A Non-Viral Plasmid DNA Delivery System Consisting on a Lysine-Derived Cationic Lipid Mixed with a Fusogenic Lipid

The insertion of biocompatible amino acid moieties in non-viral gene nanocarriers is an attractive approach that has been recently gaining interest. In this work, a cationic lipid, consisting of a lysine-derived moiety linked to a C12 chain (LYCl) was combined with a common fusogenic helper lipid (DOPE) and evaluated as a potential vehicle to transfect two plasmid DNAs (encoding green fluorescent protein GFP and luciferase) into COS-7 cells. A multidisciplinary approach has been followed: (i) biophysical characterization based on zeta potential, gel electrophoresis, small-angle X-ray scattering (SAXS), and cryo-transmission electronic microscopy (cryo-TEM); (ii) biological studies by fluorescence assisted cell sorting (FACS), luminometry, and cytotoxicity experiments; and (iii) a computational study of the formation of lipid bilayers and their subsequent stabilization with DNA. The results indicate that LYCl/DOPE nanocarriers are capable of compacting the pDNAs and protecting them efficiently against DNase I degradation, by forming Lα lyotropic liquid crystal phases, with an average size of ~200 nm and low polydispersity that facilitate the cellular uptake process. The computational results confirmed that the LYCl/DOPE lipid bilayers are stable and also capable of stabilizing DNA fragments via lipoplex formation, with dimensions consistent with experimental values. The optimum formulations (found at 20% of LYCl content) were able to complete the transfection process efficiently and with high cell viabilities, even improving the outcomes of the positive control Lipo2000*

Biological Markers of Pseudomonas aeruginosa Epidemic High-Risk Clones

A limited number of Pseudomonas aeruginosa genotypes (mainly ST-111, ST-175, and ST-235), known as high-risk clones, are responsible for epidemics of nosocomial infections by multidrug-resistant (MDR) or extensively drug-resistant (XDR) strains worldwide. We explored the potential biological parameters that may explain the success of these clones. A total of 20 isolates from each of 4 resistance groups (XDR, MDR, ModR [resistant to 1 or 2 classes], and MultiS [susceptible to all antipseudomonals]), recovered from a multicenter study of P. aeruginosa bloodstream infections performed in 10 Spanish hospitals, were analyzed. A further set of 20 XDR isolates belonging to epidemic high-risk clones (ST-175 [n = 6], ST-111 [n = 7], and ST-235 [n = 7]) recovered from different geographical locations was also studied. When unknown, genotypes were documented through multilocus sequence typing. The biological parameters evaluated included twitching, swimming, and swarming motility, biofilm formation, production of pyoverdine and pyocyanin, spontaneous mutant frequencies, and the in vitro competition index (CI) obtained with a flow cytometry assay. All 20 (100%) XDR, 8 (40%) MDR, and 1 (5%) ModR bloodstream isolate from the multicenter study belonged to high-risk clones. No significant differences were observed between clonally diverse ModR and MultiS isolates for any of the parameters. In contrast, MDR/XDR high-risk clones showed significantly increased biofilm formation and mutant frequencies but significantly reduced motility (twitching, swimming, and swarming), production of pyoverdine and pyocyanin, and fitness. The defined biological markers of high-risk clones, which resemble those resulting from adaptation to chronic infections, could be useful for the design of specific treatment and infection control strategies

Asociación entre horas de televisión, actividad física, horas de sueño y exceso de peso en población adulta joven

Objetivo: Analizar la asociación de las horas de televisión, la actividad física autorreferida y las horas de sueño con el exceso de peso corporal o el índice de masa corporal (IMC) en población universitaria. Métodos: Se han analizado de forma transversal los datos basales de 1135 participantes de 17 a 35 años de edad del proyecto «Dieta, antropometría y salud en población universitaria». Se recogió información sobre las horas de televisión y de sueño, la actividad física, el peso y la talla autorreferidos, y otras variables de interés. Se calculó el IMC (kg/m2) y se definió el exceso de peso (IMC ≥25). Se usó regresión logística múltiple para analizar la asociación entre las variables de interés y el exceso de peso (no/sí), y regresión lineal múltiple para el IMC. Resultados: La prevalencia de exceso de peso fue de 13,7% (11,2% sobrepeso y 2,5% obesidad). Se encontró una asociación significativa entre el exceso de peso y más horas de televisión. Tomando como referencia a los que veían televisión ≤1 h al día, los que la veían >2 h al día (categoría superior) presentaron una odds ratio de 2,13 (intervalo de confianza del 95%: 1,37-3,36; p tendencia: 0,002). Una menor actividad física autorreferida se asoció a un mayor riesgo de exceso de peso, aunque la asociación sólo resultó significativa en el análisis de regresión lineal múltiple (p = 0,037). No se encontró asociación entre el exceso de peso y las horas de sueño. Conclusiones: Más horas de televisión y una menor actividad física se asociaron significativamente con un aumento del IMC en la población universitaria estudiada. Ambos factores pueden modificarse con estrategias preventivas

Strategies and performance of the CMS silicon tracker alignment during LHC Run 2

The strategies for and the performance of the CMS silicon tracking system alignment during the 2015-2018 data-taking period of the LHC are described. The alignment procedures during and after data taking are explained. Alignment scenarios are also derived for use in the simulation of the detector response. Systematic effects, related to intrinsic symmetries of the alignment task or to external constraints, are discussed and illustrated for different scenarios.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: the Austrian Federal Ministry of Education, Science and Research and the Austrian Science Fund; the Belgian Fonds de la Recherche Scientifique, and Fonds voor Wetenschappelijk Onderzoek; the Brazilian Funding Agencies (CNPq, CAPES, FAPERJ, FAPERGS, and FAPESP); the Bulgarian Ministry of Education and Science, and the Bulgarian National Science Fund; CERN; the Chinese Academy of Sciences, Ministry of Science and Technology, and National Natural Science Foundation of China; the Ministerio de Ciencia Tecnología e Innovación (MINCIENCIAS), Colombia; the Croatian Ministry of Science, Education and Sport, and the Croatian Science Foundation; the Research and Innovation Foundation, Cyprus; the Secretariat for Higher Education, Science, Technology and Innovation, Ecuador; the Ministry of Education and Research, Estonian Research Council via PRG780, PRG803 and PRG445 and European Regional Development Fund, Estonia; the Academy of Finland, Finnish Ministry of Education and Culture, and Helsinki Institute of Physics; the Institut National de Physique Nucléaire et de Physique des Particules / CNRS, and Commissariat à l’Énergie Atomique et aux Énergies Alternatives / CEA, France; the Bundesministerium für Bildung und Forschung, the Deutsche Forschungsgemeinschaft (DFG), under Germany’s Excellence Strategy – EXC 2121 “Quantum Universe” – 390833306, and under project number 400140256 - GRK2497, and Helmholtz-Gemeinschaft Deutscher Forschungszentren, Germany; the General Secretariat for Research and Innovation, Greece; the National Research, Development and Innovation Fund, Hungary; the Department of Atomic Energy and the Department of Science and Technology, India; the Institute for Studies in Theoretical Physics and Mathematics, Iran; the Science Foundation, Ireland; the Istituto Nazionale di Fisica Nucleare, Italy; the Ministry of Science, ICT and Future Planning, and National Research Foundation (NRF), Republic of Korea; the Ministry of Education and Science of the Republic of Latvia; the Lithuanian Academy of Sciences; the Ministry of Education, and University of Malaya (Malaysia); the Ministry of Science of Montenegro; the Mexican Funding Agencies (BUAP, CINVESTAV, CONACYT, LNS, SEP, and UASLP-FAI); the Ministry of Business, Innovation and Employment, New Zealand; the Pakistan Atomic Energy Commission; the Ministry of Science and Higher Education and the National Science Centre, Poland; the Fundação para a Ciência e a Tecnologia, grants CERN/FIS-PAR/0025/2019 and CERN/FIS-INS/0032/2019, Portugal; JINR, Dubna; the Ministry of Education and Science of the Russian Federation, the Federal Agency of Atomic Energy of the Russian Federation, Russian Academy of Sciences, the Russian Foundation for Basic Research, and the National Research Center “Kurchatov Institute”; the Ministry of Education, Science and Technological Development of Serbia; the Secretaría de Estado de Investigación, Desarrollo e Innovación, Programa Consolider-Ingenio 2010, Plan Estatal de Investigación Científica Técnica de Innovación 2017–2020, research project IDI-2018-000174 del Principado de Asturias, and Fondo Europeo de Desarrollo Regional, Spain; the Ministry of Science, Technology and Research, Sri Lanka; the Swiss Funding Agencies (ETH Board, ETH Zurich, PSI, SNF, UniZH, Canton Zurich, and SER); the Ministry of Science and Technology, Taipei; the Thailand Center of Excellence in Physics, the Institute for the Promotion of Teaching Science and Technology of Thailand, Special Task Force for Activating Research and the National Science and Technology Development Agency of Thailand; the Scientific and Technical Research Council of Turkey, and Turkish Atomic Energy Authority; the National Academy of Sciences of Ukraine; the Science and Technology Facilities Council, UK; the US Department of Energy, and the US National Science Foundation. 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 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, 125105, 128713, 128786, and 129058 (Hungary); the Council of Scientific and Industrial Research, India; the Latvian Council of Science; the National Science Center (Poland), contracts Opus 2014/15/B/ST2/03998 and 2015/19/B/ST2/02861; the Fundação para a Ciência e a Tecnologia, grant FCT CEECIND/01334/2018; the National Priorities Research Program by Qatar National Research Fund; the Ministry of Science and Higher Education, projects no. 14.W03.31.0026 and no. FSWW-2020-0008, and the Russian Foundation for Basic Research, project No. 19-42-703014 (Russia); the Programa de Excelencia María de Maeztu, 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 (USA)