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Contains fulltext : 202685.pdf (publisher's version ) (Open Access), Mutations in the gene encoding for complement regulator factor H (FH) severely disrupt its normal function to protect human cells from unwanted complement activation, resulting in diseases such as atypical hemolytic uremic syndrome (aHUS). aHUS presents with severe hemolytic anemia, thrombocytopenia, and renal disease, leading to end-stage renal failure. Treatment of severe complement-mediated disease, such as aHUS, by inhibiting the terminal complement pathway, has proven to be successful but at the same time fails to preserve the protective role of complement against pathogens. To improve complement regulation on human cells without interfering with antimicrobial activity, we identified an anti-FH monoclonal antibody (mAb) that induced increased FH-mediated protection of primary human endothelial cells from complement, while preserving the complement-mediated killing of bacteria. Moreover, this FH-activating mAb restored complement regulation in sera from aHUS patients carrying various heterozygous mutations in FH known to impair FH function and dysregulate complement activation. Our data suggest that FH normally circulates in a less active conformation and can become more active, allowing enhanced complement regulation on human cells. Antibody-mediated potentiation of FH may serve as a highly effective approach to inhibit unwanted complement activation on human cells in a wide range of hematological diseases while preserving the protective role of complement against pathogens.

Contains fulltext : 202685.pdf (publisher's version ) (Open Access), Mutations in the gene encoding for complement regulator factor H (FH) severely disrupt its normal function to protect human cells from unwanted complement activation, resulting in diseases such as atypical hemolytic uremic syndrome (aHUS). aHUS presents with severe hemolytic anemia, thrombocytopenia, and renal disease, leading to end-stage renal failure. Treatment of severe complement-mediated disease, such as aHUS, by inhibiting the terminal complement pathway, has proven to be successful but at the same time fails to preserve the protective role of complement against pathogens. To improve complement regulation on human cells without interfering with antimicrobial activity, we identified an anti-FH monoclonal antibody (mAb) that induced increased FH-mediated protection of primary human endothelial cells from complement, while preserving the complement-mediated killing of bacteria. Moreover, this FH-activating mAb restored complement regulation in sera from aHUS patients carrying various heterozygous mutations in FH known to impair FH function and dysregulate complement activation. Our data suggest that FH normally circulates in a less active conformation and can become more active, allowing enhanced complement regulation on human cells. Antibody-mediated potentiation of FH may serve as a highly effective approach to inhibit unwanted complement activation on human cells in a wide range of hematological diseases while preserving the protective role of complement against pathogens.

This research is set to discover to what extend youth language in advertising effects the attractiveness, appraisal and persuasiveness of an advertisement. One must conclude that youth language should not be used in advertising. Common language is perceived as more attractive, understandable, target minded and appropriate. The sender of the text with common language is also perceived as more trustworthy, less obtrusive and less artificial. Dit onderzoek richt zich op de vraag in hoeverre jongerentaal in reclame effect heeft op de aantrekkelijkheid, waardering en overtuigingskracht van een reclame. Er kan worden geconcludeerd dat jongerentaal niet gebruikt moet worden in reclames. Gangbaar taalgebruik wordt namelijk aantrekkelijker, begrijpelijker, meer doelgroepgericht en gepast gevonden. De zender van de tekst met gangbaar taalgebruik wordt ook gezien als betrouwbaarder, minder opdringerig en minder gemaakt.

This research is set to discover to what extend youth language in advertising effects the attractiveness, appraisal and persuasiveness of an advertisement. One must conclude that youth language should not be used in advertising. Common language is perceived as more attractive, understandable, target minded and appropriate. The sender of the text with common language is also perceived as more trustworthy, less obtrusive and less artificial. Dit onderzoek richt zich op de vraag in hoeverre jongerentaal in reclame effect heeft op de aantrekkelijkheid, waardering en overtuigingskracht van een reclame. Er kan worden geconcludeerd dat jongerentaal niet gebruikt moet worden in reclames. Gangbaar taalgebruik wordt namelijk aantrekkelijker, begrijpelijker, meer doelgroepgericht en gepast gevonden. De zender van de tekst met gangbaar taalgebruik wordt ook gezien als betrouwbaarder, minder opdringerig en minder gemaakt.