Agonist-mediated switching of ion selectivity in TPC2 differentially promotes lysosomal function

Ion selectivity is a defining feature of a given ion channel and is considered immutable. Here we show that ion selectivity of the lysosomal ion channel TPC2, which is hotly debated (Calcraft et al., 2009; Guo et al., 2017; Jha et al., 2014; Ruas et al., 2015; Wang et al., 2012), depends on the activating ligand. A high-throughput screen identified two structurally distinct TPC2 agonists. One of these evoked robust Ca2+-signals and non-selective cation currents, the other weaker Ca2+-signals and Na+-selective currents. These properties were mirrored by the Ca2+-mobilizing messenger, NAADP and the phosphoinositide, PI(3,5)P2, respectively. Agonist action was differentially inhibited by mutation of a single TPC2 residue and coupled to opposing changes in lysosomal pH and exocytosis. Our findings resolve conflicting reports on the permeability and gating properties of TPC2 and they establish a new paradigm whereby a single ion channel mediates distinct, functionally-relevant ionic signatures on demand

Measurement of the Inclusive Semi-electronic D0D^0 Branching Fraction

Using the angular correlation between the $\pi^+$ emitted in a $D^{*+} \rightarrow D^0 \pi^+$ decay and the $e^+$ emitted in the subsequent $D^0 \rightarrow Xe^+\nu$ decay, we have measured the branching fraction for the inclusive semi-electronic decay of the $D^0$ meson to be: {\cal B}(D^0 \rightarrow X e^+ \nu) = [6.64 \pm 0.18 (stat.) \pm 0.29 (syst.)] \%. The result is based on 1.7 fb$^{-1}$ of $e^+e^-$ collisions recorded by the CLEO II detector located at the Cornell Electron Storage Ring (CESR). Combining the analysis presented in this paper with previous CLEO results we find, \frac{{\cal B} (D^0 \rightarrow X e^+ \nu)} {{\cal B} (D^0 \rightarrow K^- \pi^+)} = 1.684 \pm 0.056 (stat.) \pm 0.093(syst.) and \frac{{\cal B}(D\rightarrow K^-e^+\nu)} {{\cal B}(D\rightarrow Xe^+\nu)} = 0.581 \pm 0.023 (stat.) \pm 0.028(syst.). The difference between the inclusive rate and the sum of the measured exclusive branching fractions (measured at CLEO and other experiments) is $(3.3 \pm 7.2) \%$ of the inclusive rate.Comment: Latex file, 33pages, 4 figures Submitted to PR

Measurements of the Ratios B(Ds+→ηℓ+ν)/B(Ds+→ϕℓ+ν){\cal B}(D_s^+\to \eta\ell^+\nu)/{\cal B}(D_s^+\to \phi\ell^+\nu) and B(Ds+→η′ℓ+ν)/B(Ds+→ϕℓ+ν){\cal B}(D_s^+\to \eta'\ell^+\nu)/{\cal B}(D_s^+\to \phi\ell^+\nu)

Using the CLEO~II detector we measure ${\cal B}(D_s^+\to \eta e^+\nu)/{\cal B}(D_s^+\to \phi e^+\nu) =1.24\pm0.12\pm0.15$, ${\cal B}(D_s^+\to \eta' e^+\nu)/{\cal B}(D_s^+\to \phi e^+\nu) =0.43\pm0.11\pm0.07$ and ${\cal B}(D_s^+\to \eta' e^+\nu)/{\cal B}(D_s^+\to \eta e^+\nu) =0.35\pm0.09\pm0.07$. We find the vector to pseudoscalar ratio, ${\cal B}(D_s^+\to \phi e^+\nu)/{\cal B}(D_s^+\to (\eta+\eta') e^+\nu) =0.60\pm0.06\pm0.06$, which is similar to the ratio found in non strange $D$ decays.Comment: 11 page uuencoded postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Determination of the Michel Parameters and the tau Neutrino Helicity in tau Decay

Using the CLEO II detector at the $e^+e^-$ storage ring CESR, we have determined the Michel parameters $\rho$, $\xi$, and $\delta$ in $\tau^\mp \to l^\mp\nu\bar{\nu}$ decay as well as the tau neutrino helicity parameter $h_{\nu_\tau}$ in $\tau^\mp \to \pi^\mp\pi^0\nu$ decay. From a data sample of $3.02\times 10^6$ tau pairs produced at $\sqrt{s}=10.6 GeV$, using events of the topology $e^+e^- \to \tau^+\tau^- \to (l^\pm\nu\bar{\nu}) (\pi^\mp\pi^0\nu)$ and $e^+e^- \to \tau^+\tau^- \to (\pi^\pm\pi^0\bar{\nu}) (\pi^\mp\pi^0\nu)$, and the determined sign of $h_{\nu_\tau}$, the combined result of the three samples is: $\rho = 0.747\pm 0.010\pm 0.006$, $\xi = 1.007\pm 0.040\pm 0.015$, $\xi\delta = 0.745\pm 0.026\pm 0.009$, and $h_{\nu_\tau} = -0.995\pm 0.010\pm 0.003$. The results are in agreement with the Standard Model V-A interaction.Comment: 18 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Measurement of the Branching Ratios for the Decays of Ds+→ηπ+,η′π+,ηρ+D_{s}^{+}\to \eta\pi^{+}, \eta^{'}\pi^{+}, \eta\rho^{+}, and eta′ρ+eta^{'}\rho^{+}

Using a data sample with integrated luminosity of about 3.9 fb^{-1} collected in e+ e- annihilation with the CLEO-II detector at the Cornell Electron Storage Ring, we have measured the branching ratios for the decay modes Ds -> (eta, eta') pi and Ds -> (eta, eta') rho relative to Ds -> phi pi. These decay modes are among the most common hadronic decays of the Ds's and can be related by factorization to the semileptonic decays Ds -> (eta,eta') l nu. The results obtained are compared with previous CLEO results and with the branching ratios measured for the related semileptonic decays. We also report results on the Cabibbo-suppressed decays of the D+ to the same final states.Comment: 18 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Measurement of the Bˉ→Dℓνˉ\bar{B}\to D\ell\bar{\nu} Partila Width and Form Factor Parameters

We have studied the decay $\bar{B} \to D\ell\bar{\nu}$, where $\ell=e or \mu$. From a fit to the differential decay rate $d\Gamma/dw$ we measure the rate normalization ${\cal F}_D(1)|V_{cb}|$ and form factor slope $\hat{\rho}^2_D$, and, using measured values of $\tau_B$, find $\Gamma(\bar{B} \to D\ell\bar{\nu}) = (12.0 \pm 0.9 \pm 2.1) ns^{-1}$. The resulting branching fractions are ${\cal B}(\bar{B}^0 \to D^+\ell^-\bar{\nu})=(1.87 \pm 0.15 \pm 0.32)$ and ${\cal B}(B^- \to D^0\ell^-\bar{\nu})=(1.94 \pm 0.15 \pm 0.34)$. The form factor parameters are in agreement with those measured in $\bar{B} \to D^*\ell\bar{\nu}$ decays, as predicted by heavy quark effective theory.Comment: 11 pages, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Tau Neutrino Helicity from h±h^{\pm} Energy Correlations

We report a measurement of the magnitude of the tau neutrino helicity from tau-pair events taken with the CLEO detector at the CESR electron-positron storage ring. Events in which each tau undergoes the decay tau -> h nu, with h a charged pion or kaon, are analyzed for energy correlations between the daughter hadrons, yielding |xi| = 2*|h_nu| = 1.03 +/- 0.06 +/- 0.04, with the first error statistical and the second systematic.Comment: 11 pages, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Limit on the Two-Photon Production of the Glueball Candidate fJ(2220)f_{J}(2220) at CLEO

We use the CLEO detector at the Cornell electron-positron storage ring, CESR, to search for the two-photon production of the glueball candidate f_J(2220) in its decay to K_s K_s. We present a restrictive upper limit on the product of the two-photon partial width and the K_s K_s branching fraction. We use this limit to calculate a lower limit on the stickiness, which is a measure of the two-gluon coupling relative to the two-photon coupling. This limit on stickiness indicates that the f_J(2220) has substantial glueball content.Comment: 9 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Search for Exclusive Charmless Hadronic B Decays

We have searched for two-body charmless hadronic decays of $B$ mesons. Final states include $\pi\pi$, $K \pi$, and $KK$ with both charged and neutral kaons and pions; $\pi\rho$, $K \rho$, and $K^*\pi$; and $K\phi$, $K^*\phi$, and $\phi\phi$. The data used in this analysis consist of 2.6~million $B\bar{B}$~pairs produced at the $\Upsilon(4S)$ taken with the CLEO-II detector at the Cornell Electron Storage Ring (CESR). We measure the branching fraction of the sum of $B^0 \rightarrow \pi^+\pi^-$ and $B^0 \rightarrow K^+\pi^-$ to be $(1.8^{+0.6+0.2}_{-0.5-0.3}\pm0.2) \times 10^{-5}$. In addition, we place upper limits on individual branching fractions in the range from $10^{-4}$ to $10^{-6}$.Comment: 33 page LATEX file, uses REVTEX and psfig, 14 figures in a separate uuencoded postscript file, postscript version also available through http://w4.lns.cornell.edu/public/CLN

Study of Gluon versus Quark Fragmentation in Υ→ggγ\Upsilon\to gg\gamma and e+e−→qqˉγe^{+}e^{-}\to q\bar{q}\gamma Events at \sqrt{s}=10 GeV

Using data collected with the CLEO II detector at the Cornell Electron Storage Ring, we determine the ratio R(chrg) for the mean charged multiplicity observed in Upsilon(1S)->gggamma events, to the mean charged multiplicity observed in e+e- -> qqbar gamma events. We find R(chrg)=1.04+/-0.02+/-0.05 for jet-jet masses less than 7 GeV.Comment: 15 pages, postscript file also available through http://w4.lns.cornell.edu/public/CLN