Cav1.4 congenital stationary night blindness is associated with an increased rate of proteasomal degradation

Pathogenic, generally loss-of-function, variants in CACNA1F, encoding the Cav1.4α1 calcium channel, underlie congenital stationary night blindness type 2 (CSNB2), a rare inherited retinal disorder associated with visual disability. To establish the underlying pathomechanism, we investigated 10 clinically derived CACNA1F missense variants located across pore-forming domains, connecting loops, and the carboxy-tail domain of the Cav1.4α subunit. Homology modeling showed that all variants cause steric clashes; informatics analysis correctly predicted pathogenicity for 7/10 variants. In vitro analyses demonstrated that all variants cause a decrease in current, global expression, and protein stability and act through a loss-of-function mechanism and suggested that the mutant Cav1.4α proteins were degraded by the proteasome. We showed that the reduced current for these variants could be significantly increased through treatment with clinical proteasome inhibitors. In addition to facilitating clinical interpretation, these studies suggest that proteasomal inhibition represents an avenue of potential therapeutic intervention for CSNB2

"A Sustainable EU-27 Single Currency? Political Criteria for Optimal currency Areas"

This study tries to find which EU member states and candidate countries can sustain a currency link. I use Bayoumi and Eichengreen’s procedure of two-step least squares cross-section regression analysis for estimating exchange rate variation among 26 European countries, integrating domestic political factors into an Optimal Currency Area analysis framework. Excluding political variables a currency union is found sustainable among combinations of 2-6 countries, none including more than one major EU economy. Economically, Germany is the leading core country, followed by France and the UK. Including political variables Germany and eight other small countries are singled out, while the UK becomes an almost equal alternative core to Germany, with six potential currency partners. Considering domestic politics France and Italy are unstable Euro-zone members. The candidate countries are a long way from a sustainable currency union with the EU

The Missing Dimension of Democracy Institutional Patterns in 25 EU Member States between 1997 and 2006

By compiling data on 12 politico-institutional variables for 25 member states of the European Union over the years 1997—2006, we were able to investigate the emerging patterns of democracy in the European Union. The study addresses the questions of how direct democracy can be incorporated into Lijphart’s (1999) typology of consensus and majoritarian democracy and how empirical democratic patterns are affected by this extension. For the western democracies, three dimensions of democracy were extracted using principal component analysis, with two resembling those found by Lijphart (1999) and a third one being shaped by the interplay between direct democracy and cabinet type. East European democracies tend to have a lower degree of interest group corporatism, weaker central banks, stronger judicial review and stronger direct democracy