The well-established relative resistance to malaria observed in the Fulani as compared with other sympatric tribes in West Africa has been attributed to their higher levels of serum immunoglobulin (Ig) G antibodies to malarial antigens. In this study, we confirm and extend the previous findings by analyses of the levels of IgM, IgG and IgG subclasses of anti-malarial antibodies in asymptomatic individuals of different sympatric tribes in Burkina Faso (Fulani/Mossi) and Mali (Fulani/Dogon). The Fulani showed significantly higher median concentrations of anti-malarial IgG and IgM antibodies than the sympatric tribes at both locations. Although the overall subclass pattern of antibodies did not differ between the tribes, with IgG1 and IgG3 as dominant, the Fulani showed consistently significantly higher levels of these subclasses as compared with those of the non-Fulani individuals. No significant differences were seen in the levels of total IgG between the tribes, but the Fulani showed significantly higher levels of total IgM than their neighbours in both countries. While the antibody levels to some nonmalarial antigens showed the same pattern of differences seen for antibody levels to malaria antigens, no significant such differences were seen with antibodies to other nonmalarial antigens. In conclusion, our results show that the Fulani in two different countries show higher levels of anti-malarial antibodies than sympatric tribes, and this appears not to be a reflection of a general hyper-reactivity in the Fulani.
Antibody-mediated inhibition of Plasmodium falciparum parasites in vitro reflects the potential parasiteneutralizing activity of the antibodies in vivo. In this study, immunoglobulins and P. falciparum isolates were collected from children with asymptomatic malaria in Burkina Faso. We demonstrate a significantly lower in vitro growth inhibitory activity against the P. falciparum field isolates by autologous host immunoglobulin compared with that of immunoglobulin from other individuals. To gain further insight to possible mechanisms for the diverse sensitivity observed, analyses of consecutive isolates taken 14 days apart were performed with regard to polymerase chain reactionbased genotyping and sensitivity to growth inhibition in vitro. All the asymptomatic infections were composed of multiple, genotypically distinct parasite clones, and at least one new parasite clone appeared in most of the day 14 isolates compared with the corresponding day 0 isolates. Apparently persisting parasite clones, present in both the day 0 and day 14 isolates from the same person, were also frequently observed. The day 14 isolates were more effectively inhibited by autologous day 14 immunoglobulin than by the corresponding day 0 immunoglobulin in 57% of the cases. However, the frequent presence of persisting parasite clones in asymptomatic children indicates that the parasite may develop a relative resistance to neutralizing immune responses.
Multiple sequence alignments can be used in the template-based modelling of protein structures to build fragment-based assembly models. Therefore, useful functional information on the 3D structure of the anti-MCF-7 scFv protein can be obtained using available bioinformatics tools. This paper utilises several commonly-used bioinformatics tools and databases, including BLAST (Basic Local Alignment Search Tool), GenBank, PDB (Protein Data Bank), KABAT numbering and SWISS-MODEL, to gain specific functional insights into the anti-MCF-7 scFv protein and the assembly of single-chain fragment variable (scFv) antibodies, which consist of a variable heavy chain (VH) and a variable light chain (VL) connected by the linker (Gly 4-Ser) 3. The linker has been built as a loop structure using the Insight II software. The accuracy of the loop structure has been evaluated using Root Mean Square Deviation (RMSD). The accuracies of the VL and VH template-based structures are enhanced by using the evaluation methods Verify3D, ERRAT and Ramchandran plotting, which measure the error in the residues. In the results, 100% of the light-chain residues scored above 0.2, whereas 88.5% of the heavychain residues' scored above 0.15 in the Verify3D evaluation method. Meanwhile, using ERRAT, the alignments of both chains scored more than 70% in space. Additionally, the Ramchandran plot evaluation method showed large numbers of residues in the favoured areas in both chains; these findings demonstrated that all of the chosen templates were the best candidates.
Background: Deep venous thrombosis (DVT) can lead to a serious fatal pulmonary embolism. Many genetic risk factors may predispose to DVT; one of these is the mutation in the PROCR gene responsible for the production of endothelial protein C receptor (EPCR), which plays an important role in activation of protein C (PC). The objective of the present study was to examine the association between the rs867186 and rs9574 polymorphism in the PROCR gene and the occurrence of DVT in Sudanese individuals. Methods: A total of 100 Sudanese DVT patients and 100 apparently healthy individuals were recruited for this study. Ethylene diamine tetraacetic acie (EDTA)-anticoagulated blood samples were collected from all participants. Genomic DNA was extracted and PROCR gene product was amplified by a standard ploymerase chain reaction (PCR) reaction. PCR products were sequenced to identify PROCR gene polymorphisms. Results: The frequency of mutated allele of rs867186 was significantly higher in the DVT patient (41%) than in healthy control (21%). The presence of mutated allele of rs867486 increases the risk of DVT 3 folds. There was no significant difference in the frequency of mutated allele of rs9574 polymorphism between the DVT patients and the healthy control subjects. Further, it does not show an increase in the risk of DVT. The adjustment of gender, ethnic group, and body mass index (BMI) does not change the significance of each single nucleotide polymorphism (SNP) as a risk factor for DVT. Conclusion: It can be concluded that Sudanese individuals carrying the mutated allele rs867186 polymorphism were at risk to develop DVT, while the mutated allele of rs9574 polymorphism is not a risk factor for DVT in Sudanese individuals.
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