Modulación de la vía Glu-NO-GMPc y del aprendizaje por GMPc extracelular en cerebelo. Mecanismos moleculares implicados. Alteraciones en modelos animales de hiperamonemia y encefalopatía hepática

En modelos animales de hiperamonemia y encefalopatía hepática (EH) está disminuida la capacidad de aprendizaje de un test de discriminación condicionada en el laberinto en Y. La infusión crónica intracerebral de GMPc mediante bombas osmóticas restaura la capacidad de aprendizaje en el laberinto en Y en ratas con hiperamonemia crónica. El mecanismo por el que el GMPc extracelular modula la capacidad de aprendizaje no se conoce. La vía glutamato (Glu)-óxido nítrico (NO)-GMPc modula el aprendizaje en el laberinto en Y. La función de esta vía está alterada en modelos animales de hiperamonemia y EH, conduciendo a una disminución de la capacidad de aprendizaje en el laberinto en Y. Puesto que la adición de GMPc restaura la capacidad de aprendizaje de esta tarea, es posible que el GMPc añadido restaure la función de la vía Glu-NO-GMPc en cerebelo y de esta forma restaure la capacidad de aprendizaje. El objetivo general fue estudiar si el GMPc extracelular modula la función de la vía glutamato-óxido nítrico (NO)-GMPc en cerebelo in vivo, analizándolo por microdiálisis. También se utilizaron cortes de cerebelo ex vivo de ratas control y con hiperamonemia crónica para analizar en detalle los mecanismos de modulación de la vía por el GMPc extracelular. Los resultados obtenidos muestran que el tratamiento crónico intracerebral con GMPc extracelular restaura la actividad motora en ratas hiperamonémicas y esto podría ser consecuencia de la disminución de la neuroinflamación. Restaura la coordinación motora porque normaliza los niveles de GABA extracelular en cerebelo. Recupera (i) la memoria de referencia y el índice de aprendizaje pero no la memoria de trabajo en el laberinto radial y (ii) la capacidad de aprendizaje espacial en el test del laberinto acuático de Morris. A esta recuperación podrían contribuir la normalización de los niveles de GMPc y la reducción de la neuroinflamación en hipocampo por el GMPc extracelular. Existe un rango de concentración de GMPc extracelular para el que la función de la vía glutamato-NO-GMPc es óptima. Para concentraciones menores o mayores la función de la vía es menor. En ratas hiperamonémicas, la adición de concentraciones bajas de GMPc extracelular induce un mecanismo que activa la vía mientras que concentraciones altas la inhiben. La adición de GMPc extracelular induce los mecanismos de activación o de inhibición de la vía dependiendo de los niveles de GMPc extracelular alcanzados, la activan si están por debajo de la concentración óptima y la inhiben si están por encima. Para profundizar en los mecanismos de regulación de la vía Glu-No-GMPc por GMPc extracelular, utilizamos cortes de cerebelo. La adición de GMPc extracelular recupera la función de la vía en hiperamonemia (i) disminuyendo la actividad de la CaMKII y (ii) aumentado la actividad de la NOS. En cortes de ratas control la adición de GMPc extracelular disminuye la función de la vía aumentando (i) la actividad de la CaMKII y (ii) la fosforilación de la NOS en la Ser847, disminuyendo así su actividad. Estos efectos del GMPc extracelular sobre la NOS podrían ser mediados por inhibición de una ecto ó exo proteín-quinasa A (PKA) en cerebelo. El GMPc extracelular disminuye la fosforilación de una proteína de membrana de Mr ≈40 KDa. Ésta podría ser la molécula que media los efectos del GMPc extracelular sobre la señalización intracelular en la vía glutamato-NO-GMPc.The ability to learn a conditional discrimination task in a Y maze is decreased in animal models of hyperammonemia and hepatic encephalopathy. Chronic intracerebral infusion of (extracellular) cGMP using osmotic pumps restores learning ability in the Y maze in rats with chronic hyperammonemia. The mechanism by which extracellular cGMP modulates learning ability is not known. The glutamate (Glu) - nitric oxide (NO) - cGMP pathway modulates learning ability in the Y maze. The function of this pathway is impaired in animal models of hyperammonemia and hepatic encephalopathy, leading to reduced learning ability in the Y maze. As chronic treatment with extracellular cGMP restores learning ability in this task, it is possible that extracellular cGMP restore learning ability by restoring the function of the Glu-NO-cGMP pathway in cerebellum. The overall objective was to study whether extracellular cGMP modulates the function of the Glu- NO -cGMP pathway in cerebellum in vivo as assessed by microdialysis in freely moving rats. To analyze in detail the mechanisms of pathway modulation by extracellular cGMP we used ex vivo cerebellar slices from control and hyperammonemic rats. The results show that chronic intracerebral treatment with extracellular cGMP restores motor activity in hyperammonemic rats and this could be a consequence of reduced neuroinflammation. Extracellular cGMP restores motor coordination because it normalizes the levels of extracellular GABA in cerebellum. It restores also (i) reference memory and learning index but not the working memory in the radial maze and (ii) the spatial learning in the Morris water maze. Both normalization of cGMP levels and the reduction of neuroinflammation in hippocampus by extracellular cGMP may contribute to restore spatial learning. There is an optimal range of extracellular cGMP concentration for the function of the glutamate-NO-cGMP pathway. Lower or higher concentrations reduce the pathway function. In hyperammonemic rats, the addition of low concentrations of extracellular cGMP activates a mechanism that enhances the function of the pathway, while higher concentrations inhibit it. In hyperammonemic rats, addition of extracellular cGMP induces activation or inhibition of the pathway depending on the extracellular cGMP levels achieved, activating it when cGMP is below the optimum concentration and inhibiting if it is above. To further explore the mechanisms of regulation of the Glu-No-cGMP pathway by extracellular cGMP, we used cerebellar slices. Addition of extracellular cGMP restores the function of the pathway in hyperammonemia by (i) decreasing the activity of CaMKII and (ii) increasing the activity of nitric oxide synthase (NOS). Addition of extracellular cGMP in control rats decreases the pathway function by increasing: (i) the activity of CaMKII and (ii) the phosphorylation of the Ser847 NOS, thus decreasing their activity. These effects of extracellular cGMP on NOS may be mediated by an inhibition of exo or ecto protein kinase A (PKA) in cerebellum. Extracellular cGMP reduces phosphorylation of a membrane protein with a MW ≈ 40 kDa. This protein could be the molecule which mediates the effects of extracellular cGMP on intracellular signaling in the glutamate-NO-cGMP pathway

Interiorización del método científico en alimentación sostenible mediante la experimentación en el aula

[ES] La alimentación sostenible hace referencia a aquella alimentación saludable que se adapta al entorno y la cultura, que disminuye el impacto ambiental, respeta los recursos naturales y la biodiversidad y es económicamente accesible. El alumnado que cursa alguno de los grados de Ciencias de la Alimentación debe ser consciente del concepto de sostenibilidad, integrarlo en su vida diaria, así como saber transmitirlo a la sociedad. Este alumnado busca adquirir conocimientos a través de metodologías diferentes y complementarias. La combinación de prácticas tradicionales y modernas son vitales para promover diferentes habilidades cognitivas en el estudiantado. Es importante aumentar su conocimiento y sus competencias en la resolución de problemas pero también lo es incrementar sus habilidades de razonamiento. Teniendo en cuenta que los y las estudiantes en Ciencias de la Alimentación deben trabajar desde la aplicación del método científico, una de las maneras más adecuadas de interiorizar este es llevándolo a la práctica. Por ello, en este proyecto se pretende que el alumnado sea capaz de plantear una hipótesis de trabajo en alimentación sostenible en consonancia con los ODS relacionados y llevar a cabo un taller práctico que potencie sus competencias comunicativas en el ámbito universitario.[EN] Sustainable food refers to healthy food that is adapted to the environment and culture, that reduces environmental impact, respects natural resources and biodiversity and is economically accessible. Students taking a degree in Food Science must be aware of the concept of sustainability, integrate it into their daily lives and know how to transmit it to society. These students want to acquire knowledge through different and complementary methodologies. The combination of traditional and modern practices are vital to promote different cognitive skills in students. It is important to increase their knowledge and problem solving competences but it is also important to increase their reasoning skills. Taking into account that students in Food Science must work from the application of the scientific method, one of the most appropriate ways to learn this method is by putting it into practice. Therefore, the aim of this project is to ensure that students are able to propose a working hypothesis on sustainable food in line with the related SDGs and to carry out a practical workshop that enhances their communicative skills in the university environment.Gandía Gómez, M.; Rodríguez-Carrasco, Y.; Cabrera-Pastor, A.; Pardo, E.; Gamero, A. (2023). Interiorización del método científico en alimentación sostenible mediante la experimentación en el aula. Editorial Universitat Politècnica de València. 581-589. https://doi.org/10.4995/INRED2023.2023.1653758158

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Measurement of the correlation between the polar angles of leptons from top quark decays in the helicity basis at √s = 7 TeV using the ATLAS detector

A measurement of the correlations between the polar angles of leptons from the decay of pair-produced t and t̄ quarks in the helicity basis is reported, using proton-proton collision data collected by the ATLAS detector at the LHC. The dataset corresponds to an integrated luminosity of 4.6  fb−¹ at a center-of-mass energy of √s = 7  TeV collected during 2011. Candidate events are selected in the dilepton topology with large missing transverse momentum and at least two jets. The angles θ1 and θ2 between the charged leptons and the direction of motion of the parent quarks in the tt̄ rest frame are sensitive to the spin information, and the distribution of cosθ1 ⋅ cosθ2 is sensitive to the spin correlation between the t and t̄ quarks. The distribution is unfolded to parton level and compared to the next-to-leading order prediction. A good agreement is observed

Search for massive, long-lived particles using multitrack displaced vertices or displaced lepton pairs in pp collisions at √s = 8 TeV with the ATLAS detector

Many extensions of the Standard Model posit the existence of heavy particles with long lifetimes. This article presents the results of a search for events containing at least one long-lived particle that decays at a significant distance from its production point into two leptons or into five or more charged particles. This analysis uses a data sample of proton-proton collisions at √s=8  TeV corresponding to an integrated luminosity of 20.3  fb−1 collected in 2012 by the ATLAS detector operating at the Large Hadron Collider. No events are observed in any of the signal regions, and limits are set on model parameters within supersymmetric scenarios involving R-parity violation, split supersymmetry, and gauge mediation. In some of the search channels, the trigger and search strategy are based only on the decay products of individual long-lived particles, irrespective of the rest of the event. In these cases, the provided limits can easily be reinterpreted in different scenarios

Measurement of the CP-violating phase ϕs and the Bs0 meson decay width difference with Bs0 → J/ψϕ decays in ATLAS

A measurement of the Bs0 decay parameters in the Bs0 → J/ψϕ channel using an integrated luminosity of 14.3 fb−1 collected by the ATLAS detector from 8 TeV pp collisions at the LHC is presented. The measured parameters include the CP -violating phase ϕs, the decay width Γs and the width difference between the mass eigenstates ΔΓs. The values measured for the physical parameters are statistically combined with those from 4.9 fb−1 of 7 TeV data, leading to the following: ϕ s =−0.090±0.078(stat.)±0.041(syst.)rad ΔΓ s =0.085±0.011(stat.)±0.007(syst.)ps −1 Γ s =0.675±0.003(stat.)±0.003(syst.)ps −1 In the analysis the parameter ΔΓs is constrained to be positive. Results for ϕs and ΔΓs are also presented as 68% and 95% likelihood contours in the ϕs-ΔΓs plane. Also measured in this decay channel are the transversity amplitudes and corresponding strong phases. All measurements are in agreement with the Standard Model predictions

Measurement of the differential cross-section of highly boosted top quarks as a function of their transverse momentum in s =8 TeV proton-proton collisions using the ATLAS detector

The differential cross-section for pair production of top quarks with high transverse momentum is measured in 20.3  fb−1 of proton-proton collisions at a center-of-mass energy of 8 TeV. The measurement is performed for tt¯ events in the lepton+jets channel. The cross-section is reported as a function of the hadronically decaying top quark transverse momentum for values above 300 GeV. The hadronically decaying top quark is reconstructed as an anti-kt jet with radius parameter R=1.0 and identified with jet substructure techniques. The observed yield is corrected for detector effects to obtain a cross-section at particle level in a fiducial region close to the event selection. A parton-level cross-section extrapolated to the full phase space is also reported for top quarks with transverse momentum above 300 GeV. The predictions of a majority of next-to-leading-order and leading-order matrix-element Monte Carlo generators are found to agree with the measured cross-sections.- We thank CERN for the very successful operation of the LHC, as well as the support staff from our institutions without whom ATLAS could not be operated efficiently. We acknowledge the support of ANPCyT, Argentina; YerPhI, Armenia; ARC, Australia; BMWFW and FWF, Austria; ANAS, Azerbaijan; SSTC, Belarus; CNPq and FAPESP, Brazil; NSERC, NRC and CFI, Canada; CERN; CONICYT, Chile; CAS, MOST and NSFC, China; COLCIENCIAS, Colombia; MSMT CR, MPO CR and VSC CR, Czech Republic; DNRF, DNSRC and Lundbeck Foundation, Denmark; IN2P3-CNRS, CEA-DSM/IRFU, France; GNSF, Georgia; BMBF, HGF, and MPG, Germany; GSRT, Greece; RGC, Hong Kong SAR, China; ISF, I-CORE and Benoziyo Center, Israel; INFN, Italy; MEXT and JSPS, Japan; CNRST, Morocco; FOM and NWO, Netherlands; RCN, Norway; MNiSW and NCN, Poland; FCT, Portugal; MNE/IFA, Romania; MES of Russia and NRC KI, Russian Federation; JINR; MESTD, Serbia; MSSR, Slovakia; ARRS and MIZS, Slovenia; DST/NRF, South Africa; MINECO, Spain; SRC and Wallenberg Foundation, Sweden; SERI, SNSF and Cantons of Bern and Geneva, Switzerland; MOST, Taiwan; TAEK, Turkey; STFC, United Kingdom; DOE and NSF, United States of America. In addition, individual groups and members have received support from BCKDF, the Canada Council, CANARIE, CRC, Compute Canada, FQRNT, and the Ontario Innovation Trust, Canada; EPLANET, ERC, FP7, Horizon 2020 and Marie Sklodowska-Curie Actions, European Union; Investissements d'Avenir Labex and Idex, ANR, Region Auvergne and Fondation Partager le Savoir, France; DFG and AvH Foundation, Germany; Herakleitos, Thales and Aristeia programmes co-financed by EU-ESF and the Greek NSRF; BSF, GIF and Minerva, Israel; BRF, Norway; the Royal Society and Leverhulme Trust, United Kingdom. The crucial computing support from all WLCG partners is acknowledged gratefully, in particular from CERN and the ATLAS Tier-1 facilities at TRIUMF (Canada), NDGF (Denmark, Norway, Sweden), CC-IN2P3 (France), KIT/GridKA (Germany), INFN-CNAF (Italy), NL-T1 (Netherlands), PIC (Spain), ASGC (Taiwan), RAL (UK) an