MAF amplification licenses ERα through epigenetic remodelling to drive breast cancer metastasis

MAF amplification increases the risk of breast cancer (BCa) metastasis through mechanisms that are still poorly understood yet have important clinical implications. Oestrogen-receptor-positive (ER+) BCa requires oestrogen for both growth and metastasis, albeit by ill-known mechanisms. Here we integrate proteomics, transcriptomics, epigenomics, chromatin accessibility and functional assays from human and syngeneic mouse BCa models to show that MAF directly interacts with oestrogen receptor alpha (ERα), thereby promoting a unique chromatin landscape that favours metastatic spread. We identify metastasis-promoting genes that are de novo licensed following oestrogen exposure in a MAF-dependent manner. The histone demethylase KDM1A is key to the epigenomic remodelling that facilitates the expression of the pro-metastatic MAF/oestrogen-driven gene expression program, and loss of KDM1A activity prevents this metastasis. We have thus determined that the molecular basis underlying MAF/oestrogen-mediated metastasis requires genetic, epigenetic and hormone signals from the systemic environment, which influence the ability of BCa cells to metastasize

Study of the psi(2)(3823) and chi(c1)(3872) states in B+->(J/psi pi(+)pi(-))K(+)decays

The decays $B^+\rightarrow J/\psi \pi^+ \pi^- K^+$ are studied using a data set corresponding to an integrated luminosity of 9fb$^{-1}$ collected with the LHCb detector in proton-proton collisions between 2011 and 2018. Precise measurements of the ratios of branching fractions with the intermediate $\psi_2(3823)$, $\chi_{c1}(3872)$ and $\psi(2S)$ states are reported. The decay of $B^+\rightarrow \psi_2(3872)K^+$ with $\psi_2(3823)\rightarrow J\psi\pi^+\pi^-$ is observed for the first time with a significance of 5.1 standard deviations. The mass differences between the $\psi_2(3823)$, $\chi_{c1}(3872)$ and $\psi(2S)$ states are measured to be $$\begin{array}{rcl} m_{\chi_{c1(3872)}} - m_{\psi_2(3823)} &= & 47.50 \pm 0.53 \pm 0.13\,\mathrm{MeV/}c^2\,, \\ m_{\psi_2(3823)} - m_{\psi(2S)} &= & 137.98 \pm 0.53 \pm 0.14\,\mathrm{MeV/}c^2\,, \\ m_{\chi_{c1}(3872)} - m_{\psi(2S)} &= & 185.49 \pm 0.06 \pm 0.03\,\mathrm{MeV/}c^2\,, \end{array}$$ resulting in the most precise determination of the $\chi_{c1}(3782)$ mass. The width of the $\psi_2(3823)$ state is found to be below 5.2MeV at 90\% confidence level. The Breit-Wigner width of the $\chi_{c1}(3872)$ state is measured to be $$\Gamma^{\mathrm{BW}}_{\chi_{c1}(3872)} = 0.96^{+0.19}_{-0.18}\pm0.21 \mathrm{MeV},$$ which is inconsistent with zero by 5.5 standard deviations.Comment: 26 pages, 3 figures. All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2020-009.html (LHCb public pages

Search for the doubly heavy Xi bc0 baryon via decays to D(0)pK(-)

A search for the doubly heavy $\mathit{\Xi}_{bc}^{0}$ baryon using its decay to the $D^0pK^-$ final state is performed using proton-proton collision data at a centre-of-mass energy of 13 TeV collected by the LHCb experiment between 2016 and 2018, corresponding to an integrated luminosity of 5.4 $\mathrm{fb}^{-1}$. No significant signal is found in the invariant mass range from 6.7 to 7.2 $\mathrm{GeV}/c^2$. Upper limits are set at $95\%$ credibility level on the ratio of the $\mathit{\Xi}_{bc}^{0}$ production cross-section times its branching fraction to $D^0pK^-$ relative to that of the $\mathit{\Lambda}_{b}^{0} \to D^0pK^-$ decay. The limits are set as a function of the $\mathit{\Xi}_{bc}^{0}$ mass and lifetime hypotheses, in the rapidity range from 2.0 to 4.5 and in the transverse momentum region from 5 to 25 $\mathrm{GeV}/c$. Upper limits range from $1.7\times10^{-2}$ to $3.0\times10^{-1}$ for the considered $\mathit{\Xi}_{bc}^{0}$ mass and lifetime hypotheses

First observation of the decay Lambda(0)(b) -> eta(c) (1S)pK(-)

The decay $\Lambda_b^0 \to \eta_c(1S) p K^-$ is observed for the first time using a data sample of proton-proton collisions, corresponding to an integrated luminosity of 5.5 $fb^{-1}$, collected with the LHCb experiment at a center-of-mass energy of 13 TeV. The branching fraction of the decay is measured, using the $\Lambda_b^0 \to J/\psi p K^-$ decay as a normalization mode, to be $\mathcal{B}(\Lambda_b^0 \to \eta_c(1S) p K^-)=(1.06\pm0.16\pm0.06^{+0.22}_{-0.19})\times10^{-4}$, where the quoted uncertainties are statistical, systematic and due to external inputs, respectively. A study of the $\eta_c(1S) p$ mass spectrum is performed to search for the $P_c(4312)^+$ pentaquark state. No evidence is observed and an upper limit of \begin{equation*} \frac{\mathcal{B}(\Lambda_b^0 \to P_c(4312)^+ K^-)\times \mathcal{B}(P_c(4312)^+ \to \eta_c(1S) p)}{\mathcal{B}(\Lambda_b^0 \to \eta_c(1S) p K^-)} < 0.24 \end{equation*} is obtained at the 95% confidence level.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2020-012.html (LHCb public pages

Measurement of differential b b ¯ - and c c ¯ -dijet cross-sections in the forward region of pp collisions at s = 13 TeV

Abstract: The inclusive bb¯- and cc¯-dijet production cross-sections in the forward region of pp collisions are measured using a data sample collected with the LHCb detector at a centre-of-mass energy of 13 TeV in 2016. The data sample corresponds to an integrated luminosity of 1.6 fb−1. Differential cross-sections are measured as a function of the transverse momentum and of the pseudorapidity of the leading jet, of the rapidity difference between the jets, and of the dijet invariant mass. A fiducial region for the measurement is defined by requiring that the two jets originating from the two b or c quarks are emitted with transverse momentum greater than 20 GeV/c, pseudorapidity in the range 2.2 < η < 4.2, and with a difference in the azimuthal angle between the two jets greater than 1.5. The integrated bb¯-dijet cross-section is measured to be 53.0 ± 9.7 nb, and the total cc¯-dijet cross-section is measured to be 73 ± 16 nb. The ratio between cc¯- and bb¯-dijet cross-sections is also measured and found to be 1.37 ± 0.27. The results are in agreement with theoretical predictions at next-to-leading order

Search for the doubly heavy Ξ bc 0 baryon via decays to D 0 pK −

Abstract: A search for the doubly heavy Ξbc0 baryon using its decay to the D0pK– final state is performed using proton-proton collision data at a centre-of-mass energy of 13 TeV collected by the LHCb experiment between 2016 and 2018, corresponding to an integrated luminosity of 5.4 fb−1. No significant signal is found in the invariant mass range from 6.7 to 7.2 GeV/c2. Upper limits are set at 95% credibility level on the ratio of the Ξbc0 production cross-section times its branching fraction to D0pK− relative to that of the Λb0→D0pK− decay. The limits are set as a function of the Ξbc0 mass and lifetime hypotheses, in the rapidity range from 2.0 to 4.5 and in the transverse momentum region from 5 to 25 GeV/c. Upper limits range from 1.7 × 10−2 to 3.0 × 10−1 for the considered Ξbc0 mass and lifetime hypotheses

Strong constraints on the b → sγ photon polarisation from B 0 → K *0 e + e − decays

Abstract: An angular analysis of the B0 → K*0e+e− decay is performed using a data sample corresponding to an integrated luminosity of 9 fb−1 of pp collisions collected with the LHCb experiment. The analysis is conducted in the very low dielectron mass squared (q2) interval between 0.0008 and 0.257 GeV2, where the rate is dominated by the B0 → K*0γ transition with a virtual photon. The fraction of longitudinal polarisation of the K*0 meson, FL, is measured to be FL = (4.4 ± 2.6 ± 1.4)%, where the first uncertainty is statistical and the second systematic. The ATRe observable, which is related to the lepton forward-backward asymmetry, is measured to be ATRe = −0.06 ± 0.08 ± 0.02. The AT2 and ATIm transverse asymmetries, which are sensitive to the virtual photon polarisation, are found to be AT2 = 0.11 ± 0.10 ± 0.02 and ATIm = 0.02 ± 0.10 ± 0.01. The results are consistent with Standard Model predictions and provide the world’s best constraint on the b → sγ photon polarisation

Measurement of the CKM angle γ in B ± → DK ± and B ± → Dπ ± decays with D → K S 0 h + h −

Abstract: A measurement of CP-violating observables is performed using the decays B± → DK± and B± → Dπ±, where the D meson is reconstructed in one of the self-conjugate three-body final states KS0π+π− and KS0K+K− (commonly denoted KS0h+h−). The decays are analysed in bins of the D-decay phase space, leading to a measurement that is independent of the modelling of the D-decay amplitude. The observables are inter- preted in terms of the CKM angle γ. Using a data sample corresponding to an integrated luminosity of 9 fb−1 collected in proton-proton collisions at centre-of mass energies of 7, 8, and 13 TeV with the LHCb experiment, γ is measured to be 68.7−5.1+5.2°. The hadronic parameters rBDK, rBDπ, δBDK, andδBDπ, which are the ratios and strong-phase differences of the suppressed and favoured B± decays, are also reported