 only attenuated TNF secretion ( P ϭ 0.05). In separate in vitro experiments in whole blood, epinephrine increased LPS-induced IL-10 release by a combined effect on ␣ and ␤ adrenergic receptors. Further, in LPS-stimulated blood, the increase in IL-10 levels caused by epinephrine only marginally contributed to concurrent inhibition of TNF production. Epinephrine, either endogenously produced or administered as a component of sepsis treatment, may have a net antiinflammatory effect on the cytokine network early in the course of systemic infection. ( J. Clin. Invest. 1996. 97:713-719.

Physical model of near-Earth asteroid (1917) Cuyo from ground-based optical and thermal-IR observations

Context: The near-Earth asteroid (1917) Cuyo was subject to radar and lightcurve observations during a close approach in 1989, and observed up until 2008. It was selected as one of our ESO Large Programme targets, aimed at observational detections of the YORP effect through long-term lightcurve monitoring and physical modelling of near-Earth asteroids. Aims: We aimed to constrain physical properties of Cuyo: shape, spin-state, and spectroscopic & thermophysical properties of the surface. Methods: We acquired photometric lightcurves of Cuyo spanning the period between 2010 and 2013, which we combined with published lightcurves from 1989-2008. Our thermal-infrared observations were obtained in 2011. Rotationally-resolved optical spectroscopy data were acquired in 2011 and combined with all available published spectra to investigate any surface material variegation. Results: We developed a convex lightcurve-inversion shape of Cuyo that suggests the presence of an equatorial ridge, typical for an evolved system close to shedding mass due to fast rotation. We determine limits of YORP strength through lightcurve-based spin-state modelling, including both negative and positive acceleration values, between -0.7x10-8 rad day-2 and 1.7x10-8 rad day-2. Thermo-physical modelling with the ATPM provides constraints on the geometric albedo, PV = 0.24 ± 0.07, the effective diameter Deff = 3.15 ± 0.08 km, the thermal inertia, 44 ±- 9 J m-2s-1/2K-1, and a roughness fraction of 0.52 ± 0.26. This enabled a YORP strength prediction of (-6.39 ± 0.96)x10-10 rad day-2. We also see evidence of surface compositional variation. Conclusions: The low value of YORP predicted by means of thermophysical analysis, consistent with the results of the lightcurve study, might be due to the self-limiting properties of rotational YORP, possibly involving movement of sub-surface and surface material. This may also be consistent with the surface compositional variation that we see. The physical model of Cuyo can be used to investigate cohesive forces as a way to explain why some targets survive rotation rates faster than the fission limit

A genomic perspective on the potential of Actinobacillus succinogenes for industrial succinate production

<p>Abstract</p> <p>Background</p> <p>Succinate is produced petrochemically from maleic anhydride to satisfy a small specialty chemical market. If succinate could be produced fermentatively at a price competitive with that of maleic anhydride, though, it could replace maleic anhydride as the precursor of many bulk chemicals, transforming a multi-billion dollar petrochemical market into one based on renewable resources. <it>Actinobacillus succinogenes </it>naturally converts sugars and CO₂into high concentrations of succinic acid as part of a mixed-acid fermentation. Efforts are ongoing to maximize carbon flux to succinate to achieve an industrial process.</p> <p>Results</p> <p>Described here is the 2.3 Mb <it>A. succinogenes </it>genome sequence with emphasis on <it>A. succinogenes</it>'s potential for genetic engineering, its metabolic attributes and capabilities, and its lack of pathogenicity. The genome sequence contains 1,690 DNA uptake signal sequence repeats and a nearly complete set of natural competence proteins, suggesting that <it>A. succinogenes </it>is capable of natural transformation. <it>A. succinogenes </it>lacks a complete tricarboxylic acid cycle as well as a glyoxylate pathway, and it appears to be able to transport and degrade about twenty different carbohydrates. The genomes of <it>A. succinogenes </it>and its closest known relative, <it>Mannheimia succiniciproducens</it>, were compared for the presence of known Pasteurellaceae virulence factors. Both species appear to lack the virulence traits of toxin production, sialic acid and choline incorporation into lipopolysaccharide, and utilization of hemoglobin and transferrin as iron sources. Perspectives are also given on the conservation of <it>A. succinogenes </it>genomic features in other sequenced Pasteurellaceae.</p> <p>Conclusions</p> <p>Both <it>A. succinogenes </it>and <it>M. succiniciproducens </it>genome sequences lack many of the virulence genes used by their pathogenic Pasteurellaceae relatives. The lack of pathogenicity of these two succinogens is an exciting prospect, because comparisons with pathogenic Pasteurellaceae could lead to a better understanding of Pasteurellaceae virulence. The fact that the <it>A. succinogenes </it>genome encodes uptake and degradation pathways for a variety of carbohydrates reflects the variety of carbohydrate substrates available in the rumen, <it>A. succinogenes</it>'s natural habitat. It also suggests that many different carbon sources can be used as feedstock for succinate production by <it>A. succinogenes</it>.</p

Physics-Based Stress Corrosion Cracking Component Reliability Model cast in an R7-Compatible Cumulative Damage Framework

This is a working report drafted under the Risk-Informed Safety Margin Characterization pathway of the Light Water Reactor Sustainability Program, describing statistical models of passives component reliabilities

Physical properties of near-Earth asteroid (2102) Tantalus from multiwavelength observations

Between 2010 and 2017 we have collected new optical and radar observations of the potentially hazardous asteroid (2102) Tantalus from the ESO NTT and Danish telescopes at the La Silla Observatory and from the Arecibo planetary radar. The object appears to be nearly spherical, showing a low amplitude light-curve variation and limited large-scale features in the radar images. The spin-state is difficult to constrain with the available data; including a certain light-curve subset significantly changes the spin-state estimates, and the uncertainties on period determination are significant. Constraining any change in rotation rate was not possible, despite decades of observations. The convex lightcurve-inversion model, with rotational pole at λ = 210 ± 41○ and β = −30 ± 35○, is more flattened than the two models reconstructed by including radar observations: with prograde (λ = 36 ± 23○, β = 30 ± 15○), and with retrograde rotation mode (λ = 180 ± 24○, β = −30 ± 16○). Using data from WISE we were able to determine that the prograde model produces the best agreement in size determination between radar and thermophysical modelling. Radar measurements indicate possible variation in surface properties, suggesting one side might have lower radar albedo and be rougher at centimetre-to-decimetre scale than the other. However, further observations are needed to confirm this. Thermophysical analysis indicates a surface covered in fine-grained regolith, consistent with radar albedo and polarisation ratio measurements. Finally, geophysical investigation of the spin-stability of Tantalus shows that it could be exceeding its critical spin-rate via cohesive forces