A new set of monoclonal antibodies directed to proline-rich and central regions of p53

The p53 protein can adopt several conformations in cells - "latent," "active," or mutant - depending on cellular stress or mutations of the TP53 gene. Today, only a few antibodies discriminating these conformations are available. We produced three new anti-p53 monoclonal antibodies (MAbs) directed against epitopes of human p53. The H53C1 MAb recognizes an epitope located at the N-terminal part of the central region of p53 and can discriminate mutant from wild-type conformation. The H53C2 and H53C3 MAbs are against different epitopes within the proline-rich region of p53. Moreover, the H53C2 epitope is located in the second negative regulatory domain of p53 between residues 80 and 93. These MAbs can be used as new tools to study and modulate the cellular functions of p53

Disequilibrium of BMP2 levels in the breast stem cell niche launches epithelial transformation by overamplifying BMPR1B cell response

Understanding the mechanisms of cancer initiation will help to prevent and manage the disease. At present, the role of the breast microenvironment in transformation remains unknown. As BMP2 and BMP4 are important regulators of stem cells and their niches in many tissues, we investigated their function in early phases of breast cancer. BMP2 production by tumor microenvironment appeared to be specifically upregulated in luminal tumors. Chronic exposure of immature human mammary epithelial cells to high BMP2 levels initiated transformation toward a luminal tumor-like phenotype, mediated by the receptor BMPR1B. Under physiological conditions, BMP2 controlled the maintenance and differentiation of early luminal progenitors, while BMP4 acted on stem cells/myoepithelial progenitors. Our data also suggest that microenvironment-induced overexpression of BMP2 may result from carcinogenic exposure. We reveal a role for BMP2 and the breast microenvironment in the initiation of stem cell transformation, thus providing insight into the etiology of luminal breast cancer.Marion Chapellier, Elodie Bachelard-Cascales, Xenia Schmidt, Flora Clement ... Jean-Yves Blay, Richard Iggo ... et al

Rheology of an Ionic Liquid with Variable Carreau Exponent: A Full Picture by Molecular Simulation with Experimental Contribution

International audienceThe rheological behavior of an ionic liquid was investigated by means of molecular dynamics simulations with experimental contribution, under conditions close to those found in the elastohydrodynamic and the very-thin film lubrication regimes. The molecular model was applied to nearly 200 temperature–pressure–shear rate cases, without any parameter adjustment. Experiments were conducted on a rheometer and a high-pressure falling-body viscometer. This unique combination of numerical and experimental tools has enabled the full description of the ionic liquid rheological response to extreme conditions oftemperature, pressure and shear rate. In the linear domain, a very good consistency between the two computational approaches (nonequilibrium molecular dynamics, equilibrium molecular dynamics via the Green–Kubo formalism) and the experiments was obtained on the Newtonian viscosity. Reliable values of the pressure–viscosity coefficient, another rheological characteristic necessary for predicting film thickness in the regimes of interest in this work, were inferred. Compared with a conventional lubricant of almost identical Newtonian viscosity, the pressure– viscosity coefficient of the ionic fluid is much lower, its variations with temperature remaining, however, very similar. The application of the time–temperature–pressure superposition principle and the regression to the Carreau equation for describing the nonlinear domain have revealed, for the first time, significant variations in the exponent of the Carreau model which have been correlated with the changes in temperature and pressure