Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies

Schinzel-Giedion syndrome (SGS) is a rare developmental disorder characterized by multiple malformations, severe neurological alterations and increased risk of malignancy. SGS is caused by de novo germline mutations clustering to a 12bp hotspot in exon 4 of SETBP1. Mutations in this hotspot disrupt a degron, a signal for the regulation of protein degradation, and lead to the accumulation of SETBP1 protein. Overlapping SETBP1 hotspot mutations have been observed recurrently as somatic events in leukemia. We collected clinical information of 47 SGS patients (including 26 novel cases) with germline SETBP1 mutations and of four individuals with a milder phenotype caused by de novo germline mutations adjacent to the SETBP1 hotspot. Different mutations within and around the SETBP1 hotspot have varying effects on SETBP1 stability and protein levels in vitro and in in silico modeling. Substitutions in SETBP1 residue I871 result in a weak increase in protein levels and mutations affecting this residue are significantly more frequent in SGS than in leukemia. On the other hand, substitutions in residue D868 lead to the largest increase in protein levels. Individuals with germline mutations affecting D868 have enhanced cell proliferation in vitro and higher incidence of cancer compared to patients with other germline SETBP1 mutations. Our findings substantiate that, despite their overlap, somatic SETBP1 mutations driving malignancy are more disruptive to the degron than germline SETBP1 mutations causing SGS. Additionally, this suggests that the functional threshold for the development of cancer driven by the disruption of the SETBP1 degron is higher than for the alteration in prenatal development in SGS. Drawing on previous studies of somatic SETBP1 mutations in leukemia, our results reveal a genotype-phenotype correlation in germline SETBP1 mutations spanning a molecular, cellular and clinical phenotype

Influence of BMP-2 on early follicular development and mRNA expression of oocyte specific genes in bovine preantral follicles cultured in vitro

This study evaluates the effect of different concentrations (0, 10, 50 and 100ng/mL) of bone morphogenetic protein-2 (BMP-2) on primordial and secondary follicle development. It also investigates the effects of FSH and BMP-2 on the growth, morphology, ultrastructure and expression of mRNA for GDF9, NLRP5 and NPM2 genes in secondary follicles cultured for 18 days. The presence of BMP-2 at all tested concentrations increased the development of primordial follicles in vitro, but the highest concentration of BMP-2 (100 ng/mL) reduced the percentage of normal follicles when compared with tissues cultured with 10 ng/mL BMP-2. During culture of secondary follicles, in contrast to higher concentrations (50 or 100 ng/mL), 10 ng/mL BMP-2 kept the morphology of follicles during initial stages of in vitro culture. This concentration of BMP-2 also benefits maintenance of the ultrastructure of 18-day cultured follicles. The presence of both BMP-2 and FSH in culture medium resulted in a significant (P<0.05) increase in follicular diameter after 18 days of culture. However, both FSH and BMP-2 reduced follicular mRNA expression of GDF9 and NLRP5 when compared to follicles cultured in media containing only FSH. In combination with FSH, BMP-2 reduced the mRNA levels of NPM2, when compared to follicles cultured in control medium. It is concluded from these data that 10 ng/mL BMP-2 promotes the growth of primordial in vitro and it helps to maintain the ultrastructure of secondary follicles, while FSH is more important for better expression of follicular markers like GDF9 and NLRP5

Search for narrow resonances in the <math display="inline"><mi>b</mi></math>-tagged dijet mass spectrum in proton-proton collisions at <math display="inline"><msqrt><mi>s</mi></msqrt><mo>=</mo><mn>13</mn><mtext> </mtext><mtext> </mtext><mi>TeV</mi></math>

International audienceA search is performed for narrow resonances decaying to final states of two jets, with at least one jet originating from a b quark, in proton-proton collisions at s=13  TeV. The data set corresponds to an integrated luminosity of 138  fb-1 collected with the CMS detector at the LHC. Jets originating from energetic b hadrons are identified through a b-tagging algorithm that utilizes a deep neural network or the presence of a muon inside a jet. The invariant mass spectrum of jet pairs is well described by a smooth parametrization and no evidence for the production of new particles is observed. Upper limits on the production cross section are set for excited b quarks and other resonances decaying to dijet final states containing b quarks. These limits exclude at 95% confidence level models of Z′ bosons with masses from 1.8 TeV to 2.4 TeV and of excited b quarks with masses from 1.8 TeV to 4.0 TeV. This is the most stringent exclusion of excited b quarks to date

Measurement of inclusive and differential cross sections for single top quark production in association with a W boson in proton-proton collisions at s \sqrt{s} = 13 TeV

International audienceMeasurements of the inclusive and normalised differential cross sections are presented for the production of single top quarks in association with a W boson in proton-proton collisions at a centre-of-mass energy of 13 TeV. The data used were recorded with the CMS detector at the LHC during 2016–2018, and correspond to an integrated luminosity of 138 fb$^{−1}$. Events containing one electron and one muon in the final state are analysed. For the inclusive measurement, a multivariate discriminant, exploiting the kinematic properties of the events is used to separate the signal from the dominant $\textrm{t}\overline{\textrm{t}}$ background. A cross section of $79.2\pm 0.9{\left(\textrm{stat}\right)}_{-8.0}^{+7.7}\left(\textrm{syst}\right)\pm 1.2\left(\textrm{lumi}\right)$ pb is obtained, consistent with the predictions of the standard model. For the differential measurements, a fiducial region is defined according to the detector acceptance, and the requirement of exactly one jet coming from the fragmentation of a bottom quark. The resulting distributions are unfolded to particle level and agree with the predictions at next-to-leading order in perturbative quantum chromodynamics.[graphic not available: see fulltext

Search for pair production of vector-like quarks in leptonic final states in proton-proton collisions at s \sqrt{s} = 13 TeV

A search is presented for vector-like $\mathrm{T}$ and $\mathrm{B}$ quark-antiquark pairs produced in proton-proton collisions at a center-of-mass energy of 13 TeV. Data were collected by the CMS experiment at the CERN LHC in 2016-2018, with an integrated luminosity of 138 fb$^{-1}$. Events are separated into single-lepton, same-sign charge dilepton, and multilepton channels. In the analysis of the single-lepton channel a multilayer neural network and jet identification techniques are employed to select signal events, while the same-sign dilepton and multilepton channels rely on the high-energy signature of the signal to distinguish it from standard model backgrounds. The data are consistent with standard model background predictions, and the production of vector-like quark pairs is excluded at 95% confidence level for $\mathrm{T}$ quark masses up to 1.54 TeV and $\mathrm{B}$ quark masses up to 1.56 TeV, depending on the branching fractions assumed, with maximal sensitivity to decay modes that include multiple top quarks. The limits obtained in this search are the strongest limits to date for $\mathrm{T} \overline{\mathrm{T}}$ production, excluding masses below 1.48 TeV for all decays to third generation quarks, and are the strongest limits to date for $\mathrm{B} \overline{\mathrm{B}}$ production with $\mathrm{B}$ quark decays to tW.A search is presented for vector-like T and B quark-antiquark pairs produced in proton-proton collisions at a center-of-mass energy of 13 TeV. Data were collected by the CMS experiment at the CERN LHC in 2016–2018, with an integrated luminosity of 138 fb$^{−1}$. Events are separated into single-lepton, same-sign charge dilepton, and multi-lepton channels. In the analysis of the single-lepton channel a multilayer neural network and jet identification techniques are employed to select signal events, while the same-sign dilepton and multilepton channels rely on the high-energy signature of the signal to distinguish it from standard model backgrounds. The data are consistent with standard model background predictions, and the production of vector-like quark pairs is excluded at 95% confidence level for T quark masses up to 1.54 TeV and B quark masses up to 1.56 TeV, depending on the branching fractions assumed, with maximal sensitivity to decay modes that include multiple top quarks. The limits obtained in this search are the strongest limits to date for $\textrm{T}\overline{\textrm{T}}$ production, excluding masses below 1.48 TeV for all decays to third generation quarks, and are the strongest limits to date for $\textrm{B}\overline{\textrm{B}}$ production with B quark decays to tW.[graphic not available: see fulltext]A search is presented for vector-like T and B quark-antiquark pairs produced in proton-proton collisions at a center-of-mass energy of 13 TeV. Data were collected by the CMS experiment at the CERN LHC in 2016-2018, with an integrated luminosity of 138 fb$^{-1}$. Events are separated into single-lepton, same-sign charge dilepton, and multilepton channels. In the analysis of the single-lepton channel a multilayer neural network and jet identification techniques are employed to select signal events, while the same-sign dilepton and multilepton channels rely on the high-energy signature of the signal to distinguish it from standard model backgrounds. The data are consistent with standard model background predictions, and the production of vector-like quark pairs is excluded at 95% confidence level for T quark masses up to 1.54 TeV and B quark masses up to 1.56 TeV, depending on the branching fractions assumed, with maximal sensitivity to decay modes that include multiple top quarks. The limits obtained in this search are the strongest limits to date for $\mathrm{T\overline{T}}$ production, excluding masses below 1.48 TeV for all decays to third generation quarks, and are the strongest limits to date for $\mathrm{B\overline{B}}$ production with B quark decays to tW

Measurement of the Higgs boson inclusive and differential fiducial production cross sections in the diphoton decay channel with pp collisions at s \sqrt{s} = 13 TeV

International audienceThe measurements of the inclusive and differential fiducial cross sections of the Higgs boson decaying to a pair of photons are presented. The analysis is performed using proton-proton collisions data recorded with the CMS detector at the LHC at a centre-of-mass energy of 13 TeV and corresponding to an integrated luminosity of 137 fb$^{−1}$. The inclusive fiducial cross section is measured to be ${\sigma}_{\textrm{fid}}={73.4}_{-5.3}^{+5.4}{\left(\textrm{stat}\right)}_{-2.2}^{+2.4}\left(\textrm{syst}\right)$ fb, in agreement with the standard model expectation of 75.4 ± 4.1 fb. The measurements are also performed in fiducial regions targeting different production modes and as function of several observables describing the diphoton system, the number of additional jets present in the event, and other kinematic observables. Two double differential measurements are performed. No significant deviations from the standard model expectations are observed.[graphic not available: see fulltext

Azimuthal Correlations within Exclusive Dijets with Large Momentum Transfer in Photon-Lead Collisions

International audienceThe structure of nucleons is multidimensional and depends on the transverse momenta, spatial geometry, and polarization of the constituent partons. Such a structure can be studied using high-energy photons produced in ultraperipheral heavy-ion collisions. The first measurement of the azimuthal angular correlations of exclusively produced events with two jets in photon-lead interactions at large momentum transfer is presented, a process that is considered to be sensitive to the underlying nuclear gluon polarization. This study uses a data sample of ultraperipheral lead-lead collisions at sNN=5.02  TeV, corresponding to an integrated luminosity of 0.38  nb-1, collected with the CMS experiment at the LHC. The measured second harmonic of the correlation between the sum and difference of the two jet transverse momentum vectors is found to be positive, and rising, as the dijet transverse momentum increases. A well-tuned model that has been successful at describing a wide range of proton scattering data from the HERA experiments fails to describe the observed correlations, suggesting the presence of gluon polarization effects

Search for Higgs boson decays to a Z boson and a photon in proton-proton collisions at s \sqrt{s} = 13 TeV

International audienceResults are presented from a search for the Higgs boson decay H → Zγ, where Z → ℓ$^{+}$ℓ$^{−}$ with ℓ = e or μ. The search is performed using a sample of proton-proton (pp) collision data at a center-of-mass energy of 13 TeV, recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 138 fb$^{−1}$. Events are assigned to mutually exclusive categories, which exploit differences in both event topology and kinematics of distinct Higgs production mechanisms to enhance signal sensitivity. The signal strength μ, defined as the product of the cross section and the branching fraction \left[\sigma \left(\textrm{pp}\to \textrm{H}\right)\mathcal{B}\left(\textrm{H}\to \textrm{Z}\upgamma \right)\right] relative to the standard model prediction, is extracted from a simultaneous fit to the ℓ$^{+}$ℓ$^{−}$γ invariant mass distributions in all categories and is measured to be μ = 2.4 ± 0.9 for a Higgs boson mass of 125.38 GeV. The statistical significance of the observed excess of events is 2.7 standard deviations. This measurement corresponds to \left[\sigma \left(\textrm{pp}\to \textrm{H}\right)\mathcal{B}\left(\textrm{H}\to \textrm{Z}\upgamma \right)\right]=0.21\pm 0.08 pb. The observed (expected) upper limit at 95% confidence level on μ is 4.1 (1.8), where the expected limit is calculated under the background-only hypothesis. The ratio of branching fractions \mathcal{B}\left(\textrm{H}\to \textrm{Z}\upgamma \right)/\mathcal{B}\left(\textrm{H}\to \upgamma \upgamma \right) is measured to be ${1.5}_{-0.6}^{+0.7}$, which agrees with the standard model prediction of 0.69 ± 0.04 at the 1.5 standard deviation level.[graphic not available: see fulltext

Search for heavy resonances and quantum black holes in eμ\mu, eτ\tau, and μτ\mu\tau final states in proton-proton collisions at s\sqrt{s} = 13 TeV

A search is reported for heavy resonances and quantum black holes decaying into e$\mu$, e$\tau$, and $\mu\tau$ final states in proton-proton collision data recorded by the CMS experiment at the CERN LHC during 2016-2018 at $\sqrt{s} =$ 13 TeV, corresponding to an integrated luminosity of 138 fb$^{-1}$. The e$\mu$, e$\tau$, and $\mu\tau$ invariant mass spectra are reconstructed, and no evidence is found for physics beyond the standard model. Upper limits are set at 95% confidence level on the product of the cross section and branching fraction for lepton flavor violating signals. Three benchmark signals are studied: resonant $\tau$ sneutrino production in $R$ parity violating supersymmetric models, heavy Z' gauge bosons with lepton flavor violating decays, and nonresonant quantum black hole production in models with extra spatial dimensions. Resonant $\tau$ sneutrinos are excluded for masses up to 4.2 TeV in the e$\mu$ channel, 3.7 TeV in the e$\tau$ channel, and 3.6 TeV in the $\mu\tau$ channel. A Z' boson with lepton flavor violating couplings is excluded up to a mass of 5.0 TeV in the e$\mu$ channel, up to 4.3 TeV in the e$\tau$ channel, and up to 4.1 TeV in the $\mu\tau$ channel. Quantum black holes in the benchmark model are excluded up to the threshold mass of 5.6 TeV in the e$\mu$ channel, 5.2 TeV in the e$\tau$ channel, and 5.0 TeV in the $\mu\tau$ channel. In addition, model-independent limits are extracted to allow comparisons with other models for the same final states and similar event selection requirements. The results of these searches provide the most stringent limits available from collider experiments for heavy particles that undergo lepton flavor violating decays.A search is reported for heavy resonances and quantum black holes decaying into eμ, eτ, and μτ final states in proton-proton collision data recorded by the CMS experiment at the CERN LHC during 2016–2018 at $\sqrt{s}$ = 13 TeV, corresponding to an integrated luminosity of 138 fb$^{−1}$. The eμ, eτ, and μτ invariant mass spectra are reconstructed, and no evidence is found for physics beyond the standard model. Upper limits are set at 95% confidence level on the product of the cross section and branching fraction for lepton flavor violating signals. Three benchmark signals are studied: resonant τ sneutrino production in R parity violating supersymmetric models, heavy Z′ gauge bosons with lepton flavor violating decays, and nonresonant quantum black hole production in models with extra spatial dimensions. Resonant τ sneutrinos are excluded for masses up to 4.2TeV in the eμ channel, 3.7TeV in the eτ channel, and 3.6TeV in the μτ channel. A Z′ boson with lepton flavor violating couplings is excluded up to a mass of 5.0TeV in the eμ channel, up to 4.3Te V in the eτ channel, and up to 4.1TeV in the μτ channel. Quantum black holes in the benchmark model are excluded up to the threshold mass of 5.6TeV in the eμ channel, 5.2TeV in the eτ channel, and 5.0TeV in the μτ channel. In addition, model-independent limits are extracted to allow comparisons with other models for the same final states and similar event selection requirements. The results of these searches provide the most stringent limits available from collider experiments for heavy particles that undergo lepton flavor violating decays.[graphic not available: see fulltext]A search is reported for heavy resonances and quantum black holes decaying into e$\mu$, e$\tau$, and $\mu\tau$ final states in proton-proton collision data recorded by the CMS experiment at the CERN LHC during 2016-2018 at $\sqrt{s}$ = 13 TeV, corresponding to an integrated luminosity of 138 fb$^{-1}$. The e$\mu$, e$\tau$, and $\mu\tau$ invariant mass spectra are reconstructed, and no evidence is found for physics beyond the standard model. Upper limits are set at 95% confidence level on the product of the cross section and branching fraction for lepton flavor violating signals. Three benchmark signals are studied: resonant $\tau$ sneutrino production in $R$ parity violating supersymmetric models, heavy Z' gauge bosons with lepton flavor violating decays, and nonresonant quantum black hole production in models with extra spatial dimensions. Resonant $\tau$ sneutrinos are excluded for masses up to 4.2 TeV in the e$\mu$ channel, 3.7 TeV in the e$\tau$ channel, and 3.6 TeV in the $\mu\tau$ channel. A Z' boson with lepton flavor violating couplings is excluded up to a mass of 5.0 TeV in the e$\mu$ channel, up to 4.3 TeV in the e$\tau$ channel, and up to 4.1 TeV in the $\mu\tau$ channel. Quantum black holes in the benchmark model are excluded up to the threshold mass of 5.6 TeV in the e$\mu$ channel, 5.2 TeV in the e$\tau$ channel, and 5.0 TeV in the $\mu\tau$ channel. In addition, model-independent limits are extracted to allow comparisons with other models for the same final states and similar event selection requirements. The results of these searches provide the most stringent limits available from collider experiments for heavy particles that undergo lepton flavor violating decays