Use of a cAMP BRET Sensor to Characterize a Novel Regulation of cAMP by the Sphingosine 1-Phosphate/G13 Pathway

Regulation of intracellular cyclic adenosine 3',5'-monophosphate (cAMP) is integral in mediating cell growth, cell differentiation, and immune responses in hematopoietic cells. To facilitate studies of cAMP regulation we developed a BRET (bioluminescence resonance energy transfer) sensor for cAMP, CAMYEL (cAMP sensor using YFP-Epac-RLuc), which can quantitatively and rapidly monitor intracellular concentrations of cAMP in vivo. This sensor was used to characterize three distinct pathways for modulation of cAMP synthesis stimulated by presumed Gs-dependent receptors for isoproterenol and prostaglandin E2. Whereas two ligands, uridine 5'-diphosphate and complement C5a, appear to use known mechanisms for augmentation of cAMP via Gq/calcium and Gi, the action of sphingosine 1-phosphate (S1P) is novel. In these cells, S1P, a biologically active lysophospholipid, greatly enhances increases in intracellular cAMP triggered by the ligands for Gs-coupled receptors while having only a minimal effect by itself. The enhancement of cAMP by S1P is resistant to pertussis toxin and independent of intracellular calcium. Studies with RNAi and chemical perturbations demonstrate that the effect of S1P is mediated by the S1P2 receptor and the heterotrimeric G13 protein. Thus in these macrophage cells, all four major classes of G proteins can regulate intracellular cAMP

Signaling and crosstalk by C5a and UDP in macrophages selectively use PLCbeta 3 to regulate intracellular free calcium

Studies in fibroblasts, neurons, and platelets have demonstrated the integration of signals from different G-protein coupled receptors (GPCRs) in raising intracellular free Ca2+. To study signal integration in macrophages, we screened RAW264.7 cells and bone marrow-derived macrophages (BMDM) for their Ca2+ response to GPCR ligands. We found a synergistic response to complement component 5a (C5a) in combination with uridine 5’-diphosphate (UDP), platelet activating factor (PAF) or lysophosphatidic acid (LPA). The C5a response was Gai-dependent, while the UDP, PAF, and LPA responses were Gaqdependent. Synergy between C5a and UDP, mediated by the C5a and P2Y6 receptors, required dual receptor occupancy, and affected the initial release of Ca2+ from intracellular stores as well as sustained Ca2+ levels. C5a and UDP synergized in generating inositol-1,4,5-trisphosphate, suggesting synergy in activating phospholipase C (PLC) ß. Macrophages expressed transcripts for three PLCß isoforms (PLCß2, PLCß3, and PLCß4), but GPCR ligands selectively used these isoforms in Ca2+ signaling. C5a predominantly used PLCß3, while UDP used PLCß3 but also PLCß4. Neither ligand required PLCß2. Synergy between C5a and UDP likewise depended primarily on PLCß3. Importantly, the Ca2+ signaling deficiency observed in PLCß3-deficient BMDM was reversed by reconstitution with PLCß3. Neither PI-3 kinase nor PKC was required for synergy. In contrast to Ca2+, PI3-kinase activation by C5a was inhibited by UDP, as was macropinocytosis, which depends on PI3- kinase. PLCß3 may thus provide a selective target for inhibiting Ca2+ responses to mediators of inflammation, including C5a, UDP, PAF, and LPA

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

A study of CP violation in B-+/- -> DK +/- and B-+/- -> D pi(+/-) decays with D -> (KSK +/-)-K-0 pi(-/+) final states

A first study of CP violation in the decay modes $B^\pm\to [K^0_{\rm S} K^\pm \pi^\mp]_D h^\pm$ and $B^\pm\to [K^0_{\rm S} K^\mp \pi^\pm]_D h^\pm$, where $h$ labels a $K$ or $\pi$ meson and $D$ labels a $D^0$ or $\overline{D}^0$ meson, is performed. The analysis uses the LHCb data set collected in $pp$ collisions, corresponding to an integrated luminosity of 3 fb$^{-1}$. The analysis is sensitive to the CP-violating CKM phase $\gamma$ through seven observables: one charge asymmetry in each of the four modes and three ratios of the charge-integrated yields. The results are consistent with measurements of $\gamma$ using other decay modes

Study of the rare B-s(0) and B-0 decays into the pi(+) pi(-) mu(+) mu(-) final state

A search for the rare decays $B_s^0 \to \pi^+\pi^-\mu^+\mu^-$ and $B^0 \to \pi^+\pi^-\mu^+\mu^-$ is performed in a data set corresponding to an integrated luminosity of 3.0 fb$^{-1}$ collected by the LHCb detector in proton-proton collisions at centre-of-mass energies of 7 and 8 TeV. Decay candidates with pion pairs that have invariant mass in the range 0.5-1.3 GeV/$c^2$ and with muon pairs that do not originate from a resonance are considered. The first observation of the decay $B_s^0 \to \pi^+\pi^-\mu^+\mu^-$ and the first evidence of the decay $B^0 \to \pi^+\pi^-\mu^+\mu^-$ are obtained and the branching fractions are measured to be $\mathcal{B}(B_s^0 \to \pi^+\pi^-\mu^+\mu^-)=(8.6\pm 1.5\,({\rm stat}) \pm 0.7\,({\rm syst})\pm 0.7\,({\rm norm}))\times 10^{-8}$ and $\mathcal{B}(B^0 \to \pi^+\pi^-\mu^+\mu^-)=(2.11\pm 0.51\,({\rm stat}) \pm 0.15\,({\rm syst})\pm 0.16\,({\rm norm}) )\times 10^{-8}$, where the third uncertainty is due to the branching fraction of the decay $B^0\to J/\psi(\to \mu^+\mu^-)K^*(890)^0(\to K^+\pi^-)$, used as a normalisation.A search for the rare decays Bs0→π+π−μ+μ− and B0→π+π−μ+μ− is performed in a data set corresponding to an integrated luminosity of 3.0 fb−1 collected by the LHCb detector in proton–proton collisions at centre-of-mass energies of 7 and 8 TeV . Decay candidates with pion pairs that have invariant mass in the range 0.5–1.3 GeV/c2 and with muon pairs that do not originate from a resonance are considered. The first observation of the decay Bs0→π+π−μ+μ− and the first evidence of the decay B0→π+π−μ+μ− are obtained and the branching fractions, restricted to the dipion-mass range considered, are measured to be B(Bs0→π+π−μ+μ−)=(8.6±1.5 (stat)±0.7 (syst)±0.7(norm))×10−8 and B(B0→π+π−μ+μ−)=(2.11±0.51(stat)±0.15(syst)±0.16(norm))×10−8 , where the third uncertainty is due to the branching fraction of the decay B0→J/ψ(→μ+μ−)K⁎(892)0(→K+π−) , used as a normalisation.A search for the rare decays Bs0→π+π−μ+μ− and B0→π+π−μ+μ− is performed in a data set corresponding to an integrated luminosity of 3.0 fb−1 collected by the LHCb detector in proton–proton collisions at centre-of-mass energies of 7 and 8 TeV . Decay candidates with pion pairs that have invariant mass in the range 0.5–1.3 GeV/c2 and with muon pairs that do not originate from a resonance are considered. The first observation of the decay Bs0→π+π−μ+μ− and the first evidence of the decay B0→π+π−μ+μ− are obtained and the branching fractions, restricted to the dipion-mass range considered, are measured to be B(Bs0→π+π−μ+μ−)=(8.6±1.5 (stat)±0.7 (syst)±0.7(norm))×10−8 and B(B0→π+π−μ+μ−)=(2.11±0.51(stat)±0.15(syst)±0.16(norm))×10−8 , where the third uncertainty is due to the branching fraction of the decay B0→J/ψ(→μ+μ−)K⁎(892)0(→K+π−) , used as a normalisation.A search for the rare decays $B_s^0 \to \pi^+\pi^-\mu^+\mu^-$ and $B^0 \to \pi^+\pi^-\mu^+\mu^-$ is performed in a data set corresponding to an integrated luminosity of 3.0 fb$^{-1}$ collected by the LHCb detector in proton-proton collisions at centre-of-mass energies of 7 and 8 TeV. Decay candidates with pion pairs that have invariant mass in the range 0.5-1.3 GeV/$c^2$ and with muon pairs that do not originate from a resonance are considered. The first observation of the decay $B_s^0 \to \pi^+\pi^-\mu^+\mu^-$ and the first evidence of the decay $B^0 \to \pi^+\pi^-\mu^+\mu^-$ are obtained and the branching fractions, restricted to the dipion-mass range considered, are measured to be $\mathcal{B}(B_s^0 \to \pi^+\pi^-\mu^+\mu^-)=(8.6\pm 1.5\,({\rm stat}) \pm 0.7\,({\rm syst})\pm 0.7\,({\rm norm}))\times 10^{-8}$ and $\mathcal{B}(B^0 \to \pi^+\pi^-\mu^+\mu^-)=(2.11\pm 0.51\,({\rm stat}) \pm 0.15\,({\rm syst})\pm 0.16\,({\rm norm}) )\times 10^{-8}$, where the third uncertainty is due to the branching fraction of the decay $B^0\to J/\psi(\to \mu^+\mu^-)K^*(890)^0(\to K^+\pi^-)$, used as a normalisation

Observation of the B0 → ρ0ρ0 decay from an amplitude analysis of B0 → (π+π−)(π+π−) decays

Proton–proton collision data recorded in 2011 and 2012 by the LHCb experiment, corresponding to an integrated luminosity of 3.0 fb−1 , are analysed to search for the charmless B0→ρ0ρ0 decay. More than 600 B0→(π+π−)(π+π−) signal decays are selected and used to perform an amplitude analysis, under the assumption of no CP violation in the decay, from which the B0→ρ0ρ0 decay is observed for the first time with 7.1 standard deviations significance. The fraction of B0→ρ0ρ0 decays yielding a longitudinally polarised final state is measured to be fL=0.745−0.058+0.048(stat)±0.034(syst) . The B0→ρ0ρ0 branching fraction, using the B0→ϕK⁎(892)0 decay as reference, is also reported as B(B0→ρ0ρ0)=(0.94±0.17(stat)±0.09(syst)±0.06(BF))×10−6

Measurement of the (eta c)(1S) production cross-section in proton-proton collisions via the decay (eta c)(1S) -> p(p)over-bar

The production of the $\eta_c (1S)$ state in proton-proton collisions is probed via its decay to the $p \bar{p}$ final state with the LHCb detector, in the rapidity range $2.0 6.5$ GeV/c. The cross-section for prompt production of $\eta_c (1S)$ mesons relative to the prompt $J/\psi$ cross-section is measured, for the first time, to be $\sigma_{\eta_c (1S)}/\sigma_{J/\psi} = 1.74 \pm 0.29 \pm 0.28 \pm 0.18 _{B}$ at a centre-of-mass energy $\sqrt{s} = 7$ TeV using data corresponding to an integrated luminosity of 0.7 fb$^{-1}$, and $\sigma_{\eta_c (1S)}/\sigma_{J/\psi} = 1.60 \pm 0.29 \pm 0.25 \pm 0.17 _{B}$ at $\sqrt{s} = 8$ TeV using 2.0 fb$^{-1}$. The uncertainties quoted are, in order, statistical, systematic, and that on the ratio of branching fractions of the $\eta_c (1S)$ and $J/\psi$ decays to the $p \bar{p}$ final state. In addition, the inclusive branching fraction of $b$-hadron decays into $\eta_c (1S)$ mesons is measured, for the first time, to be $B ( b \rightarrow \eta_c X ) = (4.88 \pm 0.64 \pm 0.25 \pm 0.67 _{B}) \times 10^{-3}$, where the third uncertainty includes also the uncertainty on the $J/\psi$ inclusive branching fraction from $b$-hadron decays. The difference between the $J/\psi$ and $\eta_c (1S)$ meson masses is determined to be $114.7 \pm 1.5 \pm 0.1$ MeV/c$^2$.The production of the $\eta _c (1S)$ state in proton-proton collisions is probed via its decay to the $p\overline{p}$ final state with the LHCb detector, in the rapidity range $2.0 6.5 \mathrm{{\,GeV/}{ c}}$ . The cross-section for prompt production of $\eta _c (1S)$ mesons relative to the prompt ${{ J}}/{\psi }$ cross-section is measured, for the first time, to be $\sigma _{\eta _c (1S)}/\sigma _{{{{ J}}/{\psi }}} = 1.74\, \pm \,0.29\, \pm \, 0.28\, \pm \,0.18 _{{\mathcal{B}}}$ at a centre-of-mass energy ${\sqrt{s}} = 7 {~\mathrm{TeV}}$ using data corresponding to an integrated luminosity of 0.7 fb$^{-1}$ , and $\sigma _{\eta _c (1S)}/\sigma _{{{{ J}}/{\psi }}} = 1.60 \pm 0.29 \pm 0.25 \pm 0.17 _{{\mathcal{B}}}$ at ${\sqrt{s}} = 8 {~\mathrm{TeV}}$ using 2.0 fb$^{-1}$ . The uncertainties quoted are, in order, statistical, systematic, and that on the ratio of branching fractions of the $\eta _c (1S)$ and ${{ J}}/{\psi }$ decays to the $p\overline{p}$ final state. In addition, the inclusive branching fraction of ${b}$ -hadron decays into $\eta _c (1S)$ mesons is measured, for the first time, to be ${\mathcal{B}}( b {\rightarrow } \eta _c X ) = (4.88\, \pm \,0.64\, \pm \,0.29\, \pm \, 0.67 _{{\mathcal{B}}}) \times 10^{-3}$ , where the third uncertainty includes also the uncertainty on the ${{ J}}/{\psi }$ inclusive branching fraction from ${b}$ -hadron decays. The difference between the ${{ J}}/{\psi }$ and $\eta _c (1S)$ meson masses is determined to be $114.7 \pm 1.5 \pm 0.1 {\mathrm {\,MeV\!/}c^2}$ .The production of the $\eta_c (1S)$ state in proton-proton collisions is probed via its decay to the $p \bar{p}$ final state with the LHCb detector, in the rapidity range $2.0 6.5$ GeV/c. The cross-section for prompt production of $\eta_c (1S)$ mesons relative to the prompt $J/\psi$ cross-section is measured, for the first time, to be $\sigma_{\eta_c (1S)}/\sigma_{J/\psi} = 1.74 \pm 0.29 \pm 0.28 \pm 0.18 _{B}$ at a centre-of-mass energy $\sqrt{s} = 7$ TeV using data corresponding to an integrated luminosity of 0.7 fb$^{-1}$, and $\sigma_{\eta_c (1S)}/\sigma_{J/\psi} = 1.60 \pm 0.29 \pm 0.25 \pm 0.17 _{B}$ at $\sqrt{s} = 8$ TeV using 2.0 fb$^{-1}$. The uncertainties quoted are, in order, statistical, systematic, and that on the ratio of branching fractions of the $\eta_c (1S)$ and $J/\psi$ decays to the $p \bar{p}$ final state. In addition, the inclusive branching fraction of $b$-hadron decays into $\eta_c (1S)$ mesons is measured, for the first time, to be $B ( b \rightarrow \eta_c X ) = (4.88 \pm 0.64 \pm 0.29 \pm 0.67 _{B}) \times 10^{-3}$, where the third uncertainty includes also the uncertainty on the $J/\psi$ inclusive branching fraction from $b$-hadron decays. The difference between the $J/\psi$ and $\eta_c (1S)$ meson masses is determined to be $114.7 \pm 1.5 \pm 0.1$ MeV/c$^2$

Angular analysis of the B-0 -> K*(0) e(+) e(-) decay in the low-q(2) region

An angular analysis of the $B^0 \rightarrow K^{*0} e^+ e^-$ decay is performed using a data sample, corresponding to an integrated luminosity of 3.0 {\mbox{fb}^{-1}}, collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of 7 and 8 TeV during 2011 and 2012. For the first time several observables are measured in the dielectron mass squared ($q^2$) interval between 0.002 and 1.120${\mathrm{\,Ge\kern -0.1em V^2\!/}c^4}$. The angular observables $F_{\mathrm{L}}$ and $A_{\mathrm{T}}^{\mathrm{Re}}$ which are related to the $K^{*0}$ polarisation and to the lepton forward-backward asymmetry, are measured to be $F_{\mathrm{L}}= 0.16 \pm 0.06 \pm0.03$ and $A_{\mathrm{T}}^{\mathrm{Re}} = 0.10 \pm 0.18 \pm 0.05$, where the first uncertainty is statistical and the second systematic. The angular observables $A_{\mathrm{T}}^{(2)}$ and $A_{\mathrm{T}}^{\mathrm{Im}}$ which are sensitive to the photon polarisation in this $q^2$ range, are found to be $A_{\mathrm{T}}^{(2)} = -0.23 \pm 0.23 \pm 0.05$ and $A_{\mathrm{T}}^{\mathrm{Im}} =0.14 \pm 0.22 \pm 0.05$. The results are consistent with Standard Model predictions.An angular analysis of the B$^{0}$ → K^{*}^{0} e$^{+}$ e$^{−}$ decay is performed using a data sample, corresponding to an integrated luminosity of 3.0 fb$^{−1}$, collected by the LHCb experiment in pp collisions at centre-of-mass energies of 7 and 8 TeV during 2011 and 2012. For the first time several observables are measured in the dielectron mass squared (q$^{2}$) interval between 0.002 and 1.120 GeV$^{2}$ /c$^{4}$. The angular observables F$_{L}$ and A$_{T}^{Re}$ which are related to the K^{*}^{0} polarisation and to the lepton forward-backward asymmetry, are measured to be F$_{L}$ = 0.16 ± 0.06 ± 0.03 and A$_{T}^{Re}$  = 0.10 ± 0.18 ± 0.05, where the first uncertainty is statistical and the second systematic. The angular observables A$_{T}^{(2)}$ and A$_{T}^{Im}$ which are sensitive to the photon polarisation in this q$^{2}$ range, are found to be A$_{T}^{(2)}$  = − 0.23 ± 0.23 ± 0.05 and A$_{T}^{Im}$  = 0.14 ± 0.22 ± 0.05. The results are consistent with Standard Model predictions.An angular analysis of the $B^0 \rightarrow K^{*0} e^+ e^-$ decay is performed using a data sample, corresponding to an integrated luminosity of 3.0 {\mbox{fb}^{-1}}, collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of 7 and 8 TeV during 2011 and 2012. For the first time several observables are measured in the dielectron mass squared ($q^2$) interval between 0.002 and 1.120${\mathrm{\,Ge\kern -0.1em V^2\!/}c^4}$. The angular observables $F_{\mathrm{L}}$ and $A_{\mathrm{T}}^{\mathrm{Re}}$ which are related to the $K^{*0}$ polarisation and to the lepton forward-backward asymmetry, are measured to be $F_{\mathrm{L}}= 0.16 \pm 0.06 \pm0.03$ and $A_{\mathrm{T}}^{\mathrm{Re}} = 0.10 \pm 0.18 \pm 0.05$, where the first uncertainty is statistical and the second systematic. The angular observables $A_{\mathrm{T}}^{(2)}$ and $A_{\mathrm{T}}^{\mathrm{Im}}$ which are sensitive to the photon polarisation in this $q^2$ range, are found to be $A_{\mathrm{T}}^{(2)} = -0.23 \pm 0.23 \pm 0.05$ and $A_{\mathrm{T}}^{\mathrm{Im}} =0.14 \pm 0.22 \pm 0.05$. The results are consistent with Standard Model predictions

Precise measurements of the properties of the B-1(5721)(0,+) and B-2*(5747)(0,+) states and observation of B-+,B-0 pi(-,+) mass structures

Invariant mass distributions of $B^+\pi^-$ and $B^0\pi^+$ combinations are investigated in order to study excited B mesons. The analysis is based on a data sample corresponding to $3.0 fb^{-1}$ of $pp$ collision data, recorded by the LHCb detector at centre-of-mass energies of 7 and 8 TeV. Precise measurements of the masses and widths of the $B_1(5721)^{0,+}$ and $B_2^*(5747)^{0,+}$ states are reported. Clear enhancements, particularly prominent at high pion transverse momentum, are seen over background in the mass range $5850$-$6000$ MeV in both $B^+\pi^-$ and $B^0\pi^+$ combinations. The structures are consistent with the presence of four excited B mesons, labelled $B_J(5840)^{0,+}$ and $B_J(5960)^{0,+}$, whose masses and widths are obtained under different hypotheses for their quantum numbers.Invariant mass distributions of B$^{+}$ π$^{−}$ and B$^{0}$ π$^{+}$ combinations are investigated in order to study excited B mesons. The analysis is based on a data sample corresponding to 3.0 fb$^{−1}$ of pp collision data, recorded by the LHCb detector at centre-of-mass energies of 7 and 8 TeV. Precise measurements of the masses and widths of the B$_{1}$(5721)$^{0,+}$ and B$^{2}$(5747)$^{0,+}$ states are reported. Clear enhancements, particularly prominent at high pion transverse momentum, are seen over background in the mass range 5850-6000 MeV in both B$^{+}$ π$^{−}$ and B$^{0}$ π$^{+}$ combinations. The structures are consistent with the presence of four excited B mesons, labelled B$_{J}$ (5840)$^{0,+}$ and B$_{J}$ (5960)$^{0,+}$, whose masses and widths are obtained under different hypotheses for their quantum numbers.Invariant mass distributions of B+pi- and B0pi+ combinations are investigated in order to study excited B mesons. The analysis is based on a data sample corresponding to 3.0 fb-1 of pp collision data, recorded by the LHCb detector at centre-of-mass energies of 7 and 8 TeV. Precise measurements of the masses and widths of the B_1(5721)^(0,+) and B_2*(5747)^(0,+) states are reported. Clear enhancements, particularly prominent at high pion transverse momentum, are seen over background in the mass range 5850--6000 MeV in both B+pi- and B0pi+ combinations. The structures are consistent with the presence of four excited B mesons, labelled B_J(5840)^(0,+) and B_J(5960)^(0,+), whose masses and widths are obtained under different hypotheses for their quantum numbers

Measurement of the lifetime of the Bc+B_c^+ meson using the Bc+→J/ψπ+B_c^+\rightarrow J/\psi\pi^+ decay mode

The difference in total widths between the $B_c^+$ and $B^+$ mesons is measured using 3.0fb$^{-1}$ of data collected by the LHCb experiment in 7 and 8 TeV centre-of-mass energy proton-proton collisions at the LHC. Through the study of the time evolution of $B_c^+ \rightarrow J/\psi \pi^+$ and $B^+\rightarrow J/\psi K^+$ decays, the width difference is measured to be $\Delta\Gamma \equiv \Gamma_{B_c^+} - \Gamma_{B^+} = 4.46 \pm 0.14 \pm 0.07mm^{-1}c,$ where the first uncertainty is statistical and the second systematic. The known lifetime of the $B^+$ meson is used to convert this to a precise measurement of the $B_c^+$ lifetime, $\tau_{B_c^+} = 513.4 \pm 11.0 \pm 5.7fs,$ where the first uncertainty is statistical and the second systematic.The difference in total widths between the B+ c and B+ mesons is measured using 3.0 fb−1 of data collected by the LHCb experiment in 7 and 8 TeV centre-of-mass energy proton-proton collisions at the LHC. Through the study of the time evolution of B+ c → J/ψπ+ and B+ → J/ψK+ decays, the width difference is measured to be ∆Γ ≡ ΓB + c − ΓB+ = 4.46 ± 0.14 ± 0.07 mm−1 c, where the first uncertainty is statistical and the second systematic. The known lifetime of the B+ meson is used to convert this to a precise measurement of the B+ c lifetime, τB + c = 513.4 ± 11.0 ± 5.7 fs, where the first uncertainty is statistical and the second systematic.The difference in total widths between the Bc+ and B+ mesons is measured using a data sample corresponding to an integrated luminosity of 3.0 fb−1 collected by the LHCb experiment in 7 and 8 TeV centre-of-mass energy proton–proton collisions at the LHC. Through the study of the time evolution of Bc+→J/ψπ+ and B+→J/ψK+ decays, the width difference is measured to be ΔΓ≡ΓBc+−ΓB+=4.46±0.14±0.07 mm−1c, where the first uncertainty is statistical and the second systematic. The known lifetime of the B+ meson is used to convert this to a precise measurement of the Bc+ lifetime, τBc+=513.4±11.0±5.7 fs, where the first uncertainty is statistical and the second is systematic.The difference in total widths between the Bc+ and B+ mesons is measured using a data sample corresponding to an integrated luminosity of 3.0 fb−1 collected by the LHCb experiment in 7 and 8 TeV centre-of-mass energy proton–proton collisions at the LHC. Through the study of the time evolution of Bc+→J/ψπ+ and B+→J/ψK+ decays, the width difference is measured to be ΔΓ≡ΓBc+−ΓB+=4.46±0.14±0.07 mm−1c, where the first uncertainty is statistical and the second systematic. The known lifetime of the B+ meson is used to convert this to a precise measurement of the Bc+ lifetime, τBc+=513.4±11.0±5.7 fs, where the first uncertainty is statistical and the second is systematic