Citizenship and Collective Identity in Europe

No abstract available

The microtubule targeting agent PBOX-15 inhibits integrin-mediated cell adhesion and induces apoptosis in acute lymphoblastic leukaemia cells

Although recent decades have seen an improved cure rate for newly diagnosed paediatric acute lymphoplastic leukaemia (ALL), the treatment options for adult ALL, T-cell ALL (T-ALL) and relapsed disease remain poor. We have developed a novel series of pyrrolo-1,5-benzoxazepine (PBOX) compounds and established their anticancer efficacy in a variety of human tumour cell types. Here, we demonstrate that PBOX-15 inhibits cell growth, and induces G2/M cell cycle arrest and apoptosis in both T-ALL and B-cell ALL (B-ALL) cells. In addition, prior to PBOX-15-induced apoptosis, PBOX-15 decreases ALL cell adhesion, spreading and migration. Concurrently, PBOX-15 differentially down-regulates β1-, β2- and α4-integrin expression in ALL cells and significantly decreases integrin-mediated cell attachment. PBOX-15 interferes with the lateral mobility and clustering of integrins in both B-ALL and T-ALL cells. These data suggest that PBOX-15 is not only effective in inducing apoptosis in ALL cells, but also has the potential to disrupt integrin-mediated adhesion of malignant lymphocytes, which represents a novel avenue for regulating leukaemic cell homing and migration.

Activated protein C inhibits tumor necrosis factor and macrophage migration inhibitory factor production in monocytes

The precise regulatory mechanisms of amplification and downregulation of the pro- and anti-inflammatory cytokines in the inflammatory response have not been fully delineated. Although activated protein C (APC) and its precursor protein C (PC) have recently been reported to be promising therapeutic agents in the management of meningococcal sepsis, direct evidence for the anti-inflammatory effect remains scarce. We report that APC inhibits in vitro the release of tumor necrosis factor (TNF) and macrophage migration inhibitory factor (MIF), two known cytokine mediators of bacterial septic shock, from lipopolysaccharide (LPS)-stimulated human monocytes. The THP-1 monocytic cell line, when stimulated with LPS and concomitant APC, exhibited a marked reduction in the release of TNF and MIF protein in a concentration-dependent manner compared to cells stimulated with LPS alone. This effect was observed only when incubations were performed in serum-free media, but not in the presence of 1-10% serum. Serum-mediated inhibition could only be overcome by increasing APC concentrations to far beyond physiological levels, suggesting the presence of endogenous serum-derived APC inhibitors. Inhibition of MIF release by APC was found to be independent of TNF, as stimulation of MIF release by LPS was unaltered in the presence of anti-TNF antibodies. Our data confirm that the suggested anti-inflammatory properties of APC are due to direct inhibition of the release of the pro-inflammatory monokine TNF, and imply that the anti-inflammatory action of APC is also mediated via inhibition of MIF release.

Territoriality and Migration in a Divided Society: Lay Theories of Citizenship and Place in Northern Ireland

The study of citizenship has increasingly focused on the ways in which spatialized understandings of the concept can be used to marginalise and exclude social groups: exclusive constructions of national boundaries, local neighbourhoods and public spaces can deny marginalised groups their social and political rights. Less attention has been paid to how constructions of place can accommodate different groups’ rights and promote peaceful coexistence. This is particularly important in locations where migration disrupts existing understandings (‘lay theories’) of the relationship between residency, identity and collective rights. The present research examines how spatialized understandings of citizenship shape perceptions of intergroup mixing in previously segregated areas of a post-conflict society. Critical Discursive Social Psychological (CDSP) analysis of 30 interviews with long-term residents and recent migrants to increasingly mixed areas of Belfast shows that, while all pa
rticipants acknowledged Northern Ireland’s territorialisation, different lay theories of citizenship underpin the possibility and desirability of intergroup coexistence. Long-term residents drew upon understandings of the negative citizenry of the outgroup to argue against the possibility of peaceful coexistence within their locale, while recent incomers gave evidence of their own experiences of good citizenship within the shared spaces of neighbourhood to demonstrate that this could and should be achieved. The implications of lay theories of citizenship for the study of residential migration and mixing are discussed