La Cooperación comercial CE-ACP : Evaluación del Protocolo del Azúcar

A pesar de que estos compromisos comerciales especiales han implicado sustanciales transferencias para algunos países ACP participantes, éstas no han logrado, en general, la expansión del bienestar económico de dichos países. Dan soporte a ello determinados elementos influyentes tanto en el diseño como en la aplicación del Protocolo. En consecuencia, se pretende aportar líneas de mejora de la política europea de cooperación al desarrollo de los países ACP beneficiarios del Protocolo en el ámbito del azúcar, en el marco de la nueva cooperación comercial CE-ACP y la propuesta de reforma de la OCM del azúcar.Tot i que aquests compromisos comercials especials han implicat substancials transferències per alguns països ACP participants, aquestes no han aconseguit, en general, l'expansió del benestar econòmic d'aquests països. Donen suport a això determinats elements influents tant en el disseny com en l'aplicació del Protocol. En conseqüència, es pretén aportar línies de millora de la política europea de cooperació al desenvolupament dels països ACP beneficiaris del Protocol en l'àmbit del sucre, en el marc de la nova cooperació comercial CE-ACP i la proposta de reforma de l'OCM del sucre

The European Union trade relations with its neighbors: europeanization, internationalization or coordination?

La política de Vecindad de la Unión Europea se acostumbra a interpretar como un instrumento de europeización forzada. Gracias a su fuerza de negociación, la Unión Europea impondría a sus vecinos su modelo económico y hasta político y social. Esta sin embargo no es la evidencia que se obtiene en el ámbito del comercio. En consonancia con el modelo teórico de relaciones exteriores desarrollado por varios investigadores bajo la dirección de Esther Barbé, observamos como, en el ámbito comercial, el modelo de relaciones entre la Unión Europea y cuatro países de la política de Vecindad puede ser tanto de europeización como también de internacionalización o de coordinación. El tipo de modelo aplicado viene condicionado, como asevera el marco teórico, por el cumplimiento de las condiciones necesarias que se requieren para que Europa imponga sus normas: legitimidad, incentivos y coherencia interna. Estas condiciones varían en función tanto del tema tratado como del país vecino.___________________________________________________Most of the literature on the European Neighbourhood Policy (ENP) has assumed that it is an instrument directed at Europeanising neighbours. Through this policy, the EU would be encouraging its neighbour countries to adopt an EU-specific economic, and even social and political, model. This is not, however, the evidence one obtains analysing the EU commercial relations with four of its neighbours. Our research indicates that the convergence processes between the EU and those countries have rather been established on the basis of three different standards: international, bilateral and EU. It further highlights that the pattern of policy convergence is the result of the interplay between the EU and neighbouring countries shaped by interests, legitimacy and coherence. These results support recent research by Barbé et ál. on the ENP

Las relaciones comerciales de la Union Europea con sus vecinos: europeizacion, internacionalizacion o coordinacion?

La politica de Vecindad de la Union Europea se acostumbra a interpretar como un instrumento de europeizacion forzada. Gracias a su fuerza de negociacion, la Union Europea impondria a sus vecinos su modelo economico y hasta politico y social. Esta sin embargo no es la evidencia que se obtiene en el ambito del comercio. En consonancia con el modelo teorico de relaciones exteriores desarrollado por varios investigadores bajo la direccion de Esther Barbe, observamos como, en el ambito comercial, el modelo de relaciones entre la Union Europea y cuatro paises de la politica de Vecindad puede ser tanto de europeizacion como tambien de internacionalizacion o de coordinacion. El tipo de modelo aplicado viene condicionado, como asevera el marco teorico, por el cumplimiento de las condiciones necesarias que se requieren para que Europa imponga sus normas: legitimidad, incentivos y coherencia interna. Estas condiciones varian en funcion tanto del tema tratado como del pais vecino.trade policy, european neighbourhood policy, european union, europeanisation

Polypyrimidine tract-binding proteins are essential for B cell development.

Polypyrimidine tract-binding protein 1 (PTBP1) is a RNA-binding protein (RBP) expressed throughout B cell development. Deletion of Ptbp1 in mouse pro-B cells results in upregulation of PTBP2 and normal B cell development. We show that PTBP2 compensates for PTBP1 in B cell ontogeny as deletion of both Ptbp1 and Ptbp2 results in a complete block at the pro-B cell stage and a lack of mature B cells. In pro-B cells PTBP1 ensures precise synchronisation of the activity of cyclin dependent kinases at distinct stages of the cell cycle, suppresses S-phase entry and promotes progression into mitosis. PTBP1 controls mRNA abundance and alternative splicing of important cell cycle regulators including CYCLIN-D2, c-MYC, p107 and CDC25B. Our results reveal a previously unrecognised mechanism mediated by a RBP that is essential for B cell ontogeny and integrates transcriptional and post-translational determinants of progression through the cell cycle

Essential requirement for polypyrimidine tract binding proteins 1 and 3 in the maturation and maintenance of mature B cells in mice

Abstract: The maturation of immature B cells and the survival of mature B cells is stringently controlled to maintain a diverse repertoire of antibody specificities while avoiding self‐reactivity. At the molecular level this is regulated by signaling from membrane Ig and the BAFF‐receptor that sustain a pro‐survival program of gene expression. Whether and how posttranscriptional mechanisms contribute to B cell maturation and survival remains poorly understood. Here, we show that the polypyrimidine tract binding proteins (PTBP) PTBP1 and PTBP3 bind to a large and overlapping set of transcripts in B cells. Both PTBP1 and PTBP3 bind to introns and exons where they are predicted to regulate alternative splicing. Moreover, they also show high‐density of binding to 3’ untranslated regions suggesting they influence the transcriptome in diverse ways. We show that PTBP1 and PTBP3 are required in B cells beyond the immature cell stage to sustain transitional B cells and the B1, marginal zone and follicular B cell lineages. Therefore, PTBP1 and PTBP3 promote the maturation of quiescent B cells by regulating gene expression at the posttranscriptional level

Automated digital image quantification of histological staining for the analysis of the trilineage differentiation potential of mesenchymal stem cells

BACKGROUND Multipotent mesenchymal stem cells (MSCs) have the potential to repair and regenerate damaged tissues and are considered as attractive candidates for the development of cell-based regenerative therapies. Currently, there are more than 200 clinical trials involving the use of MSCs for a wide variety of indications. However, variations in their isolation, expansion, and particularly characterization have made the interpretation of study outcomes or the rigorous assessment of therapeutic efficacy difficult. An unbiased characterization of MSCs is of major importance and essential to guaranty that only the most suitable cells will be used. The development of standardized and reproducible assays to predict MSC potency is therefore mandatory. The currently used quantification methodologies for the determination of the trilineage potential of MSCs are usually based on absorbance measurements which are imprecise and prone to errors. We therefore aimed at developing a methodology first offering a standardized way to objectively quantify the trilineage potential of MSC preparations and second allowing to discriminate functional differences between clonally expanded cell populations. METHOD MSCs originating from several patients were differentiated into osteoblasts, adipocytes, and chondroblasts for 14, 17, and 21 days. Differentiated cells were then stained with the classical dyes: Alizarin Red S for osteoblasts, Oil Red O for adipocytes, and Alcian Blue 8GX for chondroblasts. Quantification of differentiation was then performed with our newly developed digital image analysis (DIA) tool followed by the classical absorbance measurement. The results from the two techniques were then compared. RESULT Quantification based on DIA allowed highly standardized and objective dye quantification with superior sensitivity compared to absorbance measurements. Furthermore, small differences between MSC lines in the differentiation potential were highlighted using DIA whereas no difference was detected using absorbance quantification. CONCLUSION Our approach represents a novel method that simplifies the laboratory procedures not only for the quantification of histological dyes and the degree of differentiation of MSCs, but also due to its color independence, it can be easily adapted for the quantification of a wide range of staining procedures in histology. The method is easily applicable since it is based on open source software and standard light microscopy

CD1d Expression in Paneth Cells and Rat Exocrine Pancreas Revealed by Novel Monoclonal Antibodies Which Differentially Affect NKT Cell Activation

Background: CD1d is a nonpolymorphic MHC class I-like molecule which presents nonpeptide ligands, e.g. glycolipids, to NKT cells. These cells are known to have multiple effects on innate and adaptive immune responses and on the development of pathological conditions. In order to analyze CD1d expression and function in the rat, the first rat CD1dspecific monoclonal antibodies (mAbs) were generated. Methodology/Principal Findings: Two mAbs, WTH-1 and WTH-2, were generated which bound equally well to cell surfaceexpressed rat and mouse CD1d. Their non-overlapping epitopes were mapped to the CD1d heavy chain. Flow cytometry and immunohistological analyses revealed a nearly identical degree and pattern of CD1d expression for hematopoieitic cells of both species. Notable is also the detection of CD1d protein in mouse and rat Paneth cells as well as the extremely high CD1d expression in acinar exocrine cells of the rat pancreas and the expression of CD4 on rat marginal zone B cells. Both mAbs blocked a-galactosylceramide recognition by primary rat and mouse NKT cells. Interestingly, the two mAbs differed in their impact on the activation of various autoreactive T cell hybridomas, including the XV19.2 hybridoma whose activation was enhanced by the WTH-1 mAb. Conclusions/Significance: The two novel monoclonal antibodies described in this study, allowed the analysis of CD1d expression and CD1d-restricted T cell responses in the rat for the first time. Moreover, they provided new insights into mechanisms of CD1d-restricted antigen recognition. While CD1d expression by hematopoietic cells of mice and rats was extremely similar, CD1d protein was detected at not yet described sites of non-lymphatic tissues such as the rat exocrine pancreas and Paneth cells. The latter is of special relevance given the recently reported defects of Paneth cells in CD1d2/2 mice, which resulted in an altered composition of the gut flora

Novel Endometrial Cancer Models Using Sensitive Metastasis Tracing for CXCR4-Targeted Therapy in Advanced Disease

Advanced endometrial cancer (EC) lacks therapy, thus, there is a need for novel treatment targets. CXCR4 overexpression is associated with a poor prognosis in several cancers, whereas its inhibition prevents metastases. We assessed CXCR4 expression in EC in women by using IHC. Orthotopic models were generated with transendometrial implantation of CXCR4-transduced EC cells. After in vitro evaluation of the CXCR4-targeted T22-GFP-H6 nanocarrier, subcutaneous EC models were used to study its uptake in tumor and normal organs. Of the women, 91% overexpressed CXCR4, making them candidates for CXCR4-targeted therapies. Thus, we developed CXCR4(+) EC mouse models to improve metastagenesis compared to current models and to use them to develop novel CXCR4-targeted therapies for unresponsive EC. It showed enhanced dissemination, especially in the lungs and liver, and displayed 100% metastasis penetrance at all clinically relevant sites with anti-hVimentin IHC, improving detection sensitivity. Regarding the CXCR4-targeted nanocarrier, 60% accumulated in the SC tumor; therefore, selectively targeting CXCR4(+) cancer cells, without toxicity in non-tumor organs. Our CXCR4(+) EC models will allow testing of novel CXCR4-targeted drugs and development of nanomedicines derived from T22-GFP-H6 to deliver drugs to CXCR4(+) cells in advanced EC. This novel approach provides a therapeutic option for women with metastatic, high risk or recurrent EC that have a dismal prognosis and lack effective therapies