Glycosylation is an Androgen-Regulated Process Essential for Prostate Cancer Cell Viability

Steroid androgen hormones play a key role in the progression and treatment of prostate cancer, with androgen deprivation therapy being the first-line treatment used to control cancer growth. Here we apply a novel search strategy to identify androgen-regulated cellular pathways that may be clinically important in prostate cancer. Using RNASeq data, we searched for genes that showed reciprocal changes in expression in response to acute androgen stimulation in culture, and androgen deprivation in patients with prostate cancer. Amongst 700 genes displaying reciprocal expression patterns we observed a significant enrichment in the cellular process glycosylation. Of 31 reciprocally-regulated glycosylation enzymes, a set of 8 (GALNT7, ST6GalNAc1, GCNT1, UAP1, PGM3, CSGALNACT1, ST6GAL1 and EDEM3) were significantly up-regulated in clinical prostate carcinoma. Androgen exposure stimulated synthesis of glycan structures downstream of this core set of regulated enzymes including sialyl-Tn (sTn), sialyl Lewis(X) (SLe(X)), O-GlcNAc and chondroitin sulphate, suggesting androgen regulation of the core set of enzymes controls key steps in glycan synthesis. Expression of each of these enzymes also contributed to prostate cancer cell viability. This study identifies glycosylation as a global target for androgen control, and suggests loss of specific glycosylation enzymes might contribute to tumour regression following androgen depletion therapy.

Narratively framing emergent identities in post-agreement societies: patterns of the Northern Irish identity within the provincial media

The research analyses ‘Northern Irish’ identity narratives post-agreement, and examines the configuration of frame agendas in terms of individual narrative components. A content analysis utilised news published through 1997–2014 within Northern Ireland daily newspapers – the Belfast Telegraph, the Irish News and the News Letter. A process of manifest coding produced an emergent coding scheme displaying the relative stability of media frames surrounding the Northern Irish identity as broadly partisan; however, there is also a subtle narrative shift of Northern Irish identity across the time periods; and findings of a dominant framing paradigm of political and social conceptions of identification post-agreement.

Breaking patterns of conflict in Northern Ireland: new perspectives

Central to reaching peace and settlement in Northern Ireland was a sequence of British–Irish intergovernmental discussions and negotiations, dating from the beginning of the 1980s. British and Irish state cooperation and intervention has remained central to the stability of the settlement reached in 1998. The motives of state actors, however, have been unclear, and the role of the state in the political process has been the subject of some scholarly controversy. This paper looks at the types of evidence that can help to resolve such questions. It focuses on the value of elite interviews, arguing that they can constitute an important and irreplaceable body of evidence when used critically, but it also highlights the risks of excessive reliance on this type of source. It goes on to describe a major research project in University College Dublin whose aim was to record the experiences and interpretations of the actors who engaged in British–Irish negotiations over the last four decades. It discusses the resulting elite interviews and witness seminars and the methodological and ethical difficulties encountered. It describes how these were overcome, and outlines the conditions of confidentiality imposed.