Differential protein expression in peripheral blood mononuclear cells (PBMCs) on patients withd systemic lupus erythematosus (SLE)

Comunicaciones a congreso

Expression of a barley cystatin gene in maize enhances resistance against phytophagous mites by altering their cysteine-proteases

Phytocystatins are inhibitors of cysteine-proteases from plants putatively involved in plant defence based on their capability of inhibit heterologous enzymes. We have previously characterised the whole cystatin gene family members from barley (HvCPI-1 to HvCPI-13). The aim of this study was to assess the effects of barley cystatins on two phytophagous spider mites, Tetranychus urticae and Brevipalpus chilensis. The determination of proteolytic activity profile in both mite species showed the presence of the cysteine-proteases, putative targets of cystatins, among other enzymatic activities. All barley cystatins, except HvCPI-1 and HvCPI-7, inhibited in vitro mite cathepsin L- and/or cathepsin B-like activities, HvCPI-6 being the strongest inhibitor for both mite species. Transgenic maize plants expressing HvCPI-6 protein were generated and the functional integrity of the cystatin transgene was confirmed by in vitro inhibitory effect observed against T. urticae and B. chilensis protein extracts. Feeding experiments impaired on transgenic lines performed with T. urticae impaired mite development and reproductive performance. Besides, a significant reduction of cathepsin L-like and/or cathepsin B-like activities was observed when the spider mite fed on maize plants expressing HvCPI-6 cystatin. These findings reveal the potential of barley cystatins as acaricide proteins to protect plants against two important mite pests

REA 3D-dynamic analysis in Almaraz NPP with RELAP5/PARCS v2.7 and SIMTAB cross-sections tables

[EN] The Rod Ejection Accident (REA) belongs to the Reactivity-Initiated Accidents (RIA) category of accidents and it is part of the licensing basis accident analyses required for pressurized water reactors (PWR). The REA at Hot Zero Power (HZP) is characterized by a single rod ejection from a core position with a very low power level. The evolution consists basically of a continuous reactivity insertion. The main feature limiting the consequences of the accident in a PWR is the Doppler Effect. To check the performance of the coupled code RELAP5/PARCS v2.7 a REA in Almaraz NPP is simulated. These analyses will allow knowing more accurately the PWR real plant phenomenology in the RIA most limiting conditions.This work has been partially supported by the Spanish Ministerio de Educación y Ciencia under project PHB2007-0067-PC and by the Brazilian Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) under project CAPES/DGU 159/08. This work has also been partially supported by the Spanish Ministerio de Educación y Ciencia under project ENE2008-02669, the Generalitat Valenciana under project ACOMP/2009/058, and the Universitat Politècnica de València under project PAID-05-09-4285. The authors wish to acknowledge the technical and financial support of the Almaraz-Trillo AIE for this work.Barrachina Celda, TM.; Garcia-Fenoll, M.; Ánchel Añó, FC.; Miró Herrero, R.; Verdú Martín, GJ.; Pereira, C.; Da Silva, C.... (2011). REA 3D-dynamic analysis in Almaraz NPP with RELAP5/PARCS v2.7 and SIMTAB cross-sections tables. Progress in Nuclear Energy. 53(8):1167-1180. https://doi.org/10.1016/j.pnucene.2011.07.012S1167118053

Optimized design of local shielding for the IFMIF/EVEDA beam dump

This paper describes the local shielding design process of the IFMIF/EVEDA Beam Dump and the most relevant results obtained from the simulations. Different geometries and materials have been considered, and the design has been optimized taking into account the origin of the doses, the effect of the walls of the accelerator vault and the space restrictions. The initial idea was to shield the beam stopper with a large water tank of easy transport and dismantling but it was shown to be insufficient to satisfy the dose limit requirements, basically due to photon dose, and hence a denser shield combining hydrogenous and heavy materials was preferred. It will be shown that, with this new shielding, dose rate outside the accelerator vault during operation comply with the legal limits and unrestricted maintenance operations inside most of the vault are possible after a reasonable cooling time after shutdown

Validation of 3D neutronic-thermalhydraulic coupled codes RELAP5/PARCSv2.7 and TRACEv5.0P3/PARCSv3.0 against a PWR control rod drop transient

[EN] In nuclear safety field, neutronic and thermalhydraulic codes performance is an important issue. New capabilities implementation, as well as models and tools improvements are a significant part of the community effort in looking for better Nuclear Power Plants (NPP) designs. A procedure to analyze the PWR response to local deviations on neutronic or thermalhydraulic parameters is being developed. This procedure includes the simulation of Incore and Excore neutron flux detectors signals. A control rod drop real plant transient is used to validate the used codes and their new capabilities. Cross-section data are obtained by means of the SIMTAB methodology. Detailed thermalhydraulic models were developed: RELAP5 and TRACE models simulate three different azimuthal zones. Besides, TRACE model is performed with a fully 3D core, thus, the cross-flow can be obtained. A cartesian vessel represents the fuel assemblies and a cylindrical vessel the bypass and downcomer. Simulated detectors signals are obtained and compared with the real data collected during a control rod drop trial at a PWR NPP and also with data obtained with SIMULATE-3K code.The authors would like to acknowledge the economic support provided by Centrales Nucleares Almaraz-Trillo (CNAT) and IBERDROLA Ingeniería y Construcción (Iberinco) for the realization of this work, and express their great appreciation to Arturo López, Juan Antonio Bermejo and Alberto Ortego for their valuable collaboration and their willingness to develop this work. This work has also been supported by the Spanish Ministerio de Economía y Competitividad, through the projects NUC-MULTPHYS (ENE2012-34585) and VALIUN-3D (ENE2011-22823), and the Generalitat Valenciana (GVA), through the project PROMETEO II/2014/008.Garcia-Fenoll, M.; Mesado Melia, C.; Barrachina, T.; Miró Herrero, R.; Verdú Martín, GJ.; Bermejo, JA.; López, A.... (2017). Validation of 3D neutronic-thermalhydraulic coupled codes RELAP5/PARCSv2.7 and TRACEv5.0P3/PARCSv3.0 against a PWR control rod drop transient. Journal of Nuclear Science and Technology. 54(8):908-919. https://doi.org/10.1080/00223131.2017.1329035S90891954

FUNCTIONAL GENOMICS IN PRIMARY T CELLS AND MONOCYTES IDENTIFIES MECHANISMS BY WHICH GENETIC SUSCEPTIBILITY LOCI INFLUENCE SYSTEMIC SCLEROSIS RISK.

Congresos y Conferencias: Comunicación de congreso- Conferencia invitada.Winner of EULAR 2022 Abstract Award in the category of Basic Scienc

Simvastatin inhibits TLR8 signaling in primary human monocytes and spontaneous TNF production from rheumatoid synovial membrane cultures

Simvastatin has been shown to have anti-inflammatory effects that are independent of its serum cholesterol lowering action, but the mechanisms by which these anti-inflammatory effects are mediated have not been elucidated. To explore the mechanism involved, the effect of simvastatin on Toll-like receptor (TLR) signalling in primary human monocytes was investigated. A short pre-treatment with simvastatin dose-dependently inhibited the production of tumor necrosis factor-α (TNF) in response to TLR8 (but not TLRs 2, 4, or 5) activation. Statins are known inhibitors of the cholesterol biosynthetic pathway, but intriguingly TLR8 inhibition could not be reversed by addition of mevalonate or geranylgeranyl pyrophosphate; downstream products of cholesterol biosynthesis. TLR8 signalling was examined in HEK 293 cells stably expressing TLR8, where simvastatin inhibited IKKα/β phosphorylation and subsequent NF-κB activation without affecting the pathway to AP-1. Since simvastatin has been reported to have anti-inflammatory effects in RA patients and TLR8 signalling contributes to TNF production in human RA synovial tissue in culture, simvastatin was tested in these cultures. Simvastatin significantly inhibited the spontaneous release of TNF in this model which was not reversed by mevalonate. Together, these results demonstrate a hitherto unrecognized mechanism of simvastatin inhibition of TLR8 signalling that may in part explain its beneficial anti-inflammatory effects

A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort

<p><b>Objectives</b> The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features.</p> <p><b>Methods</b> A total of 8 European populations of Caucasian ancestry were included, comprising 3014 patients with SSc and 3125 healthy controls. Four genetic variants of TNFSF4 gene promoter (rs1234314, rs844644, rs844648 and rs12039904) were selected as genetic markers.</p> <p><b>Results</b> A pooled analysis revealed the association of rs1234314 and rs12039904 polymorphisms with SSc (OR 1.15, 95% CI 1.02 to 1.31; OR 1.18, 95% CI 1.08 to 1.29, respectively). Significant association of the four tested variants with patients with limited cutaneous SSc (lcSSc) was revealed (rs1234314 OR 1.22, 95% CI 1.07 to 1.38; rs844644 OR 0.91, 95% CI 0.83 to 0.99; rs844648 OR 1.10, 95% CI 1.01 to 1.20 and rs12039904 OR 1.20, 95% CI 1.09 to 1.33). Association of rs1234314, rs844648 and rs12039904 minor alleles with patients positive for anti-centromere antibodies (ACA) remained significant (OR 1.23, 95% CI 1.10 to 1.37; OR 1.12, 95% CI 1.01 to 1.25; OR 1.22, 95% CI 1.07 to 1.38, respectively). Haplotype analysis confirmed a protective haplotype associated with SSc, lcSSc and ACA positive subgroups (OR 0.88, 95% CI 0.82 to 0.96; OR 0.88, 95% CI 0.80 to 0.96; OR 0.86, 95% CI 0.77 to 0.97, respectively) and revealed a new risk haplotype associated with the same groups of patients (OR 1.14, 95% CI 1.03 to 1.26; OR 1.20, 95% CI 1.08 to 1.35; OR 1.23, 95% CI 1.07 to 1.42, respectively).</p> <p><b>Conclusions</b> The data confirm the influence of TNFSF4 polymorphisms in SSc genetic susceptibility, especially in subsets of patients positive for lcSSc and ACA.</p&gt