Effect of mebendazole and praziquantel on glucosephosphate isomerase and glyceraldehydephosphate dehydrogenase in Echinococcus granulosus cyst wall harbored in mice.
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AIM: To study effects of antihydatid drugs on glucosephosphate isomerase (GPI) and glyceraldehydephosphate dehydrogenase (GAPDH) in Echinococcus granulosus cyst wall. METHODS: Mice infected with the parasite for 8-10 months were treated i.g. with mebendazole (Meb) or praziquantel (Pra). The activities of GPI and GAPDH in the cysts were measured by the formation of NADH or NADPH. RESULTS: GPI activity in the cyst wall was 197 +/- 103 U, while that of GAPDH was 25 +/- 13 U. When infected mice were treated i.g. with Meb 25-50 mg.kg-1.d-1 for 7-14 d, no apparent effect on the GAPDH activity in the cyst was found. In mice treated i.g. with praziquantel (Pra) 500 mg.kg-1.d-1 for 14 d, the GAPDH activity in the cyst wall was inhibited by 26.5%. As to GPI activity only the group treated i.g. with Meb 25 mg.kg-1.d-1 for 14 d showed 33.2% inhibition of the enzyme in the collapsed cyst wall. CONCLUSION: GPI and GAPDH are not the major targets attacked by the antihydatid drug. (+info)
A study of the genetical structure of the Cuban population: red cell and serum biochemical markers.
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Gene frequencies of several red cell and serum gentic markers were determined in the three main racial groups--whites, mulattoes and Negroes--of the Cuban population. The results were used to estimate the relative contribution of Caucasian and Negro genes to the genetic makeup of these three groups and to calculate the frequencies of these genes in the general Cuban population. (+info)
The crystal structure of a multifunctional protein: phosphoglucose isomerase/autocrine motility factor/neuroleukin.
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Phosphoglucose isomerase (PGI) plays a central role in both the glycolysis and the gluconeogenesis pathways. We present here the complete crystal structure of PGI from Bacillus stearothermophilus at 2.3-A resolution. We show that PGI has cell-motility-stimulating activity on mouse colon cancer cells similar to that of endogenous autocrine motility factor (AMF). PGI can also enhance neurite outgrowth on neuronal progenitor cells similar to that observed for neuroleukin. The results confirm that PGI is neuroleukin and AMF. PGI has an open twisted alpha/beta structural motif consisting of two globular domains and two protruding parts. Based on this substrate-free structure, together with the previously published biological, biochemical, and modeling results, we postulate a possible substrate-binding site that is located within the domains' interface for PGI and AMF. In addition, the structure provides evidence suggesting that the top part of the large domain together with one of the protruding loops might participate in inducing the neurotrophic activity. (+info)
Population structure and genetic divergence in Anopheles nuneztovari (Diptera: Culicidae) from Brazil and Colombia.
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Anopheles nuneztovari is considered an important vector of human malaria in several localities in Venezuela and Colombia. Its status as a vector of human malaria is still unresolved in areas of the Brazilian Amazon, in spite of have been found infected with Plasmodium sp.. For a better understanding of the genetic differentiation of populations of A. nuneztovari, electrophoretic analysis using 11 enzymes was performed on four populations from Brazil and two from Colombia. The results showed a strong differentiation for two loci: alpha-glycerophosphate dehydrogenase (alpha-Gpd) and malate dehydrogenase (Mdh) from 16 loci analyzed. Diagnostic loci were not detected. The populations of A. nuneztovari from the Brazilian Amazon showed little genetic structure and low geographic differentiation, based on the F(IS) (0.029), F(ST) (0.070), and genetic distance (0.001-0.032) values. The results of the isozyme analysis do not coincide with the indication of two lineages in the Amazon Basin by analysis of mitochondrial DNA, suggesting that this evolutionary event is recent. The mean F(ST) value (0.324) suggests that there is considerable genetic divergence among populations from the Brazilian Amazon and Colombia. The genetic distance among populations from the Brazilian Amazon and Colombia is ranges from 0.047 to 0.148, with the highest values between the Brazilian Amazon and Sitronela (SIT) (0.125-0.148). These results are consistent with those observed among members of anopheline species complexes. It is suggested that geographic isolation has reduced the gene flow, resulting in the genetic divergence of the SIT population. Dendrogram analysis showed three large groups: one Amazonian and two Colombia, indicating some genetic structuring. The present study is important because it attempted to clarify the taxonomic status of A. nuneztovari and provide a better understanding of the role of this mosquito in transmission of human malaria in northern South America. (+info)
Regulation and adaptation of glucose metabolism of the parasitic protist Leishmania donovani at the enzyme and mRNA levels.
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Adaptation of the glucose metabolism of Leishmania donovani promastigotes (insect stage) was investigated by simultaneously measuring metabolic rates, enzyme activities, message levels, and cellular parameters under various conditions. Chemostats were used to adapt cells to different growth rates with growth rate-limiting or excess glucose concentrations. L. donovani catabolized glucose to CO(2), succinate, acetate, and pyruvate in ratios that depended on growth rate and glucose availability. Rates of glucose consumption were a linear function of growth rate and were twice as high in excess glucose-grown cells as in glucose-limited organisms. The major end product was CO(2), but organic end products were also formed in ratios that varied strongly with growth conditions. The specific activities of the 14 metabolic enzymes measured varied by factors of 3 to 17. Two groups of enzymes adapted specific activities in parallel, but there was no correlation between the groups. The activities of only one group correlated with specific rates of glucose metabolism. Total RNA content per cellular protein varied by a factor of 6 and showed a linear relationship with the rate of glucose consumption. There was no correlation between steady-state message levels and activities of the corresponding enzymes, suggesting regulation at the posttranscriptional level. A comparison of the adaptation of energy metabolism in L. donovani and other species suggests that the energy metabolism of L. donovani is inefficient but is well suited to the environmental challenges that it encounters during residence in the sandfly, its insect vector. (+info)
The protozoan parasite Toxoplasma gondii expresses two functional plant-like glycolytic enzymes. Implications for evolutionary origin of apicomplexans.
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The recent discovery of a vestigial, nonphotosynthetic plastid ("apicoplast") in the Apicomplexa has considerably modified our perception of the evolutionary origin of these parasites. Phylogenetic analysis and the presence of four surrounding membranes of the apicoplast provide important support for the hypothesis that apicomplexans have acquired their apicoplast by secondary endosymbiosis, probably from a green alga. This suggests that genes encoding predicted homologs of proteins of green algae or related photosynthetic lineages could have entered the nucleus of apicomplexan parasites by transfer from the ancestor harboring the apicoplast. We describe here complementary DNAs encoding two Toxoplasma gondii glycolytic enzymes, glucose-6-phosphate isomerase (G6-PI) and enolase, which have considerable identities with land plant counterparts. Both cDNAs of T. gondii complement Escherichia coli mutants lacking G6-PI and enolase genes and lead to the expression of active enzymes. In the drug untreatable encysted bradyzoites of T. gondii, G6-PI and enolase genes are overexpressed or exclusively expressed at both transcriptional and protein levels. Moreover, three-dimensional models and protein phylogeny confirmed that G6-PIs and enolases of T. gondii, Plasmodium falciparum, and land plants are closely related. Because these glycolytic enzymes are plant homologs, which differ from those of animals, they will be useful to trace the evolutionary origin of Apicomplexa and might offer novel chemotherapeutic targets in diseases caused by apicomplexan parasites. (+info)
Developmental expression analysis of murine autotaxin (ATX).
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The murine homologue of the human motility-stimulating protein autotaxin (ATX) was identified as a BMP2 upregulated gene by subtractive cloning from mesenchymal progenitors C3H10T1/2 (Bachner, D., Ahrens, M., Betat, N., Schroder, D., Hoffmann. A., Lauber, J., Steinert, P., Flohe, L., Gross, G., 1998. Bmp-2 downstream targets in mesenchymal development identified by subtractive cloning from recombinant mesenchymal progenitors (C3H10T1/2). Dev. Dyn. 213, 398-411). ATX mRNA transcription is induced during BMP2 mediated osteo-/chondrogenic differentiation in vitro several orders of magnitude. To delineate a potential role for ATX in osteo-/chondrogenic development, its expression pattern during murine embryogenesis was examined in comparison with Col1a1 and Col2a1, a marker either of osteoblast, odontoblast and tendon or of chondrocyte development, respectively. Localization of murine ATX was first observed in the floor plate of the neural tube at day 9.5 of mouse embryonic development. Later, enhanced ATX expression levels were observed in proliferating subepithelial mesenchyme, during osteo-/chondrogenic and tooth development, in choroid plexus epithelium, in late kidney development, and in smooth muscles of the ductus deferens and the bladder. (+info)
DNA polymorphism, haplotype structure and balancing selection in the Leavenworthia PgiC locus.
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A study of DNA polymorphism and divergence was conducted for the cytosolic phosphoglucose isomerase (PGI:E.C.5.3.1.9) gene of five species of the mustard genus Leavenworthia: Leavenworthia stylosa, L. alabamica, L. crassa, L. uniflora, and L. torulosa. Sequences of an internal 2.3-kb PgiC gene region spanning exons 6-16 were obtained from 14 L. stylosa plants from two natural populations and from one to several plants for each of the other species. The level of nucleotide polymorphism in L. stylosa PgiC gene was quite high (pi = 0.051, theta = 0.052). Although recombination is estimated to be high in this locus, extensive haplotype structure was observed for the entire 2.3-kb region. The L. stylosa sequences fall into at least two groups, distinguished by the presence of several indels and nucleotide substitutions, and one of the three charge change nucleotide replacements within the region sequenced correlates with the haplotypes. The differences between the haplotypes are older than between the species, and the haplotypes are still segregating in at least two of five species studied. There is no evidence of recent or ancient population subdivision that could maintain distinct haplotypes. The age of the haplotypes and the results of Kelly's Z(nS) and Wall's B and Q tests with recombination suggest that the haplotypes are maintained due to balancing selection at or near this locus. (+info)