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Fairhurst RM Baruch DI Brittain NJ Ostera GR Wallach JS Hoang HL Hayton K Guindo A Makobongo MO Schwartz OM Tounkara A Doumbo OK Diallo DA Fujioka H Ho M Wellems TE 《Nature》2005,435(7045):1117-1121
Haemoglobin C, which carries a glutamate-to-lysine mutation in the beta-globin chain, protects West African children against Plasmodium falciparum malaria. Mechanisms of protection are not established for the heterozygous (haemoglobin AC) or homozygous (haemoglobin CC) states. Here we report a marked effect of haemoglobin C on the cell-surface properties of P. falciparum-infected erythrocytes involved in pathogenesis. Relative to parasite-infected normal erythrocytes (haemoglobin AA), parasitized AC and CC erythrocytes show reduced adhesion to endothelial monolayers expressing CD36 and intercellular adhesion molecule-1 (ICAM-1). They also show impaired rosetting interactions with non-parasitized erythrocytes, and reduced agglutination in the presence of pooled sera from malaria-immune adults. Abnormal cell-surface display of the main variable cytoadherence ligand, PfEMP-1 (P. falciparum erythrocyte membrane protein-1), correlates with these findings. The abnormalities in PfEMP-1 display are associated with markers of erythrocyte senescence, and are greater in CC than in AC erythrocytes. Haemoglobin C might protect against malaria by reducing PfEMP-1-mediated adherence of parasitized erythrocytes, thereby mitigating the effects of their sequestration in the microvasculature. 相似文献
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Summary The effects of various concentrations of ionized Ca were examined on the activity of rat brain tryptophan hydroxylase previously treated with EGTA. Within the range of ionized Ca-concentrations thought, to be physiologically important (10–8 to 10–5 M), no significant activation of the enzyme occurred, although activation was observed at higher concentrations of the metal. 相似文献
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The effects of various concentrations of ionized Ca were examined on the activity of rat brain tryptophan hydroxylase previously treated with EGTA. Within the range of ionized Ca-concentrations though to be physiologically important (10(-8) to 10(-5) M), no significant activation of the enzyme occurred, although activation was observed at higher concentrations of the metal. 相似文献
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Manske M Miotto O Campino S Auburn S Almagro-Garcia J Maslen G O'Brien J Djimde A Doumbo O Zongo I Ouedraogo JB Michon P Mueller I Siba P Nzila A Borrmann S Kiara SM Marsh K Jiang H Su XZ Amaratunga C Fairhurst R Socheat D Nosten F Imwong M White NJ Sanders M Anastasi E Alcock D Drury E Oyola S Quail MA Turner DJ Ruano-Rubio V Jyothi D Amenga-Etego L Hubbart C Jeffreys A Rowlands K Sutherland C Roper C Mangano V Modiano D Tan JC Ferdig MT Amambua-Ngwa A Conway DJ Takala-Harrison S Plowe CV 《Nature》2012,487(7407):375-379
Malaria elimination strategies require surveillance of the parasite population for genetic changes that demand a public health response, such as new forms of drug resistance. Here we describe methods for the large-scale analysis of genetic variation in Plasmodium falciparum by deep sequencing of parasite DNA obtained from the blood of patients with malaria, either directly or after short-term culture. Analysis of 86,158 exonic single nucleotide polymorphisms that passed genotyping quality control in 227 samples from Africa, Asia and Oceania provides genome-wide estimates of allele frequency distribution, population structure and linkage disequilibrium. By comparing the genetic diversity of individual infections with that of the local parasite population, we derive a metric of within-host diversity that is related to the level of inbreeding in the population. An open-access web application has been established for the exploration of regional differences in allele frequency and of highly differentiated loci in the P.?falciparum genome. 相似文献
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