Comprehensive genomic screens identify a role for PLZF-RAR alpha as a positive regulator of cell proliferation via direct regulation of c-MYC

The t(11; 17)(q23;q21) translocation is associated with a retinoic acid (RA)-insensitive form of acute promyelocytic leukemia (APL), involving the production of reciprocal fusion proteins, promyelocytic leukemia zinc finger-retinoic acid receptor alpha (PLZF-RAR alpha) and RAR alpha-PLZF. Using a combination of chromatin immuno-precipitation promotor arrays (ChIP-chip) and gene expression profiling, we identify novel, direct target genes of PLZF-RAR alpha that tend to be repressed in APL compared with other myeloid leukemias, supporting the role of PLZF-RAR alpha as an aberrant repressor in APL. In primary murine hematopoietic progenitors, PLZF-RAR alpha promotes cell growth, and represses Dusp6 and Cdkn2d, while inducing c-Myc expression, consistent with its role in leukemogenesis. PLZF-RAR alpha binds to a region of the c-MYC promoter overlapping a functional PLZF site and antagonizes PLZF-mediated repression, suggesting that PLZF-RAR alpha may act as a dominant-negative version of PLZF by affecting the regulation of shared targets. RA induced the differentiation of PLZF-RAR alpha-transformed murine hematopoietic cells and reduced the frequency of clonogenic progenitors, concomitant with c-Myc down-regulation. Surviving RA-treated cells retained the ability to be replated and this was associated with sustained c-Myc expression and repression of Dusp6, suggesting a role for these genes in maintaining a self-renewal pathway triggered by PLZF-RAR alpha. (Blood. 2009; 114: 5499-5511)

Shared or unshared parental care in overwintering brent geese (Branta bernicla hrota)

We examine brood size effects on the behaviour of wintering parent and juvenile brent geese (Branta bernicla hrota) to test predictions of shared and unshared parental care models. The behaviour of both parents and offspring appear to be influenced by declining food availability over the winter. Parental vigilance increased with brood size and may be explained by vigilance having functions in addition to antipredator behaviour where the benefits are shared among the brood. There was no increase in parental aggression with brood size and this does not fit the prediction of shared care. Nevertheless, large families are able to monopolize better feeding areas compared with smaller families and large families static feed more but walk feed less than do small families, the former apparently being the preferred mode. The presence of additional young, rather than increasing the amount of parental aggression, seems to enhance the family's competitive ability. Because parents with large broods benefit from enhanced access to resources there is likely to be no additional significant cost in the parental care of larger broods (sensu Trivers 1972).

Journeys into the unknown: shared schooling and social change in Quebec and Northern Ireland

This article compares experiences of shared schooling in societies with 2 distinctive traits: first, a history of intercommunity conflict and isolation; and second, a segregated school system. Drawing on Parekh’s (2006) reconceptualisation of multiculturalism, this article analyses issues arising from experiences of intercommunity contact in shared schools in Quebec and Northern Ireland—in one case, bringing Anglophones and Francophones together and, in the other, Protestants and Catholics. Research data from both contexts is drawn upon to reflect on how this experience is lived. The metaphor of a journey is used to capture what it represents for those involved. A need to clarify, recognize, and exploit the potential of shared schooling for the transformation of divided societies is identified.

Translating evidence into practice: A shared priority in public health?

Translational and transdisciplinary research is needed to tackle complex public health problems. This article has three aims. Firstly, to determine how academics and non-academics (practitioners, policy makers and community workers) identified with the goals of the UKCRC Centre of Excellence for Public Health in Northern Ireland and how their attitudes varied in terms of knowledge brokerage and translation. Secondly, to map and analyse the network structure of the public health sector and the placement of the Centre within this. Thirdly, to aggregate responses from members of the network by work setting to construct the trans-sectoral network and devise the Root Mean Sum of Squares to determine the quality and potential value of connections across this network.The analysis was based on data collected from 98 individuals who attended the launch of the Centre in June 2008. Analysis of participant expectations and personal goals suggests that the academic members of the network were more likely to expect the work of the Centre to produce new knowledge than non-academics, but less likely to expect the Centre to generate health interventions and influence health policy. Academics were also less strongly oriented than non-academics to knowledge transfer as a personal goal, though more confident that research findings would be diffused beyond the immediate network. A central core of five nodes is crucial to the overall configuration of the regional public health network in Northern Ireland, with the Centre being well placed to exert influence within this. Though the overall network structure is fairly robust, the connections between some component parts of the network - such as academics and the third sector - are unidirectional.Identifying these differences and core network structure is key to translational and transdisciplinary research. Though exemplified in a regional study, these techniques are generalisable and applicable to many networks of interest: public health, interdisciplinary research or organisational involvement and stakeholder linkage.

Creating Shared Public Space in the Contested City: The Role of Urban Design

This paper examines relevant characteristics of the ‘contested city’ and the concept of ‘public space’ in that problematic context. It offers an appraisal of the historical and contemporary role of urban design in shaping social space and interrogates the feasibility of using urban design to facilitate more integrated cityscapes. It presents detailed case studies of two ‘contested cities’, Nicosia and Belfast, based on content analysis of policy and planning documents, extensive site analyses in both places, interviews and seminar discussions with policy makers, planners, community and civic leaders. The paper comprises four dimensions—conceptual, descriptive, analytical and prescriptive—and in its final section identifies core values and relevant policies for the potential achievement of shared space in contested cities.

A Shared Future? Exclusion, Stigmatization, and Mental Health of Same-Sex-Attracted Young People in Northern Ireland

For more than a decade the Peace Process has fundamentally changed Northern Irish society. However, although socioreligious integration and ethnic mixing are high on the political agenda in Northern Ireland, the Peace Process has so far failed to address the needs of some of the most vulnerable young people, for example, those who identify as gay, lesbian, or bisexual. Public debates in Northern Ireland remain hostile to same-sex-attracted people. Empirical evidence from the annual Young Life and Times (YLT) survey of 16-year-olds undertaken by ARK shows that same-sex-attracted young people report worse experiences in the education sector (e.g., sex education, school bullying), suffer from poorer mental health, experience higher social pressures to engage in health-adverse behavior, and are more likely to say that they will leave Northern Ireland and not return. Equality legislation and peace process have done little to address the heteronormativity in Northern Ireland.