Rosina - Rosetta Orbiter Spectrometer for Ion and Neutral Analysis

The Rosetta Orbiter Spectrometer for Ion and Neutral Analysis (ROSINA) will answer important questions posed by the mission's main objectives. After Giotto, this will be the first time the volatile part of a comet will be analyzed in situ. This is a very important investigation, as comets, in contrast to meteorites, have maintained most of the volatiles of the solar nebula. To accomplish the very demanding objectives through all the different phases of the comet's activity, ROSINA has unprecedented capabilities including very wide mass range (1 to >300 amu), very high mass resolution (m/Δ m > 3000, i.e. the ability to resolve CO from N2 and 13C from 12CH), very wide dynamic range and high sensitivity, as well as the ability to determine cometary gas velocities, and temperature. ROSINA consists of two mass spectrometers for neutrals and primary ions with complementary capabilities and a pressure sensor. To ensure that absolute gas densities can be determined, each mass spectrometer carries a reservoir of a calibrated gas mixture allowing in-flight calibration. Furthermore, identical flight-spares of all three sensors will serve for detailed analysis of all relevant parameters, in particular the sensitivities for complex organic molecules and their fragmentation patterns in our electron bombardment ion source

Interleukin-7 Regulates Adipose Tissue Mass and Insulin Sensitivity in High-Fat Diet-Fed Mice through Lymphocyte-Dependent and Independent Mechanisms

Although interleukin (IL)-7 is mostly known as a key regulator of lymphocyte homeostasis, we recently demonstrated that it also contributes to body weight regulation through a hypothalamic control. Previous studies have shown that IL-7 is produced by the human obese white adipose tissue (WAT) yet its potential role on WAT development and function in obesity remains unknown. Here, we first show that transgenic mice overexpressing IL-7 have reduced adipose tissue mass associated with glucose and insulin resistance. Moreover, in the high-fat diet (HFD)-induced obesity model, a single administration of IL-7 to C57BL/6 mice is sufficient to prevent HFD-induced WAT mass increase and glucose intolerance. This metabolic protective effect is accompanied by a significant decreased inflammation in WAT. In lymphocyte-deficient HFD-fed SCID mice, IL-7 injection still protects from WAT mass gain. However, IL-7-triggered resistance against WAT inflammation and glucose intolerance is lost in SCID mice. These results suggest that IL-7 regulates adipose tissue mass through a lymphocyte-independent mechanism while its protective role on glucose homeostasis would be relayed by immune cells that participate to WAT inflammation. Our observations establish a key role for IL-7 in the complex mechanisms by which immune mediators modulate metabolic functions

Hemidesmosome integrity protects the colon against colitis and colorectal cancer

OBJECTIVE: Epidemiological and clinical data indicate that patients suffering from IBD with long-standing colitis display a higher risk to develop colorectal high-grade dysplasia. Whereas carcinoma invasion and metastasis rely on basement membrane (BM) disruption, experimental evidence is lacking regarding the potential contribution of epithelial cell/BM anchorage on inflammation onset and subsequent neoplastic transformation of inflammatory lesions. Herein, we analyse the role of the alpha6beta4 integrin receptor found in hemidesmosomes that attach intestinal epithelial cells (IECs) to the laminin-containing BM. DESIGN: We developed new mouse models inducing IEC-specific ablation of alpha6 integrin either during development (alpha6DeltaIEC) or in adults (alpha6DeltaIEC-TAM). RESULTS: Strikingly, all alpha6DeltaIEC mutant mice spontaneously developed long-standing colitis, which degenerated overtime into infiltrating adenocarcinoma. The sequence of events leading to disease onset entails hemidesmosome disruption, BM detachment, IL-18 overproduction by IECs, hyperplasia and enhanced intestinal permeability. Likewise, IEC-specific ablation of alpha6 integrin induced in adult mice (alpha6DeltaIEC-TAM) resulted in fully penetrant colitis and tumour progression. Whereas broad-spectrum antibiotic treatment lowered tissue pathology and IL-1beta secretion from infiltrating myeloid cells, it failed to reduce Th1 and Th17 response. Interestingly, while the initial intestinal inflammation occurred independently of the adaptive immune system, tumourigenesis required B and T lymphocyte activation. CONCLUSIONS: We provide for the first time evidence that loss of IECs/BM interactions triggered by hemidesmosome disruption initiates the development of inflammatory lesions that progress into high-grade dysplasia and carcinoma. Colorectal neoplasia in our mouse models resemble that seen in patients with IBD, making them highly attractive for discovering more efficient therapies.PMC559510

Expected Performances of the NOMAD/ExoMars instrument

NOMAD (Nadir and Occultation for MArs Discovery) is one of the four instruments on board the ExoMars Trace Gas Orbiter, scheduled for launch in March 2016. It consists of a suite of three high-resolution spectrometers – SO (Solar Occultation), LNO (Limb, Nadir and Occultation) and UVIS (Ultraviolet and Visible Spectrometer). Based upon the characteristics of the channels and the values of Signal-to-Noise Ratio obtained from radiometric models discussed in [Vandaele et al., Optics Express, 2015] and [Thomas et al., Optics Express, 2015], the expected performances of the instrument in terms of sensitivity to detection have been investigated. The analysis led to the determination of detection limits for 18 molecules, namely CO, H2O, HDO, C2H2, C2H4, C2H6, H2CO, CH4, SO2, H2S, HCl, HCN, HO2, NH3, N2O, NO2, OCS, O3. NOMAD should have the ability to measure methane concentrations <25 parts per trillion (ppt) in solar occultation mode, and 11 parts per billion in nadir mode. Occultation detections as low as 10 ppt could be made if spectra are averaged [Drummond et al., Planetary Space and Science, 2011]. Results have been obtained for all three channels in nadir and in solar occultation

Optical and radiometric models of the NOMAD instrument part II: the infrared channels - SO and LNO

NOMAD is a suite of three spectrometers that will be launched in 2016 as part of the joint ESA-Roscosmos ExoMars Trace Gas Orbiter mission. The instrument contains three channels that cover the IR and UV spectral ranges and can perform solar occultation, nadir and limb observations, to detect and map a wide variety of Martian atmospheric gases and trace species. Part I of this work described the models of the UVIS channel; in this second part, we present the optical models representing the two IR channels, SO (Solar Occultation) and LNO (Limb, Nadir and Occultation), and use them to determine signal to noise ratios (SNRs) for many expected observational cases. In solar occultation mode, both the SO and LNO channel exhibit very high SNRs >5000. SNRs of around 100 were found for the LNO channel in nadir mode, depending on the atmospheric conditions, Martian surface properties, and observation geometry

J Clin Invest

Instability in the composition of gut bacterial communities (dysbiosis) has been linked to common human intestinal disorders, such as Crohn's disease and colorectal cancer. Here, we show that dysbiosis caused by Nod2 deficiency gives rise to a reversible, communicable risk of colitis and colitis-associated carcinogenesis in mice. Loss of either Nod2 or RIP2 resulted in a proinflammatory microenvironment that enhanced epithelial dysplasia following chemically induced injury. The condition could be improved by treatment with antibiotics or an anti-interleukin-6 receptor-neutralizing antibody. Genotype-dependent disease risk was communicable via maternally transmitted microbiota in both Nod2-deficient and WT hosts. Furthermore, reciprocal microbiota transplantation reduced disease risk in Nod2-deficient mice and led to long-term changes in intestinal microbial communities. Conversely, disease risk was enhanced in WT hosts that were recolonized with dysbiotic fecal microbiota from Nod2-deficient mice. Thus, we demonstrated that licensing of dysbiotic microbiota is a critical component of disease risk. Our results demonstrate that NOD2 has an unexpected role in shaping a protective assembly of gut bacterial communities and suggest that manipulation of dysbiosis is a potential therapeutic approach in the treatment of human intestinal disorders