A ramsayite-type oxide, Ca2Sn2Al2O9

The title compound, dicalcium nonaoxidodistannate(IV)dialuminate, is the second example which crystallizes in the isotypic structure of a pyroxene silicate, Na2Ti2Si2O9 (ramsayite). ∞ 1[Sn2O8] chains and pyroxene-type ∞ 1[Al2O6] chains are formed along the b axis by sharing O atoms. The Ca atoms are situated in the resulting channels and exhibit a coordination number of 7

A mutation in SFTPA1 and pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by scattered fibrotic lesions in the lungs. The pathogenesis and genetic basis of IPF remain poorly understood. Here, we show that a homozygous missense mutation in SFTPA1 caused IPF in a consanguineous Japanese family. The mutation in SFTPA1 disturbed the secretion of SFTPA1 protein. Sftpa1 knock-in (Sftpa1-KI) mice that harbored the same mutation as patients spontaneously developed pulmonary fibrosis that was accelerated by influenza virus infection. Sftpa1-KI mice showed increased necroptosis of alveolar epithelial type II (AEII) cells with phosphorylation of IRE1α leading to JNK-mediated up-regulation of Ripk3. The inhibition of JNK ameliorated pulmonary fibrosis in Sftpa1-KI mice, and overexpression of Ripk3 in Sftpa1-KI mice treated with a JNK inhibitor worsened pulmonary fibrosis. These findings provide new insight into the mechanisms of IPF in which a mutation in SFTPA1 promotes necroptosis of AEII cells through JNK-mediated up-regulation of Ripk3, highlighting the necroptosis pathway as a therapeutic target for IPF

A QSO host galaxy and its Lyalpha emission at z=6.43

We report an optical detection of an extended structure around a QSO at z=6.43 (CFHQSJ2329-0301, the highest redshift QSO currently known) in deep z' and z_r-band images of the Subaru/Suprime-Cam. After a careful PSF (QSO) subtraction, a structure in the z'-band extends more than 4'' on the sky (R_e=11 kpc), and thus, is well-resolved (16sigma detection). The PSF-subtracted z_r-band structure is in a similar shape to that in the z'-band, but less significant with a 3 sigma detection. In the z'-band, a radial profile of the QSO+host shows a clear excess over that of the averaged PSF in 0.8-3'' radius. Since the z'-band includes a Lya emission at z=6.43, the z' flux is perhaps a mixture of the host (continuum light) and its Lya emission, whereas the z_r-band flux is from the host. Through a SED modeling, we estimate 40% of the PSF-subtracted z'-band light is from the host (continuum) and 60% is from Lya emission. The absolute magnitude of the host is M_{1450}=-23.9 (c.f. M_{1450}=-26.4 for the QSO). A lower limit of the SFR(Lya) is 1.6 Msun yr^{-1} with stellar mass ranging 6.2 x 10^8 to 1.1 x 10^10 Msun when 100 Myrs of age is assumed. The detection shows that a luminous QSO is already harbored by a large, star-forming galaxy in the early Universe only after ~840 Myr after the big bang. The host may be a forming giant galaxy, co-evolving with a super massive black hole.Comment: Accepted for publication in MNRAS. A higher resolution pdf is at http://ifa.hawaii.edu/~tomo/QSOhost/QSOhost_v7.pd

Dual effects of FGFR inhibition in lung fibrosis

[Rationale] Fibroblast growth factors (FGF) are major factors associated with the pathogenesis of pulmonary fibrosis. Nintedanib, a tyrosine kinase inhibitor targeting several growth factor receptors including the FGF receptor (FGFR), has been approved for the treatment of idiopathic pulmonary fibrosis (IPF). On the other hand, recent reports suggest that FGF are required for epithelial recovery. In this study, we focused on FGF signaling to both fibroblasts and alveolar epithelial cells (AECs), and examined the effect of a pan-FGFR blocker on experimental pulmonary fibrosis in mice. [Methods] The effects of BGJ398, a pan-FGFR inhibitor, on the migration and proliferation of fibroblasts and AECs were assessed using transwell migration or 3H-thymidine incorporation assays. The expression of FGFR was analyzed using immunoblot or flow cytometry. We also investigated the effect of BGJ398 on the pulmonary fibrosis induced by bleomycin in mice. [Results] Both lung fibroblasts and AECs expressed FGFRs. BGJ398 significantly inhibited the proliferation and migration of lung fibroblasts stimulated with FGF2. BGJ398 also reduced the proliferation of AECs in response to FGF2. Although the administration of BGJ398 ameliorated pulmonary fibrosis in bleomycin-treated mice, it increased mortality due to alveolar injury and inhibition of AEC regeneration. [Conclusions] These data suggest that the total inhibition of FGFR signaling can suppress lung fibrosis by inhibiting fibroblast activities, although alveolar injury is simultaneously caused

SILVERRUSH. III. Deep Optical and Near-Infrared Spectroscopy for Lya and UV-Nebular Lines of Bright Lya Emitters at z=6-7

We present Lya and UV-nebular emission line properties of bright Lya emitters (LAEs) at z=6-7 with a luminosity of log L_Lya/[erg s-1] = 43-44 identified in the 21-deg2 area of the SILVERRUSH early sample developed with the Subaru Hyper Suprime-Cam (HSC) survey data. Our optical spectroscopy newly confirm 21 bright LAEs with clear Lya emission, and contribute to make a spectroscopic sample of 96 LAEs at z=6-7 in SILVERRUSH. From the spectroscopic sample, we select 7 remarkable LAEs as bright as Himiko and CR7 objects, and perform deep Keck/MOSFIRE and Subaru/nuMOIRCS near-infrared spectroscopy reaching the 3sigma-flux limit of ~ 2x10^{-18} erg s-1 for the UV-nebular emission lines of He II1640, C IV1548,1550, and O III]1661,1666. Except for one tentative detection of C IV, we find no strong UV-nebular lines down to the flux limit, placing the upper limits of the rest-frame equivalent widths (EW_0) of ~2-4 A for He II, C IV, and O III] lines. Here we also investigate the VLT/X-SHOOTER spectrum of CR7 whose 6 sigma detection of He II is claimed by Sobral et al. Although two individuals and the ESO-archive service carefully re-analyze the X-SHOOTER data that are used in the study of Sobral et al., no He II signal of CR7 is detected, supportive of weak UV-nebular lines of the bright LAEs even for CR7. Spectral properties of these bright LAEs are thus clearly different from those of faint dropouts at z~7 that have strong UV-nebular lines shown in the various studies. Comparing these bright LAEs and the faint dropouts, we find anti-correlations between the UV-nebular line EW_0 and UV-continuum luminosity, which are similar to those found at z~2-3.Comment: 26 pages, 12 figures. Accepted for publication in PASJ special issu

Anti-fibrotic efficacy of nintedanib in pulmonary fibrosis via the inhibition of fibrocyte activity

Background: Nintedanib, a tyrosine kinase inhibitor that is specific for platelet-derived growth factor receptors (PDGFR), fibroblast growth factor receptors (FGFR), and vascular endothelial growth factor receptors (VEGFR), has recently been approved for idiopathic pulmonary fibrosis. Fibrocytes are bone marrow-derived progenitor cells that produce growth factors and contribute to fibrogenesis in the lungs. However, the effects of nintedanib on the functions of fibrocytes remain unclear. Methods: Human monocytes were isolated from the peripheral blood of healthy volunteers. The expression of growth factors and their receptors in fibrocytes was analyzed using ELISA and Western blotting. The effects of nintedanib on the ability of fibrocytes to stimulate lung fibroblasts were examined in terms of their proliferation. The direct effects of nintedanib on the differentiation and migration of fibrocytes were also assessed. We investigated whether nintedanib affected the accumulation of fibrocytes in mouse lungs treated with bleomycin. Results: Human fibrocytes produced PDGF, FGF2, and VEGF-A. Nintedanib and specific inhibitors for each growth factor receptor significantly inhibited the proliferation of lung fibroblasts stimulated by the supernatant of fibrocytes. Nintedanib inhibited the migration and differentiation of fibrocytes induced by growth factors in vitro. The number of fibrocytes in the bleomycin-induced lung fibrosis model was reduced by the administration of nintedanib, and this was associated with anti-fibrotic effects. Conclusions: These results support the role of fibrocytes as producers of and responders to growth factors, and suggest that the anti-fibrotic effects of nintedanib are at least partly mediated by suppression of fibrocyte function

A dozen new galaxies caught in the act: Gas stripping and extended emission line regions in the Coma cluster

We present images of extended H-alpha clouds associated with 14 member galaxies in the Coma cluster obtained from deep narrow band imaging observations with Suprime-Cam at the Subaru Telescope. The parent galaxies of the extended H-alpha clouds are distributed farther than 0.2 Mpc from the peak of X-ray emission of the cluster. Most of the galaxies have colors bluer than g-r approx 0.5 and they account for 57% of the blue (g-r<0.5) bright (r<17.8 mag) galaxies in the central region of the Coma cluster. They reside near the red- and blue-shifted edges of the Coma cluster's radial velocity distribution. These findings suggest that the most of the parent galaxies were recently captured by the Coma cluster potential and are now infalling toward the cluster center with their disk gas being stripped off and producing the observed H-alpha clouds.Comment: 22 pages, 46 figures, AJ accepte

骨髄由来線維細胞は肺がん細胞のがん幹細胞様特性を増強する

Cancer stem cells (CSCs) represent a minor population that have clonal tumor initiation and self-renewal capacity and are responsible for tumor initiation, metastasis, and therapeutic resistance. CSCs reside in niches, which are composed of diverse types of stromal cells and extracellular matrix components. These stromal cells regulate CSC-like properties by providing secreted factors or by physical contact. Fibrocytes are differentiated from bone marrow-derived CD14þ monocytes and have features of both macrophages and fibroblasts. Accumulating evidence has suggested that stromal fibrocytes might promote cancer progression. However, the role of fibrocytes in the CSC niches has not been revealed. We herein report that human fibrocytes enhanced the CSC-like properties of lung cancer cells through secreted factors, including osteopontin, CC-chemokine ligand 18, and plasminogen activator inhibitor-1. The PIK3K/AKT pathway was critical for fibrocytes to mediate the CSC-like functions of lung cancer cells. In human lung cancer specimens, the number of tumor-infiltrated fibrocytes was correlated with high expression of CSC-associated protein in cancer cells. These results suggest that fibrocytes may be a novel cell population that regulates the CSC-like properties of lung cancer cells in the CSC niches