Modeling a disease-correlated tubulin mutation in budding yeast reveals insight into MAP-mediated dynein function.

Mutations in the genes that encode α- and ß-tubulin underlie many neurological diseases, most notably malformations in cortical development. In addition to revealing the molecular basis for disease etiology, studying such mutations can provide insight into microtubule function and the role of the large family of microtubule effectors. In this study, we use budding yeast to model one such mutation-Gly436Arg in α-tubulin, which is causative of malformations in cortical development-in order to understand how it impacts microtubule function in a simple eukaryotic system. Using a combination of in vitro and in vivo methodologies, including live cell imaging and electron tomography, we find that the mutant tubulin is incorporated into microtubules, causes a shift in α-tubulin isotype usage, and dramatically enhances dynein activity, which leads to spindle-positioning defects. We find that the basis for the latter phenotype is an impaired interaction between She1-a dynein inhibitor-and the mutant microtubules. In addition to revealing the natural balance of α-tubulin isotype utilization in cells, our results provide evidence of an impaired interaction between microtubules and a dynein regulator as a consequence of a tubulin mutation and sheds light on a mechanism that may be causative of neurodevelopmental diseases.

First measurement of the form factors in the decays D0 → ρ- e+ ν(e) and D+ → ρ0 e+ ν(e).

The beauty to up quark coupling constant |V(ub)| can be extracted from B → ρ e+ ν(e) combined with the form factors for D → K* e+ ν(e) and B → V ℓ+ ℓ- and D → ρ e+ ν(e). Using the entire CLEO-c ψ(3770) → DD event sample, corresponding to an integrated luminosity of 818 pb(-1) and approximately 5.4×10(6) DD events, we measure the form factors for the decays D0 → ρ- e+ ν(e) and D+ → ρ0 e+ ν(e) for the first time and the branching fractions with improved precision. A four-dimensional unbinned maximum likelihood fit determines the form factor ratios to be V(0)/A1(0)=1.48±0.15±0.05 and A2(0)/A1(0)=0.83±0.11±0.04. Assuming Cabibbo-Kobayashi-Maskawa unitarity, the known D meson lifetimes, and our measured branching fractions we obtain the form factor normalizations A1(0), A2(0), and V(0). We also present a measurement of the branching fraction for D+ → ω e+ ν(e) with improved precision.

Observation of the h(c)(1P) Using e+ e- collisions above the DD threshold.

Using 586 pb(-1) of e+ e- collision data at E(c.m.) = 4170 MeV, produced at the Cornell Electron Storage Ring collider and collected with the CLEO-c detector, we observe the process e+ e- → π+ π- h(c)(1P). We measure its cross section to be 15.6±2.3±1.9±3.0 pb, where the third error is due to the external uncertainty on the branching fraction of ψ(2S) → π0 h(c)(1P), which we use for normalization. We also find evidence for e+ e- → ηh(c)(1P) at 4170 MeV at the 3σ level and see hints of a rise in the e+ e- → π+ π- h(c)(1P) cross section at 4260 MeV.

J/psi and psi(2S) Radiative Transitions to eta_{c}.

Using 2.45x10;{7} psi(2S) decays collected with the CLEO-c detector at the Cornell Electron Storage Ring we present the most precise measurements of magnetic dipole transitions in the charmonium system. We measure B(psi(2S)-->gammaeta_{c})=(4.32+/-0.16+/-0.60)x10;{-3}, B(J/psi-->gammaeta_{c})/B(psi(2S)-->gammaeta_{c})=4.59+/-0.23+/-0.64, and B(J/psi-->gammaeta_{c})=(1.98+/-0.09+/-0.30)%. We observe a distortion in the eta_{c} line shape due to the photon-energy dependence of the magnetic dipole transition rate. We find that measurements of the eta_{c} mass are sensitive to the line shape, suggesting an explanation for the discrepancy between measurements of the eta_{c} mass in radiative transitions and other production mechanisms.

Observation of D+ --> etae + nue.

Using a 281 pb-1 data sample collected at the psi(3770) resonance with the CLEO-c detector at the Cornell Electron Storage Ring, we report the first observation of D+ --> etae + nue. We also set upper limits for D+ --> eta'e + nue and D + --> varphie + nue that are about 2 orders of magnitude more restrictive than those obtained by previous experiments.

Observation of chicJ radiative decays to light vector mesons.

Using a total of 2.74 x 10(7) decays of the psi(2S) collected with the CLEO-c detector, we present a study of chi(cJ)-->gammaV, where V=rho(0), omega, phi. The transitions chi(c1)-->gammarho(0 and chi(c1)-->gammaomega are observed with B(chi(c1)-->gammarho(0))=(2.43+/-0.19+/-0.22) x 10(-4) and B(chi(c1)-->gammaomega)=(8.3+/-1.5+/-1.2) x 10(-5). In the chi(c1)-->gammarho(0) transition, the final state meson is dominantly longitudinally polarized. Upper limits on the branching fractions of other chi(cJ) states to light vector mesons are presented.

Measurement of the eta'-meson mass using J/psi-->gammaeta'.

We measure the mass of the eta;{'} meson using psi(2S)-->pi;{+}pi;{-}J/psi, J/psi-->gammaeta;{'} events acquired with the CLEO-c detector operating at the CESR e;{+}e;{-} collider. Using three decay modes, eta;{'}-->rho;{0}gamma, eta;{'}-->pi;{+}pi;{-}eta with eta-->gammagamma, and eta;{'}-->pi;{+}pi;{-}eta with eta-->pi;{+}pi;{-}pi;{0}, we find M_{eta;{'}}=957.793+/-0.054+/-0.036 MeV, in which the uncertainties are statistical and systematic, respectively. This result is consistent with but substantially more precise than the current world average.

Precision measurement of the mass of the hc(1P1) state of charmonium.

A precision measurement of the mass of the h_{c}(1P1) state of charmonium has been made using a sample of 24.5x10;{6} psi(2S) events produced in e;{+}e;{-} annihilation at the Cornell Electron Storage Ring (CESR). The reaction used was psi(2S)-->pi;{0}h_{c}, pi;{0}-->gammagamma, h_{c}-->gammaeta_{c}, and the reaction products were detected in the CLEO-c detector. Data have been analyzed both for the inclusive reaction and for the exclusive reactions in which eta_{c} decays are reconstructed in 15 hadronic decay channels. Consistent results are obtained in the two analyses. The averaged results of the present measurements are M(h_{c})=3525.28+/-0.19(stat.)+/-0.12(syst.) MeV, and B(psi(2S)-->pi;{0}h_{c})xB(h_{c}-->gammaeta_{c})=(4.19+/-0.32+/-0.45)x10;{-4}. Using the ;{3}P_{J} centroid mass, DeltaM_{hf}(1P) identical withM(chi_{cJ})-M(h_{c})=+0.02+/-0.19+/-0.13 MeV.

Measurement of the absolute branching fraction of Ds+ --> tau+ nutau decay.

Using a sample of tagged D(s)(+) decays collected near the D(s)(*+/-)D(s)(-/+) peak production energy in e(+)e(-) collisions with the CLEO-c detector, we study the leptonic decay D(s)(+)-->tau(+)nu(tau) via the decay channel tau(+)-->e(+)nu(e)nu(tau). We measure B(D(s)(+)-->tau(+)nu(tau))=(6.17+/-0.71+/-0.34)%, where the first error is statistical and the second systematic. Combining this result with our measurements of D(s)(+)-->mu(+)nu(mu) and D(s)(+)-->tau(+)nu(tau) (via tau(+)-->pi(+)nu(tau)), we determine f(D(s))=(274+/-10+/-5) MeV.

First observation of the decay Ds+-->pn.

Using e+e--->Ds*-Ds+ data collected near the peak Ds production energy, Ecm=4170 MeV, with the CLEO-c detector, we present the first observation of the decay Ds+-->pn. We measure a branching fraction B(Ds+-->pn)=(1.30+/-0.36(-0.16)+0.12)x10(-3). This is the first observation of a charmed meson decaying into a baryon-antibaryon final state.

Precision determination of the D0 mass.

A precision measurement of the D0 meson mass has been made using approximately 281 pb(-1) of e+e- annihilation data taken with the CLEO-c detector at the psi(3770) resonance. The exclusive decay D0-->K_{S}phi has been used to obtain M(D0)=1864.847+/-0.150(stat)+/-0.095(syst) MeV. This corresponds to M(D0D*0)=3871.81+/-0.36 MeV, and leads to a well-constrained determination of the binding energy of the proposed D0D*0 molecule X(3872), as Eb=0.6+/-0.6 MeV.

Charmonium Decays of Y(4260), psi(4160), and psi(4040).

Using data collected with the CLEO detector operating at the CESR e+e- collider at sqrt[s]=3.97-4.26 GeV, we investigate 15 charmonium decay modes of the psi(4040), psi(4160), and Y(4260) resonances. We confirm, at 11 sigma significance, the BABAR Y(4260)-->pi+pi- J/psi discovery, make the first observation of Y(4260)--> pi(0)pi(0) J/psi (5.1 sigma), and find the first evidence for Y(4260)-->K+K- J/psi(3.7 sigma). We measure e+e- cross sections at sqrt[s]=4.26 GeV as sigma(pi+pi- J/psi)=58(+12)(-10)+/-4 pb, sigma(pi(0)pi(0) J/psi)=23(+12)(-8)+/-1 pb, and sigma(K+K- J/psi)=9(+9)(-5)+/-1 pb, in which the uncertainties are statistical and systematic, respectively. Upper limits are placed on other decay rates from all three resonances.

Observation of Psi(3770)-->gammachi(c1)-->gammagammaJ/Psi.

From e(+)e(-) collision data acquired with the CLEO detector at the Cornell Electron Storage Ring, we observe the non-DD(_) decay Psi(3770))-->gammachi(c1) with a statistical significance of 6.6 standard deviations, using the two-photon cascades to J/Psi and J/Psi-->l(+)l(-). We determine sigma(e(=)e(-)-->Psi(3770))xBeta(Psi(3770)-->gammachi(c1))=(18.0 +/- 3.3 +/- 2.5) pb and branching fraction Beta(Psi(3770)-->gammachi(c1)=(2.8 +/- 0.5+/-0.4) x 10(-3). We set 90% C.L. upper limits for the transition to chi(c2) (chi(c0)): sigma x Beta<5.7 pb (<282 pb) and Beta<0.9 x 10(-3) (<44 x 10(-3)). We also determine Gamma(Psi(3770)gammachi(c1))/Gamma(Psi(3770)-->pi(+)pi(-)J/Psi)=1.5 +/- 0.3 +/- 0.3 (>1.0 at 90% C.L.), which bears upon the interpretation of X(3872).

Experimental limits on weak annihilation contributions to decays.

We present the first experimental limits on high-q2 contributions to charmless semileptonic decays of the form expected from the weak annihilation (WA) decay mechanism. Such contributions could bias determinations of /Vub/ from inclusive measurements of B-->Xulupsilon. Using a wide range of models based on available theoretical input we set a limit of GammaWA/Gammab-->u<7.4% (90% confidence level) on the WA fraction, and assess the impact on previous inclusive determinations of /Vub/.

Observation of psi(3770) --> pi pi J/psi and measurement of Gamma ee[psi(2S)].

We observe signals for the decays psi(3770) --> XJ/psi from data acquired with the CLEO detector operating at the CESR e+ e- collider with square root of s = 3773 MeV. We measure the following branching fractions Beta(psi(3770) --> XJ/psi and significances: (189 +/- 20 +/- 20) x 10(-5) (11.6sigma) for X = pi+ pi-, (80 +/- 25 +/- 16) x 10(-5) (3.4sigma) for X = pi0 pi0, and (87 +/- 33 +/- 22) x 10(-5) (3.5sigma) for X = eta, where the errors are statistical and systematic, respectively. The radiative return process e+ e- --> gamma psi(2S) populates the same event sample and is used to measure Gamma ee[psi(2S)] = (2.54 +/- 0.03 +/- 0.11) keV.

Dielectron widths of the Gamma(1S,2S,3S) resonances.

We determine the dielectron widths of the Gamma(1S), Gamma(2S), and Gamma(3S) resonances with better than 2% precision by integrating the cross section of e+e- -->Gamma over the e+e- center-of-mass energy. Using e+e- energy scans of the Gamma resonances at the Cornell Electron Storage Ring and measuring Gamma production with the CLEO detector, we find dielectron widths of 1.252+/-0.004(sigma(stat))+/-0.019(sigma(syst)) keV, 0.581+/-0.004+/-0.009 keV, and 0.413+/-0.004+/-0.006 keV for the Gamma(1S), Gamma(2S), and Gamma(3S), respectively.

Observation of Bs production at the Y(5S) resonance.

Using the CLEO detector at the Cornell Electron Storage Ring, we have observed the Bs meson in e+e- annihilation at the Y(5S) resonance. We find 14 candidates consistent with Bs decays into final states with a J/psi or a Ds(*)- . The probability that we have observed a background fluctuation is less than 8 x 10(-10) . We have established that at the energy of the Y(5S) resonance Bs production proceeds predominantly through the creation of Bs*Bs* pairs. We find sigma(e+e- --> Bs*Bs*) = [0.11(-0.03))(+0.04)(stat) +/- 0.02(syst)]nb , and set the following limits: sigma(e+e- --> BsBs)/ sigma(e+ e- --> Bs*Bs*) <0.16 and [sigma(e+e- --> BsBs*) + sigma(e+e- --> Bs*Bs)]/sigma(e+e- -->Bs*Bs*) < 0.16 (90% C.L.). The mass of the Bs* meson is measured to be M(Bs*) = [5.414+/- 0.001(stat) +/- 0.003(syst)] GeV/c2 .

Absolute branching fraction measurements for D+ and D0 inclusive semileptonic decays.

We present measurements of the inclusive branching fractions for the decays D+-->Xe+ nu(e) and D0-->Xe+ nu(e), using 281 pb(-1) of data collected on the psi(3770) resonance with the CLEO-c detector. We find B(D0-->Xe+ nu(e)) = (6.46+/-0.17+/-0.13)% and B(D+-->Xe+ nu(e)) = (16.13+/-0.20+/-0.33)%. Using the known D meson lifetimes, we obtain the ratio Gamma(D+)sl/Gamma(D0)sl = 0.985+/-0.028+/-0.015, confirming isospin invariance at the level of 3%. The positron momentum spectra from D+ and D0 have consistent shapes.

Absolute branching fraction measurements of exclusive D0 semileptonic decays.

With the first data sample collected by the CLEO-c detector at the psi(3770) resonance we have studied four exclusive semileptonic decays of the D0 meson. Our results include the first observation and absolute branching fraction measurement for D0 --> p-e+ve and improved measurements of the absolute branching fractions for D0 decays to K-e+ve, pi-e+ve, and K*-e+ve.

Search for rare and forbidden decays D+ --> h+/- e+/- e+.

Using 0.8 x 10(6) D+ D- pairs collected with the CLEO-c detector at the psi(3770) resonance, we have searched for flavor-changing neutral current and lepton-number-violating decays of D+ mesons to final states with dielectrons. We find no indication of either, obtaining 90% confidence level upper limits of B(D+ --> pi+ e+ e-) < 7.4 x 10(-6), B(D+ --> pi- e+ d+) < 3.6 x 10(-6), B(D+ --> K+ e+ e-) < 6.2 x 10(-6), and B(D+ --> K- e+ e+) < 4.5 x 10(-6).