Geographie an beruflichen Schulen in Baden-Württemberg zwischen Anspruch und Wirklichkeit – eine aktuelle Bestandsaufnahme von Innen- und Außenansichten

Das Schulfach Geographie steht immer wieder in der Diskussion um Stundenreduzierungen in den Bildungsplänen. Das berufliche Schulwesen spielt dabei häufig eine wichtige Vorreiterrolle. In dem Beitrag wird deshalb exemplarisch die aktuelle Situation des Faches Wirtschaftsgeographie an beruflichen Schulen in Baden-Württemberg dargestellt. Im Mittelpunkt steht dabei eine Befragung von Schülern, Eltern und Lehrern an kaufmännischen Gymnasien zu deren Ansichten über die Bedeutung des Faches und geographischer Fragestellungen im schulischen und außerschulischen Kontext. Demnach ist der öffentliche Ruf des Faches Geographie wesentlich besser als erwartet (befürchtet). Besonders die Bedeutung des Faches für die Umwelterziehung, die Orientierung im Raum und die Raumverhaltenskompetenz wird vielfach betont. Der Geographie wird damit eine zentrale Funktion beigemessen, die es in der öffentlichen Diskussion zu stärken gilt

The selective phosphodiesterase 4 inhibitor roflumilast and phosphodiesterase 3/4 inhibitor pumafentrine reduce clinical score and TNF expression in experimental colitis in mice.

The specific inhibition of phosphodiesterase (PDE)4 and dual inhibition of PDE3 and PDE4 has been shown to decrease inflammation by suppression of pro-inflammatory cytokine synthesis. We examined the effect of roflumilast, a selective PDE4 inhibitor marketed for severe COPD, and the investigational compound pumafentrine, a dual PDE3/PDE4 inhibitor, in the preventive dextran sodium sulfate (DSS)-induced colitis model. The clinical score, colon length, histologic score and colon cytokine production from mice with DSS-induced colitis (3.5% DSS in drinking water for 11 days) receiving either roflumilast (1 or 5 mg/kg body weight/d p.o.) or pumafentrine (1.5 or 5 mg/kg/d p.o.) were determined and compared to vehicle treated control mice. In the pumafentrine-treated animals, splenocytes were analyzed for interferon-γ (IFNγ) production and CD69 expression. Roflumilast treatment resulted in dose-dependent improvements of clinical score (weight loss, stool consistency and bleeding), colon length, and local tumor necrosis factor-α (TNFα) production in the colonic tissue. These findings, however, were not associated with an improvement of the histologic score. Administration of pumafentrine at 5 mg/kg/d alleviated the clinical score, the colon length shortening, and local TNFα production. In vitro stimulated splenocytes after in vivo treatment with pumafentrine showed a significantly lower state of activation and production of IFNγ compared to no treatment in vivo. These series of experiments document the ameliorating effect of roflumilast and pumafentrine on the clinical score and TNF expression of experimental colitis in mice

NFκB activation by Fas is mediated through FADD, caspase-8, and RIP and is inhibited by FLIP

Fas (APO-1/CD95) is the prototypic death receptor, and the molecular mechanisms of Fas-induced apoptosis are comparably well understood. Here, we show that Fas activates NFκB via a pathway involving RIP, FADD, and caspase-8. Remarkably, the enzymatic activity of the latter was dispensable for Fas-induced NFκB signaling pointing to a scaffolding-related function of caspase-8 in nonapoptotic Fas signaling. NFκB was activated by overexpressed FLIPL and FLIPS in a cell type–specific manner. However, in the context of Fas signaling both isoforms blocked FasL-induced NFκB activation. Moreover, down-regulation of both endogenous FLIP isoforms or of endogenous FLIPL alone was sufficient to enhance FasL-induced expression of the NFκB target gene IL8. As NFκB signaling is inhibited during apoptosis, FasL-induced NFκB activation was most prominent in cells that were protected by Bcl2 expression or caspase inhibitors and expressed no or minute amounts of FLIP. Thus, protection against Fas-induced apoptosis in a FLIP-independent manner converted a proapoptotic Fas signal into an inflammatory NFκB-related response

Crack-cocaine users have less family cohesion than alcohol users

Objective: Many studies correlate characteristics of family functioning and the development of drug addiction. This study sought to evaluate and compare the family environment styles of two groups of psychoactive substance users: 1) alcohol-only users and 2) crack-cocaine users. Methods: Three hundred and sixty-four users of alcohol, crack-cocaine, and other drugs, recruited from research centers in four Brazilian capitals participated in this study. Subjects were evaluated through the Family Environment Scale and the Addiction Severity Index, 6th version (ASI-6). ASI-6 t-scores were compared by analysis of variance (ANOVA) and post-hoc tests. A final model was obtained using a logistic regression analysis. All analyses were adjusted for partner, age, and psychiatric t-score. Results: We found a significant difference between groups in the cohesion subscale (p = 0.044). The post-hoc test revealed a difference of 1.06 points (95% CI 0.11-2.01) between groups 1 (6.45 +/- 0.28) and 2 (5.38 +/- 0.20). No significant between-group differences were observed in the other subscales. However, categorical analyses of variables regarding family dynamic showed that crack users more often reported that sometimes people in their family hit each other (30.4% vs. 13.2%, p = 0.007) and that people in their family frequently compared each other regarding work and/or school achievement (57.2% vs. 42.6%, p = 0.041). Conclusion: These results suggest that families of crack-cocaine users are less cohesive than families of alcohol users. This type of family environment may affect treatment outcome, and should thus be adequately approached.SENADNational Institutes of Health/National Institute on Drug AbuseUniv Fed Rio do Grande UFRGS, HCPA, CPAD, Porto Alegre, RS, BrazilHCPA, Unidade Bioestat, Porto Alegre, RS, BrazilUniv Fed Rio Grande do Sul, Lab Biossinais Fenomenol & Cognicao, Inst Psicol, Porto Alegre, RS, BrazilUniv Fed Sao Paulo UNIFESP, Dept Psicobiol, Sao Paulo, SP, BrazilUniv Fed Rio de Janeiro UFRJ, Inst Psiquiatria, Rio De Janeiro, RJ, BrazilUniv Fed Sao Paulo UNIFESP, Dept Psicobiol, Sao Paulo, SP, BrazilSENAD: TC 005/2005Web of Scienc

Visualization of Inflammation in Experimental Colitis by Magnetic Resonance Imaging Using Very Small Superparamagnetic Iron Oxide Particles

Inflammatory bowel diseases (IBD) comprise mainly ulcerative colitis (UC) and Crohn´s disease (CD). Both forms present with a chronic inflammation of the (gastro) intestinal tract, which induces excessive changes in the composition of the associated extracellular matrix (ECM). In UC, the inflammation is limited to the colon, whereas it can occur throughout the entire gastrointestinal tract in CD. Tools for early diagnosis of IBD are still very limited and highly invasive and measures for standardized evaluation of structural changes are scarce. To investigate an efficient non-invasive way of diagnosing intestinal inflammation and early changes of the ECM, very small superparamagnetic iron oxide nanoparticles (VSOPs) in magnetic resonance imaging (MRI) were applied in two mouse models of experimental colitis: the dextran sulfate sodium (DSS)-induced colitis and the transfer model of colitis. For further validation of ECM changes and inflammation, tissue sections were analyzed by immunohistochemistry. For in depth ex-vivo investigation of VSOPs localization within the tissue, Europium-doped VSOPs served to visualize the contrast agent by imaging mass cytometry (IMC). VSOPs accumulation in the inflamed colon wall of DSS-induced colitis mice was visualized in T2* weighted MRI scans. Components of the ECM, especially the hyaluronic acid content, were found to influence VSOPs binding. Using IMC, co-localization of VSOPs with macrophages and endothelial cells in colon tissue was shown. In contrast to the DSS model, colonic inflammation could not be visualized with VSOP-enhanced MRI in transfer colitis. VSOPs present a potential contrast agent for contrast-enhanced MRI to detect intestinal inflammation in mice at an early stage and in a less invasive manner depending on hyaluronic acid content

Interleukin-7 Links T Lymphocyte and Intestinal Epithelial Cell Homeostasis

Interleukin-7 (IL-7) is a major survival factor for mature T cells. Therefore, the degree of IL-7 availability determines the size of the peripheral T cell pool and regulates T cell homeostasis. Here we provide evidence that IL-7 also regulates the homeostasis of intestinal epithelial cells (IEC), colon function and the composition of the commensal microflora. In the colon of T cell-deficient, lymphopenic mice, IL-7-producing IEC accumulate. IEC hyperplasia can be blocked by IL-7-consuming T cells or the inactivation of the IL-7/IL-7R signaling pathway. However, the blockade of the IL-7/IL-7R signaling pathway renders T cell-deficient mice more sensitive to chemically-induced IEC damage and subsequent colitis. In summary, our data demonstrate that IL-7 promotes IEC hyperplasia under lymphopenic conditions. Under non-lymphopenic conditions, however, T cells consume IL-7 thereby limiting IEC expansion and survival. Hence, the degree of IL-7 availability regulates both, T cell and IEC homeostasis

Crack-cocaine users have less family cohesion than alcohol users

Objective: Many studies correlate characteristics of family functioning and the development of drug addiction. This study sought to evaluate and compare the family environment styles of two groups of psychoactive substance users: 1) alcohol-only users and 2) crack-cocaine users. Methods: Three hundred and sixty-four users of alcohol, crack-cocaine, and other drugs, recruited from research centers in four Brazilian capitals participated in this study. Subjects were evaluated through the Family Environment Scale and the Addiction Severity Index, 6th version (ASI-6). ASI-6 t-scores were compared by analysis of variance (ANOVA) and post-hoc tests. A final model was obtained using a logistic regression analysis. All analyses were adjusted for partner, age, and psychiatric t-score. Results: We found a significant difference between groups in the cohesion subscale (p = 0.044). The post-hoc test revealed a difference of 1.06 points (95%CI 0.11-2.01) between groups 1 (6.4560.28) and 2 (5.3860.20). No significant between-group differences were observed in the other subscales. However, categorical analyses of variables regarding family dynamic showed that crack users more often reported that sometimes people in their family hit each other (30.4% vs. 13.2%, p = 0.007) and that people in their family frequently compared each other regarding work and/or school achievement (57.2% vs. 42.6%, p = 0.041). Conclusion: These results suggest that families of crack-cocaine users are less cohesive than families of alcohol users. This type of family environment may affect treatment outcome, and should thus be adequately approached

Biallelic RIPK1 mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation.

RIPK1 (receptor-interacting serine/threonine kinase 1) is a master regulator of signaling pathways leading to inflammation and cell death and is of medical interest as a drug target. We report four patients from three unrelated families with complete RIPK1 deficiency caused by rare homozygous mutations. The patients suffered from recurrent infections, early-onset inflammatory bowel disease, and progressive polyarthritis. They had immunodeficiency with lymphopenia and altered production of various cytokines revealed by whole-blood assays. In vitro, RIPK1-deficient cells showed impaired mitogen-activated protein kinase activation and cytokine secretion and were prone to necroptosis. Hematopoietic stem cell transplantation reversed cytokine production defects and resolved clinical symptoms in one patient. Thus, RIPK1 plays a critical role in the human immune system

SMAC Mimetic BV6 Induces Cell Death in Monocytes and Maturation of Monocyte-Derived Dendritic Cells

Background: Compounds mimicking the inhibitory effect of SMAC / DIABLO on X-linked inhibitor of apoptosis (XIAP) have been developed with the aim to achieve sensitization for apoptosis of tumor cells resistant due to deregulated XIAP expression. It turned out that SMAC mimetics also have complex effects on the NFkB system and TNF signaling. In view of the overwhelming importance of the NFkB transcription factors in the immune system, we analyzed here the effects of the SMAC mimetic BV6 on immune cells. Principal Findings: BV6 induced apoptotic and necrotic cell death in monocytes while T-cells, dendritic cells and macrophages were largely protected against BV6-induced cell death. In immature dendritic cells BV6 treatment resulted in moderate activation of the classical NFkB pathway, but it also diminished the stronger NFkB-inducing effect of TNF and CD40L. Despite its inhibitory effect on TNF- and CD40L signaling, BV6 was able to trigger maturation of immature DCs as indicated by upregulation of CD83, CD86 and IL12. Significance: The demonstrated effects of SMAC mimetics on immune cells may complicate the development of tumor therapeutic concepts based on these compounds but also arise the possibility to exploit them for the development of immune stimulatory therapies