Identification of a novel pharmacophore for peptide toxins interacting with K+ channels

Journal ArticleқM-conotoxin RIIIK blocks TSha1 K+ channels from trout with high affinity by interacting with the ion channel pore. As opposed to many other peptides targeting K+ channels, қM-RIIIK does not possess a functional dyad. In this study we combine thermodynamic mutant cycle analysis and docking calculations to derive the binding mode of қM-conotoxin RIIIK to the TSha1 channel

3D cancer cell migration in collagen matrices

International audienceCell migration is a widely studied subject but often limited to 2D motion (Sheetz et al., 1999) on various substrates for it allows to simplify cell-substrate interactions. The important relevant parameters to 2D cell migration are substrate rigidity, adhesion, and the role of the cell cytoskeleton. More recently, new studies on 3D cell migration have been performed thanks to the development of new visualization tools such as reflectance confocal microscopy (Iordan et al. 2010, Wolf et al. 2013). In particular, it is possible to image cell and the extra-cellular matrix at the same time. This leads to interesting applications on cancer cell migration, and could possibly open new routes to the understanding of cancer development, like the mechanisms used by cancer cells to invade new tissues.Thus, the aim of this study is to study cancer migration in collagen matrices, as a model of soft tissue, to investigate their motility within the surrounding collagen matrix. Different collagen concentrations will be used and the ability of these cancer cells to move through such a complex structure will be addressed. To this aim, first results of cell migration velocity as well as the Mean Squared Displacement (MSD) will be analyzed

Atomic Force microscopy reveals a role for endothelial cell ICAM-1 expression in bladder cancer cell adherence

International audienceCancer metastasis is a complex process involving cell-cell interactions mediated by cell adhesive molecules. In this study we determine the adhesion strength between an endothelial cell monolayer and tumor cells of different metastatic potentials using Atomic Force Microscopy. We show that the rupture forces of receptor-ligand bonds increase with retraction speed and range between 20 and 70 pN. It is shown that the most invasive cell lines (T24, J82) form the strongest bonds with endothelial cells. Using ICAM-1 coated substrates and a monoclonal antibody specific for ICAM-1, we demonstrate that ICAM-1 serves as a key receptor on endothelial cells and that its interactions with ligands expressed by tumor cells are correlated with the rupture forces obtained with the most invasive cancer cells (T24, J82). For the less invasive cancer cells (RT112), endothelial ICAM-1 does not seem to play any role in the adhesion process. Moreover, a detailed analysis of the distribution of rupture forces suggests that ICAM-1 interacts preferentially with one ligand on T24 cancer cells and with two ligands on J82 cancer cells. Possible counter receptors for these interactions are CD43 and MUC1, two known ligands for ICAM-1 which are expressed by these cancer cells

Local mechanical properties of bladder cancer cells measured by AFM as a signature of metastatic potential

International audienceThe rheological properties of bladder cancer cells of different invasivities have been investigated using a microrheological technique well adapted in the range [1 - 300 Hz] of interest to understand local changes in the cytoskeleton microstructure, in particular actin fibres. Drugs disrupting actin and actomyosin functions were used to study the resistance of such cancer cells. Results on a variety of cell lines were fitted with a model revealing the importance of two parameters, the elastic shear plateau modulus GN0 as well as the glassy transition frequency f_T. These parameters are good markers for invasiveness, with the notable exception of the cell periphery, which is stiffer for less invasive cells, and could be of importance in cancer metastasis

The aromatic bicomplex for the description of divergence-free aromatic forms and volume-preserving integrators

Aromatic B-series were introduced as an extension of standard Butcher-series for the study of volume-preserving integrators. It was proven with their help that the only volume-preserving B-series method is the exact flow of the differential equation. The question was raised whether there exists a volume-preserving integrator that can be expanded as an aromatic B-series. In this work, we introduce a new algebraic tool, called the aromatic bicomplex, similar to the variational bicomplex in variational calculus. We prove the exactness of this bicomplex and use it to describe explicitly the key object in the study of volume-preserving integrators: the aromatic forms of vanishing divergence. The analysis provides us with a handful of new tools to study aromatic B-series, gives insights on the process of integration by parts of trees, and allows to describe explicitly the aromatic B-series of a volume-preserving integrator. In particular, we conclude that an aromatic Runge-Kutta method cannot preserve volume.Comment: 41 page

Variational inference of fractional Brownian motion with linear computational complexity

We introduce a simulation-based, amortised Bayesian inference scheme to infer the parameters of random walks. Our approach learns the posterior distribution of the walks' parameters with a likelihood-free method. In the first step a graph neural network is trained on simulated data to learn optimized low-dimensional summary statistics of the random walk. In the second step an invertible neural network generates the posterior distribution of the parameters from the learnt summary statistics using variational inference. We apply our method to infer the parameters of the fractional Brownian motion model from single trajectories. The computational complexity of the amortized inference procedure scales linearly with trajectory length, and its precision scales similarly to the Cram{\'e}r-Rao bound over a wide range of lengths. The approach is robust to positional noise, and generalizes well to trajectories longer than those seen during training. Finally, we adapt this scheme to show that a finite decorrelation time in the environment can furthermore be inferred from individual trajectories

Module Relocation in Heterogeneous Reconfigurable Systems-on-Chip using the Xilinx Isolation Design Flow

International audienceHeterogeneous Reconfigurable Systems-on-Chip (HRSoC) contain as their name suggests, heterogeneous processing elements in a single chip. Namely, several processors, hardware accelerators as well as communication networks between all these components. In order to leverage the programming complexity of this kind of platform, applications are described with software threads, running on processors, and hardware threads, running on FPGA partitions. Combining techniques such as dynamic and partial reconfiguration and partial readback with the knowledge of the bitstream structure offer the ability to target several partitions using a unique configuration file. Such a feature permits to save critical memory resources. In this article, we propose to tackle the issue of designing fully independent partitions, and especially to avoid the routing conflicts which can occur when using the standard Xilinx FPGA design flow. To achieve the relocation process successfully, we propose a new design flow dedicated to the module relocation, using the standard tools and based on the Isolation Design Flow (IDF), a special flow provided by Xilinx for secure FPGA applications

Interactions entre des cellules cancéreuses et l'endothélium

Les cellules cancéreuses interagissent avec l'endothélium au cours du processus de formation des métastases [1]. Nous nous intéressons aux propriétés adhésives entre ces types cellulaires. Grâce à un AFM, nous pouvons avoir accès aux forces de rupture, qui dépendent des liaisons récepteur-ligand en présence, et aussi de la vitesse de chargement. Un modèle est proposé pour cette analyse. Les résultats sont analysés pour différentes lignées de cellules cancéreuses plus ou moins invasives. [1] Haddad O. et al., Exp. Cell Res. (2010

Kinetic Modeling of the Thermal Destruction of Mustard Gas

International audienceThe destruction of stockpiles or unexploded ammunitions of bis(2-chloroethyl) sulfide, also called mustard gas or yperite, by thermal treatments requires the development of highly safe processes. The high-level of toxicity of this compound induces a high level of complexity for any experiments. Consequently, there is a considerable lack of knowledge on the behavior of this chemical under high-temperature conditions (with or without oxygen). In this work a detailed chemical kinetic model for the combustion and pyrolysis of mustard gas is proposed for the first time. A large number of thermo-kinetic parameters were calculated using quantum chemistry and reaction rate theory. The model was validated against experimental pyrolysis data of the literature. It was shown that the degradation of mustard gas is ruled by a chain reaction mechanism where the chlorine atom is the principal chain carrier. HS radical, formed in the primary mechanism by an original pathway found using quantum calculations, was also proved to be an important chain carrier. Comparison with the kinetics of the usual simulant of mustard gas, diethyl sulfide, showed that the lack of chlorine atom in the former chemical leads to an inappropriate simulation of the mustard gas behavior. Combustion and pyrolysis simulations were also compared and surprisingly demonstrated that chlorine atoms remain the main chain carrier in combustion