De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures.

Next-generation sequencing has been invaluable in the elucidation of the genetic etiology of many subtypes of intellectual disability in recent years. Here, using exome sequencing and whole-genome sequencing, we identified three de novo truncating mutations in WAS protein family member 1 (WASF1) in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling. This study provides evidence that de novo heterozygous mutations in WASF1 cause a rare form of intellectual disability

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

Biallelic Mutation of ARHGEF18, Involved in the Determination of Epithelial Apicobasal Polarity, Causes Adult-Onset Retinal Degeneration

Mutations in more than 250 genes are implicated in inherited retinal dystrophy; the encoded proteins are involved in a broad spectrum of pathways. The presence of unsolved families after highly parallel sequencing strategies suggests that further genes remain to be identified. Whole-exome and -genome sequencing studies employed here in large cohorts of affected individuals revealed biallelic mutations in ARHGEF18 in three such individuals. ARHGEF18 encodes ARHGEF18, a guanine nucleotide exchange factor that activates RHOA, a small GTPase protein that is a key component of tight junctions and adherens junctions. This biological pathway is known to be important for retinal development and function, as mutation of CRB1, encoding another component, causes retinal dystrophy. The retinal structure in individuals with ARHGEF18 mutations resembled that seen in subjects with CRB1 mutations. Five mutations were found on six alleles in the three individuals: c.808A>G (p.Thr270Ala), c.1617+5G>A (p.Asp540Glyfs∗63), c.1996C>T (p.Arg666∗), c.2632G>T (p.Glu878∗), and c.2738_2761del (p.Arg913_Glu920del). Functional tests suggest that each disease genotype might retain some ARHGEF18 activity, such that the phenotype described here is not the consequence of nullizygosity. In particular, the p.Thr270Ala missense variant affects a highly conserved residue in the DBL homology domain, which is required for the interaction and activation of RHOA. Previously, knock-out of Arhgef18 in the medaka fish has been shown to cause larval lethality which is preceded by retinal defects that resemble those seen in zebrafish Crumbs complex knock-outs. The findings described here emphasize the peculiar sensitivity of the retina to perturbations of this pathway, which is highlighted as a target for potential therapeutic strategies

A portrait of the Higgs boson by the CMS experiment ten years after the discovery

A Correction to this paper has been published (18 October 2023) : https://doi.org/10.1038/s41586-023-06164-8.Data availability: Tabulated results are provided in the HEPData record for this analysis. Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the CMS data preservation, re-use and open acess policy.Code availability: The CMS core software is publicly available on GitHub (https://github.com/cms-sw/cmssw).In July 2012, the ATLAS and CMS collaborations at the CERN Large Hadron Collider announced the observation of a Higgs boson at a mass of around 125 gigaelectronvolts. Ten years later, and with the data corresponding to the production of a 30-times larger number of Higgs bosons, we have learnt much more about the properties of the Higgs boson. The CMS experiment has observed the Higgs boson in numerous fermionic and bosonic decay channels, established its spin–parity quantum numbers, determined its mass and measured its production cross-sections in various modes. Here the CMS Collaboration reports the most up-to-date combination of results on the properties of the Higgs boson, including the most stringent limit on the cross-section for the production of a pair of Higgs bosons, on the basis of data from proton–proton collisions at a centre-of-mass energy of 13 teraelectronvolts. Within the uncertainties, all these observations are compatible with the predictions of the standard model of elementary particle physics. Much evidence points to the fact that the standard model is a low-energy approximation of a more comprehensive theory. Several of the standard model issues originate in the sector of Higgs boson physics. An order of magnitude larger number of Higgs bosons, expected to be examined over the next 15 years, will help deepen our understanding of this crucial sector.BMBWF and FWF (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, FAPERGS, and FAPESP (Brazil); MES and BNSF (Bulgaria); CERN; CAS, MoST, and NSFC (China); MINCIENCIAS (Colombia); MSES and CSF (Croatia); RIF (Cyprus); SENESCYT (Ecuador); MoER, ERC PUT and ERDF (Estonia); Academy of Finland, MEC, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRI (Greece); NKFIH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); MSIP and NRF (Republic of Korea); MES (Latvia); LAS (Lithuania); MOE and UM (Malaysia); BUAP, CINVESTAV, CONACYT, LNS, SEP, and UASLP-FAI (Mexico); MOS (Montenegro); MBIE (New Zealand); PAEC (Pakistan); MES and NSC (Poland); FCT (Portugal); MESTD (Serbia); MCIN/AEI and PCTI (Spain); MOSTR (Sri Lanka); Swiss Funding Agencies (Switzerland); MST (Taipei); MHESI and NSTDA (Thailand); TUBITAK and TENMAK (Turkey); NASU (Ukraine); STFC (United Kingdom); DOE and NSF (USA). Individuals have received support from the Marie-Curie programme and the European Research Council and Horizon 2020 Grant, contract Nos. 675440, 724704, 752730, 758316, 765710, 824093, 884104, and COST Action CA16108 (European Union); the Leventis Foundation; the Alfred P. Sloan Foundation; the Alexander von Humboldt Foundation; the Belgian Federal Science Policy Office; the Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture (FRIA-Belgium); the Agentschap voor Innovatie door Wetenschap en Technologie (IWT-Belgium); the F.R.S.-FNRS and FWO (Belgium) under the “Excellence of Science – EOS” – be.h project n. 30820817; the Beijing Municipal Science & Technology Commission, No. Z191100007219010; the Ministry of Education, Youth and Sports (MEYS) of the Czech Republic; the Stavros Niarchos Foundation (Greece); the Deutsche Forschungsgemeinschaft (DFG), under Germany’s Excellence Strategy – EXC 2121 “Quantum Universe” – 390833306, and under project number 400140256 - GRK2497; the Hungarian Academy of Sciences, the New National Excellence Program - ÚNKP, the NKFIH research grants K 124845, K 124850, K 128713, K 128786, K 129058, K 131991, K 133046, K 138136, K 143460, K 143477, 2020-2.2.1-ED-2021-00181, and TKP2021-NKTA-64 (Hungary); the Council of Science and Industrial Research, India; the Latvian Council of Science; the Ministry of Education and Science, project no. 2022/WK/14, and the National Science Center, contracts Opus 2021/41/B/ST2/01369 and 2021/43/B/ST2/01552 (Poland); the Fundação para a Ciência e a Tecnologia, grant CEECIND/01334/2018 (Portugal); the National Priorities Research Program by Qatar National Research Fund; MCIN/AEI/10.13039/501100011033, ERDF “a way of making Europe”, and the Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia María de Maeztu, grant MDM-2017-0765 and Programa Severo Ochoa del Principado de Asturias (Spain); the Chulalongkorn Academic into Its 2nd Century Project Advancement Project, and the National Science, Research and Innovation Fund via the Program Management Unit for Human Resources & Institutional Development, Research and Innovation, grant B05F650021 (Thailand); the Kavli Foundation; the Nvidia Corporation; the SuperMicro Corporation; the Welch Foundation, contract C-1845; and the Weston Havens Foundation (USA)

Observation of triple J/ψ meson production in proton-proton collisions

Data availability: Tabulated results are provided in the HEPData record for this analysis71. 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.Code availability: The CMS core software is publically available at https://github.com/cms-sw/cmssw.Copyright . Protons consist of three valence quarks, two up-quarks and one down-quark, held together by gluons and a sea of quark-antiquark pairs. Collectively, quarks and gluons are referred to as partons. In a proton-proton collision, typically only one parton of each proton undergoes a hard scattering – referred to as single-parton scattering – leaving the remainder of each proton only slightly disturbed. Here, we report the study of double- and triple-parton scatterings through the simultaneous production of three J/ψ mesons, which consist of a charm quark-antiquark pair, in proton-proton collisions recorded with the CMS experiment at the Large Hadron Collider. We observed this process – reconstructed through the decays of J/ψ mesons into pairs of oppositely charged muons – with a statistical significance above five standard deviations. We measured the inclusive fiducial cross-section to be 272+141−104(stat)±17(syst)fb, and compared it to theoretical expectations for triple-J/ψ meson production in single-, double- and triple-parton scattering scenarios. Assuming factorization of multiple hard-scattering probabilities in terms of single-parton scattering cross-sections, double- and triple-parton scattering are the dominant contributions for the measured process.SCOAP3.Change history: 27 February 2023A Correction to this paper has been published: https://doi.org/10.1038/s41567-023-01992-

Search for electroweak production of charginos and neutralinos at s\sqrt{s} = 13 TeV in final states containing hadronic decays of WW, WZ, or WH and missing transverse momentum

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”.A preprint version of this article is archived at: arXiv:2205.09597v2 [hep-ex], https://arxiv.org/abs/2205.09597v2 . Comments: Replaced with the published version. Added the journal reference. All the figures and tables, including additional supplementary figures and tables, can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/SUS-21-002 (CMS Public Pages). Report number: CMS-SUS-21-002, CERN-EP-2022-031This Letter presents a search for direct production of charginos and neutralinos via electroweak interactions. The results are based on data from proton-proton collisions at a center-of-mass energy of 13 TeV collected with the CMS detector at the LHC, corresponding to an integrated luminosity of 137 fb^{-1}. The search considers final states with large missing transverse momentum and pairs of hadronically decaying bosons WW, WZ, and WH, where H is the Higgs boson. These bosons are identified using novel algorithms. No significant excess of events is observed relative to the expectations from the standard model. Limits at the 95% confidence level are placed on the cross section for production of mass-degenerate wino-like supersymmetric particles χ~±1 and χ~02, and mass-degenerate higgsino-like supersymmetric particles χ~±1, χ~02, and χ~03. In the limit of a nearly-massless lightest supersymmetric particle χ~01, wino-like particles with masses up to 870 and 960 GeV are excluded in the cases of χ~02 → Zχ~01 and χ~02 → Hχ~01, respectively, and higgsino-like particles are excluded between 300 and 650 GeV.SCOAP3

Inclusive and differential cross section measurements of single top quark production in association with a Z boson in proton-proton collisions at √s = 13 TeV

Copyright © CERN, for the benefit of the CMS Collaboration. Inclusive and differential cross sections of single top quark production in association with a Z boson are measured in proton-proton collisions at a center-of-mass energy of 13 TeV with a data sample corresponding to an integrated luminosity of 138 fb−1 recorded by the CMS experiment. Events are selected based on the presence of three leptons, electrons or muons, associated with leptonic Z boson and top quark decays. The measurement yields an inclusive cross section of 87.9+7.5−7.3(stat)+7.3−6.0(syst) fb for a dilepton invariant mass greater than 30 GeV, in agreement with standard model (SM) calculations and represents the most precise determination to date. The ratio between the cross sections for the top quark and the top antiquark production in association with a Z boson is measured as 2.37+0.56−0.42(stat)+0.27−0.13(syst). Differential measurements at parton and particle levels are performed for the first time. Several kinematic observables are considered to study the modeling of the process. Results are compared to theoretical predictions with different assumptions on the source of the initial-state b quark and found to be in agreement, within the uncertainties. Additionally, the spin asymmetry, which is sensitive to the top quark polarization, is determined from the differential distribution of the polarization angle at parton level to be 0.54 ± 0.16 (stat) ± 0.06 (syst), in agreement with SM predictions.SCOAP3

Precision measurement of the W boson decay branching fractions in proton-proton collisions at √s=13 TeV

The leptonic and inclusive hadronic decay branching fractions of the W boson are measured using proton-proton collision data collected at ffiffi s p ¼ 13 TeV by the CMS experiment at the CERN LHC, corresponding to an integrated luminosity of 35.9 fb−1. Events characterized by the production of one or two W bosons are selected and categorized based on the multiplicity and flavor of reconstructed leptons, the number of jets, and the number of jets identified as originating from the hadronization of b quarks. A binned maximum likelihood estimate of the W boson branching fractions is performed simultaneously in each event category. The measured branching fractions of the W boson decaying into electron, muon, and tau lepton final states are ð10.83 0.10Þ%, ð10.94 0.08Þ%, and ð10.77 0.21Þ%, respectively, consistent with lepton flavor universality for the weak interaction. The average leptonic and inclusive hadronic decay branching fractions are estimated to be ð10.89 0.08Þ% and ð67.32 0.23Þ%, respec tively. Based on the hadronic branching fraction, three standard model quantities are subsequently derived: the sum of squared elements in the first two rows of the Cabibbo–Kobayashi–Maskawa (CKM) matrix P ij jVijj 2 ¼ 1.984 0.021, the CKM element jVcsj ¼ 0.967 0.011, and the strong coupling constant at the W boson mass scale, αSðm2 WÞ ¼ 0.095 0.033