PDE4 and mAKAPβ are nodal organizers of β2-ARs nuclear PKA signalling in cardiac myocytes

International audienceAims: β1- and β2-adrenergic receptors (β-ARs) produce different acute contractile effects on the heart partly because they impact on different cytosolic pools of cAMP-dependent protein kinase (PKA). They also exert different effects on gene expression but the underlying mechanisms remain unknown. The aim of this study was to understand the mechanisms by which β1- and β2-ARs regulate nuclear PKA activity in cardiomyocytes.Methods and results: We used cytoplasmic and nuclear targeted biosensors to examine cAMP signals and PKA activity in adult rat ventricular myocytes upon selective β1- or β2-ARs stimulation. Both β1- and β2-AR stimulation increased cAMP and activated PKA in the cytoplasm. Although the two receptors also increased cAMP in the nucleus, only β1-ARs increased nuclear PKA activity and up-regulated the PKA target gene and pro-apoptotic factor, inducible cAMP early repressor (ICER). Inhibition of phosphodiesterase (PDE)4, but not Gi, PDE3, GRK2 nor caveolae disruption disclosed nuclear PKA activation and ICER induction by β2-ARs. Both nuclear and cytoplasmic PKI prevented nuclear PKA activation and ICER induction by β1-ARs, indicating that PKA activation outside the nucleus is required for subsequent nuclear PKA activation and ICER mRNA expression. Cytoplasmic PKI also blocked ICER induction by β2-AR stimulation (with concomitant PDE4 inhibition). However, in this case nuclear PKI decreased ICER up-regulation by only 30%, indicating that other mechanisms are involved. Down-regulation of mAKAPβ partially inhibited nuclear PKA activation upon β1-AR stimulation, and drastically decreased nuclear PKA activation upon β2-AR stimulation in the presence of PDE4 inhibition.Conclusions: β1- and β2-ARs differentially regulate nuclear PKA activity and ICER expression in cardiomyocytes. PDE4 insulates a mAKAPβ-targeted PKA pool at the nuclear envelope that prevents nuclear PKA activation upon β2-AR stimulation

Ресурсоэффективные системы в управлении и контроле: взгляд в будущее (т. 2): сборник научных трудов VII Международной конференции школьников, студентов, аспирантов, молодых ученых, 8 -13 октября 2018 г., г. Томск

В сборнике представлены материалы VII Международной конференции школьников, студентов, аспирантов, молодых ученых "Ресурсоэффективные системы в управлении и контроле: взгляд в будущее". Более 500 авторов из 35 вузов, предприятий и научных исследовательских университетов России, ближнего и дальнего зарубежья представили тезисы своих докладов, в которых рассматриваются актуальные проблемы неразрушающего контроля и технической диагностики, внедрения систем менеджмента, качества образования, управления в современной экономике. Материалы предназначены для специалистов, преподавателей, аспирантов и студентов вузов, а также для всех интересующихся проблемами ресурсоэффективных технологий

The macrophage in HIV-1 infection: From activation to deactivation?

Macrophages play a crucial role in innate and adaptative immunity in response to microorganisms and are an important cellular target during HIV-1 infection. Recently, the heterogeneity of the macrophage population has been highlighted. Classically activated or type 1 macrophages (M1) induced in particular by IFN-γ display a pro-inflammatory profile. The alternatively activated or type 2 macrophages (M2) induced by Th-2 cytokines, such as IL-4 and IL-13 express anti-inflammatory and tissue repair properties. Finally IL-10 has been described as the prototypic cytokine involved in the deactivation of macrophages (dM). Since the capacity of macrophages to support productive HIV-1 infection is known to be modulated by cytokines, this review shows how modulation of macrophage activation by cytokines impacts the capacity to support productive HIV-1 infection. Based on the activation status of macrophages we propose a model starting with M1 classically activated macrophages with accelerated formation of viral reservoirs in a context of Th1 and proinflammatory cytokines. Then IL-4/IL-13 alternatively activated M2 macrophages will enter into the game that will stop the expansion of the HIV-1 reservoir. Finally IL-10 deactivation of macrophages will lead to immune failure observed at the very late stages of the HIV-1 disease

La dépression du post partum : qualité de l'information reçue et prévalence du risque à J3 : étude menée auprès de 208 femmes au CHU de Caen

The main aim of the study was about evaluating the impact of information on the risk of postpartum depression assessed by the Edinburgh Postnatal Depression Scale (EPDS). For this, we conducted a prospective observational study of analytic cross-type with women on the third day postpartum hospitalized in the University Hospital of Caen. No correlation was found between women who had low scores on the EPDS and quality of information. However, there is a real deficiency on the part of the medical profession in the diffusion of this information. But women are from a real demand to benefit from additional information about postpartum depression.L’objectif principal de cette étude était de mesurer l’impact de l’information sur le risque de la dépression du post partum (DPP) évalué par l’Edinburg Postnatal Depression Scale (EPDS). Pour ce fait, nous avons réalisé une étude prospective observationnelle analytique de type transversal auprès de 208 femmes au troisième jour du post partum hospitalisées en suite de naissance au CHU de Caen. Aucune corrélation n’a été retrouvée entre les femmes qui avaient un faible score à l’EPDS et la qualité de l’information. Cependant, il existe un réel défaut d’information de la part du corps médical sur la DPP alors que les femmes expriment le souhait de bénéficier de renseignements complémentaires sur cette pathologie

Mechanically Isolated Stromal Vascular Fraction by Nanofat Emulsification Techniques

International audienceno abstrac

CD54-Mediated Interaction with Pro-inflammatory Macrophages Increases the Immunosuppressive Function of Human Mesenchymal Stromal Cells

Summary: Mesenchymal stromal cells (MSCs) sense and modulate inflammation and represent potential clinical treatment for immune disorders. However, many details of the bidirectional interaction of MSCs and the innate immune compartment are still unsolved. Here we describe an unconventional but functional interaction between pro-inflammatory classically activated macrophages (M1MΦ) and MSCs, with CD54 playing a central role. CD54 was upregulated and enriched specifically at the contact area between M1MФ and MSCs. Moreover, the specific interaction induced calcium signaling and increased the immunosuppressive capacities of MSCs dependent on CD54 mediation. Our data demonstrate that MSCs can detect an inflammatory microenvironment via a direct and physical interaction with innate immune cells. This finding opens different perspectives for MSC-based cell therapy. : Mesenchymal stromal cells (MSCs) are promising for cell-based therapy in inflammatory disorders by switching off the immune response. Varin and colleagues demonstrate that MSCs and inflammatory macrophages communicate via an unconventional but functional interaction that strongly increases the immunosuppressive capacities of MSCs. This new communication between the innate immune system and MSCs opens new perspectives for MSC-based cell therapy. Keywords: macrophages, bone marrow mesenchymal stromal cells, functional interaction, CD54, immunosuppression, indoleamine 2,3-dioxygenase, cell therap

A subset of functional effector-memory CD8+ T lymphocytes in human immunodeficiency virus-infected patients

CD8+ T cells provide protective immune responses via both cytolytic and non-cytolytic mechanisms in subjects infected with human immunodeficiency virus (HIV). In the present study, we investigated the CD28 expression of CD8+ T cells present in the peripheral blood lymphocyte subset isolated from chronically HIV-infected subjects. Using flow cytometric analysis, a continuous spectrum of CD28 intensity ranging from negative to high, which could be separated into CD28-negative, intermediate (int) and high, was seen for CD8+ T cells. Our study focused mostly on the CD28int CD8+ T cells. The CD28int CD8+ T cells are CD57– CD27+ CD45RO+ CD45RA– CCR7low CD62Lint. The proliferative capacity of CD28int CD8+ T cells was intermediate between those of CD28– CD8+ T cells and CD28high CD8+ T cells. The CD28int CD8+ T cells are specific for HIV, cytomegalovirus (CMV) and Epstein–Barr virus (EBV) antigens as measured by human leucocyte antigen pentamer binding and produce both intracellular interferon-γ and tumour necrosis factor-α in response to their cognate viral peptides. The CD28int CD8+ T cells have HIV-specific, CMV-specific and EBV-specific cytotoxic activity in response to their cognate viral peptides. These findings indicate that a subset of functional effector-memory CD8+ T cells specific for HIV, CMV and EBV antigens may contribute to an efficient immune response in HIV-infected subjects