A new microtubule-targeting compound PBOX-15 inhibits T-cell migration via post-translational modifications of tubulin

The ordered, directional migration of T-lymphocytes is a key process during immune surveillance, immune response, and development. A novel series of pyrrolo-1,5-benzoxazepines have been shown to potently induce apoptosis in variety of human chemotherapy resistant cancer cell lines, indicating their potential in the treatment of both solid tumors and tumors derived from the hemopoietic system. Pyrrolobenzoxazepine 4-acetoxy-5-(1-naphtyl)naphtho[2,3-b]pyrrolo[1,2-d][1,4]-oxazepine (PBOX-15) has been shown to depolymerize tubulin in vitro and in the MCF7 breast cancer cell line. We hypothesized that this may suggest a role for this compound in modulating integrin-induced T-cell migration, which is largely dependent on the microtubule dynamics. Experiments were performed using human T lymphoma cell line Hut78 and peripheral blood T-lymphocytes isolated from healthy donors. We observed that human T-lymphocytes exposed to PBOX-15 have severely impaired ability to polarize and migrate in response to the triggering stimulus generated via cross-linking of integrin lymphocyte function associated antigen-1 receptor. Here, we show that PBOX-15 can dramatically impair microtubule network via destabilization of tubulin resulting in complete loss of the motile phenotype of T-cells. We demonstrate that PBOX-15 inhibitory mechanisms involve decreased tubulin polymerization and its post-translational modifications. Novel microtubule-targeting effects of PBOX-15 can possibly open new horizons in the treatment of overactive inflammatory conditions as well as cancer and cancer metastatic spreading.

Review of the Viability Audit process: analysis of post-primary school data

This paper provides an analysis of the post-primary school data provided in the viability audit report published in February 2012 and complements a paper already prepared with an analysis of primary school data. The Viability Audit has been led by the Education and Library Boards, working in close conjunction with CCMS. The Area Planning process was led by the Department of Education, working with the Education and Library Boards and CCMS.

The Illusions of Post-Feminism, Ghosts of Gender and the Discourses of Law

This article seeks to consider evidence of post-feminist and "post-equality" gender narratives contained in the discourses of law in the UK and European contexts. Analysis of perennial ghosts of gender in the areas of gender-neutrality in policy, legislative regulation of sexual crimes, and the adjudication of gendered issues by judges will be undertaken in order to renew and reinstate the focus of the legal feminist project and advocate for continued scrutiny in these three practical areas.

Modulating mythology in a post-traumatic era: Murals and re-imaging in Northern Ireland.

Arguably the most ancient of the social media, wall paintings have been a persistent vehicle of cultural meaning management. The dynamics of myth markets are reflected in the sectarian murals of Northern Ireland. In this paper, we draw from consumer research literature on mythology and street art to explore the continuous revision of these wallscapes that seeks to address the enduring contradictions of civic ideology in contested political space. In particular, we focus on the use of classical, historical and pop-cultural mythologies to transform private space into public place. We examine the decommissioning of murals occurring in the wake of the Peace Accords, and speculate on the implications of the creation of a shared mythology for the future of mural painting and the state.