Post-receptor IGF1 insensitivity restricted to the MAPK pathway in a Silver-Russell syndrome patient with hypomethylation at the imprinting control region on chromosome 11

Background: Hypomethylation of the paternal imprinting center region 1 (ICR1) is the most frequent molecular cause of Silver-Russell syndrome (SRS). Clinical evidence suggests that patients with this epimutation have mild IGF1 insensitivity. Objective: To assess in vitro IGF1 action in fibroblast culture from a patient with SRS and IGF1 insensitivity. Methods: Fibroblast cultures from one patient with SRS due to ICR1 demethylation and controls were established. The SRS patient has severe growth failure, elevated IGF1 level, and poor growth rate during human recombinant GH treatment. IGF1 action was assessed by cell proliferation, AKT, and p42/44-MAPK phosphorylation. Gene expression was determined by real-time PCR. Results: Despite normal IGF1R sequence and expression, fibroblast proliferation induced by IGF1 was 50% lower in SRS fibroblasts in comparison with controls. IGF1 and insulin promoted a p42/44-MAPK activation in SRS fibroblasts 40 and 36%, respectively, lower than that in control fibroblasts. On the other hand, p42/44-MAPK activation induced by EGF stimulation was only slightly reduced (75% in SRS fibroblasts in comparison with control), suggesting a general impairment in MAPK pathway with a greater impairment of the stimulation induced by insulin and IGF1 than by EGF. A PCR array analysis disclosed a defect in MAPK pathway characterized by an increase in DUSP4 and MEF2C gene expressions in patient fibroblasts. Conclusion: A post-receptor IGF1 insensitivity was characterized in one patient with SRS and ICR1 hypomethylation. Although based on one unique severely affected patient, these results raise an intriguing mechanism to explain the postnatal growth impairment observed in SRS patients that needs confirmation in larger cohorts.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [08/57915-2, 05/04726-0, 05/50144-2]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [142062/06-5, 301339/2008-9, 300938/06-3, 307951/06-5

Evidence of a J/ψΛJ/\psi\Lambda structure and observation of excited Ξ−\Xi^- states in the Ξb−→J/ψΛK−\Xi^-_b \to J/\psi\Lambda K^- decay

First evidence of a structure in the $J/\psi{\Lambda}$ invariant mass distribution is obtained from an amplitude analysis of $\Xi_b^-{\rightarrow}J/\psi{\Lambda}K^-$ decays. The observed structure is consistent with being due to a charmonium pentaquark with strangeness with a significance of $3.1\sigma$ including systematic uncertainties and look-elsewhere effect. Its mass and width are determined to be $4458.8\pm2.9^{+4.7}_{-1.1}$ MeV and $17.3\pm6.5^{+8.0}_{-5.7}$ MeV, respectively, where the quoted uncertainties are statistical and systematic. The structure is also consistent with being due to two resonances. In addition, the narrow excited $\Xi^-$ states, $\Xi(1690)^-$ and $\Xi(1820)^-$, are seen for the first time in a $\Xi^-_b$ decay, and their masses and widths are measured with improved precision. The analysis is performed using $pp$ collision data corresponding to a total integrated luminosity of 9 fb$^{-1}$, collected with the LHCb experiment at centre-of-mass energies of 7, 8 and 13 TeV

Branching Fraction Measurements of the Rare Bs0→ϕμ+μ−B^0_s\rightarrow\phi\mu^+\mu^- and Bs0→f2′(1525)μ+μ−B^0_s\rightarrow f_2^\prime(1525)\mu^+\mu^- Decays

The branching fraction of the rare $B^0_s\rightarrow\phi\mu^+\mu^-$ decay is measured using data collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV, corresponding to integrated luminosities of 1, 2, and 6 fb$^{-1}$, respectively. The branching fraction is reported in intervals of q$^2$, the square of the dimuon invariant mass. In the q$^2$ region between 1.1 and 6.0 GeV$^2$/c$^4$, the measurement is found to lie 3.6 standard deviations below a standard model prediction based on a combination of light cone sum rule and lattice QCD calculations. In addition, the first observation of the rare $B^0_s\rightarrow f_2^\prime(1525)\mu^+\mu^-$ decay is reported with a statistical significance of 9 standard deviations and its branching fraction is determined

Branching Fraction Measurements of the Rare Bs0→ϕμ+μ−B^0_s\rightarrow\phi\mu^+\mu^- and Bs0→f2′(1525)μ+μ−B^0_s\rightarrow f_2^\prime(1525)\mu^+\mu^-- Decays

International audienceThe branching fraction of the rare Bs0→ϕμ+μ- decay is measured using data collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV, corresponding to integrated luminosities of 1, 2, and 6  fb-1, respectively. The branching fraction is reported in intervals of q2, the square of the dimuon invariant mass. In the q2 region between 1.1 and 6.0  GeV2/c4, the measurement is found to lie 3.6 standard deviations below a standard model prediction based on a combination of light cone sum rule and lattice QCD calculations. In addition, the first observation of the rare Bs0→f2′(1525)μ+μ- decay is reported with a statistical significance of 9 standard deviations and its branching fraction is determined

Observation of the suppressed Λb0→DpK- decay with D→K+π- and measurement of its CP asymmetry

International audienceA study of Λb0 baryon decays to the DpK- final state is presented based on a proton-proton collision data sample corresponding to an integrated luminosity of 9  fb-1 collected with the LHCb detector. Two Λb0 decays are considered, Λb0→DpK- with D→K-π+ and D→K+π-, where D represents a superposition of D0 and D¯0 states. The latter process is expected to be suppressed relative to the former, and is observed for the first time. The ratio of branching fractions of the two decays is measured, and the CP asymmetry of the suppressed mode, which is sensitive to the Cabibbo-Kobayashi-Maskawa angle γ, is also reported

Search for the doubly heavy baryons Ωbc0\Omega^0_{bc} and Ξbc0\Xi^0_{bc} decaying to Λc+π−\Lambda^+_c \pi^- and Ξc+π−\Xi^+_c \pi^-

The first search for the doubly heavy baryon and a search for the baryon are performed using collision data collected via the experiment from 2016 to 2018 at a centre-of-mass energy of , corresponding to an integrated luminosity of 5.2 . The baryons are reconstructed via their decays to and . No significant excess is found for invariant masses between 6700 and 7300 , in a rapidity range from 2.0 to 4.5 and a transverse momentum range from 2 to 20 . Upper limits are set on the ratio of the and production cross-section times the branching fraction to ( ) relative to that of the ( ) baryon, for different lifetime hypotheses, at 95% confidence level. The upper limits range from to for the ( ) decay, and from to for the ( ) decay, depending on the considered mass and lifetime of the ( ) baryon

Simultaneous determination of CKM angle γ\gamma and charm mixing parameters

A combination of measurements sensitive to the CP violation angle γ of the Cabibbo-Kobayashi-Maskawa unitarity triangle and to the charm mixing parameters that describe oscillations between D$^{0}$ and $\overline{D} ^{0}$ mesons is performed. Results from the charm and beauty sectors, based on data collected with the LHCb detector at CERN’s Large Hadron Collider, are combined for the first time. This method provides an improvement on the precision of the charm mixing parameter y by a factor of two with respect to the current world average. The charm mixing parameters are determined to be $x=\left({0.400}_{-0.053}^{+0.052}\right)\%$ and y = $\left({0.630}_{-0.030}^{+0.033}\right)\%$. The angle γ is found to be γ = $\left({65.4}_{-4.2}^{+3.8}\right){}^{\circ}$ and is the most precise determination from a single experiment.[graphic not available: see fulltext

Simultaneous determination of CKM angle γ\gamma and charm mixing parameters

International audienceA combination of measurements sensitive to the CP violation angle γ of the Cabibbo-Kobayashi-Maskawa unitarity triangle and to the charm mixing parameters that describe oscillations between D$^{0}$ and $\overline{D} ^{0}$ mesons is performed. Results from the charm and beauty sectors, based on data collected with the LHCb detector at CERN’s Large Hadron Collider, are combined for the first time. This method provides an improvement on the precision of the charm mixing parameter y by a factor of two with respect to the current world average. The charm mixing parameters are determined to be $x=\left({0.400}_{-0.053}^{+0.052}\right)\%$ and y = $\left({0.630}_{-0.030}^{+0.033}\right)\%$. The angle γ is found to be γ = $\left({65.4}_{-4.2}^{+3.8}\right){}^{\circ}$ and is the most precise determination from a single experiment.[graphic not available: see fulltext