Beneficial effects of reconstituted high-density lipoprotein (rHDL) on circulating CD34+ cells in patients after an acute coronary syndrome

Background: High-density lipoproteins (HDL) favorably affect endothelial progenitor cells (EPC). Circulating progenitor cell level and function are impaired in patients with acute coronary syndrome (ACS). This study investigates the short-term effects of reconstituted HDL (rHDL) on circulating progenitor cells in patients with ACS. Methods and Findings: The study population consisted of 33 patients with recent ACS: 20 patients from the ERASE trial (randomized to receive 4 weekly intravenous infusions of CSL-111 40 mg/kg or placebo) and 13 additional patients recruited as controls using the same enrolment criteria. Blood was collected from 16 rHDL (CSL-111)-treated patients and 17 controls at baseline and at 6–7 weeks (i.e. 2–3 weeks after the fourth infusion of CSL-111 in ERASE). CD34+ and CD34+/kinase insert domain receptor (KDR+) progenitor cell counts were analyzed by flow cytometry. We found preserved CD34+ cell counts in CSL-111-treated subjects at follow-up (change of 1.6%), while the number of CD34+ cells was reduced (-32.9%) in controls (p = 0.017 between groups). The level of circulating SDF-1 (stromal cell-derived factor-1), a chemokine involved in progenitor cell recruitment, increased significantly (change of 21.5%) in controls, while it remained unchanged in CSL-111-treated patients (p = 0.031 between groups). In vitro exposure to CSL-111 of early EPC isolated from healthy volunteers significantly increased CD34+ cells, reduced early EPC apoptosis and enhanced their migration capacity towards SDF-1. Conclusions: The relative increase in circulating CD34+ cells and the low SDF-1 levels observed following rHDL infusions in ACS patients point towards a role of rHDL in cardiovascular repair mechanisms

Entre français général, français sur objectifs spécifiques et culture scientifique : le Campus Numérique FORPRINT, FOAD préparatoire à l'intégration dans l'enseignement supérieur.

Les actes peuvent être commandés sur le site Tice 2004 (70€).The goal of our paper is to present Forprint which is, in terms of application and uses, a training for the integration of foreign students in french Universities of Technology & Sciences and Engineering Schools. In terms of cooperation and network, Forprint associates seven institutions of higher education which share a long experience in using ICT in two major fields of education: French as a Foreign Language & for Special Purposes, Sciences & Technology. We want to favour, through -and with the help of- the linguistic learning, an approach which combines, not only autonomy with scaffolding, but also scientific and general culture.Forprint est un Campus numérique destiné à la FOAD d'étudiants scientifiques étrangers, en français et “à la française”. Il associe un ensemble d'établissements de formation et de recherche qui ont créé, sur la base d'une part d'une réflexion et d'une pratique méthodologiques commune privilégiant l'individualisation et l'accompagnement, d'autre part d'une mutualisation des ressources, un dispositif et un ensemble de modules scientifiques et linguistiques visant, dans une phase préparatoire à l'intégration dans l'enseignement supérieur français, à mettre à niveau ces étudiants dans leur (future) spécialité. L'enjeu de l'entreprise est de faire valoir une méthode d'apprentissage linguistique “sur objectifs spécifiques” et une méthodologie d'enseignement scientifique “à la française” qui ne considèrent pas la langue comme un seul outil de communication mais tend à en privilégier les aspects et les dimensions culturels, qu'il s'agisse de culture générale ou de culture spécialisée

Microglial Involvement in Neuroplastic Changes Following Focal Brain Ischemia in Rats

The pathogenesis of ischemic stroke is a complex sequence of events including inflammatory reaction, for which the microglia appears to be a major cellular contributor. However, whether post-ischemic activation of microglial cells has beneficial or detrimental effects remains to be elucidated, in particular on long term brain plasticity events. The objective of our study was to determine, through modulation of post-stroke inflammatory response, to what extent microglial cells are involved in some specific events of neuronal plasticity, neurite outgrowth and synaptogenesis. Since microglia is a source of neurotrophic factors, the identification of the brain-derived neurophic factor (BDNF) as possible molecular actor involved in these events was also attempted. As a means of down-regulating the microglial response induced by ischemia, 3-aminobenzamide (3-AB, 90 mg/kg, i.p.) was used to inhibit the poly(ADP-ribose) polymerase-1 (PARP-1). Indeed, PARP-1 contributes to the activation of the transcription factor NF-kB, which is essential to the upregulation of proinflammatory genes, in particular responsible for microglial activation/proliferation. Experiments were conducted in rats subjected to photothrombotic ischemia which leads to a strong and early microglial cells activation/proliferation followed by an infiltration of macrophages within the cortical lesion, events evaluated at serial time points up to 1 month post-ictus by immunostaining for OX-42 and ED-1. Our most striking finding was that the decrease in acute microglial activation induced by 3-AB was associated with a long term down-regulation of two neuronal plasticity proteins expression, synaptophysin (marker of synaptogenesis) and GAP-43 (marker of neuritogenesis) as well as to a significant decrease in tissue BDNF production. Thus, our data argue in favour of a supportive role for microglia in brain neuroplasticity stimulation possibly through BDNF production, suggesting that a targeted protection of microglial cells could represent an innovative approach to potentiate post-stroke neuroregeneration

Different Transport Mechanisms in Plant and Human AMT/Rh-type Ammonium Transporters

The conserved family of AMT/Rh proteins facilitates ammonium transport across animal, plant, and microbial membranes. A bacterial homologue, AmtB, forms a channel-like structure and appears to function as an NH3 gas channel. To evaluate the function of eukaryotic homologues, the human RhCG glycoprotein and the tomato plant ammonium transporter LeAMT1;2 were expressed and compared in Xenopus oocytes and yeast. RhCG mediated the electroneutral transport of methylammonium (MeA), which saturated with Km = 3.8 mM at pHo 7.5. Uptake was strongly favored by increasing the pHo and was inhibited by ammonium. Ammonium induced rapid cytosolic alkalinization in RhCG-expressing oocytes. Additionally, RhCG expression was associated with an alkali-cation conductance, which was not significantly permeable to NH4+ and was apparently uncoupled from the ammonium transport. In contrast, expression of the homologous LeAMT1;2 induced pHo-independent MeA+ uptake and specific NH4+ and MeA+ currents that were distinct from endogenous currents. The different mechanisms of transport, including the RhCG-associated alkali-cation conductance, were verified by heterologous expression in appropriate yeast strains. Thus, homologous AMT/Rh-type proteins function in a distinct manner; while LeAMT1;2 carries specifically NH4+, or cotransports NH3/H+, RhCG mediates electroneutral NH3 transport

Do universal ao pluriversal: questões e desafios do paradigma decolonial

O texto a seguir é uma tradução de « De l'universel au pluriversel. Enjeux et défis du paradigme décolonial », artigo de Claude Bourguignon Rougier e Philippe Colin, publicado na revista Raison présente (nº 199) em 2016. Citando autores como Enrique Dussel, Aníbal Quijano, Edgardo Lander, Walter Mignolo, Santiago Castro-Gómez, Arturo Escobar, Nelson Maldonado Torres, Ramón Grosfoguel e Catherine Walsh, cujas contribuições teóricas têm grande importância, Claude Bourguignon Rougier e Philippe Colin trazem questões e desafios do paradigma decolonial, que se debruça sobre a “geopolítica do poder, do saber e do ser” resultante do processo colonizatório europeu sobre partes do globo. Ressaltam a centralidade epistêmica da colonialidade e sua íntima relação com a modernidade construída sobre uma narrativa eurocêntrica; Rougier e Colin propõem, assim, uma pauta não mais baseada na elaboração de conhecimento a partir de um viés eurocentrista, mas pluriversal, conferindo a devida importância às histórias locais e possibilitando, com isso, reavaliar o lugar de enunciação convencionado pela modernidade. A tradução deste artigo ao português brasileiro visa a tornar acessível a leitura àqueles que demonstrem interesse na abordagem proposta pelos autores, possibilitando, com isso, a diversidade de pontos de vista e o consequente enriquecimento do debate acerca do giro decolonial

Cellular Models of Aggregation-Dependent Template-Directed Proteolysis to Characterize Tau Aggregation Inhibitors for Treatment of Alzheimer's Disease

Copyright © 2015, The American Society for Biochemistry and Molecular Biology. Acknowledgements-We thank Drs Timo Rager and Rolf Hilfiker (Solvias, Switzerland) for polymorph analyses.Peer reviewedPublisher PD