A novel transport mechanism for MOMP in Chlamydophila pneumoniae and its putative role in immune-therapy

Major outer membrane proteins (MOMPs) of Gram negative bacteria are one of the most intensively studied membrane proteins. MOMPs are essential for maintaining the structural integrity of bacterial outer membranes and in adaptation of parasites to their hosts. There is evidence to suggest a role for purified MOMP from Chlamydophila pneumoniae and corresponding MOMP-derived peptides in immune-modulation, leading to a reduced atherosclerotic phenotype in apoE−/− mice via a characteristic dampening of MHC class II activity. The work reported herein tests this hypothesis by employing a combination of homology modelling and docking to examine the detailed molecular interactions that may be responsible. A three-dimensional homology model of the C. pneumoniae MOMP was constructed based on the 14 transmembrane β-barrel crystal structure of the fatty acid transporter from Escherichia coli, which provides a plausible transport mechanism for MOMP. Ligand docking experiments were used to provide details of the possible molecular interactions driving the binding of MOMP-derived peptides to MHC class II alleles known to be strongly associated with inflammation. The docking experiments were corroborated by predictions from conventional immuno-informatic algorithms. This work supports further the use of MOMP in C. pneumoniae as a possible vaccine target and the role of MOMP-derived peptides as vaccine candidates for immune-therapy in chronic inflammation that can result in cardiovascular events

Mapping Molecular Orientation with Phase Sensitive Vibrationally Resonant Sum-Frequency Generation Microscopy

We demonstrate a phase sensitive, vibrationally resonant sum-frequency generation (PSVR-SFG) microscope that combines high resolution, fast image acquisition speed, chemical selectivity, and phase sensitivity. Using the PSVR-SFG microscope, we generate amplitude and phase images of the second-order susceptibility of collagen I fibers in rat tail tendon tissue on resonance with the methylene vibrations of the protein. We find that the phase of the second-order susceptibility shows dependence on the effective polarity of the fibril bundles, revealing fibrous collagen domains of opposite orientations within the tissue. The presence of collagen microdomains in tendon tissue may have implications for the interpretation of the mechanical properties of the tissue. [Image: see text

Primordial GATA6 macrophages function as extravascular platelets in sterile injury.

Most multicellular organisms have a major body cavity that harbors immune cells. In primordial species such as purple sea urchins, these cells perform phagocytic functions but are also crucial in repairing injuries. In mammals, the peritoneal cavity contains large numbers of resident GATA6+ macrophages, which may function similarly. However, it is unclear how cavity macrophages suspended in the fluid phase (peritoneal fluid) identify and migrate toward injuries. In this study, we used intravital microscopy to show that cavity macrophages in fluid rapidly form thrombus-like structures in response to injury by means of primordial scavenger receptor cysteine-rich domains. Aggregates of cavity macrophages physically sealed injuries and promoted rapid repair of focal lesions. In iatrogenic surgical situations, these cavity macrophages formed extensive aggregates that promoted the growth of intra-abdominal scar tissue known as peritoneal adhesions

EFFECT OF CAVITATION ON THE STRUCTURE OF THE BOUNDARY LAYER IN THE WAKE OF A PARTIAL CAVITY

This study investigates the modifications of the turbulent boundary layer that develops on the suction side of a NACA0015 hydrofoil when a stable partial cavity takes place near the leading edge of the foil. The velocity field measured in non cavitating conditions has been compared with its equivalent in cavitating conditions. A particular focus has been put on the evolution of the logarithmic law of the velocity profile and on the modification of the global parameters that can precise both the position of the laminar-turbulent transition and the detachment of the boundary layer. The wall friction has been estimated both by use of a numerical procedure and by treatment of the experimental results. This comparison is encouraging and gives confidence in the proposed methodology. The results have shown that the vapour phase modify the boundary layer thickness and enhance the exchanges with the external layer that lead to an increase of the velocity close to the wall. This phenomenon induces a stabilisation of the boundary layer and delays its separation

Concepts to build nonlinear optical biomaterials in a bottom-up approach

International audienceWe have performed Hyper-Rayleigh Scattering (HRS) experiments to measure the quadratic hyperpolarizability of several natural amino acids, in particular tryptophan and tyrosine. Values of (29.6+/-0.4)x10-30 esu for tryptophan and (25.7+/-0.03)x10-30 esu for tyrosine have been found. We have then investigated the dependence of the quadratic hyperpolarizability of tryptophan-rich short peptides as a function of the number of tryptophans in the sequence. The experimental findings indicate that the resulting quadratic hyperpolarizability in these peptides cannot be assumed as the mere coherent superposition of the hyperpolarizabilities of the tryptophans contained in the peptide. Our results unambiguously demonstrate that there must be strong interactions between the tryptophans contained in these short peptides. We have also investigated the case of the collagen triple helix. A second order hyperpolarizability of (1.25+/- 0.05)x10-27 esu for rat-tail type I collagen has been measured. In this case, we have been able to model this effective quadratic hyperpolarizability by summing coherently the nonlinear response of elementary moieties forming the triple helix, as opposed to the previous case of the tryptophan-rich peptides. © 2009 SPIE

Effect of Cesium and Xenon Seeding in Negative Hydrogen Ion Sources

It is well known that cesium seeding in volume hydrogen negative ion sources leads to a large reduction of the extracted electron current and in some cases to the enhancement of the negative ion current. The cooling of the electrons due to the addition of this heavy impurity was proposed as a possible cause of the mentioned observations. In order to verify this assumption, the authors seeded the hydrogen plasma with xenon, which has an atomic weight almost equal to that of cesium. The plasma properties were studied in the extraction region of the negative ion source Camembert III using a cylindrical electrostatic probe while the negative ion relative density was studied using laser photodetachment. It is shown that the xenon mixing does not enhance the negative ion density and leads to the increase of the electron density, while the cesium seeding reduces the electron density

Second order hyperpolarizability of the collagen triple helix: Measurement and determination of its physical origin

International audienceCollagen is the major protein of the extracellular matrix and plays a central role in the formation of fibrillar and microfibrillar networks, basement membranes, as well as other structures of the connective tissue. As a fundamental brick of the architecture of tissues, it guarantees organs functioning and is crucial in the adaptative response to various tissue injuries. This protein is characterized by triple helical domains and possesses remarkable non linear optical properties. Indeed, collagen fibers exhibit efficient Second Harmonic Generation (SHG) in tissues and SHG microscopy has proved to be a valuable technique to probe the three-dimensional architecture of fibrillar collagen in native and biomimetic tissues and to assess the progression of fibrotic pathologies. However, the nonlinear optical response of fibrillar collagen is not fully characterized yet and quantitative data are required to further process SHG images. We therefore performed Hyper-Rayleigh Scattering (HRS) experiments in order to measure quantitatively the nonlinear optical response of the collagen molecule, and to get insight into the physical origin of high SHG signals observed for fibrillar collagen in tissues

Nonlinear optical response of the collagen triple helix and second harmonic microscopy of collagen liquid crystals

International audienceCollagen is characterized by triple helical domains and plays a central role in the formation of fibrillar and microfibrillar networks, basement membranes, as well as other structures of the connective tissue. Remarkably, fibrillar collagen exhibits efficient Second Harmonic Generation (SHG) and SHG microscopy proved to be a sensitive tool to score fibrotic pathologies. However, the nonlinear optical response of fibrillar collagen is not fully characterized yet and quantitative data are required to further process SHG images. We therefore performed Hyper-Rayleigh Scattering (HRS) experiments and measured a second order hyperpolarisability of 1.25 10-27 esu for rat-tail type I collagen. This value is surprisingly large considering that collagen presents no strong harmonophore in its amino-acid sequence. In order to get insight into the physical origin of this nonlinear process, we performed HRS measurements after denaturation of the collagen triple helix and for a collagen-like short model peptide [(Pro-Pro-Gly)10]3. It showed that the collagen large nonlinear response originates in the tight alignment of a large number of weakly efficient harmonophores, presumably the peptide bonds, resulting in a coherent amplification of the nonlinear signal along the triple helix. To illustrate this mechanism, we successfully recorded SHG images in collagen liquid solutions by achieving liquid crystalline ordering of the collagen triple helices. © 2010 Copyright SPIE - The International Society for Optical Engineering