Statins Suppress Apolipoprotein CIII-Induced Vascular Endothelial Cell Activation and Monocyte Adhesion

Aims: Activation of vascular endothelial cells (ECs) contributes importantly to inflammation and atherogenesis. We previously reported that apolipoprotein CIII (apoCIII), found abundantly on circulating triglyceride-rich lipoproteins, enhances adhesion of human monocytes to ECs in vitro. Statins may exert lipid-independent anti-inflammatory effects. The present study examined whether statins suppress apoCIII-induced EC activation in vitro and in vivo. Methods and results: Physiologically relevant concentrations of purified human apoCIII enhanced attachment of the monocyte-like cell line THP-1 to human saphenous vein ECs (HSVECs) or human coronary artery ECs (HCAECs) under both static and laminar shear stress conditions. This process mainly depends on vascular cell adhesion molecule-1 (VCAM-1), as a blocking VCAM-1 antibody abolished apoCIII-induced monocyte adhesion. ApoCIII significantly increased VCAM-1 expression in HSVECs and HCAECs. Pre-treatment with statins suppressed apoCIII-induced VCAM-1 expression and monocyte adhesion, with two lipophilic statins (pitavastatin and atorvastatin) exhibiting inhibitory effects at lower concentration than those of hydrophilic pravastatin. Nuclear factor κB (NF-κB) mediated apoCIII-induced VCAM-1 expression, as demonstrated via loss-of-function experiments, and pitavastatin treatment suppressed NF-κB activation. Furthermore, in the aorta of hypercholesterolaemic $Ldlr^{−/−}$ mice, pitavastatin administration in vivo suppressed VCAM-1 mRNA and protein, induced by apoCIII bolus injection. Similarly, in a subcutaneous dorsal air pouch mouse model of leucocyte recruitment, apoCIII injection induced F4/80+ monocyte and macrophage accumulation, whereas pitavastatin administration reduced this effect. Conclusions: These findings further establish the direct role of apoCIII in atherogenesis and suggest that anti-inflammatory effects of statins could improve vascular disease in the population with elevated plasma apoCIII

A DOCK8-WIP-WASp complex links T cell receptors to the actin cytoskeleton

Wiskott-Aldrich syndrome (WAS) is associated with mutations in the WAS protein (WASp), which plays a critical role in the initiation of T cell receptor–driven (TCR-driven) actin polymerization. The clinical phenotype of WAS includes susceptibility to infection, allergy, autoimmunity, and malignancy and overlaps with the symptoms of dedicator of cytokinesis 8 (DOCK8) deficiency, suggesting that the 2 syndromes share common pathogenic mechanisms. Here, we demonstrated that the WASp-interacting protein (WIP) bridges DOCK8 to WASp and actin in T cells. We determined that the guanine nucleotide exchange factor activity of DOCK8 is essential for the integrity of the subcortical actin cytoskeleton as well as for TCR-driven WASp activation, F-actin assembly, immune synapse formation, actin foci formation, mechanotransduction, T cell transendothelial migration, and homing to lymph nodes, all of which also depend on WASp. These results indicate that DOCK8 and WASp are in the same signaling pathway that links TCRs to the actin cytoskeleton in TCR-driven actin assembly. Further, they provide an explanation for similarities in the clinical phenotypes of WAS and DOCK8 deficiency.United States. Public Health Service (RO1AI114588)United States. Public Health Service (K08AI114968

CD47 plays a critical role in T-cell recruitment by regulation of LFA-1 and VLA-4 integrin adhesive functions

CD47 plays an important but incompletely understood role in the innate and adaptive immune responses. CD47, also called integrin-associated protein, has been demonstrated to associate in cis with β1 and β3 integrins. Here we test the hypothesis that CD47 regulates adhesive functions of T-cell α4β1 (VLA-4) and αLβ2 (LFA-1) in in vivo and in vitro models of inflammation. Intravital microscopy studies reveal that CD47(−/−) Th1 cells exhibit reduced interactions with wild-type (WT) inflamed cremaster muscle microvessels. Similarly, murine CD47(−/−) Th1 cells, as compared with WT, showed defects in adhesion and transmigration across tumor necrosis factor-α (TNF-α)–activated murine endothelium and in adhesion to immobilized intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion protein 1 (VCAM-1) under flow conditions. Human Jurkat T-cells lacking CD47 also showed reduced adhesion to TNF-α–activated endothelium and ICAM-1 and VCAM-1. In cis interactions between Jurkat T-cell β2 integrins and CD47 were detected by fluorescence lifetime imaging microscopy. Unexpectedly, Jurkat CD47 null cells exhibited a striking defect in β1 and β2 integrin activation in response to Mn(2+) or Mg(2+)/ethylene glycol tetraacetic acid treatment. Our results demonstrate that CD47 associates with β2 integrins and is necessary to induce high-affinity conformations of LFA-1 and VLA-4 that recognize their endothelial cell ligands and support leukocyte adhesion and transendothelial migration

TRANSLATING IDIOMS OF COLOUR (an Examination of the Relationship of Idioms of Colour Between English, Arabic and Spanish Languages)

Nowadays, human communication is considered to be one of the most important topics occupying the minds of linguists, anthropologists, psychologists, and philosophers. Since it is the most important means for communication among human beings, the relation between language, history, culture, worldview and their mutual interactions have high significance. The inextricable connection highlights different indications of conventionalized language including the idiomatic expressions as one of the important and pervasive language uses reflecting culture in real life. Like different sorts of figurative language, idioms give off an impression of being the common decoders of traditions, social convictions, social traditions, and standards. Idioms, as a major component of native-like correspondence, empower a language learner to comprehend the thoughts, feelings and perspectives of the speakers of target language. Therefore, learning idioms provides learners a good opportunity to get data about the basic parameters of a language

Análise temporal de áreas degradadas pela mineração de nióbio e fosfato no sudeste de Goiás : uma contribuição do sensoriamento remoto a partir da plataforma MapBiomas

Trabalho de Conclusão de Curso (graduação)—Universidade de Brasília, Instituto de Ciências Biológicas, Instituto de Geociências, Instituto de Química, Faculdade de Administração, Contabilidade, Economia - Departamento de Economia, Centro de Desenvolvimento Sustentável, 2020.Tendo em vista a relevância dos depósitos de nióbio e fosfato para a economia brasileira, pesquisa-se sobre os efeitos da exploração mineral nas paisagens naturais de Catalão e Ouvidor, a fim de analisar a evolução das áreas degradadas entre 1985 e 2019. Para tanto, é necessário descrever os principais efeitos da degradação ambiental nas comunidades próximas aos empreendimentos, mensurar os avanços territoriais da atividade mineradora entre 1985 e 2019 e compreender a dinâmica das paisagens naturais ao longo do tempo. Realiza-se, então, uma pesquisa bibliográfica e uma análise comparativa dos mapas de uso e cobertura do solo, juntamente com as estatísticas geradas para cada classe, a partir dos dados gerados pela classificação automática, aplicada a imagens de satélite, elaborada pelo projeto MapBiomas. Diante disso, verifica-se que apesar dos vários impactos negativos inerentes à atividade mineral, desde o registro mais antigo (1985) o território já era bastante antropizado pelas atividades de agropecuária, demonstrando grande peso sob uso e ocupação da terra em Catalão e Ouvidor

Efecto de altas concentraciones de D-Glucosa sobre la adhesión leucocitaria en células endoteliales humanas

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina. Departamento Farmacología y Terpéutica. Fecha de lectura: 15 de Enero de 2009

La ley penal : estudios prácticos sobre la interpretación, inteligencia y aplicación del Código de 1870, ... / por Manuel Azcutia

FA110XI, 476 p

Território jovem : uma discussão sobre sexualidade e gravidez na adolescência no município de Matinhos - PR

Orientador :Monografia (especialização) - Universidade Federal do Paraná, Setor de ..., Curso de Especialização em ...Inclui referência

Interconexión, mediante base de datos, de célula de fabricación con su gemelo digital

El marco general de este Trabajo Fin de Grado es la interconexión de datos de determinados dispositivos situados en una célula de fabricación flexible a un Gemelo Digital. Para llevar a cabo dicha interconexión es necesario el diseño de una base de datos que realice de intermediario y almacene los datos que recibe de la planta real. Es por ello que en este trabajo se desarrolla una interconexión entre la célula de fabricación y la base de datos y otra interconexión entre la base de datos y el Gemelo Digital, implementado en Unity3D. Así como se desarrolla un aprendizaje del Gemelo Digital, a partir de los datos obtenidos, aplicado a casos concretos.The general objective of this Final Degree Project is the interconnection of data from certain devices located in a flexible manufacturing cell to a Digital Twin. In order to carry out this interconnection, it is necessary to design a database that acts as an intermediary and stores the data received from the real plant. That is why in this work an interconnection is developed between the manufacturing cell and the database and another interconnection between the database and the Digital Twin, implemented in Unity3D. It also develops a learning process for the Digital Twin, based on the data obtained, applied to specific cases.Universidad de Sevilla. Grado en Ingeniería de las Tecnologías Industriale

Funciones reales : completa y detallada descripción de las celebradas en esta corte con motivo del régio enlace de S. M. y A.

Copia digital. Valladolid : Junta de Castilla y León. Consejería de Cultura y Turismo, 201