WIP Regulates Signaling via the High Affinity Receptor for Immunoglobulin E in Mast Cells

Wiskott-Aldrich syndrome protein–interacting protein (WIP) stabilizes actin filaments and is important for immunoreceptor-mediated signal transduction leading to actin cytoskeleton rearrangement in T and B cells. Here we report a role for WIP in signaling pathways downstream of the high affinity receptor for immunoglobulin (Ig)E (FcεRI) in mast cells. WIP-deficient bone marrow–derived mast cells (BMMCs) were impaired in their capacity to degranulate and secrete interleukin 6 after FcεRI ligation. Calcium mobilization, phosphorylation of Syk, phospholipase C-g2, and c-Jun NH2-terminal kinase were markedly decreased in WIP-deficient BMMCs. WIP was found to associate with Syk after FcεRI ligation and to inhibit Syk degradation as evidenced by markedly diminished Syk levels in WIP-deficient BMMCs. WIP-deficient BMMCs exhibited no apparent defect in their subcortical actin network and were normal in their ability to form protrusions when exposed to an IgE-coated surface. However, the kinetics of actin changes and the cell shape changes that follow FcεRI signaling were altered in WIP-deficient BMMCs. These results suggest that WIP regulates FcεRI-mediated mast cell activation by regulating Syk levels and actin cytoskeleton rearrangement

The southern stellar stream spectroscopic survey (S (5)): Overview, target selection, data reduction, validation, and early science

We introduce the southern stellar stream spectroscopy survey (S5), an on-going program to map the kinematics and chemistry of stellar streams in the southern hemisphere. The initial focus of S5 has been spectroscopic observations of recently identified streams within the footprint of the dark energy survey (DES), with the eventual goal of surveying streams across the entire southern sky. Stellar streams are composed of material that has been tidally striped from dwarf galaxies and globular clusters and hence are excellent dynamical probes of the gravitational potential of the Milky Way, as well as providing a detailed snapshot of its accretion history. Observing with the 3.9 m Anglo-Australian Telescope’s 2-degree-Field fibre positioner and AAOmega spectrograph, and combining the precise photometry of DES DR1 with the superb proper motions from Gaia DR2, allows us to conduct an efficient spectroscopic survey to map these stellar streams. So far S5 has mapped nine DES streams and three streams outside of DES; the former are the first spectroscopic observations of these recently discovered streams. In addition to the stream survey, we use spare fibres to undertake a Milky Way halo survey and a low-redshift galaxy survey. This paper presents an overview of the S5 program, describing the scientific motivation for the survey, target selection, observation strategy, data reduction, and survey validation. Finally, we describe early science results on stellar streams and Milky Way halo stars drawn from the survey. Updates on S5, including future public data releases, can be found at http://s5collab.github.io

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Variability-selected active galactic nuclei from supernova search in the Chandra deep field south

Variability is a property shared by virtually all active galactic nuclei (AGNs), and was adopted as a criterion for their selection using data from multi epoch surveys. Low Luminosity AGNs (LLAGNs) are contaminated by the light of their host galaxies, and cannot therefore be detected by the usual colour techniques. For this reason, their evolution in cosmic time is poorly known. Consistency with the evolution derived from X-ray detected samples has not been clearly established so far, also because the low luminosity population consists of a mixture of different object types. LLAGNs can be detected by the nuclear optical variability of extended objects. Several variability surveys have been, or are being, conducted for the detection of supernovae (SNe). We propose to re-analyse these SNe data using a variability criterion optimised for AGN detection, to select a new AGN sample and study its properties. We analysed images acquired with the wide field imager at the 2.2 m ESO/MPI telescope, in the framework of the STRESS supernova survey. We selected the AXAF field centred on the Chandra Deep Field South where, besides the deep X-ray survey, various optical data exist, originating in the EIS and COMBO-17 photometric surveys and the spectroscopic database of GOODS. We obtained a catalogue of 132 variable AGN candidates. Several of the candidates are X-ray sources. We compare our results with an HST variability study of X-ray and IR detected AGNs, finding consistent results. The relatively high fraction of confirmed AGNs in our sample (60%) allowed us to extract a list of reliable AGN candidates for spectroscopic follow-up observations.Comment: language revised, table reformatted. To Appear on A&

FcγRIIb Inhibits Allergic Lung Inflammation in a Murine Model of Allergic Asthma

Allergic asthma is characterized by airway eosinophilia, increased mucin production and allergen-specific IgE. Fc gamma receptor IIb (FcγRIIb), an inhibitory IgG receptor, has recently emerged as a negative regulator of allergic diseases like anaphylaxis and allergic rhinitis. However, no studies to date have evaluated its role in allergic asthma. Our main objective was to study the role of FcγRIIb in allergic lung inflammation. We used a murine model of allergic airway inflammation. Inflammation was quantified by BAL inflammatory cells and airway mucin production. FcγRIIb expression was measured by qPCR and flow cytometry and the cytokines were quantified by ELISA. Compared to wild type animals, FcγRIIb deficient mice mount a vigorous allergic lung inflammation characterized by increased bronchoalveolar lavage fluid cellularity, eosinophilia and mucin content upon ragweed extract (RWE) challenge. RWE challenge in sensitized mice upregulated FcγRIIb in the lungs. Disruption of IFN-γ gene abrogated this upregulation. Treatment of naïve mice with the Th1-inducing agent CpG DNA increased FcγRIIb expression in the lungs. Furthermore, treatment of sensitized mice with CpG DNA prior to RWE challenge induced greater upregulation of FcγRIIb than RWE challenge alone. These observations indicated that RWE challenge upregulated FcγRIIb in the lungs by IFN-γ- and Th1-dependent mechanisms. RWE challenge upregulated FcγRIIb on pulmonary CD14+/MHC II+ mononuclear cells and CD11c+ cells. FcγRIIb deficient mice also exhibited an exaggerated RWE-specific IgE response upon sensitization when compared to wild type mice. We propose that FcγRIIb physiologically regulates allergic airway inflammation by two mechanisms: 1) allergen challenge mediates upregulation of FcγRIIb on pulmonary CD14+/MHC II+ mononuclear cells and CD11c+ cells by an IFN-γ dependent mechanism; and 2) by attenuating the allergen specific IgE response during sensitization. Thus, stimulating FcγRIIb may be a therapeutic strategy in allergic airway disorders

Kinematics and simulations of the stellar stream in the halo of the Umbrella Galaxy

We study the dynamics of faint stellar substructures around the Umbrella Galaxy, NGC 4651, which hosts a dramatic system of streams and shells formed through the tidal disruption of a nucleated dwarf elliptical galaxy. We elucidate the basic characteristics of the system (colours, luminosities, stellar masses) using multiband Subaru/Suprime-Cam images. The implied stellar mass ratio of the ongoing merger event is ∼1:50. We identify candidate kinematic tracers (globular clusters, planetary nebulae, H ii regions) and follow up a subset with Keck/DEIMOS (DEep Imaging Multi-object Spectrograph) spectroscopy to obtain velocities. We find that 15 of the tracers are likely associated with halo substructures, including the probable stream progenitor nucleus. These objects delineate a kinematically cold feature in position–velocity phase space. We model the stream using single test particle orbits, plus a rescaled pre-existing N-body simulation. We infer a very eccentric orbit with a period of ∼0.35 Gyr and turning points at ∼2–4 and ∼40 kpc, implying a recent passage of the satellite through the disc, which may have provoked the visible disturbances in the host galaxy. This work confirms that the kinematics of low surface brightness substructures can be recovered and modelled using discrete tracers – a breakthrough that opens up a fresh avenue for unravelling the detailed physics of minor merging

Structural Requirements of SLP-76 in Signaling via the High-Affinity Immunoglobulin E Receptor (FcɛRI) in Mast Cells

The adapter SLP-76 plays an essential role in FcɛRI signaling, since SLP-76(−/−) bone marrow-derived mast cells (BMMC) fail to degranulate and release interleukin-6 (IL-6) following FcɛRI ligation. To define the role of SLP-76 domains and motifs in FcɛRI signaling, SLP-76(−/−) BMMC were retrovirally transduced with SLP-76 and SLP-76 mutants. The SLP-76 N-terminal and Gads binding domains, but not the SH2 domain, were critical for FcɛRI-mediated degranulation and IL-6 secretion, whereas all three domains are essential for T-cell proliferation following T-cell receptor (TCR) ligation. Unexpectedly, the three tyrosine residues in SLP-76 critical for TCR signaling, Y112, Y128, and Y145, were not essential for IL-6 secretion, but were required for degranulation and mitogen-activated protein kinase activation. Furthermore, a Y112/128F SLP-76 mutant, but not a Y145F mutant, strongly reconstituted mast cell degranulation, suggesting a critical role for Y145 in FcɛRI-mediated exocytosis. These results point to important differences in the function of SLP-76 between T cells and mast cells