We need to have a conversation about OpenURL, a close look at a corpus of error reports from the 2013 academic year. Or, How I learned to stop worrying and give up on clean metadata.

Presented at Access 2014, winner of poster contest.

Bisky bats and pussy cats : the animal nonsense of Edward Lear.

Colección de poemas que tratan de animales, a veces, absurdos, y disfrazados, también, de forma absurda, rodeados asimismo, de objetos absurdos.

The EEAS and the Eastern Partnership: let the blame game stop. CEPS Commentary, 4 September 2012

In the first year and a half of its existence, the EEAS and its head have become the target of extensive criticism for the shortcomings of EU foreign policy; shortcomings that in fact date back to the creation of the European Union. The EU’s diplomatic service has been blamed variously for ‘lacking clarity,’ ‘acting too slowly’ and ‘being unable to bridge the institutional divide’. In this Commentary author Hrant Kostanyan argues that the EEAS’ discretionary power in the Eastern Partnership multilateral framework is restricted by the decision-making procedures between a wide range of stakeholders: the member states and the partner countries, as well as by the EU institutions, international organisations and the Civil Society Forum. Since this decision-making process places a substantial number of brakes on the discretionary power of the EEAS, any responsible analysis or critique of the service should take these constraints into consideration. Ultimately, the EEAS is only able to craft EU foreign policy insofar as it is allowed to do so.

Stops making sense: translational trade-offs and stop codon reassignment

Background Efficient gene expression involves a trade-off between (i) premature termination of protein synthesis; and (ii) readthrough, where the ribosome fails to dissociate at the terminal stop. Sense codons that are similar in sequence to stop codons are more susceptible to nonsense mutation, and are also likely to be more susceptible to transcriptional or translational errors causing premature termination. We therefore expect this trade-off to be influenced by the number of stop codons in the genetic code. Although genetic codes are highly constrained, stop codon number appears to be their most volatile feature. Results In the human genome, codons readily mutable to stops are underrepresented in coding sequences. We construct a simple mathematical model based on the relative likelihoods of premature termination and readthrough. When readthrough occurs, the resultant protein has a tail of amino acid residues incorrectly added to the C-terminus. Our results depend strongly on the number of stop codons in the genetic code. When the code has more stop codons, premature termination is relatively more likely, particularly for longer genes. When the code has fewer stop codons, the length of the tail added by readthrough will, on average, be longer, and thus more deleterious. Comparative analysis of taxa with a range of stop codon numbers suggests that genomes whose code includes more stop codons have shorter coding sequences. Conclusions We suggest that the differing trade-offs presented by alternative genetic codes may result in differences in genome structure. More speculatively, multiple stop codons may mitigate readthrough, counteracting the disadvantage of a higher rate of nonsense mutation. This could help explain the puzzling overrepresentation of stop codons in the canonical genetic code and most variants.

Can France really stop them? : A study grounded on the realist perspective about the French foreign policy towards Syria as the root cause of the Phenomenon of French Foreign Fighters

During the Syrian conflict the number of European Foreign Fighters has increased exponentially and has become an ever-growing concern for European policymakers. This phenomenon presents host of major security challenges for European policymakers and governments. Among European countries, France provides the highest number of citizens who have gone to Syria to fight against Assad´s regime. The French authorities have estimated that by mid-2014, over 700 French citizens have left France and travelled to Syria to fight. Historically France has had a relationship with Syria which started with its role as a border-drawing colonial power. Grounded in a framework of realism, that emphasizes nation-states as the primary actor within the international system, the analysis concentrates on the role of France´s foreign policy on the Syria as push factor for terrorism and radicalization. This paper attempts to determinate a specific correlation between the policy that France has been conducting towards Syria between 2000 and 2015, and the phenomenon of French Foreign Fighters. Findings suggest that France´s foreign policy towards Syria is the main root cause of the French Foreign Fighters phenomenon.

Identification and characterization of novel mutations of the aspartoacylase gene in non-Jewish patients with Canavan disease

Canavan disease, an inherited leukodystrophy, is caused by mutations in the aspartoacylase (ASPA) gene. It is most common among children of Ashkenazi Jewish descent but has been diagnosed in many diverse ethnic groups. Two mutations comprise the majority of mutant alleles in Jewish patients, while mutations in the ASPA gene among non-Jewish patients are different and more diverse. In the present study, the ASPA gene was analysed in 22 unrelated non-Jewish patients with Canavan disease, and 24 different mutations were found. of these,14 are novel, including five missense mutations (E24G, D68A, D249V, C152W, H244R), two nonsense mutations (Q184X, E214X), three deletions (923delT, 33del13, 244delA), one insertion mutation (698insC), two sequence variations in one allele ([10T>G; 11insG]), an elimination of the stop codon (941A>G, TAG-->TGG, X314W), and one splice acceptor site mutation (IVS1 - 2A>T). The E24G mutation resulted in substitution of an invariable amino acid residue (Glu) in the first esterase catalytic domain consensus sequence. The IVS1 - 2A>T mutation caused the retention of 40 nucleotides of intron 1 upstream of exon 2. The results of transient expression of the mutant ASPA cDNA containing these mutations in COS-7 cells and assays for ASPA activity of patient fibroblasts indicated that these mutations were responsible for the enzyme deficiency. In addition, patients with the novel D249V mutation manifested clinically at birth and died early. Also, patients with certain other novel mutations, including C152W, E214X, X314W, and frameshift mutations in both alleles, developed clinical manifestations at an earlier age than in classical Canavan disease.

Thomsen or Becker myotonia? A novel autosomal recessive nonsense mutation in the CLCN1 gene associated with a mild phenotype

We describe a large Brazilian consanguineous kindred with 3 clinically affected patients with a Thomsen myotonia phenotype. They carry a novel homozygous nonsense mutation in the CLCN1 gene (K248X). None of the 6 heterozygote carriers show any sign of myotonia on clinical evaluation or electromyography. These findings confirm the autosomal recessive inheritance of the novel mutation in this family, as well as the occurrence of phenotypic variability in the autosomal recessive forms of myotonia. Muscle Nerve, 2012

New mutations in the GLA gene in Brazilian families with Fabry disease

Fabry disease (FD) is an X-linked inborn error of glycosphingolipid catabolism that results from mutations in the alpha-galactosidase A (GLA) gene. Evaluating the enzymatic activity in male individuals usually performs the diagnosis of the disease, but in female carriers the diagnosis based only on enzyme assays is often inconclusive. In this work, we analyzed 568 individuals from 102 families with suspect of FD. Overall, 51 families presented 38 alterations in the GLA gene, among which 19 were not previously reported in literature. The alterations included 17 missense mutations, 7 nonsense mutations, 7 deletions, 6 insertions and 1 in the splice site. Six alterations (R112C, R118C, R220X, R227X, R342Q and R356W) occurred at CpG dinucleotides. Five mutations not previously described in the literature (A156D, K237X, A292V, I317S, c.1177_1178insG) were correlated with low GLA enzyme activity and with prediction of molecular damages. From the 13 deletions and insertions, 7 occurred in exons 6 or 7 (54%) and 11 led to the formation of a stop codon. The present study highlights the detection of new genomic alterations in the GLA gene in the Brazilian population, facilitating the selection of patients for recombinant enzyme-replacement trials and offering the possibility to perform prenatal diagnosis. Journal of Human Genetics (2012) 57, 347-351; doi:10.1038/jhg.2012.32; published online 3 May 2012

Analysing the role of short stop during the formation of synaptic terminals in Drosophila melanogaster

Diese Arbeit untersucht die Funktion des Spektraplakin Proteins Short Stop (Shot) während der strukturellen Differenzierung von synaptischen Endigungen in Drosophila melanogaster. Im Allgemeinen scheinen Proteine der Spektraplakin Familie multiple Protein-Protein Interaktionen mithilfe ihrer unterschiedlichen modularen Domänen zu vermitteln. In der vorgelegten Arbeit sollten spezifische Domänen identifiziert werden, die für die Ausbildung synaptischer Endigungen notwendig sind. Hierzu wurden shot-Funktionsverlustmutationen, für die zum Teil molekulare Information über die Mutationsereignisse erhältlich sind, anhand von verschiedenen Markern für synaptische Proteine analysiert. Ferner konnten einzelne Protein Domänen von Shot in neuronalen Geweben mithilfe des Gal4/UAS-Systems exprimiert und ihre Lokalisation untersucht werden. Darüber hinaus wurden immunohistochemische Studien unter Verwendung von Antikörpern, welche spezifisch für unterschiedliche Shot Protein Domänen sind, ausgeführt. Schließlich sollte das Yeast-two-Hybrid’-System sowie genetische Studien Interaktionspartner von Shot identifizieren. Die Unterschiedlichen experimentellen Ansätze deuten darauf hin, dass die einzelnen Protein Domänen von Shot unterschiedliche Protein-Protein Interaktionen vermitteln. Der N-Terminus von Shot scheint essentiell für die Ausbildung motorneuronaler Endigungen zu sein. Außerdem konnten mehrere potentielle Interaktionspartner identifiziert werden, so dass die hier beschriebenen Ergebnisse eine Grundlage für weitere Studien zur Untersuchung der strukturellen Differenzierung synaptischer Endigungen darstellen.

Neuronal differentiation and epithelial integrity: the role of Drosophila Short stop

The nervous system is the most complex organ in animals and the ordered interconnection of neurons is an essential prerequisite for normal behaviour. Neuronal connectivity requires controlled neuronal growth and differentiation. Neuronal growth essentially depends on the actin and microtubule cytoskeleton, and it has become increasingly clear, that crosslinking of these cytoskeletal fractions is a crucial regulatory process. The Drosophila Spectraplakin family member Short stop (Shot) is such a crosslinker and is crucial for several aspects of neuronal growth. Shot comprises various domains: An actin binding domain, a plakin-like domain, a rod domain, calcium responsive EF-hand motifs, a microtubule binding Gas2 domain, a GSR motif and a C-terminal EB1aff domain. Amongst other phenotypes, shot mutant animals exhibit severely reduced dendrites and neuromuscular junctions, the subcellular compartmentalisation of the transmembrane protein Fasciclin2 is affected, but it is also crucially required in other tissues, for example for the integrity of tendon cells, specialised epidermal cells which anchor muscles to the body wall. Despite these striking phenotypes, Shot function is little understood, and especially we do not understand how it can carry out functions as diverse as those described above. To bridge this gap, I capitalised on the genetic possibilities of the model system Drosophila melanogaster and carried out a structure-function analysis in different neurodevelopmental contexts and in tendon cells. To this end, I used targeted gene expression of existing and newly generated Shot deletion constructs in Drosophila embryos and larvae, analyses of different shot mutant alleles, and transfection of Shot constructs into S2 cells or cultured fibroblasts. My analyses reveal that a part of the Shot C-terminus is not essential in the nervous system but in tendon cells where it stabilises microtubules. The precise molecular mechanism underlying this activity is not yet elucidated but, based on the findings presented here, I have developed three alternative testable hypothesis. Thus, either binding of the microtubule plus-end tracking molecule EB1 through an EB1aff domain, microtubulebundling through a GSR rich motif or a combination of both may explain a context-specific requirement of the Shot C-terminus for tendon cell integrity. Furthermore, I find that the calcium binding EF-hand motif in Shot is exclusively required for a subset of neuronal functions of Shot but not in the epidermal tendon cells. These findings pave the way for complementary studies studying the impact of [Ca2+] on Shot function. Besides these differential requirements of Shot domains I find, that most Shot domains are required in the nervous system and tendon cells alike. Thus the microtubule Gas2 domain shows no context specific requirements and is equally essential in all analysed cellular contexts. Furthermore, I could demonstrate a partial requirement of the large spectrin-repeat rod domain of Shot in neuronal and epidermal contexts. I demonstrate that this domain is partially required in processes involving growth and/or tissue stability but dispensable for cellular processes where no mechanical stress resistance is required. In addition, I demonstrate that the CH1 domain a part of the N-terminal actin binding domain of Shot is only partially required for all analysed contexts. Thus, I conclude that Shot domains are functioning different in various cellular environments. In addition my study lays the base for future projects, such as the elucidation of Shot function in growth cones. Given the high degree of conservation between Shot and its mammalian orthologues MACF1/ACF7 and BPAG1, I believe that the findings presented in this study will contribute to the general understanding of spectraplakins across species borders.

Last stop expulsion - The minority question and forced migration in East-Central Europe: 1918-49

This article deals with the European minorities in the period between the two world wars and with their final expulsion from nation-states at the end of World War II. First, the tensions which arose between the organised minorities and the successor states of the Habsburg Monarchy are accounted for primarily by the argument that the various minorities located within the successor states had already undergone a comprehensive processes of nationalisation within the Habsburg Empire. Therefore they were able to resist assimilation by the political elites of the new titular nations (Czechs, Poles, Rumanians, Serbs). A second topic is that of the use made of the minorities issue by Adolf Hitler to help achieve his expansionist aims. The minorities issue was central to the international destabilisation of interwar Europe. Finally, the mass expulsion of minorities (above all, Germans) after the end of the war is explained by strategic considerations on the part of the Allied powers as well as involving the nation-state regimes. It is argued, against a commonly held view, that German atrocities during the period of occupation had little to do with the decision to expel most ethnic Germans from their territories of settlement in Poland, Czechoslovakia and Yugoslavia. The article shows that it is necessary to treat national minorities in the first half of the twentieth century as a single phenomenon which shares similar features across the various nation-states of East-Central Europe.