Mechanisms of DNA Damage Response to Targeted Irradiation in Organotypic 3D Skin Cultures

DNA damage (caused by direct cellular exposure and bystander signaling) and the complex pathways involved in its repair are critical events underpinning cellular and tissue response following radiation exposures. There are limited data addressing the dynamics of DNA damage induction and repair in the skin particularly in areas not directly exposed. Here we investigate the mechanisms regulating DNA damage, repair, intracellular signalling and their impact on premature differentiation and development of inflammatory-like response in the irradiated and surrounding areas of a 3D organotypic skin model. Following localized low-LET irradiation (225 kVp X-rays), low levels of 53BP1 foci were observed in the 3D model (3.8±0.28 foci/Gy/cell) with foci persisting and increasing in size up to 48 h post irradiation. In contrast, in cell monolayers 14.2±0.6 foci/Gy/cell and biphasic repair kinetics with repair completed before 24 h was observed. These differences are linked to differences in cellular status with variable level of p21 driving apoptotic signalling in 2D and accelerated differentiation in both the directly irradiated and bystander areas of the 3D model. The signalling pathways utilized by irradiated keratinocytes to induce DNA damage in non-exposed areas of the skin involved the NF-κB transcription factor and its downstream target COX-2.

Non-targeted effects of ionising radiation-Implications for low dose risk

Non-DNA targeted effects of ionising radiation, which include genomic instability, and a variety of bystander effects including abscopal effects and bystander mediated adaptive response, have raised concerns about the magnitude of low-dose radiation risk. Genomic instability, bystander effects and adaptive responses are powered by fundamental, but not clearly understood systems that maintain tissue homeostasis. Despite excellent research in this field by various groups, there are still gaps in our understandfng of the likely mechanisms associated with non-DNA targeted effects, particularly with respect to systemic (human health) consequences at low and intermediate doses of ionising radiation. Other outstanding questions include links between the different non-targeted responses and the variations. in response observed between individuals and cell lines, possibly a function of genetic background. Furthermore, it is still not known what the initial target and early interactions in cells are that give rise to non-targeted responses in neighbouring or descendant cells. This paper provides a commentary on the current state of the field as a result of the non-targeted effects of ionising radiation (NOTE) Integrated Project funded by the European Union. Here we critically examine the evidence for non-targeted effects, discuss apparently contradictory results and consider implications for low-dose radiation health effects. (C) 2012 Elsevier B.V. All rights reserved.

Religion, Violence and Cities

In exploring the connections between religion, violence and cities, the book probes the extent to which religion moderates or exacerbates violence in an increasingly urbanised world. Originating in a five year research project , Conflict in Cities and the Contested State, concerned with Belfast, Jerusalem and other ethno-nationally divided cities, this volume widens the geographical focus to include diverse cities from the Balkans, the Middle East, Nigeria and Japan. In addressing the understudied triangular relationships between religion, violence and cities, contributors stress the multiple forms taken by religion and violence while challenging the compartmentalisation of two highly topical debates – links between religion and violence on the one hand, and the proliferation of violent urban conflicts on the other hand. Their research demonstrates why cities have become so important in conflicts driven by state-building, fundamentalism, religious nationalism, and ethno-religious division and illuminates the conditions under which urban environments can fuel violent conflicts while simultaneously providing opportunities for managing or transforming them.

Religion, Violence and Cities: An Introduction

The catalyst for this special issue was a symposium entitled Religion, Violence and Cities, held under the auspices of a five year inter-disciplinary research project on ethno-nationally divided cities.

While this project expressly addressed cities divided by ethno-national conflict, it was clear from the beginning that there was an important religious dimension to such conflicts in most, if not all, the cities being studied.2 The rationale of the Special Issue is to examine how this religious dimension exacerbates (or moderates) urban violence within a broad comparative context. Although three of the following articles are informed by Project research, we draw the net wider to encompass a broader geographical spread from the Balkans, the Middle East, Nigeria and Japan.

Radioprotection of targeted and bystander cells by methylproamine

INTRODUCTION: Radioprotective agents are of interest for application in radiotherapy for cancer and in public health medicine in the context of accidental radiation exposure. Methylproamine is the lead compound of a class of radioprotectors which act as DNA binding anti-oxidants, enabling the repair of transient radiation-induced oxidative DNA lesions. This study tested methylproamine for the radioprotection of both directly targeted and bystander cells.

METHODS: T98G glioma cells were treated with 15 μM methylproamine and exposed to (137)Cs γ-ray/X-ray irradiation and He(2+) microbeam irradiation. Radioprotection of directly targeted cells and bystander cells was measured by clonogenic survival or γH2AX assay.

RESULTS: Radioprotection of directly targeted T98G cells by methylproamine was observed for (137)Cs γ-rays and X-rays but not for He(2+) charged particle irradiation. The effect of methylproamine on the bystander cell population was tested for both X-ray irradiation and He(2+) ion microbeam irradiation. The X-ray bystander experiments were carried out by medium transfer from irradiated to non-irradiated cultures and three experimental designs were tested. Radioprotection was only observed when recipient cells were pretreated with the drug prior to exposure to the conditioned medium. In microbeam bystander experiments targeted and nontargeted cells were co-cultured with continuous methylproamine treatment during irradiation and postradiation incubation; radioprotection of bystander cells was observed.

DISCUSSION AND CONCLUSION: Methylproamine protected targeted cells from DNA damage caused by γ-ray or X-ray radiation but not He(2+) ion radiation. Protection of bystander cells was independent of the type of radiation which the donor population received.

The European Court of Human Rights and Domestic Violence: Valiuliene v Lithuania

This article analyses the recent jurisprudence of the European Court of Human Rights on the issue of domestic violence, with a particular focus on Valiuliene v Lithuania. It seems that to date the Court’s jurisprudence on this issue is somewhat inconsistent, and with Valiuliene v Lithuania the Court was given an opportunity to clarify its approach in this area. There are certainly a number of positive aspects to the Court’s judgment, however there are also difficulties with the approach of the Court in this case. Overall it is to be hoped that the judgment in Valiuliene v Lithuania will mark the beginning of a more coherent jurisprudence as regards domestic violence.

Transitional justice, demobilization, and peacebuilding amid political violence: Examining individual preferences in the Caribbean coast of Colombia

The conventional wisdom in the transitional justice literature is that there is no one-size-fits-all approach. This article suggests that this may also be true within a given state. The current paper reports on quantitative and qualitative data from 184 participants in a survey conducted in the Caribbean coast of Colombia. Results suggest widespread support for transitional justice mechanisms – such as perpetrator accountability, public acknowledgement and structural change – but dissatisfaction with national-level initiatives, specifically the 2005 Justice and Peace Law. Yet, despite a distrust of the national government and protracted conflict, individuals report social trust, community cohesion and reliance on local government institutions. These attitudes and behaviours suggest that decentralised transitional justice mechanisms may be more effective in meeting victims' needs. Moreover, analyses indicate that individual preferences are influenced by community factors, such as the presence of demobilised paramilitaries, which can be addressed through more localised approaches to promote peacebuilding. The paper concludes with best practices derived from the findings.

Degradation, Harm and Survival in a Women’s Prison:Special Issue on Gendered Violence

This article is derived in in-depth qualitative research in the women’s unit of a male prison in Northern Ireland. The researchers had unprecedented observational and interview access and moved freely within the unit including the punishment block. What follows focuses primarily on the experiences of women and girls, recording their accounts of the impact on their lives of a harsh and neglectful regime. It demonstrates how the institutionalisation of violation and neglect within women’s prisons is often gender specific. Finally, it considers the key research recommendations, noting official responses.

OLDER WOMEN’S LIFELONG EXPERIENCES OF DOMESTIC VIOLENCE IN NORTHERN IRELAND

Violence against women is a serious criminal and public health issue with devastating consequences for women, families and society. To date, little international research has been given to understanding the needs of older women, who are experiencing domestic violence; that is, physical, sexual, emotional or financial abuse carried out by a spouse or partner. This study fills a significant gap in the literature as the needs of older women who have experienced a lifetime of domestic violence in Northern Ireland are unknown. Health professionals, service providers and policy makers often assume that violence stops at age 55 and there is a noticeable lack of literature, research and guidelines on the issue. The greatest challenge for health visitors is that abuse remains hidden, with women remaining silent and finding it difficult to speak openly or seek help.