Epstein-Barr-Virus - Ein klinisch relevanter Marker für das Nasopharynxkarzinom? = Epstein-Barr virus - a clinically relevant feature of nasopharyngeal carcinoma? (author's transl.)

Nasopharyngeal carcinoma (NPC) has been linked to Epstein-Barr Virus (EBV) by seroepidemiological evidence and by the regular proof of EBV-DNA in the epithelial tumor cells. We have been able to study the serological parameters of 62 NPC patients of the local ENT-Clinic. All patients were kaukasians in contrast to a previous study by Henle et al. Our results emphasize the remarkable predominance of EBV-IgA antibodies to viral capsid antigen (VCA) and early antigen (EA) in NPC patients and prove the value of the test for the initial diagnosis of the disease. Follow-up studies with subsequent serological tests strongly suggest that this test is related to the stage of the disease. We have also found NPC-typical serological EBV-IgA titers in 3 lymphoepithelial carcinomas of the tonsil and the soft palate. Similar titers have been found in two cases of poorly differentiated carcinomas of the base of the tongue. All these tumors arise in the lymphoepithelial tissue of Waldeyer's ring. We conclude that possibly some carcinomas of Waldeyer's ring are similarly related to EBV as nasopharyngeal carcinomas are

Etablierung Entscheidungshilfesystem

Zur Umsetzung der Ziele der EU-Wasserrahmenrichtlinie sind in Sachsen bis 2015 für Gewässereinzugsgebiete entsprechende Maßnahmen zur Erreichung bzw. Sicherung eines guten Gewässerzustandes durchzuführen. Für die hierzu erforderliche integrierte Planung und Entscheidungsfindung auf Einzugsgebietsebene stellen Entscheidungshilfesysteme den daran beteiligten Akteuren (Flächennutzer, -besitzer, Fachbehörden usw.) die technische Unterstützung bereit. Am Beispiel des überwiegend landwirtschaftlich genutzten Fließgewässereinzugsgebietes der Jahna (Sächsisches Lösshügelland) wurde ein Entscheidungshilfesystem entwickelt und erprobt. Es umfasst zum einen Werkzeuge zur Analyse der Belastungen der Oberflächengewässer und des Grundwassers durch Nährstoffaustrag (z.B. Modell Stoffbilanz) bzw. durch Wassererosion (Modell EROSION 3D). Zum anderen bietet das Entscheidungshilfesystem verschiedene Modelle und Verfahren an, mit deren Hilfe stoffaustragsmindernde landwirtschaftliche Maßnahmen ausgewählt und hinsichtlich ihrer Wirksamkeit abgeschätzt werden können. Ergänzend dazu wurde ein computergestützter Maßnahmenkatalog zur Unterstützung bei der Auswahl stoffaustragsmindernder Maßnahmen im Bereich Landwirtschaft erstellt. Die Priorisierung der verschiedenen Maßnahmenalternativen unter Berücksichtigung ökologischer und ökonomischer Ziele wurde beispielhaft mit Hilfe der Nutzwertanalyse durchgeführt

Some Ethical Questions in Particle Physics

Authors will discuss a few ethical questions in today's particle physics: high costs and purported dangers of Big Science projects, relevance of fundamental research for society and the way particle physicists fill their duty to communicate with the public. Examples will be given including the story of a possible mini-black hole creation at CERN and two outreach activities for high school students, International Particle Physics Masterclasses and Cascade competition

CXCR7 Functions as a Scavenger for CXCL12 and CXCL11

CXCR7 (RDC1), the recently discovered second receptor for CXCL12, is phylogenetically closely related to chemokine receptors, but fails to couple to G-proteins and to induce typical chemokine receptor mediated cellular responses. The function of CXCR7 is controversial. Some studies suggest a signaling activity in mammalian cells and zebrafish embryos, while others indicate a decoy activity in fish. Here we investigated the two propositions in human tissues. We provide evidence and mechanistic insight that CXCR7 acts as specific scavenger for CXCL12 and CXCL11 mediating effective ligand internalization and targeting of the chemokine cargo for degradation. Consistently, CXCR7 continuously cycles between the plasma membrane and intracellular compartments in the absence and presence of ligand, both in mammalian cells and in zebrafish. In accordance with the proposed activity as a scavenger receptor CXCR7-dependent chemokine degradation does not become saturated with increasing ligand concentrations. Active CXCL12 sequestration by CXCR7 is demonstrated in adult mouse heart valves and human umbilical vein endothelium. The finding that CXCR7 specifically scavenges CXCL12 suggests a critical function of the receptor in modulating the activity of the ubiquitously expressed CXCR4 in development and tumor formation. Scavenger activity of CXCR7 might also be important for the fine tuning of the mobility of hematopoietic cells in the bone marrow and lymphoid organs

Genome-wide comparison between IL-17 and combined TNF-alpha/IL-17 induced genes in primary murine hepatocytes

<p>Abstract</p> <p>Background</p> <p>Cytokines such as TNF-alpha and IL-1beta are known for their contribution to inflammatory processes in liver. In contrast, the cytokine IL-17 has not yet been assigned a role in liver diseases. IL-17 can cooperate with TNF-alpha to induce a synergistic response on several target genes in different cell lines, but no data exist for primary hepatocytes. To enhance our knowledge on the impact of IL-17 alone and combined with TNF-alpha in primary murine hepatocytes a comprehensive microarray study was designed. IL-1beta was included as this cytokine is suggested to act in a similar manner as the combination of TNF-alpha and IL-17, especially with respect to its role in mRNA stabilization.</p> <p>Results</p> <p>The present microarray analysis demonstrates that primary murine hepatocytes responded to IL-17 stimulation by upregulation of chemokines and genes, which are functionally responsible to increase and sustain inflammation. Cxcl2, Nfkbiz and Zc3h12a were strongly induced, whereas the majority of the genes were only very moderately up-regulated. Promoter analysis revealed involvement of NF-kappaB in the activation of many genes. Combined stimulation of TNF-alpha/IL-17 resulted in enhanced induction of gene expression, but significantly synergistic effects could be applied only to a few genes, such as Nfkbiz, Cxcl2, Zc3h12 and Steap4. Comparison of the gene expression profile obtained after stimulation of TNF-alpha/IL-17 versus IL-1beta proposed an "IL-1beta-like effect" of the latter cytokine combination. Moreover, evidence was provided that modulation of mRNA stability may be a major mechanism by which IL-17 regulates gene expression in primary hepatocytes. This assumption was exemplarily proven for Nfkbiz mRNA for the first time in hepatocytes. Our studies also suggest that RNA stability can partially be correlated to the existence of AU rich elements, but further mechanisms like the RNase activity of the up-regulated Zc3h12a have to be considered.</p> <p>Conclusions</p> <p>Our microarray analysis gives new insights in IL-17 induced gene expression in primary hepatocytes highlighting the crosstalk with the NF-kappaB signaling pathway. Gene expression profile suggests IL-17 alone and in concert with TNF-alpha a role in sustaining liver inflammatory processes. IL-17 might exceed this function by RNA stabilization.</p

Sulfite Reductase Co-suppression in Tobacco Reveals Detoxification Mechanisms and Downstream Responses Comparable to Sulfate Starvation

Sulfite reductase (SIR) is a key enzyme in higher plants in the assimilatory sulfate reduction pathway. SIR, being exclusively localized in plastids, catalyzes the reduction of sulfite (SO32−) to sulfide (S2−) and is essential for plant life. We characterized transgenic plants leading to co-suppression of the SIR gene in tobacco (Nicotiana tabacum cv. Samsun NN). Co-suppression resulted in reduced but not completely extinguished expression of SIR and in a reduction of SIR activity to about 20–50% of the activity in control plants. The reduction of SIR activity caused chlorotic and necrotic phenotypes in tobacco leaves, but with varying phenotype strength even among clones and increasing from young to old leaves. In transgenic plants compared to control plants, metabolite levels upstream of SIR accumulated, such as sulfite, sulfate and thiosulfate. The levels of downstream metabolites were reduced, such as cysteine, glutathione (GSH) and methionine. This metabolic signature resembles a sulfate deprivation phenotype as corroborated by the fact that O-acetylserine (OAS) accumulated. Further, chlorophyll contents, photosynthetic electron transport, and the contents of carbohydrates such as starch, sucrose, fructose, and glucose were reduced. Amino acid compositions were altered in a complex manner due to the reduction of contents of cysteine, and to some extent methionine. Interestingly, sulfide levels remained constant indicating that sulfide homeostasis is crucial for plant performance and survival. Additionally, this allows concluding that sulfide does not act as a signal in this context to control sulfate uptake and assimilation. The accumulation of upstream compounds hints at detoxification mechanisms and, additionally, a control exerted by the downstream metabolites on the sulfate uptake and assimilation system. Co-suppression lines showed increased sensitivity to additionally imposed stresses probably due to the accumulation of reactive compounds because of insufficient detoxification in combination with reduced GSH levels

Clec12a Is an Inhibitory Receptor for Uric Acid Crystals that Regulates Inflammation in Response to Cell Death

SummaryRecognition of cell death by the innate immune system triggers inflammatory responses. However, how these reactions are regulated is not well understood. Here, we identify the inhibitory C-type lectin receptor Clec12a as a specific receptor for dead cells. Both human and mouse Clec12a could physically sense uric acid crystals (monosodium urate, MSU), which are key danger signals for cell-death-induced immunity. Clec12a inhibited inflammatory responses to MSU in vitro, and Clec12a-deficient mice exhibited hyperinflammatory responses after being challenged with MSU or necrotic cells and after radiation-induced thymocyte killing in vivo. Thus, we identified a negative regulatory MSU receptor that controls noninfectious inflammation in response to cell death that has implications for autoimmunity and inflammatory disease

CXCR7 functions as a scavenger for CXCL12 and CXCL11

Background: CXCR7 (RDC1), the recently discovered second receptor for CXCL12, is phylogenetically closely related to chemokine receptors, but fails to couple to G-proteins and to induce typical chemokine receptor mediated cellular responses. The function of CXCR7 is controversial. Some studies suggest a signaling activity in mammalian cells and zebrafish embryos, while others indicate a decoy activity in fish. Here we investigated the two propositions in human tissues. Methodology/Principal Findings: We provide evidence and mechanistic insight that CXCR7 acts as specific scavenger for CXCL12 and CXCL11 mediating effective ligand internalization and targeting of the chemokine cargo for degradation. Consistently, CXCR7 continuously cycles between the plasma membrane and intracellular compartments in the absence and presence of ligand, both in mammalian cells and in zebrafish. In accordance with the proposed activity as a scavenger receptor CXCR7-dependent chemokine degradation does not become saturated with increasing ligand concentrations. Active CXCL12 sequestration by CXCR7 is demonstrated in adult mouse heart valves and human umbilical vein endothelium. Conclusions/Significance: The finding that CXCR7 specifically scavenges CXCL12 suggests a critical function of the receptor in modulating the activity of the ubiquitously expressed CXCR4 in development and tumor formation. Scavenger activity of CXCR7 might also be important for the fine tuning of the mobility of hematopoietic cells in the bone marrow and lymphoid organs