Europe’s reactive and protective muddling through: the results of a summit in fire fighting mode. EPC Post-Summit Analysis, 19 October 2015

The EU’s October summit was dominated by one issue; the migration and refugee crisis, with EU leaders intent on putting on a public display of unity after weeks of bitter arguments, and concentrating on fire-fighting and immediate measures to tackle the most pressing reasons for, and impacts of, the crisis. Longer-term measures to address some of the root causes of increased migratory flows, support for the integration of newly arrived refugees or the introduction of new channels of legal migration, were not discussed. The Summit also spent little time on two issues that had originally been expected to be a key part of the agenda: the forthcoming British referendum on EU membership, where irritation with the slow pace of talks and British vagueness about its demands were in evidence; and the governance of Economic and Monetary Union (EMU), where EU leaders missed another opportunity for a thorough debate about future perspectives on the basis of the ‘Five Presidents’ Report’.

The European Union as a Mediator in Israel-Palestine: Operations Cast Lead and Protective Edge. EU Diplomacy Paper 01/2016

The European Union (EU) has played an important, yet inconsistent role in the Israel-Palestine conflict since the1980 Venice Declaration. This paper analyses how the EU’s role as a mediator has changed more recently in the Israel-Gaza conflict. Specifically, it examines how the ‘Concept on Strengthening EU Mediation and Dialogue Capacities’ adopted in 2009 and the creation of the European External Action Service and the High Representative by the Lisbon Treaty have changed the EU’s resources and strategies as a mediator as well as how these developments improved cooperation and coordination with other mediators. This analysis is done through a comparison of the EU’s role in the Israeli Operation Cast Lead in 2008/2009 and Operation Protective Edge in 2014. It is argued that the aforementioned changes made the EU a more capable mediator and facilitated internal coordination. However, these changes did not create more resources for the EU as a mediator, rather they changed how the EU used its resources.

Genetically attenuated, P36p-deficient malarial sporozoites induce protective immunity and apoptosis of infected liver cells.

Immunization with Plasmodium sporozoites that have been attenuated by gamma-irradiation or specific genetic modification can induce protective immunity against subsequent malaria infection. The mechanism of protection is only known for radiation-attenuated sporozoites, involving cell-mediated and humoral immune responses invoked by infected hepatocytes cells that contain long-lived, partially developed parasites. Here we analyzed sporozoites of Plasmodium berghei that are deficient in P36p (p36p(-)), a member of the P48/45 family of surface proteins. P36p plays no role in the ability of sporozoites to infect and traverse hepatocytes, but p36p(-) sporozoites abort during development within the hepatocyte. Immunization with p36p(-) sporozoites results in a protective immunity against subsequent challenge with infectious wild-type sporozoites, another example of a specifically genetically attenuated sporozoite (GAS) conferring protective immunity. Comparison of biological characteristics of p36p(-) sporozoites with radiation-attenuated sporozoites demonstrates that liver cells infected with p36p(-) sporozoites disappear rapidly as a result of apoptosis of host cells that may potentiate the immune response. Such knowledge of the biological characteristics of GAS and their evoked immune responses are essential for further investigation of the utility of an optimized GAS-based malaria vaccine.

Multiple regulatory variants located in cell type-specific enhancers within the PKP2 locus form major risk and protective haplotypes for canine atopic dermatitis in German shepherd dogs.

BACKGROUND Canine atopic dermatitis (CAD) is a chronic inflammatory skin disease triggered by allergic reactions involving IgE antibodies directed towards environmental allergens. We previously identified a ~1.5 Mb locus on canine chromosome 27 associated with CAD in German shepherd dogs (GSDs). Fine-mapping indicated association closest to the PKP2 gene encoding plakophilin 2. RESULTS Additional genotyping and association analyses in GSDs combined with control dogs from five breeds with low-risk for CAD revealed the top SNP 27:19,086,778 (p = 1.4 × 10(-7)) and a rare ~48 kb risk haplotype overlapping the PKP2 gene and shared only with other high-risk CAD breeds. We selected altogether nine SNPs (four top-associated in GSDs and five within the ~48 kb risk haplotype) that spanned ~280 kb forming one risk haplotype carried by 35 % of the GSD cases and 10 % of the GSD controls (OR = 5.1, p = 5.9 × 10(-5)), and another haplotype present in 85 % of the GSD cases and 98 % of the GSD controls and conferring a protective effect against CAD in GSDs (OR = 0.14, p = 0.0032). Eight of these SNPs were analyzed for transcriptional regulation using reporter assays where all tested regions exerted regulatory effects on transcription in epithelial and/or immune cell lines, and seven SNPs showed allelic differences. The DNA fragment with the top-associated SNP 27:19,086,778 displayed the highest activity in keratinocytes with 11-fold induction of transcription by the risk allele versus 8-fold by the control allele (pdifference = 0.003), and also mapped close (~3 kb) to an ENCODE skin-specific enhancer region. CONCLUSIONS Our experiments indicate that multiple CAD-associated genetic variants located in cell type-specific enhancers are involved in gene regulation in different cells and tissues. No single causative variant alone, but rather multiple variants combined in a risk haplotype likely contribute to an altered expression of the PKP2 gene, and possibly nearby genes, in immune and epithelial cells, and predispose GSDs to CAD.