A Quantitative Characterization of Nucleoplasmin/Histone Complexes Reveals Chaperone Versatility.

Nucleoplasmin (NP) is an abundant histone chaperone in vertebrate oocytes and embryos involved in storing and releasing maternal histones to establish and maintain the zygotic epigenome. NP has been considered a H2A-H2B histone chaperone, and recently it has been shown that it can also interact with H3-H4. However, its interaction with different types of histones has not been quantitatively studied so far. We show here that NP binds H2A-H2B, H3-H4 and linker histones with Kd values in the subnanomolar range, forming different complexes. Post-translational modifications of NP regulate exposure of the polyGlu tract at the disordered distal face of the protein and induce an increase in chaperone affinity for all histones. The relative affinity of NP for H2A-H2B and linker histones and the fact that they interact with the distal face of the chaperone could explain their competition for chaperone binding, a relevant process in NP-mediated sperm chromatin remodelling during fertilization. Our data show that NP binds H3-H4 tetramers in a nucleosomal conformation and dimers, transferring them to DNA to form disomes and tetrasomes. This finding might be relevant to elucidate the role of NP in chromatin disassembly and assembly during replication and transcription

Iron therapy substantially restores qEEG maturational lag among iron-deficient anemic infants

Objective: To use quantitative electroencephalography (qEEG) to assess the impact of iron-deficiency anemia on central nervous system maturation in the first year of life. Method: Twenty-five infants (3–12 months old) presenting ferropenic anemia (IDA) and 25 healthy controls (CTL1), matched by age/gender with the former, were studied in two stages. Electroencephalogram during spontaneous sleep was recorded from all participants; the fast Fourier transform was calculated to obtain absolute power (AP) and relative power (RP) qEEG measures. In the first stage, a qEEG comparison between CTL1 and IDA was performed. Second stage consisted in comparing qEEG of the IDA infants before and after supplementation with iron (IDA-IS group), and comparing qEEG of the IDA-IS group with another control age-matched group (CTL2). Non-parametric multivariate permutation tests (NPT) were applied to assess differences between CTL1 and IDA groups, as well as IDA vs. IDA-IS, and IDA-IS vs. CTL2. Results: More power in slow frequency bands and less power in fast frequency bands in 64% of IDA babies were observed. NPT evinced higher alpha AP and RP (P < 0.001), less theta AP, and less delta and theta RP in CTL1 than in IDA. After iron-restoration therapy, alpha AP and RP increased while theta AP and theta and delta RP decreased, reaching almost normal values. Discussion: This work reveals CNS developmental delay through the study of qEEG (less rapid and more slow frequencies) which recovered significantly with iron supplementation. It is concluded that IDA constitutes a high risk factor for a lag of CNS maturation.CONACYT-Project No. CO1/40257-A1

The intrinsically disordered distal face of nucleoplasmin recognizes distinct oligomerization states of histones

The role of Nucleoplasmin (NP) as a H2A-H2B histone chaperone has been extensively characterized. To understand its putative interaction with other histone ligands, we have characterized its ability to bind H3-H4 and histone octamers. We find that the chaperone forms distinct complexes with histones, which differ in the number of molecules that build the assembly and in their spatial distribution. When complexed with H3-H4 tetramers or histone octamers, two NP pentamers form an ellipsoidal particle with the histones located at the center of the assembly, in stark contrast with the NP/H2A-H2B complex that contains up to five histone dimers bound to one chaperone pentamer. This particular assembly relies on the ability of H3-H4 to form tetramers either in solution or as part of the octamer, and it is not observed when a variant of H3 (H3C110E), unable to form stable tetramers, is used instead of the wild-type protein. Our data also suggest that the distal face of the chaperone is involved in the interaction with distinct types of histones, as supported by electron microscopy analysis of the different NP/histone complexes. The use of the same structural region to accommodate all type of histones could favor histone exchange and nucleosome dynamics

Diagnostic performance of serum pentraxin-3 in pediatric acute appendicitis: a prospective diagnostic validation study

Introduction Pediatric acute appendicitis (PAA) is a pathology with a high rate of diagnostic error. The search for new diagnostic tools is justified by the high morbidity and healthcare costs associated with diagnostic error. Methods We designed a prospective study to validate serum pentraxin-3 (PTX3) as a diagnostic tool in PAA. Participants were divided into three groups: (1) patients with no underlying pathology (2) patients with non-surgical abdominal pain and (3) patients with a confirmed diagnosis of PAA. For further analyses, patients in group 3 were divided into complicated or uncomplicated PAA. Quantitative variables were expressed as medians and interquartile ranges and categorical variables as percentages. Quantitative variables were compared using the Kruskal–Wallis test and the Mann–Whitney U test. Diagnostic performance was evaluated with ROC curves. Results This study included 215 patients divided into group 1 (n : 63), group 2 (n : 53) and group 3 (n : 99). Median serum PTX3 values were 2.54 (1.70–2.95) ng/mL, 3.29 (2.19–7.64) ng/mL and 8.94 (6.16–14.05) in groups 1, 2 and 3, respectively (p : 0.001). Patients with complicated PAA showed significantly higher values than patients with uncomplicated PAA (p = 0.04). The AUC (group 2 vs. 3) was 0.77 (95/100 CI 0.69–0.85) and the best cut-off point was at 7.28 ng/mL, with a sensitivity of 61.3/100 and a specificity of 73.1/100. The AUC (complicated vs. uncomplicated PAA) was 0.65 (95/100 CI 0.54–0.77) and the best cut-off point was 12.33 ng/mL, with a sensitivity of 51.72/100 and a specificity of 72.73/100. Conclusions The diagnostic ability of serum PTX3 in PAA is only moderate and therefore it cannot be considered a definitive diagnostic test. The discriminatory ability of PTX3 between complicated and uncomplicated PAA is poor. These findings, which contrast with those reported to date, should be validated with future properly designed prospective studies

Measurements of tt¯ spin correlations and top quark polarization using dilepton final states in pp collisions at √s=8 TeV

et al.Measurements of the top quark-antiquark (tt¯) spin correlations and the top quark polarization are presented for tt¯ pairs produced in pp collisions at √s=8  TeV. The data correspond to an integrated luminosity of 19.5  fb−1 collected with the CMS detector at the LHC. The measurements are performed using events with two oppositely charged leptons (electrons or muons) and two or more jets, where at least one of the jets is identified as originating from a bottom quark. The spin correlations and polarization are measured from the angular distributions of the two selected leptons, both inclusively and differentially, with respect to the invariant mass, rapidity, and transverse momentum of the tt¯ system. The measurements are unfolded to the parton level and found to be in agreement with predictions of the standard model. A search for new physics in the form of anomalous top quark chromo moments is performed. No evidence of new physics is observed, and exclusion limits on the real part of the chromo-magnetic dipole moment and the imaginary part of the chromo-electric dipole moment are evaluated.Individuals have received support from the Marie-Curie programme and the European Research Council and EPLANET (European Union); the Leventis Foundation; the A. 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 (IWTBelgium); the Ministry of Education, Youth and Sports (MEYS) of the Czech Republic; the Council of Science and Industrial Research, India; the HOMING PLUS programme of the Foundation for Polish Science, cofinanced from European Union, Regional Development Fund; the OPUS programme of the National Science Center (Poland); the Compagnia di San Paolo (Torino); MIUR project 20108T4XTM (Italy); the Thalis and Aristeia programmes cofinanced by EU-ESF and the Greek NSRF; the National Priorities Research Program by Qatar National Research Fund; the Rachadapisek Sompot Fund for Postdoctoral Fellowship, Chulalongkorn University (Thailand); the Chulalongkorn Academic into Its 2nd Century Project Advancement Project (Thailand); and the Welch Foundation, Contract No. C-1845.Peer Reviewe

Observation of two excited Bc+ states and measurement of the Bc+ (2S) mass in pp collisions at √s = 13 TeV

CMS Collaboration: et al.Signals consistent with the Bc+(2S) and Bc∗+(2S) states are observed in proton-proton collisions at √s = 13 TeV, in an event sample corresponding to an integrated luminosity of 143 fb-1, collected by the CMS experiment during the 2015-2018 LHC running periods. These excited bc states are observed in the Bc+π+π- invariant mass spectrum, with the ground state Bc+ reconstructed through its decay to J/ψπ+. The two states are reconstructed as two well-resolved peaks, separated in mass by 29.1±1.5(stat)±0.7(syst) MeV. The observation of two peaks, rather than one, is established with a significance exceeding five standard deviations. The mass of the Bc+(2S) meson is measured to be 6871.0±1.2(stat)±0.8(syst)±0.8(Bc+) MeV, where the last term corresponds to the uncertainty in the world-average Bc+ mass

The British Influence in the Birth of Spanish Sport

Sports started to gain relevance in Spain around the end of the nineteenth century and the beginning of the twentieth century as a leisure and health option of the upper classes imported from Britain. Its early development was intertwined with the spread of other kinds of physical activities with much more tradition on the continent: gymnastics and physical education. First played by the ruling classes – aristocracy and high bourgeoisie – sports permeated towards petty bourgeoisie and middle classes in urban areas such as Madrid, Barcelona, San Sebastián and Santander. This pattern meant that the expansion of sports was unavoidably tied to the degree of industrialisation and cultural modernisation of the country. Since 1910, and mainly during the 1920s, sport grew in popularity as a spectacle and, toa much lesser degree, as a practice among the Spanish population

Probing effective field theory operators in the associated production of top quarks with a Z boson in multilepton final states at root s=13 TeV

ABSTRACT: A search for new top quark interactions is performed within the framework of an effective field theory using the associated production of either one or two top quarks with a Z boson in multilepton final states. The data sample corresponds to an integrated luminosity of 138 fb-¹ of proton-proton collisions at √s = 13 TeV collected by the CMS experiment at the LHC. Five dimension-six operators modifying the electroweak interactions of the top quark are considered. Novel machine-learning techniques are used to enhance the sensitivity to effects arising from these operators. Distributions used for the signal extraction are parameterized in terms of Wilson coefficients describing the interaction strengths of the operators. All five Wilson coefficients are simultaneously fit to data and 95% confidence level intervals are computed. All results are consistent with the SM expectations.We congratulate our colleagues in the CERN accelerator departments for the excellent performance of the LHC and thank the technical and administrative staffs at CERN and at other CMS institutes for their contributions to the success of the CMS effort. In addition, we gratefully acknowledge the computing centers and personnel of the Worldwide LHC Computing Grid and other centers for delivering so effectively the computing infrastructure essential to our analyses. Finally, we acknowledge the enduring support for the construction and operation of the LHC, the CMS detector, and the supporting computing infrastructure provided by the following funding agencies: BMBWF and FWF (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, FAPERGS, and FAPESP (Brazil); MES (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); GSRT (Greece); NKFIA (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); MSHE and NSC (Poland); FCT (Portugal); JINR (Dubna); MON, RosAtom, RAS, RFBR, and NRC KI (Russia); MESTD (Serbia); SEIDI, CPAN, PCTI, and FEDER (Spain); MOSTR (Sri Lanka); Swiss Funding Agencies (Switzerland); MST (Taipei); ThEPCenter, IPST, STAR, and NSTDA (Thailand); TUBITAK and TAEK (Turkey); NASU (Ukraine); STFC (United Kingdom); DOE and NSF (U.S.A.). Individuals have received support from the Marie-Curie program and the European Research Council and Horizon 2020 Grant, contract Nos. 675440, 724704, 752730, 758316, 765710, 824093, 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 Deutsche Forschungsgemeinschaft (DFG), under Germany’s Excellence Strategy — EXC 2121 “Quantum Universe” — 390833306, and under project number 400140256 — GRK2497; the Lendület (“Momentum”) Program and the János Bolyai Research Scholarship of the Hungarian Academy of Sciences, the New National Excellence Program ÚNKP, the NKFIA research grants 123842, 123959, 124845, 124850, 125105, 128713, 128786, and 129058 (Hungary); the Council of Science and Industrial Research, India; the Latvian Council of Science; the Ministry of Science and Higher Education and the National Science Center, contracts Opus 2014/15/B/ST2/03998 and 2015/19/B/ST2/02861 (Poland); the National Priorities Research Program by Qatar National Research Fund; the Ministry of Science and Higher Education, project no. 0723- 2020-0041 (Russia); the Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia María de Maeztu, grant MDM-2015-0509 and the Programa Severo Ochoa del Principado de Asturias; the Stavros Niarchos Foundation (Greece); the Rachadapisek Sompot Fund for Postdoctoral Fellowship, Chulalongkorn University and the Chulalongkorn Academic into Its 2nd Century Project Advancement Project (Thailand); the Kavli Foundation; the Nvidia Corporation; the SuperMicro Corporation; the Welch Foundation, contract C-1845; and the Weston Havens Foundation (U.S.A.)

Search for supersymmetry in proton-proton collisions at 13 TeV in final states with jets and missing transverse momentum

Results are reported from a search for supersymmetric particles in the final state with multiple jets and large missing transverse momentum. The search uses a sample of proton-proton collisions at s = 13 TeV collected with the CMS detector in 2016–2018, corresponding to an integrated luminosity of 137 fb, representing essentially the full LHC Run 2 data sample. The analysis is performed in a four-dimensional search region defined in terms of the number of jets, the number of tagged bottom quark jets, the scalar sum of jet transverse momenta, and the magnitude of the vector sum of jet transverse momenta. No significant excess in the event yield is observed relative to the expected background contributions from standard model processes. Limits on the pair production of gluinos and squarks are obtained in the framework of simplified models for supersymmetric particle production and decay processes. Assuming the lightest supersymmetric particle to be a neutralino, lower limits on the gluino mass as large as 2000 to 2310 GeV are obtained at 95% confidence level, while lower limits on the squark mass as large as 1190 to 1630 GeV are obtained, depending on the production scenario.Individuals have received support from the Marie-Curie program and the European Research Council and Horizon 2020 Grant, contract No. 675440 (European Union); the Leventis Foundation; the A.P. Sloan Foundation; the Alexander von Humboldt Foundation; the Belgian Federal Science Policy Office; the Fonds pour la Formation a 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 Ministry of Education, Youth and Sports (MEYS) of the Czech Republic; the Lendület (“Momentum”) Program and the J´anos Bolyai Research Scholarship of the Hungarian Academy of Sciences, the New National Excellence Program UNKP, the NKFIA research grants 123842, 123959, 124845, 124850 and 125105 (Hungary); the Council of Science and Industrial Research, India; the HOMING PLUS program of the Foundation for Polish Science, cofinanced from European Union, Regional Development Fund, the Mobility Plus program of the Ministry of Science and Higher Education, the National Science Center (Poland), contracts Harmonia 2014/14/M/ST2/00428, Opus 2014/13/B/ST2/02543, 2014/15/B/ST2/03998, and 2015/19/B/ST2/02861, Sonata-bis 2012/07/E/ST2/01406; the National Priorities Research Program by Qatar National Research Fund; the Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia María de Maeztu, grant MDM-2015-0509 and the Programa Severo Ochoa del Principado de Asturias; the Thalis and Aristeia programs cofinanced by EU-ESF and the Greek NSRF; the Rachadapisek Sompot Fund for Postdoctoral Fellowship, Chulalongkorn University and the Chulalongkorn Academic into Its 2nd Century Project Advancement Project (Thailand); the Welch Foundation, contract C-1845; and the Weston Havens Foundation (U.S.A.)

Search for a W' boson decaying to a τ lepton and a neutrino in proton-proton collisions at s=13TeV

A search for a new high-mass resonance decaying to a τlepton and a neutrino is reported. The analysis uses proton-proton collision data collected by the CMS experiment at the LHC at √s=13 TeV, corresponding to an integrated luminosity of 35.9 fb−1. The search utilizes hadronically decaying τleptons. No excess in the event yield is observed at high transverse masses of the τand missing transverse momentum. An interpretation of results within the sequential standard model excludes W′boson masses below 4.0 TeV at 95% confidence level. Existing limits are also improved on models in which the W′boson decays preferentially to fermions of the third generation. Heavy W′bosons with masses less than 1.7–3.9 TeV, depending on the coupling in the non-universal G(221) model, are excluded at 95% confidence level. These are the most stringent limits on this model to dateIndividuals have received support from the Marie-Curie programme and the European Research Council and Horizon 2020 Grant, contract No. 675440 (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 Ministry of Education, Youth and Sports (MEYS) of the Czech Republic; the Lendület (“Momentum”) Programme and the János Bolyai Research Scholarship of the Hungarian Academy of Sciences, the New National Excellence Program ÚNKP, the NKFIA research grants 123842, 123959, 124845, 124850 and 125105 (Hungary); the Council of Science and Industrial Research, India; the HOMING PLUS programme of the Foundation for Polish Science, cofinanced from European Union, Regional Development Fund, the Mobility Plus programme of the Ministry of Science and Higher Education, the National Science Centre (Poland), contracts Harmonia 2014/14/M/ST2/00428, Opus 2014/13/B/ST2/02543, 2014/15/B/ST2/03998, and 2015/19/B/ST2/02861, Sonata-bis 2012/07/E/ST2/01406; the National Priorities Research Program by Qatar National Research Fund; the Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia María de Maeztu, grant MDM-2015-0509 and the Programa Severo Ochoa del Principado de Asturias; the Thalis and Aristeia programmes cofinanced by EU-ESF and the Greek NSRF; the Rachadapisek Sompot Fund for Postdoctoral Fellowship, Chulalongkorn University and the Chulalongkorn Academic into Its 2nd Century Project Advancement Project (Thailand); the Welch Foundation, contract C-1845; and the Weston Havens Foundation (USA)