From Pierre and Marie Curie University to the Sorbonne: A radical management reform in French universities

Wychodząc w swoich rozważaniach od akcentów historycznych i kontekstu międzynarodowego, autor próbuje uzasadnić potrzebę radykalnych reform szkolnictwa wyższego i organizacji badań naukowych we Francji. Wskazuje przy tym na bariery występujące w codziennej praktyce, na konieczność wzmocnienia powiązań między szkolnictwem wyższym i badaniami naukowymi, na potrzebę rozwoju kontaktów między uniwersytetami i przedsiębiorstwami. Jako profesor i wieloletni prezydent Uniwersytetu Piotra i Marii Curie (Paris VI), wielokrotnie odwołuje się do doświadczeń tej uczelni w racjonalizowaniu finansowania i zarządzania kształceniem studentów oraz badaniami.Using historical aspects and the international context as his point of departure, the author attempts to justify the need for radical reforms in higher education and the organisation of research in France. He also identifies day-to-day barriers, pointing to the need to strengthen the links between higher education and research and the need to develop networking between universities and industry. A professor and a long-time president of the Pierre and Marie Curie University, Gilbert Bereziat makes multiple references to the experience of his school in rationalising funding and managing the teaching and research functions

Strategies for international excellence of european universities: From UPMC to La Sorbonne University 10 years of reforms

Proceeding of: Strategies for International Excellence of European Research Universities. Sharing best practices. April 16, 2010. Getafe, MadridPublicad

Transcriptional regulation of apolipoprotein A-I expression in Hep G2 cells by phorbol ester

AbstractThe regulation of apolipoprotein A-I (apo A-I) gene expression by 12-O-tetradecanoylphorbol 13-acetate (TPA) was investigated in the human hepatoma cell line Hep G2. TPA treatment decreased apo A-I mRNA levels in a time-dependent manner, by up to 50% versus control cells within 24 h. Nuclear run-on transcription assays demonstrated a transcriptional effect of TPA. Using transfection analysis with a plasmid construct containing the −1378/+11 apo A-I promoter fused to the secreted placental alkaline phosphatase (SPAP) reporter gene, we showed that the SPAP activity was decreased to 50% when Hep G2 cells were incubated in the presence of TPA. The inhibitory effect of TPA was still maintained when fragment −253 to −4 of apo A-I promoter was linked to the CAT reporter gene. These data indicate that transcriptional modulation of apolipoprotein A-I gene expression following phorbol ester treatment is transduced by gene elements located between −253 and −4 of the apo A-I promoter

Od Uniwersytetu Piotra i Marii Curie do Uniwersytetu Sorbony. Radykalna reforma zarządzania francuskimi uniwersytetami

Wychodząc w swoich rozważaniach od akcentów historycznych i kontekstu międzynarodowego, autor próbuje uzasadnić potrzebę radykalnych reform szkolnictwa wyższego i organizacji badań naukowych we Francji. Wskazuje przy tym na bariery występujące w codziennej praktyce, na konieczność wzmocnienia powiązań między szkolnictwem wyższym i badaniami naukowymi, na potrzebę rozwoju kontaktów między uniwersytetami i przedsiębiorstwami. Jako profesor i wieloletni prezydent Uniwersytetu Piotra i Marii Curie (Paris VI), wielokrotnie odwołuje się do doświadczeń tej uczelni w racjonalizowaniu finansowania i zarządzania kształceniem studentów oraz badaniami

The Modulation of Apolipoprotein E Gene Expression by 3,3'-5-triiodothyronine in HepG2 Cells Occurs at Transcriptional and Post-transcriptional Levels

International audienc

Thyroid Hormone Modulates Apolipoprotein-AI Gene Expression at the Post-Transcriptional Level in Hep G2 Cells

International audienc

-amyloid context intensifies vascular smooth muscle cells induced inflammatory response and de-differentiation

International audienceSeveral studies have shown that the accumulation of -amyloid peptides in the brain parenchyma or vessel wall generates an inflammatory environment. Some even suggest that there is a cause-and-effect relationship between inflammation and the development of Alzheimer's disease and/or cerebral amyloid angiopathy (CAA). Here, we studied the ability of wild-type A1-40-peptide (the main amyloid peptide that accumulates in the vessel wall in sporadic forms of CAA) to modulate the phenotypic transition of vascular smooth muscle cells (VSMCs) toward an inflammatory/de-differentiated state. We found that A1-40-peptide alone neither induces an inflammatory response, nor decreases the expression of contractile markers; however, the inflammatory response of VSMCs exposed to A1-40-peptide prior to the addition of the pro-inflammatory cytokine IL-1 is greatly intensified compared with IL-1-treated VSMCs previously un-exposed to A1-40-peptide. Similar conclusions could be drawn when tracking the decline of contractile markers. Furthermore, we found that the mechanism of this potentiation highly depends on an A1-40 preactivation of the PI3Kinase and possibly NFB pathway; indeed, blocking the activation of these pathways during A1-40-peptide treatment completely suppressed the observed potentiation. Finally, strengthening the possible in vivo relevance of our findings, we evidenced that endothelial cells exposed to A1-40-peptide generate an inflammatory context and have similar effects than the ones described with IL-1. These results reinforce the idea that intraparietal amyloid deposits triggering adhesion molecules in endothelial cells, contribute to the transition of VSMCs to an inflammatory/de-differentiated phenotype. Therefore, we suggest that acute inflammatory episodes may increase vascular alterations and contribute to the ontogenesis of CAA

Transcriptional regulation of the rat type IIA phospholipase A2 gene by cAMP and interleukin-1beta in vascular smooth muscle cells: interplay of the CCAAT/enhancer binding protein (C/EBP), nuclear factor-kappaB and Ets transcription factors.

The abundant secretion of type IIA secreted phospholipase A(2) (sPLA(2)) is a major feature of the inflammatory process of atherosclerosis. sPLA(2) is crucial for the development of inflammation, as it catalyses the production of lipid mediators and induces the proliferation of smooth muscle cells. We have analysed the activation of sPLA(2) transcription by cAMP and interleukin-1beta (IL-1beta), and shown that the 500 bp region upstream of the transcription start site of the rat sPLA(2) gene is implicated in activation by synergistically acting cAMP and IL-1beta. We transiently transfected and stimulated rat smooth muscle cells in primary culture and measured the promoter activities of serial and site-directed deletion mutants of sPLA(2)-luciferase constructs. A distal region, between -488 and -157 bp, bearing a CAAT/enhancer binding protein (C/EBP)-responsive element (-242 to -223) was sufficient for cAMP/protein kinase A-mediated sPLA(2) promoter activation. We find evidence for the first time that activation of the sPLA(2) promoter by IL-1beta requires activation of an Ets-responsive element in the -184 to -180 region of the distal promoter via the Ras pathway and a nuclear factor-kappaB site at positions -141 to -131 of the proximal promoter. We also used electrophoretic mobility shift assays to identify five binding sites for the Sp1 factor; a specific inhibitor of Sp1, mithramycin A, showed that this factor is crucial for the basal activity of the sPLA(2) promoter

Wild-type amyloid beta 1-40 peptide induces vascular smooth muscle cell death independently from matrix metalloprotease activity

International audienceCerebral amyloid angiopathy (CAA) is an important cause of intracerebral hemorrhages in the elderly, characterized by amyloid-beta (A beta) peptide accumulating in central nervous system blood vessels. Within the vessel walls, A beta-peptide deposits [composed mainly of wild-type (WT) A beta 1-40 peptide in sporadic forms] induce impaired adhesion of vascular smooth muscle cells (VSMCs) to the extracellular matrix (ECM) associated with their degeneration. This process often results in a loss of blood vessel wall integrity and ultimately translates into cerebral ischemia and microhemorrhages, both clinical features of CAA. In this study, we decipher the molecular mechanism of matrix metalloprotease (MMP)-2 activation in WT-A beta 1-40-treated VSMC and provide evidence that MMP activity, although playing a critical role in cell detachment disrupting ECM components, is not involved in the WT-A beta 1-40-induced degeneration of VSMCs. Indeed, whereas this peptide clearly induced VSMC apoptosis, neither preventing MMP-2 activity nor hampering the expression of membrane type1-MMP, or preventing tissue inhibitors of MMPs-2 (TIMP-2) recruitment (two proteins evidenced here as involved in MMP-2 activation), reduced the number of dead cells. Even the use of broad-range MMP inhibitors (GM6001 and Batimastat) did not affect WT-A beta 1-40-induced cell apoptosis. Our results, in contrast to those obtained using the A beta 1-40 Dutch variant suggesting a link between MMP-2 activity, VSMC mortality and degradation of specific matrix components, indicate that the ontogenesis of the Dutch familial and sporadic forms of CAAs is different. ECM degradation and VSMC degeneration would be tightly connected in the Dutch familial form while being two independent processes in sporadic forms of CAA