Autophagy and ATP-induced anti-apoptosis in antigen presenting cells (APC) follows the cytokine storm in patients after major trauma

Severe trauma and the systemic inflammatory response syndrome (SIRS) occur as a result of a cytokine storm which is in part due to ATP released from damaged tissue. This pathology also leads to increased numbers of immature antigen presenting cells (APC) sharing properties of dendritic cells (DC) or macrophages (MΦ). The occurrence of immature APC appears to coincide with the reactivation of herpes virus infections such as Epstein Barr virus (EBV). The aim of this study was the comparative analysis of the ultrastructural and functional characteristics of such immature APC. In addition, we investigated EBV infection/ reactivation and whether immature APC might be targets for natural killers (NK). Significant macroautophagy, mitochondrial degradation and multivesicular body formation together with the identification of herpes virus particles were morphological findings associated with immature APC. Exogenous stressors such as ATP further increased morphological signs of autophagy, including LC3 expression. Functional tests using fluorescent bacteria proved impaired phagolysosome fusion. However, immature APC were susceptible to NK-92-mediated cytolysis. We found evidence for EBV latency state II infection by detecting EBV-specific LMP1 and EBNA2 in immature APC and in whole blood of these patients. In summary, trauma-induced cytokine storms may induce maturation arrest of APC, promote ATP-induced autophagy, support EBV persistence and impair the degradation of phagocytozed bacteria through inefficient phagolysosome fusion. The susceptibility to NK-mediated cytolysis supports the hypothesis that NK function is likely to contribute to immune reconstitution after major trauma by regulating immature APC, and ATP-induced autophagy and survival

Understanding participatory innovations: a multiple streams account of the creation of parents’ councils in swiss schools

In response to a perceived ‘democratic malaise’, the adaptation and the design of democratic innovations of citizen participation have drawn increasing scholarly attention. Knowledge of the processes leading to the introduction of participatory arrangements is still scarce, however. Drawing on a study of the creation of new participatory school councils for parents of schoolchildren in Switzerland, this article investigates the processes and the conditions for the advent of democratic innovations. The analytical perspective uses Kingdon’s Multiple Streams Approach to show how policy entrepreneurs use persuasion strategies to couple the problem, the policy and the politics streams in education policy reforms, eventually leading to the introduction of new participatory devices. Empirically, the case studies of four Swiss cantons show that the creation of participatory school councils was part of broader reforms in school governance. We conclude that participatory innovations cannot be regarded in isolation, but must be understood in the context of wider processes of policy change in the sector concerned, whose outcome depends on actor strategies, ideational framing as well as the availability of windows of opportunity

Deliberative democracy in local governance: the impact of institutional design on legitimacy

Deliberative democracy is expected to increase legitimacy and effectiveness of democratic governance. In recent years, a growing body of research has reported on different instances of participatory innovations across the globe. Nevertheless, quantitative evidence on the determinants of legitimate and effective deliberative procedures is still scarce. Examining parents’ participation in school governance in Switzerland, this article explores the effect of the design of deliberative institutions on perceptions of legitimacy and effectiveness. Based on an original survey of 312 parent councils of public primary schools in Switzerland, the results of our analysis corroborate theoretical expectations about the impact of institutional design on legitimacy and effectiveness of deliberative procedures: More authority granted to parent councils clearly enhances the output-legitimacy of these bodies

Bürgerbeteiligung im Kontext der School Governance: Befunde einer Dokumentenanalyse zur Vorgeschichte und zur Ausgestaltung schulischer Teilautonomie in der Schweiz

Der vorliegende Artikel behandelt Aspekte der Bürgerbeteiligung im Kontext der School Governance in der Schweiz. Diese Bürgerbeteiligung thematisieren wir unter dem Oberbegriff der Laienpartizipation, der hier die Einbeziehung von nichtprofessionellen Akteuren in Prozesse institutionalisierten Entscheidungshandelns bezeichnen soll. Im Rahmen der obligatorischen Schule der Schweiz sind drei Varianten der Laienpartizipation zu unterscheiden: zum einen lokale Schulkommissionen, zum zweiten Elternräte und zum dritten multilaterale Gremien, in denen Schulleitungen, Lehrpersonen, Eltern, Gemeinderepräsentanten und andere Stakeholder vertreten sein können. Beim vorliegenden Artikel steht die Beteiligung in Schulkommissionen im Mittelpunkt, die historisch gesehen in den letzten beiden Jahrhunderten die dominante Form der Laienpartizipation gewesen ist

Dkk3 levels in patients with myeloproliferative neoplasms

Dickkopf-3 (Dkk3) has been proposed as tumor suppressor gene and a marker for tumor blood vessels and has pro-angiogenic properties. Dkk3 is expressed in platelets and megakaryocytes from healthy controls and patients with BCR-ABL1-negative myeloproliferative neoplasms (MPN). The aim of this study is, to find out whether patients with MPN have higher Dkk3 serum levels than normal controls.; We analyzed Dkk3 serum levels with ELISA in patients with newly diagnosed and untreated MPN, including 10 essential thrombocythemia (ET), 10 polycythemia vera (PV), 10 primary meylofibrosis (PMF) and 10 healthy blood donors and correlated these findings with biological and clinical key data and the JAK2-V617F status. Dkk3 levels were corrected to platelet count, Dkk3c, as patients with MPN have higher platelet counts than controls.; As expected, patients with MPN have higher platelet counts than normal controls. Dkk3 serum levels of patients with MPN (5.4 ± 6.1 ng/ml) showed no significant difference compared to normal controls (4.4 ± 3.8 ng/ml). Regarding Dkk3c, a significant difference to controls was found in PV (8.5 ± 8.7 ng/ml; p=0.04), but not in ET and PMF (5.7 ± 3.8 ng/ml; p=0.07 and 2.7 ± 3.6 ng/ml; p=0.9; respectively. Dkk3c correlated with the JAK2-V617F mutational burden (p=0.014, Rho=0.445).; Dkk3 levels corrected to platelet count showed higher levels in PV than normal controls. Elevated Dkk3c level could possibly correlate to platelet activation in PV patients and increased Dkk3 release. Whether this remains a surrogate marker of platelet release or it contributes to the thrombophilic state through its pro-angiogenic properties remains to be shown