Multiple Regulatory Mechanisms to Inhibit Untimely Initiation of DNA Replication Are Important for Stable Genome Maintenance

Genomic instability is a hallmark of human cancer cells. To prevent genomic instability, chromosomal DNA is faithfully duplicated in every cell division cycle, and eukaryotic cells have complex regulatory mechanisms to achieve this goal. Here, we show that untimely activation of replication origins during the G1 phase is genotoxic and induces genomic instability in the budding yeast Saccharomyces cerevisiae. Our data indicate that cells preserve a low level of the initiation factor Sld2 to prevent untimely initiation during the normal cell cycle in addition to controlling the phosphorylation of Sld2 and Sld3 by cyclin-dependent kinase. Although untimely activation of origin is inhibited on multiple levels, we show that deregulation of a single pathway can cause genomic instability, such as gross chromosome rearrangements (GCRs). Furthermore, simultaneous deregulation of multiple pathways causes an even more severe phenotype. These findings highlight the importance of having multiple inhibitory mechanisms to prevent the untimely initiation of chromosome replication to preserve stable genome maintenance over generations in eukaryotes

Proteome and Membrane Fatty Acid Analyses on Oligotropha carboxidovorans OM5 Grown under Chemolithoautotrophic and Heterotrophic Conditions

Oligotropha carboxidovorans OM5 T. (DSM 1227, ATCC 49405) is a chemolithoautotrophic bacterium able to utilize CO and H2 to derive energy for fixation of CO2. Thus, it is capable of growth using syngas, which is a mixture of varying amounts of CO and H2 generated by organic waste gasification. O. carboxidovorans is capable also of heterotrophic growth in standard bacteriologic media. Here we characterize how the O. carboxidovorans proteome adapts to different lifestyles of chemolithoautotrophy and heterotrophy. Fatty acid methyl ester (FAME) analysis of O. carboxidovorans grown with acetate or with syngas showed that the bacterium changes membrane fatty acid composition. Quantitative shotgun proteomic analysis of O. carboxidovorans grown in the presence of acetate and syngas showed production of proteins encoded on the megaplasmid for assimilating CO and H2 as well as proteins encoded on the chromosome that might have contributed to fatty acid and acetate metabolism. We found that adaptation to chemolithoautotrophic growth involved adaptations in cell envelope, oxidative homeostasis, and metabolic pathways such as glyoxylate shunt and amino acid/cofactor biosynthetic enzymes

Metalloproteinases and their inhibitors—diagnostic and therapeutic opportunities in orthopedics

Matrix metalloproteinases (MMPs) and related enzymes (ADAMs, ADAMTS) and their inhibitors control matrix turnover and function. Recent advances in our understanding of musculoskeletal conditions such as tendinopathy, arthritis, Dupuytren's disease, degenerative disc disease, and bone and soft tissue healing suggest that MMPs have prominant roles. Importantly, MMPs are amenable to inhibition by cheap, safe, and widely available drugs such as the tetracycline antibiotics and the bisphosphonates. This indicates that these MMP inhibitors, if proven effective for any novel indication, may be quickly brought into clinical practice

Observation of a New Excited Beauty Strange Baryon Decaying to Ξb- π+π-

The Ξb-π+π- invariant mass spectrum is investigated with an event sample of proton-proton collisions at s=13 TeV, collected by the CMS experiment at the LHC in 2016-2018 and corresponding to an integrated luminosity of 140 fb-1. The ground state Ξb- is reconstructed via its decays to J/ψΞ- and J/ψΛK-. A narrow resonance, labeled Ξb(6100)-, is observed at a Ξb-π+π- invariant mass of 6100.3±0.2(stat)±0.1(syst)±0.6(Ξb-) MeV, where the last uncertainty reflects the precision of the Ξb- baryon mass. The upper limit on the Ξb(6100)- natural width is determined to be 1.9 MeV at 95% confidence level. The low Ξb(6100)- signal yield observed in data does not allow a measurement of the quantum numbers of the new state. However, following analogies with the established excited Ξc baryon states, the new Ξb(6100)- resonance and its decay sequence are consistent with the orbitally excited Ξb- baryon, with spin and parity quantum numbers JP=3/2-

Measurement of the inclusive and differential Higgs boson production cross sections in the decay mode to a pair of τ Leptons in pp collisions at sqrt[s]=13 TeV

Measurements of the inclusive and differential fiducial cross sections of the Higgs boson are presented, using the τ lepton decay channel. The differential cross sections are measured as functions of the Higgs boson transverse momentum, jet multiplicity, and transverse momentum of the leading jet in the event, if any. The analysis is performed using proton-proton collision data collected with the CMS detector at the LHC at a center-of-mass energy of 13  TeV and corresponding to an integrated luminosity of 138  fb^{-1}. These are the first differential measurements of the Higgs boson cross section in the final state of two τ leptons. In final states with a large jet multiplicity or with a Lorentz-boosted Higgs boson, these measurements constitute a significant improvement over measurements performed in other final states

Search for new Higgs bosons via same-sign top quark pair production in association with a jet in proton-proton collisions at √s = 13 TeV

Data availability: Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the CMS policy as stated in “CMS data preservation, re-use and open access policy” available online at: https://cms-docdb.cern.ch/cgi-bin/PublicDocDB/RetrieveFile?docid=6032&filename=CMSDataPolicyV1.2.pdf&version=2 .A preprint of this article is available online at arXiv:2311.03261v2 [hep-ex] https://arxiv.org/abs/2311.03261v2 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/TOP-22-010 (CMS Public Pages)A search is presented for new Higgs bosons in proton-proton (pp) collision events in which a same-sign top quark pair is produced in association with a jet, via the pp → tH/A → tt¯c and pp → tH/A → tt¯u processes. Here, H and A represent the extra scalar and pseudoscalar boson, respectively, of the second Higgs doublet in the generalized two-Higgs-doublet model (g2HDM). The search is based on pp collision data collected at a center-of-mass energy of 13 TeV with the CMS detector at the LHC, corresponding to an integrated luminosity of 138 fb−1. Final states with a same-sign lepton pair in association with jets and missing transverse momentum are considered. New Higgs bosons in the 200-1000 GeV mass range and new Yukawa couplings between 0.1 and 1.0 are targeted in the search, for scenarios in which either H or A appear alone, or in which they coexist and interfere. No significant excess above the standard model prediction is observed. Exclusion limits are derived in the context of the g2HDM.SCOAP3

Search for long-lived heavy neutral leptons with lepton flavour conserving or violating decays to a jet and a charged lepton

A preprint version of the article is available at arXiv:2312.07484v3 [hep-ex], https://arxiv.org/abs/2312.07484 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/EXO-21-013 (CMS Public Pages)A search for long-lived heavy neutral leptons (HNLs) is presented, which considers the hadronic final state and coupling scenarios involving all three lepton generations in the 2-20 GeV HNL mass range for the first time. Events comprising two leptons (electrons or muons) and jets are analyzed in a data sample of proton-proton collisions, recorded with the CMS experiment at the CERN LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 138 fb−1. A novel jet tagger, based on a deep neural network, has been developed to identify jets from an HNL decay using various features of the jet and its constituent particles. The network output can be used as a powerful discriminating tool to probe a broad range of HNL lifetimes and masses. Contributions from background processes are determined from data. No excess of events in data over the expected background is observed. Upper limits on the HNL production cross section are derived as functions of the HNL mass and the three coupling strengths VℓN to each lepton generation ℓ and presented as exclusion limits in the coupling-mass plane, as lower limits on the HNL lifetime, and on the HNL mass. In this search, the most stringent limit on the coupling strength is obtained for pure muon coupling scenarios; values of |VμN|2 > 5 (4) × 10−7 are excluded for Dirac (Majorana) HNLs with a mass of 10 GeV at a confidence level of 95% that correspond to proper decay lengths of 17 (10) mm.SCOAP3

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

A preprint version of the article is available at arXiv:2204.12945v2 [hep-ex], https://arxiv.org/abs/2204.12945v2 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/HIG-19-014 (CMS Public Pages). Report number: CMS-HIG-19-014, CERN-EP-2022-019.Results 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 [σ(pp → H)B(H → Zγ)] 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 found 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 σ(pp → H)B(H → Zγ) = 0.21 ± 0.08 pb. The observed (expected) upper limit at 95% confidence level on μ is 4.1 (1.8). The ratio of branching fractions B(H → Zγ)/B(H → γγ) is measured to be 1.5 +0.7−0.6, which agrees with the standard model prediction of 0.69 ± 0.04 at the 1.5 standard deviation level.SCOAP3

Measurements of the Higgs boson production cross section and couplings in the W boson pair decay channel in proton-proton collisions at s\sqrt{s} = 13 TeV

A preprint version of the article is available at arXiv:2206.09466v2 [hep-ex], https://arxiv.org/abs/2206.09466v2 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at httpS://cms-results.web.cern.ch/cms-results/public-results/publications/HIG-20-013 (CMS Public Pages). Report number: CMS-HIG-20-013, CERN-EP-2022-120.Production cross sections of the standard model Higgs boson decaying to a pair of W bosons are measured in proton-proton collisions at a center-of-mass energy of 13 TeV. The analysis targets Higgs bosons produced via gluon fusion, vector boson fusion, and in association with a W or Z boson. Candidate events are required to have at least two charged leptons and moderate missing transverse momentum, targeting events with at least one leptonically decaying W boson originating from the Higgs boson. Results are presented in the form of inclusive and differential cross sections in the simplified template cross section framework, as well as couplings of the Higgs boson to vector bosons and fermions. The data set collected by the CMS detector during 2016-2018 is used, corresponding to an integrated luminosity of 138 fb^−1. The signal strength modifier μ, defined as the ratio of the observed production rate in a given decay channel to the standard model expectation, is measured to be μ = 0.95 +0.10−0.09. All results are found to be compatible with the standard model within the uncertainties.SCOAP3

Search for supersymmetry in final states with two or three soft leptons and missing transverse momentum in proton-proton collisions at root s=13 TeV

ArXiv ePrint: 2111.06296 (https://arxiv.org/abs/2111.06296).Copyright © 2022 CERN, for the benefit of the CMS Collaboration. A search for supersymmetry in events with two or three low-momentum leptons and missing transverse momentum is performed. The search uses proton-proton collisions at s√ = 13 TeV collected in the three-year period 2016–2018 by the CMS experiment at the LHC and corresponding to an integrated luminosity of up to 137 fb−1. The data are found to be in agreement with expectations from standard model processes. The results are interpreted in terms of electroweakino and top squark pair production with a small mass difference between the produced supersymmetric particles and the lightest neutralino. For the electroweakino interpretation, two simplified models are used, a wino-bino model and a higgsino model. Exclusion limits at 95% confidence level are set on χ∼02/χ∼±1 masses up to 275 GeV for a mass difference of 10 GeV in the wino-bino case, and up to 205(150) GeV for a mass difference of 7.5 (3) GeV in the higgsino case. The results for the higgsino are further interpreted using a phenomenological minimal supersymmetric standard model, excluding the higgsino mass parameter μ up to 180 GeV with the bino mass parameter M1 at 800 GeV. In the top squark interpretation, exclusion limits are set at top squark masses up to 540 GeV for four-body top squark decays and up to 480 GeV for chargino-mediated decays with a mass difference of 30 GeV.SCOAP3