Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
|---|
| mitochondrial origin-binding protein umsbp mediates dna replication and segregation in trypanosomes. | kinetoplast dna (kdna) is the remarkable mitochondrial genome of trypanosomatids. its major components are several thousands of topologically linked dna minicircles, whose replication origins are bound by the universal minicircle sequence-binding protein (umsbp). the cellular function of umsbp has been studied in trypanosoma brucei by using rnai analysis. silencing of the trypanosomal umsbp genes resulted in remarkable effects on the trypanosome cell cycle. it significantly inhibited the initiat ... | 2007 | 18048338 |
| trypanosoma brucei brucei induces alteration in the head proteome of the tsetse fly vector glossina palpalis gambiensis. | parasitic manipulations of host behaviour are known from a wide range of host-parasite associations. however, the understanding of these phenomena is far from complete and detailed investigation of their proximate causes is needed. many studies report behavioural modifications, such as altered feeding rates in tsetse fly (glossina) infected with the mature transmissible stage (i.e. metacyclic) of the trypanosomes. here, bidimensional (2d) gel electrophoresis and mass spectrometry were employed t ... | 2007 | 18092995 |
| the first crystal structure of phosphofructokinase from a eukaryote: trypanosoma brucei. | the crystal structure of the atp-dependent phosphofructokinase (pfk) from trypanosoma brucei provides the first detailed description of a eukaryotic pfk, and enables comparisons to be made with the crystal structures of bacterial atp-dependent and ppi-dependent pfks. the structure reveals that two insertions (the 17-20 and 329-348 loops) that are characteristic of trypanosomatid pfks, but absent from bacterial and mammalian atp-dependent pfks, are located within and adjacent to the active site, ... | 2007 | 17207816 |
| nuclear repositioning of the vsg promoter during developmental silencing in trypanosoma brucei. | interphase nuclear repositioning of chromosomes has been implicated in the epigenetic regulation of rna polymerase (pol) ii transcription. however, little is known about the nuclear position-dependent regulation of rna pol i-transcribed loci. trypanosoma brucei is an excellent model system to address this question because its two main surface protein genes, procyclin and variant surface glycoprotein (vsg), are transcribed by pol i and undergo distinct transcriptional activation or downregulation ... | 2007 | 17210949 |
| a sirtuin in the african trypanosome is involved in both dna repair and telomeric gene silencing but is not required for antigenic variation. | silent information regulator 2 (sir2)-related proteins or sirtuins function as nad(+)-dependent deacetylases or adp ribosylases that target a range of substrates, thereby influencing chromatin structure and a diverse range of other biological functions. genes encoding three sir2-related proteins (sir2rp1-3) have been identified in the parasitic trypanosomatids, early branching protozoa with no previously reported transcriptional silencing machinery. here we show that, in the mammalian-infective ... | 2007 | 17214740 |
| de novo sphingolipid synthesis is essential for viability, but not for transport of glycosylphosphatidylinositol-anchored proteins, in african trypanosomes. | de novo sphingolipid synthesis is required for the exit of glycosylphosphatidylinositol (gpi)-anchored membrane proteins from the endoplasmic reticulum in yeast. using a pharmacological approach, we test the generality of this phenomenon by analyzing the transport of gpi-anchored cargo in widely divergent eukaryotic systems represented by african trypanosomes and hela cells. myriocin, which blocks the first step of sphingolipid synthesis (serine + palmitate --> 3-ketodihydrosphingosine), inhibit ... | 2007 | 17220466 |
| crosstalk between the subunits of the homodimeric enzyme triosephosphate isomerase. | homodimeric triosephosphate isomerase (tim) from trypanosoma cruzi (tctim) and t. brucei (tbtim) are markedly similar in amino acid sequence and three-dimensional structure. in their dimer interfaces, each monomer has a cys15 that is surrounded by loop3 of the adjoining subunit. perturbation of cys15 by methylmethane thiosulfonate (mmts) induces abolition of catalysis and structural changes. in the two tims, the structural arrangements of their cys15 are almost identical. nevertheless, the susce ... | 2007 | 17221869 |
| crystal structures of a bacterial 6-phosphogluconate dehydrogenase reveal aspects of specificity, mechanism and mode of inhibition by analogues of high-energy reaction intermediates. | crystal structures of recombinant lactococcus lactis 6-phosphogluconate dehydrogenase (llpdh) in complex with substrate, cofactor, product and inhibitors have been determined. llpdh shares significant sequence identity with the enzymes from sheep liver and the protozoan parasite trypanosoma brucei for which structures have been reported. comparisons indicate that the key residues in the active site are highly conserved, as are the interactions with the cofactor and the product ribulose 5-phospha ... | 2007 | 17222187 |
| golgi biogenesis in simple eukaryotes. | the accurate duplication of cellular organelles is important to ensure propagation through successive generations. the semi-conserved replication of dna and dna-containing organelles has been well studied, but the mechanisms used to duplicate most other organelles remain elusive. these include the centrosomes, which act as microtubule organizing centres during interphase and orient the mitotic spindle poles during mitosis. centrosomes can also act as basal bodies, nucleating the growth of cilia ... | 2007 | 17223925 |
| functional genomics in trypanosoma brucei identifies evolutionarily conserved components of motile flagella. | cilia and flagella are highly conserved, complex organelles involved in a variety of important functions. flagella are required for motility of several human pathogens and ciliary defects lead to a variety of fatal and debilitating human diseases. many of the major structural components of cilia and flagella are known, but little is known about regulation of flagellar beat. trypanosoma brucei, the causative agent of african sleeping sickness, provides an excellent model for studying flagellar mo ... | 2007 | 17227795 |
| a family of stage-specific alanine-rich proteins on the surface of epimastigote forms of trypanosoma brucei. | a 'two coat' model of the life cycle of trypanosoma brucei has prevailed for more than 15 years. metacyclic forms transmitted by infected tsetse flies and mammalian bloodstream forms are covered by variant surface glycoproteins. all other life cycle stages were believed to have a procyclin coat, until it was shown recently that epimastigote forms in tsetse salivary glands express procyclin mrnas without translating them. as epimastigote forms cannot be cultured, a procedure was devised to compar ... | 2007 | 17229212 |
| differential effects of arginine methylation on rbp16 mrna binding, guide rna (grna) binding, and grna-containing ribonucleoprotein complex (grnp) formation. | mitochondrial gene expression in trypanosoma brucei involves the coordination of multiple events including polycistronic transcript cleavage, polyadenylation, rna stability, and rna editing. arg methylation of rna binding proteins has the potential to influence many of these processes via regulation of protein-protein and protein-rna interactions. here we demonstrate that arg methylation differentially regulates the rna binding capacity and macromolecular interactions of the mitochondrial gene r ... | 2007 | 17229732 |
| loss of the high-affinity pentamidine transporter is responsible for high levels of cross-resistance between arsenical and diamidine drugs in african trypanosomes. | treatment of many infectious diseases is under threat from drug resistance. understanding the mechanisms of resistance is as high a priority as the development of new drugs. we have investigated the basis for cross-resistance between the diamidine and melaminophenyl arsenical classes of drugs in african trypanosomes. we induced high levels of pentamidine resistance in a line without the tbat1 gene that encodes the p2 transporter previously implicated in drug uptake. we isolated independent clone ... | 2007 | 17234896 |
| a novel phospholipase from trypanosoma brucei. | phospholipase a(1) activities have been detected in most cells where they have been sought and yet their characterization lags far behind that of the phospholipases a(2), c and d. the study presented here details the first cloning and characterization of a cytosolic pla(1) that exhibits preference for phosphatidylcholine (gpcho) substrates. trypanosoma brucei phospholipase a(1) (tbpla(1)) is unique from previously identified eukaryotic pla(1) because it is evolutionarily related to bacterial sec ... | 2007 | 17238918 |
| antitrypanosomal activity of quaternary naphthalimide derivatives. | sleeping sickness caused by trypanosoma brucei gambiense and rhodesiense is fatal if left untreated. due to the toxicity of drugs currently used and the emerging resistance against these drugs new lead compounds are urgently needed. within the frame of a broad screening program for drugs with antitrypanosomal activity, some highly potent tertiary and quaternary mono- and bisnaphthalimides being active in the lower micromolar and nanomolar range of concentration have been identified. these compou ... | 2007 | 17239596 |
| deletion of a trypanosome telomere leads to loss of silencing and progressive loss of terminal dna in the absence of cell cycle arrest. | eukaryotic chromosomes are capped with telomeres which allow complete chromosome replication and prevent the ends from being recognized by the repair machinery. the african trypanosome, trypanosoma brucei, is a protozoan parasite where antigenic variation requires reversible silencing of a repository of telomere-adjacent variant surface glycoprotein (vsg) genes. we have investigated the role of the telomere adjacent to a repressed vsg. in cells lacking telomerase, the rate of telomere-repeat los ... | 2007 | 17251198 |
| spliced leader rna gene transcription in trypanosoma brucei requires transcription factor tfiih. | trypanosomatid parasites share a gene expression mode which differs greatly from that of their human and insect hosts. in these unicellular eukaryotes, protein-coding genes are transcribed polycistronically and individual mrnas are processed from precursors by spliced leader (sl) trans splicing and polyadenylation. in trans splicing, the sl rna is consumed through a transfer of its 5'-terminal part to the 5' end of mrnas. since all mrnas are trans spliced, the parasites depend on strong and cont ... | 2007 | 17259543 |
| diversification of function by different isoforms of conventionally shared rna polymerase subunits. | eukaryotic nuclei contain three classes of multisubunit dna-directed rna polymerase. at the core of each complex is a set of 12 highly conserved subunits of which five--rpb5, rpb6, rpb8, rpb10, and rpb12--are thought to be common to all three polymerase classes. here, we show that four distantly related eukaryotic lineages (the higher plant and three protistan) have independently expanded their repertoire of rpb5 and rpb6 subunits. using the protozoan parasite trypanosoma brucei as a model organ ... | 2007 | 17267688 |
| substrate determinants for rna editing and editing complex interactions at a site for full-round u insertion. | multisubunit rna editing complexes catalyze uridylate insertion/deletion rna editing directed by complementary guide rnas (grnas). editing in trypanosome mitochondria is transcript-specific and developmentally controlled, but the molecular mechanisms of substrate specificity remain unknown. here we used a minimal a6 pre-mrna/grna substrate to define functional determinants for full-round insertion and editing complex interactions at the editing site 2 (es2). editing begins with pre-mrna cleavage ... | 2007 | 17158098 |
| telomere structure and function in trypanosomes: a proposal. | telomeres are specialized dna-protein complexes that stabilize chromosome ends, protecting them from nucleolytic degradation and illegitimate recombination. telomeres form a heterochromatic structure that can suppress the transcription of adjacent genes. these structures might have additional roles in trypanosoma brucei, as the major surface antigens of this parasite are expressed during its infectious stages from subtelomeric loci. we propose that the telomere protein complexes of trypanosomes ... | 2007 | 17160000 |
| mitochondrial fatty acid synthesis in trypanosoma brucei. | whereas other organisms utilize type i or type ii synthases to make fatty acids, trypanosomatid parasites such as trypanosoma brucei are unique in their use of a microsomal elongase pathway (elo) for de novo fatty acid synthesis (fas). because of the unusual lipid metabolism of the trypanosome, it was important to study a second fas pathway predicted by the genome to be a type ii synthase. we localized this pathway to the mitochondrion, and rna interference (rnai) or genomic deletion of acyl car ... | 2007 | 17166831 |
| the trypanosoma brucei camp phosphodiesterases tbrpdeb1 and tbrpdeb2: flagellar enzymes that are essential for parasite virulence. | cyclic nucleotide specific phosphodiesterases (pdes) are pivotal regulators of cellular signaling. they are also important drug targets. besides catalytic activity and substrate specificity, their subcellular localization and interaction with other cell components are also functionally important. in contrast to the mammalian pdes, the significance of pdes in protozoal pathogens remains mostly unknown. the genome of trypanosoma brucei, the causative agent of human sleeping sickness, codes for fiv ... | 2007 | 17167070 |
| kinetoplastid ppef phosphatases: dual acylated proteins expressed in the endomembrane system of leishmania. | bioinformatic analyses have been used to identify potential downstream targets of the essential enzyme n-myristoyl transferase in the tritryp species, leishmania major, trypanosoma brucei and trypanosoma cruzi. these database searches predict approximately 60 putative n-myristoylated proteins with high confidence, including both previously characterised and novel molecules. one of the latter is an n-myristoylated protein phosphatase which has high sequence similarity to the protein phosphatase w ... | 2007 | 17169445 |
| trypanosoma brucei arf1 plays a central role in endocytosis and golgi-lysosome trafficking. | the adp ribosylation factor (arf)1 orthologue in the divergent eukaryote trypanosoma brucei (tb) shares characteristics with both arf1 and arf6 and has a vital role in intracellular protein trafficking. tbarf1 is golgi localized in trypanosomes but associates with the plasma membrane when expressed in human cells. depletion of tbarf1 by rna interference causes a major decrease in endocytosis, which correlates with rab5 dissociation from early endosomes. although the golgi remains intact, parasit ... | 2007 | 17182848 |
| molecular interactions underlying the unusually high adenosine affinity of a novel trypanosoma brucei nucleoside transporter. | trypanosoma brucei encodes a relatively high number of genes of the equilibrative nucleoside transporter (ent) family. we report here the cloning and in-depth characterization of one t. brucei brucei ent member, tbnt9/at-d. this transporter was expressed in saccharomyces cerevisiae and displayed a uniquely high affinity for adenosine (km = 0.068 +/- 0.013 microm), as well as broader selectivity for other purine nucleosides in the low micromolar range, but was not inhibited by nucleobases or pyri ... | 2007 | 17185380 |
| regulated expression of glycosomal phosphoglycerate kinase in trypanosoma brucei. | in trypanosoma brucei, the pgkb and pgkc genes-encoding phosphoglycerate kinase are co-transcribed as part of a polycistronic rna. pgkb mrna and the cytosolic pgkb protein are much more abundant in the procyclic life-cycle stage than in bloodstream forms, whereas pgkc mrna and glycosomal pgkc protein are specific to bloodstream forms. we here show that a sequence between nucleotides 558 and 779 in the 3'-untranslated region of the pgkc mrna causes low expression of the chloramphenicol acetyltran ... | 2007 | 17187872 |
| characterization of glycosomal ring finger proteins of trypanosomatids. | the glycosomes of trypanosomatids are essential organelles that are evolutionarily related to peroxisomes of other eukaryotes. the peroxisomal ring proteins-pex2, pex10 and pex12-comprise a network of integral membrane proteins that function in the matrix protein import cycle. here, we describe pex10 and pex12 in trypanosoma brucei, leishmania major, and trypanosoma cruzi. we expressed gfp fusions of each t. brucei coding region in procyclic form t. brucei, where they localized to glycosomes and ... | 2007 | 17188680 |
| utp-bound and apo structures of a minimal rna uridylyltransferase. | 3'-uridylylation of rna is emerging as a phylogenetically widespread phenomenon involved in processing events as diverse as uridine insertion/deletion rna editing in mitochondria of trypanosomes and small nuclear rna (snrna) maturation in humans. this reaction is catalyzed by terminal uridylyltransferases (tutases), which are template-independent rna nucleotidyltransferases that specifically recognize utp and belong to a large enzyme superfamily typified by dna polymerase beta. multiple tutases, ... | 2007 | 17189640 |
| deletion of the trypanosoma brucei superoxide dismutase gene sodb1 increases sensitivity to nifurtimox and benznidazole. | it has been more than 25 years since it was first reported that nifurtimox and benznidazole promote superoxide production in trypanosomes. however, there has been no direct evidence of an association between the drug-induced free radicals and trypanocidal activity. here, we identify a superoxide dismutase required to protect trypanosoma brucei from drug-generated superoxide. | 2007 | 17145786 |
| cholesterol import fails to prevent catalyst-based inhibition of ergosterol synthesis and cell proliferation of trypanosoma brucei. | trypanosoma brucei (tb) cultured in rat blood, bovine serum, or lipid-depleted serum generated distinct differences in cholesterol availability. whereas cell proliferation of the parasite was relatively unaffected by cholesterol availability, the ratios of cellular ergostenols to cholesterol varied from close to unity to 3 orders of magnitude different with cholesterol as the major sterol (>99%) of bloodstream form cells. in the procyclic form cultured with lipid-depleted serum, 15 sterols at 52 ... | 2007 | 17127773 |
| metabolic control analysis to identify optimal drug targets. | this chapter describes the basic principles of metabolic control analysis (mca) which is a quantitative methodology to evaluate the importance and relative contribution of individual metabolic steps in the overall functioning of a particular system. the control on the flux through a metabolic pathway or subsystem can be quantified by the control coefficients of the individual enzymes or components which reflects the extent to which the component is rate-limiting. the perturbation of an individua ... | 2007 | 17195475 |
| mechanism of translation based on intersubunit complementarities of ribosomal rnas and trnas. | a universal rule is found about nucleotide sequence complementarities between the regions 2653-2666 in the gtpase-binding site of 23s rrna and 1064-1077 of 16s rrna as well as between the region 1103-1107 of 16s rrna and guucg (or guuca) of trnas. this rule holds for all species in the living kingdoms except for two protista mitochondrial rrnas of trypanosoma brucei and plasmodium falciparum. we found that quite similar relationships for the two species hold under the assumption presented in the ... | 2007 | 17196221 |
| three dimensional structure and implications for the catalytic mechanism of 6-phosphogluconolactonase from trypanosoma brucei. | enzymes from the pentose phosphate pathway (ppp) are potential drug targets for the development of new drugs against trypanosoma brucei, the causative agent of african sleeping disease: for instance, the 6-phosphogluconate dehydrogenase is currently studied actively for such purposes. structural and functional studies are necessary to better characterize the associated enzymes and compare them to their human homologues, in order to undertake structure-based drug design studies on such targets. i ... | 2007 | 17196981 |
| high-throughput screening affords novel and selective trypanothione reductase inhibitors with anti-trypanosomal activity. | trypanothione reductase (tr), an enzyme that buffers oxidative stress in trypanosomatid parasites, was screened against commercial libraries containing approximately 134,500 compounds. after secondary screening, four chemotypes were identified as screening positives with selectivity for tr over human glutathione reductase. thirteen compounds from these four chemotypes were purchased, and their in vitro activity against tr and trypanosoma brucei is described. | 2007 | 17197182 |
| an essential quality control mechanism at the eukaryotic basal body prior to intraflagellar transport. | constructing a eukaryotic cilium/flagellum is a demanding task requiring the transport of proteins from their cytoplasmic synthesis site into a spatially and environmentally distinct cellular compartment. the clear potential hazard is that import of aberrant proteins could seriously disable cilia/flagella assembly or turnover processes. here, we reveal that tubulin protein destined for incorporation into axonemal microtubules interacts with a tubulin cofactor c (tbcc) domain-containing protein t ... | 2007 | 17645436 |
| pentatricopeptide repeat proteins in trypanosoma brucei function in mitochondrial ribosomes. | the pentatricopeptide repeat (ppr), a degenerate 35-amino-acid motif, defines a novel eukaryotic protein family. plants have 400 to 500 distinct ppr proteins, whereas other eukaryotes generally have fewer than 5. the few ppr proteins that have been studied have roles in organellar gene expression, probably via direct interaction with rna. here we show that the parasitic protozoan trypanosoma brucei encodes 28 distinct ppr proteins, an extraordinarily high number for a nonplant organism. a compar ... | 2007 | 17646387 |
| type 3 peptide deformylases are required for oxidative phosphorylation in trypanosoma brucei. | peptide deformylase (pdf) catalyses the removal of the formyl group from the first methionine of nascent proteins. type 1 pdfs are found in bacteria and have orthologues in most eukaryotes. type 2 pdfs are restricted to bacteria. type 3 enzymes are found in archaea and trypanosomatids and have not been studied experimentally yet. thus, tbpdf1 and tbpdf2, the two pdf orthologues of the parasitic protozoa trypanosoma brucei, are of type 3. an experimental analysis of these enzymes shows that both ... | 2007 | 17651388 |
| analysis of the vsg gene silent archive in trypanosoma brucei reveals that mosaic gene expression is prominent in antigenic variation and is favored by archive substructure. | trypanosoma brucei evades host acquired immunity through differential activation of its large archive of silent variant surface glycoprotein (vsg) genes, most of which are pseudogenes in subtelomeric arrays. we have analyzed 940 vsgs, representing one half to two thirds of the arrays. sequence types a and b of the vsg n-terminal domains were confirmed, while type c was found to be a constituent of type a. two new c-terminal domain types were found. nearly all combinations of domain types occurre ... | 2007 | 17652423 |
| correlative light and electron microscopy using immunolabeled resin sections. | in correlative microscopy, light microscopy provides the overview and orientation in the complex cells and tissue, whereas electron microscopy offers the detailed localization and correlation to subcellular structures. in this chapter, we offer the detailed high-quality electron microscopical preparation methods for the optimum preservation of the cellular ultrastructure. from such preparations, serial thin sections are collected and used for comparative histochemical, immunofluorescence, and im ... | 2007 | 17656754 |
| trypanosoma brucei polo-like kinase is essential for basal body duplication, kdna segregation and cytokinesis. | polo-like kinases (plks) are conserved eukaryotic cell cycle regulators, which play multiple roles, particularly during mitosis. the function of trypanosoma brucei plk was investigated in procyclic and bloodstream-form parasites. in procyclic trypanosomes, rna interference (rnai) of plk, or overexpression of ty1-epitope-tagged plk (plkty), but not overexpression of a kinase-dead variant, resulted in the accumulation of cells that had divided their nucleus but not their kinetoplast (2n1k cells). ... | 2007 | 17662039 |
| gene conversion is a convergent strategy for pathogen antigenic variation. | recent studies on three unrelated vector-borne pathogens, anaplasma marginale, borrelia hermsii and trypanosoma brucei, illustrate the central importance of gene conversion as a mechanism for antigenic variation, which results in subsequent evasion of the immune response and persistence in the reservoir host. the combination of genome sequence data and in vivo studies tracking variant emergence not only provides insight into the genetic mechanisms for variant generation and hierarchy in variant ... | 2007 | 17662656 |
| isolation and compositional analysis of trypanosomatid editosomes. | most mitochondrial (mt) mrnas in trypanosomes undergo posttranscriptional rna editing, which inserts and deletes uridines (us) to produce the mature and functional mrna. the editing process is catalyzed by multiple enzymatic steps and is carried out by an approximately 20s macromolecular complex, the editosome. editosomes have been purified from trypanosoma brucei using various techniques including combinations of column chromatography, gradient sedimentation, monoclonal antibody affinity, and t ... | 2007 | 17662834 |
| uridine insertion/deletion editing activities. | the uridine nucleotide insertion and deletion editing of trypanosomatid mitochondrial mrnas is catalyzed by a macromolecular complex, the editosome. many investigations of rna editing involve some assessment of editosome activity either in vitro or in vivo. assays to detect insertion or deletion editing activity on rnas in vitro have been particularly useful, and can include the initial endonucleolytic step (full-round) or bypass it (precleaved). additional assays to examine individual catalytic ... | 2007 | 17662835 |
| rna editing uridylyltransferases of trypanosomatids. | terminal rna uridylyltransferases (tutases) catalyze the transfer of ump residues to the 3' hydroxyl group of rna. these enzymes belong to the dna polymerase beta superfamily, which also includes poly(a) polymerases, cca-adding enzymes, and other nucleotidyltransferases. studies of uridylyl insertion/deletion rna editing in mitochondria of trypanosomatids provided the first examples of biological functions for tutases: posttranscriptional uridylylation of guide rnas by rna editing tutase 1 (ret1 ... | 2007 | 17662836 |
| isolation of rna binding proteins involved in insertion/deletion editing. | rna editing is a collective term referring to a plethora of reactions that ultimately lead to changes in rna nucleotide sequences apart from splicing, 5' capping, or 3' end processing. in the mitochondria of trypanosomatids, insertion and deletion of uridines must occur, often on a massive scale, in order to generate functional messenger rnas. the current state of knowledge perceives the editing machinery as a dynamic system, in which heterogeneous protein complexes undergo multiple transient rn ... | 2007 | 17662837 |
| rna-protein interactions in assembled editing complexes in trypanosomes. | multisubunit rna editing complexes recognize thousands of pre-mrna sites in the single mitochondrion of trypanosomes. specific determinants at each editing site must trigger the complexes to catalyze a complete cycle of either uridylate insertion or deletion. while a wealth of information on the protein composition and catalytic activities of these complexes is currently available, the precise mechanisms that govern substrate recognition and editing site specificity remain unknown. this chapter ... | 2007 | 17662838 |
| functional genomics and immunological approaches toward a comprehensive view of protozoan parasite virulence factors. | 2007 | 17678416 | |
| tbarf1 influences lysosomal function but not endocytosis in procyclic stage trypanosoma brucei. | the adp ribosylation factors (arfs) are a highly conserved subfamily of the ras small gtpases with crucial roles in vesicle budding and membrane trafficking. unlike in other eukaryotes, the orthologue of arf1 in the host bloodstream form of trypanosoma brucei is essential for the maintenance of endocytosis. in contrast, as shown in this study, knockdown of tbarf1 by rna interference has no effect on fluid-phase endocytosis in the insect stage of the parasite. the protein remains essential for th ... | 2007 | 17681620 |
| antiproliferative effect of dihydroxyacetone on trypanosoma brucei bloodstream forms: cell cycle progression, subcellular alterations, and cell death. | we evaluated the effects of dihydroxyacetone (dha) on trypanosoma brucei bloodstream forms. dha is considered an energy source for many different cell types. t. brucei takes up dha readily due to the presence of aquaglyceroporins. however, the parasite is unable to use it as a carbon source because of the absence of dha kinase (dhak). we could not find a homolog of the relevant gene in the genomic database of t. brucei and have been unable to detect dhak activity in cell lysates of the parasite, ... | 2007 | 17682096 |
| the hydrocephalus inducing gene product, hydin, positions axonemal central pair microtubules. | impairment of cilia and flagella function underlies a growing number of human genetic diseases. mutations in hydin in hy3 mice cause lethal communicating hydrocephalus with early onset. hydin was recently identified as an axonemal protein; however, its function is as yet unknown. | 2007 | 17683645 |
| ku heterodimer-independent end joining in trypanosoma brucei cell extracts relies upon sequence microhomology. | dna double-strand breaks (dsbs) are repaired primarily by two distinct pathways: homologous recombination and nonhomologous end joining (nhej). nhej has been found in all eukaryotes examined to date and has been described recently for some bacterial species, illustrating its ancestry. trypanosoma brucei is a divergent eukaryotic protist that evades host immunity by antigenic variation, a process in which homologous recombination plays a crucial function. while homologous recombination has been e ... | 2007 | 17693593 |
| adenosine kinase of trypanosoma brucei and its role in susceptibility to adenosine antimetabolites. | trypanosoma brucei cannot synthesize purines de novo and relies on purine salvage from its hosts to build nucleic acids. with adenosine being a preferred purine source of bloodstream-form trypanosomes, adenosine kinase (ak; ec 2.7.1.20) is likely to be a key player in purine salvage. adenosine kinase is also of high pharmacological interest, since for many adenosine antimetabolites, phosphorylation is a prerequisite for activity. here, we cloned and functionally characterized adenosine kinase fr ... | 2007 | 17698621 |
| 2,n6-disubstituted adenosine analogs with antitrypanosomal and antimalarial activities. | a library of 2,n(6)-disubstituted adenosine analogs was synthesized and the analogs were tested for their antiprotozoal activities. it was found that 2-methoxy and 2-histamino and n(6)-m-iodobenzyl substitutions generally produced analogs with low levels of antiprotozoal activity. the best antiplasmodial activity was achieved with large aromatic substitutions, such as n(6)-2,2-diphenylethyl and naphthylmethyl, which could indicate a mechanism of action through aromatic stacking with heme in the ... | 2007 | 17698622 |
| uridylate-specific 3' 5'-exoribonucleases involved in uridylate-deletion rna editing in trypanosomatid mitochondria. | in kinetoplastid protists, maturation of mitochondrial pre-mrnas involves the insertion and deletion of uridylates (us) within coding regions, as specified by mitochondrial dna-encoded guide rnas. u-deletion editing involves endonucleolytic cleavage of the pre-mrna at the editing site followed by u-specific 3'-5'-exonucleolytic removal of nonbase-paired us prior to ligation of the two mrna cleavage fragments. we showed previously that an exonuclease/endonuclease/phosphatase (eep) motif protein f ... | 2007 | 17699520 |
| genetic characterisation of trypanosoma brucei s.l. using microsatellite typing: new perspectives for the molecular epidemiology of human african trypanosomiasis. | the pathogenic agent of human african trypanosomiasis (hat) is a trypanosome belonging to the species trypanosoma brucei s.l. molecular methods developed for typing t. brucei s.l. stocks are for the most part not polymorphic enough to study genetic diversity within t. brucei gambiense (t. b. gambiense) group 1, the main agent of hat in west and central africa. furthermore, these methods require high quantities of parasite material and consequently are hampered by a selection bias of the isolatio ... | 2007 | 17704009 |
| jbp2, a swi2/snf2-like protein, regulates de novo telomeric dna glycosylation in bloodstream form trypanosoma brucei. | synthesis of the modified thymine base, beta-d-glucosyl-hydroxymethyluracil or j, within telomeric dna of trypanosoma brucei correlates with the bloodstream form specific epigenetic silencing of telomeric variant surface glycoprotein genes involved in antigenic variation. in order to analyze the function of base j in the regulation of antigenic variation, we are characterizing the regulatory mechanism of j biosynthesis. we have recently proposed a model in which chromatin remodeling by a swi2/sn ... | 2007 | 17706299 |
| quinuclidine derivatives as potential antiparasitics. | there is an urgent need for the development of new drugs for the treatment of tropical parasitic diseases such as chagas' disease and leishmaniasis. one potential drug target in the organisms that cause these diseases is sterol biosynthesis. this paper describes the design and synthesis of quinuclidine derivatives as potential inhibitors of a key enzyme in sterol biosynthesis, squalene synthase (sqs). a number of compounds that were inhibitors of the recombinant leishmania major sqs at submicrom ... | 2007 | 17709461 |
| histone modifications in trypanosoma brucei. | several biological processes in trypanosoma brucei are affected by chromatin structure, including gene expression, cell cycle regulation, and life-cycle stage differentiation. in saccharomyces cerevisiae and other organisms, chromatin structure is dependent upon posttranslational modifications of histones, which have been mapped in detail. the tails of the four core histones of t. brucei are highly diverged from those of mammals and yeasts, so sites of potential modification cannot be reliably i ... | 2007 | 17714803 |
| two trypanosome-specific proteins are essential factors for 5s rrna abundance and ribosomal assembly in trypanosoma brucei. | we have previously identified and characterized two novel nuclear rna binding proteins, p34 and p37, which have been shown to bind 5s rrna in trypanosoma brucei. these two proteins are nearly identical, with one major difference, an 18-amino-acid insert in the n-terminal region of p37, as well as three minor single-amino-acid differences. homologues to p34 and p37 have been found only in other trypanosomatids, suggesting that these proteins are unique to this ancient family. we have employed rna ... | 2007 | 17715362 |
| down-regulation of the trypanosomatid signal recognition particle affects the biogenesis of polytopic membrane proteins but not of signal peptide-containing proteins. | protein translocation across the endoplasmic reticulum is mediated by the signal recognition particle (srp). in this study, the srp pathway in trypanosomatids was down-regulated by two approaches: rna interference (rnai) silencing of genes encoding srp proteins in trypanosoma brucei and overexpression of dominant-negative mutants of 7sl rna in leptomonas collosoma. the biogenesis of both signal peptide-containing proteins and polytopic membrane proteins was examined using endogenous and green fl ... | 2007 | 17715370 |
| in vitro and in vivo evaluation of the antitrypanosomal activity of fractions of holarrhena africana. | the aqueous extract of young leaves of holarrhena africana, a plant used in the nigerian traditional medicine, exhibited good activity against trypanosoma brucei spp. the extract was fractionated and eight fractions were obtained. one fraction designated as haf(5) showed in vitro activity against trypanosoma brucei rhodesiense with an ic(50) value of 0.785 microg/mg and no overt cytotoxicity against l-6 cells. fraction haf(5) was tested in vivo at two doses and found to exhibit in vivo efficacy ... | 2007 | 17728085 |
| dual role of the rna substrate in selectivity and catalysis by terminal uridylyl transferases. | terminal rna uridylyltransferases (tutases) catalyze template-independent ump addition to the 3' hydroxyl of rna. tutases belong to the dna polymerase beta superfamily of nucleotidyltransferases that share a conserved catalytic domain bearing three metal-binding carboxylate residues. we have previously determined crystal structures of the utp-bound and apo forms of the minimal trypanosomal tutase, tbtut4, which is composed solely of the n-terminal catalytic and c-terminal base-recognition domain ... | 2007 | 17785418 |
| a glycosylphosphatidylinositol-based treatment alleviates trypanosomiasis-associated immunopathology. | the gpi-anchored trypanosome variant surface glycoprotein (vsg) triggers macrophages to produce tnf, involved in trypanosomiasis-associated inflammation and the clinical manifestation of sleeping sickness. aiming at inhibiting immunopathology during experimental trypanosoma brucei infections, a vsg-derived gpi-based treatment approach was developed. to achieve this, mice were exposed to the gpi before an infectious trypanosome challenge. this gpi-based strategy resulted in a significant prolonge ... | 2007 | 17785839 |
| dihydroxyacetone induced autophagy in african trypanosomes. | dihydroxyacetone (dha) was examined to explore its trypanocidal activity. the compound is easily taken up by trypanosomes via its aquaglyceroporins but is not converted to a glycolytic intermediate due to the lack of a respective kinase. investigating the dha-induced cell death it became evident that parasites die by autophagy rather than by necrosis or apoptosis. since autophagy is not well studied in african trypanosomes our work offers a way to investigate the importance of autophagy for tryp ... | 2007 | 17786028 |
| structural flexibility in trypanosoma brucei enolase revealed by x-ray crystallography and molecular dynamics. | enolase is a validated drug target in trypanosoma brucei. to better characterize its properties and guide drug design efforts, we have determined six new crystal structures of the enzyme, in various ligation states and conformations, and have carried out complementary molecular dynamics simulations. the results show a striking structural diversity of loops near the catalytic site, for which variation can be interpreted as distinct modes of conformational variability that are explored during the ... | 2007 | 17822439 |
| the argonaute protein tbago1 contributes to large and mini-chromosome segregation and is required for control of rime retroposons and rhs pseudogene-associated transcripts. | the protist trypanosoma brucei possesses a single argonaute gene called tbago1 that is necessary for rnai silencing. we previously showed that in strain 427, tbago1 knock-out leads to a slow growth phenotype and to chromosome segregation defects. here we report that the slow growth phenotype is linked to defects in segregation of both large and mini-chromosome populations, with large chromosomes being the most affected. these phenotypes are completely reversed upon inducible re-expression of tba ... | 2007 | 17822785 |
| hemoglobin is a co-factor of human trypanosome lytic factor. | trypanosome lytic factor (tlf) is a high-density lipoprotein (hdl) subclass providing innate protection to humans against infection by the protozoan parasite trypanosoma brucei brucei. two primate-specific plasma proteins, haptoglobin-related protein (hpr) and apolipoprotein l-1 (apol-1), have been proposed to kill t. b. brucei both singularly or when co-assembled into the same hdl. to better understand the mechanism of t. b. brucei killing by tlf, the protein composition of tlf was investigated ... | 2007 | 17845074 |
| elongation factor 1a mediates the specificity of mitochondrial trna import in t. brucei. | mitochondrial trna import is widespread in eukaryotes. yet, the mechanism that determines its specificity is unknown. previous in vivo experiments using the trnas(met), trna(ile) and trna(lys) have suggested that the t-stem nucleotide pair 51:63 is the main localization determinant of trnas in trypanosoma brucei. in the cytosol-specific initiator trna(met), this nucleotide pair is identical to the main antideterminant that prevents interaction with cytosolic elongation factor (eef1a). here we sh ... | 2007 | 17853889 |
| dileucine signal-dependent and ap-1-independent targeting of a lysosomal glycoprotein in trypanosoma brucei. | sorting of trans-membrane proteins destined for the lysosome is achieved by selective inclusion into post-golgi transport vesicles. in higher eukaryotes sorting may be mediated by a peptidic motif, principally acidic clusters and tyrosine- or dileucine-based cytoplasmic signals or by inclusion of mannose-6-phosphate (m6p) into the n-glycans of lysosomal proteins. in african trypanosomes a major lysosomal trans-membrane protein is cb-1/p67. the cytoplasmic domain of p67 lacks tyrosine and lysine, ... | 2007 | 17869353 |
| novel membrane-bound eif2alpha kinase in the flagellar pocket of trypanosoma brucei. | translational control mediated by phosphorylation of the alpha subunit of the eukaryotic initiation factor 2 (eif2alpha) is central to stress-induced programs of gene expression. trypanosomatids, important human pathogens, display differentiation processes elicited by contact with the distinct physiological milieu found in their insect vectors and mammalian hosts, likely representing stress situations. trypanosoma brucei, the agent of african trypanosomiasis, encodes three potential eif2alpha ki ... | 2007 | 17873083 |
| small trypanosome rna-binding proteins tbubp1 and tbubp2 influence expression of f-box protein mrnas in bloodstream trypanosomes. | in the african trypanosome trypanosoma brucei nearly all control of gene expression is posttranscriptional; sequences in the 3'-untranslated regions of mrnas determine the steady-state mrna levels by regulation of rna turnover. here we investigate the roles of two related proteins, tbubp1 and tbubp2, containing a single rna recognition motif, in trypanosome gene expression. tbubp1 and tbubp2 are in the cytoplasm and nucleus, comprise ca. 0.1% of the total protein, and are not associated with pol ... | 2007 | 17873084 |
| trypanocidal and antileishmanial dihydrochelerythrine derivatives from garcinia lucida. | three benzo[ c]phenanthridine alkaloids have been isolated from the stem bark of garcinia lucida: dihydrochelerythrine ( 1), 6-acetonyldihydrochelerythrine ( 2), and its new derivative, ( s)1''-(9,10-dihydro-2',3'-dihydroxy-7,8-dimethoxy-10-methyl-1,2-benzophenanthridin-9-yl)propan-2''-one (lucidamine a) ( 3). the new diisoprenylated derivative of lucidamine b ( 4) was obtained by semisynthesis. these dihydrochelerythrine derivatives as well as the crude extract displayed attractive antiprotozoa ... | 2007 | 17880175 |
| activation of endocytosis as an adaptation to the mammalian host by trypanosomes. | immune evasion in african trypanosomes is principally mediated by antigenic variation, but rapid internalization of surface-bound immune factors may contribute to survival. endocytosis is upregulated approximately 10-fold in bloodstream compared to procyclic forms, and surface coat remodeling accompanies transition between these life stages. here we examined expression of endocytosis markers in tsetse fly stages in vivo and monitored modulation during transition from bloodstream to procyclic for ... | 2007 | 17905918 |
| members of a large retroposon family are determinants of post-transcriptional gene expression in leishmania. | trypanosomatids are unicellular protists that include the human pathogens leishmania spp. (leishmaniasis), trypanosoma brucei (sleeping sickness), and trypanosoma cruzi (chagas disease). analysis of their recently completed genomes confirmed the presence of non-long-terminal repeat retrotransposons, also called retroposons. using the 79-bp signature sequence common to all trypanosomatid retroposons as bait, we identified in the leishmania major genome two new large families of small elements--lm ... | 2007 | 17907803 |
| human serum lyses trypanosoma brucei by triggering uncontrolled swelling of the parasite lysosome. | trypanosoma brucei brucei infects a wide range of mammals, but is unable to infect humans because this subspecies is lysed by normal human serum (nhs). the phenotype of cellular lysis is debated. for some authors the lysosome undergoes osmotic swelling due to massive influx of chloride ions from the cytoplasmic compartment, but others describe multiple small cytoplasmic vacuoles and general swelling of the cellular body. using population-level imaging of live immobilized trypanosomes throughout ... | 2007 | 17910690 |
| [human resistance to african trypanosoma infections]. | african trypanosomes (prototype: trypanosoma brucei) are protozoan flagellates that infect a wide range of different mammals. in humans, these parasites have to counteract innate immunity because human serum possesses efficient trypanolytic activity. resistance to this activity has arisen in two t. brucei subspecies, termed t. b. rhodesiense and t. b. gambiense, allowing them to infect humans where they cause sleeping sickness in east and west africa respectively. the study of the mechanism by w ... | 2007 | 18429487 |
| isolation of mitochondria from procyclic trypanosoma brucei. | the mitochondrion of the parasitic protozoon trypanosoma brucei shows a number of unique features, many of which represent highly interesting research topics. studies of these subjects require the purification of mitochondrial fractions. here, we describe and discuss the two most commonly used methods to isolate mitochondria from insect stage t. brucei. in the first protocol, the cells are lysed under hypotonic conditions, and mitoplast vesicles are isolated on percoll gradients; in the second m ... | 2007 | 18314718 |
| atp production in isolated mitochondria of procyclic trypanosoma brucei. | this chapter describes a luciferase-based protocol to measure adenosine triphosphate (atp) production in isolated mitochondria of trypanosoma brucei. the assay represents an excellent method to characterize the functionality of isolated mitochondria. comparing the atp production induced by substrates for oxidative phosphorylation to the one induced by substrates for substrate-level phosphorylation allows conclusions regarding the integrity of the outer and inner mitochondrial membranes. furtherm ... | 2007 | 18314740 |
| the trypanothione system. | trypanosomes and leishmania, the causative agents of severe tropical diseases, employ 2-cys-peroxiredoxins together with cysteine-homologues of glutathione peroxidases and ascorbate-dependent peroxidases for the detoxification of hydroperoxides. all three types of peroxidases gain their reducing equivalents from the parasite-specific dithiol trypanothione [bis(glutathionyl)spermidine]. based on their primary structure and cellular localization, the trypanosomatid 2-cys-peroxiredoxins are subdivi ... | 2007 | 18084897 |
| antioxidants promote establishment of trypanosome infections in tsetse. | efficient, cyclical transmission of trypanosomes through tsetse flies is central to maintenance of human sleeping sickness and nagana across sub-saharan africa. infection rates in tsetse are normally very low as most parasites ingested with the fly bloodmeal die in the fly gut, displaying the characteristics of apoptotic cells. here we show that a range of antioxidants (glutathione, cysteine, n-acetyl-cysteine, ascorbic acid and uric acid), when added to the insect bloodmeal, can dramatically in ... | 2007 | 17306056 |
| rna polymerase i transcription stimulates homologous recombination in trypanosoma brucei. | 2007 | 17316839 | |
| 1,2,3-triazolylalkylribitol derivatives as nucleoside hydrolase inhibitors. | a range of novel 1,2,3-triazolylalkylribitol derivatives were synthesized and evaluated as nucleoside hydrolase inhibitors. the most active compound (11a) has low micromolar potency and is structurally diverse from previously reported nucleoside hydrolase inhibitors, which, along with the simplicity of the chemistry involved in its synthesis, makes it a good lead for the further development of novel nucleoside hydrolase inhibitors. | 2007 | 17317181 |
| factors affecting trypanosome maturation in tsetse flies. | trypanosoma brucei brucei infections which establish successfully in the tsetse fly midgut may subsequently mature into mammalian infective trypanosomes in the salivary glands. this maturation is not automatic and the control of these events is complex. utilising direct in vivo feeding experiments, we report maturation of t. b. brucei infections in tsetse is regulated by antioxidants as well as environmental stimuli. dissection of the maturation process provides opportunities to develop transmis ... | 2007 | 17318257 |
| origins of amino acid transporter loci in trypanosomatid parasites. | large amino acid transporter gene families were identified from the genome sequences of three parasitic protists, trypanosoma brucei, trypanosoma cruzi and leishmania major. these genes encode molecular sensors of the external host environment for trypanosomatid cells and are crucial to modulation of gene expression as the parasite passes through different life stages. this study provides a comprehensive phylogenetic account of the origins of these genes, redefining each locus according to a pos ... | 2007 | 17319943 |
| characterization of the role of the receptors pex5 and pex7 in the import of proteins into glycosomes of trypanosoma brucei. | peroxins 5 and 7 are receptors for protein import into the peroxisomal matrix. we studied the involvement of these peroxins in the biogenesis of glycosomes in the protozoan parasite trypanosoma brucei. glycosomes are peroxisome-like organelles in which a major part of the glycolytic pathway is sequestered. we here report the characterization of the t. brucei homologue of pex7 and provide several data strongly suggesting that it can bind to pex5. depletion of pex5 or pex7 by rna interference had ... | 2007 | 17320990 |
| toxicity and anti-trypanosomal effects of ethanolic extract of butyrospermum paradoxum (sapotaceae) stem bark in rats infected with trypanosoma brucei and trypanosoma congolense. | the ethanolic extract of butyrospermum paradoxum stem bark, commonly used in the traditional treatment of various diseases including animal and human trypanosomosis in north-eastern nigeria, was tested for toxicity and anti-trypanosomal efficacy in rats infected with trypanosoma congolense and trypanosoma brucei. following intra-peritoneal administration, the extract induced behavioural changes, morbidity and mortality in the rats. the symptoms observed included anorexia, dehydration, depression ... | 2007 | 17321088 |
| an essential cell cycle-regulated nucleolar protein relocates to the mitotic spindle where it is involved in mitotic progression in trypanosoma brucei. | tbnop86 and tbnop66 are two novel nucleolar proteins isolated in trypanosoma brucei. they share 92.6% identity, except for an additional c-terminal domain of tbnop86 of 182 amino acids in length. both proteins are found in trypanosomatidae, but similarity to other eukaryotic proteins could not be found. tbnop86 and tbnop66 are expressed at similar level in procyclic and bloodstream forms, although the relative level of expression of tbnop66 is 11 times lower. tbnop86 undergoes post-translational ... | 2007 | 17322293 |
| antiparasitic activity of some new caledonian medicinal plants. | twenty-nine extracts of 18 medicinal plants used in new caledonia by traditional healers to treat inflammation, fever and in cicatrizing remedies were evaluated in vitro against several parasites (leishmania donovani, trypanosoma brucei brucei, trichomonas vaginalis and caenorhabditis elegans). among the selected plants, scaevola balansae and premna serratifolia l. were the most active against leishmania donovani with ic(50) values between 5 and 10microg/ml. the almond and aril extracts from myr ... | 2007 | 17329051 |
| conserved motifs reveal details of ancestry and structure in the small tim chaperones of the mitochondrial intermembrane space. | the mitochondrial inner and outer membranes are composed of a variety of integral membrane proteins, assembled into the membranes posttranslationally. the small translocase of the inner mitochondrial membranes (tims) are a group of approximately 10 kda proteins that function as chaperones to ferry the imported proteins across the mitochondrial intermembrane space to the outer and inner membranes. in yeast, there are 5 small tim proteins: tim8, tim9, tim10, tim12, and tim13, with equivalent prote ... | 2007 | 17329230 |
| expression, purification, characterization, and in vivo targeting of trypanosome ctp synthetase for treatment of african sleeping sickness. | african sleeping sickness is a fatal disease caused by two parasite subspecies: trypanosoma brucei gambiense and t. b. rhodesiense. we previously reported that trypanosomes have extraordinary low ctp pools compared with mammalian cells. trypanosomes also lack salvage of cytidine/cytosine making the parasite ctp synthetase a potential target for treatment of the disease. in this study, we have expressed and purified recombinant t. brucei ctp synthetase. the enzyme has a higher k(m) value for utp ... | 2007 | 17331943 |
| cell cycle regulation in trypanosoma brucei. | cell division is regulated by intricate and interconnected signal transduction pathways that precisely coordinate, in time and space, the complex series of events involved in replicating and segregating the component parts of the cell. in trypanosoma brucei, considerable progress has been made over recent years in identifying molecular regulators of the cell cycle and elucidating their functions, although many regulators undoubtedly remain to be identified, and there is still a long way to go wi ... | 2007 | 17335918 |
| chemotherapeutic strategies against trypanosoma brucei: drug targets vs. drug targeting. | trypanosoma brucei rhodesiense and t. b. gambiense are the causative agents of sleeping sickness, a fatal disease that affects 36 countries in sub-saharan africa. nevertheless, only a handful of clinically useful drugs are available. these drugs suffer from severe side-effects. the situation is further aggravated by the alarming incidence of treatment failures in several sleeping sickness foci, apparently indicating the occurrence of drug-resistant trypanosomes. because of these reasons, and sin ... | 2007 | 17346174 |
| spliced-leader rna silencing: a novel stress-induced mechanism in trypanosoma brucei. | the signal-recognition particle (srp) mediates the translocation of membrane and secretory proteins across the endoplasmic reticulum upon interaction with the srp receptor. in trypanosomes, the main rna molecule is the spliced-leader (sl) rna, which donates the sl sequence to all messenger rna through trans-splicing. here, we show that rna interference silencing of the srp receptor (sralpha) in trypanosoma brucei caused the accumulation of srp on ribosomes and triggered silencing of sl rna (sls) ... | 2007 | 17347669 |
| repetitive dna is associated with centromeric domains in trypanosoma brucei but not trypanosoma cruzi. | trypanosomes are parasitic protozoa that diverged early from the main eukaryotic lineage. their genomes display several unusual characteristics and, despite completion of the trypanosome genome projects, the location of centromeric dna has not been identified. | 2007 | 17352808 |
| distinct roles of haptoglobin-related protein and apolipoprotein l-i in trypanolysis by human serum. | apolipoprotein l-i (apol-i) is a human high-density lipoprotein (hdl) component able to kill trypanosoma brucei brucei by forming anion-selective pores in the lysosomal membrane of the parasite. another hdl component, haptoglobin-related protein (hpr), has been suggested as an additional toxin required for full trypanolytic activity of normal human serum. we recently reported the case of a human lacking apol-i (apol-i(-/-)hs) as the result of frameshift mutations in both apol-i alleles. here, we ... | 2007 | 17360487 |
| a fatty-acid synthesis mechanism specialized for parasitism. | most cells use either a type i or type ii synthase to make fatty acids. trypanosoma brucei, the sleeping sickness parasite, provides the first example of a third mechanism for this process. trypanosomes use microsomal elongases to synthesize fatty acids de novo, whereas other cells use elongases to make long-chain fatty acids even longer. the modular nature of the pathway allows synthesis of different fatty-acid end products, which have important roles in trypanosome biology. indeed, this newly ... | 2007 | 17363967 |
| co-administration of na-edta and diminazene aceturate (da) to mice infected with da-resistant trypanosoma brucei. | this study investigated the effects of co-administration of na-edta and diminazene aceturate (da) on the level of parasitaemia (lop), parasite clearance, packed cell volume (pcv) and post-infection survival time (pist) in mice infected with da-resistant trypanosoma brucei. five groups of 10 mice were treated as follows: infected and treated with na-edta+da; infected and treated with da alone; infected and treated with na-edta alone; infected-untreated; and uninfected-untreated. the co-administra ... | 2007 | 17367805 |
| a mitogen-activated protein kinase of trypanosoma brucei confers resistance to temperature stress. | 2007 | 17368580 | |
| an essential role of krepb4 in rna editing and structural integrity of the editosome in trypanosoma brucei. | rna editing in the sleeping sickness parasite trypanosoma brucei remodels mitochondrial transcripts by the addition and deletion of uridylates as specified by guide rnas. editing is catalyzed by at least three distinct approximately 20s multiprotein editosomes, all of which contain krepb4, a protein with rnase iii and pumilio motifs. rnai repression of krepb4 expression in procyclic forms (pfs) strongly inhibited growth and in vivo rna editing, greatly diminished the abundance of 20s editosomes, ... | 2007 | 17369311 |
| bis-acridines as lead antiparasitic agents: structure-activity analysis of a discrete compound library in vitro. | parasitic diseases are of enormous public health significance in developing countries-a situation compounded by the toxicity of and resistance to many current chemotherapeutics. we investigated a focused library of 18 structurally diverse bis-acridine compounds for in vitro bioactivity against seven protozoan and one helminth parasite species and compared the bioactivities and the cytotoxicities of these compounds toward various mammalian cell lines. structure-activity relationships demonstrated ... | 2007 | 17371810 |