Europeanisation should meet international constructivism: the Nordic Plus group and the internalisation of political conditionality by France and the United Kingdom

This article is a plausibility probe for the significance of international constructivist ‘mediating factors’ to explain variation in Europeanisation outcomes. It applies a most similar systems design (or Mill's method of difference) to show that the UK has internalised political conditionality to a larger extent than France at least partially because it has been the object of stronger socialisation pressures within the ‘Nordic Plus’ group. The article contributes to the literature on Europeanisation and development cooperation in two important ways. First, it enlarges its scope of analysis, both geographically (beyond new European Union member states) and thematically (beyond simple measures of aid quality and/or quantity). Second, it emphasises the importance of international (versus domestic) mediating factors. The empirical analysis focusses on three cases of aid sanctions in response to human rights abuses and democratic setbacks: Zimbabwe 2002, Madagascar 2009 and Mozambique 2009

Identification and Characterization of Antifungal Compounds Using a Saccharomyces cerevisiae Reporter Bioassay

New antifungal drugs are urgently needed due to the currently limited selection, the emergence of drug resistance, and the toxicity of several commonly used drugs. To identify drug leads, we screened small molecules using a Saccharomyces cerevisiae reporter bioassay in which S. cerevisiae heterologously expresses Hik1, a group III hybrid histidine kinase (HHK) from Magnaporthe grisea. Group III HHKs are integral in fungal cell physiology, and highly conserved throughout this kingdom; they are absent in mammals, making them an attractive drug target. Our screen identified compounds 13 and 33, which showed robust activity against numerous fungal genera including Candida spp., Cryptococcus spp. and molds such as Aspergillus fumigatus and Rhizopus oryzae. Drug-resistant Candida albicans from patients were also highly susceptible to compounds 13 and 33. While the compounds do not act directly on HHKs, microarray analysis showed that compound 13 induced transcripts associated with oxidative stress, and compound 33, transcripts linked with heavy metal stress. Both compounds were highly active against C. albicans biofilm, in vitro and in vivo, and exerted synergy with fluconazole, which was inactive alone. Thus, we identified potent, broad-spectrum antifungal drug leads from a small molecule screen using a high-throughput, S. cerevisiae reporter bioassay