Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

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

Peer reviewe

Measurement of the top quark mass using events with a single reconstructed top quark in pp collisions at root s=13 TeV

Abstract:A measurement of the top quark mass is performed using a data sample en-riched with single top quark events produced in thetchannel. The study is based on proton-proton collision data, corresponding to an integrated luminosity of 35.9 fb−1, recorded at√s= 13TeV by the CMS experiment at the LHC in 2016. Candidate events are selectedby requiring an isolated high-momentum lepton (muon or electron) and exactly two jets,of which one is identified as originating from a bottom quark. Multivariate discriminantsare designed to separate the signal from the background. Optimized thresholds are placedon the discriminant outputs to obtain an event sample with high signal purity. The topquark mass is found to be172.13+0.76−0.77GeV, where the uncertainty includes both the sta-tistical and systematic components, reaching sub-GeV precision for the first time in thisevent topology. The masses of the top quark and antiquark are also determined separatelyusing the lepton charge in the final state, from which the mass ratio and difference aredetermined to be0.9952+0.0079−0.0104and0.83+1.79−1.35GeV, respectively. The results are consistentwithCPTinvariance

Search for a heavy Higgs boson decaying into two lighter Higgs bosons in the tau tau bb final state at 13 TeV

A search for a heavy Higgs boson H decaying into the observed Higgs boson h with a mass of 125 GeV and another Higgs boson h(S) is presented. The h and h(S) bosons are required to decay into a pair of tau leptons and a pair of b quarks, respectively. The search uses a sample of proton-proton collisions collected with the CMS detector at a center-of-mass energy of 13TeV, corresponding to an integrated luminosity of 137 fb(-1). Mass ranges of 240-3000 GeV for m(H) and 60-2800 GeV for m(hS) are explored in the search. No signal has been observed. Model independent 95% confidence level upper limits on the product of the production cross section and the branching fractions of the signal process are set with a sensitivity ranging from 125 fb (for m(H) = 240 GeV) to 2.7 fb (for m(H) = 1000 GeV). These limits are compared to maximally allowed products of the production cross section and the branching fractions of the signal process in the next-to-minimal supersymmetric extension of the standard model.Peer reviewe

The m6A reader YTHDC1 and the RNA helicase DDX5 control the production of rhabdomyosarcoma-enriched circRNAs

Rhabdomyosarcoma (RMS) is the most diffused soft tissue sarcoma in children and adolescents. Herein, the authors identify the m6A machinery and the RNA helicase DDX5 as factors responsible for the increase of a subset of circRNAs in RMS, providing protein and RNA candidates for the study of its tumorigenicity

Circular RNA ZNF609/CKAP5 mRNA interaction regulates microtubule dynamics and tumorigenicity

Circular RNAs (circRNAs) are widely expressed in eukaryotes and are regulated in many biological processes. Although several studies indicate their activity as microRNA (miRNA) and protein sponges, little is known about their ability to directly control mRNA homeostasis. We show that the widely expressed circZNF609 directly interacts with several mRNAs and increases their stability and/or translation by favoring the recruitment of the RNA-binding protein ELAVL1. Particularly, the interaction with CKAP5 mRNA, which interestingly overlaps the back-splicing junction, enhances CKAP5 translation, regulating microtubule function in cancer cells and sustaining cell-cycle progression. Finally, we show that circZNF609 downregulation increases the sensitivity of several cancer cell lines to different microtubule-targeting chemotherapeutic drugs and that locked nucleic acid (LNA) protectors against the pairing region on circZNF609 phenocopy such effects. These data set an example of how the small effects tuned by circZNF609/CKAP5 mRNA interaction might have a potent output in tumor growth and drug response

The long noncoding RNA Charme supervises cardiomyocyte maturation by controlling cell differentiation programs in the developing heart

Long noncoding RNAs (lncRNAs) are emerging as critical regulators of heart physiology and disease, although the studies unveiling their modes of action are still limited to few examples. We recently identified pCharme, a chromatin-associated lncRNA whose functional knockout in mice results in defective myogenesis and morphological remodeling of the cardiac muscle. Here, we combined Cap-Analysis of Gene Expression (CAGE), single-cell (sc)RNA sequencing, and whole-mount in situ hybridization analyses to study pCharme cardiac expression. Since the early steps of cardiomyogenesis, we found the lncRNA being specifically restricted to cardiomyocytes, where it assists the formation of specific nuclear condensates containing MATR3, as well as important RNAs for cardiac development. In line with the functional significance of these activities, pCharme ablation in mice results in a delayed maturation of cardiomyocytes, which ultimately leads to morphological alterations of the ventricular myocardium. Since congenital anomalies in myocardium are clinically relevant in humans and predispose patients to major complications, the identification of novel genes controlling cardiac morphology becomes crucial. Our study offers unique insights into a novel lncRNA-mediated regulatory mechanism promoting cardiomyocyte maturation and bears relevance to Charme locus for future theranostic applications

Trans-generational epigenetic regulation associated with the amelioration of Duchenne Muscular Dystrophy

Exon skipping is an effective strategy for the treatment of many Duchenne Muscular Dystrophy (DMD) mutations. Natural exon skipping observed in several DMD cases can help in identifying novel therapeutic tools. Here, we show a DMD study case where the lack of a splicing factor (Celf2a), which results in exon skipping and dystrophin rescue, is due to a maternally inherited trans-generational epigenetic silencing. We found that the study case and his mother express a repressive long non-coding RNA, DUXAP8, whose presence correlates with silencing of the Celf2a coding region. We also demonstrate that DUXAP8 expression is lost upon cell reprogramming and that, upon induction of iPSCs into myoblasts, Celf2a expression is recovered leading to the loss of exon skipping and loss of dystrophin synthesis. Finally, CRISPR/Cas9 inactivation of the splicing factor Celf2a was proven to ameliorate the pathological state in other DMD backgrounds establishing Celf2a ablation or inactivation as a novel therapeutic approach for the treatment of Duchenne Muscular Dystrophy.This work was partially supported by grants from ERC‐2019‐SyG (855923‐ASTRA), Telethon (GGP16213), Parent Project Italia, AIRC (IG 2019 Id. 23053) and PRIN 2017 (2017P352Z4) to I.B.; Spanish Ministry of Economy, Industry and Competitiveness (MEIC) (BFU2016‐75008‐P) to L.D.C. and Sapienza Research Calls (RM118164363B1D21) to J.M

A KO mouse model for the lncRNA Lhx1os produces motor neuron alterations and locomotor impairment

Summary: Here, we describe a conserved motor neuron-specific long non-coding RNA, Lhx1os, whose knockout in mice produces motor impairment and postnatal reduction of mature motor neurons (MNs). The ER stress-response pathway result specifically altered with the downregulation of factors involved in the unfolded protein response (UPR). Lhx1os was found to bind the ER-associated PDIA3 disulfide isomerase and to affect the expression of the same set of genes controlled by this protein, indicating that the two factors act in conjunction to modulate the UPR. Altogether, the observed phenotype and function of Lhx1os indicate its important role in the control of MN homeostasis and function

Participação comunitária em um programa de intervenção em área de proteção ambiental Community participation in an intervention program developed in a protected area

Este artigo discute os conceitos de participação e empowerment em Promoção da Saúde e Desenvolvimento Sustentável, considerando as agendas de implementação local, Municípios/Cidades Saudáveis e Agenda 21, e a importância dos processos de avaliação nesse contexto, por meio da análise de uma intervenção em área de mananciais - o Programa Bairro Ecológico (PBE), desenvolvido em 51 bairros do município de São Bernardo do Campo, Estado de São Paulo, Brasil. O estudo teve por objetivo avaliar os processos de participação e empowerment da comunidade, a partir das ações desencadeadas pelo PBE. Foram aplicados questionários e realizados grupos focais com moradores de bairros que sofreram a intervenção. Também foram realizadas entrevistas individuais com gestores do programa e do poder judiciário. Os resultados indicaram que a participação na implementação do PBE favoreceu o empowerment individual e grupal, presente nas duas comunidades estudadas. As comunidades tornaram-se mais organizadas. Há indícios de que os processos de tomada de decisões são centralizados. Apesar disso, as comunidades entendem que sua participação no programa lhes traz muitas coisas boas. Houve um processo participativo no desenvolvimento do programa, ainda que alguns relatos apontem para o caráter obrigatório da participação. Deve-se destacar o impacto do envolvimento e fortalecimento das lideranças na implementação e sustentabilidade do programa. No que diz respeito a esta última, verificou-se que a sensibilização ambiental tem sido fator determinante para a execução e manutenção das ações ao longo do tempo.<br>This article discusses the concepts of participation and empowerment in Health Promotion and Sustainable Development, considering the local implementation agendas:/ Healthy Cities and Agenda 21, and taking into account the importance of evaluation in this context. This was achieved through the analysis of an intervention in an area of water springs - Programa Bairro Ecológico (PBE - Ecological/ Neighborhood Program) -, which/ was developed in 51 neighborhoods of/ the city of São Bernardo do Campo, state of São Paulo, Brazil. The study aimed to evaluate the processes of community/ participation and empowerment through the actions triggered by the PBE. Questionnaires were administered to and/ focal groups were conducted with residents of neighborhoods where the intervention took place./ Individual interviews were performed with managers of the program and/ of the Judiciary. Results indicated that participation/ in the implementation of/ PBE favored the individual and group empowerment, present in both the studied communities. The communities became more organized. There is evidence that the decision-making processes are centralized. Nevertheless, the communities feel that their participation in the program brings them many good things. There was a participatory process in the development of the program, although some accounts point to mandatory participation. It is important to highlight the impact of leadership involvement and strengthening in the implementation and sustainability of the program. Regarding the latter, it was found that environmental awareness has been a determining factor for the implementation and maintenance of actions over time