Polycomb Target Genes Are Silenced in Multiple Myeloma

Multiple myeloma (MM) is a genetically heterogeneous disease, which to date remains fatal. Finding a common mechanism for initiation and progression of MM continues to be challenging. By means of integrative genomics, we identified an underexpressed gene signature in MM patient cells compared to normal counterpart plasma cells. This profile was enriched for previously defined H3K27-tri-methylated genes, targets of the Polycomb group (PcG) proteins in human embryonic fibroblasts. Additionally, the silenced gene signature was more pronounced in ISS stage III MM compared to stage I and II. Using chromatin immunoprecipitation (ChIP) assay on purified CD138+ cells from four MM patients and on two MM cell lines, we found enrichment of H3K27me3 at genes selected from the profile. As the data implied that the Polycomb-targeted gene profile would be highly relevant for pharmacological treatment of MM, we used two compounds to chemically revert the H3K27-tri-methylation mediated gene silencing. The S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin (DZNep) and the histone deacetylase inhibitor LBH589 (Panobinostat), reactivated the expression of genes repressed by H3K27me3, depleted cells from the PRC2 component EZH2 and induced apoptosis in human MM cell lines. In the immunocompetent 5T33MM in vivo model for MM, treatment with LBH589 resulted in gene upregulation, reduced tumor load and increased overall survival. Taken together, our results reveal a common gene signature in MM, mediated by gene silencing via the Polycomb repressor complex. The importance of the underexpressed gene profile in MM tumor initiation and progression should be subjected to further studies

Measurement of double-parton scattering in inclusive production of four jets with low transverse momentum in proton-proton collisions at root s=13 TeV

A measurement of inclusive four-jet production in proton-proton collisions at a center-of-mass energy of 13 TeV is presented. The transverse momenta of jets within vertical bar eta vertical bar 4.7 are required to exceed 35, 30, 25, and 20 GeV for the first-, second-, third-, and fourth-leading jet, respectively. Differential cross sections are measured as functions of the jet transverse momentum, jet pseudorapidity, and several other observables that describe the angular correlations between the jets. The measured distributions show sensitivity to different aspects of the underlying event, parton shower modeling, and matrix element calculations. In particular, the interplay between angular correlations caused by parton shower and double-parton scattering contributions is shown to be important. The double-parton scattering contribution is extracted by means of a template fit to the data, using distributions for single-parton scattering obtained from Monte Carlo event generators and a double-parton scattering distribution constructed from inclusive single-jet events in data. The effective double-parton scattering cross section is calculated and discussed in view of previous measurements and of its dependence on the models used to describe the single-parton scattering background

Measurement of the Higgs boson width and evidence of its off-shell contributions to ZZ production

Since the discovery of the Higgs boson in 2012, detailed studies of its properties have been ongoing. Besides its mass, its width—related to its lifetime—is an important parameter. One way to determine this quantity is to measure its off-shell production, where the Higgs boson mass is far away from its nominal value, and relating it to its on-shell production, where the mass is close to the nominal value. Here we report evidence for such off-shell contributions to the production cross-section of two Z bosons with data from the CMS experiment at the CERN Large Hadron Collider. We constrain the total rate of the off-shell Higgs boson contribution beyond the Z boson pair production threshold, relative to its standard model expectation, to the interval [0.0061, 2.0] at the 95% confidence level. The scenario with no off-shell contribution is excluded at a p-value of 0.0003 (3.6 standard deviations). We measure the width of the Higgs boson as $\Gamma$$_H$=3.2$^{+2.4}_{−1.7}$MeV, in agreement with the standard model expectation of 4.1 MeV. In addition, we set constraints on anomalous Higgs boson couplings to W and Z boson pairs

Measurement of the inclusive and differential t(t)over-bar gamma cross sections in the single-lepton channel and EFT interpretation at root s=13 TeV

Peer reviewe

Measurement of differential t(t)over-bar production cross sections in the full kinematic range using lepton plus jets events from proton-proton collisions at root s=13 TeV

Measurements of differential and double-differential cross sections of top-quark pair (t (t) over bar) production arc presented in the lepton + jets channels with a single electron or muon and jets in the final state. The analysis combines for the first time signatures of top quarks with low transverse momentum p(T), where the top-quark decay products can be identified as separated jets and isolated leptons, and with high p(T), where the decay products are collimated and overlap. The measurements arc based on proton-proton collision data at is - = 13 TeV collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 137 fb(-1). The cross sections are presented at the parton and particle levels, where the latter minimizes extrapolations based on theoretical assumptions. Most of the measured differential cross sections are well described by standard model predictions with the exception of some double-differential distributions. The inclusive t (t) over bar production cross section is measured to be sigma(t (t) over bar) = 791 +/- 25 pb, which constitutes the most precise measurement in the lepton + jets channel to date.Peer reviewe

Search for new particles in an extended Higgs sector with four b quarks in the final state at √s = 13 TeV

A search for a massive resonance X decaying to a pair of spin-0 bosons ϕ that themselves decay to pairs of bottom quarks, is presented. The analysis is restricted to the mass ranges from 25 to 100 GeV and from 1 to 3 TeV. For these mass ranges, the decay products of each ϕ boson are expected to merge into a single large-radius jet. Jet substructure and flavor identification techniques are used to identify these jets. The search is based on CERN LHC proton-proton collision data at , collected with the CMS detector in 2016–2018, corresponding to an integrated luminosity of 138 . Model-specific limits, where the two new particles arise from an extended Higgs sector, are set on the product of the production cross section and branching fraction for as a function of the resonances' masses, where both the and branching fractions are assumed to be 100%. These limits are the first of their kind on this process, ranging between 30 and 1 fb at 95% confidence level for the considered mass ranges

Bacteria-inducing legume nodules involved in the improvement of plant growth, health and nutrition

Bacteria-inducing legume nodules are known as rhizobia and belong to the class Alphaproteobacteria and Betaproteobacteria. They promote the growth and nutrition of their respective legume hosts through atmospheric nitrogen fixation which takes place in the nodules induced in their roots or stems. In addition, rhizobia have other plant growth-promoting mechanisms, mainly solubilization of phosphate and production of indoleacetic acid, ACC deaminase and siderophores. Some of these mechanisms have been reported for strains of rhizobia which are also able to promote the growth of several nonlegumes, such as cereals, oilseeds and vegetables. Less studied are the mechanisms that have the rhizobia to promote the plant health; however, these bacteria are able to exert biocontrol of some phytopathogens and to induce the plant resistance. In this chapter, we revised the available data about the ability of the legume nodule-inducing bacteria for improving the plant growth, health and nutrition of both legumes and nonlegumes. These data showed that rhizobia meet all the requirements of sustainable agriculture to be used as bio-inoculants allowing the total or partial replacement of chemicals used for fertilization or protection of crops