The proposed Caroline ESA M3 mission to a Main Belt Comet

We describe Caroline, a mission proposal submitted to the European Space Agency in 2010 in response to the Cosmic Visions M3 call for medium-sized missions. Caroline would have travelled to a Main Belt Comet (MBC), characterizing the object during a flyby, and capturing dust from its tenuous coma for return to Earth. MBCs are suspected to be transition objects straddling the traditional boundary between volatile–poor rocky asteroids and volatile–rich comets. The weak cometary activity exhibited by these objects indicates the presence of water ice, and may represent the primary type of object that delivered water to the early Earth. The Caroline mission would have employed aerogel as a medium for the capture of dust grains, as successfully used by the NASA Stardust mission to Comet 81P/Wild 2. We describe the proposed mission design, primary elements of the spacecraft, and provide an overview of the science instruments and their measurement goals. Caroline was ultimately not selected by the European Space Agency during the M3 call; we briefly reflect on the pros and cons of the mission as proposed, and how current and future mission MBC mission proposals such as Castalia could best be approached

Loss of MECP2 Leads to Activation of P53 and Neuronal Senescence.

To determine the role for mutations of MECP2 in Rett syndrome, we generated isogenic lines of human induced pluripotent stem cells, neural progenitor cells, and neurons from patient fibroblasts with and without MECP2 expression in an attempt to recapitulate disease phenotypes in vitro. Molecular profiling uncovered neuronal-specific gene expression changes, including induction of a senescence-associated secretory phenotype (SASP) program. Patient-derived neurons made without MECP2 showed signs of stress, including induction of P53, and senescence. The induction of P53 appeared to affect dendritic branching in Rett neurons, as P53 inhibition restored dendritic complexity. The induction of P53 targets was also detectable in analyses of human Rett patient brain, suggesting that this disease-in-a-dish model can provide relevant insights into the human disorder

Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I

Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism presenting with striatal lesions anatomically and symptomatically similar to Huntington disease. Affected children commonly suffer acute brain injury in the context of a catabolic state associated with nonspecific illness. The mechanisms underlying injury and age-dependent susceptibility have been unknown, and lack of a diagnostic marker heralding brain injury has impeded intervention efforts. Using a mouse model of GA-I, we show that pathologic events began in the neuronal compartment while enhanced lysine accumulation in the immature brain allowed increased glutaric acid production resulting in age-dependent injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance (1H NMR) spectroscopy as a diagnostic marker. Blocking brain lysine uptake reduced glutaric acid levels and brain injury. These findings provide what we believe are new monitoring and treatment strategies that may translate for use in human GA-I

Plasma Ketone and Medium Chain Fatty Acid Response in Humans Consuming Different Medium Chain Triglycerides During a Metabolic Study Day

Background: Medium chain triglycerides (MCT) are ketogenic but the relationship between the change in plasma ketones and the change plasma medium chain fatty acids (MCFA)—octanoate, decanoate, or dodecanoate—after an oral dose of MCT is not well-known. An 8 h metabolic study day is a suitable model to assess the acute effects on plasma ketones and MCFA after a dose of tricaprylin (C8), tricaprin (C10), trilaurin (C12) or mixed MCT (C8C10).Objective: To assess in healthy humans the relationship between the change in plasma ketones, and octanoate, decanoate and dodecanoate in plasma total lipids during an 8 h metabolic study day in which a first 20 ml dose of the homogenized test oil is taken with breakfast and a second 20 ml dose is taken 4 h later without an accompanying meal.Results: The change in plasma acetoacetate, β-hydroxybutyrate and total ketones was highest after C8 (0.5 to 3 h post-dose) and was lower during tests in which octanoate was absent or was diluted by C10 in the test oil. The plasma ketone response was also about 2 fold higher without an accompanying meal (P = 0.012). However, except during the pure C10 test, the response of octanoate, decanoate or dodecanoate in plasma total lipids to the test oils was not affected by consuming an accompanying meal. Except with C12, the 4 h area-under-the-curve of plasma β-hydroxybutyrate/acetoacetate was 2–3 fold higher when no meal was consumed (P < 0.04).Conclusion: C8 was about three times more ketogenic than C10 and about six times more ketogenic than C12 under these acute metabolic test conditions, an effect related to the post-dose increase in octanoate in plasma total lipids

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

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

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.

Complete genome sequence of Meiothermus silvanus type strain (VI-R2).

Meiothermus silvanus (Tenreiro et al. 1995) Nobre et al. 1996 belongs to a thermophilic genus whose members share relatively low degrees of 16S rRNA gene sequence similarity. Meiothermus constitutes an evolutionary lineage separate from members of the genus Thermus, from which they can generally be distinguished by their slightly lower temperature optima. M. silvanus is of special interest as it causes colored biofilms in the paper making industry and may thus be of economic importance as a biofouler. This is the second completed genome sequence of a member of the genus Meiothermus and only the third genome sequence to be published from a member of the family Thermaceae. The 3,721,669 bp long genome with its 3,667 protein-coding and 55 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project