Vaccination with Recombinant Aspartic Hemoglobinase Reduces Parasite Load and Blood Loss after Hookworm Infection in Dogs

BACKGROUND: Hookworms infect 730 million people in developing countries where they are a leading cause of intestinal blood loss and iron-deficiency anemia. At the site of attachment to the host, adult hookworms ingest blood and lyse the erythrocytes to release hemoglobin. The parasites subsequently digest hemoglobin in their intestines using a cascade of proteolysis that begins with the Ancylostoma caninum aspartic protease 1, APR-1. METHODS AND FINDINGS: We show that vaccination of dogs with recombinant Ac-APR-1 induced antibody and cellular responses and resulted in significantly reduced hookworm burdens (p = 0.056) and fecal egg counts (p = 0.018) in vaccinated dogs compared to control dogs after challenge with infective larvae of A. caninum. Most importantly, vaccinated dogs were protected against blood loss (p = 0.049) and most did not develop anemia, the major pathologic sequela of hookworm disease. IgG from vaccinated animals decreased the catalytic activity of the recombinant enzyme in vitro and the antibody bound in situ to the intestines of worms recovered from vaccinated dogs, implying that the vaccine interferes with the parasite's ability to digest blood. CONCLUSION: To the best of our knowledge, this is the first report of a recombinant vaccine from a hematophagous parasite that significantly reduces both parasite load and blood loss, and it supports the development of APR-1 as a human hookworm vaccine

Frequency, efficiency and flexibility of indirect addition in two learning environments

This study examined the development of indirect addition as an alternative for solving multidigit subtractions, by means of two learning environments in traditionally schooled third-graders in Flanders (Belgium). Thirty-five third-graders, who did not demonstrate mastery of indirect addition, participated in an Explicit (n = 20) or Implicit (n = 15) learning environment that aimed to encourage the development of indirect addition. Over a period of six weeks, children participated in nine individual sessions: four practice sessions, three test sessions, one transfer session, and one retention session. The results revealed that throughout the study indirect addition was rarely used, even by the children in the explicit learning environment. However, when indirect addition was used, it was executed very efficiently. (C) 2009 Elsevier Ltd. All rights reserved.status: publishe

Solving subtraction problems by means of indirect addition

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‘Computer’ and ‘information and communication technology’: Students’ culture specific interpretations

Given the use of information and communication technology (ICT) and computer as synonyms in ICTintegration research on the one hand, and the potential problems in doing so on the other, this contribution tries to gain insight in the understanding of the words computer and ICT in different settings. In five different countries (Belgium, Finland, Germany, Ghana and South-Africa) participants engaged in a word-association study. Each study addressed the following research question “Can the notion ‘computer’ be used as a proxy for the notion ‘information and communication technology’? A word-association task with ‘computer’ and ‘information and communication technology’ as stimuli words was used in the different studies. Data gathering methods followed the same basic principles but were adopted to diverse contexts of study. In order to analyse the data a shared classification scheme was developed. A chi square test was used to check the similarities and dissimilarities of the categories. In the results, while similar associations are generated by the two stimulus words, it is also clear that computer has a more technical connotation and ICT a broader, more communicationoriented connotation. Different findings in the different cultural settings constitute a warning for naïve use of culture-specific research instruments.status: publishe

Coagulation factor Xa cleaves protease-activated receptor-1 and mediates signaling dependent on binding to the endothelial protein C receptor

BACKGROUND AND OBJECTIVE: Coagulation is intrinsically tied to inflammation, and both proinflammatory and anti-inflammatory responses are modulated by coagulation protease signaling through protease-activated receptor-1 (PAR1). Activated factor X (FXa) can elicit cellular signaling through PAR1, but little is known about the role of cofactors in this pathway. Endothelial protein C receptor (EPCR) supports PAR1 signaling by the protein C pathway, and in the present study we tested whether EPCR mediates surface recruitment and signaling of FXa. METHODS AND RESULTS: Here, we show that FXa binds to overexpressed as well as native endothelial EPCR. PAR1 cleavage by FXa as analyzed with conformation-sensitive antibodies and a tagged PAR1 reporter construct was strongly enhanced if EPCR was available. Anti-EPCR failed to affect the tissue factor-dependent activation of FX, but high concentrations of FXa decreased EPCR-dependent protein C activation. Most importantly, the FXa-mediated induction of Erk1/2 activation, expression of the transcript for connective tissue growth factor and barrier protection in endothelial cells required binding to EPCR. CONCLUSIONS: Our results demonstrate that EPCR plays an unexpected role in supporting cell surface recruitment, PAR1 activation, and signaling by FXa