Direct and indirect europeanisation of national administrative systems. Implementation and spillover effects of the environmental information directives in a comparative perspective

Until the 1980s, a culture of administrative secrecy prevailed in most European countries. This general approach only changed with the adoption of the first administrative procedure laws, which codified a right of access to files, albeit usually limited to the parties of an administrative procedure. At European level, a trend towards freedom of information started to evolve in the field of environmental procedure law on adoption of the two Environmental Information Directives 90/313/EEC and 2003/4/EC, of which the latter was itself a reaction to the adoption of the Aarhus Convention. This article analyses how these directives were implemented into national legislation and how this also gradually affected other areas of law. Taking examples from France, Germany and Italy, it is argued that the transposition of the Environmental Information Directives ‘europeanised’ these three national administrative systems not only directly, but also in other, more subtle and indirect ways

Effects of different leukocyte subpopulations and flow conditions on leukocyte accumulation during reperfusion

Background/Aims: The study examined the interdependent effects of shear stress and different leukocyte subpopulations on endothelial cell activation and cell interactions during low flow and reperfusion. Methods: Human umbilical venous endothelial cells were perfused with either neutrophils or monocytes at different shear stress (2-0.25 dyn/cm 2) and adhesion was quantified by microscopy. Effects of adherent neutrophils and monocytes on endothelial cell adhesion molecule expression were analyzed by flow cytometry after 4-hour static coincubation. After coincubation, the cocultures were reperfused with labeled neutrophils at 2 dyn/cm 2 and their adhesion was quantified selectively. For the control, endothelium monocultures with and without lipopolysaccharide activation were used. Results: At 2 dyn/cm 2, adhesion did not exceed baseline levels on nonactivated endothelium. Decreasing shear stress to 0.25 dyn/cm 2 largely increased the adhesion of both leukocyte subpopulations, similar to the effect of lipopolysaccharide at 2 dyn/cm 2. However, only adherent monocytes increased adhesion molecule expression, whereas neutrophils had no effect. As a functional consequence, adherent monocytes largely increased neutrophil adhesion during reperfusion, whereas adherent neutrophils did not. Conclusion: Compromised shear stress is an autonomous trigger of leukocyte adhesion even in the absence of additional activators. Exceeding this immediate effect, adherent monocytes induce further endothelial activation and enhance further neutrophil adhesion during reperfusion. Copyrigh

Phosphorylation Modulates the Subcellular Localization of SOX11

SOX11 is a key Transcription Factor (TF) in the regulation of embryonic and adult neurogenesis, whose mutation has recently been linked to an intellectual disability syndrome in humans. SOX11’s transient activity during neurogenesis is critical to ensure the precise execution of the neurogenic program. Here, we report that SOX11 displays differential subcellular localizations during the course of neurogenesis. Western-Blot analysis of embryonic mouse brain lysates indicated that SOX11 is post-translationally modified by phosphorylation. Using Mass Spectrometry, we found 10 serine residues in the SOX11 protein that are putatively phosphorylated. Systematic analysis of phospho-mutant SOX11 resulted in the identification of the S30 residue, whose phosphorylation promotes nuclear over cytoplasmic localization of SOX11. Collectively, these findings uncover phosphorylation as a novel layer of regulation of the intellectual disability gene Sox11

Oxygen-Independent Stabilization of Hypoxia Inducible Factor (HIF)-1 during RSV Infection

BACKGROUND: Hypoxia-inducible factor 1 (HIF)-1alpha is a transcription factor that functions as master regulator of mammalian oxygen homeostasis. In addition, recent studies identified a role for HIF-1alpha as transcriptional regulator during inflammation or infection. Based on studies showing that respiratory syncytial virus (RSV) is among the most potent biological stimuli to induce an inflammatory milieu, we hypothesized a role of HIF-1alpha as transcriptional regulator during infections with RSV. METHODOLOGY, PRINCIPAL FINDINGS: We gained first insight from immunohistocemical studies of RSV-infected human pulmonary epithelia that were stained for HIF-1alpha. These studies revealed that RSV-positive cells also stained for HIF-1alpha, suggesting concomitant HIF-activation during RSV infection. Similarly, Western blot analysis confirmed an approximately 8-fold increase in HIF-1alpha protein 24 h after RSV infection. In contrast, HIF-1alpha activation was abolished utilizing UV-treated RSV. Moreover, HIF-alpha-regulated genes (VEGF, CD73, FN-1, COX-2) were induced with RSV infection of wild-type cells. In contrast, HIF-1alpha dependent gene induction was abolished in pulmonary epithelia following siRNA mediated repression of HIF-1alpha. Measurements of the partial pressure of oxygen in the supernatants of RSV infected epithelia or controls revealed no differences in oxygen content, suggesting that HIF-1alpha activation is not caused by RSV associated hypoxia. Finally, studies of RSV pneumonitis in mice confirmed HIF-alpha-activation in a murine in vivo model. CONCLUSIONS/SIGNIFICANCE: Taking together, these studies suggest hypoxia-independent activation of HIF-1alpha during infection with RSV in vitro and in vivo

Europeización directa e indirecta de los sistemas administrativos nacionales. Implementación y efectos indirectos de las directivas sobre información medioambiental en una perspectiva comparada

Until the 1980s, a culture of administrative secrecy prevailed in most European countries. This general approach only changed with the adoption of the first administrative procedure laws, which codified a right of access to files, albeit usually limited to the parties of an administrative procedure. At European level, a trend towards freedom of information started to evolve in the field of environmental procedure law on adoption of the two Environmental Information Directives 90/313/EEC and 2003/4/EC, of which the latter was itself a reaction to the adoption of the Aarhus Convention. This article analyses how these directives were implemented into national legislation and how this also gradually affected other areas of law. Taking examples from France, Germany and Italy, it is argued that the transposition of the Environmental Information Directives ‘europeanised’ these three national administrative systems not only directly, but also in other, more subtle and indirect ways.Fins a la dècada dels anys vuitanta, una certa cultura del secret administratiu va prevaldre en la majoria dels països europeus. Aquesta realitat generalitzada tan sols es va superar amb l’adopció de les primeres lleis de procediment administratiu, les quals van establir el dret d’accés a arxius, si bé se solia limitar a les parts implicades en un procediment administratiu. En l’àmbit europeu, la tendència cap a la llibertat d’informació va començar a evolucionar en el camp de la normativa en matèria de procediment mediambiental amb l’adopció de les dues directives d’informació mediambiental 90/313/EEC i 2003/4/EC, l’última de les quals va ser una reacció a l’adopció de la Convenció Aarhus. Aquest article analitza com aquestes directives han estat implementades en les legislacions estatals i com això ha afectat gradualment altres àrees del dret. Per mitjà d’exemples a França, Alemanya i Itàlia es discuteix com la transposició de les directives d’informació mediambiental han europeïtzat aquests tres sistemes administratius estatals no tan sols de forma directa, sinó també d’una forma més subtil i indirecta. Hasta la década de los años ochenta, una cierta cultura del secreto administrativo prevaleció en la mayoría de los países europeos. Esta realidad generalizada tan sólo se superó con la adopción de las primeras leyes de procedimiento administrativo, las cuales establecieron el derecho de acceso a archivos, si bien se solía limitar a las partes implicadas en un procedimiento administrativo. En el ámbito europeo, la tendencia hacia la libertad de información empezó a evolucionar en el campo de la normativa en materia de procedimiento medioambiental con la adopción de las dos directivas de información medioambiental 90/313/EEC y 2003/4/EC, la última de las cuales fue una reacción a la adopción de la Convención Aarhus. Este artículo analiza cómo estas directivas han sido implementadas en las legislaciones estatales y como eso ha afectado gradualmente a otras áreas del derecho. Por medio de ejemplos en Francia, Alemania e Italia se discute como la transposición de las directivas de información medioambiental han europeizado estos tres sistemas administrativos estatales no tan sólo de forma directa, sino también de una forma más sutil e indirecta

Praxis der Richtlinienumsetzung im Europäischen Verwaltungsverbund

Verfolgen die Mitgliedstaaten der Europäischen Union bei der Umsetzung des Unionsrechts unterschiedliche Anpassungsstrategien oder lassen sich die jeweiligen Regelungen zur Umsetzung eher situativ deuten? Der vorliegende Band untersucht in einem ersten Teil, welche Veränderungen in der Verwaltungsorganisation und dem Verwaltungsverfahren die Umsetzung von Richtlinien aus dem Bereich des Umweltschutzes in ausgewählten EU-Mitgliedstaaten bewirkt hat. Der zweite Teil befasst sich daran anknüpfend speziell mit der Transformationswirkung von Richtlinien auf die nationale Regulierungsverwaltung im Energiesektor. Der Band versteht sich als ein Beitrag zur EU-Implementationsforschung

Automated manufacturing of stiffened composite shells using dry fibre material

Appropriate manufacturing concepts need to be developed to meet the growing demand for CFRP parts and the increasing production rates in the aviation sector. Therefore, a development stream is ongoing to evaluate the potential of dry fibre placement (DFP) processes in largescale shell manufacturing. A research project funded by the NBank of Lower Saxony concentrated on layup, infusion and curing processes for a full-scale dry fibre material shell as part of a close collaboration between CTC GmbH and the German Aerospace Center (DLR) in Stade

First manifestation of citrullinemia type I as Sandifer syndrome

WOS: 000438382300013PubMed: 30035404We report an eleven-month-old infant girl who presented as Sandifer syndrome clinically but was later diagnosed with citrullinemia type I. Metabolic evaluation and molecular analysis confirmed the correct diagnosis. Despite the fact that many patients are already known in the literature, this is the first report of a Sandifer syndrome-like presentation of citrullinemia type I. This paper suggests that suspicion of Sandifer syndrome should also lead to inclusion of urea cycle disorders in the list of differential diagnoses

Glutamine supplementation in a child with inherited GS deficiency improves the clinical status and partially corrects the peripheral and central amino acid imbalance

Glutamine synthetase (GS) is ubiquitously expressed in mammalian organisms and is a key enzyme in nitrogen metabolism. It is the only known enzyme capable of synthesising glutamine, an amino acid with many critical roles in the human organism. A defect in GLUL, encoding for GS, leads to congenital systemic glutamine deficiency and has been described in three patients with epileptic encephalopathy. There is no established treatment for this condition. Here, we describe a therapeutic trial consisting of enteral and parenteral glutamine supplementation in a four year old patient with GS deficiency. The patient received increasing doses of glutamine up to 1020 mg/kg/day. The effect of this glutamine supplementation was monitored clinically, biochemically, and by studies of the electroencephalogram (EEG) as well as by brain magnetic resonance imaging and spectroscopy. Treatment was well tolerated and clinical monitoring showed improved alertness. Concentrations of plasma glutamine normalized while levels in cerebrospinal fluid increased but remained below the lower reference range. The EEG showed clear improvement and spectroscopy revealed increasing concentrations of glutamine and glutamate in brain tissue. Concomitantly, there was no worsening of pre-existing chronic hyperammonemia. In conclusion, supplementation of glutamine is a safe therapeutic option for inherited GS deficiency since it corrects the peripheral biochemical phenotype and partially also improves the central biochemical phenotype. There was some clinical improvement but the patient had a long standing severe encephalopathy. Earlier supplementation with glutamine might have prevented some of the neuronal damage