308 research outputs found

    TLR ligand-induced podosome disassembly in dendritic cells is ADAM17 dependent

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    Toll-like receptor (TLR) signaling induces a rapid reorganization of the actin cytoskeleton in cultured mouse dendritic cells (DC), leading to enhanced antigen endocytosis and a concomitant loss of filamentous actin–rich podosomes. We show that as podosomes are lost, TLR signaling induces prominent focal contacts and a transient reduction in DC migratory capacity in vitro. We further show that podosomes in mouse DC are foci of pronounced gelatinase activity, dependent on the enzyme membrane type I matrix metalloprotease (MT1-MMP), and that DC transiently lose the ability to degrade the extracellular matrix after TLR signaling. Surprisingly, MMP inhibitors block TLR signaling–induced podosome disassembly, although stimulated endocytosis is unaffected, which demonstrates that the two phenomena are not obligatorily coupled. Podosome disassembly caused by TLR signaling occurs normally in DC lacking MT1-MMP, and instead requires the tumor necrosis factor α–converting enzyme ADAM17 (a disintegrin and metalloprotease 17), which demonstrates a novel role for this “sheddase” in regulating an actin-based structure

    A New Population of High Redshift, Dusty Lyman-Alpha Emitters and Blobs Discovered by WISE

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    We report a new technique to select 1.6<z<4.6 dusty Lyman-alpha emitters (LAEs), over a third of which are `blobs' (LABs) with emission extended on scales of 30-100kpc. Combining data from the NASA Wide-field Infrared Survey Explorer (WISE) mission with optical spectroscopy from the W.M. Keck telescope, we present a color criteria that yields a 78% success rate in identifying rare, dusty LAEs of which at least 37% are LABs. The objects have a surface density of only ~0.1 per square degree, making them rare enough that they have been largely missed in narrow surveys. We measured spectroscopic redshifts for 92 of these WISE-selected, typically radio-quiet galaxies and find that the LAEs (LABs) have a median redshift of 2.3 (2.5). The WISE photometry coupled with data from Herschel reveals that these galaxies have extreme far-infrared luminosities (L_IR>10^{13-14}L_sun) and warm colors, typically larger than submillimeter-selected galaxies (SMGs) and dust-obscured galaxies (DOGs). These traits are commonly associated with the dust being energized by intense AGN activity. We hypothesize that the combination of spatially extended Lyman-alpha, large amounts of warm IR-luminous dust, and rarity (implying a short-lived phase) can be explained if the galaxies are undergoing strong `feedback' transforming them from an extreme dusty starburst to a QSO.Comment: Submitted to ApJ Letters, 6 pages, 4 figures. Comments welcom

    Is diagnostic tonsillectomy indicated in all children with asymmetrically enlarged tonsil?

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    Objectives. The aims of the study were: (i) to determine the necessity for diagnostic tonsillectomy in children with asymmetrically enlarged tonsils; (ii) to determine the accuracy of clinical assessment of tonsillar asymmetry; and (iii) to determine how to manage children with clinical tonsillar asymmetry in a developing-world practice. Methods. A prospective study was carried out at Red Cross War Memorial Children’s Hospital in Cape Town, over an 8-month period. All children undergoing tonsillectomy or adenotonsillectomy had a clinical assessment of tonsil symmetry done, and all tonsil and adenoid specimens were examined histologically. The maximum diameter and volume of the resected tonsils were measured. A comparison was done of true tonsil asymmetry in patients with asymmetrical tonsils and a subgroup of matched controls with symmetrical tonsils. Results. A total of 344 tonsils were analysed (172 patients). The 13 patients (7.6%) diagnosed as having clinically asymmetrically enlarged tonsils had no significant pathological diagnosis. In the patients with symmetrical tonsils there were abnormal pathological findings (tuberculosis of the adenoids and T-cell lymphoma of the tonsils and adenoids). In the clinically asymmetrical tonsil group, true tonsillar asymmetry was 3 mm (maximum diameter), and 2.2 cm3 (volume), compared with 1.9 mm and 1.5 cm3 in the symmetrical tonsil group. When patients with clinical tonsillar asymmetry and symmetry were compared, the difference in maximum diameter (p = 0.62) and volume (p = 0.73) was not significantly different. Conclusions. Clinical tonsillar asymmetry is usually apparent rather than real. The incidence of significant pathology in children with asymptomatic, asymmetrical tonsils is low. Diagnostic tonsillectomy is indicated in children with asymmetrically enlarged tonsils associated with constitutional symptoms, cervical lymphadenopathy, rapid tonsil enlargement or significant tonsillar asymmetry

    The PDK1-Rsk signaling pathway controls Langerhans cell proliferation and patterning

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    Langerhans cells (LC), the dendritic cells of the epidermis, are distributed in a distinctive regularly spaced array. In the mouse, the LC array is established in the first few days of life from proliferating local precursors, but the regulating signaling pathways are not fully understood. We found that mice lacking the kinase phosphoinositide-dependent kinase 1 selectively lack LC. Deletion of the phosphoinositide-dependent kinase 1 target kinases, ribosomal S6 kinase 1 (Rsk1) and Rsk2, produced a striking perturbation in the LC network: LC density was reduced 2-fold, but LC size was increased by the same magnitude. Reduced LC numbers in Rsk1/2?/? mice was not due to accelerated emigration from the skin but rather to reduced proliferation at least in adults. Rsk1/2 were required for normal LC patterning in neonates, but not when LC were ablated in adults and replaced by bone marrow–derived cells. Increased LC size was an intrinsic response to reduced LC numbers, reversible on LC emigration, and could be observed in wild type epidermis where LC size also correlated inversely with LC density. Our results identify a key signaling pathway needed to establish a normal LC network and suggest that LC might maintain epidermal surveillance by increasing their “footprint” when their numbers are limite

    Constraining Dust and Molecular Gas Properties in Lyα Blobs at z ~ 3

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    In order to constrain the bolometric luminosities, dust properties, and molecular gas content of giant Lyα nebulae, the so-called Lyα blobs, we have carried out a study of dust continuum and CO line emission in two well-studied representatives of this population at z ~ 3: an Lyα blob discovered by its strong Spitzer Multiband Infrared Photometer 24 ÎŒm detection (LABd05) and the Steidel blob 1 (SSA22-LAB01). We find that the spectral energy distribution of LABd05 is well described by an active-galactic-nucleus-starburst composite template with L_(FIR) = (4.0 ± 0.5) × 10^(12) L_☉, comparable to high-z submillimeter galaxies and ultraluminous infrared galaxies. New Large APEX Bolometer Camera 870 ÎŒm measurements rule out the reported Submillimeter Common-User Bolometer Array detection of the SSA22-LAB01 (S_(850 ÎŒm) = 16.8 mJy) at the >4σ level. Consistent with this, ultradeep Plateau de Bure Interferometer observations with ~2'' spatial resolution also fail to detect any 1.2 mm continuum source down to ≈0.45 mJy beam^(–1) (3σ). Combined with the existing (sub)millimeter observations in the literature, we conclude that the FIR luminosity of SSA22-LAB01 remains uncertain. No CO line is detected in either case down to integrated flux limits of S_ΜΔV ≟ 0.25-1.0 Jy km s^(–1), indicating a modest molecular gas reservoir, M(H_2) < (1-3) × 10^(10) M_☉. The non-detections exclude, with high significance (12σ), the previous tentative detection of a CO J = 4-3 line in the SSA22-LAB01. The increased sensitivity afforded by the Atacama Large Millimeter/submillimeter Array will be critical in studying molecular gas and dust in these interesting systems
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