Hyperoxia Causes Mitochondrial Fragmentation in Pulmonary Endothelial Cells by Increasing Expression of Pro-Fission Proteins

Objective—We explored mechanisms that alter mitochondrial structure and function in pulmonary endothelial cells (PEC) function after hyperoxia. Approach and Results—Mitochondrial structures of PECs exposed to hyperoxia or normoxia were visualized and mitochondrial fragmentation quantified. Expression of pro-fission or fusion proteins or autophagy-related proteins were assessed by Western blot. Mitochondrial oxidative state was determined using mito-roGFP. Tetramethylrhodamine methyl ester estimated mitochondrial polarization in treatment groups. The role of mitochondrially derived reactive oxygen species in mt-fragmentation was investigated with mito-TEMPOL and mitochondrial DNA (mtDNA) damage studied by using ENDO III (mt-tat-endonuclease III), a protein that repairs mDNA damage. Drp-1 (dynamin-related protein 1) was overexpressed or silenced to test the role of this protein in cell survival or transwell resistance. Hyperoxia increased fragmentation of PEC mitochondria in a time-dependent manner through 48 hours of exposure. Hyperoxic PECs exhibited increased phosphorylation of Drp-1 (serine 616), decreases in Mfn1 (mitofusion protein 1), but increases in OPA-1 (optic atrophy 1). Pro-autophagy proteins p62 (LC3 adapter–binding protein SQSTM1/p62), PINK-1 (PTEN-induced putative kinase 1), and LC3B (microtubule-associated protein 1A/1B-light chain 3) were increased. Returning cells to normoxia for 24 hours reversed the increased mt-fragmentation and changes in expression of pro-fission proteins. Hyperoxia-induced changes in mitochondrial structure or cell survival were mitigated by antioxidants mito-TEMPOL, Drp-1 silencing, or inhibition or protection by the mitochondrial endonuclease ENDO III. Hyperoxia induced oxidation and mitochondrial depolarization and impaired transwell resistance. Decrease in resistance was mitigated by mito-TEMPOL or ENDO III and reproduced by overexpression of Drp-1. Conclusions—Because hyperoxia evoked mt-fragmentation, cell survival and transwell resistance are prevented by ENDO III and mito-TEMPOL and Drp-1 silencing, and these data link hyperoxia-induced mt-DNA damage, Drp-1 expression, mt-fragmentation, and PEC dysfunction

Measurement of CP asymmetry in D 0 → K - K + and D 0 → π - π decays

Time-integrated CP asymmetries in D 0 decays to the final states K - K + and π - π + are measured using proton-proton collisions corresponding to 3fb-1 of integrated luminosity collected at centre-of-mass energies of 7 TeV and 8 TeV. The D 0 mesons are produced in semileptonic b-hadron decays, where the charge of the accompanying muon is used to determine the initial flavour of the charm meson. The difference in CP asymmetries between the two final states is measured to be Δ ACP = ACP (K- K +) ACP (π- π+) = (+ 0.14 ± 0.16 (stat) ± 0.08 (syst)) %. A measurement of A CP (K - K +) is obtained assuming negligible CP violation in charm mixing and in Cabibbo-favoured D decays. It is found to be ACP (K- K+) = (- 0.06 ± 0.15 (stat) ± 0.10 (syst)) %, where the correlation coefficient between ΔA CP and A CP (K - K +) is ρ = 0.28. By combining these results, the CP asymmetry in the D 0 → π - π + channel is A CP (π - π +) = (-0.20 ± 0.19 (stat) ± 0.10 (syst))%

Measurement of the Xi(-)(b) and Omega(-)(b) baryon lifetimes

Using a data sample of pp collisions corresponding to an integrated luminosity of 3 fb−1, the Ξ−b and Ω−b baryons are reconstructed in the Ξ−b → J/ψΞ− and Ω−b → J/ψΩ− decay modes and their lifetimes measured to be τ(Ξ−b) = 1.55+0.10−0.09 (stat) ± 0.03 (syst) ps, τ(Ω−b) = 1.54+0.26−0.21 (stat) ± 0.05 (syst) ps. These are the most precise determinations to date. Both measurements are in good agreement with previous experimental results and with theoretical predictions

Measurement of the resonant and CP components in B¯ 0 → J=ψπþπ− decays

The resonant structure of the reaction B¯0→J/ψπ+π− is studied using data from 3  fb−1 of integrated luminosity collected by the LHCb experiment, one third at 7 TeV center-of-mass energy and the remainder at 8 TeV. The invariant mass of the π+π− pair and three decay angular distributions are used to determine the fractions of the resonant and nonresonant components. Six interfering π+π− states, ρ(770), f0(500), f2(1270), ρ(1450), ω(782) and ρ(1700), are required to give a good description of invariant mass spectra and decay angular distributions. The positive and negative charge parity fractions of each of the resonant final states are determined. The f0(980) meson is not seen and the upper limit on its presence, compared with the observed f0(500) rate, is inconsistent with a model where these scalar mesons are formed from two quarks and two antiquarks (tetraquarks) at the eight standard deviation level. In the qq¯ model, the absolute value of the mixing angle between the f0(980) and the f0(500) scalar mesons is limited to be less than 17° at 90% confidence level

Study of beauty hadron decays into pairs of charm hadrons

First observations of the decays Λb 0 → Λc +D(s) - are reported using data corresponding to an integrated luminosity of 3fb-1 collected at 7 and 8 TeV center-of-mass energies in proton-proton collisions with the LHCb detector. In addition, the most precise measurement of the branching fraction B(Bs 0→D+Ds -) is made and a search is performed for the decays B(s) 0→Λc +Λc -. The results obtained are B(Λb 0→Λc +D-)/ B(Λb 0→Λc +D s -)=0.042±0.003(stat)±0.003(syst), [B(Λb 0→Λc +D s -)/B(B̄0→D+D s -)]/[B(Λb 0→Λ c +π-)/B(B̄0→D +π-)]=0.96±0.02(stat)±0.06(syst),B(B s 0→D+Ds -)/ B(B̄0→D+Ds -)=0. 038±0.004(stat)±0.003(syst),B(B̄0→Λ c +Λc -)/B(B̄ 0→D+Ds -)<0.0022[95%C.L.], B(Bs 0→Λc +Λ c -)/B(Bs 0→D+D s -)<0.30[95%C.L.]. Measurement of the mass of the Λb 0 baryon relative to the B̄0 meson gives M(Λb 0)-M(B̄0)=339. 72±0.24(stat)±0.18(syst)MeV/c2. This result provides the most precise measurement of the mass of the Λb 0 baryon to date

Effective lifetime measurements in the B-s(0) -> K+K-, B-0 -> K+pi(-) and B-s(0) -> pi K-+(-) decays

Measurements of the effective lifetimes in the View the MathML source, B0→K+π− and View the MathML source decays are presented using 1.0 fb−1 of pp collision data collected at a centre-of-mass energy of 7 TeV by the LHCb experiment. The analysis uses a data-driven approach to correct for the decay time acceptance. This is the most precise determination to date of the effective lifetime in the View the MathML source decay and provides constraints on contributions from physics beyond the Standard Model to the View the MathML source mixing phase and the width difference ΔΓs

Measurement of ψ(2S) polarisation in pp collisions at √s = 7 TeV

The polarisation of prompt ψ(2S) mesons is measured by performing an angular analysis of ψ(2S) → μ+μ- decays using proton-proton collision data, corresponding to an integrated luminosity of 1.0 fb-1, collected by the LHCb detector at a centre-of-mass energy of 7 TeV. The polarisation is measured in bins of transverse momentum pT and rapidity y in the kinematic region 3.5 < pT < 15 GeV/c and 2.0 < y < 4.5, and is compared to theoretical models. No significant polarisation is observed