[14 juillet 1919, foule place du Palais Royal, les Grands magasins du Louvre décorés et illuminés] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54995

[14 juillet 1919, foule place du Palais Royal, les Grands magasins du Louvre décorés et illuminés] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54995 bis

[14 juillet 1919, Hôtel de ville et place de l'Hôtel de ville de Paris décorés et illuminés] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54998

[14 juillet 1919, Hôtel de ville et place de l'Hôtel de ville de Paris décorés et illuminés] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54999

[14 juillet 1919, Hôtel de ville et place de l'Hôtel de ville de Paris décorés et illuminés] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 55000

[14 juillet 1919, un bal populaire dans Paris] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 55001

[14 juillet 1919, un bal populaire dans Paris] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 55002

[Segni. Porta Saracena]

Référence bibliographique : Weigert, 658

Molecular substitution rate increases in myrmecophilous lycaenid butterflies (Lepidoptera)

Is species diversification driven by neutral- or niche-based processes? Butterflies of the Lycaenidae family have developed mutualistic interactions with ants. This biotic requirement increased the spatial fragmentation of populations of lower effective population size (Ne) compared with autonomous species. The nearly neutral theory predicts that species with smaller Ne should fix more mutations because of the increased strength of drift. Taking into account the phylogenetic relatedness among species, this study shows that species with a stronger dependence on ants displayed more intra-specific Single Nucleotide Polymorphisms compared with species with low or no myrmecophily. This phenomenon can cause more pronounced genetic differentiation between populations and could ultimately promote speciation in a similar manner as on physical islands. The large species diversity observed in this family could be the consequence of this neutral process enhancing the diversification of lineages.

The integrin antagonist cilengitide activates alphaVbeta3, disrupts VE-cadherin localization at cell junctions and enhances permeability in endothelial cells.

Cilengitide is a high-affinity cyclic pentapeptdic alphaV integrin antagonist previously reported to suppress angiogenesis by inducing anoikis of endothelial cells adhering through alphaVbeta3/alphaVbeta5 integrins. Angiogenic endothelial cells express multiple integrins, in particular those of the beta1 family, and little is known on the effect of cilengitide on endothelial cells expressing alphaVbeta3 but adhering through beta1 integrins. Through morphological, biochemical, pharmacological and functional approaches we investigated the effect of cilengitide on alphaVbeta3-expressing human umbilical vein endothelial cells (HUVEC) cultured on the beta1 ligands fibronectin and collagen I. We show that cilengitide activated cell surface alphaVbeta3, stimulated phosphorylation of FAK (Y(397) and Y(576/577)), Src (S(418)) and VE-cadherin (Y(658) and Y(731)), redistributed alphaVbeta3 at the cell periphery, caused disappearance of VE-cadherin from cellular junctions, increased the permeability of HUVEC monolayers and detached HUVEC adhering on low-density beta1 integrin ligands. Pharmacological inhibition of Src kinase activity fully prevented cilengitide-induced phosphorylation of Src, FAK and VE-cadherin, and redistribution of alphaVbeta3 and VE-cadherin and partially prevented increased permeability, but did not prevent HUVEC detachment from low-density matrices. Taken together, these observations reveal a previously unreported effect of cilengitide on endothelial cells namely its ability to elicit signaling events disrupting VE-cadherin localization at cellular contacts and to increase endothelial monolayer permeability. These effects are potentially relevant to the clinical use of cilengitide as anticancer agent.

Lettre de M. l'abbé de ***, à un curé de ses amis, à l'occasion du serment civique décrété le 16 novembre dernier ([Reprod.])

Collection : Les archives de la Révolution française ; 8.658

RETINOBLASTOMA RELATED1 Regulates Asymmetric Cell Divisions in Arabidopsis.

Formative, also called asymmetric, cell divisions produce daughter cells with different identities. Like other divisions, formative divisions rely first of all on the cell cycle machinery with centrally acting cyclin-dependent kinases (CDKs) and their cyclin partners to control progression through the cell cycle. However, it is still largely obscure how developmental cues are translated at the cellular level to promote asymmetric divisions. Here, we show that formative divisions in the shoot and root of the flowering plant Arabidopsis thaliana are controlled by a common mechanism that relies on the activity level of the Cdk1 homolog CDKA;1, with medium levels being sufficient for symmetric divisions but high levels being required for formative divisions. We reveal that the function of CDKA;1 in asymmetric cell divisions operates through a transcriptional regulation system that is mediated by the Arabidopsis Retinoblastoma homolog RBR1. RBR1 regulates not only cell cycle genes, but also, independent of the cell cycle transcription factor E2F, genes required for formative divisions and cell fate acquisition, thus directly linking cell proliferation with differentiation. This mechanism allows the implementation of spatial information, in the form of high kinase activity, with intracellular gating of developmental decisions.

Population pharmacokinetics in chronic myeloid leukaemia patients: observations under field-conditions

Introduction: Therapeutic drug monitoring (TDM) of imatinib has been increasingly proposed for chronic myeloid leukaemia (CML) patients, as several studies have found a correlation between trough concentrations (Cmin) >=1000ng/ml and improved response. The pharmacological monitoring project of EUTOS (European Treatment and Outcome Study) was launched to increase the availability of imatinib TDM, standardize labs, and validate proposed Cmin thresholds. Using the collected data, the objective of this analysis was to characterize imatinib Population pharmacokinetics (Pop-PK) in a large cohort of European patients, to quantify its variability and the influence of demographic factors and comedications, and to derive individual exposure variables suitable for further concentration-effect analyses.¦Methods: 4095 PK samples from 2478 adult patients were analyzed between 2006 and 2010 by LC-MS-MS and considered for Pop-PK analysis by NONMEM®. Model building used data from 973 patients with >=2 samples available (2590 samples). A sensitivity analysis was performed using all data. Available comedications (27%) were classified into inducers or inhibitors of P-glycoprotein, CYP3A4/5 and organic-cation-transporter-1 (hOCT-1).¦Results: A one-compartment model with linear elimination, zero-order absorption fitted the data best. Estimated Pop-PK parameters (interindividual variability, IIV %CV) for a 40-year old male patient were: clearance CL = 17.3 L/h (37.7%), volume V = 429L (51.1%), duration of absorption D1 = 3.2h. Outliers, reflecting potential compliance and time recording errors, were taken into account by estimating an IIV on the residual error (35.4%). Intra-individual residuals were 29.1% (proportional) plus ± 84.6 ng/mL (additive). Female patients had a 15.2% lower CL (14.6 L/h). A piece-wise linear effect of age estimated a CL of 18.7 L/h at 20 years, 17.3 L/h at 40 and 13.8 L/h at 60 years. These covariates explained 2% (CL) and 4.5% (V) of IIV variability. No effect of comedication was found. The sensitivity analysis expectedly estimated increased IIV, but similar fixed effect parameters.¦Conclusion: Imatinib PK was well described in a large cohort of CML patients under field conditions and results were concordant with previous studies. Patient characteristics explain only little IIV, confirming limited utility of prior dosage adjustment. As intra-variability is smaller than inter-patient variability, dose adjustment guided by TDM could however be beneficial in order to bring Cmin into a given therapeutic target.