Els Plans locals de joventut: una forma de participació juvenil

Aquest treball neix de l’interès per conèixer quin és el funcionament dels Plans Locals de Joventut (PLJ), com a instrument per treballar les polítiques de joventut, i el paper de la participació juvenil entorn aquest context. La temàtica principal és els PLJ però en relació amb la participació, el jovent i les polítiques de joventut actuals

New insights into trypanosomatid U5 small nuclear ribonucleoproteins

Several protozoan parasites exist in the Trypanosomatidae family, including various agents of human diseases. Multiple lines of evidence suggest that important differences are present between the translational and mRNA processing (trans splicing) systems of trypanosomatids and other eukaryotes. In this context, certain small complexes of RNA and protein, which are named small nuclear ribonucleoproteins (U snRNPs), have an essential role in pre-mRNA processing, mainly during splicing. Even though they are well defined in mammals, snRNPs are still not well characterized in trypanosomatids. This study shows that a U5-15K protein is highly conserved among various trypanosomatid species. Tandem affinity pull-down assays revealed that this protein interacts with a novel U5-102K protein, which suggests the presence of a sub-complex that is potentially involved in the assembly of U4/U6-U5 tri-snRNPs. Functional analyses showed that U5-15K is essential for cell viability and is somehow involved with the trans and cis splicing machinery. Similar tandem affinity experiments with a trypanonosomatid U5-Cwc21 protein led to the purification of four U5 snRNP specific proteins and a Sm core, suggesting U5-Cwc-21 participation in the 35S U5 snRNP particle. Of these proteins, U5-200K was molecularly characterized. U5-200K has conserved domains, such as the DEAD/DEAH box helicase and Sec63 domains and displays a strong interaction with U5 snRNA.

Gene transfer of interleukin-18-binding protein attenuates cardiac allograft rejection.

Interleukin (IL) 18 is a potent pro-inflammatory Th1 cytokine that exerts pleiotropic effector functions in both innate and acquired immune responses. Increased IL-18 production during acute rejection has been reported in experimental heart transplantation models and in kidney transplant recipients. IL-18-binding protein (IL-18BP) binds IL-18 with high affinity and neutralizes its biologic activity. We have analyzed the efficacy of an adenoviral vector expressing an IL-18BP-Ig fusion protein in a rat model of heart transplantation. IL-18BP-Ig gene transfer into Fisher (F344) rat donor hearts resulted in prolonged graft survival in Lewis recipients (15.8 +/- 1.4 days vs. 10.3 +/- 2.5 and 10.1 +/- 2.1 days with control virus and buffer solution alone, respectively; P < 0.001). Immunohistochemical analysis revealed decreased intra-graft infiltrates of monocytes/macrophages, CD4(+), CD8alpha(+) and T-cell receptor alphabeta(+) cells after IL-18BP-Ig versus mock gene transfer (P < 0.05). Real-time reverse transcriptase polymerase chain reaction analysis showed decreased cytokine transcripts for the RANTES chemokine and transforming growth factor-beta after IL-18BP-Ig gene transfer (P < 0.05). IL-18BP-Ig gene transfer attenuates inflammatory cell infiltrates and prolongs cardiac allograft survival in rats. These results suggest a contributory role for IL-18 in acute rejection. Further studies aiming at defining the therapeutic potential of IL-18BP are warranted.

Projecte d'ampliació d'una nau destinada a l'exposició i venda de materials de construcció

El peticionari és el propietari d’una nau industrial aïllada del terme municipal de Cassà de la Selva destinada a la venda i exposició de materials per a la construcció. A causa de la creixent demanda en el sector es vol ampliar la superfície de la nau, amb la intenció d’augmentar la zona comercial. El disseny i càlcul de l’ampliació de la nau aïllada inclou moviment de terres, fonaments, estructura, tancaments, coberta, paviments, obra de paleta, fusteria, i pintura. També s’inclourà el disseny i càlcul de les instal·lacions (aigua, baixa tensió, il·luminació, climatització, ventilació, contra incendis, plaques solars, sanejament) de l’ampliació

Efficient generation of human alloantigen-specific CD4+ regulatory T cells from naive precursors by CD40-activated B cells.

CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) play an important role in the induction and maintenance of immune tolerance. Although adoptive transfer of bulk populations of Treg can prevent or treat T cell-mediated inflammatory diseases and transplant allograft rejection in animal models, optimal Treg immunotherapy in humans would ideally use antigen-specific rather than polyclonal Treg for greater specificity of regulation and avoidance of general suppression. However, no robust approaches have been reported for the generation of human antigen-specific Treg at a practical scale for clinical use. Here, we report a simple and cost-effective novel method to rapidly induce and expand large numbers of functional human alloantigen-specific Treg from antigenically naive precursors in vitro using allogeneic nontransformed B cells as stimulators. By this approach naive CD4(+)CD25(-) T cells could be expanded 8-fold into alloantigen-specific Treg after 3 weeks of culture without any exogenous cytokines. The induced alloantigen-specific Treg were CD45RO(+)CCR7(-) memory cells, and had a CD4(high), CD25(+), Foxp3(+), and CD62L (L-selectin)(+) phenotype. Although these CD4(high)CD25(+)Foxp3(+) alloantigen-specific Treg had no cytotoxic capacity, their suppressive function was cell-cell contact dependent and partially relied on cytotoxic T lymphocyte antigen-4 expression. This approach may accelerate the clinical application of Treg-based immunotherapy in transplantation and autoimmune diseases.

Desarrollo de un método para acoplar arenos a metalacarboranos

El uso de metalacarboranos en la síntesis de compuestos aril-cobaltobis(dicarballuro) ha despertado un nuevo tema de interés y de estudio en el grupo de Síntesi Inorgànica i Catàlisi del ICMAB-CSIC. Los metalacarboranos presentan diversas aplicaciones innovadoras como la BNCT (Boron Neutron Capture Therapy), el tratamiento de aguas residuales, actividades catalíticas, como agentes dopantes en membranas poliméricas conductoras, y como integrantes en sensores potenciométricos, entre otros. El principal objetivo de este trabajo de investigación ha consistido en desarrollar un método de acoplamiento B–C sobre el anión sándwich [3,3’-Co-(1,2-C2B9H11)2]- para la formación de nuevos derivados aril-cobalto-bis(dicarballuro); éstos se han sintetizado por su posible capacidad fotoactiva. Este acoplamiento transcurre mediante una reacción de sustitución electrófila aromática (SEAr) sobre el anillo aromático o desde la óptica del metalacarborano, mediante una sustitución nucleófila inducida electrofilicamente (EINS). Dicha reacción requiere el uso de un ácido de Lewis como catalizador. El hecho que se haya utilizado AlCl3 como catalizador, hace que la reacción que se desarrolla en este trabajo recuerde de alguna manera a una reacción de Friedel-Crafts, pese a que la reacción está dirigida a la formación de un enlace B–C mediado por un ácido de Lewis. El principal problema de las reacciones de Friedel-Crafts es la elevada cantidad de areno que se precisa para llevar a cabo la reacción, debido a que el disolvente empleado puede actuar como fuente de electrófilos. El procedimiento empleado en nuestro caso utiliza el mesitileno como disolvente, el cual posee un gran impedimento estérico y un alto punto de ebullición. De esta manera, se puede realizar esta reacción utilizando entre 1.5 y 10 equivalentes de areno respecto al cobalto-bis(dicarballuro) sin que el disolvente actúe como reactivo. Se han estudiado y optimizado las condiciones experimentales para que el método sintético que genera el enlace B–C sea lo más universal posible para cualquier tipo de anillo aromático. Se han probado una gran diversidad de anillos aromáticos, desde anillos aromáticos fuertemente activados a los más desactivados, así como anillos aromáticos heterocíclicos. Finalmente, las condiciones de síntesis extraídas de este estudio son muy satisfactorias para los anillos activados probados y para los anillos débilmente desactivados. En cambio, para los arenos fuertemente desactivados, los rendimientos de la reacción han sido bajos. Por otro lado, las pruebas realizadas sobre los anillos heterocíclicos no han sido exitosas y no se ha producido el acoplamiento B–C.

A genome-wide association search for type 2 diabetes genes in African Americans.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.

Theory of mind and social functioning in first episode psychosis

There is evidence of associations between social functioning and theory of mind performance and between social functioning and negative symptoms in chronic psychosis. This study investigates these associations in those with first episode psychosis who are unaffected by factors related to long-term mental illness. Our first hypothesis states that there is an association between theory of mind and social functioning. The second hypothesis states that there is no association between symptoms of psychosis and social functioning. Methods. Fifty-two individuals with first episode psychosis were assessed for social functioning, theory of mind ability (using the Hinting test with verbal stimuli and the Visual Cartoon test with pictorial stimuli), and symptoms of psychosis. Multivariable logistic regression was used to examine associations. Results. Social functioning and theory of mind were associated when measured by the Hinting test (OR 1.70, 95% CI 1.08, 2.66), but not with the Visual Cartoon test (ToM jokes OR 0.61, 95% CI 0.15, 2.53). There was no association between social functioning and symptoms (psychotic symptoms; OR 0.95, 95% CI 0.81, 1.12; selected negative symptoms; OR 1.33, 95% CI 0.78, 2.25). Conclusions. Theory of mind assessed by verbal stimuli is associated with social functioning in a population with first episode psychosis. These findings may be related to language disorders in psychosis.

Anti-vascular endothelial growth factor acts on retinal microglia/macrophage activation in a rat model of ocular inflammation.

PURPOSE: To evaluate whether anti-vascular endothelial growth factor (VEGF) neutralizing antibodies injected in the vitreous of rat eyes influence retinal microglia and macrophage activation. To dissociate the effect of anti-VEGF on microglia and macrophages subsequent to its antiangiogenic effect, we chose a model of acute intraocular inflammation. METHODS: Lewis rats were challenged with systemic lipopolysaccharide (LPS) injection and concomitantly received 5 µl of rat anti-VEGF-neutralizing antibody (1.5 mg/ml) in the vitreous. Rat immunoglobulin G (IgG) isotype was used as the control. The effect of anti-VEGF was evaluated at 24 and 48 h clinically (uveitis scores), biologically (cytokine multiplex analysis in ocular media), and histologically (inflammatory cell counts on eye sections). Microglia and macrophages were immunodetected with ionized calcium-binding adaptor molecule 1 (IBA1) staining and counted based on their differential shapes (round amoeboid or ramified dendritiform) on sections and flatmounted retinas using confocal imaging and automatic quantification. Activation of microglia was also evaluated with inducible nitric oxide synthase (iNOS) and IBA1 coimmunostaining. Coimmunolocalization of VEGF receptor 1 and 2 (VEGF-R1 and R2) with IBA1 was performed on eye sections with or without anti-VEGF treatment. RESULTS: Neutralizing rat anti-VEGF antibodies significantly decreased ocular VEGF levels but did not decrease the endotoxin-induced uveitis (EIU) clinical score or the number of infiltrating cells and cytokines in ocular media (interleukin [IL]-1β, IL-6, tumor necrosis factor [TNF]-α, and monocyte chemoattractant protein [MCP]-1). Eyes treated with anti-VEGF showed a significantly decreased number of activated microglia and macrophages in the retina and the choroid and decreased iNOS-positive microglia. IBA1-positive cells expressed VEGF-R1 and R2 in the inflamed retina. CONCLUSIONS: Microglia and macrophages expressed VEGF receptors, and intravitreous anti-VEGF influenced the microglia and macrophage activation state. Taking into account that anti-VEGF drugs are repeatedly injected in the vitreous of patients with retinal diseases, part of their effects could result from unsuspected modulation of the microglia activation state. This should be further studied in other ocular pathogenic conditions and human pathology.

Liver safety assessment: required data elements and best practices for data collection and standardization in clinical trials.

A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials. In a breakout session, workshop attendees discussed necessary data elements and standards for the accurate measurement of DILI risk associated with new therapeutic agents in clinical trials. There was agreement that in order to achieve this goal the systematic acquisition of protocol-specified clinical measures and lab specimens from all study subjects is crucial. In addition, standard DILI terms that address the diverse clinical and pathologic signatures of DILI were considered essential. There was a strong consensus that clinical and lab analyses necessary for the evaluation of cases of acute liver injury should be consistent with the US Food and Drug Administration (FDA) guidance on pre-marketing risk assessment of DILI in clinical trials issued in 2009. A recommendation that liver injury case review and management be guided by clinicians with hepatologic expertise was made. Of note, there was agreement that emerging DILI signals should prompt the systematic collection of candidate pharmacogenomic, proteomic and/or metabonomic biomarkers from all study subjects. The use of emerging standardized clinical terminology, CRFs and graphic tools for data review to enable harmonization across clinical trials was strongly encouraged. Many of the recommendations made in the breakout session are in alignment with those made in the other parallel sessions on methodology to assess clinical liver safety data, causality assessment for suspected DILI, and liver safety assessment in special populations (hepatitis B, C, and oncology trials). Nonetheless, a few outstanding issues remain for future consideration.

Adaptation of AHRQ patient safety indicators for use in ICD-10 administrative data by an international consortium.

Objective: The Agency for Healthcare Research and Quality (AHRQ) developed Patient Safety Indicators (PSIs) for use with ICD-9-CM data. Many countries have adopted ICD-10 for coding hospital diagnoses. We conducted this study to develop an internationally harmonized ICD-10 coding algorithm for the AHRQ PSIs. Methods: The AHRQ PSI Version 2.1 has been translated into ICD-10-AM (Australian Modification), and PSI Version 3.0a has been independently translated into ICD-10-GM (German Modification). We converted these two country-specific coding algorithms into ICD-10-WHO (World Health Organization version) and combined them to form one master list. Members of an international expert panel-including physicians, professional medical coders, disease classification specialists, health services researchers, epidemiologists, and users of the PSI-independently evaluated this master list and rated each code as either "include," "exclude," or "uncertain," following the AHRQ PSI definitions. After summarizing the independent rating results, we held a face-to-face meeting to discuss codes for which there was no unanimous consensus and newly proposed codes. A modified Delphi method was employed to generate a final ICD-10 WHO coding list. Results: Of 20 PSIs, 15 that were based mainly on diagnosis codes were selected for translation. At the meeting, panelists discussed 794 codes for which consensus had not been achieved and 2,541 additional codes that were proposed by individual panelists for consideration prior to the meeting. Three documents were generated: a PSI ICD-10-WHO version-coding list, a list of issues for consideration on certain AHRQ PSIs and ICD-9-CM codes, and a recommendation to WHO to improve specification of some disease classifications. Conclusion: An ICD-10-WHO PSI coding list has been developed and structured in a manner similar to the AHRQ manual. Although face validity of the list has been ensured through a rigorous expert panel assessment, its true validity and applicability should be assessed internationally.

PUC: préstamo consorciado de las bibliotecas del CBUC

Se describe brevemente el estado de la cuestión sobre el préstamo interbibliotecario (PI) consorciado a nivel internacional, y se explican las limitaciones del anterior servicio de PI del Consorci de Biblioteques Universitàries de Catalunya (CBUC) y su evolución hacia el nuevo servicio de préstamo de libros, el PUC, que se ha implementado recientemente. Se detalla la selección del software, el reglamento, la logística del PUC y su funcionamiento técnico. Se destacan las mejoras que ha supuesto el PUC como la de ser un servicio iniciado por el propio usuario, que puede pedir el libro a través del Catàleg Col·lectiu de les Universitats de Catalunya (CCUC) directamente a la biblioteca que lo tiene, sin mediación del personal de biblioteca y la reducción del tiempo de espera y de costes que esto supone.

Pathways for the synthesis of polyesters in plants; cutin, suberin, and polyhydroxyalkanoates

Plants naturally produce the lipid-derived polyester cutin, which is found in the plant cuticle that is deposited at the outermost extracellular matrix of the epidermis covering nearly all aboveground tissues. Being at the interface between the cell and the external environment, cutin and the cuticle play important roles in the protection of plants from several stresses. A number of enzymes involved in the synthesis of cutin monomers have recently been identified, including several P450s and one acyl-CoA synthetase, thus representing the first steps toward the understanding of polyester formation and, potentially, polyester engineering to improve the tolerance of plants to stresses, such as drought, and for industrial applications. However, numerous processes underlying cutin synthesis, such as a controlled polymerization, still remain elusive. Suberin is a second polyester found in the extracellular matrix, most often synthesized in root tissues and during secondary growth. Similar to cutin, the function of suberin is to seal off the respective tissue to inhibit water loss and contribute to resistance to pathogen attack. Being the main constituent of cork, suberin is a plant polyester that has already been industrially exploited. Genetic engineering may be worth exploring in order to change the polyester properties for either different applications or to increase cork production in other species. Polyhydroxyalkanoates (PHAs) are attractive polyesters of 3-hydroxyacids because of their properties as bioplastics and elastomers. Although PHAs are naturally found in a wide variety of bacteria, biotechnology has aimed at producing these polymers in plants as a source of cheap and renewable biodegradable plastics. Synthesis of PHA containing various monomers has been demonstrated in the cytosol, plastids, and peroxisomes of plants. Several biochemical pathways have been modified in order to achieve this, including the isoprenoid pathway, the fatty acid biosynthetic pathway, and the fatty acid β-oxidation pathway. PHA synthesis has been demonstrated in a number of plants, including monocots and dicots, and up to 40% PHA per gram dry weight has been demonstrated in Arabidopsis thaliana. Despite some successes, production of PHA in crop plants remains a challenging project. PHA synthesis at high level in vegetative tissues, such as leaves, is associated with chlorosis and reduced growth. The challenge for the future is to succeed in synthesis of PHA copolymers with a narrow range of monomer compositions, at levels that do not compromise plant productivity. This goal will undoubtedly require a deeper understanding of plant biochemical pathways and how carbon fluxes through these pathways can be manipulated, areas where plant "omics" can bring very valuable contributions.

Adaptation au codage CIM-10 de 15 indicateurs de la sécurité des patients proposés par l'Agence étasunienne pour la recherche et la qualité des soins de santé (AHRQ) [ICD-10 adaptation of 15 Agency for Healthcare Research and Quality patient safety indicators].

BACKGROUND: In the United States, the Agency for Healthcare Research and Quality (AHRQ) has developed 20 Patient Safety Indicators (PSIs) to measure the occurrence of hospital adverse events from medico-administrative data coded according to the ninth revision of the international classification of disease (ICD-9-CM). The adaptation of these PSIs to the WHO version of ICD-10 was carried out by an international consortium. METHODS: Two independent teams transcoded ICD-9-CM diagnosis codes proposed by the AHRQ into ICD-10-WHO. Using a Delphi process, experts from six countries evaluated each code independently, stating whether it was "included", "excluded" or "uncertain". During a two-day meeting, the experts then discussed the codes that had not obtained a consensus, and the additional codes proposed. RESULTS: Fifteen PSIs were adapted. Among the 2569 proposed diagnosis codes, 1775 were unanimously adopted straightaway. The 794 remaining codes and 2541 additional codes were discussed. Three documents were prepared: (1) a list of ICD-10-WHO codes for the 15 adapted PSIs; (2) recommendations to the AHRQ for the improvement of the nosological frame and the coding of PSI with ICD-9-CM; (3) recommendations to the WHO to improve ICD-10. CONCLUSIONS: This work allows international comparisons of PSIs among the countries using ICD-10. Nevertheless, these PSIs must still be evaluated further before being broadly used.

Investigating the genetic variation underlying episodicity in major depressive disorder: Suggestive evidence for a bipolar contribution.

BACKGROUND: Highly recurrent major depressive disorder (MDD) has reportedly increased risk of shifting to bipolar disorder; high recurrence frequency has, therefore, featured as evidence of 'soft bipolarity'. We aimed to investigate the genetic underpinnings of total depressive episode count in recurrent MDD. METHODS: Our primary sample included 1966 MDD cases with negative family history of bipolar disorder from the RADIANT studies. Total episode count was adjusted for gender, age, MDD duration, study and center before being tested for association with genotype in two separate genome-wide analyses (GWAS), in the full set and in a subset of 1364 cases with positive family history of MDD (FH+). We also calculated polygenic scores from the Psychiatric Genomics Consortium MDD and bipolar disorder studies. RESULTS: Episodicity (especially intermediate episode counts) was an independent index of MDD familial aggregation, replicating previous reports. The GWAS produced no genome-wide significant findings. The strongest signals were detected in the full set at MAGI1 (p=5.1×10(-7)), previously associated with bipolar disorder, and in the FH+ subset at STIM1 (p=3.9×10(-6) after imputation), a calcium channel signaling gene. However, these findings failed to replicate in an independent Munich cohort. In the full set polygenic profile analyses, MDD polygenes predicted episodicity better than bipolar polygenes; however, in the FH+ subset, both polygenic scores performed similarly. LIMITATIONS: Episode count was self-reported and, therefore, subject to recall bias. CONCLUSIONS: Our findings lend preliminary support to the hypothesis that highly recurrent MDD with FH+ is part of a 'soft bipolar spectrum' but await replication in larger cohorts.