No abstract

Previous observations indicated that C3G (RAPGEF1) promotes α-granule release, evidenced by the increase in P-selectin exposure on the platelet surface following its activation. The goal of the present study is to further characterize the potential function of C3G as a modulator of the platelet releasate and its implication in the regulation of angiogenesis.Proteomic analysis revealed a decreased secretion of anti-angiogenic factors from activated transgenic C3G and C3G∆Cat platelets. Accordingly, the secretome from both transgenic platelets had an overall pro-angiogenic effect as evidenced by an in vitro capillary-tube formation assay with HUVECs (human umbilical vein endothelial cells) and by two in vivo models of heterotopic tumor growth. In addition, transgenic C3G expression in platelets greatly increased mouse melanoma cells metastasis. Moreover, immunofluorescence microscopy showed that the pro-angiogenic factors VEGF and bFGF were partially retained into α-granules in thrombin- and ADP-activated mouse platelets from both, C3G and C3GΔCat transgenic mice. The observed interaction between C3G and Vesicle-associated membrane protein (Vamp)-7 could explain these results. Concomitantly, increased platelet spreading in both transgenic platelets upon thrombin activation supports this novel function of C3G in α-granule exocytosis.Collectively, our data point out to the co-existence of Rap1GEF-dependent and independent mechanisms mediating C3G effects on platelet secretion, which regulates pathological angiogenesis in tumors and other contexts. The results herein support an important role for platelet C3G in angiogenesis and metastasis.

It was shown in a series of recent publications that the eigenvalues of n × n Toeplitz matrices generated by so-called simple-loop symbols admit certain regular asymptotic expansions into negative powers of n + 1. On the other hand, recently two of the authors considered the pentadiagonal Toeplitz matrices generated by the symbol g(x) = (2 sin(x/2)) 4 , which does not satisfy the simple-loop conditions, and derived asymptotic expansions of a more complicated form. We here use these results to show that the eigenvalues of the pentadiagonal Toeplitz matrices do not admit the expected regular asymptotic expansion. This also delivers a counterexample to a conjecture by Ekström, Garoni, and Serra-Capizzano and reveals that the simple-loop condition is essential for the existence of the regular asymptotic expansion.MSC 2010: Primary 15B05, Secondary 15A18, 41A60, 65F15.

This seminal article analyses the current structural crisis and instability in an ever more polarised world in relation to earlier systemic crises that were resolved through fascism or through Fordist-Keynesian 'class compromise' (the 1930s) and the emergence of capitalist globalisation (the 1970s). The authors identify three basic responses to the crisis: popular insurgency from below; reformist stabilisation from above; and, a twenty-first century neo-fascism. Looking specifically at the US, they analyse political and economic developments that demonstrate fascistic characteristics. While no simple replication of the past, the emergence of a Christian Right since the mid-1980s, the growth of certain currents within the Tea Party movement, the sharp increase in violent hate groups, the spread of a vicious anti-immigrant movement, the psychopathology of white decline, sharp militarisation and pervasive policing give some indications of the rise of fascist tendencies. But what is crucial today is the sophistication of such a project, made possible by the ideological domination of media together with new surveillance and social control technologies that allow it to rely more on selective than generalised repression. In calling for a co-ordinated fightback, both in the US and beyond, the authors see the only viable solution to the crisis of global capitalism as a massive redistribution of wealth and power downward towards

No abstract