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Digital.CSIC (162.855 recursos)

Repositorio institucional del Consejo Superior de Investigaciones Científicas. Digital.CSIC es un depósito de documentos digitales, cuyo objetivo es organizar, archivar, preservar y difundir en modo de acceso abierto la producción intelectual resultante de la actividad investigadora del CSIC.

(IPBLN) Artículos post-print

Mostrando recursos 1 - 16 de 16

  1. Characterization of an immunodominant antigenic epitope from Trypanosoma cruzi as a biomarker of chronic Chagas' disease pathology

    Thomas, María del Carmen; Fernández-Villegas, A.; Carrilero, Bartolomé; Marañón, Concepción; Saura, Daniel; Noya, Óscar; Segovia, Manuel; Alarcón de Noya, Belkisyolé; Alonso, Carlos; López López, Manuel Carlos
    Nowadays, the techniques available for chronic Chagas' disease diagnosis are very sensitive; however, they do not allow discrimination of the patient's clinical stages of the disease. The present paper describes that three out of the five different repeats contained in the Trypanosoma cruzi TcCA-2 membrane protein (3972-FGQAAAGDKPPP, 6303-FGQAAAGDKPAP, and 3973-FGQ AAAGDKPSL) are recognized with high sensitivity (>90%) by sera from chronic Chagas' disease patients and that they are not recognized by sera from patients in the acute phase of the disease. A total of 133 serum samples from chagasic patients and 50 serum samples from healthy donors were tested. In...

  2. Efficient HIV-1 inhibition by a 16 nt-long RNA aptamer designed by combining in vitro selection and in silico optimisation strategies

    Sánchez-Luque, Francisco J.; Stich, Michael; Manrubia Cuevas, Susanna; Briones, Carlos; Berzal-Herranz, Alfredo
    The human immunodeficiency virus type-1 (HIV-1) genome contains multiple, highly conserved structural RNA domains that play key roles in essential viral processes. Interference with the function of these RNA domains either by disrupting their structures or by blocking their interaction with viral or cellular factors may seriously compromise HIV-1 viability. RNA aptamers are amongst the most promising synthetic molecules able to interact with structural domains of viral genomes. However, aptamer shortening up to their minimal active domain is usually necessary for scaling up production, what requires very time-consuming, trial-and-error approaches. Here we report on the in vitro selection of 64...

  3. A candidate gene approach identifies an IL33 genetic variant as a novel genetic risk factor for GCA

    Márquez, Ana; Solans, Roser; Hernández-Rodríguez, José; Cid, María C.; Castañeda, S.; Ramentol, Marc; Rodriguez-Rodriguez, Luis; Narváez, J.; Blanco, Ricardo; Ortego-Centeno, N.; Palm, Øyvind; Diamantopoulos, Andreas P.; Braun, N.; Moosig, Frank; Witte, Torsten; Beretta, Lorenzo; Lunardi, C.; Cimmino, Augusto Vaglio; Salvarani, C.; González-Gay, M. A.; Martín, J.
    © 2014 Márquez et al. Introduction: Increased expression of IL-33 and its receptor ST2, encoded by the IL1RL1 gene, has been detected in the inflamed arteries of giant cell arteritis (GCA) patients. The aim of the present study was to investigate for the first time the potential influence of the IL33 and IL1RL1 loci on GCA predisposition. Methods: A total of 1,363 biopsy-proven GCA patients and 3,908 healthy controls from four European cohorts (Spain, Italy, Germany and Norway) were combined in a meta-analysis. Six genetic variants: rs3939286, rs7025417 and rs7044343, within the IL33 gene, and rs2058660, rs2310173 and rs13015714, within...

  4. Two Functional Variants of IRF5 Influence the Development of Macular Edema in Patients with Non-Anterior Uveitis

    Márquez, Ana; Cénit, M.C.; Cordero-Coma, Miguel; Ortego-Centeno, Norberto; Adán, Alfredo; Fonollosa, Alejandro; Díaz Valle, David; Pato, Esperanza; Blanco, Ricardo; Cañal, Joaquín; Díaz-Llopis, Manuel; Ramón, Enrique de; Rio, María J. del; García Serrano, José L.; Artaraz, Joseba; Martín-Villa, José M.; Llorenç, Victor; Gorroño-Echebarría, M.B.; Martín, J.
    Objective:Interferon (IFN) signaling plays a crucial role in autoimmunity. Genetic variation in interferon regulatory factor 5 (IRF5), a major regulator of the type I interferon induction, has been associated with risk of developing several autoimmune diseases. In the current study we aimed to evaluate whether three sets of correlated IRF5 genetic variants, independently associated with SLE and with different functional roles, are involved in uveitis susceptibility and its clinical subphenotypes.Methods:Three IRF5 polymorphisms, rs2004640, rs2070197 and rs10954213, representative of each group, were genotyped using TaqMan® allelic discrimination assays in a total of 263 non-anterior uveitis patients and 724 healthy controls of...

  5. Analysis of the Interferon Gamma (rs2430561, +874T/A) Functional Gene Variant in Relation to the Presence of Cardiovascular Events in Rheumatoid Arthritis

    García-Bermúdez, Mercedes; López-Mejías, Raquel; González-Juanatey, Carlos; Corrales, Alfonso; Robledo, G.; Castañeda, S.; Miranda-Filloy, J.A.; Blanco, Ricardo; Fernández-Gutiérrez, B.; Balsa, Alejandro; González-Alvaro, I.; Gómez-Vaquero, C.; Llorca, Javier; Martín, J.; González-Gay, M. A.
    Objective: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular (CV) morbidity and mortality. Since interferon-gamma (IFN-γ) has a direct effect on inflammation, in this study we assessed the potential association of the IFNG functional gene variant rs2430561 with CV disease in patients with RA. Methods: One thousand six hundred and thirty-five patients fulfilling the 1987 American College of Rheumatology classification criteria for RA were genotyped for the IFNG (rs2430561, +874T/A) gene polymorphism using TaqMan genotyping assay. Patients were stratified according to the presence of CV events or not. Logistic regression models to explain the presence of...

  6. Ghrelin protects against experimental sepsis by inhibiting high-mobility group box 1 release and by killing bacteria

    Chorny, Alejo; Anderson, Per; Gonzalez-Rey, E.; Delgado, M
    Sepsis, a life-threatening complication of infections and the most common cause of death in intensive care units, is characterized by a hyperactive and out-of-balance network of endogenous proinflammatory cytokines. None of the current therapies are entirely effective, illustrating the need for novel therapeutic approaches. Ghrelin (GHR) is an orexigenic peptide that has emerged as a potential endogenous anti-inflammatory factor. In this study, we show that the delayed administration of GHR protects against the mortality in various models of established endotoxemia and sepsis. The therapeutic effect of GHR is mainly mediated by decreasing the secretion of the high mobility box 1...

  7. NPSR1 gene is associated with reduced risk of rheumatoid arthritis

    Robledo, G.; González-Gay, M. A.; Fernández-Gutiérrez, B.; Lamas, José Ramón; Balsa, A.; Pascual-Salcedo, Dora; Castañeda, S.; Blanco, Ricardo; González-Alvaro, I.; García, Antonio Hidalgo; Raya-Álvarez, E.; Gómez-Vaquero, C.; Delgado, M.; Martín, J.
    Objective. Neuropeptide S receptor 1 (NPSR1) is a G protein-coupled receptor involved in immune response and is associated with several inflammatory diseases. We investigated the possible contribution of several polymorphisms in the intronic region of NPSR1 to rheumatoid arthritis (RA). Methods. Genotyping of 7 single-nucleotide polymorphisms (SNP) was performed in a total of 1232 patients with RA and 983 healthy controls of Spanish white origin by real-time polymerase chain reaction technology, using the TaqMan 5'-allele discrimination assay. Results. One out of the 7 SNP analyzed (rs740347) was associated with RA [p after Bonferroni correction (pBNF) = 1.2 × 10 -3,...

  8. The endocytic adaptor Numb regulates thymus size by modulating pre-TCR signaling during asymmetric division

    Aguado, Rocío; Martín-Blanco, Nadia M.; Caraballo, Michael; Canelles, Matilde
    Stem cells must proliferate and differentiate to generate the lineages that shape mature organs; understanding these 2 processes and their interaction is one of the central themes in current biomedicine. An intriguing aspect is asymmetric division, by which 2 daughter cells with different fates are generated. Several cell fate determinants participate in asymmetric division, with the endocytic adaptor Numb as the best-known example. Here, we have explored the role of asymmetric division in thymocyte development, visualizing the differential segregation of Numb and pre-TCR in thymic precursors. Analysis of mice where Numb had been inhibited by expressing a dominant negative revealed...

  9. Characterization of the MAL2-positive compartment in oligodendrocytes

    Bello-Morales, R.; Marco, M. Carmen de; Aranda, J. F.; Matesanz, F.; Alcina, Antonio; López-Guerrero, J. A.
    Oligodendrocytes (OLs), the myelin-producing cells of the central nervous system, segregate different surface subdomains at the plasma membrane as do other differentiated cells such as polarized epithelia and neurons. To generate the complex membrane system that characterizes myelinating OLs, large amounts of membrane proteins and lipids need to be synthesized and correctly targeted. In polarized epithelia, a considerable fraction of apical proteins are transported by an indirect pathway involving a detour to the basolateral membrane before being internalized and transported across the cell to the apical membrane by a process known as transcytosis. The apical recycling endosome (ARE) or its...

  10. Stimulation of phosphatidylinositol turnover is a key event for fas-dependent, activation-induced apoptosis in human T lymphocyte

    Izquierdo, Manuel; Ruiz-Ruiz, M. Carmen; López-Rivas, Abelardo
    We have analyzed the requirements for activation-induced apoptosis in Jurkat T cells expressing the heterologous human muscarinic type 1 receptor (HM1R; J-HM1-2.2 cells) that is coupled to phosphatidylinositol turnover through a protein tyrosine kinase-independent, G protein-regulated mechanism. Triggering of HM1R with the agonist carbachol is sufficient to induce apoptosis in J-HM1-2.2 cells. Apoptosis is also induced in J-HM1-2.2 cells by triggering of the TCR. Calcium influx, intracellular Ca2+ increase, calcineurin function, and de novo protein synthesis are necessary for receptor-controlled apoptosis. However, blocking protein kinase C with a specific inhibitor does not abrogate receptor-induced apoptosis. Furthermore, HM1R-induced apoptosis is inhibited...

  11. Lack of association of a functional single nucleotide polymorphism of PTPN22, encoding lymphoid protein phosphatase, with susceptibility to biopsy-proven giant cell arteritis

    González-Gay, M. A.; Oliver, Francisco Javier; Orozco, G.; García-Porrua, C.; López-Nevot, M. A.; Martín, J.
    Objective. To assess the possible association between PTPN22 1858C→T polymorphism and susceptibility to giant cell arteritis (GCA) and to determine if this polymorphism is implicated in the clinical expression of this vasculitis. Methods. Ninety-six patients with biopsy-proven GCA and 229 ethnically matched controls from the Lugo region of Northwest Spain were studied using molecular methods. All individuals were of Spanish Caucasian origin. Genotyping of PTPN22 gene 1858C→T polymorphism was performed by real time polymerase chain reaction technology, using TaqMan 5′ allelic discrimination assay. Results. No significant differences in allele or genotype frequencies for PTPN22 polymorphism were observed between patients with...

  12. Association of a functional inducible nitric oxide synthase promoter variant with susceptibility to biopsy-proven giant cell arteritis

    González-Gay, M. A.; Oliver, Francisco Javier; Sánchez, Elena; García-Porrua, C.; Paco, Laura; López-Nevot, M. A.; Ollier, W. E. R.; Martín, J.
    Objective. To assess the contribution of 2 polymorphisms within the inducible nitric oxide (NOS2A) promoter region to susceptibility to giant cell arteritis (GCA). Methods. One hundred three patients with biopsy-proven GCA and 198 ethnically matched controls from the Lugo region (Northwest Spain) were studied. Patients and controls were genotyped using polymerase chain reaction techniques for a multiallelic (CCTTT)n and for the TAAA repeat polymorphism in the promoter region of the NOS2A gene. Results. No significant differences in allele or genotype frequencies for the (CCTTT)n repeat polymorphism in the NOS2A gene between patients with GCA and controls were observed. However, significant...

  13. Cutting edge: Natural DNA repetitive extragenic sequences from gram-negative pathogens strongly stimulate TLR9

    Magnusson, M.; Tobes, R.; Sancho, Jaime; Pareja, E.
    Bacterial DNA exerts immunostimulatory effects on mammalian cells via the intracellular TLR9. Although broad analysis of TLR9-mediated immunostimulatory potential of synthetic oligonucleotides has been developed, which kinds of natural bacterial DNA sequences are responsible for immunostimulation are not known. This work provides evidence that the natural DNA sequences named repetitive extragenic palindromic (REPs) sequences present in Gram-negative bacteria are able to produce innate immune system stimulation via TLR9. A strong induction of IFN-α production by REPs from Escherichia coli, Salmonella enterica, Pseudomonas aeruginosa, and Neisseria meningitidis was detected in splenocytes from 129 mice. In addition, the involvement of TLR9 in...

  14. RNA self-cleavage activated by ultraviolet light-induced oxidation

    Ariza-Mateos, Ascensión; Prieto-Vega, S.; Díaz-Toledano, Rosa; Birk, A.; Szeto, H.; Mena, I.; Berzal-Herranz, Alfredo; Gómez, J.
    A novel UV-C-light-induced ribozyme activity was discovered within the highly structured 5′-genomic regions of both Hepatitis C Virus (HCV) and the related Classic Swine Fever Virus (CSFV). Cleavage is mediated by exposure to UV-C light but not by exogenous oxygen radicals. It is also very selective, occurring at base positions HCV C 79 and CSFV A45 in some molecules and at the immediately adjacent 5′-positions HCV U 78 and CSFV U 44 in others. Among other reaction products, the majority of biochemically active products detected contained 3′-phosphate and 5′-phosphate-end groups at the newly generated termini, along with a much lower...

  15. Differential association of two PTPN22 coding variants with Crohn’s disease and ulcerative colitis

    Díaz-Gallo, L. M.; Gómez-García, M.; Mendoza, Juan L.; Taxonera, Carlos; Nieto, M. Ángela; López-Nevot, M. A.; Alizadeh, B. Z.; Martín, J.
    2 páginas.-- Póster presentado al 5º European Workshop on Immune-Mediated Inflammatory Diseases celebrado en Sitges (Barcelona) dxel 1 al 3 de Diciembre de 2010.-- et al.

  16. Analysis of LMP and TAP polymorphisms by polymerase chain reaction-restriction fragment length polymorphism in rheumatoid arthritis

    Vinasco, J.; Fraile, A.; Nieto, M. Ángela; Beraun, Y.; Pareja, E.; Mataran, L.; Martín, J.
    5 pages, 1 figure, 2 tables.-- PMID: 9536820 [PubMed].-- PMCID: PMC1752462.

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