Inflammatory properties of inhibitor of DNA binding 1 secreted by synovial fibroblasts in rheumatoid arthritis

Abstract Background Inhibitor of DNA binding 1 (Id1) is a nuclear protein containing a basic helix-loop-helix (bHLH) domain that regulates cell growth by selective binding and prevention of gene transcription. Sources of Id1 production in rheumatoid arthritis synovial tissue (RA ST) and its range of functional effects in RA remain to be clarified. Methods We analyzed Id1 produced from synovial fibroblasts and endothelial cells (ECs) with histology and real-time polymerase chain reaction (RT-PCR). Fibroblast supernatants subjected to differential centrifugation to isolate and purify exosomes were measured for Id1 by enzyme-linked immunosorbent assay (ELISA). Western blotting of Id1-stimulated ECs was performed to determine the kinetics of intracellular protein phosphorylation. EC intracellular signaling pathways induced by Id1 were subsequently targeted with silencing RNA (siRNA) for angiogenesis inhibition. Results By PCR and histologic analysis, we found that the primary source of Id1 in STs is from activated fibroblasts that correlate with inflammatory scores in human RA ST and in joints from K/BxN serum-induced mice. Normal (NL) and RA synovial fibroblasts increase Id1 production with stimulation by transforming growth factor beta (TGF-β). Most of the Id1 released by RA synovial fibroblasts is contained within exosomes. Endothelial progenitor cells (EPCs) and human dermal microvascular ECs (HMVECs) activate the Jnk signaling pathway in response to Id1, and Jnk siRNA reverses Id1-induced HMVEC vessel formation in Matrigel plugs in vivo. Conclusions Id1 is a pleotropic molecule affecting angiogenesis, vasculogenesis, and fibrosis. Our data shows that Id1 is not only an important nuclear protein, but also can be released from fibroblasts via exosomes. The ability of extracellular Id1 to activate signaling pathways expands the role of Id1 in the orchestration of tissue inflammation.http://deepblue.lib.umich.edu/bitstream/2027.42/134552/1/13075_2016_Article_984.pd

Observation of the Λb0→χc1(3872)pK−\Lambda_b^0\rightarrow \chi_{c1}(3872)pK^- decay

International audienceUsing proton-proton collision data, collected with the LHCb detector and corresponding to 1.0, 2.0 and 1.9 fb$^{−1}$ of integrated luminosity at the centre-of-mass energies of 7, 8, and 13 TeV, respectively, the decay {\Lambda}_{\mathrm{b}}^0\to {\upchi}_{\mathrm{c}1} (3872)pK$^{−}$ with χ$_{c1}$(3872) → J/ψ π$^{+}$π$^{−}$ is observed for the first time. The significance of the observed signal is in excess of seven standard deviations. It is found that (58 ± 15)% of the decays proceed via the two-body intermediate state χ$_{c1}$(3872)Λ(1520). The branching fraction with respect to that of the ${\Lambda}_{\mathrm{b}}^0$ → ψ(2S)pK$^{−}$ decay mode, where the ψ(2S) meson is reconstructed in the J/ψ π$^{+}$π$^{−}$ final state, is measured to be: $ \frac{\beta \left({\Lambda}_{\mathrm{b}}^0\to {\upchi}_{\mathrm{c}1}(3872){\mathrm{pK}}^{-}\right)}{\beta \left({\Lambda}_{\mathrm{b}}^0\to \uppsi \left(2\mathrm{S}\right){\mathrm{pK}}^{-}\right)}\times \frac{\beta \left({\upchi}_{\mathrm{c}1}(3872)\to \mathrm{J}/\uppsi {\uppi}^{+}{\uppi}^{-}\right)}{\beta \left(\uppsi \left(2\mathrm{S}\right)\to \mathrm{J}/\uppsi {\uppi}^{+}{\uppi}^{-}\right)}=\left(5.4\pm 1.1\pm 0.2\right)\times {10}^{-2},

Measurement of fs/fuf_s / f_u Variation with Proton-Proton Collision Energy and BB-Meson Kinematics

International audienceThe ratio of the Bs0 and B+ fragmentation fractions fs and fu is studied with Bs0→J/ψϕ and B+→J/ψK+ decays using data collected by the LHCb experiment in proton-proton collisions at 7, 8, and 13 TeV center-of-mass energies. The analysis is performed in bins of B-meson momentum, longitudinal momentum, transverse momentum, pseudorapidity, and rapidity. The fragmentation-fraction ratio fs/fu is observed to depend on the B-meson transverse momentum with a significance of 6.0σ. This dependency is driven by the 13 TeV sample (8.7σ), while the results for the other collision energies are not significant when considered separately. Furthermore, the results show a 4.8σ evidence for an increase of fs/fu as a function of collision energy

Updated measurement of time-dependent CP-violating observables in Bs0→J/ψK+K−B^{0}_{s}\to J/\psi K^+ K^- decays

International audienceThe decay-time-dependent $CP$ asymmetry in ${{B} ^0_{s}} \rightarrow J/\psi {{K} ^+} {{K} ^-}$ decays is measured using proton–proton collision data, corresponding to an integrated luminosity of $1.9\,\mathrm{fb}^{-1}$ , collected with the LHCb detector at a centre-of-mass energy of $13\,\mathrm {TeV}$ in 2015 and 2016. Using a sample of approximately 117 000 signal decays with an invariant ${{K} ^+} {{K} ^-}$ mass in the vicinity of the $\phi (1020)$ resonance, the $CP$ -violating phase $\phi _s$ is measured, along with the difference in decay widths of the light and heavy mass eigenstates of the ${{B} ^0_{s}}$ - ${{\overline{B}{}} {}^0_{s}}$ system, $\Delta \Gamma _s$ . The difference of the average ${{B} ^0_{s}}$ and ${{B} ^0}$ meson decay widths, $\Gamma _s-\Gamma _d$ , is determined using in addition a sample of ${{B} ^0} \rightarrow J/\psi {{K} ^+} {{\pi } ^-}$ decays. The values obtained are $\phi _s = -0.083\pm 0.041\pm 0.006\mathrm { \,rad}$ , $\Delta \Gamma _s = 0.077 \pm 0.008 \pm 0.003 {\mathrm { \,ps^{-1}}}$ and $\Gamma _s-\Gamma _d = -0.0041 \pm 0.0024 \pm 0.0015{\mathrm { \,ps^{-1}}}$ , where the first uncertainty is statistical and the second systematic. These are the most precise single measurements of these quantities to date and are consistent with expectations based on the Standard Model and with a previous LHCb analysis of this decay using data recorded at centre-of-mass energies 7 and 8 TeV. Finally, the results are combined with recent results from ${{B} ^0_{s}} \rightarrow J/\psi {{\pi } ^+} {{\pi } ^-}$ decays obtained using the same dataset as this analysis, and with previous independent LHCb results

Observation of the semileptonic decay B+→pp‾μ+νμB^{+}\to p\overline{p}\mu^{+}\nu_{\mu}

International audienceThe Cabibbo-suppressed semileptonic decay ${B}^{+}\to p\overline{p}{\mu}^{+}{\nu}_{\mu }$ is observed for the first time using a sample of pp collisions corresponding to an integrated luminosity of 1.0, 2.0 and 1.7 fb$^{−1}$ at centre-of-mass energies of 7, 8 and 13 TeV, respectively. The differential branching fraction is measured as a function of the $p\overline{p}$ invariant mass using the decay mode B$^{+}$→ J/ψK$^{+}$ for normalisation. The total branching fraction is measured to be$\mathrm{\mathcal{B}}\left({B}^{+}\to p\overline{p}{\mu}^{+}{\nu}_{\mu}\right)=\left({5.27}_{-0.24}^{+0.23}\pm 0.21\pm 0.15\right)\times {10}^{-6},$where the first uncertainty is statistical, the second systematic and the third is from the uncertainty on the branching fraction of the normalisation channel.[graphic not available: see fulltext

First observation of excited Ωb−\Omega_b^- states

International audienceWe report four narrow peaks in the Ξb0K- mass spectrum obtained using pp collisions at center-of-mass energies of 7, 8, and 13 TeV, corresponding to a total integrated luminosity of 9  fb-1 recorded by the LHCb experiment. Referring to these states by their mass, the mass values are m[Ωb(6316)-]=6315.64±0.31±0.07±0.50  MeV, m[Ωb(6330)-]=6330.30±0.28±0.07±0.50  MeV, m[Ωb(6340)-]=6339.71±0.26±0.05±0.50  MeV, m[Ωb(6350)-]=6349.88±0.35±0.05±0.50  MeV, where the uncertainties are statistical, systematic, and the last is due to the knowledge of the Ξb0 mass. The natural widths of the three lower mass states are consistent with zero, and the 90% confidence-level upper limits are determined to be Γ[Ωb(6316)-]<2.8  MeV, Γ[Ωb(6330)-]<3.1  MeV and Γ[Ωb(6340)-]<1.5  MeV. The natural width of the Ωb(6350)- peak is 1.4-0.8+1.0±0.1  MeV, which is 2.5σ from zero and corresponds to an upper limit of 2.8 MeV. The peaks have local significances ranging from 3.6σ to 7.2σ. After accounting for the look-elsewhere effect, the significances of the Ωb(6316)- and Ωb(6330)- peaks are reduced to 2.1σ and 2.6σ, respectively, while the two higher mass peaks exceed 5σ. The observed peaks are consistent with expectations for excited Ωb- resonances

Isospin amplitudes in Λb0→J/ψΛ(Σ0)\Lambda_b^0\to J/\psi \Lambda(\Sigma^0) and Ξb0→J/ψΞ0(Λ)\Xi_b^0\to J/\psi \Xi^0(\Lambda) decays

International audienceRatios of isospin amplitudes in hadron decays are a useful probe of the interplay between weak and strong interactions and allow searches for physics beyond the standard model. We present the first results on isospin amplitudes in b-baryon decays, using data corresponding to an integrated luminosity of 8.5  fb-1, collected with the LHCb detector in pp collisions at center of mass energies of 7, 8, and 13 TeV. The isospin amplitude ratio |A1(Λb0→J/ψΣ0)/A0(Λb0→J/ψΛ)|, where the subscript on A indicates the final-state isospin, is measured to be less than 1/21.8 at 95% confidence level. The Cabibbo suppressed Ξb0→J/ψΛ decay is observed for the first time, allowing for the measurement |A0(Ξb0→J/ψΛ)/A1/2(Ξb0→J/ψΞ0)|=0.37±0.06±0.02, where the uncertainties are statistical and systematic, respectively