120 research outputs found
Blurring of Colour Lines? Ethnoracially Mixed Youth in Spain Navigating Identity
The recent rise in Spain of mixed unions between people born in different countries has brought about a significant increase in the number of multiethnic and multiracial individuals in the country. However, no research currently exists in Spain on the life experiences and identity processes of these mixed-parentage youth. Drawing on 124 in-depth interviews, this article examines the narratives of ethnoracially mixed descendants from diverse backgrounds in Catalonia, Spain. Our results show that identity processes and experiences of being mixed are very heterogeneous and multifaceted, and that some individuals have more choices, versus constraints, when navigating mixedness. A crucial factor affecting these outcomes is visibility - i.e. visible markers of difference from the native society, such as phenotype, language, or religious affiliation. We find that while ethnoracially mixed individuals who have more outer characteristics shared with the native majority population can develop more advantageous, symbolic, and malleable identities, individuals whose heritage involves an ancestry that is negatively minoritised within the country of residence experience greater identity mismatch, stigmatisation, and discrimination. This finding is at odds with the 'postracial' or 'colour-blind' future that might ostensibly be heralded by an ever-growing Spanish population of mixed individuals
Análisis de la eficiencia de las políticas contra la desertificación llevada a cabo en la cuenca del río Guadalentin mediante Análisis Envolvente de Datos (DEA)
Mediante análisis envolvente de datos (DEA) CCR-input-orientado y DEA con ponderación cruzada se ha analizado la eficiencia de las diversas actuaciones aplicadas en ocho municipios de la cuenca del río Guadalentín, en búsqueda de la mejor política aplicada entre los años 1978 y 2003. Con el análisis CCR-input-orientado se han detectado los municipios claramente ineficientes y las causas de ineficiencia. Mediante el segundo análisis se ha obtenido una valoración de la eficiencia global de cada municipio y se ha podido estudiar la contribución unitaria de cada recurso en cada término municipal
p21-activated kinase-1 signaling regulates transcription of tissue factor and tissue factor pathway inhibitor.
Tissue factor (TF) is a cell-surface glycoprotein responsible for initiating the coagulation cascade. Besides its role in homeostasis, studies have shown the implication of TF in embryonic development, cancer related events, and inflammation via coagulation-dependent and -independent (signaling) mechanisms. Tissue factor pathway inhibitor (TFPI) plays an important role in regulating TF-initiated blood coagulation. Therefore, transcriptional regulation of TF expression and its physiologic inhibitor TFPI, would allow us to understand the critical step that control many different processes. From a gene profiling study aimed to identify differentially regulated genes between wild type (WT) and p21-activated kinase 1-null (PAK1-KO) mouse embryonic fibroblasts (MEFs), we found TF and TFPI are differentially expressed in the PAK1-KO MEFs in comparison to wild-type MEFs. Based on these findings, we further investigated in the present study the transcriptional regulation of TF and TFPI by PAK1, a serine/threonine kinase. We found that PAK1/c-Jun complex stimulates the transcription of TF and consequently, its procoagulant activity. Moreover, PAK1 negatively regulates the expression of TFPI and thus, additionally, contributes to increased TF activity. For the first time, this study implicates PAK1 in coagulation processes, through its dual transcriptional regulation of TF and its inhibitor
Olfactory fMRI Connectivity Analysis Based on Granger Causality with Application in Anosmia Assessment
In this work, we describe hubs organization within the olfactory network with Functional Magnetic Resonance Imaging (fMRI). Granger causality analyses were applied in the supposed regions of interest (ROIs) involved in olfactory tasks, as described in [1]. We aim to get deeper knowledge about the hierarchy of the regions within the olfactory network and to describe which of these regions, in terms of strength of the connectivity, impair in different types of anosmia
Mouse resistin modulates adipogenesis and glucose uptake in 3t3-l1 preadipocytes through the ror1 receptor.
Mouse resistin, a cysteine-rich protein primarily secreted from mature adipocytes, is involved in insulin resistance and type 2 diabetes. Human resistin, however, is mainly secreted by immune mononuclear cells, and it competes with lipopolysaccharide for the binding to Toll-like receptor 4, which could mediate some of the well-known pro-inflammatory effects of resistin in humans. In addition, resistin has been involved in the regulation of cell differentiation and proliferation processes, suggesting that different receptors could be involved in mediating its numerous effects. Thus, a recent work identifies an isoform of Decorin (Decorin) as a functional resistin receptor in adipocyte progenitors that may regulate white adipose tissue expansion. In this work, we have observed an interaction of mouse resistin with specific domains of the extracellular region of the mouse receptor tyrosine kinase-like orphan receptor 1 (ROR1). This interaction results in the inhibition of ROR1 phosphorylation, modulates ERK1/2 phosphorylation, and regulates the expression of suppressor of cytokine signaling 3, glucose transporter 4, and glucose transporter 1. We show also that the ROR1 receptor mediates the described effects of resistin in 3T3-L1 adipogenesis and glucose uptake. Our results identify mouse resistin as a potential inhibitory ligand for the ROR1 receptor and demonstrate, for the first time, that ROR1 plays an important role in adipogenesis and glucose homeostasis in 3T3-L1 cells. These data open a new line of research that could explain important questions about the mechanism of action of resistin in adipogenesis and in the development of insulin resistance and type 2 diabetes
Building an IP-based community wireless mesh network: Assessment
Wireless mesh networks are experiencing rapid progress and inspiring numerous applica tions in different scenarios, due to features such as autoconfiguration, self healing, connec tivity coverage extension and support for dynamic topologies. These particular characteristics make wireless mesh networks an appropriate architectural basis for the design of easy to deploy community or neighbourhood networks. One of the main chal lenges in building a community network using mesh networks is the minimisation of user intervention in the IP address configuration of the network nodes. In this paper we first consider the process of building an IP based mesh network using typical residential rou ters, exploring the options for the configuration of their wireless interfaces. Then we focus on IP address autoconfiguration, identifying the specific requirements for community mesh networks and analysing the applicability of existing solutions. As a result of that analysis, we select PACMAN, an efficient distributed address autoconfiguration mechanism origi nally designed for ad hoc networks, and we perform an experimental study using off the shelf routers and assuming worst case scenarios analysing its behaviour as an IP address autoconfiguration mechanism for community wireless mesh networks. The results of the conducted assessment show that PACMAN meets all the identified requirements of the community scenario.European Community´s Seventh Framework ProgramPublicad
CMV latent infection improves CD8+T response to SEB due to expansion of polyfunctional CD57+cells in young individuals
La infección latente por citomegalovirus (CMV) tiene un efecto perjudicial sobre la eficacia de la vacunación contra la influenza en los ancianos, lo que sugiere que el CMV restringe la diversidad inmunológica que afecta la funcionalidad del sistema inmune en la vejez. Las células T polifuncionales producen citoquinas múltiples y cantidades más altas que las células T monofuncionales. El alto número de células T polifuncionales se correlaciona con un mejor pronóstico durante la infección. Por lo tanto, la eficacia de la respuesta de células T se asocia con la calidad (polifuncionalidad) en lugar de con la cantidad (porcentaje de células T). Analizamos el efecto de la infección por CMV en la polifuncionalidad de las células T CD8 +: la desgranulación (CD107a), la producción de IFN-gamma y TNF-alfa ---, de seropositivos jóvenes CMV y seronegativos CMV y en donantes seropositivos CMV de edad media , En respuesta a los productores de enterotoxina B estafilocócica, principalmente TNF-alfa o TNF-alfa / IFN-gamma, mientras que el porcentaje de células polifuncionales (IFN-gamma / TNFalfa / CD107a) es similar a los porcentajes encontrados en los jóvenes seropositivos al CMV. Por lo tanto, mientras que se ha demostrado que la infección latente por CMV puede ser perjudicial para la respuesta inmune en los ancianos, nuestros resultados indican que la seropositividad a CMV se asocia a niveles más altos de células T CD8 + polifuncionales en donantes jóvenes y de mediana edad. Este aumento de la polifuncionalidad, que puede proporcionar una ventaja inmunológica en la respuesta a otros patógenos, se debe a una expansión de células T CD8 + CD57 + en individuos seropositivos para CMV y es independiente de la edad. Por el contrario, la edad podría contribuir a la inflamación que se encuentra en los individuos de edad mediante el aumento del porcentaje de células que producen citocinas pro-inflamatorias. Estos hallazgos destacan la necesidad de nuevos estudios sobre los beneficios / efectos perjudiciales de la infección por CMV en la respuesta a la vacunación y otras infecciones.Cytomegalovirus (CMV) latent infection has a deleterious effect on the efficacy of influenza vaccination in the elderly, suggesting that CMV restricts immunological diversity impairing the immune system functionality in old age. Polyfunctional T cells produce multiple cytokines and higher amounts than mono-functional T cells. High number of polyfunctional T cells correlates with better prognosis during infection. Thus, the efficiency of T cell response associates with quality (polyfunctionality) rather than with quantity (percentage of T cells). We analyze the effect of CMV infection on CD8+ T cells polyfunctionality ---degranulation (CD107a), IFN-gamma and TNF-alpha production---, from young CMV-seropositive and CMV-seronegative individuals and in middle age CMV-seropositive donors, in response to Staphylococcal Enterotoxin B mainly TNF-alpha or TNF-alpha/IFN-gamma producers, whereas the percentage of polyfunctional cells (IFN-gamma/TNFalpha/ CD107a) is similar to the percentages found in young CMV-seropositive. Therefore, whereas it has been shown that CMV latent infection can be detrimental for immune response in old individuals, our results indicate that CMV-seropositivity is associated to higher levels of polyfunctional CD8+ T cells in young and middle age donors. This increase in polyfunctionality, which can provide an immunological advantage in the response to other pathogens, is due to a CD8+CD57+ T cell expansion in CMV-seropositive individuals and it is independent of age. Conversely, age could contribute to the inflammation found in old individuals by increasing the percentage of cells producing pro-inflammatory cytokines. These findings highlight the necessity of further studies on the benefits/detrimental effects of CMV infection in the response to vaccination and other infections.Trabajo financiado por:
• Ministerio de Economía y Competitividad. Instituto Carlos III: FIS Ref PS09/00723
• Ministerio de Educación y Ciencia: SAF2009-09711
• Junta de Extremadura: GRU10104
• Universidad de Extremadura. Ayuda a INPATT, grupo de investigación “Inmunopatología tumoral”, cofinanciado por la European Regional Development Fund (Fondos FEDER)peerReviewe
DNAM-1 and the TIGIT/PVRIG/TACTILE Axis: Novel Immune Checkpoints for Natural Killer Cell-Based Cancer Immunotherapy
Natural killer (NK) cells are lymphocytes of the innate immune response characterized by their role in the destruction of tumor cells. Activation of NK cells depend on a fine balance between activating and inhibitory signals mediated by different receptors. In recent years, a family of paired receptors that interact with ligands of the Nectin/Nectin-like (Necl) family has attracted great interest. Two of these ligands, Necl-5 (usually termed CD155 or PVR) and Nectin-2 (CD112), frequently expressed on different types of tumor cells, are recognized by a group of receptors expressed on T and NK cells that exert opposite functions after interacting with their ligands. These receptors include DNAM-1 (CD226), TIGIT, TACTILE (CD96) and the recently described PVRIG. Whereas activation through DNAM-1 after recognition of CD155 or CD112 enhances NK cell-mediated cytotoxicity against a wide range of tumor cells, TIGIT recognition of these ligands exerts an inhibitory effect on NK cells by diminishing IFN-γ production, as well as NK cell-mediated cytotoxicity. PVRIG has also been identified as an inhibitory receptor that recognizes CD112 but not CD155. However, little is known about the role of TACTILE as modulator of immune responses in humans. TACTILE control of tumor growth and metastases has been reported in murine models, and it has been suggested that it negatively regulates the anti-tumor functions mediated by DNAM-1. In NK cells from patients with solid cancer and leukemia, it has been observed a decreased expression of DNAM-1 that may shift the balance in favor to the inhibitory receptors TIGIT or PVRIG, further contributing to the diminished NK cell-mediated cytotoxic capacity observed in these patients. Analysis of DNAM-1, TIGIT, TACTILE and PVRIG on human NK cells from solid cancer or leukemia patients will clarify the role of these receptors in cancer surveillance. Overall, it can be speculated that in cancer patients the TIGIT/PVRIG pathways are upregulated and represent novel targets for checkpoint blockade immunotherapy
Disparate connectivity for structural and functional networks is revealed when physical location of the connected nodes is considered
Macroscopic brain networks have been widely described with the manifold of metrics available using graph theory. However, most analyses do not incorporate information about the physical position of network nodes. Here, we provide a multimodal macroscopic network characterization while considering the physical positions of nodes. To do so, we examined anatomical and functional macroscopic brain networks in a sample of twenty healthy subjects. Anatomical networks are obtained with a graph based tractography algorithm from diffusion-weighted magnetic resonance images (DW-MRI). Anatomical con- nections identified via DW-MRI provided probabilistic constraints for determining the connectedness of 90 dif- ferent brain areas. Functional networks are derived from temporal linear correlations between blood-oxygenation level-dependent signals derived from the same brain areas. Rentian Scaling analysis, a technique adapted from very- large-scale integration circuits analyses, shows that func- tional networks are more random and less optimized than the anatomical networks. We also provide a new metric that allows quantifying the global connectivity arrange- ments for both structural and functional networks. While the functional networks show a higher contribution of inter-hemispheric connections, the anatomical networks highest connections are identified in a dorsal?ventral arrangement. These results indicate that anatomical and functional networks present different connectivity organi- zations that can only be identified when the physical locations of the nodes are included in the analysis
Effect of Cytomegalovirus (CMV) and Ageing on T-Bet and Eomes Expression on T-Cell Subsets
The differential impact of ageing and cytomegalovirus (CMV) latent infection on human T-cell subsets remains to some extent controversial. The purpose of this study was to analyse the expression of the transcription factors T-bet and Eomes and CD57 on CD4+, CD4hiCD8lo and CD8+ T-cell subsets in healthy individuals, stratified by age and CMV serostatus. The percentage of CD4+ T-cells expressing T-bet or Eomes was very low, in particular in CD4+ T-cells from young CMV-seronegative individuals, and were higher in CMV-seropositive older individuals, in both CD57− and CD57+ CD4+ T-cells. The study of the minor peripheral blood double-positive CD4hiCD8lo T-cells showed that the percentage of these T-cells expressing both Eomes and T-bet was higher compared to CD4+ T-cells. The percentage of CD4hiCD8lo T-cells expressing T-bet was also associated with CMV seropositivity and the coexpression of Eomes, T-bet and CD57 on CD4hiCD8lo T-cells was only observed in CMV-seropositive donors, supporting the hypothesis that these cells are mature effector memory cells. The percentage of T-cells expressing Eomes and T-bet was higher in CD8+ T-cells than in CD4+ T-cells. The percentages of CD8+ T-cells expressing Eomes and T-bet increased with age in CMV-seronegative and -seropositive individuals and the percentages of CD57− CD8+ and CD57+ CD8+ T-cells coexpressing both transcription factors were similar in the different groups studied. These results support that CMV chronic infection and/or ageing are associated to the expansion of highly differentiated CD4+, CD4hiCD8lo and CD8+ T-cells that differentially express T-bet and Eomes suggesting that the expression of these transcription factors is essential for the generation and development of an effector-memory and effector T lymphocytes involved in conferring protection against chronic CMV infection
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