A de novo substitution in BCL11B leads to loss of interaction with transcriptional complexes and craniosynostosis

Craniosynostosis, the premature ossification of cranial sutures, is a developmental disorder of the skull vault, occurring in approximately 1 in 2250 births. The causes are heterogeneous, with a monogenic basis identified in ~25% of patients. Using whole-genome sequencing, we identified a novel, de novo variant in BCL11B, c.7C>A, encoding an R3S substitution (p.R3S), in a male patient with coronal suture synostosis. BCL11B is a transcription factor that interacts directly with the nucleosome remodelling and deacetylation complex (NuRD) and polycomb-related complex 2 (PRC2) through the invariant proteins RBBP4 and RBBP7. The p.R3S substitution occurs within a conserved amino-terminal motif (RRKQxxP) of BCL11B and reduces interaction with both transcriptional complexes. Equilibrium binding studies and molecular dynamics simulations show that the p.R3S substitution disrupts ionic coordination between BCL11B and the RBBP4-MTA1 complex, a subassembly of the NuRD complex, and increases the conformational flexibility of Arg-4, Lys-5 and Gln-6 of BCL11B. These alterations collectively reduce the affinity of BCL11B p.R3S for the RBBP4-MTA1 complex by nearly an order of magnitude. We generated a mouse model of the BCL11B p.R3S substitution using a CRISPR-Cas9-based approach, and we report herein that these mice exhibit craniosynostosis of the coronal suture, as well as other cranial sutures. This finding provides strong evidence that the BCL11B p.R3S substitution is causally associated with craniosynostosis and confirms an important role for BCL11B in the maintenance of cranial suture patency

Measurement of CP asymmetries in D(s)+→ηπ+ {D}_{(s)}^{+}\to \eta {\pi}^{+} and D(s)+→η′π+ {D}_{(s)}^{+}\to {\eta}^{\prime }{\pi}^{+} decays

Searches for CP violation in the decays ${D}_{(s)}^{+}\to \eta {\pi}^{+}$ and ${D}_{(s)}^{+}\to {\eta}^{\prime }{\pi}^{+}$ are performed using pp collision data corresponding to 6 fb$^{−1}$ of integrated luminosity collected by the LHCb experiment. The calibration channels ${D}_{(s)}^{+}\to \phi {\pi}^{+}$ are used to remove production and detection asymmetries. The resulting CP-violating asymmetries are${\displaystyle \begin{array}{l}{\mathcal{A}}^{CP}=\left({D}^{+}\to \eta {\pi}^{+}\right)=\left(0.34\pm 0.66\pm 0.16\pm 0.05\right)\%,\\ {}{\mathcal{A}}^{CP}=\left({D}_s^{+}\to \eta {\pi}^{+}\right)=\left(0.32\pm 0.51\pm 0.12\right)\%,\\ {}\begin{array}{l}{\mathcal{A}}^{CP}=\left({D}^{+}\to {\eta}^{\prime }{\pi}^{+}\right)=\left(0.49\pm 0.18\pm 0.06\pm 0.05\right)\%,\\ {}{\mathcal{A}}^{CP}=\left({D}_s^{+}\to {\eta}^{\prime }{\pi}^{+}\right)=\left(0.01\pm 0.12\pm 0.08\right)\%,\end{array}\end{array}}$where the first uncertainty is statistical, the second is systematic and the third, relevant for the D$^{+}$ channels, is due to the uncertainty on ${\mathcal{A}}^{CP}=\left({D}^{+}\to \phi {\pi}^{+}\right)$. These measurements, currently the most precise for three of the four channels considered, are consistent with the absence of CP violation. A combination of these results with previous LHCb measurements is presented.[graphic not available: see fulltext]Searches for $CP$ violation in the decays $D^+_{(s)}\rightarrow \eta \pi^+$ and $D^+_{(s)}\rightarrow \eta^{\prime} \pi^+$ are performed using $pp$ collision data corresponding to 6 fb$^{-1}$ of integrated luminosity collected by the LHCb experiment. The calibration channels $D^+_{(s)}\rightarrow \phi \pi^+$ are used to remove production and detection asymmetries. The resulting $CP$-violating asymmetries are $A^{CP}(D^+ \rightarrow \eta \pi^+) = (0.34 \pm 0.66 \pm 0.16 \pm 0.05)\%$, $A^{CP}(D^+_s \rightarrow \eta \pi^+) = (0.32 \pm 0.51 \pm 0.12)\%$, $A^{CP}(D^+ \rightarrow \eta^{\prime} \pi^+) = (0.49 \pm 0.18 \pm 0.06 \pm 0.05)\%$, $A^{CP}(D^+_s \rightarrow \eta^{\prime} \pi^+) = (0.01 \pm 0.12 \pm 0.08)\%$, where the first uncertainty is statistical, the second is systematic and the third, relevant for the $D^+$ channels, is due to the uncertainty on $A^{CP}(D^+ \to \phi \pi^+)$. These measurements, currently the most precise for three of the four channels considered, are consistent with the absence of $CP$ violation. A combination of these results with previous LHCb measurements is presented

Observation of the Bs0 ⁣→D∗+D∗−B^0_s\!\to D^{*+}D^{*-} decay

International audienceThe first observation of the ${B}_s^0$→ D$^{∗+}$D$^{∗−}$ decay and the measurement of its branching ratio relative to the B$^{0}$→ D$^{∗+}$D$^{∗−}$ decay are presented. The data sample used corresponds to an integrated luminosity of 9 fb$^{−1}$ of proton-proton collisions recorded by the LHCb experiment at centre-of-mass energies of 7, 8 and 13 TeV between 2011 and 2018. The decay is observed with more than 10 standard deviations and the time-integrated ratio of branching fractions is determined to be$\frac{\mathcal{B}\left({B}_s^0\to {D}^{\ast +}{D}^{\ast -}\right)}{\mathcal{B}\left({B}^0\to {D}^{\ast +}{D}^{\ast -}\right)}=0.269\pm 0.032\pm 0.011\pm 0.008,$where the first uncertainty is statistical, the second systematic and the third due to the uncertainty of the fragmentation fraction ratio f$_{s}$/f$_{d}$. The ${B}_s^0$→ D$^{*+}$D$^{*−}$ branching fraction is calculated to be$\mathcal{B}\left({B}_s^0\to {D}^{\ast +}{D}^{\ast -}\right)=\left(2.15\pm 0.26\pm 0.09\pm 0.06\pm 0.16\right)\times {10}^{-4},$where the fourth uncertainty is due to the B$^{0}$→ D$^{*+}$D$^{*−}$ branching fraction. These results are calculated using the average ${B}_s^0$ meson lifetime in simulation. Correction factors are reported for scenarios where either a purely heavy or a purely light ${B}_s^0$ eigenstate is considered.[graphic not available: see fulltext

First observation and branching fraction measurement of the Λb0→Ds−p {\Lambda}_b^0\to {D}_s^{-}p decay

International audienceThe first observation of the ${\Lambda}_b^0\to {D}_s^{-}p$ decay is presented using proton-proton collision data collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}$ = 13 TeV, corresponding to a total integrated luminosity of 6 fb$^{−1}$. Using the ${\Lambda}_b^0\to {\Lambda}_c^{+}{\pi}^{-}$ decay as the normalisation mode, the branching fraction of the ${\Lambda}_b^0\to {D}_s^{-}p$ decay is measured to be $\mathcal{B}\left({\Lambda}_b^0\to {D}_s^{-}p\right)=\left(12.6\pm 0.5\pm 0.3\pm 1.2\right)\times {10}^{-6}$, where the first uncertainty is statistical, the second systematic and the third due to uncertainties in the branching fractions of the ${\Lambda}_b^0\to {\Lambda}_c^{+}{\pi}^{-}$, ${D}_s^{-}\to {K}^{-}{K}^{+}{\pi}^{-}$ and ${\Lambda}_c^{+}\to p{K}^{-}{\pi}^{+}$ decays.[graphic not available: see fulltext

Measurement of the Z boson production cross-section in proton-lead collisions at sNN \sqrt{s_{\textrm{NN}}} = 8.16 TeV

This article presents the first measurement of the differential $Z$-boson production cross-section in the forward region using proton-lead collisions with the LHCb detector. The dataset was collected at a nucleon-nucleon centre-of-mass energy of $\sqrt{s_\mathrm{NN}}=8.16\,\mathrm{TeV}$ in 2016, corresponding to an integrated luminosity of $30.8\,\mathrm{nb}^{-1}$. The forward-backward ratio and the nuclear modification factors are measured together with the differential cross-section as functions of the $Z$ boson rapidity in the centre-of-mass frame, the transverse momentum of the $Z$ boson and a geometric variable $\phi^{*}$. The results are in good agreement with the predictions from nuclear parton distribution functions, providing strong constraining power at small Bjorken-$x$.This article presents the first measurement of the differential Z-boson production cross-section in the forward region using proton-lead collisions with the LHCb detector. The dataset was collected at a nucleon-nucleon centre-of-mass energy of $\sqrt{s_{\textrm{NN}}}$ = 8.16 TeV in 2016, corresponding to an integrated luminosity of 30.8 nb$^{−1}$. The forward-backward ratio and the nuclear modification factors are measured together with the differential cross-section as functions of the Z boson rapidity in the centre-of-mass frame, the transverse momentum of the Z boson and a geometric variable ϕ$^{*}$. The results are in good agreement with the predictions from nuclear parton distribution functions, providing strong constraining power at small Bjorken-x.[graphic not available: see fulltext]This article presents the first measurement of the differential $Z$-boson production cross-section in the forward region using proton-lead collisions with the LHCb detector. The dataset was collected at a nucleon-nucleon centre-of-mass energy of $\sqrt{s_\mathrm{NN}}=8.16\,\mathrm{TeV}$ in 2016, corresponding to an integrated luminosity of $30.8\,\mathrm{nb}^{-1}$. The forward-backward ratio and the nuclear modification factors are measured together with the differential cross-section as functions of the $Z$ boson rapidity in the centre-of-mass frame, the transverse momentum of the $Z$ boson and a geometric variable $\phi^{*}$. The results are in good agreement with the predictions from nuclear parton distribution functions, providing strong constraining power at small Bjorken-$x$

Measurement of the CKM angle γγ with B±→D[K∓π±π±π∓]h± B^\pm \to D[K^\mp π^\pm π^\pm π^\mp] h^\pm decays using a binned phase-space approach

The CKM angle $\gamma$ is determined from $C\!P$-violating observables measured in ${B^\pm \to D[ K^\mp \pi^\pm\pi^\pm\pi^\mp] h^\pm}$, $(h = K,\pi)$ decays, where the measurements are performed in bins of the decay phase-space of the $D$ meson. Using proton-proton collision data collected by the LHCb experiment at centre-of-mass energies of $7, 8$ and $13\,\text{TeV}$, corresponding to a total integrated luminosity of $9\,\text{fb}^{-1}$, $\gamma$ is determined to be \begin{equation*} \gamma = \left( 54.8 \: ^{+\:6.0 }_{-\:5.8} \: ^{+\:0.6}_{-\:0.6} \: ^{+\:6.7}_{-\:4.3} \right)^\circ, \end{equation*} where the first uncertainty is statistical, the second systematic and the third from the external inputs on the coherence factors and strong phases of the $D$-meson decays.The CKM angle γ is determined from CP-violating observables measured in B$^{±}$ → D[K$^{∓}$π$^{±}$π$^{±}$π$^{∓}$]h$^{±}$, (h = K, π) decays, where the measurements are performed in bins of the decay phase-space of the D meson. Using proton-proton collision data collected by the LHCb experiment at centre-of-mass energies of 7, 8 and 13 TeV, corresponding to a total integrated luminosity of 9 fb$^{−1}$, γ is determined to be$\gamma ={\left(54.8\begin{array}{c}+6.0\\ {}-5.8\end{array}\begin{array}{c}+0.6\\ {}-0.6\end{array}\begin{array}{c}+6.7\\ {}-4.3\end{array}\right)}^{\circ },$where the first uncertainty is statistical, the second systematic and the third from the external inputs on the coherence factors and strong phases of the D-meson decays.[graphic not available: see fulltext]The CKM angle $\gamma$ is determined from $C\!P$-violating observables measured in ${B^\pm \to D[ K^\mp \pi^\pm\pi^\pm\pi^\mp] h^\pm}$, $(h = K,\pi)$ decays, where the measurements are performed in bins of the decay phase-space of the $D$ meson. Using proton-proton collision data collected by the LHCb experiment at centre-of-mass energies of $7, 8$ and $13\,\text{TeV}$, corresponding to a total integrated luminosity of $9\,\text{fb}^{-1}$, $\gamma$ is determined to be \begin{equation*} \gamma = \left( 54.8 \: ^{+\:6.0 }_{-\:5.8} \: ^{+\:0.6}_{-\:0.6} \: ^{+\:6.7}_{-\:4.3} \right)^\circ, \end{equation*} where the first uncertainty is statistical, the second systematic and the third from the external inputs on the coherence factors and strong phases of the $D$-meson decays

Search for the lepton-flavour violating decays B0→K∗0μ±e∓B^0 \to K^{*0} \mu^\pm e^\mp and Bs0→ϕμ±e∓B_s^0 \to \phi \mu^\pm e^\mp

A search for the lepton-flavour violating decays $B^0 \to K^{*0} \mu^\pm e^\mp$ and $B_s^0 \to \phi \mu^\pm e^\mp$ is presented, using proton-proton collision data collected by the LHCb detector at the LHC, corresponding to an integrated luminosity of $9\,\text{fb}^{-1}$. No significant signals are observed and upper limits of \begin{align} {\cal B}( B^0 \to K^{*0} \mu^+ e^- ) &< \phantom{1}5.7\times 10^{-9}~(6.9\times 10^{-9}),\newline {\cal B}( B^0 \to K^{*0} \mu^- e^+ ) &< \phantom{1}6.8\times 10^{-9}~(7.9\times 10^{-9}),\newline {\cal B}( B^0 \to K^{*0} \mu^\pm e^\mp ) &< 10.1\times 10^{-9}~(11.7\times 10^{-9}),\newline {\cal B}( B_s^0 \to \phi \mu^\pm e^\mp ) &< 16.0\times 10^{-9}~(19.8\times 10^{-9}) \end{align} are set at $90\%~(95\%)$ confidence level. These results constitute the world's most stringent limits to date, with the limit on the decay $B_s^0 \to \phi \mu^\pm e^\mp$ the first being set. In addition, limits are reported for scalar and left-handed lepton-flavour violating New Physics scenarios.A search for the lepton-flavour violating decays B$^{0}$ → K$^{*0}$μ$^{±}$e$^{∓}$ and ${B}_s^0$→ ϕμ$^{±}$e$^{∓}$ is presented, using proton-proton collision data collected by the LHCb detector at the LHC, corresponding to an integrated luminosity of 9 fb$^{−1}$. No significant signals are observed and upper limits of${\displaystyle \begin{array}{c}\mathcal{B}\left({B}^0\to {K}^{\ast 0}{\mu}^{+}{e}^{-}\right)<5.7\times {10}^{-9}\left(6.9\times {10}^{-9}\right),\\ {}\mathcal{B}\left({B}^0\to {K}^{\ast 0}{\mu}^{-}{e}^{+}\right)<6.8\times {10}^{-9}\left(7.9\times {10}^{-9}\right),\\ {}\mathcal{B}\left({B}^0\to {K}^{\ast 0}{\mu}^{\pm }{e}^{\mp}\right)<10.1\times {10}^{-9}\left(11.7\times {10}^{-9}\right),\\ {}\mathcal{B}\left({B}_s^0\to \phi {\mu}^{\pm }{e}^{\mp}\right)<16.0\times {10}^{-9}\left(19.8\times {10}^{-9}\right)\end{array}}$are set at 90% (95%) confidence level. These results constitute the world’s most stringent limits to date, with the limit on the decay ${B}_s^0$→ ϕμ$^{±}$e$^{∓}$ the first being set. In addition, limits are reported for scalar and left-handed lepton-flavour violating New Physics scenarios.[graphic not available: see fulltext]A search for the lepton-flavour violating decays $B^0 \to K^{*0} \mu^\pm e^\mp$ and $B_s^0 \to \phi \mu^\pm e^\mp$ is presented, using proton-proton collision data collected by the LHCb detector at the LHC, corresponding to an integrated luminosity of $9\,\text{fb}^{-1}$. No significant signals are observed and upper limits of \begin{align} {\cal B}( B^0 \to K^{*0} \mu^+ e^- ) &< \phantom{1}5.7\times 10^{-9}~(6.9\times 10^{-9}),\newline {\cal B}( B^0 \to K^{*0} \mu^- e^+ ) &< \phantom{1}6.8\times 10^{-9}~(7.9\times 10^{-9}),\newline {\cal B}( B^0 \to K^{*0} \mu^\pm e^\mp ) &< 10.1\times 10^{-9}~(11.7\times 10^{-9}),\newline {\cal B}( B_s^0 \to \phi \mu^\pm e^\mp ) &< 16.0\times 10^{-9}~(19.8\times 10^{-9}) \end{align} are set at $90\%~(95\%)$ confidence level. These results constitute the world's most stringent limits to date, with the limit on the decay $B_s^0 \to \phi \mu^\pm e^\mp$ the first being set. In addition, limits are reported for scalar and left-handed lepton-flavour violating New Physics scenarios