Metaloproteinasas y Osteoartritis

Las metaloproteinasas (MMPs) son una familia de enzimas proteolíticas  capaces de procesar o degradar proteínas de la matriz extracelular. Las MMPs tienen un prodominio, prodominio catalítico, una región bisagra y un dominio tipo hemopexina (excepto en las matrilisinas). Pueden ser activadas in vivo por otras MMPs,  proteinasas tisulares o proteinasas plasmáticas. La regulación de estas enzimas puede ocurrir a nivel de su síntesis, secreción, activación del zimógeno. Los inhibidores tisulares de metaloproteinasas (TIMPs) son inhibidores específicos de las MMPs que participan en el control local de su actividad. En el cartílago  normal existe bajo recambio de las moléculas de la matriz extracelular. Existe un delicado balance entre la síntesis y degradación de los componentes del cartílago articular. Este balance se  pierde en enfermedades degenerativas como la osteoartritis en dónde participan algunas MMPs tales como las gelatinasas, estromelisinas y colagenasas. Estos procesos podrían ser blancos farmacológicos en el tratamiento de esta enfermedad

Green Synthesis of Silver Nanoparticles Using <em>Heterotheca inuloides</em> and Its Antimicrobial Activity in Catgut Suture Threads

Silver nanoparticles were synthesized through a green method, using Heterotheca inuloides as a bioreducing agent. Moreover, catgut suture threads were decorated with those biogenic silver nanoparticles, and their antibacterial activity versus highly resistant pathogenic microorganisms was evaluated. The principles of green chemistry and nanotechnology allow us to obtain advanced materials, such as suture threads, which can reduce or avoid the prevalence of infectious processes in the medical field. Mexican medicinal plants, such as H. inuloides, represent an adequate alternative for biosynthesis; this plant species is known for its medicinal benefits and its antibacterial activity, and for that reason, it is being used in folk medicine

Identification of Solanum pimpinellifolium genome regions for increased resilience to nitrogen deficiency in cultivated tomato

14 Pág.High-quality crop production with minimal fertilizer inputs is a key goal for the agriculture of the future. Globally, tomato is one of the most important vegetable crops and its intensive production and breeding has been based on the application of large quantities of nitrogen (N) fertilizers. Therefore, the development of N use efficient (NUE) cultivars with low N inputs needs to be addressed. Some variability in plant growth, fruit quality and NUE traits among tomato (Solanum lycopersicum L.) varieties under low N supply has been reported, however, the relevance of wild relatives of tomato has not yet been assessed. In this study, we found that S. pimpinellifolium accession To-937 (SP) may be a suitable resource to increase NUE in tomato. We studied a set of 29 introgression lines (IL) from SP into the Moneymaker cultivar (MM) in different seasons to investigate the potential of SP introgressions to maintain the tomato plant performance during the growth cycle under low N input in greenhouse conditions. We identified specific regions in the SP genome, on chromosomes 1, 3 and 10, involved in the responses to N inputs of fruit production and fruit quality. Notably, the line SP_10-4 maintained vegetative biomass and fruit yield production under limiting N supply. The introgressed region contained putative candidate genes as sucrose phosphate phosphatase (SPP), invertases (INV) and glutamine synthase 1 (GS1) genes, implicated in C and N metabolism. Genomic and expression analyses revealed differences in coding and non-coding sequences as well as in mRNA levels in SP_10-4, suggesting that these genes might well contribute to the reported biomass responses to N. Additionally, line SP_1-4 showed stable fruit amino acid contents under both sufficient and limiting N supplies, indicating that assimilated N partitioning to the fruit is maintained in response to N. Altogether, our results confirmed the suitability of SP as a source of NUE related traits and the interest in the studied ILs for developing new tomato cultivars with improved NUE under sustainable fertilization conditions.This work was supported by the Ministerio de Ciencia e Innovación (MCIN) and the Agencia Estatal de Investigación (grants RTA2015-00014-c02-00 to SGN and JM, PID2020-114165RR-C21 to JM, and PID2022-136541OB-I00 to SGN), the Agroalnext program (MCIN with funding of NextGenEU-PRTR-C17.I1 Generalitat Valenciana AGROALNEXT/2022/056 to SGN), Vicerrectorado de Investigación de la Universitat Politècnica de València (PAID-11-21 to SGN; PAID-10-20 and PAID-PD-22 to RM), Ministerio de Ciencia e Innovación (TED2021-129296B-I00 to SGN) and European Commission H2020 research and innovation program through HARNESSTOM grant agreement no. 101000716 (to AG) and RoxyCOST CA18210 for networking activities (to AG). We also want to acknowledge the "Severo Ochoa Program for Centers of Excellence in R&D" (CEX2020-000999-S) supported by MCIN/AEI/10.13039/501100011033. We thank Mike Bennett for revising the English language and Javier Forment from the IBMCP Bioinformatics service for support on genomic analyses.With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2020‐000999‐S)Peer reviewe

Seeking organisational excellence by using the information coming from the EFQM excellence model as starting point: application to a real case

This paper describes how to use the information coming from applying the EFQM excellence model to analyse the perception that the members of an organisation have of it regarding their business vision. Such an analysis is made on the basis of the EFQM excellence model criteria and by applying statistical data analysis techniques. With this study, besides detecting both the strong and weak areas of actuation on which an organisation should focus and act, it is also possible to detect the relationships between the personal characteristics of members of the organisation and their business vision. The main goal is that organisations are able to reach excellence by jointly using an assessment method (the EFQM excellence model) and posterior statistical data analysis techniques (uni-variant and multi-variant). These techniques enable one to complement and enlarge the potential of the EFQM excellence model. Finally, the procedure is illustrated by presenting the main results of applying it to a real case of the Permanent Training Centre of the Polytechnic University of Valencia in Spain. © 2011 Taylor & Francis.Alfaro Saiz, JJ.; Carot Sierra, JM.; Rodríguez Rodríguez, R.; Jabaloyes Vivas, JM. (2011). Seeking organisational excellence by using the information coming from the EFQM excellence model as starting point: application to a real case. Total Quality Management and Business Excellence. 22(8):853-868. doi:10.1080/14783363.2011.597595S853868228Carlos Bou‐Llusar, J., Escrig‐Tena, A. B., Roca‐Puig, V., & Beltrán‐Martín, I. (2005). To what extent do enablers explain results in the EFQM excellence model? International Journal of Quality & Reliability Management, 22(4), 337-353. doi:10.1108/02656710510591192Calvo‐Mora, A., Leal, A., & Roldán, J. L. (2006). Using enablers of the EFQM model to manage institutions of higher education. Quality Assurance in Education, 14(2), 99-122. doi:10.1108/09684880610662006Dale, B. G., Zairi, M., Van der Wiele, A., & Williams, A. R. T. (2000). Quality is dead in Europe – long live excellence ‐ true or false? Measuring Business Excellence, 4(3), 4-10. doi:10.1108/13683040010377737Eskildsen, J. K., Kristensen, K., & Jørn Juhl, H. (2001). The criterion weights of the EFQM excellence model. International Journal of Quality & Reliability Management, 18(8), 783-795. doi:10.1108/eum0000000006033Farrar, M. (2000). Structuring success: A case study in the use of the EFQM Excellence Model in school improvement. Total Quality Management, 11(4-6), 691-696. doi:10.1080/09544120050008084Hides, M. T., Davies, J., & Jackson, S. (2004). Implementation of EFQM excellence model self‐assessment in the UK higher education sector – lessons learned from other sectors. The TQM Magazine, 16(3), 194-201. doi:10.1108/09544780410532936Li, M., & Yang, J. B. (2003). A decision model for self‐assessment of business process based on the EFQM excellence model. International Journal of Quality & Reliability Management, 20(2), 164-188. doi:10.1108/02656710310456608Martín‐Castilla, J. I., & Rodríguez‐Ruiz, Ó. (2008). EFQM model: knowledge governance and competitive advantage. Journal of Intellectual Capital, 9(1), 133-156. doi:10.1108/14691930810845858McAdam, R., & Welsh, W. (2000). A critical review of the business excellence quality model applied to further education colleges. Quality Assurance in Education, 8(3), 120-130. doi:10.1108/09684880010372716Ruiz-Carrillo, J. I. C., & Fernández-Ortiz, R. (2005). Theoretical foundation of the EFQM model: the resource-based view. Total Quality Management & Business Excellence, 16(1), 31-55. doi:10.1080/1478336042000309857Rusjan, B. (2005). Usefulness of the EFQM excellence model: Theoretical explanation of some conceptual and methodological issues. Total Quality Management & Business Excellence, 16(3), 363-380. doi:10.1080/14783360500053972José Tarí, J. (2006). An EFQM model self‐assessment exercise at a Spanish university. Journal of Educational Administration, 44(2), 170-188. doi:10.1108/09578230610652051Wongrassamee, S., Simmons, J. E. L., & Gardiner, P. D. (2003). Performance measurement tools: the Balanced Scorecard and the EFQM Excellence Model. Measuring Business Excellence, 7(1), 14-29. doi:10.1108/13683040310466690Yang, J. B., Dale, B. G., & Siow, C. H. R. (2001). Self-assessment of excellence: An application of the evidential reasoning approach. International Journal of Production Research, 39(16), 3789-3812. doi:10.1080/0020754011006907

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe

An embedding technique to determine ττ backgrounds in proton-proton collision data

An embedding technique is presented to estimate standard model tau tau backgrounds from data with minimal simulation input. In the data, the muons are removed from reconstructed mu mu events and replaced with simulated tau leptons with the same kinematic properties. In this way, a set of hybrid events is obtained that does not rely on simulation except for the decay of the tau leptons. The challenges in describing the underlying event or the production of associated jets in the simulation are avoided. The technique described in this paper was developed for CMS. Its validation and the inherent uncertainties are also discussed. The demonstration of the performance of the technique is based on a sample of proton-proton collisions collected by CMS in 2017 at root s = 13 TeV corresponding to an integrated luminosity of 41.5 fb(-1).Peer reviewe

Measurement of nuclear modification factors of gamma(1S)), gamma(2S), and gamma(3S) mesons in PbPb collisions at root s(NN)=5.02 TeV

The cross sections for ϒ(1S), ϒ(2S), and ϒ(3S) production in lead-lead (PbPb) and proton-proton (pp) collisions at √sNN = 5.02 TeV have been measured using the CMS detector at the LHC. The nuclear modification factors, RAA, derived from the PbPb-to-pp ratio of yields for each state, are studied as functions of meson rapidity and transverse momentum, as well as PbPb collision centrality. The yields of all three states are found to be significantly suppressed, and compatible with a sequential ordering of the suppression, RAA(ϒ(1S)) > RAA(ϒ(2S)) > RAA(ϒ(3S)). The suppression of ϒ(1S) is larger than that seen at √sNN = 2.76 TeV, although the two are compatible within uncertainties. The upper limit on the RAA of ϒ(3S) integrated over pT, rapidity and centrality is 0.096 at 95% confidence level, which is the strongest suppression observed for a quarkonium state in heavy ion collisions to date. © 2019 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Funded by SCOAP3.Peer reviewe

Electroweak production of two jets in association with a Z boson in proton-proton collisions root s =13 TeV

A measurement of the electroweak (EW) production of two jets in association with a Z boson in proton-proton collisions at root s = 13 TeV is presented, based on data recorded in 2016 by the CMS experiment at the LHC corresponding to an integrated luminosity of 35.9 fb(-1). The measurement is performed in the lljj final state with l including electrons and muons, and the jets j corresponding to the quarks produced in the hard interaction. The measured cross section in a kinematic region defined by invariant masses m(ll) > 50 GeV, m(jj) > 120 GeV, and transverse momenta P-Tj > 25 GeV is sigma(EW) (lljj) = 534 +/- 20 (stat) fb (syst) fb, in agreement with leading-order standard model predictions. The final state is also used to perform a search for anomalous trilinear gauge couplings. No evidence is found and limits on anomalous trilinear gauge couplings associated with dimension-six operators are given in the framework of an effective field theory. The corresponding 95% confidence level intervals are -2.6 <cwww/Lambda(2) <2.6 TeV-2 and -8.4 <cw/Lambda(2) <10.1 TeV-2. The additional jet activity of events in a signal-enriched region is also studied, and the measurements are in agreement with predictions.Peer reviewe