Methane storms as a driver of Titan's dune orientation

Titan's equatorial regions are covered by eastward propagating linear dunes. This direction is opposite to mean surface winds simulated by Global Climate Models (GCMs), which are oriented westward at these latitudes, similar to trade winds on Earth. Different hypotheses have been proposed to address this apparent contradiction, involving Saturn's gravitational tides, large scale topography or wind statistics, but none of them can explain a global eastward dune propagation in the equatorial band. Here we analyse the impact of equinoctial tropical methane storms developing in the superrotating atmosphere (i.e. the eastward winds at high altitude) on Titan's dune orientation. Using mesoscale simulations of convective methane clouds with a GCM wind profile featuring superrotation, we show that Titan's storms should produce fast eastward gust fronts above the surface. Such gusts dominate the aeolian transport, allowing dunes to extend eastward. This analysis therefore suggests a coupling between superrotation, tropical methane storms and dune formation on Titan. Furthermore, together with GCM predictions and analogies to some terrestrial dune fields, this work provides a general framework explaining several major features of Titan's dunes: linear shape, eastward propagation and poleward divergence, and implies an equatorial origin of Titan's dune sand.Comment: Published online on Nature Geoscience on 13 April 201

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Solar wind sputtering of dust on the surface of 67P/Churyumov-Gerasimenko

International audienceFar away from the Sun, at around 3 AU, the activity of comet 67P/Churyumov-Gerasimenko is low and changes with local time (solar insolation), with location (chemical heterogeneity of the surface), and with season. When the activity is very low because the total cross section of the comet against the Sun is small, the solar wind has access to the surface of the comet and causes ion-induced sputtering of surface material, which we wish to observe.Methods. We used the Double Focussing Mass Spectrometer (DFMS) of the ROSINA experiment on ESA’s Rosetta mission to search for mass spectrometric evidence of sputtered refractory species. In high-resolution mode, DFMS can separate some of the mass peaks of refractory elements from the many volatile species present in the coma.Results. At present, the locations of solar wind surface access are in the southern hemisphere of the comet (the local winter). Of particular interest is sputtering of dust grains on the surface. We observe global averages over the winter hemisphere of the refractory elements Na, K, Si, and Ca, presumably sputtered from grains residing on the surface. Compared to carbonaceous chondrites, the comet has the same Na abundance, is depleted in Ca, and has an excess of K. In addition, for Si the signal strength is strong enough to compile a coarse compositional map of the southern hemisphere. Most, perhaps all, of the observed variation can be explained by the solar wind being affected by the atmosphere of the comet

Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT) beyond SMARCA4 Mutations: A Comprehensive Genomic Analysis.

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an aggressive malignancy that occurs in young women, is characterized by recurrent loss-of-function mutations in the SMARCA4 gene, and for which effective treatments options are lacking. The aim of this study was to broaden the knowledge on this rare malignancy by reporting a comprehensive molecular analysis of an independent cohort of SCCOHT cases. We conducted Whole Exome Sequencing in six SCCOHT, and RNA-sequencing and array comparative genomic hybridization in eight SCCOHT. Additional immunohistochemical, Sanger sequencing and functional data are also provided. SCCOHTs showed remarkable genomic stability, with diploid profiles and low mutation load (mean, 5.43 mutations/Mb), including in the three chemotherapy-exposed tumors. All but one SCCOHT cases exhibited 19p13.2-3 copy-neutral LOH. SMARCA4 deleterious mutations were recurrent and accompanied by loss of expression of the SMARCA2 paralog. Variants in a few other genes located in 19p13.2-3 (e.g., PLK5) were detected. Putative therapeutic targets, including MAGEA4, AURKB and CLDN6, were found to be overexpressed in SCCOHT by RNA-seq as compared to benign ovarian tissue. Lastly, we provide additional evidence for sensitivity of SCCOHT to HDAC, DNMT and EZH2 inhibitors. Despite their aggressive clinical course, SCCOHT show remarkable inter-tumor homogeneity and display genomic stability, low mutation burden and few somatic copy number alterations. These findings and preliminary functional data support further exploration of epigenetic therapies in this lethal disease

On the aerodynamic redistribution of chondrite components in protoplanetary disks

Despite being all roughly of solar composition, primitive meteorites (chondrites) present a diversity in their chemical, isotopic and petrographic properties, and in particular a first-order dichotomy between carbonaceous and non-carbonaceous chondrites. We investigate here analytically the dynamics of their components (chondrules, refractory inclusions, metal/sulfide and matrix grains) in protoplanetary disks prior to their incorporation in chondrite parent bodies. We find the dynamics of the solids, subject to gas drag, to be essentially controlled by the "gas-solid decoupling parameter" $S\equiv \textrm{St}/\alpha$, the ratio of the dimensionless stopping time to the turbulence parameter. The decoupling of the solid particles relative to the gas is significant when $S$ exceeds unity. $S$ is expected to increase with time and heliocentric distance. On the basis of (i) abundance of refractory inclusions (ii) proportion of matrix (iii) lithophile element abundances and (iv) oxygen isotopic composition of chondrules, we propose that non-matrix chondritic components had $S1$ when the other chondrites accreted. This suggests that accretion of carbonaceous chondrites predated on average that of the other chondrites and that refractory inclusions are genetically related to their host carbonaceous chondrites.Comment: 13 pages, 6 figures, accepted to Icaru

Masitinib (AB1010), a Potent and Selective Tyrosine Kinase Inhibitor Targeting KIT

International audienceBackground: The stem cell factor receptor, KIT, is a target for the treatment of cancer, mastocytosis, and inflammatory diseases. Here, we characterise the in vitro and in vivo profiles of masitinib (AB1010), a novel phenylaminothiazole-type tyrosine kinase inhibitor that targets KIT. Methodology/Principal Findings: In vitro, masitinib had greater activity and selectivity against KIT than imatinib, inhibiting recombinant human wild-type KIT with an half inhibitory concentration (IC50) of 200 ± 40 nM and blocking stem cell factor-induced proliferation and KIT tyrosine phosphorylation with an IC50 of 150 ± 80 nM in Ba/F3 cells expressing human or mouse wild-type KIT. Masitinib also potently inhibited recombinant PDGFR and the intracellular kinase Lyn, and to a lesser extent, fibroblast growth factor receptor 3. In contrast, masitinib demonstrated weak inhibition of ABL and c-Fms and was inactive against a variety of other tyrosine and serine/threonine kinases. This highly selective nature of masitinib suggests that it will exhibit a better safety profile than other tyrosine kinase inhibitors; indeed, masitinib-induced cardiotoxicity or genotoxicity has not been observed in animal studies. Molecular modelling and kinetic analysis suggest a different mode of binding than imatinib, and masitinib more strongly inhibited degranulation, cytokine production, and bone marrow mast cell migration than imatinib. Furthermore, masitinib potently inhibited human and murine KIT with activating mutations in the juxtamembrane domain. In vivo, masitinib blocked tumour growth in mice with subcutaneous grafts of Ba/F3 cells expressing a juxtamembrane KIT mutant. Conclusions: Masitinib is a potent and selective tyrosine kinase inhibitor targeting KIT that is active, orally bioavailable in vivo, and has low toxicit

Sulphur-bearing species in the coma of comet 67P/Churyumov–Gerasimenko

Several sulphur-bearing species have already been observed in different families of comets. However, the knowledge on the minor sulphur species is still limited. The comet’s sulphur inventory is closely linked to the pre-solar cloud and holds important clues to the degree of reprocessing of the material in the solar nebula and during comet accretion. Sulphur in pre-solar clouds is highly depleted, which is quite puzzling as the S/O ratio in the diffuse interstellar medium is cosmic. This work focuses on the abundance of the previously known species H2S, OCS, SO, S2, SO2 and CS2 in the coma of comet 67P/Churyumov–Gerasimenko measured by Rosetta Orbiter Spectrometer for Ion and Neutral Analysis/Double Focusing Mass Spectrometer between equinox and perihelion 2015. Furthermore, we present the first detection of S3, S4, CH3SH and C2H6S in a comet, and we determine the elemental abundance of S/O in the bulk ice of (1.47 ± 0.05) × 10−2. We show that SO is present in the coma originating from the nucleus, but not CS in the case of 67P, and for the first time establish that S2 is present in a volatile and a refractory phase. The derived total elemental sulphur abundance of 67P is in agreement with solar photospheric elemental abundances and shows no sulphur depletion as reported for dense interstellar clouds. Also the presence of S2 at heliocentric distances larger than 3 au indicates that sulphur-bearing species have been processed by radiolysis in the pre-solar cloud and that at least some of the ice from this cloud has survived in comets up the present

A Genome-Wide RNAi Screen Identifies Regulators of Cholesterol-Modified Hedgehog Secretion in Drosophila

Hedgehog (Hh) proteins are secreted molecules that function as organizers in animal development. In addition to being palmitoylated, Hh is the only metazoan protein known to possess a covalently-linked cholesterol moiety. The absence of either modification severely disrupts the organization of numerous tissues during development. It is currently not known how lipid-modified Hh is secreted and released from producing cells. We have performed a genome-wide RNAi screen in Drosophila melanogaster cells to identify regulators of Hh secretion. We found that cholesterol-modified Hh secretion is strongly dependent on coat protein complex I (COPI) but not COPII vesicles, suggesting that cholesterol modification alters the movement of Hh through the early secretory pathway. We provide evidence that both proteolysis and cholesterol modification are necessary for the efficient trafficking of Hh through the ER and Golgi. Finally, we identified several putative regulators of protein secretion and demonstrate a role for some of these genes in Hh and Wingless (Wg) morphogen secretion in vivo. These data open new perspectives for studying how morphogen secretion is regulated, as well as provide insight into regulation of lipid-modified protein secretion

Suppressing star formation in quiescent galaxies with supermassive black hole winds.

This is the author accepted manuscript. The final version is available from the Nature Publishing Group via https://doi.org/10.1038/nature18006Quiescent galaxies with little or no ongoing star formation dominate the population of galaxies with masses above 2 × 10(10) times that of the Sun; the number of quiescent galaxies has increased by a factor of about 25 over the past ten billion years (refs 1-4). Once star formation has been shut down, perhaps during the quasar phase of rapid accretion onto a supermassive black hole, an unknown mechanism must remove or heat the gas that is subsequently accreted from either stellar mass loss or mergers and that would otherwise cool to form stars. Energy output from a black hole accreting at a low rate has been proposed, but observational evidence for this in the form of expanding hot gas shells is indirect and limited to radio galaxies at the centres of clusters, which are too rare to explain the vast majority of the quiescent population. Here we report bisymmetric emission features co-aligned with strong ionized-gas velocity gradients from which we infer the presence of centrally driven winds in typical quiescent galaxies that host low-luminosity active nuclei. These galaxies are surprisingly common, accounting for as much as ten per cent of the quiescent population with masses around 2 × 10(10) times that of the Sun. In a prototypical example, we calculate that the energy input from the galaxy's low-level active supermassive black hole is capable of driving the observed wind, which contains sufficient mechanical energy to heat ambient, cooler gas (also detected) and thereby suppress star formation.We are grateful to Yu-Yen Chang for checks on the SED fitting and implied SFR. We thank Stephanie Juneau, Jeffrey Newman, Hai Fu, and Kristina Nyland for discussions and comments. This work was supported by World Premier International Research Center Initiative (WPI Initia- tive), MEXT, Japan, and JSPS KAKENHI Grant Number 15K17603. AW acknowledges support of a Leverhulme Trust Early Career Fellowship. S.P. acknowledges support from the Japan Society for the Promotion of Science (JSPS long-term invitation fellowship). Funding for the Sloan Digital Sky Survey IV has been provided by the Alfred P. Sloan Foundation, the U.S. Department of Energy Office of Science, and the Participating Institutions. SDSS- IV acknowledges support and resources from the Center for High-Performance Computing at the University of Utah. The SDSS web site is www.sdss.org. SDSS-IV is managed by the Astrophysical Research Consortium for the Participating Institutions of the SDSS Collaboration including the Brazilian Participation Group, the Carnegie Institution for Science, Carnegie Mellon University, the Chilean Participation Group, the French Participation Group, Harvard-Smithsonian Center for Astrophysics, Instituto de Astrofísica de Canarias, The Johns Hopkins University, Kavli Institute for the Physics and Mathematics of the Universe (IPMU) / University of Tokyo, Lawrence Berkeley National Laboratory, Leibniz Institut für Astrophysik Potsdam (AIP), Max-Planck-Institut für Astronomie (MPIA Heidelberg), Max-Planck-Institut für Astrophysik (MPA Garching), Max-Planck-Institut für Extraterrestrische Physik (MPE), National Astronomical Observatory of China, New Mexico State University, New York University, Uni- versity of Notre Dame, Observatório Nacional / MCTI, The Ohio State University, Pennsylvania State University, Shanghai Astronomical Observatory, United Kingdom Participation Group, Uni- versidad Nacional Autónoma de México, University of Arizona, University of Colorado Boulder, University of Oxford, University of Portsmouth, University of Utah, University of Virginia, Uni- versity of Washington, University of Wisconsin, Vanderbilt University, and Yale University

Halogens as tracers of protosolar nebula material in comet 67P/Churyumov–Gerasimenko

We report the first in situ detection of halogens in a cometary coma, that of 67P/ChuryumovGerasimenko. Neutral gas mass spectra collected by the European Space Agency’s Rosetta spacecraft during four periods of interest from the first comet encounter up to perihelion indicate that the main halogen-bearing compounds are HF, HCl and HBr. The bulk elemental abundances relative to oxygen are ~8.9 × 10⁻⁵ for F/O, ~1.2 × 10⁻⁴ for Cl/O and ~2.5 × 10⁻⁶ for Br/O, for the volatile fraction of the comet. The cometary isotopic ratios for ³⁷Cl/³⁵Cl and ⁸¹Br/⁷⁹Br match the Solar system values within the error margins. The observations point to an origin of the hydrogen halides in molecular cloud chemistry, with frozen hydrogen halides on dust grains, and a subsequent incorporation into comets as the cloud condensed and the Solar system formed