Dynamic phosphoregulation of the cortical actin cytoskeleton and endocytic machinery revealed by real-time chemical genetic analysis

We used chemical genetics to control the activity of budding yeast Prk1p, which is a protein kinase that is related to mammalian GAK and AAK1, and which targets several actin regulatory proteins implicated in endocytosis. In vivo Prk1p inhibition blocked pheromone receptor endocytosis, and caused cortical actin patches to rapidly aggregate into large clumps that contained Abp1p, Sla2p, Pan1p, Sla1p, and Ent1p. Clump formation depended on Arp2p, suggesting that this phenotype might result from unregulated Arp2/3-stimulated actin assembly. Electron microscopy/immunoelectron microscopy analysis and tracking of the endocytic membrane marker FM4-64 revealed vesicles of likely endocytic origin within the actin clumps. Upon inhibitor washout, the actin clumps rapidly disassembled, and properly polarized actin patches reappeared. Our results suggest that actin clumps result from blockage at a normally transient step during which actin assembly is stimulated by endocytic proteins. Thus, we revealed tight phosphoregulation of an intrinsically dynamic, actin patch–related process, and propose that Prk1p negatively regulates the actin assembly–stimulating activity of endocytic proteins

Systems Genetics Analysis of Mouse Chondrocyte Differentiation

One of the goals of systems genetics is the reconstruction of gene networks that underlie key processes in development and disease. To identify cartilage gene networks that play an important role in bone development, we used a systems genetics approach that integrated microarray gene expression profiles from cartilage and bone phenotypic data from two sets of recombinant inbred strains. Microarray profiles generated from isolated chondrocytes were used to generate weighted gene coexpression networks. This analysis resulted in the identification of subnetworks (modules) of coexpressed genes that then were examined for relationships with bone geometry and density. One module exhibited significant correlation with femur length (r = 0.416), anteroposterior diameter (r = 0.418), mediolateral diameter (r = 0.576), and bone mineral density (r = 0.475). Highly connected genes (n = 28) from this and other modules were tested in vitro using prechondrocyte ATDC5 cells and RNA interference. Five of the 28 genes were found to play a role in chondrocyte differentiation. Two of these, Hspd1 and Cdkn1a, were known previously to function in chondrocyte development, whereas the other three, Bhlhb9, Cugbp1, and Spcs3, are novel genes. Our integrative analysis provided a systems-level view of cartilage development and identified genes that may be involved in bone development. © 2011 American Society for Bone and Mineral Research

Search for the X(1812) in B±→K±ωϕB^{\pm} \to K^{\pm} \omega \phi

We report on a search for the X(1812) state in the decay $B^{\pm} \to K^{\pm} \omega \phi$ with a data sample of $657\times10^6$ $B\bar{B}$ pairs collected with the Belle detector at the KEKB $e^+e^-$ collider. No significant signal is observed. An upper limit ${\cal B}(B^{\pm} \to K^{\pm} X(1812),X(1812) \to \omega \phi)<3.2\times 10^{-7}$ (90% C.L.) is determined. We also constrain the three-body decay branching fraction to be ${\cal B}(B^{\pm} \to K^{\pm} \omega \phi)$ $<$ 1.9 $\times 10^{-6}$ (90% C.L.).Comment: 5pages,2 figures(3 figure files). submitted to PRD(RC

Time-dependent CP Asymmetries in B0→KS0ρ0γB^0\to K^0_S\rho^0\gamma Decays

We report the first measurement of CP-violation parameters in B^0 -> K_S^0\rho^0\gamma decays based on 657 million B\bar B pairs collected with the Belle detector at the KEKB asymmetric-energy collider. We measure the time-dependent CP violating parameter S_{K_S^0\rho^0\gamma}= 0.11 +/- 0.33(stat.)^{+0.05}_{-0.09}(syst.). We also obtain the effective direct CP violating parameter A_eff=0.05 +/- 0.18(stat.) +/- 0.06(syst.) for m_{K_S\pi^+\pi^-}<1.8 GeV/c^2 and 0.6 GeV/c^2<m_{\pi^+\pi^-}<0.9 GeV/c^2.Comment: 6 pages, 3 figures, to be submitted to PR

Evidence for B0→χc1π0B^0 \to \chi_{c1} \pi ^0 at Belle

We present a measurement of the branching fraction for the Cabibbo- and color-suppressed $B^0 \to \chi_{c1}\pi^0$ decay based on a data sample of $657\times 10^6$ $B\bar B$ events collected at the $\Upsilon(4S)$ resonance with the Belle detector at the KEKB asymmetric-energy $e^+e^-$ collider. We observe a signal of $40\pm9$ events with a significance of $4.7\sigma$ including systematic uncertainties. The measured branching fraction is $\mathcal {B}(B^0 \to \chi_{c1} \pi^0) = (1.12\pm 0.25(\rm {stat.})\pm 0.12({\rm syst.}))\times 10^{-5}$.Comment: 5 pages, 5 figure

Search for B+ -> D*+ pi0 decay

We report on a search for the doubly Cabibbo suppressed decay B+ -> D*+ pi0, based on a data sample of 657 million BBbar pairs collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric energy e+ e- collider. We find no significant signal and set an upper limit of Br(B+ -> D*+ pi0) < 3.6 x 10^-6 at the 90% confidence level. This limit can be used to constrain the ratio between suppressed and favored B -> D* pi decay amplitudes, r < 0.051, at the 90% confidence level.Comment: 5pages, 2figures, submitted to PRL (v1); PRL published version (v2: minor corrections in the text

Measurements of Charmless Hadronic b->s Penguin Decays in the pi+pi-K+pi- Final State and First Observation of B0 -> rho0K+pi-

We report measurements of charmless hadronic B^0 decays into the pi+pi-K+pi+ final state. The analysis uses a sample of 657x10^6 BBbar pairs collected with the Belle detector at the KEKB asymmetric-energy e+e- collider at the Y(4S) resonance. The decay B^0 -> rho0 Kpi is observed for the first time; the significance is 5.0sigma and the corresponding partial branching fraction for M_Kpi in (0.75,1.20) GeV/c^2 is [2.8 +- 0.5(stat) +-0.5(syst)] x 10^{-6}. We also obtain the first evidence for B^0 -> f0Kpi with 3.5sigma significance and for B^0 -> pi+pi-K*0 with 4.5sigma significance. For the two-body decays B^0 -> rho0K*0 and B^0 -> f0K*0, the significances are 2.7sigma and 2.5sigma, respectively, and the upper limits on the branching fractions are 3.4x10^{-6} and 2.2x10^{-6} at 90% confidence level.Comment: 6 pages, 3 figures. accepted by PRD(RC

Dalitz analysis of B --> K pi psi' decays and the Z(4430)+

From a Dalitz plot analysis of B --> K pi psi' decays, we find a signal for Z(4430)+ --> pi+ psi' with a mass M= (4443(+15-12)(+19-13))MeV/c^2, width Gamma= (107(+86-43)(+74-56))MeV, product branching fraction BR(B0 --> K- Z(4430)+) x BR(Z(4430)+ --> pi+ psi')= (3.2(+1.8-0.9)(+5.3-1.6)) x 10^{-5}, and significance of 6.4sigma that agrees with previous Belle measurements based on the same data sample. In addition, we determine the branching fraction BR(B^0 --> K*(892)^0 psi')= (5.52(+0.35-0.32)(+0.53-0.58)) x 10^{-4} and the fraction of K*(892)^0 mesons that are longitudinally polarized f_L= 44.8(+4.0-2.7)(+4.0-5.3)%. These results are obtained from a 605fb^{-1} data sample that contains 657 million B-anti-B pairs collected near the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric energy e+e- collider.Comment: Final version published in PRD(RC

Observation of Two Resonant Structures in e+e- to pi+ pi- psi(2S) via Initial State Radiation at Belle

The cross section for e+e- to pi+ pi- psi(2S) between threshold and \sqrt{s}=5.5 GeV is measured using 673 fb^{-1} of data on and off the \Upsilon(4S) resonance collected with the Belle detector at KEKB. Two resonant structures are observed in the pi+ pi- psi(2S) invariant mass distribution, one at 4361\pm 9\pm 9 MeV/c2 with a width of 74\pm 15\pm 10 MeV/c2, and another at 4664\pm 11\pm 5 MeV/c2 with a width of 48\pm 15\pm 3 MeV/c2, if the mass spectrum is parameterized with the coherent sum of two Breit-Wigner functions. These values do not match those of any of the known charmonium states.Comment: 10 pages, 5 figures, 2 tables, version to appear in Phys. Rev. Let

Zds1/Zds2-PP2ACdc55 complex specifies signaling output from Rho1 GTPase

Acknowledgments We thank David Pellman, John Pringle, Daniel Lew, Masaki Mizunuma, Kenji Irie, and the Yeast Genome Resource Center for yeast strains and plasmids and members of Yoshida Laboratory and Keiko Kono for their support. Multicopy suppressor screening for gef∆ was initiated in the Pellman Laboratory with the help of Didem Ilter. This research was supported by Sprout grant from Brandeis University (E.M. Jonasson and S. Yoshida), an American-Italian Cancer Foundation Postdoctoral fellowship (V. Rossio), and a Massachusetts Life Sciences Center grant (S. Yoshida).Peer reviewedPublisher PD