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Functional Identification of Catalytic Metal Ion Binding Sites within RNA
The viability of living systems depends inextricably on enzymes that catalyze phosphoryl transfer reactions. For many enzymes in this class, including several ribozymes, divalent metal ions serve as obligate cofactors. Understanding how metal ions mediate catalysis requires elucidation of metal ion interactions with both the enzyme and the substrate(s). In the Tetrahymena group I intron, previous work using atomic mutagenesis and quantitative analysis of metal ion rescue behavior identified three metal ions (MA, MB, and MC) that make five interactions with the ribozyme substrates in the reaction's transition state. Here, we combine substrate atomic mutagenesis with site-specific phosphorothioate substitutions in the ribozyme backbone to develop a powerful, general strategy for defining the ligands of catalytic metal ions within RNA. In applying this strategy to the Tetrahymena group I intron, we have identified the pro-SP phosphoryl oxygen at nucleotide C262 as a ribozyme ligand for MC. Our findings establish a direct connection between the ribozyme core and the functionally defined model of the chemical transition state, thereby extending the known set of transition-state interactions and providing information critical for the application of the recent group I intron crystallographic structures to the understanding of catalysis.</p
Functional Identification of Catalytic Metal Ion Binding Sites within RNA
The viability of living systems depends inextricably on enzymes that catalyze phosphoryl transfer reactions. For many enzymes in this class, including several ribozymes, divalent metal ions serve as obligate cofactors. Understanding how metal ions mediate catalysis requires elucidation of metal ion interactions with both the enzyme and the substrate(s). In the Tetrahymena group I intron, previous work using atomic mutagenesis and quantitative analysis of metal ion rescue behavior identified three metal ions (M(A), M(B), and M(C)) that make five interactions with the ribozyme substrates in the reaction's transition state. Here, we combine substrate atomic mutagenesis with site-specific phosphorothioate substitutions in the ribozyme backbone to develop a powerful, general strategy for defining the ligands of catalytic metal ions within RNA. In applying this strategy to the Tetrahymena group I intron, we have identified the pro-S (P) phosphoryl oxygen at nucleotide C262 as a ribozyme ligand for M(C). Our findings establish a direct connection between the ribozyme core and the functionally defined model of the chemical transition state, thereby extending the known set of transition-state interactions and providing information critical for the application of the recent group I intron crystallographic structures to the understanding of catalysis
Predictive capability of Cys112Arg single nucleotide polymorphisms of the apolipoprotein E gene in assessing the risk of immediate and early post-traumatic seizures
This study is aimed at investigating epileptic seizures, one of the consequences of traumatic brain injury (TBI). Immediate and early post-traumatic seizures, as well as late post-traumatic epileptic seizures or post-traumatic epilepsy, can have different pathogenetic bases. The following key risk factors associated with post-traumatic epilepsy are known: duration of unconsciousness, gunshot wounds, intracranial hemorrhage, diffuse axonal injury, prolonged (more than 3 days) post-traumatic amnesia, acute subdural hematoma with surgical evacuation, immediate and early post-traumatic epileptic seizures, fracture of the skull bones. The role of genetic factors in post-traumatic seizures is poorly understood due to the complexity and multiple causal mechanisms. This paper addresses the role of genetic factors in the occurrence and severity of epileptic events in patients with TBI. In particular, we investigated the role of the Cys112Arg single nucleotide polymorphism of the apolipoprotein E gene. Apolipoprotein E is known for its role in the transport and metabolism of lipids and, therefore, the development of cardiovascular diseases; it is also associated with Alzheimer's disease and has recently been studied in the context of association with epilepsy. The study shows an association between this polymorphism and the risk of immediate and early epileptic seizures in patients with severe TBI
Measurement of the CKM angle Îł from a combination of B±âDh± analyses
A combination of three LHCb measurements of the CKM angle Îł is presented. The decays B±âD K± and
B±âDϱ are used, where D denotes an admixture of D0 and D0 mesons, decaying into K+Kâ, Ï+Ïâ, K±Ïâ, K±ÏâϱÏâ, K0SÏ+Ïâ, or K0S K+Kâ ïŹnal states. All measurements use a dataset corresponding to 1.0 fbâ1 of integrated luminosity. Combining results from B±âD K± decays alone a best-ïŹt value of
Îł =72.0⊠is found, and conïŹdence intervals are set
Îł â [56.4,86.7]⊠at 68% CL,
Îł â [42.6,99.6]⊠at 95% CL.
The best-ïŹt value of Îł found from a combination of results from B±âDϱ decays alone, is Îł =18.9âŠ,
and the conïŹdence intervals
Îł â [7.4,99.2]⊠âȘ [167.9,176.4]⊠at 68% CL
are set, without constraint at 95% CL. The combination of results from B± â D K± and B± â Dϱ
decays gives a best-ïŹt value of Îł =72.6⊠and the conïŹdence intervals
Îł â [55.4,82.3]⊠at 68% CL,
Îł â [40.2,92.7]⊠at 95% CL
are set. All values are expressed modulo 180âŠ, and are obtained taking into account the effect of D0âD0
mixing
Measurement of the ratio of branching fractions BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma)
The ratio of branching fractions of the radiative B decays B0 -> K*0 gamma
and Bs0 -> phi gamma has been measured using 0.37 fb-1 of pp collisions at a
centre of mass energy of sqrt(s) = 7 TeV, collected by the LHCb experiment. The
value obtained is BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma) = 1.12 +/- 0.08
^{+0.06}_{-0.04} ^{+0.09}_{-0.08}, where the first uncertainty is statistical,
the second systematic and the third is associated to the ratio of fragmentation
fractions fs/fd. Using the world average for BR(B0 -> K*0 gamma) = (4.33 +/-
0.15) x 10^{-5}, the branching fraction BR(Bs0 -> phi gamma) is measured to be
(3.9 +/- 0.5) x 10^{-5}, which is the most precise measurement to date.Comment: 15 pages, 1 figure, 2 table
Differential branching fraction and angular analysis of the decay B0âKâ0ÎŒ+ÎŒâ
The angular distribution and differential branching fraction of the decay B 0â K â0 ÎŒ + ÎŒ â are studied using a data sample, collected by the LHCb experiment in pp collisions at sâ=7 TeV, corresponding to an integrated luminosity of 1.0 fbâ1. Several angular observables are measured in bins of the dimuon invariant mass squared, q 2. A first measurement of the zero-crossing point of the forward-backward asymmetry of the dimuon system is also presented. The zero-crossing point is measured to be q20=4.9±0.9GeV2/c4 , where the uncertainty is the sum of statistical and systematic uncertainties. The results are consistent with the Standard Model predictions
Measurements of the branching fractions of B+âppK+ decays
The branching fractions of the decay B+ â ppÌK+ for different intermediate states are measured using data, corresponding to an integrated luminosity of 1.0 fb-1, collected by the LHCb experiment. The total branching fraction, its charmless component MppÌ < 2.85 GeV/c2 and the branching fractions via the resonant ccÌ states η c(1S) and Ï(2S) relative to the decay via a J/Ï intermediate state are [Equation not available: see fulltext.] Upper limits on the B + branching fractions into the η c(2S) meson and into the charmonium-like states X(3872) and X(3915) are also obtained
Search for the decay Bs0âD*âϱ
A search for the decay Bs0âD*âϱ is presented using a data sample corresponding to an integrated luminosity of 1.0ââfb-1 of pp collisions collected by LHCb. This decay is expected to be mediated by a W-exchange diagram, with little contribution from rescattering processes, and therefore a measurement of the branching fraction will help us to understand the mechanism behind related decays such as Bs0âÏ+Ï- and Bs0âDD- . Systematic uncertainties are minimized by using B0âD*âϱ as a normalization channel. We find no evidence for a signal, and set an upper limit on the branching fraction of B(Bs0âD*âϱ)<6.1(7.8)Ă10-6 at 90% (95%) confidence level
Observation of an Excited Bc+ State
Using pp collision data corresponding to an integrated luminosity of 8.5 fb-1 recorded by the LHCb experiment at center-of-mass energies of s=7, 8, and 13 TeV, the observation of an excited Bc+ state in the Bc+Ï+Ï- invariant-mass spectrum is reported. The observed peak has a mass of 6841.2±0.6(stat)±0.1(syst)±0.8(Bc+) MeV/c2, where the last uncertainty is due to the limited knowledge of the Bc+ mass. It is consistent with expectations of the Bcâ(2S31)+ state reconstructed without the low-energy photon from the Bcâ(1S31)+âBc+Îł decay following Bcâ(2S31)+âBcâ(1S31)+Ï+Ï-. A second state is seen with a global (local) statistical significance of 2.2Ï (3.2Ï) and a mass of 6872.1±1.3(stat)±0.1(syst)±0.8(Bc+) MeV/c2, and is consistent with the Bc(2S10)+ state. These mass measurements are the most precise to date
Search for CP violation in decays
A model-independent search for direct CP violation in the Cabibbo suppressed
decay in a sample of approximately 370,000 decays is
carried out. The data were collected by the LHCb experiment in 2010 and
correspond to an integrated luminosity of 35 pb. The normalized Dalitz
plot distributions for and are compared using four different
binning schemes that are sensitive to different manifestations of CP violation.
No evidence for CP asymmetry is found.Comment: 13 pages, 8 figures, submitted to Phys. Rev.
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