Inhibition of WNT signaling attenuates self-renewal of SHH-subgroup medulloblastoma

The SMOOTHENED inhibitor vismodegib is FDA approved for advanced basal cell carcinoma (BCC), and shows promise in clinical trials for SONIC HEDGEHOG (SHH)-subgroup medulloblastoma (MB) patients. Clinical experience with BCC patients shows that continuous exposure to vismodegib is necessary to prevent tumor recurrence, suggesting the existence of a vismodegib-resistant reservoir of tumor-propagating cells. We isolated such tumor-propagating cells from a mouse model of SHH-subgroup MB and grew them as sphere cultures. These cultures were enriched for the MB progenitor marker SOX2 and formed tumors in vivo. Moreover, while their ability to self-renew was resistant to SHH inhibitors, as has been previously suggested, this self-renewal was instead WNT-dependent. We show here that loss of Trp53 activates canonical WNT signaling in these SOX2-enriched cultures. Importantly, a small molecule WNT inhibitor was able to reduce the propagation and growth of SHH-subgroup MB in vivo, in an on-target manner, leading to increased survival. Our results imply that the tumor- propagating cells driving the growth of bulk SHH-dependent MB are themselves WNT dependent. Further, our data suggest combination therapy with WNT and SHH inhibitors as a therapeutic strategy in patients with SHH-subgroup MB, in order to decrease the tumor recurrence commonly observed in patients treated with vismodegi

Measurement of the direct CPCP asymmetry in Bˉ→Xs+dγ\bar{B}\rightarrow X_{s+d}\gamma decays with a lepton tag

We report the measurement of the direct $CP$ asymmetry in the radiative $\bar{B}\rightarrow X_{s+d}\gamma$ decay using a data sample of $(772 \pm 11)\times 10^6$ $B\bar{B}$ pairs collected at the $\Upsilon(4S)$ resonance with the Belle detector at the KEKB asymmetric-energy $e^+e^-$ collider. The $CP$ asymmetry is measured as a function of the photon energy threshold. For $E^{\rm{*}}_{\gamma} \geq 2.1~{\rm{GeV}}$, where $E^{\rm{*}}_{\gamma}$ is the photon energy in the center-of-mass frame, we obtain $\mathcal{A}_{CP}(\bar{B}\rightarrow X_{s+d}\gamma)= (2.2 \pm 3.9 \pm 0.9) \%$, consistent with the Standard Model prediction.Comment: Published at PR

Measurement of B(/\c->pKpi)

The /\c->pKpi yield has been measured in a sample of two-jet continuum events containing a both an anticharm tag (Dbar) as well as an antiproton (e+e- -> Dbar pbar X), with the antiproton in the hemisphere opposite the Dbar. Under the hypothesis that such selection criteria tag e+e- -> Dbar pbar (/\c) X events, the /\c->pkpi branching fraction can be determined by measuring the pkpi yield in the same hemisphere as the antiprotons in our Dbar pbar X sample. Combining our results from three independent types of anticharm tags, we obtain B(/\c->pKpi)=(5.0+/-0.5+/-1.2)

Update of the Search for the Neutrinoless Decay τ→μγ\tau\to \mu\gamma

We present an update of the search for the lepton family number violating decay $\tau \to \mu\gamma$ using a complete CLEO II data sample of 12.6 million $\tau^+\tau^-$ pairs. No evidence of a signal has been found and the corresponding upper limit is \BR(\tau \to \mu\gamma) < 1.0 \times 10^{-6} at 90% CL, significantly smaller than previous limits. All quoted results are preliminary.Comment: 9 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN

Measurement of Charge Asymmetries in Charmless Hadronic in B Meson Decays

We search for CP-violating asymmetries (Acp) in the B meson decays to K+- pi-+, K+- pi0, Ks pi+-, K+- eta', and omega pi+-. Using 9.66 million Upsilon(4S) decays collected with the CLEO detector, the statistical precision on Acp is in the range of \pm 0.12 to \pm 0.25 depending on decay mode. While CP-violating asymmetries of up to \pm 0.5 are possible within the Standard Model, the measured asymmetries are consistent with zero in all five decay modes studied.Comment: 10 pages, 3 figure

Observation of Radiative Leptonic Decay of the Tau Lepton

Using 4.68 fb^{-1} of e^+e^- annihilation data collected with the CLEO II detector at the Cornell Electron Storage Ring (CESR) we have studied tau radiative decays tau -> mu nu nu gamma and tau -> e nu nu gamma. For a 10 MeV minimum photon energy in the tau rest frame, the branching fraction of radiative tau decay to a muon or electron is measured to be (3.61+-0.16+-0.35)*10^{-3} or (1.75+-0.06+-0.17)*10^{-2}, respectively. The branching fractions are in agreement with the Standard Model theoretical predictions.Comment: 11 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN

Hadronic Structure in the Decay τ−→π−π0ντ\tau^{-}\to \pi^{-}\pi^{0}\nu_{\tau}

We report on a study of the invariant mass spectrum of the hadronic system in the decay tau- -> pi- pi0 nu_tau. This study was performed with data obtained with the CLEO II detector operating at the CESR e+ e- collider. We present fits to phenomenological models in which resonance parameters associated with the rho(770) and rho(1450) mesons are determined. The pi- pi0 spectral function inferred from the invariant mass spectrum is compared with data on e+ e- -> pi+ pi- as a test of the Conserved Vector Current theorem. We also discuss the implications of our data with regard to estimates of the hadronic contribution to the muon anomalous magnetic moment.Comment: 39 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN

APC/CCdh1-Mediated Degradation of the F-Box Protein NIPA Is Regulated by Its Association with Skp1

NIPA (Nuclear Interaction Partner of Alk kinase) is an F-box like protein that targets nuclear Cyclin B1 for degradation. Integrity and therefore activity of the SCFNIPA E3 ligase is regulated by cell-cycle-dependent phosphorylation of NIPA, restricting substrate ubiquitination to interphase. Here we show that phosphorylated NIPA is degraded in late mitosis in an APC/CCdh1-dependent manner. Binding of the unphosphorylated form of NIPA to Skp1 interferes with binding to the APC/C-adaptor protein Cdh1 and therefore protects unphosphorylated NIPA from degradation in interphase. Our data thus define a novel mode of regulating APC/C-mediated ubiquitination

Limit on Tau Neutrino Mass from τ−→π−π+π−π0ντ\tau^{-}\to \pi^{-}\pi^{+}\pi^{-}\pi^{0}\nu_{\tau}

From a data sample of 29058 $\tau^\pm\to\pi^\pm\pi^+\pi^-\pi^0\nu_\tau$ decays observed in the CLEO detector we derive a 95% confidence upper limit on the tau neutrino mass of 28 MeV.Comment: 17 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN