Activation of r20-dependent recombination and horizontal gene transfer in Mycoplasma genitalium

In the human pathogen Mycoplasma genitalium, homologous recombination is under the control of r, an alternative sigma factor that boosts the generation of genetic and antigenic diversity in the population. Under laboratory growth conditions, r activation is rare and the factors governing its intermittent activity are unknown. Two r-regulated genes, rrlA and rrlB, showed to be important for recombination of homologous DNA sequences in this bacterium. Herein, we demonstrate that rrlA and rrlB code for two small proteins that participate in a feed-forward loop essential for r function. In addition, we identify novel genes regulated by r and show that several non-coding regions, which function as a reservoir for the generation of antigenic diversity, are also activated by this alternative sigma factor. Finally, we reveal that M. genitalium cells can transfer DNA horizontally by a novel mechanism that requires RecA and is facilitated by r overexpression. This DNA transfer system is arguably fundamental for persistence of M. genitalium within the host since it could facilitate a rapid dissemination of successful antigenic variants within the population. Overall, these findings impose a novel conception of genome evolution, genetic variation and survival of M. genitalium within the hos

Recombinant vaccines in 2022 : a perspective from the cell factory

The last big outbreaks of Ebola fever in Africa, the thousands of avian influenza outbreaks across Europe, Asia, North America and Africa, the emergence of monkeypox virus in Europe and specially the COVID-19 pandemics have globally stressed the need for efficient, cost-effective vaccines against infectious diseases. Ideally, they should be based on transversal technologies of wide applicability. In this context, and pushed by the above-mentioned epidemiological needs, new and highly sophisticated DNA-or RNA-based vaccination strategies have been recently developed and applied at large-scale. Being very promising and effective, they still need to be assessed regarding the level of conferred long-term protection. Despite these fast-developing approaches, subunit vaccines, based on recombinant proteins obtained by conventional genetic engineering, still show a wide spectrum of interesting potentialities and an important margin for further development. In the 80's, the first vaccination attempts with recombinant vaccines consisted in single structural proteins from viral pathogens, administered as soluble plain versions. In contrast, more complex formulations of recombinant antigens with particular geometries are progressively generated and explored in an attempt to mimic the multifaceted set of stimuli offered to the immune system by replicating pathogens. The diversity of recombinant antimicrobial vaccines and vaccine prototypes is revised here considering the cell factory types, through relevant examples of prototypes under development as well as already approved products

Lymphocyte infiltration and antitumoral effect promoted by cytotoxic inflammatory proteins formulated as self-assembling, protein-only nanoparticles

Two human proteins involved in the inflammatory cell death, namely Gasdermin D (GSDMD) and the Mixed Lineage Kinase Domain-Like (MLKL) protein have been engineered to accommodate an efficient ligand of the tumoral cell marker CXCR4, and a set of additional peptide agents that allow their spontaneous self-assembling. Upon production in bacterial cells and further purification, both proteins organized as stable nanoparticles of 46 and 54 nm respectively, that show, in this form, a moderate but dose-dependent cytotoxicity in cell culture. In vivo, and when administered in mouse models of colorectal cancer through repeated doses, the nanoscale forms of tumor-targeted GSDMD and, at a lesser extent, of MLKL promoted CD8+ and CD20+ lymphocyte infiltration in the tumor and an important reduction of tumor size, in absence of systemic toxicity. The potential of these novel pharmacological agents as anticancer drugs is discussed in the context of synergistic approaches to more effective cancer treatments

Congreso de Estudiantes de Química de la Comunidad Valenciana. Otra forma de aprender es posible

En abril de 2013 se celebró en la Universidad de Alicante el I Congreso de Estudiantes de Química de la Comunidad Valenciana. Estas jornadas presentan como principal novedad que la totalidad del comité organizador está compuesto por estudiantes de Química (cinco de la Universidad de Alicante y dos de la Universidad de Valencia) apoyados por un comité científico formado por profesores de ambas universidades. Estos estudiantes habían participado en años anteriores en redes de innovación docente o proyectos similares, mostrando interés por proponer alternativas a las clases magistrales para la adquisición de competencias, tanto de tipo transversal como específicas de la titulación. El congreso se enfocó teniendo en cuenta tres puntos básicos que son de especial interés para estudiantes de Química: (i) Salidas profesionales; (ii) Búsqueda activa de empleo y como enfrentarse a una entrevista de trabajo; (iii) Estudios de postgrado. Además, los más de 100 estudiantes que participaron en las jornadas ya sea mediante una comunicación oral, un póster o una actividad de divulgación científica se mostraron muy satisfechos con la experiencia. Actividades de este tipo y su gran acogida son capaces de mostrarnos, tanto a estudiantes como profesores, que existen formas de aprendizaje fuera de las aulas que permiten la adquisición de competencias transversales y específicas

Jet energy measurement with the ATLAS detector in proton-proton collisions at sqrt(s) = 7 TeV

The jet energy scale (JES) and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of sqrt(s) = 7 TeV corresponding to an integrated luminosity of 38 inverse pb. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0.4 or R=0.6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pt > 20 GeV and pseudorapidities eta 50 GeV after a dedicated correction for this effect. The JES is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pt, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pt jets recoiling against a high-pt jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, providing an improved jet energy resolution and a reduced flavour dependence of the jet response. The JES systematic uncertainty determined from a combination of in situ techniques are consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pt jets

Charged-particle multiplicities in pp interactions at root s=900 GeV measured with the ATLAS detector at the LHC

22 páginas, 4 figuras, 1 tabla.-- et al.(ATLAS Collaboration).-- arXiv:1003.3124v2The first measurements from proton-proton collisions recorded with the ATLAS detector at the LHC are presented. Data were collected in December 2009 using a minimum-bias trigger during collisions at a centre-of-mass energy of 900 GeV. The charged-particle multiplicity, its dependence on transverse momentum and pseudorapidity. and the relationship between mean transverse momentum and charged-particle multiplicity are measured for events with at least one charged particle in the kinematic range vertical bar eta vertical bar 500 MeV. The measurements are compared to Monte Carlo models of proton-proton collisions and to results from other experiments at the same centre-of-mass energy. The charged-particle multiplicity per event and unit of pseudorapidity eta = 0 is measured to be 1.333 +/- 0.003(stat.) +/- 0.040(syst.), which is 5-15% higher than the Monte Carlo models predict.We are greatly indebted to all CERN’s departments and to the LHC project for their immense efforts not only in building the LHC, but also for their direct contributions to the construction and installation of the ATLAS detector and its infrastructure. All our congratulations go to the LHC operation team for the superb performance during this initial data-taking period. We acknowledge equally warmly all our technical colleagues in the collaborating Institutions without whom the ATLAS detector could not have been built. Furthermore we are grateful to all the funding agencies which supported generously the construction and the commissioning of the ATLAS detector and also provided the computing infrastructure. The ATLAS detector design and construction has taken about fifteen years, and our thoughts are with all our colleagues who sadly could not see its final realisation. We acknowledge the support of ANPCyT, Argentina; Yerevan Physics Institute, Armenia; ARC and DEST, Australia; Bundesministerium für Wissenschaft und Forschung, Austria; National Academy of Sciences of Azerbaijan; State Committee on Science & Technologies of the Republic of Belarus; CNPq and FINEP, Brazil; NSERC, NRC, and CFI, Canada; CERN; CONICYT, Chile; NSFC, China; COLCIENCIAS, Colombia; Ministry of Education, Youth and Sports of the Czech Republic, Ministry of Industry and Trade of the Czech Republic, and Committee for Collaboration of the Czech Republic with CERN; Danish Natural Science Research Council and the Lundbeck Foundation; European Commission, through the ARTEMIS Research Training Network; IN2P3-CNRS and Dapnia-CEA, France; Georgian Academy of Sciences; BMBF, HGF, DFG and MPG, Germany; Ministry of Education and Religion, through the EPEAEK program PYTHAGORAS II and GSRT, Greece; ISF, MINERVA, GIF, DIP, and Benoziyo Center, Israel; INFN, Italy; MEXT, Japan; CNRST, Morocco; FOM and NWO, Netherlands; The Research Council of Norway; Ministry of Science and Higher Education, Poland; GRICES and FCT, Portugal; Ministry of Education and Research, Romania; Ministry of Education and Science of the Russian Federation and State Atomic Energy Corporation “Rosatom”; JINR; Ministry of Science, Serbia; Department of International Science and Technology Cooperation, Ministry of Education of the Slovak Republic; Slovenian Research Agency, Ministry of Higher Education, Science and Technology, Slovenia; Ministerio de Educación y Ciencia, Spain; The Swedish Research Council, The Knut and Alice Wallenberg Foundation, Sweden; State Secretariat for Education and Science, Swiss National Science Foundation, and Cantons of Bern and Geneva, Switzerland; National Science Council, Taiwan; TAEK, Turkey; The Science and Technology Facilities Council and The Leverhulme Trust, United Kingdom; DOE and NSF, United States of America.Peer reviewe