CLEC-2 activates Syk through dimerization

The C-type lectin receptor CLEC-2 activates platelets through Src and Syk tyrosine kinases, leading to tyrosine phosphorylation of downstream adapter proteins and effector enzymes, including phospholipase-C gamma2. Signaling is initiated through phosphorylation of a single conserved tyrosine located in a YxxL sequence in the CLEC-2 cytosolic tail. The signaling pathway used by CLEC-2 shares many similarities with that used by receptors that have 1 or more copies of an immunoreceptor tyrosine-based activation motif, defined by the sequence Yxx(L/I)x(6-12)Yxx(L/I), in their cytosolic tails or associated receptor chains. Phosphorylation of the conserved immunoreceptor tyrosine-based activation motif tyrosines promotes Syk binding and activation through binding of the Syk tandem SH2 domains. In this report, we present evidence using peptide pull-down studies, surface plasmon resonance, quantitative Western blotting, tryptophan fluorescence measurements, and competition experiments that Syk activation by CLEC-2 is mediated by the cross-linking through the tandem SH2 domains with a stoichiometry of 2:1. In support of this model, cross-linking and electron microscopy demonstrate that CLEC-2 is present as a dimer in resting platelets and converted to larger complexes on activation. This is a unique mode of activation of Syk by a single YxxL-containing receptor.

Phosphorylation of CLEC-2 is dependent on lipid rafts, actin polymerization, secondary mediators, and Rac

The C-type lectin-like receptor 2 (CLEC-2) activates platelets through Src and Syk tyrosine kinases via a single cytoplasmic YxxL motif known as a hem immunoreceptor tyrosine-based activation motif (hemITAM). Here, we demonstrate using sucrose gradient ultracentrifugation and methyl-beta-cyclodextrin treatment that CLEC-2 translocates to lipid rafts upon ligand engagement and that translocation is essential for hemITAM phosphorylation and signal initiation. HemITAM phosphorylation, but not translocation, is also critically dependent on actin polymerization, Rac1 activation, and release of ADP and thromboxane A(2) (TxA(2)). The role of ADP and TxA(2) in mediating phosphorylation is dependent on ligand engagement and rac activation but is independent of platelet aggregation. In contrast, tyrosine phosphorylation of the GPVI-FcRgamma-chain ITAM, which has 2 YxxL motifs, is independent of actin polymerization and secondary mediators. These results reveal a unique series of proximal events in CLEC-2 phosphorylation involving actin polymerization, secondary mediators, and Rac activation.

Les dangers de la guerre. L'image du guerrier dans le Brut de La3amon

A study of the lexis and imagery of warfare in the early C13 English adaptation of Wace's Roman de Brut by the English poet La3amon. The narrator's stance is analysed the light of the poet's priestly identity, revealing an undercurrent of disapproval of the glorification of the warrior found in La3amon's sources, and moral concern for combatants engaged in 'unjust' wars of conquest.

Season changes in water quality and Sargassum biomass in Southwest Australia

Sargassum C. Agardh is one of the most diverse genera of marine macro-algae and commonly inhabits shallow tropical and sub-tropical waters. This study aimed to investigate the effect of seasonality and the associated water quality changes on the distribution, canopy cover, mean thallus length and the biomass of Sargassum beds around Point Peron, Shoalwater Islands Marine Park, Southwest Australia. Samples of Sargassum and seawater were collected every three months from summer 2012 to summer 2014 from four different reef zones. A combination of in situ observations and WorldView-2 satellite remote-sensing images were used to map the spatial distribution of Sargassum beds and other associated benthic habitats. The results demonstrated a strong seasonal variation in the environmental parameters, canopy cover, mean thallus length, and biomass of Sargassum, which were significantly (P < 0.05) influenced by the nutrient concentration (PO43-, NO3-, NH4+) and rainfall. However, no variation in any studied parameter was observed among the four reef zones. The highest Sargassum biomass peaks occurred between late spring and early summer (from September to January). The results provide essential information to guide effective conservation and management, as well as sustainable utilisation of this coastal marine renewable resource.

Les variations formelles d'un moule stylistique: rubrique, texte et image à la charnière du Merlin et de sa Suite Vulgate

Le passage du Merlin propre à sa Suite Vulgate, espace de suture entre le texte et sa continuation est dans la tradition manuscrite l'objet de variances et de déplacements. A la paix annoncée à la fin du Merlin succède en effet le conflit qui oppose le jeune roi Arthur à ses barons. Les passages de rubrication et d'entrelacement sont le lieu privilégié de variations formelles gommées par l'adoption et la reprise de moules stylistiques attendus. Ceux-ci exhibent tout en les masquant de subtiles divergences relevant de partis pris à la fois narratifs, interprétatifs et idéologiques.

Estimation of sea surface temperature from the Spinning Enhanced Visible and Infra Red Imager, improved using numerical weather prediction

Most of the operational Sea Surface Temperature (SST) products derived from satellite infrared radiometry use multi-spectral algorithms. They show, in general, reasonable performances with root mean square (RMS) residuals around 0.5 K when validated against buoy measurements, but have limitations, particularly a component of the retrieval error that relates to such algorithms' limited ability to cope with the full variability of atmospheric absorption and emission. We propose to use forecast atmospheric profiles and a radiative transfer model to simulate the algorithmic errors of multi-spectral algorithms. In the practical case of SST derived from the Spinning Enhanced Visible and Infrared Imager (SEVIRI) onboard Meteosat Second Generation (MSG), we demonstrate that simulated algorithmic errors do explain a significant component of the actual errors observed for the non linear (NL) split window algorithm in operational use at the Centre de Météorologie Spatiale (CMS). The simulated errors, used as correction terms, reduce significantly the regional biases of the NL algorithm as well as the standard deviation of the differences with drifting buoy measurements. The availability of atmospheric profiles associated with observed satellite-buoy differences allows us to analyze the origins of the main algorithmic errors observed in the SEVIRI field of view: a negative bias in the inter-tropical zone, and a mid-latitude positive bias. We demonstrate how these errors are explained by the sensitivity of observed brightness temperatures to the vertical distribution of water vapour, propagated through the SST retrieval algorithm.