The CRIRES Search for Planets Around the Lowest-Mass Stars. I. High-Precision Near-Infrared Radial Velocities with an Ammonia Gas Cell

Radial velocities measured from near-infrared spectra are a potentially powerful tool to search for planets around cool stars and sub-stellar objects. However, no technique currently exists that yields near-infrared radial velocity precision comparable to that routinely obtained in the visible. We describe a method for measuring high-precision relative radial velocities of these stars from K-band spectra. The method makes use of a glass cell filled with ammonia gas to calibrate the spectrograph response similar to the "iodine cell" technique that has been used very successfully in the visible. Stellar spectra are obtained through the ammonia cell and modeled as the product of a Doppler-shifted template spectrum of the object and a spectrum of the cell, convolved with a variable instrumental profile model. A complicating factor is that a significant number of telluric absorption lines are present in the spectral regions containing useful stellar and ammonia lines. The telluric lines are modeled simultaneously as well using spectrum synthesis with a time-resolved model of the atmosphere over the observatory. The free parameters in the complete model are the wavelength scale of the spectrum, the instrumental profile, adjustments to the water and methane abundances in the atmospheric model, telluric spectrum Doppler shift, and stellar Doppler shift. Tests of the method based on the analysis of hundreds of spectra obtained for late M dwarfs over six months demonstrate that precisions of ~5 m/s are obtainable over long timescales, and precisions of better than 3 m/s can be obtained over timescales up to a week. The obtained precision is comparable to the predicted photon-limited errors, but primarily limited over long timescales by the imperfect modeling of the telluric lines.Comment: Accepted for publication in Ap

CD40L Deficiency Attenuates Diet-Induced Adipose Tissue Inflammation by Impairing Immune Cell Accumulation and Production of Pathogenic IgG-Antibodies

BACKGROUND: Adipose tissue inflammation fuels the metabolic syndrome. We recently reported that CD40L--an established marker and mediator of cardiovascular disease--induces inflammatory cytokine production in adipose cells in vitro. Here, we tested the hypothesis that CD40L deficiency modulates adipose tissue inflammation in vivo. METHODOLOGY/PRINCIPAL FINDINGS: WT or CD40L(-/-) mice consumed a high fat diet (HFD) for 20 weeks. Inflammatory cell recruitment was impaired in mice lacking CD40L as shown by a decrease of adipose tissue macrophages, B-cells, and an increase in protective T-regulatory cells. Mechanistically, CD40L-deficient mice expressed significantly lower levels of the pro-inflammatory chemokine MCP-1 both, locally in adipose tissue and systemically in plasma. Moreover, levels of pro-inflammatory IgG-antibodies against oxidized lipids were reduced in CD40L(-/-) mice. Also, circulating low-density lipoproteins and insulin levels were lower in CD40L(-/-) mice. However, CD40L(-/-) mice consuming HFD were not protected from the onset of diet-induced obesity (DIO), insulin resistance, and hepatic steatosis, suggesting that CD40L selectively limits the inflammatory features of diet-induced obesity rather than its metabolic phenotype. Interestingly, CD40L(-/-) mice consuming a low fat diet (LFD) showed both, a favorable inflammatory and metabolic phenotype characterized by diminished weight gain, improved insulin tolerance, and attenuated plasma adipokine levels. CONCLUSION: We present the novel finding that CD40L deficiency limits adipose tissue inflammation in vivo. These findings identify CD40L as a potential mediator at the interface of cardiovascular and metabolic disease

The proposed giant planet orbiting VB 10 does not exist

We present high-precision relative radial velocities of the very low mass star VB 10 that were obtained over a time span of 0.61 years as part of an ongoing search for planets around stars at the end of the main sequence. The radial velocities were measured from high-resolution near-infrared spectra obtained using the CRIRES instrument on the Very Large Telescope with an ammonia gas cell. The typical internal precision of the measurements is 10 m s(-1). These data do not exhibit significant variability and are essentially constant at a level consistent with the measurement uncertainties. Therefore, we do not detect the radial velocity variations of VB 10 expected due to the presence of an orbiting giant planet similar to that recently proposed by Pravdo & Shaklan based on apparent astrometric perturbations. In addition, we do not confirm the similar to 1 km s(-1) radial velocity variability of the star tentatively detected by Zapatero Osorio and colleagues with lower precision measurements. Our measurements rule out planets with M-p > 3 M-Jup and the orbital period and inclination suggested by Pravdo & Shaklan at better than 5 sigma confidence. We conclude that the planet detection claimed by Pravdo & Shaklan is spurious on the basis of this result. Although the outcome of this work is a non-detection, it illustrates the potential of using ammonia cell radial velocities to detect planets around very low mass stars

Binding of CD40L to Mac-1's i-domain involves the EQLKKSKTL motif and mediates leukocyte recruitment and atherosclerosis-but does not affect immunity and thrombosis in mice

Rationale: CD40L figures prominently in chronic inflammatory diseases such as atherosclerosis. However, since CD40L potently regulates immune function and hemostasis by interaction with CD40 receptor and the platelet integrin GPIIb/IIIa, its global inhibition compromises host defense and generated thromboembolic complications in clinical trials. We recently reported that CD40L mediates atherogenesis independently of CD40 and proposed Mac-1 as an alternate receptor. Objective: Here, we molecularly characterized the CD40L-Mac-1 interaction and tested whether its selective inhibition by a small peptide modulates inflammation and atherogenesis in vivo. Methods and Results: CD40L concentration-dependently bound to Mac-1 I-domain in solid phase binding assays, and a high-affinity interaction was revealed by surface-plasmon-resonance analysis. We identified the motif EQLKKSKTL, an exposed loop between the α1 helix and the β-sheet B, on Mac-1 as binding site for CD40L. A linear peptide mimicking this sequence, M7, specifically inhibited the interaction of CD40L and Mac-1. A cyclisized version optimized for in vivo use, cM7, decreased peritoneal inflammation and inflammatory cell recruitment in vivo. Finally, LDLr -/- mice treated with intraperitoneal injections of cM7 developed smaller, less inflamed atherosclerotic lesions featuring characteristics of stability. However, cM7 did not interfere with CD40L-CD40 binding in vitro and CD40L-GPIIb/IIIa-mediated thrombus formation in vivo. Conclusions: We present the novel finding that CD40L binds to the EQLKKSKTL motif on Mac-1 mediating leukocyte recruitment and atherogenesis. Specific inhibition of CD40L-Mac-1 binding may represent an attractive anti-inflammatory treatment strategy for atherosclerosis and other inflammatory conditions, potentially avoiding the unwanted immunologic and thrombotic effects of global inhibition of CD40L.Fil: Wolf, Dennis. Albert-Ludwigs-Universität Freiburg; Alemania. Baker IDI Heart and Diabetes Institute; AustraliaFil: Hohmann, Jan David. Baker IDI Heart and Diabetes Institute; AustraliaFil: Wiedemann, Ansgar. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Bledzka, Kamila. Cleveland Clinic. Department of Molecular Cardiology; Estados UnidosFil: Blankenbach, Hermann. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Marchini, Timoteo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Gutte, Katharina. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Zeschky, Katharina. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Bassler, Nicole. Baker IDI Heart and Diabetes Institute; AustraliaFil: Hoppe, Natalie. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Rodriguez, Alexandra Ortiz. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Herr, Nadine. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Hilgendorf, Ingo. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Stachon, Peter. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Willecke, Florian. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Duerschmied, Daniel. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: von zur Muhlen, Constantin. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Soloviev, Dmitry A.. Cleveland Clinic. Department of Molecular Cardiology; Estados UnidosFil: Zhang, Li. University of Maryland; Estados UnidosFil: Bode, Christoph. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Plow, Edward F.. Cleveland Clinic. Department of Molecular Cardiology; Estados UnidosFil: Libby, Peter. Harvard Medical School; Estados UnidosFil: Peter, Karlheinz. Baker IDI Heart and Diabetes Institute; AustraliaFil: Zirlik, Andreas. Albert-Ludwigs-Universität Freiburg; Alemani

Baseline study characteristics.

<p>Data are presented as mean ± SEM, ND not determined, LFD low fat diet, HFD high fat diet, WT wildtype, PC Phosphatidylcholine, BW body weight.</p

CD40L deficiency does not affect basic energy metabolism.

<p>WT and CD40L^−/− mice consumed a high fat diet (HFD) for 20 weeks. Plasma levels of leptin (A) and adiponectin (B) were determined at the indicated time points by ELISA. Food intake (C), heat production (D), ambulatory movement (E), and respiratory exchange ratio (RER, F) were analyzed in metabolic cages. CaH and fat indicate carbohydrate and fat metabolism (F). Data are presented as mean ± SEM of at least 9 mice per group.</p

Absence of CD40L does not ameliorate insulin sensitivity in diet-induced obesity.

<p>Plasma glucose (A) and insulin levels (B) were determined in animals fasted overnight (A) and for 6 hours (B) overnight. Insulin tolerance (ITT) and glucose tolerance testing (GTT) were performed after intraperitoneal insulin (0.5 U/kg lean body mass) or glucose (1 g/kg lean body mass) injection (C–F). Inlays represent area under the curve calculation (AUC) of the indicated glucose curve.</p