Suppression of planar cell polarity signaling and migration in glioblastoma by Nrdp1-mediated Dvl polyubiquitination.

The lethality of the aggressive brain tumor glioblastoma multiforme (GBM) results in part from its strong propensity to invade surrounding normal brain tissue. Although oncogenic drivers such as epidermal growth factor receptor activation and Phosphatase and Tensin homolog inactivation are thought to promote the motility and invasiveness of GBM cells via phosphatidylinostitol 3-kinase activation, other unexplored mechanisms may also contribute to malignancy. Here we demonstrate that several components of the planar cell polarity (PCP) arm of non-canonical Wnt signaling including VANGL1, VANGL2 and FZD7 are transcriptionally upregulated in glioma and correlate with poorer patient outcome. Knockdown of the core PCP pathway component VANGL1 suppresses the motility of GBM cell lines, pointing to an important mechanistic role for this pathway in glioblastoma malignancy. We further observe that restoration of Nrdp1, a RING finger type E3 ubiquitin ligase whose suppression in GBM also correlates with poor prognosis, reduces GBM cell migration and invasiveness by suppressing PCP signaling. Our observations indicate that Nrdp1 physically interacts with the Vangl1 and Vangl2 proteins to mediate the K63-linked polyubiquitination of the Dishevelled, Egl-10 and Pleckstrin (DEP) domain of the Wnt pathway protein Dishevelled (Dvl). Ubiquitination hinders Dvl binding to phosphatidic acid, an interaction necessary for efficient Dvl recruitment to the plasma membrane upon Wnt stimulation of Fzd receptor and for the propagation of downstream signals. We conclude that the PCP pathway contributes significantly to the motility and hence the invasiveness of GBM cells, and that Nrdp1 acts as a negative regulator of PCP signaling by inhibiting Dvl through a novel polyubiquitination mechanism. We propose that the upregulation of core PCP components, together with the loss of the key negative regulator Nrdp1, act coordinately to promote GBM invasiveness and malignancy

Velocity-selective sublevel resonance of atoms with an array of current-carrying wires

Resonance transitions between the Zeeman sublevels of optically-polarized Rb atoms traveling through a spatially periodic magnetic field are investigated in a radio-frequency (rf) range of sub-MHz. The atomic motion induces the resonance when the Zeeman splitting is equal to the frequency at which the moving atoms feel the magnetic field oscillating. Additional temporal oscillation of the spatially periodic field splits a motion-induced resonance peak into two by an amount of this oscillation frequency. At higher oscillation frequencies, it is more suitable to consider that the resonance is mainly driven by the temporal field oscillation, with its velocity-dependence or Doppler shift caused by the atomic motion through the periodic field. A theoretical description of motion-induced resonance is also given, with emphasis on the translational energy change associated with the internal transition.Comment: 7 pages, 3 figures, final versio

CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy.

Ovarian cancer and triple-negative breast cancer are among the most lethal diseases affecting women, with few targeted therapies and high rates of metastasis. Cancer cells are capable of evading clearance by macrophages through the overexpression of anti-phagocytic surface proteins called 'don't eat me' signals-including CD471, programmed cell death ligand 1 (PD-L1)2 and the beta-2 microglobulin subunit of the major histocompatibility class I complex (B2M)3. Monoclonal antibodies that antagonize the interaction of 'don't eat me' signals with their macrophage-expressed receptors have demonstrated therapeutic potential in several cancers4,5. However, variability in the magnitude and durability of the response to these agents has suggested the presence of additional, as yet unknown 'don't eat me' signals. Here we show that CD24 can be the dominant innate immune checkpoint in ovarian cancer and breast cancer, and is a promising target for cancer immunotherapy. We demonstrate a role for tumour-expressed CD24 in promoting immune evasion through its interaction with the inhibitory receptor sialic-acid-binding Ig-like lectin 10 (Siglec-10), which is expressed by tumour-associated macrophages. We find that many tumours overexpress CD24 and that tumour-associated macrophages express high levels of Siglec-10. Genetic ablation of either CD24 or Siglec-10, as well as blockade of the CD24-Siglec-10 interaction using monoclonal antibodies, robustly augment the phagocytosis of all CD24-expressing human tumours that we tested. Genetic ablation and therapeutic blockade of CD24 resulted in a macrophage-dependent reduction of tumour growth in vivo and an increase in survival time. These data reveal CD24 as a highly expressed, anti-phagocytic signal in several cancers and demonstrate the therapeutic potential for CD24 blockade in cancer immunotherapy

Ground-state electric quadrupole moment of 31Al

Ground-state electric quadrupole moment of 31Al (I =5/2+, T_1/2 = 644(25) ms) has been measured by means of the beta-NMR spectroscopy using a spin-polarized 31Al beam produced in the projectile fragmentation reaction. The obtained Q moment, |Q_exp(31Al)| = 112(32)emb, are in agreement with conventional shell model calculations within the sd valence space. Previous result on the magnetic moment also supports the validity of the sd model in this isotope, and thus it is concluded that 31Al is located outside of the island of inversion.Comment: 5 page

Searching for νμ→ντ\nu_\mu \to \nu_\tau Oscillations with Extragalactic Neutrinos

We propose a novel approach for studying $\nu_\mu \to \nu_\tau$ oscillations with extragalactic neutrinos. Active Galactic Nuclei and Gamma Ray Bursts are believed to be sources of ultrahigh energy muon neutrinos. With distances of 100 Mpc or more, they provide an unusually long baseline for possible detection of $\nu_\mu \to \nu_\tau$ with mixing parameters $\Delta m^2$ down to $10^{-17}$eV$^2$, many orders of magnitude below the current accelerator experiments. By solving the coupled transport equations, we show that high-energy $\nu_\tau$'s, as they propagate through the earth, cascade down in energy, producing the enhancement of the incoming $\nu_\tau$ flux in the low energy region, in contrast to the high-energy $\nu_\mu$'s, which get absorbed. For an AGN quasar model we find the $\nu_\tau$ flux to be a factor of 2 to 2.5 larger than the incoming flux in the energy range between $10^2$ GeV and $10^4$ GeV, while for a GRB fireball model, the enhancement is 10%-27% in the same energy range and for zero nadir angle. This enhancement decreases with larger nadir angle, thus providing a novel way to search for $\nu_\tau$ appearance by measuring the angular dependence of the muons. To illustrate how the cascade effect and the $\nu_\tau$ final flux depend on the steepness of the incoming $\nu_\tau$, we show the energy and angular distributions for several generic cases of the incoming tau neutrino flux, $F_\nu^0 \sim E^{-n}$ for n=1,2 and 3.6. We show that for the incoming flux that is not too steep, the signal for the appearance of high-energy $\nu_\tau$ is the enhanced production of lower energy $\mu$ and their distinctive angular dependence, due to the contribution from the $\tau$ decay into $\mu$ just below the detector.Comment: 11 pages, including 4 color figure

Classification of Light-Induced Desorption of Alkali Atoms in Glass Cells Used in Atomic Physics Experiments

We attempt to provide physical interpretations of light-induced desorption phenomena that have recently been observed for alkali atoms on glass surfaces of alkali vapor cells used in atomic physics experiments. We find that the observed desorption phenomena are closely related to recent studies in surface science, and can probably be understood in the context of these results. If classified in terms of the photon-energy dependence, the coverage and the bonding state of the alkali adsorbates, the phenomena fall into two categories: It appears very likely that the neutralization of isolated ionic adsorbates by photo-excited electron transfer from the substrate is the origin of the desorption induced by ultraviolet light in ultrahigh vacuum cells. The desorption observed in low temperature cells, on the other hand, which is resonantly dependent on photon energy in the visible light range, is quite similar to light-induced desorption stimulated by localized electronic excitation on metallic aggregates. More detailed studies of light-induced desorption events from surfaces well characterized with respect to alkali coverage-dependent ionicity and aggregate morphology appear highly desirable for the development of more efficient alkali atom sources suitable to improve a variety of atomic physics experiments.Comment: 6 pages, 1 figure; minor corrections made, published in e-Journal of Surface Science and Nanotechnology at http://www.jstage.jst.go.jp/article/ejssnt/4/0/4_63/_articl

The HST Cosmos Project: Contribution from the Subaru Telescope

The Cosmic Evolution Survey (COSMOS) is a Hubble Space Telescope (HST) treasury project.The COSMOS aims to perform a 2 square degree imaging survey of an equatorial field in $I$(F814W) band, using the Advanced Camera for Surveys (ACS). Such a wide field survey, combined with ground-based photometric and spectroscopic data, is essential to understand the interplay between large scale structure, evolution and formation of galaxies and dark matter. In 2004, we have obtained high-quality, broad band images of the COSMOS field ($B, V, r^\prime, i^\prime,$ and $z^\prime$) using Suprime-Cam on the Subaru Telescope, and we have started our new optical multi-band program, COSMOS-21 in 2005. Here, we present a brief summary of the current status of the COSMOS project together with contributions from the Subaru Telescope. Our future Subaru program, COSMOS-21, is also discussed briefly.Comment: 4 pages, 3 figures, to appear in the Proceedings of the 6th East Asian Meeting on Astronomy, JKAS, 39, in pres