pp56Lck mediates TCR zeta-chain binding to the microfilament cytoskeleton

The TCR zeta-chain (zeta) on mature murine T lymphocytes binds to the microfilament cytoskeleton in response to Ag receptor ligation. Here, we report the role of Src family kinases in zeta-cytoskeletal binding, using mutant mice and a cell-free model system. Binding of zeta to actin in the cell-free system has a specific requirement for ATP and divalent cations, with an apparent Michaelis-Menton constant for ATP in the millimolar range, and can be disrupted by either EDTA or the microfilament poison, cytochalasin D, suggesting that microfilaments provide the structural framework for an active process involving cellular kinases. Indeed, tyrosine-phosphorylated zeta is a predominant form of the zeta-chain bound to polymerized actin, while challenge with alkaline phosphatase prevents zeta-chain association in solution and releases zeta-chain from the bound state. Phosphorylated Src-family kinase pp56Lck also associates with membrane skeleton upon TCR engagement and is a component of the reconstituted cytoskeletal pellet. Zeta-chain phosphorylation and zeta-cytoskeletal binding are abrogated in cell lysates with reduced levels of pp56Lck and in activated mutant murine T cells lacking pp56Lck, implicating pp56Lck as the kinase involved in zeta-chain tyrosine phosphorylation and zeta-cytoskeletal binding. Finally, recombinant Lck Src homology 2 domain preferentially inhibits reconstituted zeta-cytoskeleton association, suggesting that zeta-microfilament binding is dependent on interactions between phosphorylated tyrosine residues in zeta-chain activation motifs and the Src homology 2 domain of the Lck protein tyrosine kinase.     

Effects of 1,4-Benzoxazin-3-One Derivatives from Maize on Survival and Fecundity of Metopolophium dirhodum (Walker) on Artificial Diet

Effects of 2--D-glucopyranosyloxy-4-hydroxy-7-methoxy-1,4benzoxazin-3-one (DIMBOA-Glc) and DIMBOA-Glc N-O-methylated (HDMBOA-Glc), two compounds present in high concentration in maize, were tested on the aphid Metopolophium dirhodum reared on artificial diet. HDMBOA-Glc and DIMBOA-Glc decrease survival of adults with an LD₅₀ of 1 mM and 5.6 mM, respectively, after 72 hr of feeding. These compounds also decrease the fecundity of the aphids at concentrations of 2 mM and 1 mM, respectively. At concentrations of 2 mM HDMBOA-Glc and 8 mM DIMBOA-Glc in the diet, the average lifetime fecundity of 10 females is near zero. Offspring mortality on diet with 2 mM DIMBOA-Glc is significantly higher than with the control diet. In contrast, HDMBOA-Glc has no effect on the survival of offspring. The possibility that these compounds protect Poaceae against aphids is discussed.     

Multiscale MAS modelling to simulate the soil environment: Application to soil ecology

Soils are important components of ecosystem and their functioning is of great importance for human well-being. Describing, understanding, foreseeing, and controlling biological activities and functions in soil in the context of global change are major objectives for scientists. Modelling soil bioturbation by soil engineers is of great importance although it is faced with the difficulty to describe the soil physical environment. Creating a model of a soil leads to complexity problems: a soil is a multi-scale heterogeneous, three-dimensional and dynamic environment that cannot be modelled and simulated without defining a suitable and optimized representation and taking assumptions about the studied system. An approach based on fractal theory (often used in soil sciences) was chosen to model such a real complex environment; it was integrated into a multi-agent system (MAS). MAS allows to simulate situated agents (earthworms) in an virtual world. The originality of this present MAS is that it is based on a dynamic environment which builds itself, on demand, according to an abstract canvas tree and agent movements. The aim of this paper is to present this approach and its originality, and to describe the model and the simulator. A theoretical view of the approach is given and applied to a case study: the impact of earthworms on soil structure and organic matter dynamics.     

Densification of alumina by SPS and HP: A comparative study

In this study, the densification of alumina by spark plasma sintering (SPS) was investigated and compared to conventional hot pressing. It was shown that SPS is very effective in the sintering of alumina leading to higher densities and allows to work at lower temperatures and with shorter sintering cycles. The effect of the heating rate is dependent on the heating mode (SPS or HP). The identification of active sintering mechanisms was attempted by an isothermal and an anisothermal methods, showing that other mechanisms probably related to electrical effects enhance the densification. We suggest the higher contribution of surface diffusion mainly during the initial stage of sintering and an influence of the presence of impurities segregated at the grain boundaries. They could create conductive layers and also introduce ions with a lower valence than Al³⁺; defects are created in the surface layers and the diffusion of the species is increased.     

Interaction between laser beam and BaTiO3 powders in selective laser sintering treatments

The research work reported in this paper is an investigation of the behavior of barium titanate powders under selective laser irradiation. Our goal is to determine suitable conditions to sinter the powders and form dense layers usable in some electronic components. On that purpose, compacts of micro/nano BaTiO₃ powder mixes are used for a parametric investigation of the laser scans parameters (power, speed, etc.) with a Nd-YVO₄ laser (23 W). The microstructures obtained after laser treatments are evaluated by XRD, SEM and EDS and compared to a reference specimen manufactured in a conventional way. From this work it can be concluded that a high laser beam power is required to obtain a consolidation of the powder grains and the use of a high scan speed avoids the melting. The scanning speed also influences the final crystallographic state of BaTiO₃. Optimal parameters were founded in order to form a dense and homogeneous tetragonal BaTiO₃ surface.     

Signal transduction by T- and B-cell antigen receptors: converging structures and concepts

Recent evidence demonstrates that the antigen receptor complexes of T and B lymphocytes are very similar in general architecture and primary and secondary structure of component polypeptides, and that they use common mechanisms for transmembrane signal transduction. Most importantly, multiple subunits of each receptor (Ig-alpha, Ig-beta and Ig-gamma, CD3 gamma, CD3 delta and CD3 epsilon, and T-cell receptor zeta and eta) possess a motif of approximately 26 amino-acids, denoted ARH1, which appears to carry sufficient structural information for receptor-mediated lymphocyte activation.     

Initial results on computational performance of Intel many integrated core,sandy bridge,and graphical processing unit architectures: implementation of a 1D c++/OpenMP electrostatic particle‐in‐cell code

We present initial comparison performance results for Intel many integrated core (MIC), Sandy Bridge (SB), and graphical processing unit (GPU). A 1D explicit electrostatic particle‐in‐cell code is used to simulate a two‐stream instability in plasma. We compare the computation times for various number of cores/threads and compiler options. The parallelization is implemented via OpenMP with a maximum thread number of 128. Parallelization and vectorization on the GPU is achieved with modifying the code syntax for compatibility with CUDA. We assess the speedup due to various auto‐vectorization and optimization level compiler options. Our results show that the MIC is several times slower than SB for a single thread, and it becomes faster than SB when the number of cores increases with vectorization switched on. The compute times for the GPU are consistently about six to seven times faster than the ones for MIC. Compared with SB, the GPU is about two times faster for a single thread and about an order of magnitude faster for 128 threads. The net speedup, however, for MIC and GPU are almost the same. An initial attempt to offload parts of the code to the MIC coprocessor shows that there is an optimal number of threads where the speedup reaches a maximum. Copyright © 2014 John Wiley & Sons, Ltd.     

CD72-mediated B cell activation involves recruitment of CD19 and activation of phosphatidylinositol 3-kinase

Occupancy of the B cell glycoprotein, CD72 results in syk-independent activation of phospholipase-C gamma and calcium mobilization. The cytoplasmic tail of CD72 does not contain an immunoreceptor tyrosine-based activation motif to directly transduce signals into the B lymphocyte. Hence, we investigated whether other coreceptors such as CD19 and its associated phosphatidylinositol 3-kinase (PI 3-K) were involved in CD72 signaling. Two specific inhibitors of PI 3-K inhibited CD72-stimulated B cell proliferation in a dose-dependent manner. Activation of B lymphocytes via CD72 resulted in recruitment and activation of PI 3-K, which was mediated by CD19. Accordingly, CD72 ligation induced CD19 tyrosine phosphorylation. Thus, lipid products generated as a result of PI 3-K activation may have an important function in CD72-mediated B lymphocyte activation. The kinetics of CD19 tyrosine phosphorylation induced by CD72 ligation were strikingly different from those seen following B cell antigen receptor (BCR) stimulation. A transient increase in the tyrosine phosphorylation of the complement receptors, CD21 and CD35 was observed in BCR- but not CD72-stimulated cells. Co-cross-linking of CD72 and CD19 failed to induce syk tyrosine phosphorylation suggesting that even under these conditions, CD72 signaling was independent of syk activation. A transient and stimulation-dependent physical association between CD19 and CD72 was observed in CD72-ligated cells. These observations suggest a mechanism by which CD72 can recruit CD19 and influence activation of CD19-associated PI 3-K, which appears to be critical for CD72-mediated B cell activation.     

BCR-ABL activates pathways mediating cytokine independence and protection against apoptosis in murine hematopoietic cells in a dose-dependent manner

The hallmark of chronic myeloid leukemia (CML) is the chimeric tyrosine kinase oncogene bcr-abl. Since expression of bcr-abl mRNA frequently increases with disease progression and a duplication of the Philadelphia chromosome (harbouring the bcr-abl hybrid locus) represents the most frequent karyotypic abnormality in acute phase CML, we hypothesized that the level of BCR-ABL protein may affect the disease phenotype. Therefore, the biological effects of high and low levels of BCR-ABL expression were compared in growth factor-dependent and -independent myeloid and lymphoid cell lines. Our results demonstrated that low levels of BCR - ABL were sufficient to render these cell lines growth factor independent and tumorigenic, but higher levels were mandatory for additional protection against apoptotic stimuli. The provision of growth factor or an activated ras oncogene did not afford the same degree of protection as high levels of BCR-ABL and there were qualitative differences between the survival signals mediated by BCR-ABL and Bcl-2. These results have enabled us to establish a dose-dependent hierarchy of BCR-ABL induced biological effects, thus distinguishing the activation of pathways mediating protection from cytokine withdrawal from those protecting against other apoptotic stimuli.