A Genome-Wide Collection of Mos1 Transposon Insertion Mutants for the C. elegans Research Community

Methods that use homologous recombination to engineer the genome of C. elegans commonly use strains carrying specific insertions of the heterologous transposon Mos1. A large collection of known Mos1 insertion alleles would therefore be of general interest to the C. elegans research community. We describe here the optimization of a semi-automated methodology for the construction of a substantial collection of Mos1 insertion mutant strains. At peak production, more than 5,000 strains were generated per month. These strains were then subject to molecular analysis, and more than 13,300 Mos1 insertions characterized. In addition to targeting directly more than 4,700 genes, these alleles represent the potential starting point for the engineered deletion of essentially all C. elegans genes and the modification of more than 40% of them. This collection of mutants, generated under the auspices of the European NEMAGENETAG consortium, is publicly available and represents an important research resource

Zippin’ up my boots, goin’ back to my roots: Radical left parties in Southern Europe

Radical left parties actively encourage the participation of their members in internal decision-making and insist on promoting organised links to trade unions and social movements. As a party family, they deviate from what is considered to be the trend in which Western political parties have turned their backs on their social roots. Drawing on the experience of South European radical left parties from the fall of the Berlin Wall until the recent financial crisis, we argue that ideology, electoral incentives, party competition and external events explain the radical left's pronounced emphasis on linkage, while organisational trajectory explains variation within the party family in terms of the linkage strategies pursued

Third-Party Strategy under Plurality Rule: The British Liberal Democrats and the New Zealand Social Credit Party

This paper examines the strategic options facing small centrist third parties in two-party parliamentary systems operating under the single-member district plurality (SMDP) electoral system. It uses a spatial model to show that centrist third parties are better off targeting the 'safe' districts of a major party rather than marginal districts. Furthermore, it is optimal to target one party's districts, not both, to benefit from tactical and protest voting. The paper also questions the implicit conclusion of the median-legislator theorem that pivotality-seeking is the best strategy for a third party, at least under SMDP, because that would usurp voters' ability to select the executive directly, a key feature of two-partism. Finally, the paper shows that third parties can damage themselves if they 'flip' from opposition to one major party to support for it. Evidence is provided for the British Liberal Democrats and New Zealand?s historic Social Credit Party

The geo-constitution: Understanding the intersection of geography and political institutions

This is the author accepted manuscript. The final version is available from SAGE Publications via the DOI in this record.This paper draws on existing work in the discipline of human geography and cognate fields in order to develop the concept of the ‘geo-constitution’. This concept aims to: (1) highlight the importance of intersections between geography and political institutions in the constitution of government; (2) consider the path-dependent development of political institutions and their impact on statecraft and citizenship; (3) explore the implications of this for political reform. The paper provides an overview of current thinking in political geography and applies the concept of the geo-constitution to the example of devolution and localism in the United Kingdom

Genome-wide interaction analysis of menopausal hormone therapy use and breast cancer risk among 62,370 women

Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values < 5 × 10–8 as genome-wide significant, and p-values < 1 × 10–5 as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants. None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values < 1 × 105. The strongest evidence was found for rs4674019 (p-value = 2.27 × 10–7), which showed genome-wide significant interaction (p-value = 3.8 × 10–8) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen–progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT–breast cancer risk association