The mitochondrial and autosomal mutation landscapes of prostate cancer

BACKGROUND: Prostate cancer (PCa) is the most common cancer in men. PCa is strongly age associated; low death rates in surveillance cohorts call into question the widespread use of surgery, which leads to overtreatment and a reduction in quality of life. There is a great need to increase the understanding of tumor characteristics in the context of disease progression.

OBJECTIVE: To perform the first multigenome investigation of PCa through analysis of both autosomal and mitochondrial DNA, and to integrate exome sequencing data, and RNA sequencing and copy-number alteration (CNA) data to investigate how various different tumor characteristics, commonly analyzed separately, are interconnected.

DESIGN, SETTING, AND PARTICIPANTS: Exome sequencing was applied to 64 tumor samples from 55 PCa patients with varying stage and grade. Integrated analysis was performed on a core set of 50 tumors from which exome sequencing, CNA, and RNA sequencing data were available.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Genes, mutated at a significantly higher rate relative to a genomic background, were identified. In addition, mitochondrial and autosomal mutation rates were correlated to CNAs and proliferation, assessed as a cell cycle gene expression signature.

RESULTS AND LIMITATIONS: Genes not previously reported to be significantly mutated in PCa, such as cell division cycle 27 homolog (Saccharomyces cerevisiae) (CDC27), myeloid/lymphoid or mixed-lineage leukemia 3 (MLL3), lysine (K)-specific demethylase 6A (KDM6A), and kinesin family member 5A (KIF5A) were identified. The mutation rate in the mitochondrial genome was 55 times higher than that of the autosomes. Multilevel analysis demonstrated a tight correlation between high reactive-oxygen exposure, chromosomal damage, high proliferation, and in parallel, a transition from multiclonal indolent primary PCa to monoclonal aggressive disease. As we only performed targeted sequence analysis; copy-number neutral rearrangements recently described for PCa were not accounted for.

CONCLUSIONS: The mitochondrial genome displays an elevated mutation rate compared to the autosomal chromosomes. By integrated analysis, we demonstrated that different tumor characteristics are interconnected, providing an increased understanding of PCa etiology.

Who Knows What's Going On? Mapping New Security Landscapes in Contemporary Espionage Fiction

This article explores whether or to what extent the contemporary espionage novel is able to map and interrogate transformations in the post-9/11security environment. It asks how well a form or genre of writing, typically handcuffed to the machinations and demands of the Cold War and state sovereignty, is able to adapt to a new security environment characterized by strategies of “risk assessment” and “resilience-building” and by modes or regimes of power not reducible to, or wholly controlled by, the state. In doing so, it thinks about the capacities of this type of fiction for “resisting” the formations of power it wants to make visible and is partly complicit with.

Making Ireland Modern

Making Ireland Modern is a cross-disciplinary, inter-institutional, inter-media design and research project which emerged from an open competition (won by Boyd and McLaughlin) to commission/curate the Irish pavilion for the Venice biennale 2014. It explores the relationship between architecture, infrastructure and technology in the building of a new nation. Constructed as a demountable, open matrix of drawings, photographs, models and other artefacts, the exhibition (12 x 5 x 6 metres) presents ten infrastructural episodes – Negation, Electricity, Health, Transportation, Television, Aviation, Education, Telecommunications, Motorways, Data – spanning a period of one hundred years from 1916-2016. Exploring a range of scales from the detail design of objects to entire landscapes and other territories, Making Ireland Modern describes architecture’s role in transforming the physical and cultural identity of the new state through its intersession in the everyday lives of its population. In 2015, we were commissioned by the Arts Council of Ireland to expand and develop the pavilion for a three cities tour of Ireland as one of the five major strands of the Arts Council’s Art2016 programme of Irish State’s 1916-2016 centennial celebrations (2016).

Punishment, youth justice and cultural contingency: Towards a balanced approach

Reflecting developments in the broader penological realm, accounts have been advanced over the last number of decades about a ‘punitive turn’ in the youth justice systems of Western democracies. Against the background of this work, this project seeks to identify convergent and divergent trends in the youth justice systems of England, the Republic of Ireland and Northern Ireland as well as the rationalities and discourses animating these. The results lend support to research emphasising the continued salience of national, regional and local factors on penal outcomes but also suggest the need to steer an analytical path somewhere between nomothetic (convergent) and idiographic (divergent) accounts.