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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A serological investigation by a repeat cross-sectional survey was conducted in Thar desert (Rajasthan) during and after one year of malaria outbreak to determine malaria endemicity using ELISA as a tool. The assay was based on indirect ELISA to measure antibody levels against a nonapeptide R1 (EENVEHDA-cys) derived from Pf 155/Resa and Plasmodium falciparum crude antigen. Finger prick blood samples were collected from individuals belonging to all age groups. Sera were tested at already standardized optimum dilution to detect antigen specific immunoglobulin isotype. The mean ELISA O.D. values 0.153 for anti R1 peptide and 0.162 for anti Pf antigen reflected the seronegative profile, when the focal malaria outbreak occurred in 1994. A substantial increase in antibody levels was detected in individuals after one year showing mean ELISA values for anti-R1 and anti-Pf antigens as 0.52 and 0.58 and seropositivity as 75.2% and 52% respectively. Data obtained from the present study indicate that serological survey could be done to assess the situation in case of reappearing or disappearing status of malaria in a defined population.
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PMID:Serological investigation of malaria outbreak in Thar desert of Rajasthan. 1119 97

Plasmodium falciparum, the human malaria parasite, is evolutionarily distant from other eukaryotes. Genome-wide analyses of transcription-associated proteins have revealed a relative paucity of putative regulatory transcription factors and an abundance of putative chromatin remodeling machinery, suggesting that this parasite has a transcription regulatory system that is distinct from those of other eukaryotes. Here, we have analyzed transcriptional regulation of the peroxiredoxin genes, pf1-cys-prx and pftpx-1, which show different expression patterns in P. falciparum. The reporter assays revealed the presence of putative enhancers in the 5' regions of these genes. Although pf1-cys-prx shows trophozoite/schizont stage-specific transcription, a putative cis-acting enhancer sequence in pf1-cys-prx was constitutively active when inserted into the 5' region of pftpx-1. Electrophoretic mobility shift and DNase I footprinting assays showed that this enhancer region is the target of trophozoite/schizont stage-specific DNA binding proteins. In addition, chromatin immunoprecipitation assays showed that the increased levels of histone acetylation in the 5' region of pf1-cys-prx and pftpx-1 correlate with the transcriptional activity of these genes. Recruitment of PfGCN5 histone acetyltransferase to the pf1-cys-prx enhancer in trophozoite/schizont stage was observed. These results suggest that P. falciparum possesses a sophisticated system of transcriptional regulation during intraerythrocytic stages that is managed by coordinated interactions of unique cis-elements and trans-acting factors and chromatin modifications.
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PMID:5' sequence- and chromatin modification-dependent gene expression in Plasmodium falciparum erythrocytic stage. 1869 28

Nicotinic acetylcholine receptors (nAChRs) are the members of the cys-loop ligand-gated ion channel superfamily and are formed by five subunits arranged around a central ion channel. Each subunit is encoded by a separate gene and is classified as either alpha or non-alpha depending on the presence or absence, respectively, of two adjacent cysteine residues which are important for acetylcholine binding. Here, we report for the first time a single nAChR gene encoding both alpha and non-alpha subunits. Specifically, alternative splicing of the Anopheles gambiae nAChR subunit, previously called Agamalpha9 and renamed here Agamalphabeta9, generates two variants, one possessing the two cysteines (denoted Agamalphabeta9(alpha)) and the other lacking the cysteine doublet (Agamalphabeta9(beta)). Attempts to heterologously express functional nAChRs consisting of the Agamalphabeta9 splice variants in Xenopus laevis oocytes were unsuccessful. Our findings further characterise a potential target to control the malaria mosquito as well as provide insights into the diversification of nAChRs.
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PMID:Alternative splicing of the Anopheles gambiae nicotinic acetylcholine receptor, Agamalphabeta9, generates both alpha and beta subunits. 1966 15

A number of cysteine proteases of malaria parasites have been described and many more are suggested by analysis of the Plasmodium falciparum genome sequence. The best characterized of these proteases are the falcipains, a family of four papain-family enzymes. Falcipain-2 and falcipain-3 act in concert with other proteases to hydrolyze host erythrocyte hemoglobin in the parasite food vacuole. Disruption of the falcipain-2 gene led to a transient block in hemoglobin hydrolysis and parasites with increased sensitivity to protease inhibitors. Disruption of the falcipain-3 gene was not possible, strongly suggesting that this protease is essential for erythrocytic parasites. Disruption of the falcipain-1 gene did not alter development in erythrocytes, but led to decreased production of oocysts in mosquitoes. other papain-family proteases predicted by the genome sequence include dipeptidyl peptidases, a calpain homolog and serine-repeat antigens (SERAs). Dipeptidyl aminopeptidase 1 appears to be essential and localized to the food vacuole, suggesting a role in hemoglobin hydrolysis. Dipeptidyl aminopeptidase 3 appears to play a role in the rupture of erythrocytes by mature parasites. the P. falciparum calpain homolog gene could not be disrupted, suggesting that the protein is essential and a role in the parasite cell cycle has been suggested. Nine P. falciparum SERAs have cysteine protease motifs, but in some the active site cys is replaced by a Ser. Gene disruption studies suggested that SERA-5 and SERA-6 are essential. activation of SERA-5 by a serine protease seems to be required for merozoite egress from the erythrocyte. New drugs for malaria are greatly needed and cysteine proteases represent potential drug targets. cysteine protease inhibitors have demonstrated potent antimalarial effects and the optimization and testing of falcipain inhibitor antimalarials is underway.
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PMID:Falcipains and other cysteine proteases of malaria parasites. 2166 Jun 57

The genomes of Plasmodium parasites that cause malaria in humans, other primates, birds, and rodents all encode multiple 6-cys proteins. Distinct 6-cys protein family members reside on the surface at each extracellular life cycle stage and those on the surface of liver infective and sexual stages have been shown to play important roles in hepatocyte growth and fertilization respectively. However, 6-cys proteins associated with the blood-stage forms of the parasite have no known function. Here we investigate the biochemical nature and function of two blood-stage 6-cys proteins in Plasmodium falciparum, the most pathogenic species to afflict humans. We show that native P12 and P41 form a stable heterodimer on the infective merozoite surface and are secreted following invasion, but could find no evidence that this complex mediates erythrocyte-receptor binding. That P12 and P41 do not appear to have a major role as adhesins to erythrocyte receptors was supported by the observation that antisera to these proteins did not substantially inhibit erythrocyte invasion. To investigate other functional roles for these proteins their genes were successfully disrupted in P. falciparum, however P12 and P41 knockout parasites grew at normal rates in vitro and displayed no other obvious phenotypic changes. It now appears likely that these blood-stage 6-cys proteins operate as a pair and play redundant roles either in erythrocyte invasion or in host-immune interactions.
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PMID:Biochemical and functional analysis of two Plasmodium falciparum blood-stage 6-cys proteins: P12 and P41. 2284 65

The mechanisms of stage-specific gene regulation in the malaria parasite Plasmodium falciparum are largely unclear, with only a small number of specific regulatory transcription factors (AP2 family) having been identified. In particular, the transcription factors that function in the intraerythrocytic stage remain to be elucidated. Previously, as a model case for stage-specific transcription in the P. falciparum intraerythrocytic stage, we analyzed the transcriptional regulation of pf1-cys-prx, a trophozoite/schizont-specific gene, and suggested that some nuclear factors bind specifically to the cis-element of pf1-cys-prx and enhance transcription. In the present study, we purified nuclear factors from parasite nuclear extract by 5 steps of chromatography, and identified a factor termed PREBP. PREBP is not included in the AP2 family, and is a novel protein with four K-homology (KH) domains. The KH domain is known to be found in RNA-binding or single-stranded DNA-binding proteins. PREBP is well conserved in Plasmodium species and partially conserved in phylum Apicomplexa. To evaluate the effects of PREBP overexpression, we used a transient overexpression and luciferase assay combined approach. Overexpression of PREBP markedly enhanced luciferase expression under the control of the pf1-cys-prx cis-element. These results provide the first evidence of a novel transcription factor that activates the gene expression in the malaria parasite intraerythrocytic stage. These findings enhance our understanding of the evolution of specific transcription machinery in Plasmodium and other eukaryotes.
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PMID:Identification of a novel and unique transcription factor in the intraerythrocytic stage of Plasmodium falciparum. 2404 Mar 27