The Impact of Unemployment on Individual Well-Being in the EU. CEPS ENEPRI Working Papers No. 29, 1 July 2004

Among the working-age population, one of the most damaging individual experiences is unemployment. Many previous studies have confirmed the devastating effects of unemployment on individual well-being, both pecuniary and non-pecuniary. Using the data from the European Community Household Panel survey, this paper examines the factors that affect unemployed workers’ well-being with respect to their situations in their main vocational activity, income, housing, leisure time and health in Europe. The research finds that unemployment substantially reduces an individual’s satisfaction levels with his or her main vocational activity and finance, while it greatly increases his or her satisfaction levels with leisure time. With respect to health, it has a small negative effect. Unemployment duration also has a small, negative impact on individual well-being, suggesting that unemployment has a lasting and aggravating effect throughout the spells of unemployment, contradicting the theory of adaptation

Analysis of the role of Granzyme-A in the development of colorectal cancer stem cells

Colorectal cancer is the third leading cause of cancer death worldwide with nearly 150.000 new cases diagnose annually. New therapies have been developed for the last years targeting different proliferation and survival signalling pathways but few advances have been done to avoid relapse in patients. Cancer stem cells are proposed as the main mechanism of resistance in current therapies. These cells have been described as a subset among all the tumour cell populations which have stemness properties such as self-renewal and differentiation capabilities. These features allow them to survive after antitumour treatments and regenerate the entire tumour mass. Also, cancer stem cells have been proposed as the responsible of metastasis. Inflammation in colorectal cancer is a sign of poor prognosis and it has been proposed as the main driver of the tumour progression. Its relation with cancer stem cells has not been clasified yet but pro-inflammatory molecules such as TNF-α or IL-1B are able to activate cancer stem cells-related signalling pathways such as Wnt or Notch pathways. Granzyme-A, a protease released by immune cells, is involved in implication during like bacterial sepsis or arthritis. Our preliminary data indicate it is involved in development of colorectal cancer. The current study analyse the implication of Granzyme-A in the activation of CSCs during inflammation-associated colorectal cancer in a mouse model

Identificación de células madre tumorales y desarrollo de cultivos en 3D para líneas celulares de carcinoma colorectal

El carcinoma colorectal es el cáncer de mayor prevalencia entre la población, con una incidencia creciente en la población occidental acostumbrada a dietas saturadas en productos procesados y bajo consumo de frutas y verduras. Los tratamientos convencionales son efectivos pero en algunos casos el carcinoma resiste el tratamiento y resurge con una mayor patogenicidad. Se piensa que las células involucradas en esta reaparición del tumor son un tipo concreto celular que existe en todos los tumores, las células madre tumorales o CSCs. Estas células presentan una serie de características que las hace fundamentales para el mantenimiento del nicho del tumor y son estas propiedades las que les permite sobrevivir frente a las terapias y regenerar de nuevo la masa tumoral. Entre estas características se encuentran la capacidad de autorenovación y diferenciación y la alta resistencia a fármacos y terapias antitumorales. Su identificación y caracterización podría permitir dirigir las futuras terapias contra ellas y eliminar aquellos tumores más resistentes. En este trabajo hemos evaluado diversos marcadores para CSCs en las líneas de carcinoma colorectal HT29, HCT116 y CaCo2. Entre ellos se encuentran los marcadores de superficie CD24, CD44 y CD133 y los marcadores funcionales de actividad ALDH y expulsión del colorante Hoechst 33342. Tras su evaluación, hemos puesto a punto un protocolo de identificación de CSCs está basado en el marcador de superficie CD44 y el marcador funcional de actividad ALDH. Ambos marcadores correlacionan con una población nueva de células que aparece ante un tratamiento con el fármaco Paclitaxel. A su vez, hemos puesto a punto el desarrollo de cultivos 3D en forma de esferoides con el fin de utilizar estudios in vitro más cercanos a la realidad fisiológica en la que las células están dispuestas formando estructuras tridimensionales

Desarrollo de anticuerpos bi-específicos de unión a células NK (BiKE) frente al antígeno Tn para inmunoterapia en cáncer

Introduction and objective. BiKEs (bispecific killer cell engagers) are a new form of immunotherapy that consists of two connected scFv. One scFv recognizes a tumor antigen and the other binds to CD16 on the NK cell membrane, thus NK cells are activated and specifically target the tumor. It’s thought that BiKEs would have the advantage over monoclonal antibodies of more easily penetrating solid tumors and generating a stronger stimulus to NK cells that would be capable of activating them even in the immunosuppressive conditions of the tumor microenvironment. The objective of this work is to design and recombinantly express two BiKEs, in addition to three other proteins, using the Tn antigen as a target. This antigen is an aberrant glycosylation pattern specific to tumor cells and highly abundant in tumors of epithelial origin.Results. The 5 proteins have been expressed in HEK 293 6F cells with a good yield and degree of purity. We have been able to demonstrate that these proteins are correctly folded, dimerized and glycosylated. We also have probed that the scFvs of the BiKEs recognize Tn antigen as is described in the literature. However, the ability of BiKEs to activate NK cells against tumor cells in in vitro cultures couldn’t be demonstrated due to the lack of an adequate positive control.<br /

Efficient multi-click approach to well-defined two-faced octasilsesquioxanes: the first perfect Janus nanocube

The preparation of the first structurally well-defined Janus nanocube showing two chemically distinct opposed faces is described. The synthetic approach is based on a highly efficient and symmetrycontrolled CuAAC functionalization of an octa-azido cubic silsesquioxane with a conformationally constrained tetra-alkyne with an appropriate spatial orientation of the triple bonds.with two sets of orthogonally reactive functional groups. We gratefully acknowledge financial support by the Spanish Ministerio de Ciencia e Innovación (project MAT2010-20646- C04-03) and Ministerio de Economía y Competitividad (project MAT2014-51937-C3-1-P). We also acknowledge the Spanish Ministerio de Economía y Competitividad for a FPI contract to A. B., and CSIC for a JAEDOC contract to J. R. S. and a JAEPRE contract to M. E. P.-O., and for support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).Peer reviewe

Solid-phase synthesis of imprinted nanoparticles as artificial antibodies against the C-terminus of the cannabinoid CB1 receptor: exploring a viable alternative for bioanalysis

[EN]The production of artificial anti-CB1 antibodies in nanoparticle format is described using the solid-phase imprinting approach. Instead of whole protein imprinting, a linear C-terminus sequence of the receptor comprising 15 amino acids (458-KVTMSVSTDTSAEAL-472) has been used as template, in accordance with the epitope imprinting approach. This sequence is located intracellularly, and it is involved in coupling to G(i/o) proteins, being responsible for CB1 receptor desensitisation and internalisation. Developed molecularly imprinted materials were found to be in the nanometre scale, with a particle size of 126.4 +/- 10.5 nm at pH 3 (25 oC) and spherical shape. It was also observed that the size was sensible to temperature changes being reduced to 106.3 +/- 15.2 nm at 35 degrees C. Lower critical solution temperature of this polymer was found to be approximate to 33.4 degrees C. The affinity and selectivity of the artificial antibody were assessed through dot blot and Western blot experiments. For the latter, recombinant fusion proteins GST-CB1(414-472) and GST-CB1(414-442) were produced to work respectively as target and negative control proteins. The control protein did not carry the target epitope for being devoid of last 30 amino acids at the C-terminus. The results demonstrated that the anti-CB1 material recognised selectively the target protein, thanks to the presence of the 15-amino acid sequence selected as epitope, which revealed that binding occurred at the C-terminus of the receptor itself. The methodology presented may pave the way for the development of novel imprinted nanomaterials for other proteins included in the superfamily of the G-protein-coupled receptors (GPCR).Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. Funding for this research was provided by the Spanish Ministry of Science, Innovation and Universities (project CTQ2017-85686-R) and by the Basque Government (Research Groups of the Basque University System, Project No IT 1186-19

A Spectroscopic study of colchicine in the solid state and in solution by multinuclear magnetic resonance and vibrational circular dichroism

Although almost 200-years-old, several unknown aspects remain to be explored of colchicine, the unique available drug for acute flares of gout. In this article, we report density-functional theory (DFT) studies of geometry, energy, and NMR; 1H-, 13C-, and 15N-NMR chemical shifts and some spin-spin coupling constants, including the complete analysis of the saturated part (ring B); the assignment of both enantiomers by NMR using a chiral solvating agent; solid-state NMR experiments of the different forms of natural and racemic colchicine, and IR and vibrational circular dichroism (VCD) studies of these same forms. Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.Peer Reviewe

Tumor P70S6K hyperactivation is inversely associated with tumor-infiltrating lymphocytes in triple-negative breast cancer

Purpose: Triple-negative breast cancer (TNBC) is characterized by large heterogeneity and relative lack of available targeted therapies. To find therapeutic strategies for distinct patients with TNBC, several approaches have been used for TNBC clustering, including recently immune and phosphoproteomic patterns. Based on 70-kDa ribosomal protein S6 kinase (P70S6K)-TNBC clustering, the current study explores the immune profiling in TNBC tumors. Methods: Stromal tumor-infiltrating lymphocytes (sTILs) were evaluated in human TNBC tumor samples. Furthermore, immunohistochemistry staining for CD8, CD4, Foxp3, and CD20 was performed in tissue microarrays (TMA) sections. Results: Histological analysis showed decreased sTILs, CD20+ cells, and CD8+/CD4+ ratio in high phosphorylated P70S6K (p-P70S6K) tumors. Moreover, p-P70S6K score was directly correlated with CD4+ and Foxp3+ T cells, while it was inversely correlated with CD8+/CD4+ and CD8+/Foxp3+ ratios. Conclusion: sTIL infiltration and lymphocyte profiling vary in the context of hyperactivation of P70S6K in TNBC tumorsThe project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 893597. RC is a recipient of the ISCIII grants: PI17/01865 and PI20/01458. MQF is a recipient of the following Grants: AES-PI19/00454 funded by the ISCIII and co-funded by the European Regional Development Fund (ERDF) and B2017/BMD3733 (Immunothercan-CM)—Call for Coordinated Research Groups from Madrid Region—Madrid Regional Government—ERDF funds. The study was also funded by CRIS Contra el Cancer Foundatio

Relationship between the order of permanent tooth eruption and the predominance of motor function laterality: A cross-sectional study

Objetivos Evaluar si el orden de la erupción dental es un buen indicador de la lateralidad motora. Métodos Estudio transversal en escolares de ambos sexos de 6 a 8 años tratados mediante las revisiones orales rutinarias anuales realizadas en los colegios incluidos en un área de atención primaria urbana en Barcelona (España). También se evaluaron las lateralidades de manos, pies, ojos y oídos mediante una serie de ejercicios simples. Se realizaron análisis bivariantes y multivariantes de los datos. Resultados La muestra comprendió 388 escolares, 51,3% niñas, con una edad media de 6,5 años. La lateralidad derecha predominó en todas las variables de estudio, especialmente en la dentición (310 escolares; 80%), la mano (349; 89,9%) y el pie (337; 86.8%). En el estudio bivariante se observó una asociación estadísticamente significativa (p < 0,001) entre la lateralidad de la dentición y la de la mano y el pie, así como entre la lateralidad de la dentición y las lateralidades de oído y de ojo. En el estudio multivariante, las lateralidades de la dentición y del pie se asociaron significativamente a la lateralidad de la mano. En lo concerniente a la precisión de la lateralidad de la dentición y del pie como prueba diagnóstica de la lateralidad de la mano, ambas mostraron una sensibilidad y valores predictivos positivos y negativos similares, pero la especificidad de la lateralidad de la dentición fue mayor (79% vs. 66%). Conclusiones La lateralidad en el orden de la erupción dental es un buen indicador para determinar la lateralidad motora durante el desarrollo, que podría ser particularmente útil para ayudar a precisar la lateralidad más predominante en casos de lateralidad cruzada.Objectives To assess whether the order of permanent tooth eruption may be a useful indicator of motor function laterality. Methods We conducted a cross-sectional study in schoolchildren aged 6 to 8 years old evaluated in the annual school-based routine dental health examinations conducted by the staff of the primary care centre of an urban district in Barcelona, Spain. We also evaluated hand, foot, eye, and auditory lateralities using a series of simple exercises. Bivariate and multivariate analysis of data was performed. Results The study sample included 388 children, 51.3% female, with a mean age of 6.5 years. Right laterality was the predominant side in every variable under study, especially in tooth eruption (310 children; 80%), handedness (349; 89.9%), and footedness (337; 86.8%). In the bivariate analysis, we found a statistically significant association of tooth eruption laterality with handedness and footedness, an of tooth eruption laterality with ocular and auditory lateralities (P<.001). In the multivariate analysis, tooth eruption laterality and foot laterality were independent variables significantly associated with hand laterality. The diagnostic accuracy of tooth eruption laterality and foot laterality in relation to hand laterality as reference, showed a similar sensitivity and positive and negative predictive values, but the specificity of dentition laterality was higher (79% versus 66%). Conclusions Laterality in the order of dental eruption is a useful indicator of right or left motor function laterality in developing individuals that may be particularly helpful to determine the main dominance in cases of crossed laterality

A cloud-enabled small cell architecture in 5G networks for broadcast/multicast services

© 2019 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes,creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.The evolution of 5G suggests that communication networks become sufficiently flexible to handle a wide variety of network services from various domains. The virtualization of small cells as envisaged by 5G, allows enhanced mobile edge computing capabilities, thus enabling network service deployment and management near the end user. This paper presents a cloud-enabled small cell architecture for 5G networks developed within the 5G-ESSENCE project. This paper also presents the conformity of the proposed architecture to the evolving 5G radio resource management architecture. Furthermore, it examines the inclusion of an edge enabler to support a variety of virtual network functions in 5G networks. Next, the improvement of specific key performance indicators in a public safety use case is evaluated. Finally, the performance of a 5G enabled evolved multimedia broadcast multicast services service is evaluated.Peer ReviewedPostprint (author's final draft