Novel evasion strategies of Staphylococcus aureus against the human innate immune response

There is an ongoing competition between the human host and pathogenic microbes. The immune system, especially the immediately acting innate response, recognizes pathogens, prevents their spreading, and eliminates them. By contrast, certain microbes have developed sophisticated strategies to evade and suppress the host immune response. This thesis focuses on the functions of the plasma proteins apolipoprotein E (apoE)and plasmin in the interactions between the human host and the pathogen Staphylococcus aureus. Here, it is shown that antimicrobial peptides (AMPs) were generated from apoE upon cleavage by neutrophil elastase. The bactericidal activity was located to the heparin-binding site of the LDL-receptor-binding domain of apoE (SHL14). Full-length apoE had no antibacterial, but opsonic activity. Additionally, a new function of plasmin is reported. The serine protease degraded the AMPs C3a and SHL14. Thereby plasmin terminated bactericidal activity and may facilitate clearance of no longer needed effector molecules. Plasminogen, the precursor of plasmin, is bound by S. aureus. Here, a novel type of plasminogen-binding proteins, unique for S. aureus, is shown. Sbi and Efb recruited plasminogen together with the complement component C3. Plasminogen, fixed in these complexes, remained accessible to its activators uPa and staphylokinase. In the presence of Sbi or Efb, plasmin-mediated degradation of C3(C3b) was accelerated, likely due to conformational changes in C3(C3b). Thus, S. aureus efficiently inactivates complement activity. Plasmin and the metalloprotease aureolysin were also used by S. aureus to degrade the AMP SHL14 and inactivate the anti-opsonic activity of apoE. Taken together, apoE and plasmin have different functions in the interactions between host and pathogen. ApoE is part of the immune response against S. aureus and thus degraded by the pathogen. By contrast, plasmin restricts immune reactions and its activity is therefore exploited by S. aureus

Storytelling with UK Centenarians: Being a hundred - it’s just luck

What is it like to have lived one hundred years? In the opinion of those who are active and well, what has contributed to their longevity? If asked to tell a story about being 100 years old what would they talk about? In 2010 we interviewed 16 UK centenarians. We travelled to Scotland, Northern Ireland, Wales and England to interview participants in their own homes. We (Koch, Smith, Hutnik and Turner) asked centenarians to tell us their story. We heard about celebrating their 100th birthday with friends and family. We heard that there were 100 balloons or 100 roses or 100 reasons to continue partying into the future. Many chose to talk about aspects of their life that were foremost in their minds. Each person was given space to retell, using their own words, something about themselves and the social context that had shaped their lives. Interviews often included interested friends or relatives. Their accounts ran to several thousand words. Together these stories comprise a social history of ordinary lives lived during the 20th century and into the 21st. Let us introduce you to some of these remarkable older people

ECONOMICS OF VARIABLE RATE NEMATICIDE FOR SUGAR BEETS

The benefit of applying fumigant for control of the sugar beet nematode on a variable versus uniform rate basis is examined. Compared to fumigating an entire filed at a constant full-label rate, varialbe rate application provides a savings ranging from $31/ac (heavily infested field) to$69/ac (lightly infested field).Crop Production/Industries,

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

Vignetteninterview zur Erfassung des Sprachförderwissens pädagogischer Fachkräfte (VSW)

Die Autoren präsentieren ihr Vignetteninterview zur Erfassung von sprachförderdiagnostischem Wissen (VSW), mit dessen Hilfe das Sprachförderwissen pädagogischer Fachkräfte in Kitas in drei Bereichen (Diagnostik, Sprachfördertechniken, Kontext) erfasst werden kann. Es basiert auf einer Filmvignette, die eine dialogische Bilderbuchbetrachtung zwischen einer Fachkraft und einem Kind zeigt. Im leitfadengestützten Interview werden die pädagogischen Fachkräfte gebeten, Fragen zu den sprachlichen Kompetenzen des Kindes und den förderdiagnostischen Kompetenzen der Fachkraft im Video zu beantworten. (DIPF/Orig.