Structural and Genetic Studies Demonstrate Neurologic Dysfunction in Triosephosphate Isomerase Deficiency Is Associated with Impaired Synaptic Vesicle Dynamics

Triosephosphate isomerase (TPI) deficiency is a poorly understood disease characterized by hemolytic anemia, cardiomyopathy, neurologic dysfunction, and early death. TPI deficiency is one of a group of diseases known as glycolytic enzymopathies, but is unique for its severe patient neuropathology and early mortality. The disease is caused by missense mutations and dysfunction in the glycolytic enzyme, TPI. Previous studies have detailed structural and catalytic changes elicited by disease-associated TPI substitutions, and samples of patient erythrocytes have yielded insight into patient hemolytic anemia; however, the neuropathophysiology of this disease remains a mystery. This study combines structural, biochemical, and genetic approaches to demonstrate that perturbations of the TPI dimer interface are sufficient to elicit TPI deficiency neuropathogenesis. The present study demonstrates that neurologic dysfunction resulting from TPI deficiency is characterized by synaptic vesicle dysfunction, and can be attenuated with catalytically inactive TPI. Collectively, our findings are the first to identify, to our knowledge, a functional synaptic defect in TPI deficiency derived from molecular changes in the TPI dimer interface

Dividing disasters in Aceh, Indonesia: Separatist conflict and tsunami, human rights and humanitarianism

This paper examines the interface between human rights and humanitarian action in the context of the conflict and tsunami in Aceh, Indonesia, between 1998 and 2007. It looks at the challenges international humanitarian non-governmental organisations (NGOs) faced as they engaged in human rights work in the conflict period and in conflict-related activities in the post-tsunami period. The paper argues that many large NGOs may have compromised what some would hold to be essential principles for humanitarian action because of domestic political concerns, donor restrictions and resistance among certain NGO chiefs. In contrast with the pre-tsunami period, in which NGOs worked for years amid military operations, in the post-tsunami period NGOs were decidedly apolitical, neglecting the conflict in their tsunami response-despite significant developments that permitted greater political engagement in Aceh's post-conflict transformation. The evidence suggests that NGOs are challenged in contextualising humanitarian responses and that there is a need to underscore donor flexibility and independence in humanitarian action

The dilemmas of new humanitarianism : NGO responses to the separatist conflict and the Indian Ocean tsunami between 1998 and 2008 in Aceh, Indonesia

This thesis is about the theory and practice of 'new humanitarianism' in the context of converging disasters in Aceh, Indonesia. The main question of this thesis is: what is the relationship between humanitarian assistance and human rights in practice? In order to answer this question, the study examines the challenges local and international non-governmental organisations (NGOs) faced as they engaged in human rights and humanitarian work during both the conflict (1998-2004) and post-tsunami (2004-2008) periods. It investigates the tensions inherent in the 'new humanitarian' approach of combining 'traditional' humanitarian assistance, such as the provision of food, shelter and medical care, with more political, human rights-oriented activities including advocacy, protection and conflict transformation. Discussing the relationship between humanitarian assistance and human rights, the study stresses the fundamental, practical dimensions of new humanitarianism rather than theoretical concerns. It finds that juxtaposing humanitarian principles with human rights and political activities treats humanitarianism as consisting of extremes only. The key to new humanitarianism in practice might not lie in fundamental revisiting of first principles. Rather, the study argues for a 'grounded humanitarianism' approach to the field of humanitarian studies that considers the day-to-day realities and challenges faced in humanitarian action. Grounded humanitarianism should not be limited to the study of international humanitarian actors alone. The findings illustrate that local NGO approaches, while deeply embedded in local political contexts and struggles, were not dissimilar to those that international 'new humanitarian' NGOs espoused. Both groups regularly weighed up the costs and benefits of any particular action. Conventional approaches to the study of humanitarian action tend to overlook the vital role that local humanitarian actors play. Yet locals are always the first to respond to disasters and have a lasting stake in ensuring a beneficial outcome for their community. Local groups in Aceh provided many examples of strategies in combining advocacy, protection and conflict transformation activities alongside humanitarian assistance, often at great personal risk. For theorists of humanitarian action, bringing local actors into the picture allows us to appreciate a more complete, nuanced understanding of the challenges and opportunities for humanitarian assistance. New humanitarians need to be modest in their goals, rather than believing that humanitarianism has the power to transform political structures. The form that humanitarian action will take in any crisis will depend on a range of features, including domestic politics, funding exigencies, the presence of 'competing disasters', and organisational culture. Ultimately, greater consideration should be given to the day-to-day realities that contribute to, or deduct from, new humanitarian approaches. -- provided by Candidate

Die USA rufen, das Grundgesetz antwortet

Soll sich die Bundeswehr an einem militärischen Einsatz in der Straße von Hormus beteiligen? Gefühlt im Stundentakt positionieren sich im Augenblick die unterschiedlichsten Minister und Ministerinnen, teilweise unter interessanter Auslegung der eigenen Ressortkompetenz, ob die Bundesregierung dem Ruf der USA folgen soll oder nicht. Die USA verfolgen damit konsequent ihre außenpolitische Strategie, weiter auf bi- oder multinationale Armeebündnisse zu setzen, anstatt auf die kollektiven Sicherheitssysteme wie NATO oder UN zu vertrauen. Diese Strategie stellt die verfassungsrechtlichen Vorgaben zu Einsätzen der Bundeswehr vor große Herausforderungen.</p

CHARACTERIZATION AND EVOLUTION OF GTPASES OF IMMUNITY ASSOCIATED PROTEINS (GIMAP) IN CNIDARIANS AND DINOFLAGELLATES

Corals are critical to the coral reef ecosystem in that they provide shelter for many types of marine life, which in turn provides tourism to many countries and supports various fishing industries. Currently, coral disease is a major threat to coral reefs, yet very little is currently known about the cellular pathways it impacts. One group of proteins that could play a role in the cnidarian immune response are GTPases of immunity associated proteins (GIMAPs). In vertebrates, GIMAPs are known to regulate the fate of developing lymphocytes, potentially by associating with apoptotic factors. However, cnidarians do not have lymphocytes, and therefore the function of GIMAPs remains unclear. GIMAPs were previously characterized in the coral Acropora millepora, but were not found in the genome of the anemone Nematostella vectensis, making the phylogenetic distribution of GIMAPs a topic of interest. In this study, we utilized genomic and transcriptomic databases to search for GIMAPs in both cnidarians and dinoflagellates to better understand the evolutionary history of this gene family. The sequence searches yielded a multitude of GIMAP-like sequences in both cnidarians and dinoflagellates. In addition, two different forms of GIMAPs were discovered within cnidarians, where some species possess both, others have one, and some have none. This represents the first characterization of GIMAP sequences in dinoflagellates. Overall, this work provides a greater understanding of the cnidaran immune repertoire, and also the evolutionary history of GIMAPS in both basal metazoans and protists