A bright FIT-PNA hybridization probe for the hybridization state specific analysis of a C → U RNA edit via FRET in a binary system

Oligonucleotide probes that show enhanced fluorescence upon nucleic acid hybridization enable the detection and visualization of specific mRNA molecules, in vitro and in cellulo. A challenging problem is the analysis of single nucleotide alterations that occur, for example, when cellular mRNA is subject to C → U editing. Given the length required for uniqueness of the targeted segment, the commonly used probes do not provide the level of sequence specificity needed to discriminate single base mismatched hybridization. Herein we introduce a binary probe system based on fluorescence resonance energy transfer (FRET) that distinguishes three possible states i.e. (i) absence of target, (ii) presence of edited (matched) and (iii) unedited (single base mismatched) target. To address the shortcomings of read-out via FRET, we designed donor probes that avoid bleed through into the acceptor channel and nevertheless provide a high intensity of FRET signaling. We show the combined use of thiazole orange (TO) and an oxazolopyridine analogue (JO), linked as base surrogates in modified PNA FIT-probes that serve as FRET donor for a second, near-infrared (NIR)-labeled strand. In absence of target, donor emission is low and FRET cannot occur in lieu of the lacking co-alignment of probes. Hybridization of the TO/JO-PNA FIT-probe with the (unedited RNA) target leads to high brightness of emission at 540 nm. Co-alignment of the NIR-acceptor strand ensues from recognition of edited RNA inducing emission at 690 nm. We show imaging of mRNA in fixed and live cells and discuss the homogeneous detection and intracellular imaging of a single nucleotide mRNA edit used by nature to post-transcriptionally modify the function of the Glycine Receptor (GlyR)

Transport by molecular motors in the presence of static defects

The transport by molecular motors along cytoskeletal filaments is studied theoretically in the presence of static defects. The movements of single motors are described as biased random walks along the filament as well as binding to and unbinding from the filament. Three basic types of defects are distinguished, which differ from normal filament sites only in one of the motors' transition probabilities. Both stepping defects with a reduced probability for forward steps and unbinding defects with an increased probability for motor unbinding strongly reduce the velocities and the run lengths of the motors with increasing defect density. For transport by single motors, binding defects with a reduced probability for motor binding have a relatively small effect on the transport properties. For cargo transport by motors teams, binding defects also change the effective unbinding rate of the cargo particles and are expected to have a stronger effect.Comment: 20 pages, latex, 7 figures, 1 tabl

The Q2Q^2-dependence of the generalised Gerasimov-Drell-Hearn integral for the deuteron, proton and neutron

The Gerasimov-Drell-Hearn (GDH) sum rule connects the anomalous contribution to the magnetic moment of the target nucleus with an energy-weighted integral of the difference of the helicity-dependent photoabsorption cross sections. The data collected by HERMES with a deuterium target are presented together with a re-analysis of previous measurements on the proton. This provides a measurement of the generalised GDH integral covering simultaneously the nucleon-resonance and the deep inelastic scattering regions. The contribution of the nucleon-resonance region is seen to decrease rapidly with increasing $Q^2$. The DIS contribution is sizeable over the full measured range, even down to the lowest measured $Q^2$. As expected, at higher $Q^2$ the data are found to be in agreement with previous measurements of the first moment of $g_1$. From data on the deuteron and proton, the GDH integral for the neutron has been derived and the proton--neutron difference evaluated. This difference is found to satisfy the fundamental Bjorken sum rule at $Q^2 = 5$ GeV$^2$.Comment: 12 pages, 10 figure

Measurement of single-spin azimuthal asymmetries in semi-inclusive electroproduction of pions and kaons on a longitudinally polarised deuterium target

Single-spin asymmetries have been measured for semi-inclusive electroproduction of $\pi^+$, $\pi^-$, $\pi^0$ and $K^+$ mesons in deep-inelastic scattering off a longitudinally polarised deuterium target. The asymmetries appear in the distribution of the hadrons in the azimuthal angle $\phi$ around the virtual photon direction, relative to the lepton scattering plane. The corresponding analysing powers in the $\sin \phi$ moment of the cross section are $0.012 \pm 0.002 {(stat.)} \pm 0.002 {(syst.)}$ for $\pi^+$, $0.006 \pm 0.003 {(stat.)} \pm 0.002 {(syst.)}$ for $\pi^-$, $0.021 \pm 0.005 {(stat.)} \pm 0.003 {(syst.)}$ for $\pi^0$ and $0.013 \pm 0.006 {(stat.)} \pm 0.003 {(syst.)}$ for $K^+$. The $\sin 2\phi$ moments are compatible with zero for all particles.Comment: Revised version shortened 9 pages, 3 tables, 7 figure

Double-Spin Asymmetry in the Cross Section for Exclusive rho^0 Production in Lepton-Proton Scattering

Evidence for a positive longitudinal double-spin asymmetry = 0.24 +-0.11 (stat) +-0.02 (syst) in the cross section for exclusive diffractive rho^0(770) vector meson production in polarised lepton-proton scattering was observed by the HERMES experiment. The longitudinally polarised 27.56 GeV HERA positron beam was scattered off a longitudinally polarised pure hydrogen gas target. The average invariant mass of the photon-proton system has a value of = 4.9 GeV, while the average negative squared four-momentum of the virtual photon is = 1.7 GeV^2. The ratio of the present result to the corresponding spin asymmetry in inclusive deep-inelastic scattering is in agreement with an early theoretical prediction based on the generalised vector meson dominance model.Comment: 10 pages, 4 embedded figures, LaTe

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters

Measurement of the Lambda(b) cross section and the anti-Lambda(b) to Lambda(b) ratio with Lambda(b) to J/Psi Lambda decays in pp collisions at sqrt(s) = 7 TeV

The Lambda(b) differential production cross section and the cross section ratio anti-Lambda(b)/Lambda(b) are measured as functions of transverse momentum pt(Lambda(b)) and rapidity abs(y(Lambda(b))) in pp collisions at sqrt(s) = 7 TeV using data collected by the CMS experiment at the LHC. The measurements are based on Lambda(b) decays reconstructed in the exclusive final state J/Psi Lambda, with the subsequent decays J/Psi to an opposite-sign muon pair and Lambda to proton pion, using a data sample corresponding to an integrated luminosity of 1.9 inverse femtobarns. The product of the cross section times the branching ratio for Lambda(b) to J/Psi Lambda versus pt(Lambda(b)) falls faster than that of b mesons. The measured value of the cross section times the branching ratio for pt(Lambda(b)) > 10 GeV and abs(y(Lambda(b))) < 2.0 is 1.06 +/- 0.06 +/- 0.12 nb, and the integrated cross section ratio for anti-Lambda(b)/Lambda(b) is 1.02 +/- 0.07 +/- 0.09, where the uncertainties are statistical and systematic, respectively.Comment: Submitted to Physics Letters