DRAM-1 is required for mTORC1 activation by facilitating lysosomal amino acid efflux

Sensing nutrient availability is essential for appropriate cellular growth, and mTORC1 is a major regulator of this process. Mechanisms causing mTORC1 activation are, however, complex and diverse. We report here an additional important step in the activation of mTORC1, which regulates the efflux of amino acids from lysosomes into the cytoplasm. This process requires DRAM-1, which binds the membrane carrier protein SCAMP3 and the amino acid transporters SLC1A5 and LAT1, directing them to lysosomes and permitting efficient mTORC1 activation. Consequently, we show that loss of DRAM-1 also impacts pathways regulated by mTORC1, including insulin signaling, glycemic balance, and adipocyte differentiation. Interestingly, although DRAM-1 can promote autophagy, this effect on mTORC1 is autophagy independent, and autophagy only becomes important for mTORC1 activation when DRAM-1 is deleted. These findings provide important insights into mTORC1 activation and highlight the importance of DRAM-1 in growth control, metabolic homeostasis, and differentiation

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

Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

Measurement of the ratios of branching fractions R(D∗)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

The ratios of branching fractions $\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu})$ and $\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu})$ are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb${ }^{-1}$ of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode $\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}$. The measured values are $\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024$ and $\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066$, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is $\rho=-0.43$. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages

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

Observation of the decay B0s→ψ(2S)K+π−

The decay B¯s0→ψ(2S)K+π− is observed using a data set 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. The branching fraction relative to the B0→ψ(2S)K+π− decay mode is measured to be B(B¯s0→ψ(2S)K+π−)B(B0→ψ(2S)K+π−)=5.38±0.36(stat)±0.22(syst)±0.31(fs/fd)%, where fs/fd indicates the uncertainty due to the ratio of probabilities for a b quark to hadronise into a Bs0 or B0 meson. Using an amplitude analysis, the fraction of decays proceeding via an intermediate K⁎(892)0 meson is measured to be 0.645±0.049(stat)±0.049(syst) and its longitudinal polarisation fraction is 0.524±0.056(stat)±0.029(syst) . The relative branching fraction for this component is determined to be B(B¯s0→ψ(2S)K⁎(892)0)B(B0→ψ(2S)K⁎(892)0)=5.58±0.57(stat)±0.40(syst)±0.32(fs/fd)%. In addition, the mass splitting between the Bs0 and B0 mesons is measured as M(Bs0)−M(B0)=87.45±0.44(stat)±0.09(syst) MeV/c2

Measurement of CP violation parameters and polarisation fractions in Bs0→J/ψK‾∗0 {\mathrm{B}}_{\mathrm{s}}^0\to \mathrm{J}/\psi {\overline{\mathrm{K}}}^{\ast 0} decays

The first measurement of ${C\!P}$ asymmetries in the decay ${B_s^0\to J/\psi \overline{K}^{*}(892)^{0}}$ and an updated measurement of its branching fraction and polarisation fractions are presented. The results are obtained using data corresponding to an integrated luminosity of $3.0\,fb^{-1}$ of proton-proton collisions recorded with the LHCb detector at centre-of-mass energies of $7$ and $8\,\mathrm{TeV}$. Together with constraints from ${B^0\to J/\psi \rho^0}$, the results are used to constrain additional contributions due to penguin diagrams in the ${C\!P}$-violating phase ${{\phi}_{s}}$, measured through ${B_s^0}$ decays to charmonium.The first measurement of CP asymmetries in the decay ${B}_s^0\to J/\psi {\overline{\mathrm{K}}}^{\ast }{(892)}^0$ and an updated measurement of its branching fraction and polarisation fractions are presented. The results are obtained using data corresponding to an integrated luminosity of 3.0 fb^{−}^{1} of proton-proton collisions recorded with the LHCb detector at centre-of-mass energies of 7 and 8 TeV. Together with constraints from B$^{0}$ → J/ψ ρ$^{0}$, the results are used to constrain additional contributions due to penguin diagrams in the CP -violating phase ϕ$_{s}$ , measured through B$_{s}^{0}$ decays to charmonium.The first measurement of ${C\!P}$ asymmetries in the decay ${B_s^0\to J/\psi \overline{K}^{*}(892)^{0}}$ and an updated measurement of its branching fraction and polarisation fractions are presented. The results are obtained using data corresponding to an integrated luminosity of $3.0\,fb^{-1}$ of proton-proton collisions recorded with the LHCb detector at centre-of-mass energies of $7$ and $8\,\mathrm{TeV}$. Together with constraints from ${B^0\to J/\psi \rho^0}$, the results are used to constrain additional contributions due to penguin diagrams in the ${C\!P}$-violating phase ${{\phi}_{s}}$, measured through ${B_s^0}$ decays to charmonium

Measurement of forward W→eνW\to e\nu production in pppp collisions at s=8 \sqrt{s}=8\,TeV

A measurement of the cross-section for $W \to e\nu$ production in $pp$ collisions is presented using data corresponding to an integrated luminosity of $2\,$fb$^{-1}$ collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}=8\,$TeV. The electrons are required to have more than $20\,$GeV of transverse momentum and to lie between 2.00 and 4.25 in pseudorapidity. The inclusive $W$ production cross-sections, where the $W$ decays to $e\nu$, are measured to be \begin{align*} \begin{split} \sigma_{W^{+} \to e^{+}\nu_{e}}&=1124.4\pm 2.1\pm 21.5\pm 11.2\pm 13.0\,\mathrm{pb},\\ \sigma_{W^{-} \to e^{-}\bar{\nu}_{e}}&=\,\,\,809.0\pm 1.9\pm 18.1\pm\,\,\,7.0\pm \phantom{0}9.4\,\mathrm{pb}, \end{split} \end{align*} where the first uncertainties are statistical, the second are systematic, the third are due to the knowledge of the LHC beam energy and the fourth are due to the luminosity determination. Differential cross-sections as a function of the electron pseudorapidity are measured. The $W^{+}/W^{-}$ cross-section ratio and production charge asymmetry are also reported. Results are compared with theoretical predictions at next-to-next-to-leading order in perturbative quantum chromodynamics. Finally, in a precise test of lepton universality, the ratio of $W$ boson branching fractions is determined to be \begin{align*} \begin{split} \mathcal{B}(W \to e\nu)/\mathcal{B}(W \to \mu\nu)=1.020\pm 0.002\pm 0.019, \end{split} \end{align*} where the first uncertainty is statistical and the second is systematic.A measurement of the cross-section for $W \to e\nu$ production in $pp$ collisions is presented using data corresponding to an integrated luminosity of $2\,$fb$^{-1}$ collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}=8\,$TeV. The electrons are required to have more than $20\,$GeV of transverse momentum and to lie between 2.00 and 4.25 in pseudorapidity. The inclusive $W$ production cross-sections, where the $W$ decays to $e\nu$, are measured to be \begin{equation*} \sigma_{W^{+} \to e^{+}\nu_{e}}=1124.4\pm 2.1\pm 21.5\pm 11.2\pm 13.0\,\mathrm{pb}, \end{equation*} \begin{equation*} \sigma_{W^{-} \to e^{-}\bar{\nu}_{e}}=\,\,\,809.0\pm 1.9\pm 18.1\pm\,\,\,7.0\pm \phantom{0}9.4\,\mathrm{pb}, \end{equation*} where the first uncertainties are statistical, the second are systematic, the third are due to the knowledge of the LHC beam energy and the fourth are due to the luminosity determination. Differential cross-sections as a function of the electron pseudorapidity are measured. The $W^{+}/W^{-}$ cross-section ratio and production charge asymmetry are also reported. Results are compared with theoretical predictions at next-to-next-to-leading order in perturbative quantum chromodynamics. Finally, in a precise test of lepton universality, the ratio of $W$ boson branching fractions is determined to be \begin{equation*} \mathcal{B}(W \to e\nu)/\mathcal{B}(W \to \mu\nu)=1.020\pm 0.002\pm 0.019, \end{equation*} where the first uncertainty is statistical and the second is systematic.A measurement of the cross-section for W → eν production in pp collisions is presented using data corresponding to an integrated luminosity of 2 fb$^{−1}$ collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}=8$ TeV. The electrons are required to have more than 20 GeV of transverse momentum and to lie between 2.00 and 4.25 in pseudorapidity. The inclusive W production cross-sections, where the W decays to eν, are measured to be ${\sigma}_{W^{+}\to {e}^{+}{\nu}_e}=1124.4\pm 2.1\pm 21.5\pm 11.2\pm 13.0\kern0.5em \mathrm{p}\mathrm{b},$ ${\sigma}_{W^{-}\to {e}^{-}{\overline{\nu}}_e}=809.0\pm 1.9\pm 18.1\pm \kern0.5em 7.0\pm \kern0.5em 9.4\,\mathrm{p}\mathrm{b},$ where the first uncertainties are statistical, the second are systematic, the third are due to the knowledge of the LHC beam energy and the fourth are due to the luminosity determination

Measurements of prompt charm production cross-sections in pp collisions at s=5 \sqrt{s}=5 TeV

Production cross-sections of prompt charm mesons are measured using data from $pp$ collisions at the LHC at a centre-of-mass energy of $5\,$TeV. The data sample corresponds to an integrated luminosity of $8.60\pm0.33\,$pb$^{-1}$ collected by the LHCb experiment. The production cross-sections of $D^0$, $D^+$, $D_s^+$, and $D^{*+}$ mesons are measured in bins of charm meson transverse momentum, $p_{\text{T}}$, and rapidity, $y$. They cover the rapidity range $2.0 < y < 4.5$ and transverse momentum ranges $0 < p_{\text{T}} < 10\, \text{GeV}/c$ for $D^0$ and $D^+$ and $1 < p_{\text{T}} < 10\, \text{GeV}/c$ for $D_s^+$ and $D^{*+}$ mesons. The inclusive cross-sections for the four mesons, including charge-conjugate states, within the range of $1 < p_{\text{T}} < 8\, \text{GeV}/c$ are determined to be \begin{equation*} \sigma(pp\rightarrow D^0 X) = 1190 \pm 3 \pm 64\,\mu\text{b} \end{equation*} \begin{equation*} \sigma(pp\rightarrow D^+ X) = 456 \pm 3 \pm 34\,\mu\text{b} \end{equation*} \begin{equation*} \sigma(pp\rightarrow D_s^+ X) = 195 \pm 4 \pm 19\,\mu\text{b} \end{equation*} \begin{equation*} \sigma(pp\rightarrow D^{*+} X)= 467 \pm 6 \pm 40\,\mu\text{b} \end{equation*} where the uncertainties are statistical and systematic, respectively.Production cross-sections of prompt charm mesons are measured using data from pp collisions at the LHC at a centre-of-mass energy of 5 TeV. The data sample corresponds to an integrated luminosity of 8.60 ± 0.33 pb$^{−1}$ collected by the LHCb experiment. The production cross-sections of D$^{0}$, D$^{+}$, D$_{s}^{+}$ , and D$^{∗+}$ mesons are measured in bins of charm meson transverse momentum, p$_{T}$, and rapidity, y. They cover the rapidity range 2.0 < y < 4.5 and transverse momentum ranges 0 < p$_{T}$ < 10 GeV/c for D$^{0}$ and D$^{+}$ and 1 < p$_{T}$ < 10 GeV/c for D$_{s}^{+}$ and D$^{∗+}$ mesons. The inclusive cross-sections for the four mesons, including charge-conjugate states, within the range of 1 < p$_{T}$ < 8 GeV/c are determined to be $\begin{array}{l}\sigma \left( pp\to {D}^0X\right)=1004\pm 3\pm 54\mu \mathrm{b},\\ {}\sigma \left( pp\to {D}^{+}X\right)=402\pm 2\pm 30\mu \mathrm{b},\\ {}\sigma \left( pp\to {D}_s^{+}X\right)=170\pm 4\pm 16\mu \mathrm{b},\\ {}\sigma \left( pp\to {D}^{\ast +}X\right)=421\pm 5\pm 36\mu \mathrm{b},\end{array}$ where the uncertainties are statistical and systematic, respectively.Production cross-sections of prompt charm mesons are measured using data from $pp$ collisions at the LHC at a centre-of-mass energy of $5\,$TeV. The data sample corresponds to an integrated luminosity of $8.60\pm0.33\,$pb$^{-1}$ collected by the LHCb experiment. The production cross-sections of $D^0$, $D^+$, $D_s^+$, and $D^{*+}$ mesons are measured in bins of charm meson transverse momentum, $p_{\text{T}}$, and rapidity, $y$. They cover the rapidity range $2.0<y<4.5$ and transverse momentum ranges $0 < p_{\text{T}} < 10\, \text{GeV}/c$ for $D^0$ and $D^+$ and $1 < p_{\text{T}} < 10\, \text{GeV}/c$ for $D_s^+$ and $D^{*+}$ mesons. The inclusive cross-sections for the four mesons, including charge-conjugate states, within the range of $1 < p_{\text{T}} < 8\, \text{GeV}/c$ are determined to be \sigma(pp\rightarrow D^0 X) = 1004 \pm 3 \pm 54\,\mu\text{b} \sigma(pp\rightarrow D^+ X) = 402 \pm 2 \pm 30\,\mu\text{b} \sigma(pp\rightarrow D_s^+ X) = 170 \pm 4 \pm 16\,\mu\text{b} \sigma(pp\rightarrow D^{*+} X)= 421 \pm 5 \pm 36\,\mu\text{b} where the uncertainties are statistical and systematic, respectively