Abstract. The intercellular adhesion molecule-1 (ICAM-1) is thought to be a receptor that mediates binding of Plasmodium falciparum-infected erythrocytes. Especially in vital organs, the binding of parasitized cells to the endothelium via ICAM-1 may lead to severe disease and death. Recently, a mutation in the coding region of ICAM-1, termed ICAM-1 Kilifi , was described, causing a change from Lys to Met in the loop that interacts with rhinoviruses, lymphocytes, and parasitized red blood cells. Surprisingly, this mutation was shown to increase susceptibility of Kenyan children to severe malaria in one study. When we compared the distribution of ICAM-1 Kilifi in two groups of Gabonese children enrolled in a case-control, matched-pair study who presented with either mild or severe malaria, we found that 55% of the patients with mild malaria were carriers whereas only 39% of those with severe malaria were carriers. The difference in the distribution of ICAM-1 Kilifi homozygous pairs between the groups, as well as the distribution of ICAM-1 Kilifi carriers, was statistically highly significant (P ϭ 0.027 and P ϭ 0.012, by the McNemar test). In a group of healthy school children from the same region, a distribution of 52% ICAM-1 Kilifi carriers to 48%
A method that has been successfully used to generate recombinant Hansenula polymorpha strains by transformation with rDNA-targeting vectors was applied in the present study to a range of alternative yeast hosts, using vectors with an H. polymorpha-derived integration sequence. The dimorphic yeast Arxula adeninivorans, which is currently being assessed for heterologous gene expression, was the main focus of the study. As in H. polymorpha, it was possible to co-integrate more than a single plasmid carrying an expressible gene. Additionally, the vectors were examined in two further species, Pichia stipitis and Saccharomyces cerevisiae. Based on these results the design of a 'universal' fungal vector appears to be feasible.
The mannan-binding lectin (MBL) is a serum protein, which is involved in the immune defence against viruses, bacteria and parasites. Children who have mutations in the MBL gene that lead to a MBL deficiency are more susceptible to infectious diseases and are more likely to suffer from severe malaria. In this report we investigate the interaction between MBL and the proteins of red blood cells infected with the parasite Plasmodium falciparum. Protein extracts were separated on MBL-sepharose columns. After the elution of bound material, the proteins were detected either by Western blot with human antibodies, or radioactive labelling with 35S-methionine or 3H-glucosamine. MBL recognises proteins of P. falciparum-infected erythrocytes that are immunogenic in humans, parasite-derived and glycosylated. Whether the proteins identified in the different assays are identical remains to be explored. MBL added to in vitro cultures of P. falciparum, however, does not inhibit parasite growth. The positive effect of MBL in the blood of malaria patients could be caused by detoxification of parasite products.
An Arxula adeninivorans integration vector was applied to a range of alternative yeast species including Saccharomyces cerevisiae, Debaryomyces hansenii, Debaryomyces polymorphus, Hansenula polymorpha and Pichia pastoris. The vector harbours a conserved A. adeninivorans-derived 25S rDNA sequence for targeting, the A. adeninivorans-derived TEF1 promoter for expression control of the reporter sequence, and the Escherichia coli-derived hph gene conferring resistance against hygromycin B for selection of recombinants. Heterologous gene expression was assessed using a green fluorescent protein (GFP) reporter gene. The plasmid was found to be integrated into the genome of the various hosts tested; recombinant strains of all species exhibited heterologous gene expressions of a similar high level.
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