328 research outputs found

    ALS/FTD‐associated FUS activates GSK‐3β to disrupt the VAPB–PTPIP51 interaction and ER–mitochondria associations

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    Defective FUS metabolism is strongly associated with amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD), but the mechanisms linking FUS to disease are not properly understood. However, many of the functions disrupted in ALS/FTD are regulated by signalling between the endoplasmic reticulum (ER) and mitochondria. This signalling is facilitated by close physical associations between the two organelles that are mediated by binding of the integral ER protein VAPB to the outer mitochondrial membrane protein PTPIP51, which act as molecular scaffolds to tether the two organelles. Here, we show that FUS disrupts the VAPB–PTPIP51 interaction and ER–mitochondria associations. These disruptions are accompanied by perturbation of Ca2+ uptake by mitochondria following its release from ER stores, which is a physiological read‐out of ER–mitochondria contacts. We also demonstrate that mitochondrial ATP production is impaired in FUS‐expressing cells; mitochondrial ATP production is linked to Ca2+ levels. Finally, we demonstrate that the FUS‐induced reductions to ER–mitochondria associations and are linked to activation of glycogen synthase kinase‐3β (GSK‐3β), a kinase already strongly associated with ALS/FTD

    Using isotopic dilution to assess chemical extraction of labile Ni, Cu, Zn, Cd and Pb in soils

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    Chemical extractants used to measure labile soil metal must ideally select for and solubilise the labile fraction, with minimal solubilisation of non-labile metal. We assessed four extractants (0.43 M HNO3, 0.43 M CH3COOH, 0.05 M Na2H2EDTA and 1 M CaCl2) against these requirements. For soils contaminated by contrasting sources, we compared isotopically exchangeable Ni, Cu, Zn, Cd and Pb (EValue, mg kg-1), with the concentrations of metal solubilised by the chemical extractants (MExt, mg kg-1). Crucially, we also determined isotopically exchangeable metal in the soil–extractant systems (EExt, mg kg-1). Thus ‘EExt - EValue’ quantifies the concentration of mobilised non-labile metal, while ‘EExt - MExt’ represents adsorbed labile metal in the presence of the extractant. Extraction with CaCl2 consistently underestimated EValue for Ni, Cu, Zn and Pb, while providing a reasonable estimate of EValue for Cd. In contrast, extraction with HNO3 both consistently mobilised non-labile metal and overestimated the EValue. Extraction with CH3COOH appeared to provide a good estimate of EValue for Cd; however, this was the net outcome of incomplete solubilisation of labile metal, and concurrent mobilisation of non-labile metal by the extractant (MExt EValue). The Na2H2EDTA extractant mobilised some non-labile metal in three of the four soils, but consistently solubilised the entire labile fraction for all soil-metal combinations (MExt ≈ EExt). Comparison of EValue, MExt and EExt provides a rigorous means of assessing the underlying action of soil chemical extraction methods and could be used to refine long-standing soil extraction methodologies

    Rice plants overexpressing OsEPF1 show reduced stomatal density and increased root cortical aerenchyma formation

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    Stomata are adjustable pores in the aerial epidermis of plants. The role of stomata is usually described in terms of the trade-off between CO2 uptake and water loss. Little consideration has been given to their interaction with below-ground development or diffusion of other gases. We overexpressed the rice EPIDERMAL PATTERNING FACTOR1 (OsEPF1) to produce rice plants with reduced stomatal densities, resulting in lowered leaf stomatal conductance and enhanced water use efficiency. Surprisingly, we found that root cortical aerenchyma (RCA) is formed constitutively in OsEPF1OE lines regardless of tissue age and position. Aerenchyma is tissue containing air-spaces that can develop in the plant root during stressful conditions, e.g. oxygen deficiency when it functions to increase O2 diffusion from shoot to root. The relationship with stomata is unknown. We conclude that RCA development and stomatal development are linked by two possible mechanisms: first that reduced stomatal conductance inhibits the diffusion of oxygen to the root, creating an oxygen deficit and stimulating the formation of RCA, second that an unknown EPF signalling pathway may be involved. Our observations have fundamental implications for the understanding of whole plant gas diffusion and root-to-shoot signalling events

    Production and Decay of D_1(2420)^0 and D_2^*(2460)^0

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    We have investigated D+π−D^{+}\pi^{-} and D∗+π−D^{*+}\pi^{-} final states and observed the two established L=1L=1 charmed mesons, the D1(2420)0D_1(2420)^0 with mass 2421−2−2+1+22421^{+1+2}_{-2-2} MeV/c2^{2} and width 20−5−3+6+320^{+6+3}_{-5-3} MeV/c2^{2} and the D2∗(2460)0D_2^*(2460)^0 with mass 2465Âą3Âą32465 \pm 3 \pm 3 MeV/c2^{2} and width 28−7−6+8+628^{+8+6}_{-7-6} MeV/c2^{2}. Properties of these final states, including their decay angular distributions and spin-parity assignments, have been studied. We identify these two mesons as the jlight=3/2j_{light}=3/2 doublet predicted by HQET. We also obtain constraints on {\footnotesize ΓS/(ΓS+ΓD)\Gamma_S/(\Gamma_S + \Gamma_D)} as a function of the cosine of the relative phase of the two amplitudes in the D1(2420)0D_1(2420)^0 decay.Comment: 15 pages in REVTEX format. hardcopies with figures can be obtained by sending mail to: [email protected]

    Measurement of the branching fraction for Υ(1S)→τ+τ−\Upsilon (1S) \to \tau^+ \tau^-

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    We have studied the leptonic decay of the Υ(1S)\Upsilon (1S) resonance into tau pairs using the CLEO II detector. A clean sample of tau pair events is identified via events containing two charged particles where exactly one of the particles is an identified electron. We find B(Υ(1S)→τ+τ−)=(2.61 ± 0.12 +0.09−0.13)B(\Upsilon(1S) \to \tau^+ \tau^-) = (2.61~\pm~0.12~{+0.09\atop{-0.13}})%. The result is consistent with expectations from lepton universality.Comment: 9 pages, RevTeX, two Postscript figures available upon request, CLNS 94/1297, CLEO 94-20 (submitted to Physics Letters B

    Observation of a Narrow Resonance of Mass 2.46 GeV/c^2 Decaying to D_s^*+ pi^0 and Confirmation of the D_sJ^* (2317) State

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    Using 13.5 inverse fb of e+e- annihilation data collected with the CLEO II detector we have observed a narrow resonance in the Ds*+pi0 final state, with a mass near 2.46 GeV. The search for such a state was motivated by the recent discovery by the BaBar Collaboration of a narrow state at 2.32 GeV, the DsJ*(2317)+ that decays to Ds+pi0. Reconstructing the Ds+pi0 and Ds*+pi0 final states in CLEO data, we observe peaks in both of the corresponding reconstructed mass difference distributions, dM(Dspi0)=M(Dspi0)-M(Ds) and dM(Ds*pi0)=M(Ds*pi0)-M(Ds*), both of them at values near 350 MeV. We interpret these peaks as signatures of two distinct states, the DsJ*(2317)+ plus a new state, designated as the DsJ(2463)+. Because of the similar dM values, each of these states represents a source of background for the other if photons are lost, ignored or added. A quantitative accounting of these reflections confirms that both states exist. We have measured the mean mass differences = 350.0 +/- 1.2 [stat] +/- 1.0 [syst] MeV for the DsJ*(2317) state, and = 351.2 +/- 1.7 [stat] +/- 1.0 [syst] MeV for the new DsJ(2463)+ state. We have also searched, but find no evidence, for decays of the two states via the channels Ds*+gamma, Ds+gamma, and Ds+pi+pi-. The observations of the two states at 2.32 and 2.46 GeV, in the Ds+pi0 and Ds*+pi0 decay channels respectively, are consistent with their interpretations as (c anti-strange) mesons with orbital angular momentum L=1, and spin-parities of 0+ and 1+.Comment: 16 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, version to be published in Physical Review D; minor modifications and fixes to typographical errors, plus an added section on production properties. The main results are unchanged; they supersede those reported in hep-ex/030501

    Measurement of the Charge Asymmetry in B→K∗(892)±π∓B\to K^* (892)^{\pm}\pi^{\mp}

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    We report on a search for a CP-violating asymmetry in the charmless hadronic decay B -> K*(892)+- pi-+, using 9.12 fb^-1 of integrated luminosity produced at \sqrt{s}=10.58 GeV and collected with the CLEO detector. We find A_{CP}(B -> K*(892)+- pi-+) = 0.26+0.33-0.34(stat.)+0.10-0.08(syst.), giving an allowed interval of [-0.31,0.78] at the 90% confidence level.Comment: 7 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR

    Study of the q^2-Dependence of B --> pi ell nu and B --> rho(omega)ell nu Decay and Extraction of |V_ub|

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    We report on determinations of |Vub| resulting from studies of the branching fraction and q^2 distributions in exclusive semileptonic B decays that proceed via the b->u transition. Our data set consists of the 9.7x10^6 BBbar meson pairs collected at the Y(4S) resonance with the CLEO II detector. We measure B(B0 -> pi- l+ nu) = (1.33 +- 0.18 +- 0.11 +- 0.01 +- 0.07)x10^{-4} and B(B0 -> rho- l+ nu) = (2.17 +- 0.34 +0.47/-0.54 +- 0.41 +- 0.01)x10^{-4}, where the errors are statistical, experimental systematic, systematic due to residual form-factor uncertainties in the signal, and systematic due to residual form-factor uncertainties in the cross-feed modes, respectively. We also find B(B+ -> eta l+ nu) = (0.84 +- 0.31 +- 0.16 +- 0.09)x10^{-4}, consistent with what is expected from the B -> pi l nu mode and quark model symmetries. We extract |Vub| using Light-Cone Sum Rules (LCSR) for 0<= q^2<16 GeV^2 and Lattice QCD (LQCD) for 16 GeV^2 <= q^2 < q^2_max. Combining both intervals yields |Vub| = (3.24 +- 0.22 +- 0.13 +0.55/-0.39 +- 0.09)x10^{-3}$ for pi l nu, and |Vub| = (3.00 +- 0.21 +0.29/-0.35 +0.49/-0.38 +-0.28)x10^{-3} for rho l nu, where the errors are statistical, experimental systematic, theoretical, and signal form-factor shape, respectively. Our combined value from both decay modes is |Vub| = (3.17 +- 0.17 +0.16/-0.17 +0.53/-0.39 +-0.03)x10^{-3}.Comment: 45 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR

    Study of the B^0 Semileptonic Decay Spectrum at the Upsilon(4S) Resonance

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    We have made a first measurement of the lepton momentum spectrum in a sample of events enriched in neutral B's through a partial reconstruction of B0 --> D*- l+ nu. This spectrum, measured with 2.38 fb**-1 of data collected at the Upsilon(4S) resonance by the CLEO II detector, is compared directly to the inclusive lepton spectrum from all Upsilon(4S) events in the same data set. These two spectra are consistent with having the same shape above 1.5 GeV/c. From the two spectra and two other CLEO measurements, we obtain the B0 and B+ semileptonic branching fractions, b0 and b+, their ratio, and the production ratio f+-/f00 of B+ and B0 pairs at the Upsilon(4S). We report b+/b0=0.950 (+0.117-0.080) +- 0.091, b0 = (10.78 +- 0.60 +- 0.69)%, and b+ = (10.25 +- 0.57 +- 0.65)%. b+/b0 is equivalent to the ratio of charged to neutral B lifetimes, tau+/tau0.Comment: 14 page, postscript file also available at http://w4.lns.cornell.edu/public/CLN

    Measurement of the Decay Asymmetry Parameters in Λc+→Λπ+\Lambda_c^+ \to \Lambda\pi^+ and Λc+→Σ+π0\Lambda_c^+ \to \Sigma^+\pi^0

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    We have measured the weak decay asymmetry parameters (\aLC ) for two \LC\ decay modes. Our measurements are \aLC = -0.94^{+0.21+0.12}_{-0.06-0.06} for the decay mode Λc+→Λπ+\Lambda_c^+ \to \Lambda\pi^+ and \aLC = -0.45\pm 0.31 \pm 0.06 for the decay mode Λc→Σ+π0\Lambda_c \to \Sigma^+\pi^0 . By combining these measurements with the previously measured decay rates, we have extracted the parity-violating and parity-conserving amplitudes. These amplitudes are used to test models of nonleptonic charmed baryon decay.Comment: 11 pages including the figures. Uses REVTEX and psfig macros. Figures as uuencoded postscript. Also available as http://w4.lns.cornell.edu/public/CLNS/1995/CLNS95-1319.p
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