Complex Challenges, Comprehensive Responses - Linking Security and Development: 11th International Summer School 2007

"The link between international security and development constitutes a nexus that is only beginning to be understood and addressed by the international community and by regional security and development actors. During the International Summer School, participants and renowned speakers examine the complexity of contemporary development and security challenges, such as transnational warfare, terrorism, poor governance and state failure, migration and resource conflicts, as well as the transformation of traditional security and development concepts and policies (human security paradigm etc.). New interfaces between security and development (e.g. the concept of Security Sector Reform) and the need for an integrated approach to address global challenges are discussed. In this light, efforts and strategies of global actors like the EU, US, NATO, UN and OSCE as well as sensitivities and prospects for cooperation are assessed. Case studies on Africa, the Middle East, Asia and the Balkans provide regional insights to the topic." (author's abstract

10th International Summer School "Global Challenges, Global Actors - Sharing Responsibility for a Secure World in the 21st Century": Berlin, 9-22 July 2006 ; final report

"Security challenges in the 21st century have trans-border effects and can no longer be dealt with by nation states alone. To address these challenges a wide spectrum of actors, including international and regional organizations, national and local institutions, as well as NGOs and civil society need to engage in a multilateral and concerted approach. During the International Summer School, participants and renowned speakers examine contemporary security challenges, such as terrorism and homeland security, state failure and democratization, energy security, demography and migration. In this light, prioritites and strategies of global actors like the EU, US, China, NATO, UN and OSCE, but also NGOs and private actors are assessed." (author's abstract

Europäische Streitkräfte im Treibsand: ein zweifelhafter "europäischer" Einsatz im Tschad und in der Zentralafrikanischen Republik

"Die EUFOR Tschad/ZAR ist in ihrer gegenwärtigen Konzeption ein zweifelhafter Einsatz mit geringen Erfolgsaussichten. Schlecht geplante Einsätze mit unklaren Zielen dienen weder der Sichtbarkeit noch der Stärkung der EU als internationalem Krisenmanager. Eine strategische Herangehensweise, in der die zu erreichenden Ziele mit den entsprechenden Kapazitäten in Einklang stehen, ist bei der Planung zukünftiger Einsätze oberstes Gebot. Langwierige und peinliche Ad-hoc-Lösungen, basierend auf Interessen einzelner Mitgliedstaaten, müssen vermieden werden. Mit zweifelhaften Einsätzen wie der EUFOR Tschad/ ZAR schadet die EU ihrer Glaubwürdigkeit und riskiert mittel- bis langfristig die Unterminierung der bisher breiten öffentlichen Zustimmung zur ESVP. Die Begrenztheit ihrer militärischen Kapazitäten sowie die unzureichende Definition wirklich gemeinsamer Interessen ihrer Mitgliedstaaten machen eine ehrliche Debatte über die Art der Einsätze, welche die EU leisten kann und will, überfällig. Ohne eine solche Debatte gefährdet die Union nicht nur ihren eigenen Ruf, sondern auch die Beziehungen zu anderen Akteuren wie UN, NATO und USA." (Autorenreferat

Phenotypische Charakterisierung der Spinocerebellären Ataxie Typ 17 (SCA 17)

Die spinocerebelläre Ataxie Typ 17 (SCA17) ist eine autosomal dominant vererbte Form der hereditären cerebellären Ataxien mit progredienter Degeneration in Kleinhirn, Hirnstamm, Rückenmark und Kortex. Ätiologisch liegt der SCA17 eine pathologische CAG Repeat Expansion im TATA-Binding-Protein-Gen (TBP-Gen), welches für den Transkriptionsfaktor TBP codiert, zugrunde. Diese CAG Elongation zeigt eine negative Korrelation mit dem Erstmanifestationsalter. Klinisch imponiert die SCA17 sehr heterogen mit cerebellären Dysfunktionen (Ataxie, Dysarthrie, Nystagmus) und Demenz, häufig jedoch auch mit extrapyramidalen Bewegungsstörungen und psychiatrischer Symptomatik

Was nützt Seamless Learning als neues didaktisches Konzept in der Politikwissenschaft?

Der Werkstattbericht zeigt am Beispiel eines politikwissenschaftlichen Online-Seminars, welchen Beitrag Seamless Learning (SL) leisten kann, Studierende zu kontinuierlicher, aktiver Mitarbeit anzuregen und sie bei der Verknüpfung von theoretischen Inhalten mit empirischen Beispielen zu unterstützen. Die Erfahrungen zeigen, dass SL die problemorientierte Wahrnehmung der Studierenden zwar schärfen kann, der erfolgreiche Einsatz des Konzepts jedoch an hohe Voraussetzungen gebunden ist. 12.08.2016 | Nils Arne Brockmann & Kathrin Loer (Hagen

Dermal Phospho-Alpha-Synuclein Deposition in Patients With Parkinson's Disease and Mutation of the Glucocerebrosidase Gene

Heterozygous mutations in the glucocerebrosidase gene (GBA1) represent the most common genetic risk factor for Parkinson's disease (PD) and are histopathologically associated with a widespread load of alpha-synuclein in the brain. Therefore, PD patients with GBA1 mutations are a cohort of high interest for clinical trials on disease-modifying therapies targeting alpha-synuclein. There is evidence that detection of phospho-alpha-synuclein (p-syn) in dermal nerve fibers might be a biomarker for the histopathological identification of PD patients even at premotor or very early stages of disease. It is so far unknown whether dermal p-syn deposition can also be found in PD patients with GBA1 mutations and may serve as a biomarker for PD in these patients. Skin biopsies of 10 PD patients with different GBA1 mutations (six N370S, three E326K, one L444P) were analyzed by double-immunofluorescence labeling with anti-p-syn and anti-protein gene product 9.5 (PGP9.5, axonal marker) to detect intraaxonal p-syn deposition. Four biopsy sites (distal, proximal leg, paravertebral Th10, and C7) per patient were studied. P-syn was found in six patients (three N370S, three E326K). P-syn deposition was mainly detected in autonomic nerve fibers, but also in somatosensory fibers and was not restricted to a certain GBA1 mutation. In summary, dermal p-syn in PD patients with GBA1 mutations seems to offer a similar distribution and frequency as observed in patients without a known mutation. Skin biopsy may be suitable to study p-syn deposition in these patients or even to identify premotor patients with GBA1 mutations

Kinetic parameters of alpha-synuclein seed amplification assay correlate with cognitive impairment in patients with Lewy body disorders

The alpha-synuclein (aSyn) seed amplification assay (SAA) can identify aSyn aggregates as indicator for Lewy body pathology in biomaterials of living patients and help in diagnosing Parkinson ' s disease and dementia syndromes. Our objective was to confirm that qualitative results of aSyn SAA are reproducible across laboratories and to determine whether quantitative findings correlate with patient clinical characteristics. Therefore cerebrospinal fluid samples were re-analysed by aSyn SAA in a second laboratory with four technical replicates for each sample. Kinetic parameters derived from each aggregation curve were summarized and correlated with patient characteristics. We found that qualitative findings were identical between the two laboratories for 54 of 55 patient samples. The number of positive replicates for each sample also showed good agreement between laboratories. Moreover, specific kinetic parameters of the SAA showed a strong correlation with clinical parameters, notably with cognitive performance evaluated by the Montreal Cognitive Assessment. We concluded that SAA findings are highly reproducible across laboratories following the same protocol. SAA reports not only the presence of Lewy pathology but is also associated with clinical characteristics. Thus, aSyn SAA can potentially be used for patient stratification and determining the target engagement of aSyn targeting treatments

The Parkinson's disease-linked Leucine-rich repeat kinase 2 (LRRK2) is required for insulin-stimulated translocation of GLUT4

Mutations within Leucine-rich repeat kinase 2 (LRRK2) are associated with late-onset Parkinson's disease. The physiological function of LRRK2 and molecular mechanism underlying the pathogenic role of LRRK2 mutations remain uncertain. Here, we investigated the role of LRRK2 in intracellular signal transduction. We find that deficiency of Lrrk2 in rodents affects insulin-dependent translocation of glucose transporter type 4 (GLUT4). This deficit is restored during aging by prolonged insulin-dependent activation of protein kinase B (PKB, Akt) and Akt substrate of 160 kDa (AS160), and is compensated by elevated basal expression of GLUT4 on the cell surface. Furthermore, we find a crucial role of Rab10 phosphorylation by LRRK2 for efficient insulin signal transduction. Translating our findings into human cell lines, we find comparable molecular alterations in fibroblasts from Parkinson's patients with the known pathogenic G2019S LRRK2 mutation. Our results highlight the role of LRRK2 in insulin-dependent signalling with potential therapeutic implications

GBA-associated PD: chances and obstacles for targeted treatment strategies.

Given the clear role of GBA in the pathogenesis of Parkinson's disease (PD) and its impact on phenotypical characteristics, this review provides an overview of the current knowledge of GBA-associated PD with a special focus on clinical trajectories and the underlying pathological mechanisms. Importantly, differences and characteristics based on mutation severity are recognized, and current as well as potential future treatment options are discussed. These findings will inform future strategies for patient stratification and cohort enrichment as well as suitable outcome measures when designing clinical trials