Die sprachliche Realisierung des Auftragscharakters in EU-Richtlinien: Modalität und Sprechakte.

Die Europäische Union ist ein Zusammenschluss souveräner Staaten. Aus dieser politischen und rechtlichen Konzeption resultiert ein Spannungsfeld, welches versucht, den Gedanken der unionsweiten Harmonisierung sowie die unionsrechtlichen Zielvorstellungen mit der nationalen Souveränität aller Mitgliedstaaten in Einklang zu bringen. Dieses Prinzip findet sich in den unterschiedlichen Rechtsakten der Europäischen Union, insbesondere den Richtlinien, wieder. Um dieses Prinzip zu erkennen, spielen die authentischen Sprachfassungen der einzelnen Rechtsakte eine entscheidende Rolle. Seit dem 01. Juli 2013 besteht die Europäische Union aus 28 Mitgliedstaaten. Dies bedeutet eine umfassende sprachliche und kulturelle Vielfalt. Aktuell erkennt die Europäische Union 24 Amts- und Arbeitssprachen an. Hinzu kommt, dass gem. Art. 342 AEUV i.V.m. Art. 4 VO (EG) Nr.1/1958 alle EU-Rechtsakte in allen Amtssprachen abgefasst werden müssen. Es ist insbesondere für EU-Richtlinien aufgrund ihrer Umsetzungspflicht entscheidend, dass die Sprachfassungen identisch sind. Der Auftragscharakter der Richtlinie muss in allen Sprachfassungen so ausgedrückt werden, dass die Mitgliedstaaten als Adressaten der Richtlinie die von der Europäischen Union auferlegte Aufforderung bereits auf sprachlicher Ebene erkennen und in der außersprachlichen Wirklichkeit umsetzen können. Dabei sind ebenso sprachspezifische wie auch nationalrechtliche Konventionen zu berücksichtigen

Geographien der Macht: für einen integrierten Blick auf Raumproduktionen mit Foucault

Mit dem spatial turn artikulieren die Geistes- und Sozialwissenschaften das Bedürfnis, sich mit der Räumlichkeit gesellschaftlicher Verhältnisse auseinanderzusetzen. Der vorliegende Beitrag greift dieses Anliegen auf und lotet exemplarisch das Potenzial der Arbeiten Michel Foucaults für eine konsequente Erschließung „materialisierter Geographien“ aus. An drei Beispielen aus seinem Schaffen gehen wir der Frage nach, wie sich Techniken der Wissensproduktion und der Machtausübung mit räumlichen Anordnungs- und Interventionspraktiken verschränken. Unser Plädoyer gilt einem integrierten Blick auf Raumproduktionen, der keine künstliche Trennung von repräsentationalen und materialisierten Geographien vornimmt.The spatial turn in the social sciences and humanities articulates a newfound interest in the spatiality of the social and a desire to further theorize this spatiality. Our article picks up on this debate and explores the potential of the work of Michel Foucault for a conceptualization of „material geographies“. By turning to three examples in Foucault’s work, we highlight the importance of spatial practices for the production of knowledge and the exercise of power. By focusing on these examples, we argue that Foucault offers a unique view on the production of space that rejects an artificial separation between „representational“ and „material geographies“

Comparative results of transluminal extraction coronary atherectomy in saphenous vein graft lesions with and without thrombus

AbstractObjectives. The purpose of this retrospective study was to compare the results of transluminal extraction coronary atherectomy in saphenous vein graft lesions with and without angiographic thrombus.Background. Percutaneous interventions in lesions with thrombus are associated with reduced procedural success and increased risk of complications. Use of the transluminal extraction catheter, which cuts and aspirates atheroma and thrombus, has been advocated as a potential revascularization strategy for lesions with thrombus.Methods. Baseline patient characteristics, lesion morphology, immediate angiographic results, in-hospital complications and follow-up were prospectively entered into an interventional cardiology data base. The results of transluminal extraction coronary atherectomy in saphenous vein bypass grafts with angiographic thrombus were compared with results in similar grafts without angiographic thrombus.Results. Transluminal extraction coronary atherectomy was performed in 175 patients with 183 vein graft lesions, including 59 lesions (32%) with thrombus (Group 1) and 124 (68%) without thrombus (Group 2). Compared with lesions in Group 2, lesions in Group 1 were associated with a higher incidence of baseline total occlusion, diffuse disease and abnormal Thrombolysis in Myocardial Infarction (TIMI) grade flow (p < 0.05); more severe diameter stenosis at baseline, after atherectomy and after final angiography (p < 0.05); a lower rate of clinical success (69% vs, 88%, p < 0.01); and more angiographic and clinical complications, including no reflow (p < 0.05), vascular repair (p < 0.05) and Q wave myocardial infarction (p = 0.09).Conclusions. In transluminal extraction coronary atherectomy of saphenous vein bypass grafts, the presence of thrombus is associated with more baseline lesion complexity, reduced clinical success and increased risk of no reflow, Q wave myocardial infarction and vascular repair

Plasmodium falciparum variant STEVOR antigens are expressed in merozoites and possibly associated with erythrocyte invasion

<p>Abstract</p> <p>Background</p> <p><it>Plasmodium falciparum </it>STEVOR proteins, encoded by the multicopy <it>stevor </it>gene family have no known biological functions. Their expression and unique locations in different parasite life cycle stages evoke multiple functionalities. Their abundance and hypervariability support a role in antigenic variation.</p> <p>Methods</p> <p>Immunoblotting of total parasite proteins with an anti-STEVOR antibody was used to identify variant antigens of this gene family and to follow changes in STEVOR expression in parasite populations panned on CSA or CD36 receptors. Immunofluorescence assays and immunoelectron microscopy were performed to study the subcellular localization of STEVOR proteins in different parasite stages. The capacity of the antibody to inhibit merozoite invasion of erythrocytes was assessed to determine whether STEVOR variants were involved in the invasion process.</p> <p>Results</p> <p>Antigenic variation of STEVORs at the protein level was observed in blood stage parasites. STEVOR variants were found to be present on the merozoite surface and in rhoptries. An insight into a participation in erythrocyte invasion was gained through an immunofluorescence analysis of a sequence of thin slides representing progressive steps in erythrocyte invasion. An interesting feature of the staining pattern was what appeared to be the release of STEVORs around the invading merozoites. Because the anti-STEVOR antibody did not inhibit invasion, the role of STEVORs in this process remains unknown.</p> <p>Conclusion</p> <p>The localization of STEVOR proteins to the merozoite surface and the rhoptries together with its prevalence as a released component in the invading merozoite suggest a role of these antigens in adhesion and/or immune evasion in the erythrocyte invasion process. These observations would also justify STEVORs for undergoing antigenic variation. Even though a role in erythrocyte invasion remains speculative, an association of members of the STEVOR protein family with invasion-related events has been shown.</p

Crebinostat: A novel cognitive enhancer that inhibits histone deacetylase activity and modulates chromatin-mediated neuroplasticity

Long-term memory formation is known to be critically dependent upon de novo gene expression in the brain. As a consequence, pharmacological enhancement of the transcriptional processes mediating long-term memory formation provides a potential therapeutic strategy for cognitive disorders involving aberrant neuroplasticity. Here we focus on the identification and characterization of small molecule inhibitors of histone deacetylases (HDACs) as enhancers of CREB (cAMP response element-binding protein)-regulated transcription and modulators of chromatin-mediated neuroplasticity. Using a CREB reporter gene cell line, we screened a library of small molecules structurally related to known HDAC inhibitors leading to the identification of a probe we termed crebinostat that produced robust activation of CREB-mediated transcription. Further characterization of crebinostat revealed its potent inhibition of the deacetylase activity of recombinant class I HDACs 1, 2, 3, and class IIb HDAC6, with weaker inhibition of the class I HDAC8 and no significant inhibition of the class IIa HDACs 4, 5, 7, and 9. In cultured mouse primary neurons, crebinostat potently induced acetylation of both histone H3 and histone H4 as well as enhanced the expression of the CREB target gene Egr1 (early growth response 1). Using a hippocampus-dependent, contextual fear conditioning paradigm, mice systemically administered crebinostat for a ten day time period exhibited enhanced memory. To gain insight into the molecular mechanisms of memory enhancement by HDAC inhibitors, whole genome transcriptome profiling of cultured mouse primary neurons treated with crebinostat, combined with bioinformatic analyses of CREB-target genes, was performed revealing a highly connected protein–protein interaction network reflecting modules of genes important to synaptic structure and plasticity. Consistent with these findings, crebinostat treatment increased the density of synapsin-1 punctae along dendrites in cultured neurons. Finally, crebinostat treatment of cultured mouse primary neurons was found to upregulate Bdnf (brain-derived neurotrophic factor) and Grn (granulin) and downregulate Mapt (tau) gene expression—genes implicated in aging-related cognitive decline and cognitive disorders. Taken together, these results demonstrate that crebinostat provides a novel probe to modulate chromatin-mediated neuroplasticity and further suggests that pharmacological optimization of selective of HDAC inhibitors may provide an effective therapeutic approach for human cognitive disorders.National Institutes of Health (U.S.) (R01DA028301)National Institutes of Health (U.S.) (R01NS051874)Stanley Medical Research InstituteHoward Hughes Medical Institut

Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus

Emerging evidence emphasizes the strong impact of regulatory genomic elements in neurodevelopmental processes and the complex pathways of brain disorders. The present genome-wide quantitative trait loci analyses explore the cis-regulatory effects of single-nucleotide polymorphisms (SNPs) on DNA methylation (meQTL) and gene expression (eQTL) in 110 human hippocampal biopsies. We identify cis-meQTLs at 14,118 CpG methylation sites and cis-eQTLs for 302 3'-mRNA transcripts of 288 genes. Hippocampal cis-meQTL-CpGs are enriched in flanking regions of active promoters, CpG island shores, binding sites of the transcription factor CTCF and brain eQTLs. Cis-acting SNPs of hippocampal meQTLs and eQTLs significantly overlap schizophrenia-associated SNPs. Correlations of CpG methylation and RNA expression are found for 34 genes. Our comprehensive maps of cis-acting hippocampal meQTLs and eQTLs provide a link between disease-associated SNPs and the regulatory genome that will improve the functional interpretation of non-coding genetic variants in the molecular genetic dissection of brain disorders

Malaria incidence and efficacy of intermittent preventive treatment in infants (IPTi).

BACKGROUND: Intermittent preventive antimalarial treatment in infants (IPTi) is currently evaluated as a malaria control strategy. Among the factors influencing the extent of protection that is provided by IPTi are the transmission intensity, seasonality, drug resistance patterns, and the schedule of IPTi administrations. The aim of this study was to determine how far the protective efficacy of IPTi depends on spatio-temporal variations of the prevailing incidence of malaria. METHODS: One thousand seventy infants were enrolled in a registered controlled trial on the efficacy of IPTi with sulphadoxine-pyrimethamine (SP) in the Ashanti Region, Ghana, West Africa (ClinicalTrial.gov: NCT00206739). Stratification for the village of residence and the month of birth of study participants demonstrated that the malaria incidence was dependent on spatial (range of incidence rates in different villages 0.6-2.0 episodes/year) and temporal (range of incidence rates in children of different birth months 0.8-1.2 episodes/year) factors. The range of spatio-temporal variation allowed ecological analyses of the correlation between malaria incidence rates, anti-Plasmodium falciparum lysate IgG antibody levels and protective efficacies provided by IPTi. RESULTS: Protective efficacy of the first SP administration was positively correlated with malaria incidences in children living in a distinct village or born in a distinct month (R2 0.48, p < 0.04 and R2 0.63, p < 0.003, respectively). Corresponding trends were seen after the second and third study drug administration. Accordingly, IgG levels against parasite lysate increased with malaria incidence. This correlation was stronger in children who received IPTi, indicating an effect modification of the intervention. CONCLUSION: The spatial and temporal variations of malaria incidences in a geographically and meteorologically homogeneous study area exemplify the need for close monitoring of local incidence rates in all types of intervention studies. The increase of the protective efficacy of IPTi with malaria incidences may be relevant for IPTi implementation strategies and, possibly, for other malaria control measures