The Anti-Migratory Effects of FKBPL and Its Peptide Derivative, AD-01: Regulation of CD44 and the Cytoskeletal Pathway

FK506 binding protein-like (FKBPL) and its peptide derivatives exert potent anti-angiogenic activity and and control tumour growth in xenograft models, when administered exogenously. However, the role of endogenous FKBPL in angiogenesis is not well characterised. Here we investigated the molecular effects of the endogenous protein and its peptide derivative, AD-01, leading to their anti-migratory activity. Inhibition of secreted FKBPL using a blocking antibody or siRNA-mediated knockdown of FKBPL accelerated the migration of human microvascular endothelial cells (HMEC-1). Furthermore, MDA-MB-231 tumour cells stably overexpressing FKBPL inhibited tumour vascular development suggesting that FKBPL secreted from tumour cells could inhibit angiogenesis. Whilst FKBPL and AD-01 target CD44, the nature of this interaction is not known and here we have further interrogated this aspect. We have demonstrated that FKBPL and AD-01 bind to the CD44 receptor and inhibit tumour cell migration in a CD44 dependant manner; CD44 knockdown abrogated AD-01 binding as well as its anti-migratory activity. Interestingly, FKBPL overexpression and knockdown or treatment with AD-01, regulated CD44 expression, suggesting a co-regulatory pathway for these two proteins. Downstream of CD44, alterations in the actin cytoskeleton, indicated by intense cortical actin staining and a lack of cell spreading and communication were observed following treatment with AD-01, explaining the anti-migratory phenotype. Concomitantly, AD-01 inhibited Rac-1 activity, up-regulated RhoA and the actin binding proteins, profilin and vinculin. Thus the anti-angiogenic protein, FKBPL, and AD-01, offer a promising and alternative approach for targeting both CD44 positive tumours and vasculature networks.

Chasing the Green Buck? Environmental Activism in Post-communist Baltic States

The paper investigates the dynamics and volution of issues on the agenda of Baltic environmental non-governmental organisations (NGOs) since the collapse of communism. The past research on Baltic environment activism suggests that these enjoy high visibility because they tapped the core societal views of natural environment as a crucial asset of a nation. As we demonstrate in this paper, the changes in agendas of Baltic environmental non-governmental organisations (ENGOs) make clear that the rhetorical toolbox of ‘national environment’ is often used to mainly achieve greater financial gains for individual members, rather than for society at large. We illustrate how the dearth of economic opportunities for domestic public has impacted perceptions of ‘nature’ advocated by the environmental activists, focussing specifically on national perceptions of ownership and the resulting actions appropriating ‘nature’ as a source for economic development, only tangentially attaining environmental outcomes on the way. The vision that the ‘environment’ is an economic resource allowed ENGO activists to cooperate with the domestic policymaking, while tapping international networks and donors for funding. Throughout the past decades they worked to secure their own and their members' particularistic economic interests and, as we demonstrate, remained disengaged from the political process and failed to develop broader reproach with publics.

Shared Education in contested spaces: How collaborative networks improve communities and schools

Societies which suffer from ethnic and political divisions are often characterised by patterns of social and institutional separation, and sometimes these divisions remain even after political conflict has ended. This has occurred in Northern Ireland where there is, and remains, a long-standing pattern of parallel institutions and services for the different communities. A socially significant example lies in the education system where a parallel system of Catholic and Protestant schools has been in place since the establishment of a national school system in the 1830s. During the years of political violence in Northern Ireland a variety of educational interventions were implemented to promote reconciliation, but most of them failed to create any systemic change. This paper describes a post-conflict educational initiative known as Shared Education which aims to promote social cohesion and school improvement by encouraging sustained and regular shared learning between students and broader collaboration between teachers and school leaders from different schools. The paper examines the background to work on Shared Education, describes a ‘sharing continuum’ which emerged as an evaluation and policy tool from this work and considers evidence from a case study of a Shared Education school partnership in a divided city in Northern Ireland. The paper will conclude by highlighting some of the significant social and policy impact of the Shared Education work.