ESO observations of the Nucleus of Rosetta Target 67P/C-G

Rosetta is ESA's new comet orbiter mission, launched in March 2004 and currently en route to Jupiter-family comet 67P/Churyumov-Gerasimenko. The probe will rendezvous with the comet in 2014 and remain in orbit around the nucleus for on-going detailed physical and compositional analysis. Pre-encounter observations of the target are important for characterization of the heliocentric light-curve behaviour and the physical properties of the nucleus, information that is critical for mission planning. The nucleus was first characterized using HST observations in 2003 (Lamy et al. 2006) and observed directly in May 2005 by ground based telescopes (Lowry et al. 2006) when it was at 5.6 AU from the Sun. An extensive database of nucleus observations have since been acquired, not only from large ground-based telescopes like the ESO VLT (Tubiana et al. 2008 & 2011), but also from Spitzer (Kelley et al. 2006 & 2009; Lamy et al. 2008).

Turbulent Fluctuations in G-band and K-line Intensities Observed with the Rapid Oscillations in the Solar Atmosphere (ROSA) Instrument

Using the Rapid Oscillation in the Solar Atmosphere (ROSA) instrument at the Dunn Solar Telescope we have found that the spectra of fluctuations of the G-band (cadence 1.05 s) and Ca II K-line (cadence 4.2 s) intensities show correlated fluctuations above white noise out to frequencies beyond 300 mHz and up to 70 mHz, respectively. The noise-corrected G-band spectrum presents a scaling range (Ultra High Frequency “UHF”) for f = 25-100 mHz, with an exponent consistent with the presence of turbulent motions. The UHF power, is concentrated at the locations of magnetic bright points in the intergranular lanes, it is highly intermittent in time and characterized by a positive kurtosis κ. Combining values of G-band and K-line intensities, the UHF power, and κ, reveals two distinct “states” of the internetwork solar atmosphere. State 1, with κ ≍ 6, which includes almost all the data, is characterized by low intensities and low UHF power. State 2, with κ ≍ 3, including a very small fraction of the data, is characterized by high intensities and high UHF power. Superposed epoch analysis shows that for State 1, the K-line intensity presents 3.5 min chromospheric oscillations with maxima occurring 21 s after G-band intensity maxima implying a 150-210 km effective height difference. For State 2, the G-band and K-line intensity maxima are simultaneous, suggesting that in the highly magnetized environment sites of G-band and K-line emission may be spatially close together. Analysis of observations obtained with Hinode/SOT confirm a scaling range in the G-band spectrum up to 53 mHz also consistent with turbulent motions as well as the identification of two distinct states in terms of the H-line intensity and G-band power as functions of G-band intensity.

Interspecific comparison of estrogen and testosterone concentrations in three species of amphipods (Gammarus duebeni celticus, G. pseudolimnaeus, and G. pulex)

The presence and biological significance of vertebrate-related steroid sex hormones in aquatic invertebrates are poorly understood. We compared the concentrations of estrogen (17β-estradiol) and testosterone between amplexing male and female freshwater amphipods of three species from two continents: Gammarus duebeni celticusLiljeborg, 1852 and G. pulex(L., 1758) from Europe, and G. pseudolimnaeusBousfield, 1958 from North America. All three species were found to have measureable concentrations of both hormones in whole body lysate samples but the concentrations differed between species, with testosterone differing significantly between species only for male amphipods and estradiol differing significantly between species only for female amphipods. Concentrations of both testosterone and estrogen differed between males and females in two of the three species ( G. duebeni celticusand G. pseudolimnaeus). Females had the highest concentration of both hormones in G. duebeni celticusand the lowest concentration of both hormones in G. pseudolimnaeus. These results contribute to a growing body of evidence that these hormones are endogenously produced and biologically relevant in amphipods. Such evidence is particularly important in light of increasing prevalence of endocrine-disrupting compounds in the environment and the central role played by amphipods in aquatic ecosystems.

The cyclin D1 (CCND1) rs9344 G>A polymorphism predicts clinical outcome in colon cancer patients treated with adjuvant 5-FU-based chemotherapy

Recent evidence indicates a potential prognostic and predictive value for germline polymorphisms in genes involved in cell cycle control. We investigated the effect of cyclin D1 (CCND1) rs9344 G>A in stage II/III colon cancer patients and validated the findings in an independent study cohort. For evaluation and validation set, a total of 264 and 234 patients were included. Patients treated with 5-fluorouracil-based chemotherapy, carrying the CCND1 rs9344 A/A genotype had significantly decreased time-to-tumor recurrence (TTR) in univariate analysis and multivariate analysis (hazard ratio (HR) 2.47; 95% confidence interval (CI) 1.16-5.29; P=0.019). There was no significant association between CCND1 rs9344 G>A and TTR in patients with curative surgery alone. In the validation set, the A allele of CCND1 rs9344 G>A remained significantly associated with decreased TTR in univariate and multivariate analyses (HR 1.94; 95% CI 1.05-3.58; P=0.035). CCND1 rs9344 G>A may be a predictive and/or prognostic biomarker in stage II/III colon cancer patients, however, prospective trials are warranted to confirm our findings.

A Molecular Mechanism for Sequential Activation of a G Protein-Coupled Receptor

Ligands targeting G protein-coupled receptors (GPCRs) are currently classified as either orthosteric, allosteric, or dualsteric/bitopic. Here, we introduce a new pharmacological concept for GPCR functional modulation: sequential receptor activation. A hallmark feature of this is a stepwise ligand binding mode with transient activation of a first receptor site followed by sustained activation of a second topographically distinct site. We identify 4-CMTB (2-(4-chlorophenyl)-3-methyl-N-(thiazol-2-yl)butanamide), previously classified as a pure allosteric agonist of the free fatty acid receptor 2, as the first sequential activator and corroborate its two-step activation in living cells by tracking integrated responses with innovative label-free biosensors that visualize multiple signaling inputs in real time. We validate this unique pharmacology with traditional cellular readouts, including mutational and pharmacological perturbations along with computational methods, and propose a kinetic model applicable to the analysis of sequential receptor activation. We envision this form of dynamic agonism as a common principle of nature to spatiotemporally encode cellular information.