Guanosine effect on cholesterol efflux and apolipoprotein E expression in astrocytes

The main source of cholesterol in the central nervous system (CNS) is represented by glial cells, mainly astrocytes, which also synthesise and secrete apolipoproteins, in particular apolipoprotein E (ApoE), the major apolipoprotein in the brain, thus generating cholesterol-rich high density lipoproteins (HDLs). This cholesterol trafficking, even though still poorly known, is considered to play a key role in different aspects of neuronal plasticity and in the stabilisation of synaptic transmission. Moreover, cell cholesterol depletion has recently been linked to a reduction in amyloid beta formation. Here we demonstrate that guanosine, which we previously reported to exert several neuroprotective effects, was able to increase cholesterol efflux from astrocytes and C6 rat glioma cells in the absence of exogenously added acceptors. In this effect the phosphoinositide 3 kinase/extracellular signal-regulated kinase 1/2 (PI3K/ERK1/2) pathway seems to play a pivotal role. Guanosine was also able to increase the expression of ApoE in astrocytes, whereas it did not modify the levels of ATP-binding cassette protein A1 (ABCA1), considered the main cholesterol transporter in the CNS. Given the emerging role of cholesterol balance in neuronal repair, these effects provide evidence for a role of guanosine as a potential pharmacological tool in the modulation of cholesterol homeostasis in the brain

SmCL3, a Gastrodermal Cysteine Protease of the Human Blood Fluke Schistosoma mansoni

Parasitic infection caused by blood flukes of the genus Schistosoma is a major global health problem. More than 200 million people are infected. Identifying and characterizing the constituent enzymes of the parasite's biochemical pathways should reveal opportunities for developing new therapies (i.e., vaccines, drugs). Schistosomes feed on host blood, and a number of proteolytic enzymes (proteases) contribute to this process. We have identified and characterized a new protease, SmCL3 (for Schistosoma mansoni cathepsin L3), that is found within the gut tissue of the parasite. We have employed various biochemical and molecular biological methods and sequence similarity analyses to characterize SmCL3 and obtain insights into its possible functions in the parasite, as well as its evolutionary position among cathepsin L proteases in general. SmCL3 hydrolyzes major host blood proteins (serum albumin and hemoglobin) and is expressed in parasite life stages infecting the mammalian host. Enzyme substrate specificity detected by positional scanning-synthetic combinatorial library was confirmed by molecular modeling. A sequence analysis placed SmCL3 to the cluster of other cathepsins L in accordance with previous phylogenetic analyses

Des psychanalystes gardiens de la cité

Tort Michel. Des psychanalystes gardiens de la cité. In: Communications, 59, 1994. Générations et filiation, sous la direction de Claudine Attias-Donfut et Nicole Lapierre. pp. 137-147

Psychiatrie, psychanalyse, histoire (Eléments pour une discussion sur le discours psychiatrique et psychanalytique. Vers une interrogation critique sur l'actualité de leurs "limites")

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Les Esquisses: texte de Charles Darwin, The Origins of Species

International audienc

Contribution aux recherches sur l'origine du transsexualisme (traumas au stade du cocon)

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Acte médical, différence des sexes et métamorphose sexuelle (les médicalisations et les représentations du corps sexué dans les conceptions sur l'hermaphrodisme, la masturbation, la pédérastie, l'inversion sexuelle et le transsexualisme)

MONTPELLIER-BU Médecine (341722104) / SudocPARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF