Solar-Simulated Ultraviolet Radiation Induces Abnormal Maturation and Defective Chemotaxis of Dendritic Cells

Exposure to ultraviolet (UV) light induces immunosuppression. Different evidences indicate that this phenomenon is mainly a consequence of the effect of UV light on skin dendritic cells (DC). To investigate the cellular and molecular basis of this type of immunosuppression, we assessed in vitro the effect of solar-simulated UV radiation on the phenotypic and functional characteristics of human monocyte-derived DC and Langerhans-like DC. UV radiation induced a decreased expression of molecules involved in antigen capture as DC-SIGN and the mannose receptor. This effect was accompanied by a diminished endocytic capacity, an enhanced expression of molecules involved in antigen presentation such as major histocompatibility complex-II and CD86, and a significant increase in their capability to stimulate T cells. Furthermore, irradiated DC failed to acquire a full mature phenotype upon treatment with lipopolysaccharide. On the other hand, solar-simulated radiation induced the secretion of tumor necrosis factor-αand interleukin (IL)-10 by DC, but no IL-12. Interestingly, solar-simulated UV radiation also caused an altered migratory phenotype, with an increased expression of CXCR4, and a lack of induction of CCR7, thus correlating with a high chemotactic response to stromal cell-derived factor 1(SDF-1) (CXCL12), but not to secondary lymphoid tissue chemokine (SLC) (CCL21). These data indicate that solar-simulated UV radiation induces a defective maturation and an anomalous migratory phenotype of DC

Identidad territorial : globalización y patrimonio

El presente libro analiza la relación entre los tres con¬ceptos que dan cuerpo a su nombre, con el fin parti¬cular de examinar los impactos que la globalización ha traído sobre el patrimonio construido. Con ello busca explorar los posibles caminos que, para la re¬flexión académica, la investigación aplicada o la polí¬tica pública, pudieran derivarse de las reflexiones que al respecto concentra aquí la mirada de numerosos investigadores provenientes de distintos países. Sobre el particular, el trabajo ofrece un marco con¬ceptual desde donde se ha abordado el fenóme¬no, y a partir del cual se analizan temas como el pensamiento en red; los conflictos socio espaciales que genera el turismo; la relación entre identidad y memoria histórica, así como entre patrimonio y de¬rechos humanos; las tensiones y dilemas que sobre la identidad y el patrimonio trae la globalización y, finalmente, el tema del, denominado en el trabajo, “pensar situado”, como condición a la hora de estu¬diar y entender lo que frente al tema ocurre en cada contexto. Enfoque desde el cual se analizan casos en España, Portugal, Italia, Colombia, Perú, Ecuador, Brasil, Uruguay, Argentina, México, Croacia y, entre otros, Turquía, país, este último, donde los investiga¬dores en pleno efectuaron un trabajo de campo que, junto con las exploraciones en otros contextos, per¬mitió contrastar la teoría con la práctica y extrapolar desde aquí sus conclusiones.Resumen-Abstract. CAPÍTULO 1. Identidad territorial: Elementos transversales y temas críticos, a manera de preámbulo y marco científico. CAPÍTULO 2. Identidad territorial y globalización: Pensar en red. Un reto y un compromiso. CAPÍTULO 3. Morir de éxito. Conflictos socioespaciales del turismo globalizado en ciudades patrimoniales. CAPÍTULO 4. El patrimonio industrial y su compleja puesta en valor: Identidades y memorias en disputa. CAPÍTULO 5. Patrimônio e direitos humanos: A ação do icomos no caso de Bento Rodrigues. CAPÍTULO 6. Tensiones y dilemas de la identidad y el patrimonio en tiempos de globalización CAPÍTULO 7. Identidad territorial, globalización y patrimonio en el valle del Colca, Arequipa, Perú. CAPÍTULO 8. O dilema da patrimonialização em tempos de globalização: Cidade de Paraty, Rio de Janeiro, Brasil. CAPÍTULO 9. Territorialización del paisaje cultural mexicano. Imaginarios y realidades ante la globalización. CAPÍTULO 10. Temas críticos en la relación entre identidad territorial, globalización y patrimonio. CAPÍTULO 11. Pensar situado, identidad territorial y patrimonio. CAPÍTULO 12. Tensiones y desafíos para las relaciones entre lo local y lo global1a

Graves' disease is associated with a defective expression of the immune regulatory molecule galectin-9 in antigen-presenting dendritic cells

Introduction Patients with autoimmune thyroid disease (AITD) show defects in their immune-regulatory mechanisms. Herein we assessed the expression and function of galectin-1 and galectin-9 (Gal-1, Gal-9) in dendritic cells (DCs) from patients with AITD. Materials and Methods Peripheral blood samples from 25 patients with Graves’ disease (GD), 11 Hashimoto’s thyroiditis (HT), and 24 healthy subjects were studied. Thyroid tissue samples from 44 patients with AITD and 22 patients with goiter were also analyzed. Expression and function of Gal-1 and Gal-9 was assessed by quantitative RT-PCR, immunofluorescence and flow cytometry. Results A diminished expression of Gal-9, but not of Gal-1, by peripheral blood DCs was observed in GD patients, mainly in those with Graves´ ophthalmopathy, and a significant negative association between disease severity and Gal-9 expression was detected. In addition, the mRNA levels of Gal-9 and its ligand TIM-3 were increased in thyroid tissue from AITD patients and its expression was associated with the levels of Th1/Th12/Th17 cytokines. Immunofluorescence studies proved that intrathyroidal Gal-9 expression was confined to DCs and macrophages. Finally, in vitro functional assays showed that exogenous Gal-9 had a suppressive effect on the release of Th1/Th2/Th17 cytokines by DC/lymphocyte autologous co-cultures from both AITD patients and healthy controls. Conclusions The altered pattern of expression of Gal-9 in peripheral blood DCs from GD patients, its correlation with disease severity as well as its ability to suppress cytokine release suggest that Gal-9 could be involved in the pathogenesis of AITDThis work was supported by grants from the Fondo de Investigaciones Sanitarias (FISS) PI10/ 02521 and S2010/BMD-2328 TIRONET (Comunidad de Madrid), Spain (to MM) and the Fondo de Cooperación Internacional en Ciencia y Tecnología (FONCICYT) 95395, European Union-México (to RGA

Definition of a temporal distribution index for high temporal resolution precipitation data over Peninsular Spain and the Balearic Islands: the fractal dimension; and its synoptic implications

Precipitation on the Spanish mainland and in the Balearic archipelago exhibits a high degree of spatial and temporal variability, regardless of the temporal resolution of the data considered. The fractal dimension indicates the property of self-similarity, and in the case of this study, wherein it is applied to the temporal behaviour of rainfall at a fine (10-min) resolution from a total of 48 observatories, it provides insights into its more or less convective nature. The methodology of Jenkinson & Collison which automatically classifies synoptic situations at the surface, as well as an adaptation of this methodology at 500 hPa, was applied in order to gain insights into the synoptic implications of extreme values of the fractal dimension. The highest fractal dimension values in the study area were observed in places with precipitation that has a more random behaviour over time with generally high totals. Four different regions in which the atmospheric mechanisms giving rise to precipitation at the surface differ from the corresponding above-ground mechanisms have been identified in the study area based on the fractal dimension. In the north of the Iberian Peninsula, high fractal dimension values are linked to a lower frequency of anticyclonic situations, whereas the opposite occurs in the central region. In the Mediterranean, higher fractal dimension values are associated with a higher frequency of the anticyclonic type and a lower frequency of the advective type from the east. In the south, lower fractal dimension values indicate higher frequency with respect to the anticyclonic type from the east and lower frequency with respect to the cyclonic type

Gi/o-protein coupled receptors in the aging brain

Cells translate extracellular signals to regulate processes such as differentiation, metabolism and proliferation, via transmembranar receptors. G protein-coupled receptors (GPCRs) belong to the largest family of transmembrane receptors, with over 800 members in the human species. Given the variety of key physiological functions regulated by GPCRs, these are main targets of existing drugs. During normal aging, alterations in the expression and activity of GPCRs have been observed. The central nervous system (CNS) is particularly affected by these alterations, which results in decreased brain functions, impaired neuroregeneration, and increased vulnerability to neuropathologies, such as Alzheimer's and Parkinson diseases. GPCRs signal via heterotrimeric G proteins, such as Go, the most abundant heterotrimeric G protein in CNS. We here review age-induced effects of GPCR signaling via the Gi/o subfamily at the CNS. During the aging process, a reduction in protein density is observed for almost half of the Gi/o-coupled GPCRs, particularly in age-vulnerable regions such as the frontal cortex, hippocampus, substantia nigra and striatum. Gi/o levels also tend to decrease with aging, particularly in regions such as the frontal cortex. Alterations in the expression and activity of GPCRs and coupled G proteins result from altered proteostasis, peroxidation of membranar lipids and age-associated neuronal degeneration and death, and have impact on aging hallmarks and age-related neuropathologies. Further, due to oligomerization of GPCRs at the membrane and their cooperative signaling, down-regulation of a specific Gi/o-coupled GPCR may affect signaling and drug targeting of other types/subtypes of GPCRs with which it dimerizes. Gi/o-coupled GPCRs receptorsomes are thus the focus of more effective therapeutic drugs aiming to prevent or revert the decline in brain functions and increased risk of neuropathologies at advanced ages.This work was supported by Fundação para a Ciência e Tecnologia, Centro 2020 and Portugal 2020, the COMPETE program, QREN, and the European Union (FEDER program) via the GoBack project (PTDC/CVT-CVT/32261/2017), the pAGE program (Centro-01-0145-FEDER-000003), and Institute for Biomedicine iBiMED (UID/BIM/04501/2013; UID/BIM/04501/2019).publishe

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

The Ca²⁺ Channel Blocker Verapamil Inhibits the In Vitro Activation and Function of T Lymphocytes:A 2022 Reappraisal

Ca(2+) channel blockers (CCBs) are commonly used to treat different cardiovascular conditions. These drugs disrupt the intracellular Ca(2+) signaling network, inhibiting numerous cellular functions in different cells, including T lymphocytes. We explored the effect of the CCB verapamil on normal human peripheral blood T cell activation, proliferation, and cytokine production. Cells were activated by ligating CD3 or CD3/CD28 in the presence or absence of verapamil, and the expression of activation-induced cell surface molecules (CD25, CD40L, CD69, PD-1, and OX40), cell proliferation, and cytokine release were assessed by flow cytometry. Verapamil exerted a dose-dependent inhibitory effect on the expression of all the activation-induced cell surface molecules tested. In addition, verapamil diminished T cell proliferation induced in response to CD3/CD28 stimulation. Likewise, the production of Th1/Th17 and Th2 cytokines was also reduced by verapamil. Our data substantiate a potent in vitro suppressive effect of verapamil on T lymphocytes, a fact that might be relevant in patients receiving CCBs