SLAP/SLAP2 prevent excessive platelet (hem)ITAM signaling in thrombosis and ischemic stroke in mice

Glycoprotein VI and C-type lectin-like receptor 2 are essential platelet activating receptors in hemostasis and thrombo-inflammatory disease, which signal through a (hem)immunoreceptor tyrosine-based activation motif (ITAM)-dependent pathway. The adapter molecules Src-like adapter proteins (SLAP and SLAP2) are involved in the regulation of immune cell surface expression and signaling, but their function in platelets is unknown. In this study, we show that platelets expressed both SLAP isoforms and that overexpression of either protein in a heterologous cell line almost completely inhibited glycoprotein VI and C-type lectin-like receptor 2 signaling. In mice, single deficiency of SLAP or SLAP2 had only moderate effects on platelet function, whereas double deficiency of both adapters resulted in markedly increased signal transduction, integrin activation, granule release, aggregation, procoagulant activity, and thrombin generation in response to (hem)ITAM-coupled, but not G protein-coupled, receptor activation. In vivo, constitutive SLAP/SLAP2 knockout mice displayed accelerated occlusive arterial thrombus formation and a dramatically worsened outcome after focal cerebral ischemia. This was attributed to the absence of both adapter proteins in platelets, as demonstrated by adoptive transfer of Slap(-/-)/Slap2(-/-) platelets into wild-type mice. Our results establish SLAP and SLAP2 as critical inhibitors of platelet (hem)ITAM signaling in the setting of arterial thrombosis and ischemic stroke.

Understanding digital literacies: a practical introduction

Understanding Digital Literacies provides an accessible and timely introduction to new media literacies. It supplies readers with the theoretical and analytical tools with which to explore the linguistic and social impact of a host of new digital literacy practices. Each chapter in the volume covers a different topic, presenting an overview of the major concepts, issues, problems and debates surrounding the topic, while also encouraging students to reflect on and critically evaluate their own language and communication practices. Features include: coverage of a diverse range of digital media texts, tools and practices including blogging, hypertextual organisation, Facebook, Twitter, YouTube, Wikipedia, websites and games an extensive range of examples and case studies to illustrate each topic, such as how blogs have affected our thinking about communication, how the creation and sharing of digital images and video can bring about shifts in social roles, and how the design of multiplayer online games for children can promote different ideologies a variety of discussion questions and mini-ethnographic research projects involving exploration of various patterns of media production and communication between peers, for example in the context of Wikinomics and peer production, social networking and civic participation, and digital literacies at work end of chapter suggestions for further reading and links to key web and video resources a companion website providing supplementary material for each chapter, including summaries of key issues, additional web-based exercises, and links to further resources such as useful websites, articles, videos and blogs.

Plague of diagrams

Group exhibition curated by Plastique Fantastique. Organised by David Burrows and Dean Kenning in collaboration with Ami Clarke, Andrew Conio, John Cussans and David Osbaldeston. Contributors: David Burrows, Rachel Cattle & Jenna Collins, Neil Chapman & Gillian Wylde, Ami Clarke, Richard Cochrane, Andrew Conio, John Cussans, David Burrows, Benedict Drew, English Heretic, Nikolaus Gansterer, Joey Holder, Dean Kenning, Christoph Lueder, Stine Llungdalh, Adelheid Mers, Mike Nelson, Paul O'Kane, David Osbaldeston, Plastique Fantastique, Patricia Reed, John Russell, Erica Scourti, Andy Sharp, Kamini Vellodi, Martin Westwood and Carey Young.

Early changes in apoplast composition associated with defence and disease in interactions between Phaseolus vulgaris and the halo blight pathogen Pseudomonas syringae pv. phaseolicola

The apoplast is the arena in which endophytic pathogens such as Pseudomonas syringae grow and interact with plant cells. Using metabolomic and ion analysis techniques, this study shows how the composition of Phaseolus vulgaris leaf apoplastic fluid changes during the first six hours of compatible and incompatible interactions with two strains of Pseudomonas syringae pv. phaseolicola (Pph) that differ in the presence of the genomic island PPHGI-1. Leaf inoculation with the avirulent island-carrying strain Pph 1302A elicited effector-triggered immunity (ETI) and resulted in specific changes in apoplast composition, including increases in conductivity, pH, citrate, γ-aminobutyrate (GABA) and K+, that are linked to the onset of plant defence responses. Other apoplastic changes, including increases in Ca2+, Fe2/3+ Mg2+, sucrose, β-cyanoalanine and several amino acids, occurred to a relatively similar extent in interactions with both Pph 1302A and the virulent, island-less strain Pph RJ3. Metabolic footprinting experiments established that Pph preferentially metabolizes malate, glucose and glutamate, but excludes certain other abundant apoplastic metabolites, including citrate and GABA, until preferred metabolites are depleted. These results demonstrate that Pph is well-adapted to the leaf apoplast metabolic environment and that loss of PPHGI-1 enables Pph to avoid changes in apoplast composition linked to plant defences.