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Query: UMLS:C0024530 (malaria)
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The calmodulin gene and its flanking sequences from the malaria parasite, Plasmodium falciparum, have been analysed. The structure of this gene is unique amongst other known calmodulin genes. It exists as a single copy on chromosome 14 and has a single intron. The nucleotide sequence of this 4-kb region suggests the existence of three transcriptional units, each separated by a highly A+T-rich sequence. Sequences controlling gene expression might be expected to occur in these intergenic regions. The predicted protein sequences suggest that these other genes are transcribed in different orientations. Primer extension studies suggest that calmodulin mRNA has a major start site 62 bases upstream of the initial ATG. The calmodulin gene possesses consensus eukaryotic TATA, CAAT box, polyadenylation and splice junction sequences. This is the first detailed report of the DNA sequence surrounding a housekeeping gene in P. falciparum.
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PMID:The structure of the calmodulin gene of Plasmodium falciparum. 185 74

The molecular karyotypes of four isolates of Plasmodium chabaudi, three of the subspecies P. chabaudi adami and one P. chabaudi chabaudi, as well as P. berghei and P. vinckei were studied by means of pulsed field gradient (PFG) gel electrophoresis. Each species appears to have 14 chromosomes, ranging in size from approximately 730 kb to greater than 2000 kb. The three P. chabaudi adami isolates did not appear any more similar to each other than to the P. c. chabaudi isolate. The chromosome locations of genes for a heat shock protein (hsp) 70, ribosomal RNA (rRNA), the precursor to the major merozoite surface proteins, dihydrofolate reductase and P. falciparum antigen 352 as well as four cloned DNA markers and a telomere probe were determined. However, a number of probes representing cloned P. falciparum antigens failed to hybridize to P. chabaudi DNA. Hence genes for malaria antigens appear to be much more divergent than genes for housekeeping functions.
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PMID:Molecular karyotyping of the rodent malarias Plasmodium chabaudi, Plasmodium berghei and Plasmodium vinckei. 265 17

Just over a year ago, the Occupational Safety and Health Administration (OSHA) issued the final bloodborne pathogens standard, "Occupational Exposure to Bloodborne Pathogens; Final Rule," which requires healthcare institutions to protect their employees from all occupational exposure to bloodborne pathogens." According to OSHA, the only criterion for applying the standard is the likelihood of exposure to blood and other potentially infectious materials (OPIMs). Thus, the standard is designed to protect all vulnerable personnel, from the clinical engineers who service contaminated equipment to the staff in clinical laboratories, patient care or treatment areas, and housekeeping and laundry services--any location where the nature of the work poses the risk of exposure to bloodborne pathogens. All department heads and employees must have access to the standard and should carefully review our analysis of the regulations and recommendations for implementing them, as presented in this special issue of Health Devices. The standard is aimed at protecting employees from occupational exposure to all bloodborne pathogens and, especially, to the human immunodeficiency virus (HIV) and the hepatitis B virus (HBV)--the most infamous pathogens transmitted through occupational exposure to blood and body fluids. Other bloodborne diseases referenced by OSHA in the preamble to the standard include arboviral infections, babesiosis, brucellosis, Creutzfeldt-Jakob disease, hepatitis C, human T-lymphotropic virus type I, leptospirosis, malaria, relapsing fever, syphilis, and viral hemorrhagic fever. In this issue, we provide a clinical overview of HIV and HBV and the diseases they cause, as well as a brief discussion of other bloodborne pathogens; an analysis of the most significant regulations affecting hospitals; and our recommendations for compliance. The recommendations presented in this article do not exhaust the possibilities for reducing exposure and complying with the standard. We invite you to communicate your ideas and practices regarding compliance issues to the ECRI-sponsored Center for Healthcare Environmental Management (CHEM) for possible inclusion in a future update to its loose-leaf reference publication, the Healthcare Environmental Management System. We wish to acknowledge CHEM's contribution in developing this special report, which was reviewed by the Centers for Disease Control and Prevention (CDC), the National Institute for Occupational Safety and Health (NIOSH), and OSHA. Also see "CDC's Recommendations for Hepatitis B Vaccination and Postexposure Follow-up" and "A Minimal Training Syllabus" in this issue.
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PMID:OSHA's bloodborne pathogens standard: analysis and recommendations. 844 29

Many malarial antigens contain extensive arrays of tandemly repeated short amino acid sequences, and much of the antibody response induced by malaria infections is directed against these repeats. Indeed, it has been hypothesized that these repeats function to elicit a relatively ineffective T-cell-independent antibody response by the host. In order to test this hypothesis, tandem repeats of Plasmodium species were examined for a bias in composition favoring amino acids likely to form epitopes for the antibody. The genome of Plasmodium is very A+T-rich, and nucleotide compositional bias will, in itself, lead to a high proportion of hydrophilic amino acids. When this bias was controlled for, Plasmodium antigens did not show a higher proportion of hydrophilic amino acids than expected, but there was a significant reduction in the proportion of hydrophobic amino acids in the repeats of the antigens. The amino acid composition of the repeats was thus strikingly different from those seen both in the remainder of the antigens and in a sample of Plasmodium falciparum housekeeping genes.
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PMID:Biased amino acid composition in repeat regions of Plasmodium antigens. 1033 56

The karyotype and chromosomes of the human malaria parasite Plasmodium falciparum have been well characterized in recent years. Here we present karyotype maps of the three other human malaria species, P. vivax, P. malariae and P. ovale. Chromosomes of these species were found to be of significantly higher molecular weight than those of P. falciparum. Some 14 P. vivax chromosomes were distinguishable, and 12-14 P. malariae and P. ovale chromosomes. The chromosome location of 15 genes, known to be present within five synteny groups between P. falciparum and the rodent malarias, were analyzed, and four of these synteny groups were found to be conserved between all of the human malaria species. In addition, a more detailed genome map of P. vivax was made using ten housekeeping and antigen genes. These data represent the first karyotype maps of all species of malaria which infect man.
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PMID:Karyotype and synteny among the chromosomes of all four species of human malaria parasite. 1041 40

Resistance to commonly used malaria drugs is spreading and new drugs are required urgently. The recent identification of a relict chloroplast (apicoplast) in malaria and related parasites offers numerous new targets for drug therapy using well-characterized compounds. The apicoplast contains a range of metabolic pathways and housekeeping processes that differ radically to those of the host thereby presenting ideal strategies for drug therapy. Indeed, many compounds targeting these plastid pathways are antimalarial and have favourable profiles based on extensive knowledge from their use as antibacterials.
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PMID:The apicoplast as an antimalarial drug target. 1176 28

Anopheles stephensi is the main urban mosquito vector of malaria in the Indian subcontinent, and belongs to the same subgenus as Anopheles gambiae, the main malaria vector in Africa. Recently the genome and proteome sets of An. gambiae have been described, as well as several protein sequences expressed in its salivary glands, some of which had their expression confirmed by amino terminal sequencing. In this paper, we randomly sequenced a full-length cDNA library of An. stephensi and performed Edman degradation of polyvinylidene difluoride (PVDF)-transferred protein bands from salivary homogenates. Twelve of 13 proteins found by aminoterminal degradation were found among the cDNA clusters of the library. Thirty-three full-length novel cDNA sequences are reported, including a novel secreted galectin; the homologue of anophelin, a thrombin inhibitor; a novel trypsin/chymotrypsin inhibitor; an apyrase; a lipase; and several new members of the D7 protein family. Most of the novel proteins have no known function. Comparison of the putatively secreted and putatively housekeeping proteins of An. stephensi with An. gambiae proteins indicated that the salivary gland proteins are at a faster evolutionary pace. The possible role of these proteins in blood and sugar feeding by the mosquito is discussed. The electronic tables and supplemental material are available at http://www.ncbi.nlm.nih.gov/projects/Mosquito/A_stephensi_sialome/ .
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PMID:Exploring the salivary gland transcriptome and proteome of the Anopheles stephensi mosquito. 1282 99

Mutations and/or overexpression of various transporters are known to confer drug resistance in a variety of organisms. In the malaria parasite Plasmodium falciparum, a homologue of P-glycoprotein, PfMDR1, has been implicated in responses to chloroquine (CQ), quinine (QN) and other drugs, and a putative transporter, PfCRT, was recently demonstrated to be the key molecule in CQ resistance. However, other unknown molecules are probably involved, as different parasite clones carrying the same pfcrt and pfmdr1 alleles show a wide range of quantitative responses to CQ and QN. Such molecules may contribute to increasing incidences of QN treatment failure, the molecular basis of which is not understood. To identify additional genes involved in parasite CQ and QN responses, we assayed the in vitro susceptibilities of 97 culture-adapted cloned isolates to CQ and QN and searched for single nucleotide polymorphisms (SNPs) in DNA encoding 49 putative transporters (total 113 kb) and in 39 housekeeping genes that acted as negative controls. SNPs in 11 of the putative transporter genes, including pfcrt and pfmdr1, showed significant associations with decreased sensitivity to CQ and/or QN in P. falciparum. Significant linkage disequilibria within and between these genes were also detected, suggesting interactions among the transporter genes. This study provides specific leads for better understanding of complex drug resistances in malaria parasites.
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PMID:Multiple transporters associated with malaria parasite responses to chloroquine and quinine. 1289 22

Patterns of expression of the 2-Cys and 1-Cys peroxiredoxin (Prx) proteins of the rodent malaria parasite Plasmodium yoelii during its life cycle were observed by immunofluorescent antibody staining and confocal laser scanning microscopy. 2-Cys Prx was expressed in the parasite cytoplasm throughout the life cycle, and the thioredoxin (Trx)-peroxidase activity of 2-Cys Prx revealed with the recombinant protein suggested that the Prx is constitutively expressed and, thus, likely plays a housekeeping role in the parasite's intracellular redox control. In contrast, 1-Cys Prx showed stage-specific expression in blood-stage parasites. The limited expression of 1-Cys Prx in the trophozoite cytoplasm suggests that 1-Cys Prx may be involved in haemoglobin metabolism by the parasite, which generates a prooxidative haem iron and increases intracellular oxidative stress. The antioxidant activity of 1-Cys Prx was tested for its ability to protect yeast enolase against inactivation of the mixed-function oxidation system. Differential expression of the two Prx proteins during the erythrocytic and insect stages suggests the importance of these proteins in protecting parasites against oxidative stress, which is generated by the parasite's metabolism and also from the environment.
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PMID:Expression profiles of peroxiredoxin proteins of the rodent malaria parasite Plasmodium yoelii. 1457 8

Anopheles (Nyssorhynchus) darlingi is an important malaria vector in South and Central America; however, little is known about molecular aspects of its biology. Genomic and proteomic analyses were performed on the salivary gland products of Anopheles darlingi. A total of 593 randomly selected, salivary gland-derived cDNAs were sequenced and assembled based on their similarities into 288 clusters. The putative translated proteins were classified into three categories: (S) secretory products, (H) housekeeping products and (U) products with unknown cell location and function. Ninety-three clusters encode putative secreted proteins and several of them, such as an anophelin, a thrombin inhibitor, apyrases and several new members of the D7 protein family, were identified as molecules involved in haematophagy. Sugar-feeding related enzymes (alpha-glucosidases and alpha-amylase) also were found among the secreted salivary products. Ninety-nine clusters encode housekeeping proteins associated with energy metabolism, protein synthesis, signal transduction and other cellular functions. Ninety-seven clusters encode proteins with no similarity with known proteins. Comparison of the sequence divergence of the S and H categories of proteins of An. darlingi and An. gambiae revealed that the salivary proteins are less conserved than the housekeeping proteins, and therefore are changing at a faster evolutionary rate. Tabular and supplementary material containing the cDNA sequences and annotations are available at http://www.ncbi.nlm.nih.gov/projects/Mosquito/A_darlingi_sialome/
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PMID:The transcriptome of adult female Anopheles darlingi salivary glands. 1472 69


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