Elevated expression of artemis in human fibroblast cells is associated with cellular radiosensitivity and increased apoptosis

Copyright @ 2012 Nature Publishing GroupThis article has been made available through the Brunel Open Access Publishing Fund.Background: The objective of this study was to determine the molecular mechanism(s) responsible for cellular radiosensitivity in two human fibroblast cell lines 84BR and 175BR derived from two cancer patients. Methods: Clonogenic assays were performed following exposure to increasing doses of gamma radiation to confirm radiosensitivity. γ-H2AX foci assays were used to determine the efficiency of DNA double strand break (DSB) repair in cells. Quantitative-PCR (Q-PCR) established the expression levels of key DNA DSB repair proteins. Imaging flow cytometry using Annexin V-FITC was used to compare artemis expression and apoptosis in cells. Results: Clonogenic cellular hypersensitivity in the 84BR and 175BR cell lines was associated with a defect in DNA DSB repair measured by the γ-H2AX foci assay. Q-PCR analysis and imaging flow cytometry revealed a two-fold overexpression of the artemis DNA repair gene which was associated with an increased level of apoptosis in the cells before and after radiation exposure. Over-expression of normal artemis protein in a normal immortalised fibroblast cell line NB1-Tert resulted in increased radiosensitivity and apoptosis. Conclusion: We conclude elevated expression of artemis is associated with higher levels of DNA DSB, radiosensitivity and elevated apoptosis in two radio-hypersensitive cell lines. These data reveal a potentially novel mechanism responsible for radiosensitivity and show that increased artemis expression in cells can result in either radiation resistance or enhanced sensitivity.This work was supported in part by The Vidal Sassoon Foundation USA. This article is made available through the Brunel Open Access Publishing Fund

Business under adverse home country institutions: The case of international sanctions against Myanmar

We expand the institutional perspective of international business by exploring the range of institutions outside the host country that influence international business. We use a critical case, Myanmar, to explore the dynamics of institutional constraints and the reaction of business to such constraints. Our in-depth case analysis focuses on four industries for the period 1996–2011. On this basis, we develop the concept of ‘low profile strategy’ and propose a conceptual framework of home country pressures influencing multinational enterprises’ international operation, and the variation of their impact across industries and firms. This framework provides a foundation for future work on the extra-territorial effects of institutions in international business

Fortifying or fragmenting the state? The political economy of the drug trade in Shan State, Myanmar, 1988-2012

Over the past twenty-five years, the government of Myanmar (Burma) has consolidated control over large parts of Shan State, neutralizing much of the threat posed by armed groups and strengthening its hold over revenue extraction. During this period Myanmar has retained its position as the world's second largest producer of illicit opium, much of which is converted into heroin within the country's borders. This article explores the relationship between state-building processes and the illicit opium/heroin economy in Shan State since 1988. The author has four aims. First, to reassess the theoretical assumptions that equate illicit economies with state fragility and demonstrate instead why illicit drug economies can become embedded in processes of conflict reduction and state consolidation. Second, to explain why establishing control over Shan State has become so important to the Myanmar government's state-building ambitions. Third, to analyze how the state's engagement with the drug trade has become a vital part of its attempts to consolidate control, in terms of financing military expansion and brokering deals with strongmen who are able to govern local populations. Finally, to assess how these strategies embody a form of “negotiated statehood” in which the state's growing control has been defined by attempts to manage, rather than monopolize, the means of coercion and extraction