昆虫信息素研究III: 拟蚜虫警戒素的研究

合成了一系列碳数为十五和十四的倍半萜类蚜虫警戒素,并进行了生物活性测定,从中筛选有效化合物.     

Thermal denaturing of mutant lysozyme with both the OPLSAA and the CHARMM force fields

Biomolecular simulations enabled by massively parallel supercomputers such as BlueGene/L promise to bridge the gap between the currently accessible simulation time scale and the experimental time scale for many important protein folding processes. In this study, molecular dynamics simulations were carried out for both the wild-type and the mutant hen lysozyme (TRP62GLY) to study the single mutation effect on lysozyme stability and misfolding. Our thermal denaturing simulations at 400-500 K with both the OPLSAA and the CHARMM force fields show that the mutant structure is indeed much less stable than the wild-type, which is consistent with the recent urea denaturing experiment (Dobson et al. Science 2002, 295, 1719-1722; Nature 2003, 424, 783-788). Detailed results also reveal that the single mutation TRP62GLY first induces the loss of native contacts in the beta-domain region of the lysozyme protein at high temperatures, and then the unfolding process spreads into the alpha-domain region through Helix C. Even though the OPLSAA force field in general shows a more stable protein structure than does the CHARMM force field at high temperatures, the two force fields examined here display qualitatively similar results for the misfolding process, indicating that the thermal denaturing of the single mutation is robust and reproducible with various modern force fields.     

The acylation state of mycobacterial lipomannans modulates innate immunity response through toll-like receptor 2

Detection of Mycobacterium tuberculosis antigens by professional phagocytes via toll-like receptors (TLR) contributes to controlling chronic M. tuberculosis infection. Lipomannans (LM), which are major lipoglycans of the mycobacterial envelope, were recently described as agonists of TLR2 with potent activity on proinflammatory cytokine regulation. LM correspond to a heterogeneous population of acyl- and glyco-forms. We report here the purification and the complete structural characterization of four LM acyl-forms from Mycobacterium bovis BCG using MALDI MS and 2D (1)H-(31)P NMR analyses. All this biochemical work provided the tools to investigate the implication of LM acylation degree on its proinflammatory activity. The latter was ascribed to the triacylated LM form, essentially an agonist of TLR2, using TLR2/TLR1 heterodimers for signaling. Altogether, these findings shed more light on the molecular basis of LM recognition by TLR.     

Atmospheric pressure photoionization coupled to porous graphitic carbon liquid chromatography for the analysis of globotriaosylceramides. Application to Fabry disease

Globotriaosylceramides (Gb(3)) are biological compounds implicated in Fabry disease, a lysosomal storage disease due to the deficient activity of alpha-D-galactosidase A, which results in an accumulation of Gb(3) in many organs. The naturally occurring samples are composed of mixtures of several molecular species differing by the structure of the alkyl chains and the nature of the sphingoid base. Atmospheric pressure photoionization mass spectrometry (APPI-MS) proved to be an efficient method for the analysis of globotriaosylceramide molecular species, both in direct injection and by coupling with liquid chromatography (LC). In the positive ion mode, in-source fragmentations yield very precious information that can be used to determine the structure of the alkyl chains. In the negative ion mode, the chloroform solvent participates to the analyte ionization by forming an adduct with chloride ions generated in situ. Combination of LC on a Porous Graphitic Carbon stationary phase and APPI-MS allowed the detection of a great number of species from biological samples isolated from Fabry patients. This method could be an interesting analytical tool for the biochemical investigation of (sphingo) lipid metabolism.     

POD investigation of the unsteady turbulent boundary layer developing over porous moving flexible fishing net structure

Particle image velocimetry (PIV) measurements are made to investigate the boundary layer developing over a modeled bottom trawl. The random motion of the fishing net structure as well as the flexibility and the porosity of this structure means that it is not enable to access the main characteristics of such a flow, using classical post-processing mathematical tools. An innovative post-treatment tool based on proper orthogonal decomposition (POD) is then developed to extract the mean velocity flow field from each available PIV instantaneous unsteady velocity field. In order to do so, the whole available velocity database is used to compute POD eigenfunctions and the first POD modes are identified as representing the mean flow field. It is then possible to deduce the mean boundary layer flow field for each position of the fishing net structure during PIV measurements. It is then observed that the mean flow field strongly depends on multiple parameters such as surface curvature, structure porosity, random motion of the structure. Streamwise evolution of classical thicknesses of boundary layer flow are also analyzed. The present work also provides benchmark PIV data of the unsteady flow developing on fishing net porous structures, which helps the progress in unsteady numerical codes for this investigation.     

Chemically triggered C–ON bond homolysis in alkoxyamines. Part 7. Remote polar effect

In a recent work (Org. Lett. 2012, 14, 358–361), we showed that the activation by benzylation of alkoxyamine 1 (diethyl (1‐(tert‐butyl(1‐(pyridin‐4‐yl)ethoxy)amino)‐2,2‐dimethylpropyl)phosphonate) afforded a surprisingly large C–ON bond homolysis rate constant k_d. Taking advantage of the easy preparation of para‐X‐benzyl‐activated alkoxyamines 2 and of the presence of a shielding methylene group between the two aromatic moieties, we investigated the long range (10 bonds between the X group and the C–ON bond) polar effect for X = H, F, OMe, CN, NO₂, NMe₂, ⁺NHMe₂,Br^?. It was observed that the effect was weak (4‐fold) and mainly due to the zwiterionic mesomeric forms generated by the presence of group X on the para position, i.e. k_d increased for CN and NO₂ and decreased for OMe, NMe₂ and ⁺NMe₂H,Br^?. DFT calculations at the B3LYP/6‐31G(d,p) level were performed to determine orbital interactions (natural bond orbital (NBO) analysis), Mulliken and NBO charges which support the reactivity described. Copyright © 2014 John Wiley & Sons, Ltd.     

Bilinear Dispersive Estimates Via Space Time Resonances,Dimensions Two and Three

Consider a bilinear interaction between two linear dispersive waves with a generic resonant structure (roughly speaking, space and time resonant sets intersect transversally). We derive an asymptotic equivalent of the solution for data in the Schwartz class, and bilinear dispersive estimates for data in weighted Lebesgue spaces. An application to water waves with infinite depth, gravity and surface tension is also presented.     

Non-ergodicity transition and multiple glasses in binary mixtures: on the accuracy of the input static structure in the mode coupling theory

We examine the question of the accuracy of the static correlation functions used as input in the mode coupling theory (MCT) of non-ergodic states in binary mixtures. We first consider hard-sphere mixtures and compute the static pair structure from the Ornstein-Zernike equations with the Percus-Yevick closure and more accurate ones that use bridge functions deduced from Rosenfeld's fundamental measures functional. The corresponding MCT predictions for the non-ergodicity lines and the transitions between multiple glassy states are determined from the long-time limit of the density autocorrelation functions. We find that while the non-ergodicity transition line is not very sensitive to the input static structure, up to diameter ratios D(2)/D(1)?=?10, quantitative differences exist for the transitions between different glasses. The discrepancies with the more accurate closures become even qualitative for sufficiently asymmetric mixtures. They are correlated with the incorrect behavior of the PY structure at high size asymmetry. From the example of ultra-soft potential it is argued that this issue is of general relevance beyond the hard-sphere model.     

On the experimental study of the flow around a fishing net

Selectivity of fishing gears like trawls is obviously conditioned by the fish behaviour but also by the net and the flow. As well, flow may affect fish behaviour. With the aim of a better understanding of the flow in presence of a net and a catch, we suggest, through the experimental study below, to determine and to analyze the flow over a rigid cod-end in two configurations: with a closed and an open net entrance. Trials took place in a free surface flume tank and the flow characteristics were determined from velocity measurements obtained by laser velocimetry (inside, outside and through the meshes of the stiff cod-end). The experimental device, the measures and their analyzes are given here.