Structure and Mechanism of a Metal-Sensing Regulatory RNA

SummaryOrganisms maintain the correct balance of intracellular metals primarily through metal-sensing proteins that control transport and storage of the target ion(s). Here, we reveal the basis of metal sensing and genetic control by a metalloregulatory RNA. Our data demonstrate that a previously uncharacterized orphan riboswitch, renamed the “M-box,” is a divalent metal-sensing RNA involved in Mg2+ homeostasis. A combination of genetic, biochemical, and biophysical techniques demonstrate that Mg2+ induces a compacted tertiary architecture for M-box RNAs that regulates the accessibility of nucleotides involved in genetic control. Molecular details are provided by crystallographic structure determination of a Mg2+-bound M-box RNA. Given the distribution of this RNA element, it may constitute a common mode for bacterial metal ion regulation, and its discovery suggests the possibility of additional RNA-based metal sensors in modern and primordial organisms

Nicastrin Functions as a γ-Secretase-Substrate Receptor

Summaryγ-secretase catalyzes the intramembrane cleavage of amyloid precursor protein (APP) and Notch after their extracellular domains are shed by site-specific proteolysis. Nicastrin is an essential glycoprotein component of the γ-secretase complex but has no known function. We now show that the ectodomain of nicastrin binds the new amino terminus that is generated upon proteolysis of the extracellular APP and Notch domains, thereby recruiting the APP and Notch substrates into the γ-secretase complex. Chemical- or antibody-mediated blocking of the free amino terminus, addition of purified nicastrin ectodomain, or mutations in the ectodomain markedly reduce the binding and cleavage of substrate by γ-secretase. These results indicate that nicastrin is a receptor for the amino-terminal stubs that are generated by ectodomain shedding of type I transmembrane proteins. Our data are consistent with a model where nicastrin presents these substrates to γ-secretase and thereby facilitates their cleavage via intramembrane proteolysis

Search for supersymmetry with a dominant R-parity violating LQDbar couplings in e+e- collisions at centre-of-mass energies of 130GeV to 172 GeV

A search for pair-production of supersymmetric particles under the assumption that R-parity is violated via a dominant LQDbar coupling has been performed using the data collected by ALEPH at centre-of-mass energies of 130-172 GeV. The observed candidate events in the data are in agreement with the Standard Model expectation. This result is translated into lower limits on the masses of charginos, neutralinos, sleptons, sneutrinos and squarks. For instance, for m_0=500 GeV/c^2 and tan(beta)=sqrt(2) charginos with masses smaller than 81 GeV/c^2 and neutralinos with masses smaller than 29 GeV/c^2 are excluded at the 95% confidence level for any generation structure of the LQDbar coupling.Comment: 32 pages, 30 figure

Measurement of the W mass in e+e−e^+ e^- collisions at 183 GeV

The mass of the W boson is obtained from reconstructed invariant mass distributions in W-pair events. The sample of W pairs is selected from 57 pb$^{-1}$ collected with the ALEPH detector in 1997 at a centre-of-mass energy of 183 GeV. The invariant mass distributions of reweighted Monte Carlo events are fitted separately to the experimental distributions in the $qqbarqqbar$ and all l\nuqqbar channels to give the following W masses: $m_{W}^{hadronic} = 80.461 \pm 0.177(stat.) \pm 0.045(syst.) \pm 0.056(theory) GeV/c^2$, $m_{W}^{semileptonic} = 80.326 \pm 0.184(stat.) \pm 0.040(syst.) GeV/c^2$ where the theory error represents the possible effects of final state interactions. The combination of these two measurements, including the LEP energy calibration uncertainty, gives $m_{W} = 80.393 \pm 0.128(stat.)\pm 0.041(syst.) \pm 0.028(theory)\pm 0.021(LEP) GeV/c^2

Measurement of the W-pair cross section in e+e−e^+ e^- collisions at 172 GeV

The e+e- --> W+W- cross section is measured in a data sample collected by ALEPH at a mean centre--of--mass energy of 172.09 GEV, corresponding to an integrated luminosity of 10.65 pb-1. Cross sections are given for the three topologies, fully leptonic, semi-leptonic and hadronic of a W-pair decay. Under the assumption that no other decay modes are present, the W-pair cross section is measured to be 11.7 +- 1.2 (stat.) +- 0.3 (syst.) pb. The existence of the triple gauge boson vertex of the Standard Model is clearly preferred by the data. The decay branching ratio of the W boson into hadrons is measured to be B(W --> hadrons) = 67.7 +- 3.1 (stat.) +- 0.7 (syst.)%, allowing a determination of the CKM matrix element |Vcs|= 0.98 +- 0.14 (stat.) +- 0.03 (syst.)

Search for the bcb_c meson in hadronic Z decays

A search for the Bc meson decaying into the channels J/psi pi+ and J/psi l nu (l = e or mu) is performed in a sample of 3.9 million hadronic Z decays collected by the ALEPH detector. This search results in the observation of 0 and 2 candidates in each of these channels, respectively, while 0.44 and 0.81 background events are expected. The following 90\% confidence level upper limits are derived: Br(Z->Bc X)/Br(Z->q q )*Br(Bc->J/psi pi+) 3.6 10^-5 Br(Z->Bc X)/Br(Z->q q )*Br(Bc->J/psi l nu) 5.2 10^-5 An additional Bc->J/psi(e+e-) mu nu candidate with very low background probability, found in an independent analysis, is also described in detail

Measurement of the W mass in e+e−e^+e^- collisions at production threshold

In June 1996, the LEP centre-of-mass energy was raised to 161 GeV. Pair production of W bosons in e+e- collisions was observed for the first time by the LEP experiments. An integrated luminosity of 11 pb-1 was recorded in the ALEPH detector, in which WW candidate events were observed. In 6 events both Ws decay leptonically. In 16 events, one W decays leptonically, the other into hadrons. In the channel where both Ws decay into hadrons, a signal was separated from the large background by means of several multi-variate analyses. The W pair cross-section is measured to be sigma_WW = 4.23 +-0.73 (stat.) +- 0.19 (syst.) pb From this cross-section, the W mass is derived within the framework of the Standard Model: MW = 80.14 +- 0.34 (stat.) +- 0.09 (syst.) +- 0.03 (LEP~energy) GeV/c2

Search for Bs0B^{0}_{s} oscillations using inclusive lepton events

A search for Bs oscillations is performed using a sample of semileptonic b-hadron decays collected by the ALEPH experiment during 1991-1995. Compared to previous inclusive lepton analyses, the prop er time resolution and b-flavour mistag rate are significantly improved. Additional sensitivity to Bs mixing is obtained by identifying subsamples of events having a Bs purity which is higher than the average for the whole data sample. Unbinned maximum likelihood amplitude fits are performed to derive a lower limit of Dms>9.5 ps-1 at 95% CL. Combining with the ALEPH Ds based analyses yields Dms>9.6 ps-1 at 95% CL.A search for B0s oscillations is performed using a sample of semileptonic b-hadron decays collected by the ALEPH experiment during 1991-1995. Compared to previous inclusive lepton analyses, the proper time resolution and b-flavour mistag rate are significantly improved. Additional sensitivity to B0s mixing is obtained by identifying subsamples of events having a B0s purity which is higher than the average for the whole data sample. Unbinned maximum likelihood amplitude fits are performed to derive a lower limit of Deltam_s>9.5ps^-1 at 95% CL. Combining with the ALEPH D-s based analyses yields Deltam_s>9.6ps^-1 at 95% CL

Measurement of the W mass by direct reconstruction in e+e−e^+ e^- collisions at 172 GeV

The mass of the W boson is obtained from reconstructed invariant mass distributions in W-pair events. The sample of W pairs is selected from 10.65~pb$^{-1}$ collected with the ALEPH detector at a mean centre-of-mass energy of 172.09 \GEV. The invariant mass distribution of simulated events are fitted to the experimental distributions and the following W masses are obtained: $WW \to q\overline{q}q\overline{q } m_W = 81.30 +- 0.47(stat.) +- 0.11(syst.) GeV/c^2$, $WW \to l\nu q\overline{q}(l=e,\mu) m_W = 80.54 +- 0.47(stat.) +- 0.11(syst.) GeV/c^2$, $WW \to \tau\nu q\overline{q} m_W = 79.56 +- 1.08(stat.) +- 0.23(syst.) GeV/C62$. The statistical errors are the expected errors for Monte Carlo samples of the same integrated luminosity as the data. The combination of these measurements gives: $m_W = 80.80 +- 0.11(syst.) +- 0.03(LEP energy) GeV/^2$