According to a recently proposed hypothesis, initiation of signal transduction via immunoreceptors depends on interactions of the engaged immunoreceptor with glycosphingolipid-enriched membrane microdomains (GEMs). In this study, we describe a novel GEM-associated transmembrane adaptor protein, termed phosphoprotein associated with GEMs (PAG). PAG comprises a short extracellular domain of 16 amino acids and a 397-amino acid cytoplasmic tail containing ten tyrosine residues that are likely phosphorylated by Src family kinases. In lymphoid cell lines and in resting peripheral blood α/β T cells, PAG is expressed as a constitutively tyrosine-phosphorylated protein and binds the major negative regulator of Src kinases, the tyrosine kinase Csk. After activation of peripheral blood α/β T cells, PAG becomes rapidly dephosphorylated and dissociates from Csk. Expression of PAG in COS cells results in recruitment of endogenous Csk, altered Src kinase activity, and impaired phosphorylation of Src-specific substrates. Moreover, overexpression of PAG in Jurkat cells downregulates T cell receptor–mediated activation of the transcription factor nuclear factor of activated T cells. These findings collectively suggest that in the absence of external stimuli, the PAG–Csk complex transmits negative regulatory signals and thus may help to keep resting T cells in a quiescent state.

A series of Omega experiments have produced and characterized high velocity counter-streaming plasma flows relevant for the creation of collisionless shocks. Single and double CH2 foils have been irradiated with a laser intensity of ∼10 16 W/cm 2 . The laser ablated plasma was characterized 4 mm from the foil surface using Thomson scattering. A peak plasma flow velocity of 2,000 km/s, an electron temperature of ∼110 eV, an ion temperature of ∼30 eV, and a density of ∼10 18 cm −3 were measured in the single foil configuration. Significant increases in electron and ion temperatures were seen in the double foil geometry. The measured single foil plasma conditions were used to calculate the ion skin depth, c/ωpi ∼0.16 mm, the interaction length, int, of ∼8 mm, and the Coulomb mean free path, λ mf p ∼27 mm. With c/ωpi int < λ mf p we are in a regime where collisionless shock formation is possible.

Self-organization 1,2 occurs in plasmas when energy progressively transfers from smaller to larger scales in an inverse cascade 3 . Global structures that emerge from turbulent plasmas can be found in the laboratory 4 and in astrophysical settings; for example, the cosmic magnetic field 5,6 , collisionless shocks in supernova remnants 7 and the internal structures of newly formed stars known as Herbig-Haro objects 8 . Here we show that large, stable electromagnetic field structures can also arise within counter-streaming supersonic plasmas in the laboratory. These surprising structures, formed by a yet unexplained mechanism, are predominantly oriented transverse to the primary flow direction, extend for much larger distances than the intrinsic plasma spatial scales and persist for much longer than the plasma kinetic timescales. Our results challenge existing models of counter-streaming plasmas and can be used to better understand large-scale and long-time plasma self-organization.Our experiments were performed at the OMEGA EP laser facility, where two kilojoule-class lasers irradiated two polyethylene (CH 2 ) plastic discs that faced each other at a distance of 8 mm, creating a system of high-velocity laser-ablated counter-streaming plasma flows. The experimental details are described in Fig. 1 and in the Methods. At early times, up to at least 8 ns, intra-jet ion collisions are known to be strong (owing to relatively low-particle thermal velocities) but inter-jet ion collisions are rare (owing to relatively high flow velocities), permitting the evolution of both hydrodynamic and collisionless plasma instabilities 9,10 (Table 1). We visualized the electric and magnetic field structures in the counter-streaming plasmas with short-pulse laser-generated proton beam imaging 11,12 , taken from two orthogonal views to evaluate the possible azimuthal symmetry of the field structures. After roughly 3 ns, caustics (large-intensity variations 13 ) in the proton images indicate the formation of strong field zones within the plasma, probably due to sharp structures with strong gradients, as reported elsewhere 14 . By 4 ns, the features have changed markedly into two large swaths of straight transverse caustics that extend for up to 5 mm. This extent is large compared with the fundamental scale lengths of the plasma (Table 1) such as the Debye length (50,000 times larger) and the ion inertial length (nearly 100 times larger), indicating a high degree of self-organization. This organization

We investigated the time evolution of a strong collisionless shock in counterstreaming plasmas produced using a high-power laser pulse. The counterstreaming plasmas were generated by irradiating a CH double-plane target with the laser. In self-emission streaked optical pyrometry data, steepening of the self-emission profile as the two-plasma interaction evolved indicated shock formation. The shock thickness was less than the mean free path of the counterstreaming ions. Two-dimensional snapshots of the self-emission and shadowgrams also showed very thin shock structures. The Mach numbers estimated from the flow velocity and the brightness temperatures are very high.

To identify proteins that could be molecular targets for diagnosis and treatment of hepatitis C virus-related hepatocellular carcinoma (HCV-related HCC), we used a proteomic approach to analyze protein expression in samples of human liver. Twenty-six pairs of tumorous and corresponding nontumorous liver samples from patients with HCV-related HCC and six normal liver samples were analyzed by two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometry. One of the numerous spots that showed stronger intensity in tumorous than in nontumorous samples was identified as alpha enolase, a key enzyme in the glycolytic pathway. Expression of this protein increased with tumor dedifferentiation and was significantly higher in poorly differentiated HCC than in well-differentiated HCC. This pattern was reproduced by immunoblot analysis and immunohistochemistry. Expression of alpha enolase also correlated positively with tumor size and venous invasion. These results suggest that alpha enolase is one of the candidates for biomarkers for tumor progression that deserves further investigation in HCV-related HCC.