Sarcoidosis of the hypothalamus and pituitary stalk

We report a rare case of sarcoidosis of the hypothalamic and suprasellar region, with clinical course and the magnetic resonance imaging follow-up

Genetic evidence for an essential role of neuronally expressed IL-6 signal transducer gp130 in the induction and maintenance of experimentally induced mechanical hypersensitivity in vivo and in vitro

Tenderness and mechanical allodynia are key symptoms of malignant tumor, inflammation and neuropathy. The proinflammatory cytokine interleukin-6 (IL-6) is causally involved in all three pathologies. IL-6 not only regulates innate immunity and inflammation but also causes nociceptor sensitization and hyperalgesia. In general and in most cell types including immune cells and sensory neurons, IL-6 binds soluble μ receptor subunits which heteromerizes with membrane bound IL-6 signal transducer gp130. In the present study, we used a conditional knock-out strategy to investigate the importance of signal transducer gp130 expressed in C nociceptors for the generation and maintenance of mechanical hypersensitivity. Nociceptors were sensitized to mechanical stimuli by experimental tumor and this nociceptor sensitization was preserved at later stages of the pathology in control mice. However, in mice with a conditional deletion of gp130 in Nav1.8 expressing nociceptors mechanical hypersensitivity by experimental tumor, nerve injury or inflammation recovery was not preserved in the maintenance phase and nociceptors exhibited normal mechanical thresholds comparable to untreated mice. Together, the results argue for IL-6 signal transducer gp130 as an essential prerequisite in nociceptors for long-term mechanical hypersensitivity associated with cancer, inflammation and nerve injury

Extracellular MRP8/14 is a regulator of β2 integrin-dependent neutrophil slow rolling and adhesion

Myeloid-related proteins (MRPs) 8 and 14 are cytosolic proteins secreted from myeloid cells as proinflammatory mediators. Currently, the functional role of circulating extracellular MRP8/14 is unclear. Our present study identifies extracellular MRP8/14 as an autocrine player in the leukocyte adhesion cascade. We show that E-selectin-PSGL-1 interaction during neutrophil rolling triggers Mrp8/14 secretion. Released MRP8/14 in turn activates a TLR4-mediated, Rap1-GTPase-dependent pathway of rapid beta 2 integrin activation in neutrophils. This extracellular activation loop reduces leukocyte rolling velocity and stimulates adhesion. Thus, we identify Mrp8/14 and TLR4 as important modulators of the leukocyte recruitment cascade during inflammation in vivo

Extracellular MRP8/14 is a regulator of β2 integrin-dependent neutrophil slow rolling and adhesion

Myeloid-related proteins (MRPs) 8 and 14 are cytosolic proteins secreted from myeloid cells as proinflammatory mediators. Currently, the functional role of circulating extracellular MRP8/14 is unclear. Our present study identifies extracellular MRP8/14 as an autocrine player in the leukocyte adhesion cascade. We show that E-selectin-PSGL-1 interaction during neutrophil rolling triggers Mrp8/14 secretion. Released MRP8/14 in turn activates a TLR4-mediated, Rap1-GTPase-dependent pathway of rapid beta 2 integrin activation in neutrophils. This extracellular activation loop reduces leukocyte rolling velocity and stimulates adhesion. Thus, we identify Mrp8/14 and TLR4 as important modulators of the leukocyte recruitment cascade during inflammation in vivo

Lessons for Research Policy and Practice: The Case of Co-enquiry Research With Rural Communities

This article explores the relationship between institutional funding for research and community-based or co-enquiry research practice. It examines the implementation of co-enquiry research in the COMBIOSERVE project, which was funded by the European Commission’s Seventh Framework Programme for research and innovation, between the years 2012 and 2015. Research partnerships between Latin American and European civil society organisations, research institutions, and Latin American rural communities are analysed. Challenges for effective collaboration in co-enquiry and lessons learned for research policy and practice are outlined. Based on our case study we suggest that: (1) the established values and practices of academia seem largely unfavourable towards alternative forms of research, such as co-enquiry; (2) the policies and administrative practices of this European Commission funding are unsuitable for adopting participatory forms of enquiry; and (3) the approach to research funding supports short engagements with communities whereas long-term collaborations are more desirable. Based on our case study, we propose more flexible funding models that support face-to-face meetings between researchers and communities from the time of proposal drafting, adaptation of research processes to local dynamics, adaptation of administrative processes to the capacities of all participants, and potential for long-term collaborations. Large-scale funding bodies such as European Commission research programmes are leaders in the evolution of research policy and practice. They have the power and the opportunity to publicly acknowledge the value of partnerships with civil society organisations and communities, actively support co-enquiry, and foment interest in innovative forms of research

Chronic CRH depletion from GABAergic, long-range projection neurons in the extended amygdala reduces dopamine release and increases anxiety

The interplay between corticotropin-releasing hormone (CRH) and the dopaminergic system has predominantly been studied in addiction and reward, while CRH-dopamine interactions in anxiety are scarcely understood. We describe a new population of CRH-expressing, GABAergic, long-range-projecting neurons in the extended amygdala that innervate the ventral tegmental area and alter anxiety following chronic CRH depletion. These neurons are part of a distinct CRH circuit that acts anxiolytically by positively modulating dopamine release.Fil: Dedic, Nina. Max Planck Institute Of Psychiatry; AlemaniaFil: Kühne, Claudia. Max Planck Institute Of Psychiatry; AlemaniaFil: Jakovcevski, Mira. Max Planck Institute Of Psychiatry; AlemaniaFil: Hartmann, Jakob. Max Planck Institute Of Psychiatry; AlemaniaFil: Genewsky, Andreas J.. Max Planck Institut Of Psychiatry; AlemaniaFil: Gomes, Karina S.. Max Planck Institute Of Psychiatry; AlemaniaFil: Anderzhanova, Elmira. Max Planck Institute Of Psychiatry; AlemaniaFil: Pöhlmann, Max L.. Max Planck Institute Of Psychiatry; AlemaniaFil: Chang, Simon. Max Planck Institute Of Psychiatry; AlemaniaFil: Kolarz, Adam. Max Planck Institute Of Psychiatry; AlemaniaFil: Vogl, Annette M.. Max Planck Institute Of Psychiatry; AlemaniaFil: Dine, Julien. Max Planck Institute Of Psychiatry; AlemaniaFil: Metzger, Michael W.. Max Planck Institute of Psychiatry; ArmeniaFil: Schmid, Bianca. Max Planck Institute Of Psychiatry; AlemaniaFil: Almada, Rafael C.. Max Planck Institute Of Psychiatry; AlemaniaFil: Ressler, Kerry J.. Harvard Medical School; Estados UnidosFil: Wotjak, Carsten T.. Max Planck Institute Of Psychiatry; AlemaniaFil: Grinevich, Valery. University of Heidelberg; AlemaniaFil: Chen, Alon. Max Planck Institute Of Psychiatry; AlemaniaFil: Schmidt, Mathias V.. Institute Of Developmental Genetics, Helmholtz Zentrum; AlemaniaFil: Wurst, Wolfgang. German Center for Neurodegenerative Diseases; AlemaniaFil: Refojo, Damian. Max Planck Institute Of Psychiatry; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Deussing, Jan M.. Max Planck Institute Of Psychiatry; Alemani

Tight-binding approach to excitons bound to monolayer impurity planes: strong radiative properties of InAs in GaAs

A theory of Wannier-Mott excitons bound to monolayer (ML) impurity planes in semiconductors, which is based on Green's function tight-binding calculations of the single-particle states, is presented. Binding energies and oscillator strengths for one and two MLs of InAs in GaAs are predicted to be much larger than in the usual InxGa1-xAs/GaAs thick quantum wells. The reason is the increase of effective mass of both carriers due to folding of the InAs bands along the growth direction. The results suggest that ML insertions can be used as intense light sources in light-emitting devices

The genetic study of three population microisolates in South Tyrol (MICROS): study design and epidemiological perspectives

<p>Abstract</p> <p>Background</p> <p>There is increasing evidence of the important role that small, isolated populations could play in finding genes involved in the etiology of diseases. For historical and political reasons, South Tyrol, the northern most Italian region, includes several villages of small dimensions which remained isolated over the centuries.</p> <p>Methods</p> <p>The MICROS study is a population-based survey on three small, isolated villages, characterized by: old settlement; small number of founders; high endogamy rates; slow/null population expansion. During the stage-1 (2002/03) genealogical data, screening questionnaires, clinical measurements, blood and urine samples, and DNA were collected for 1175 adult volunteers. Stage-2, concerning trait diagnoses, linkage analysis and association studies, is ongoing. The selection of the traits is being driven by expert clinicians. Preliminary, descriptive statistics were obtained. Power simulations for finding linkage on a quantitative trait locus (QTL) were undertaken.</p> <p>Results</p> <p>Starting from participants, genealogies were reconstructed for 50,037 subjects, going back to the early 1600s. Within the last five generations, subjects were clustered in one pedigree of 7049 subjects plus 178 smaller pedigrees (3 to 85 subjects each). A significant probability of familial clustering was assessed for many traits, especially among the cardiovascular, neurological and respiratory traits. Simulations showed that the MICROS pedigree has a substantial power to detect a LOD score ≥ 3 when the QTL specific heritability is ≥ 20%.</p> <p>Conclusion</p> <p>The MICROS study is an extensive, ongoing, two-stage survey aimed at characterizing the genetic epidemiology of Mendelian and complex diseases. Our approach, involving different scientific disciplines, is an advantageous strategy to define and to study population isolates. The isolation of the Alpine populations, together with the extensive data collected so far, make the MICROS study a powerful resource for the study of diseases in many fields of medicine. Recent successes and simulation studies give us confidence that our pedigrees can be valuable both in finding new candidates loci and to confirm existing candidate genes.</p

Sustainable Regional Integration in West Africa/ Intégration régionale durable en Afrique de l´Ouest/ Integração regional sustentavel na África Ocidental. ZEI Discussion Paper C 208, 2011

Since the end of the Cold War, the world has observed a change in terms of political entities. Regional integration processes and regional institutions have been reinforced all around the globe with a strong concentration of this occurring in Africa. In this context, the European integration process is for better or for worse, a source of inspiration. Nevertheless, regional integration and cooperation outside of Europe is not yet supported by sufficient and sound analysis, targeted capacity development and by the dissemination of knowledge and information about the phenomenon to the wider public. It is due to these three principal shortcomings, that the West Africa Institute (WAI) in Praia was launched. The WAI is a one-of-a-kind initiative to establish the first ever research institution dealing in particular with issues of regional integration in West Africa. It was started in 2008 by the five promoters, ECOWAS, WAEMU, ECOBANK, UNESCO and the Government of Cape Verde and is based in Praia, Cape Verde. Since then, the Center for European Integration Studies (ZEI) and the West Africa Institute (WAI) have developed an ever closer partnership. On the basis of its academic and analytical work on European integration and of its experience in setting up structures for sustainable research and education, ZEI supports WAI on its way to becoming a center of knowledge and expertise on regional integration in West Africa in the framework of a joint cooperation project funded by the German Ministry of Education and Research (BMBF). Within this framework, the thematic outline of this Discussion Paper deals with the three most pressing questions of the West African integration process which double as the focus of the cooperation between ZEI and WAI. These three questions are: 1. How can conditions for regional trade be improved and can regional trade be enhanced? 2. How can different security challenges be dealt with in the region and how can human security best be provided in West Africa? 3. How can human capacities be trained in order to foster the integration process and how can citizens be informed about matters of regional integration? The topics of economics, security and education/outreach were chosen firstly because of their topicality on the political agenda, secondly because of their obvious interconnectedness and thirdly because of the fact that regional approaches can help to find practical solutions in those three fields. The Discussion Paper brings together researchers affiliated with WAI and ZEI. The structure of the paper and its articles reflect an interdisciplinary approach based on the Africa-Europe partnership. Specifically, the respective contributions focus on the following: In his introductory article, ZEI Director Ludger Kühnhardt analyzes some basic obstacles for sustainable regional integration and draws the conclusion that there is a global demand for more quality research and study opportunities in the field of regional integration, which he calls a "growth industry". He shows that this is especially true for West Africa and that the WAI-ZEI cooperation is a first step in this direction. WAI´s past project coordinator and current researcher Corsino Tolentino writes a broad introduction to regional integration as a worldwide phenomenon. He gives an overview of different attempts to create regional groupings on all continents, and suggests that the knowledge deficit is the main obstacle to regional integration in Africa. Djénéba Traoré, who is a board member of WAI, describes in her article that education is a crucial precondition for any development. However, she states that it is not sufficient to act in only the field of education. She claims that it is equally important to execute research on how knowledge can be best built, transferred and distributed. Using the Educational Research Network for West and Central Africa (ERNWACA) as an example, she shows that working at the regional level can have a lot of positive effects in this field. After concentrating on the need for research and education on regional integration, the paper turns toward economic concerns. Here John Igue, also a board member of WAI and former Minister of Industry and Small and Medium Size Enterprises of Benin gives a complete overview about the efforts for regional economic integration in West Africa. He provides a critical assessment of the current situation and states that some questions on the multi-level nature of integration, on the special constellations of interests and on financial responsibilities have to be clarified before real integration success can be achieved. ZEI fellow Claudia Rommel adds to this a more specialized perspective on issues of intra-regional trade within West Africa. She shows how important it is to increase the effort of removing various trade barriers and that so far, facilitating commercial relations through reducing tariffs has not proven effective. She argues that ECOWAS should work on non-tariff barriers and focus in particular on improving the border controls and customs procedures in order to speed up the transportation of goods within the region. The last section of the paper deals with the relationship of human security and regional integration. WAI board member and former rector of the University of Lomé and former Minister of Education of Togo Francisco Komlavi Seddoh gives an empirical overview of challenges to human security in Africa. Using a broad interpretation of human security, he argues that areas like life expectancy, infant mortality, education or alphabetization are indicators of human security and that West Africa is far behind in these areas. Seddoh mentions that some progress can be seen but that this is not nearly enough. Therefore, he makes a plea for better implementation of regional approaches. In the last article, ZEI fellow Matthias Vogl presents the different definitions of human security and shows the abstractness and ambiguity of the concept. His analysis shows that the definitions are rather vague and cannot serve as a solid basis for evaluating West African security. Due to the fact that security is one of the biggest obstacles to development and that regional organizations can generate added-value in this sector, he claims that it is essential to develop a West African definition of human security that can be connected with regional monitoring tools to determine the necessity of action. On this basis adequate solutions can be developed. This WAI-ZEI Discussion Paper reveals that there are a lot of open questions that make profound research all the more necessary. On these grounds, the cooperation between WAI and ZEI will enter into a phase of stronger partnership in the near future. During this period, the issues that have been raised here will be analyzed with an aim toward making the process of regional integration in West Africa in general and the work of WAI in particular more sustainable