Staphylococcus aureus proteins Sbi and Efb recruit human plasmin to degrade complement C3 and C3b

Upon host infection, the human pathogenic microbe Staphylococcus aureus (S. aureus) immediately faces innate immune reactions such as the activated complement system. Here, a novel innate immune evasion strategy of S. aureus is described. The staphylococcal proteins surface immunoglobulin-binding protein (Sbi) and extracellular fibrinogen-binding protein (Efb) bind C3/C3b simultaneously with plasminogen. Bound plasminogen is converted by bacterial activator staphylokinase or by host-specific urokinase-type plasminogen activator to plasmin, which in turn leads to degradation of complement C3 and C3b. Efb and to a lesser extend Sbi enhance plasmin cleavage of C3/C3b, an effect which is explained by a conformational change in C3/C3b induced by Sbi and Efb. Furthermore, bound plasmin also degrades C3a, which exerts anaphylatoxic and antimicrobial activities. Thus, S. aureus Sbi and Efb comprise platforms to recruit plasmin(ogen) together with C3 and its activation product C3b for efficient degradation of these complement components in the local microbial environment and to protect S. aureus from host innate immune reactions

E+E-Projekt „Integration von Naturschutzzielen in den Ökologischen Landbau am Beispiel der Hessischen Staatsdomäne Frankenhausen“ - Maßnahmen in der bewirtschafteten Fläche

On the Hessian state domain Frankenhausen near Kassel the project “The Integration of Nature Conservation into Organic Farming” (supported by the German Federal Agency for Nature Conservation with funds of the Federal Environmental Ministry) aims to support biodiversity not only by restoring biotopes on the farmland. The focus lies on measures to enhance the diversity on the arable land and the pastures of the farm. A participatory approach is striven for, in which the scientists and planners take the role of a companion catalyst or moderator

Stochastic Hydrodynamics of Complex Fluids: Discretisation and Entropy Production

Many complex fluids can be described by continuum hydrodynamic field equations, to which noise must be added in order to capture thermal fluctuations. In almost all cases, the resulting coarse-grained stochastic partial differential equations carry a short-scale cutoff, which is also reflected in numerical discretisation schemes. We draw together our recent findings concerning the construction of such schemes and the interpretation of their continuum limits, focusing, for simplicity, on models with a purely diffusive scalar field, such as ‘Model B’ which describes phase separation in binary fluid mixtures. We address the requirement that the steady-state entropy production rate (EPR) must vanish for any stochastic hydrodynamic model in a thermal equilibrium. Only if this is achieved can the given discretisation scheme be relied upon to correctly calculate the nonvanishing EPR for ‘active field theories’ in which new terms are deliberately added to the fluctuating hydrodynamic equations that break detailed balance. To compute the correct probabilities of forward and time-reversed paths (whose ratio determines the EPR), we must make a careful treatment of so-called ‘spurious drift’ and other closely related terms that depend on the discretisation scheme. We show that such subtleties can arise not only in the temporal discretisation (as is well documented for stochastic ODEs with multiplicative noise) but also from spatial discretisation, even when noise is additive, as most active field theories assume. We then review how such noise can become multiplicative via off-diagonal couplings to additional fields that thermodynamically encode the underlying chemical processes responsible for activity. In this case, the spurious drift terms need careful accounting, not just to evaluate correctly the EPR but also to numerically implement the Langevin dynamics itself

Stochastic Hydrodynamics of Complex Fluids: Discretisation and Entropy Production.

Many complex fluids can be described by continuum hydrodynamic field equations, to which noise must be added in order to capture thermal fluctuations. In almost all cases, the resulting coarse-grained stochastic partial differential equations carry a short-scale cutoff, which is also reflected in numerical discretisation schemes. We draw together our recent findings concerning the construction of such schemes and the interpretation of their continuum limits, focusing, for simplicity, on models with a purely diffusive scalar field, such as 'Model B' which describes phase separation in binary fluid mixtures. We address the requirement that the steady-state entropy production rate (EPR) must vanish for any stochastic hydrodynamic model in a thermal equilibrium. Only if this is achieved can the given discretisation scheme be relied upon to correctly calculate the nonvanishing EPR for 'active field theories' in which new terms are deliberately added to the fluctuating hydrodynamic equations that break detailed balance. To compute the correct probabilities of forward and time-reversed paths (whose ratio determines the EPR), we must make a careful treatment of so-called 'spurious drift' and other closely related terms that depend on the discretisation scheme. We show that such subtleties can arise not only in the temporal discretisation (as is well documented for stochastic ODEs with multiplicative noise) but also from spatial discretisation, even when noise is additive, as most active field theories assume. We then review how such noise can become multiplicative via off-diagonal couplings to additional fields that thermodynamically encode the underlying chemical processes responsible for activity. In this case, the spurious drift terms need careful accounting, not just to evaluate correctly the EPR but also to numerically implement the Langevin dynamics itself

Insights into the structure-function relationships of dimeric C3d fragments

Cleavage of C3 to C3a and C3b plays a central role in the generation of complement-mediated defences. Although the thioester-mediated surface deposition of C3b has been well-studied, fluid phase dimers of C3 fragments remain largely unexplored. Here we show C3 cleavage results in the spontaneous formation of C3b dimers and present the first X-ray crystal structure of a disulphide-linked human C3d dimer. Binding studies reveal these dimers are capable of crosslinking complement receptor 2 and preliminary cell-based analyses suggest they could modulate B cell activation to influence tolerogenic pathways. Altogether, insights into the physiologically-relevant functions of C3d(g) dimers gained from our findings will pave the way to enhancing our understanding surrounding the importance of complement in the fluid phase and could inform the design of novel therapies for immune system disorders in the future

Why are the 2-oxoacid dehydrogenase complexes so large? Generation of an active trimeric complex

The four-component polypeptides of the 2-oxoacid dehydrogenase complex from the thermophilic archaeon Thermoplasma acidophilum assemble to give an active multienzyme complex possessing activity with the branched-chain 2-oxoacids derived from leucine, isoleucine and valine, and with pyruvate. The dihydrolipoyl acyl-transferase (E2) core of the complex is composed of identical trimer-forming units that assemble into a novel 42-mer structure comprising octahedral and icosahedral geometric aspects. From our previously determined structure of this catalytic core, the inter-trimer interactions involve a tyrosine residue near the C-terminus secured in a hydrophobic pocket of an adjacent trimer like a ball-and-socket joint. In the present study, we have deleted the five C-terminal amino acids of the E2 polypeptide (IIYEI) and shown by equilibrium centrifugation that it now only assembles into a trimeric enzyme. This was confirmed by SAXS analysis, although this technique showed the presence of approximately 20% hexamers. The crystal structure of the trimeric truncated E2 core has been determined and shown to be virtually identical with the ones observed in the 42-mer, demonstrating that removal of the C-terminal anchor does not significantly affect the individual monomer or trimer structures. The truncated E2 is still able to bind both 2-oxoacid decarboxylase (E1) and dihydrolipoamide dehydrogenase (E3) components to give an active complex with catalytic activity similar to the native multienzyme complex. This is the first report of an active mini-complex for this enzyme, and raises the question of why all 2-oxoacid dehydrogenase complexes assemble into such large structures.</jats:p

Nachgefragt: 25 Antworten zum Stand des Wissens rund um Öko-Landbau und Bio-Lebensmittel

Die Broschüre „Nachgefragt: 25 Antworten zum Stand des Wissens rund um Öko-Landbau und Bio-Lebensmittel“ wurde 2006 in Kooperation mit externen Experten ausgearbeitet, in zwei Auflagen gedruckt und 2008 durch 3 Fragen ergänzt, die derzeit nur Online verfügbar sind. Die erste Auflage mit 5.000 Stück hat der BÖLW kostenlos an Multiplikatoren verschickt. Die zweite Auflage – ebenfalls in einer Auflage von 5.000 Exemplaren gedruckt – wurde zu den Kosten für Druck und Versand verkauft. Der Argumentationsleitfaden ist nahezu vergriffen. Hauptabnehmer waren Verbände und Wirtschaft. So fragten den Leitfaden beispielsweise viele Einzelhändler und Einzelhandelsketten für die Schulung ihres Verkaufspersonals nach. Für Journalisten und Politiker ist der Argumentationsleitfaden eine prägnante Einführung in aktuelle Fragen der Ökologischen Lebensmittelwirtschaft und übersichtliches Nachschlagewerk. Gerade in der Politik kann damit Verständnis für die Leistungen und die Bedeutung des Ökologischen Landbaus erreicht werden. Auch viele Privatpersonen haben den Leitfaden bestellt, um sich fundiert über die Ökologische Landwirtschaft zu informieren. Der Argumentationsleitfaden hat eine Lücke bei den Informationsmaterialien und Nachschlagewerken zur Ökologischen Lebensmittelwirtschaft geschlossen. Dazu und zu der inhaltlichen Aufarbeitung der Themen haben wir sehr gute Resonanzen erhalten und sind davon überzeugt, dass auch eine Neuauflage gut angenommen würde. Der Leitfaden ist bereits in der kurzen Zeit seit der Erstauflage ein Grundlagenwerk zum Ökologischen Landbau geworden, sodass Aktualität gewährleistet werden muss. Zentrales Qualitätsmerkmal eines Argumentationsleitfadens ist seine Aktualität. Besonderes Merkmal des Argumentationsleitfadens ist, dass er kurze prägnante Antworten auf zentrale Fragen zur Ökologischen Lebensmittelwirtschaft gibt und dabei den aktuellen Stand des Wissens zur Grundlage hat. Einerseits hat sich seit der Erstauflage die gesetzliche Grundlage für die Bio-Branche wesentlich verändert, da die EU-Öko-Verordnung einer Totalrevision unterzogen wurde. Andererseits wurden seither zahlreiche neue wissenschaftliche Studien veröffentlicht – insbesondere auch im Rahmen des Bundesprogramms Ökologischer Landbau – die bei der Fragenbeantwortung im Leitfaden berücksichtigt werden müssten. Aus diesen Gründen ist es unerlässlich, den Leitfaden inhaltlich gründlich zu überarbeiten und neu aufzulegen, damit seine bisherige erfolgreiche Leistung weiter zur Verfügung stehen kann. Ziel des Projektes ist daher die Überarbeitung und Veröffentlichung einer 4. Auflage des Argumentationsleitfadens, der Antworten auf grundlegende und besonders kritische Fragen zum ökologischen Landbau gibt. Auf einen Blick wird Wissen verfügbar gemacht, das über das allgemeine Grundlagenwissen zum Ökologischen Landbau hinaus geht und auf aktuellsten wissenschaftlichen Erkenntnissen beruht. Der neue Argumentationsleitfaden soll sowohl in elektronischer, als auch in gedruckter Form der Zielgruppe zugänglich gemacht werden. Wie die zweite Auflage soll auch diese der Zielgruppe zu einem Preis, der Druck und Versand abdeckt, zu Verfügung gestellt werden, so dass veraltete Exemplare ausgetauscht werden können. Für Journalisten und Politiker soll der Argumentationsleitfaden kostenlos zur Verfügung gestellt werden

Potential effects of warmer worms and vectors on onchocerciasis transmission in West Africa

Development times of eggs, larvae and pupae of vectors of onchocerciasis (Simulium spp.) and of Onchocerca volvulus larvae within the adult females of the vectors decrease with increasing temperature. At and above 25C,the parasite could reach its infective stage in less than 7 days when vectors could transmit after only two gonotrophic cycles. After incorporating exponential functions for vector development into a novel blackfly population model, it was predicted that fly numbers in Liberia and Ghana would peak at air temperatures of 29C and 34C, about 3C and 7C above current monthly averages, respectively; parous rates of forest flies (Liberia) would peak at 298C and of savannah flies (Ghana) at 308C. Small temperature increases (less than 28C) might lead to changes in geographical distributions of different vector taxa. When the new model was linked to an existing framework for the population dynamics of onchocerciasis in humans and vectors, transmission rates and worm loads were projected to increase with temperature to at least 338C. By contrast, analyses of field data on forest flies in Liberia and savannah flies in Ghana, in relation to regional climate change predictions, suggested, on the basis of simple regressions, that 13–41% decreases in fly numbers would be expected between the present and before 2040. Further research is needed to reconcile these conflicting conclusions