The Zinc Finger Protein A20 Inhibits TNF-induced NF-κB–dependent Gene Expression by Interfering with an RIP- or TRAF2-mediated Transactivation Signal and Directly Binds to a Novel NF-κB–inhibiting Protein ABIN

The zinc finger protein A20 is a tumor necrosis factor (TNF)– and interleukin 1 (IL-1)-inducible protein that negatively regulates nuclear factor-kappa B (NF-κB)–dependent gene expression. However, the molecular mechanism by which A20 exerts this effect is still unclear. We show that A20 does not inhibit TNF- induced nuclear translocation and DNA binding of NF-κB, although it completely prevents the TNF- induced activation of an NF-κB–dependent reporter gene, as well as TNF-induced IL-6 and granulocyte macrophage–colony stimulating factor gene expression. Moreover, NF-κB activation induced by overexpression of the TNF receptor–associated proteins TNF receptor–associated death domain protein (TRADD), receptor interacting protein (RIP), and TNF recep- tor–associated factor 2 (TRAF2) was also inhibited by expression of A20, whereas NF-κB activation induced by overexpression of NF-κB–inducing kinase (NIK) or the human T cell leukemia virus type 1 (HTLV-1) Tax was unaffected. These results demonstrate that A20 inhibits NF-κB–dependent gene expression by interfering with a novel TNF-induced and RIP- or TRAF2-mediated pathway that is different from the NIK–IκB kinase pathway and that is specifically involved in the transactivation of NF-κB. Via yeast two-hybrid screening, we found that A20 binds to a novel protein, ABIN, which mimics the NF-κB inhibiting effects of A20 upon overexpression, suggesting that the effect of A20 is mediated by its interaction with this NF-κB inhibiting protein, ABIN

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Study of D-(*())(+)(sJ) mesons decaying to D*K-+(S)0 and D*K-0(+) final states

A search is performed for $D^{(*)+}_{sJ}$ mesons in the reactions $pp \to D^{*+} K^0_{\rm S} X$ and $pp \to D^{*0} K^+ X$ using data collected at centre-of-mass energies of 7 and 8 TeV with the LHCb detector. For the $D^{*+} K^0_{\rm S}$ final state, the decays $D^{*+} \to D^0 \pi^+$ with $D^0 \to K^- \pi^+$ and $D^0 \to K^- \pi^+ \pi^+ \pi^-$ are used. For $D^{*0} K^+$, the decay $D^{*0} \to D^0 \pi^0$ with $D^0 \to K^- \pi^+$ is used. A prominent $D_{s1}(2536)^+$ signal is observed in both $D^{*+} K^0_{\rm S}$ and $D^{*0} K^+$ final states. The resonances $D^*_{s1}(2700)^+$ and $D^*_{s3}(2860)^+$ are also observed, yielding information on their properties, including spin-parity assignments. The decay $D^*_{s2}(2573)^+ \to D^{*+} K^0_{\rm S}$ is observed for the first time, at a significance of 6.9 $\sigma$, and its branching fraction relative to the $D^*_{s2}(2573)^+ \to D^+ K^0_{\rm S}$ decay mode is measured

Search for Violations of Lorentz Invariance and CPT Symmetry in B-(s)(0) Mixing

Violations of CPT symmetry and Lorentz invariance are searched for by studying interference effects in B^{0} mixing and in B_{s}^{0} mixing. Samples of B^{0}→J/ψK_{S}^{0} and B_{s}^{0}→J/ψK^{+}K^{-} decays are recorded by the LHCb detector in proton-proton collisions at center-of-mass energies of 7 and 8 TeV, corresponding to an integrated luminosity of 3  fb^{-1}. No periodic variations of the particle-antiparticle mass differences are found, consistent with Lorentz invariance and CPT symmetry. Results are expressed in terms of the standard model extension parameter Δa_{μ} with precisions of O(10^{-15}) and O(10^{-14})  GeV for the B^{0} and B_{s}^{0} systems, respectively. With no assumption on Lorentz (non)invariance, the CPT-violating parameter z in the B_{s}^{0} system is measured for the first time and found to be Re(z)=-0.022±0.033±0.005 and Im(z)=0.004±0.011±0.002, where the first uncertainties are statistical and the second systematic

Study of the doubly charmed tetraquark T+cc

Quantum chromodynamics, the theory of the strong force, describes interactions of coloured quarks and gluons and the formation of hadronic matter. Conventional hadronic matter consists of baryons and mesons made of three quarks and quark-antiquark pairs, respectively. Particles with an alternative quark content are known as exotic states. Here a study is reported of an exotic narrow state in the D0D0π+ mass spectrum just below the D*+D0 mass threshold produced in proton-proton collisions collected with the LHCb detector at the Large Hadron Collider. The state is consistent with the ground isoscalar T+cc tetraquark with a quark content of ccu⎯⎯⎯d⎯⎯⎯ and spin-parity quantum numbers JP = 1+. Study of the DD mass spectra disfavours interpretation of the resonance as the isovector state. The decay structure via intermediate off-shell D*+ mesons is consistent with the observed D0π+ mass distribution. To analyse the mass of the resonance and its coupling to the D*D system, a dedicated model is developed under the assumption of an isoscalar axial-vector T+cc state decaying to the D*D channel. Using this model, resonance parameters including the pole position, scattering length, effective range and compositeness are determined to reveal important information about the nature of the T+cc state. In addition, an unexpected dependence of the production rate on track multiplicity is observed

First study of the CP-violating phase and decay-width difference in Bs 0→ψ(2S)ϕ decays

A time-dependent angular analysis of Bs 0→ψ(2S)ϕ decays is performed using data recorded by the LHCb experiment. The data set corresponds to an integrated luminosity of 3.0fb−1 collected during Run 1 of the LHC. The CP-violating phase and decay-width difference of the Bs 0 system are measured to be ϕs=0.23−0.28 +0.29±0.02rad and ΔΓs=0.066−0.044 +0.041±0.007ps−1, respectively, where the first uncertainty is statistical and the second systematic. This is the first time that ϕs and ΔΓs have been measured in a decay containing the ψ(2S) resonance. © 2016 The Author(s

Observation of Lambda(0)(b) -> psi (2S)pK(-) and Lambda(0)(b) -> J/psi pi(+)pi(-)pK(-) decays and a measurement of the A(b)(0) baryon mass

The decays Lambda(0)(b) -> psi(2S)pK(-) and Lambda(0)(b) -> J/psi pi(+)pi(-)pK(-) are observed in a data sample corresponding to an integrated luminosity of 3 fb(-1), collected in proton-proton collisions at 7 and 8 TeV centre-of-mass energies by the LHCb detector. The psi(2S) mesons are reconstructed through the decay modes psi(2S) -> mu(+)mu(-) and psi(2S) -> J/psi pi(+)pi(-) The branching fractions relative to that of Lambda(0)(b) -> J/psi pk(-) are measured to be [GRAPHICS] where the first uncertainties are statistical, the second are systematic and the third is related to the knowledge of J/psi and psi(2S) branching fractions. The mass of the Ai baryon is measured to be M(Lambda(0)(b)) = 5619.65 +/- 0.17 0.17 MeV/c(2), where the uncertainties are statistical and systematic

A new algorithm for identifying the flavour of B-s(0) mesons at LHCb

A new algorithm for the determination of the initial flavour of B-s(0) mesons is presented. The algorithm is based on two neural networks and exploits the b hadron production mechanism at a hadron collider. The first network is trained to select charged kaons produced in association with the B-s(0) meson. The second network combines the kaon charges to assign the B-s(0) flavour and estimates the probability of a wrong assignment. The algorithm is calibrated using data corresponding to an integrated luminosity of 3 fb(-1) collected by the LHCb experiment in proton-proton collisions at 7 and 8 TeV centre-of-mass energies. The calibration is performed in two ways: by resolving the B-s(0)-B-s(0) flavour oscillations in B-s(0) -> D-s(-)pi(+) decays, and by analysing flavour-specific B-s2*(5840)(0) -> B+K- decays. The tagging power measured in B-s(0) -> D-s(-)pi(+) decays is found to be (1.80 +/- 0.19 ( stat) +/- 0.18 (syst)) which is an improvement of about 50% compared to a similar algorithm previously used in the LHCb experiment

Measurement of the CP Asymmetry in Bs0 - B s0 Mixing

The CP asymmetry in the mixing of Bs0 and Bs0 mesons is measured in proton-proton collision data corresponding to an integrated luminosity of 3.0 fb-1, recorded by the LHCb experiment at center-of-mass energies of 7 and 8 TeV. Semileptonic Bs0 and Bs0 decays are studied in the inclusive mode Ds\u3bc\ub1\u3bd(-)\u3bcX with the Ds mesons reconstructed in the K\u3c0 final state. Correcting the observed charge asymmetry for detection and background effects, the CP asymmetry is found to be asls=(0.39\ub10.26\ub10.20)%, where the first uncertainty is statistical and the second systematic. This is the most precise measurement of asls to date. It is consistent with the prediction from the standard model and will constrain new models of particle physics