Publications

the two cytoplasmic dynein-2 isoforms in leishmania mexicana perform separate functions.	eukaryotic organisms with cilia or flagella typically express two non-axonemal or "cytoplasmic" dyneins, dynein-1 and dynein-2. interestingly, we find that leishmania mexicana is unusual and contains two distinct cytoplasmic dynein-2 heavy chain genes (designated lmxdhc2.1 and lmxdhc2.2) along with a single dynein-1 heavy chain (lmxdhc1). disruption of lmxdhc2.2 resulted in immotile parasites that had a rounded cell body. although they assume amastigote morphology, immunoblot analysis of these c ...	2005	16054709
downregulation of the essential trypanosoma brucei la protein affects accumulation of elongator methionyl-trna.		2005	16055205
characterization of a multisubunit transcription factor complex essential for spliced-leader rna gene transcription in trypanosoma brucei.	in the unicellular human parasites trypanosoma brucei, trypanosoma cruzi, and leishmania spp., the spliced-leader (sl) rna is a key molecule in gene expression donating its 5'-terminal region in sl addition trans splicing of nuclear pre-mrna. while there is no evidence that this process exists in mammals, it is obligatory in mrna maturation of trypanosomatid parasites. hence, throughout their life cycle, these organisms crucially depend on high levels of sl rna synthesis. as putative sl rna gene ...	2005	16055738
trypanosomal tbp functions with the multisubunit transcription factor tsnap to direct spliced-leader rna gene expression.	protein-coding genes of trypanosomes are mainly transcribed polycistronically and cleaved into functional mrnas in a process that requires trans splicing of a capped 39-nucleotide rna derived from a short transcript, the spliced-leader (sl) rna. sl rna genes are individually transcribed from the only identified trypanosome rna polymerase ii promoter. we have purified and characterized a sequence-specific sl rna promoter-binding complex, tsnap(c), from the pathogenic parasite trypanosoma brucei, ...	2005	16055739
the induction of a type 1 immune response following a trypanosoma brucei infection is myd88 dependent.	the initial host response toward the extracellular parasite trypanosoma brucei is characterized by the early release of inflammatory mediators associated with a type 1 immune response. in this study, we show that this inflammatory response is dependent on activation of the innate immune system mediated by the adaptor molecule myd88. in the present study, myd88-deficient macrophages are nonresponsive toward both soluble variant-specific surface glycoprotein (vsg), as well as membrane-bound vsg pu ...	2005	16081822
fast, simple, and low-cost test for drug-resistant pathogens.		2005	16084237
detection of arsenical drug resistance in trypanosoma brucei with a simple fluorescence test.	the resurgence of human african trypanosomiasis (hat), coupled with an increased incidence of drug resistance, is of concern. we report a quick, simple, and sensitive test for identification of parasites resistant to melarsoprol, the main drug used to treat late stage hat. resistant parasites are defective in a plasma membrane transporter responsible for drug uptake. the same transporter carries the fluorescent diamidine db99 (2,5-bis-(4-amidinophenyl)-3,4-dimethylfuran) into trypanosomes. the t ...	2005	16084257
vitamin c biosynthesis in trypanosomes: a role for the glycosome.	the capacity to synthesize vitamin c (ascorbate) is widespread in eukaryotes but is absent from humans. the last step in the biosynthetic pathway involves the conversion of an aldonolactone substrate to ascorbate, a reaction catalyzed by members of an fad-dependent family of oxidoreductases. here we demonstrate that both the african trypanosome, trypanosoma brucei, and the american trypanosome, trypanosoma cruzi, have the capacity to synthesize vitamin c and show that this reaction occurs in a u ...	2005	16087875
telomere structure and shortening in telomerase-deficient trypanosoma brucei.	telomerase consists of a reverse transcriptase (tert) and an rna that contains a template for telomere-repeat extension. telomerase is required to prevent telomere erosion and its activity or lack thereof is important for tumorigenesis and ageing. telomerase has been identified in numerous organisms but it has not been studied in kinetoplastid protozoa. trypanosoma brucei, the causative agent of african sleeping sickness, evades the host immune response by frequently changing its variant surface ...	2005	16091631
effects of rna interference of trypanosoma brucei structure-specific endonuclease-i on kinetoplast dna replication.	kinetoplast dna, the mitochondrial dna of trypanosomatid protozoa, is a network containing several thousand topologically interlocked dna minicircles. kinetoplast dna synthesis involves release of minicircles from the network, replication of the free minicircles, and reattachment of the progeny back onto the network. one enzyme involved in this process is structure-specific endonuclease-i. this enzyme, originally purified from crithidia fasciculata, has been proposed to remove minicircle replica ...	2005	16096280
design and synthesis of a series of melamine-based nitroheterocycles with activity against trypanosomatid parasites.	the parasites that give rise to human african trypanosomiasis (hat) are auxotrophs for various nutrients from the human host, including purines. they have specialist nucleoside transporters to import these metabolites. in addition to uptake of purine nucleobases and purine nucleosides, one of these transporters, the p2 transporter, can carry melamine derivatives; these derivatives are not substrates for the corresponding mammalian transporters. in this paper, we report the coupling of the melami ...	2005	16107157
elucidating the role of h/aca-like rnas in trans-splicing and rrna processing via rna interference silencing of the trypanosoma brucei cbf5 pseudouridine synthase.	most pseudouridinylation in eukaryotic rrna and small nuclear rnas is guided by h/aca small nucleolar rnas. in this study, the trypanosoma brucei pseudouridine synthase, cbf5p, a snornp protein, was identified and silenced by rnai. depletion of this protein destabilized all small nucleolar rnas of the h/aca-like family. following silencing, defects in rrna processing, such as accumulation of precursors and inhibition of cleavages to generate the mature rrna, were observed. snr30, an h/aca rna in ...	2005	16107339
signalling the genome: the ras-like small gtpase family of trypanosomatids.	the genomes of the three principle experimental-model species of kinetoplastida -trypanosoma brucei brucei, trypanosoma cruzi and leishmania major - are now complete, providing both a milestone for trypanosome biology and an opportunity to consider a multitude of questions at the genome level. of the >40 members of the ras-like gtpase family in t. brucei, at least 30 are involved in intracellular transport, whereas fewer than eight are likely to have a classical role in signal transduction. ther ...	2005	16112905
deletion of the glucosidase ii gene in trypanosoma brucei reveals novel n-glycosylation mechanisms in the biosynthesis of variant surface glycoprotein.	the trypanosomatids are generally aberrant in their protein n-glycosylation pathways. however, protein n-glycosylation in the african trypanosome trypanosoma brucei, etiological agent of human african sleeping sickness, is not well understood. here, we describe the creation of a bloodstream-form t. brucei mutant that is deficient in the endoplasmic reticulum enzyme glucosidase ii. characterization of the variant surface glycoprotein, the main glycoprotein synthesized by the parasite with two n-g ...	2005	16120601
regulation of antigen gene expression in trypanosoma brucei.	the trypanosome genome is organized into long polycistronic units that seem to be permanently transcribed in proliferative stages of the parasite. cellular differentiation is controlled primarily at the level of individual mrna maturation and stability. the transcription units of the two major stage-specific antigens, the variant surface glycoprotein (vsg) of the bloodstream form and procyclin of the procyclic form, are subject to an additional layer of control: the mutually exclusive activation ...	2005	16126458
purine nucleobase transport in amastigotes of leishmania mexicana: involvement in allopurinol uptake.	nucleobase and nucleoside transporters play central roles in the biochemistry of parasitic protozoa, as they lack the ability to synthesize purines de novo and are absolutely reliant upon purine salvage from their hosts. furthermore, such transporters are potentially critical to the pharmacology of these important human pathogens, because they mediate the uptake of purine analogues, as well as some nonpurine drugs, that can be selectively cytotoxic to the parasites. we here report the first iden ...	2005	16127040
the central roles of telomeres and subtelomeres in antigenic variation in african trypanosomes.	telomeres and subtelomeres are important to the virulence of a number of pathogens, as they harbour large diverse gene families associated with the maintenance of infection. evasion of immunity by african trypanosomes involves the differential expression of variant surface glycoproteins (vsgs), which are encoded by a family of >1500 genes and pseudogenes. this silent archive is located subtelomerically and is activated by gene conversion into specialized transcription units, which themselves are ...	2005	16132817
vsg switching in trypanosoma brucei: antigenic variation analysed using rnai in the absence of immune selection.	trypanosoma brucei relies on antigenic variation of its variant surface glycoprotein (vsg) coat for survival. we show that vsg switching can be efficiently studied in vitro using vsg rnai in place of an immune system to select for switch variants. contrary to models predicting an instant switch after inhibition of vsg synthesis, switching was not induced by vsg rnai and occurred at a rate of 10(-4) per division. we find a highly reproducible hierarchy of vsg activation, which appears to be capab ...	2005	16135228
parasite genome similarities offer hope for new drugs and vaccines.		2005	16138182
repression of gene expression by the coliphage ms2 coat protein in trypanosoma brucei.		2005	16139377
distinct cytoskeletal modulation and regulation of g1-s transition in the two life stages of trypanosoma brucei.	procyclic-form trypanosoma brucei is arrested in g1 phase with extended and/or branched posterior morphology when expression of its cdc2-related kinases 1 and 2 (crk1 and crk2) is knocked down by rna interference. transmission electron microscopy indicated that the mitochondrion in the cell is also extended and branched and associated with cortical microtubules in each elongated/branched posterior end. this posterior extension is apparently driven by the growing microtubule corset, as it can be ...	2005	16144864
a feast of protozoan genomes.		2005	16145753
application of multiple dna fingerprinting techniques to study the genetic relationships among three members of the subgenus trypanozoon (protozoa: trypanosomatidae).	three different dna fingerprinting techniques, the mobile genetic element (mge)-pcr, simple sequence repeat (ssr)-pcr and random amplified polymorphic dna (rapd)-pcr, were used to define a large set of genetic markers to study genetic similarity within and among trypanosoma brucei, trypanosoma equiperdum and trypanosoma evansi strains (n=18) from china, africa and south america and to investigate their genetic relationships. using the three fingerprinting techniques, >890 bands (ranging in size ...	2005	16146682
trypanosoma brucei: expression of multiple purine transporters prevents the development of allopurinol resistance.	allopurinol is a hypoxanthine analogue used to treat leishmania infections that also displays activity against the related parasite trypanosoma brucei. we have investigated the ease by which resistance to this drug is established in trypanosoma brucei brucei and correlated this to the mechanisms by which it is accumulated by the parasite. long-term exposure of procyclic t. b. brucei to 3mm allopurinol did not induce resistance. this appears to be related to the fact that allopurinol was taken up ...	2005	15687014
bisphosphonate inhibition of the exopolyphosphatase activity of the trypanosoma brucei soluble vacuolar pyrophosphatase.	trypanosoma brucei, the causative agent of african trypanosomiasis, contains a soluble, vacuolar pyrophosphatase, tbvsp1, not present in humans, which is essential for the growth of bloodstream forms in their mammalian host. here, we report the inhibition of a recombinant tbvsp1 expressed in escherichia coli by a panel of 81 bisphosphonates. the ic50 values were found to vary from approximately 2 to 850 microm. we then used 3d qsar (comparative molecular field and comparative molecular similarit ...	2005	16162013
downregulation of the nuclear-encoded subunits of the complexes iii and iv disrupts their respective complexes but not complex i in procyclic trypanosoma brucei.	the function, stability and mutual interactions of selected nuclear-encoded subunits of respiratory complexes iii and iv were studied in the trypanosoma brucei procyclics using rna interference (rnai). the growth rates and oxygen consumption of clonal cell lines of knock-downs for apocytochrome c1 (apoc1) and the rieske fe-s protein (rieske) of complex iii, and cytochrome c oxidase subunit 6 (cox6) of complex iv were markedly decreased after rnai induction. western analysis of mitochondrial lysa ...	2005	16164553
trypanosomes change their transferrin receptor expression to allow effective uptake of host transferrin.	in its mammalian host, trypanosoma brucei covers its iron requirements by receptor-mediated uptake of host transferrin (tf). the tf-receptor (tf-r) is a heterodimeric membrane protein encoded by expression site-associated gene (esag) 6 and 7 located promoter-proximal in a polycistronic expression site (es). each of the 20 ess encodes a slightly different tf-r; these differences strongly affect the binding affinity for tfs of different hosts. the tf-r encoded in the 221 es has a low affinity for ...	2005	16164555
comparative analysis of the kinomes of three pathogenic trypanosomatids: leishmania major, trypanosoma brucei and trypanosoma cruzi.	the trypanosomatids leishmania major, trypanosoma brucei and trypanosoma cruzi cause some of the most debilitating diseases of humankind: cutaneous leishmaniasis, african sleeping sickness, and chagas disease. these protozoa possess complex life cycles that involve development in mammalian and insect hosts, and a tightly coordinated cell cycle ensures propagation of the highly polarized cells. however, the ways in which the parasites respond to their environment and coordinate intracellular proc ...	2005	16164760
trypanosoma brucei: tbrab4 regulates membrane recycling and expression of surface proteins in procyclic forms.	tbrab4 is the trypanosoma brucei orthologue of the small gtpase rab4, which is implicated in the control of early endocytosis and recycling processes. tbrab4 is expressed constitutively in the procyclic and bloodstream stages suggesting an important function throughout the trypanosome life-cycle. previous work from our laboratory has shown tbrab4 to be essential in the bloodstream form. induction of double-stranded tbrab4 rna expression leads to a specific reduction in tbrab4 protein levels and ...	2005	16168414
the trypanosoma brucei signal recognition particle lacks the alu-domain-binding proteins: purification and functional analysis of its binding proteins by rnai.	trypanosomes are protozoan parasites that have a major impact on human health and that of livestock. these parasites represent a very early branch in the eukaryotic lineage, and possess unique rna processing mechanisms. the trypanosome signal recognition particle (srp) is also unusual in being the first signal recognition particle described in nature to be comprised of two rna molecules, the 7sl rna and a trna-like molecule. in this study, we further elucidated the unique properties of this part ...	2005	16179612
tagging a t. brucei rrna locus improves stable transfection efficiency and circumvents inducible expression position effects.	in trypanosoma brucei, rna interference (rnai) and recombinant protein expression are established as powerful approaches for functional genomics, particularly when combined with inducible expression. the favoured methods involve exploiting homologous recombination to target expression cassettes to a chromosome sub-set to establish stable cell lines. unfortunately, bloodstream-form cells, those that cause disease in mammals, exhibit low efficiency stable transfection. current expression systems c ...	2005	16182389
golgi duplication in trypanosoma brucei requires centrin2.	centrins are highly conserved components of the centrosome, which in the parasitic protozoan t. brucei comprises the basal body and nucleates the flagellum used for locomotion. here, we found tbcentrin2 in an additional bi-lobed structure near to the golgi apparatus. one lobe was associated with the old golgi, and the other became associated with the newly forming golgi as the cell grew. depletion of tbcentrin1 inhibited duplication of the basal body, whereas depletion of tbcentrin2 also inhibit ...	2005	16254149
energy metabolism and its compartmentation in trypanosoma brucei.	african trypanosomes are parasitic protozoa of the order of kinetoplastida, which cause sleeping sickness and nagana. trypanosomes are not only of scientific interest because of their clinical importance, but also because these protozoa contain several very unusual biological features, such as their special energy metabolism. the energy metabolism of trypanosoma brucei differs significantly from that of its host, not only because it comprises distinct enzymes and metabolic pathways, but also bec ...	2005	16221581
systematic study of sequence motifs for rna trans splicing in trypanosoma brucei.	mrna maturation in trypanosoma brucei depends upon trans splicing, and variations in trans-splicing efficiency could be an important step in controlling the levels of individual mrnas. rna splicing requires specific sequence elements, including conserved 5' splice sites, branch points, pyrimidine-rich regions [poly(y) tracts], 3' splice sites (3'ss), and sometimes enhancer elements. to analyze sequence requirements for efficient trans splicing in the poly(y) tract and around the 3'ss, we constru ...	2005	16227607
the extraordinary mitochondrion and unusual citric acid cycle in trypanosoma brucei.	african trypanosomes are parasitic protozoa that cause sleeping sickness and nagana. trypanosomes are not only of scientific interest because of their clinical importance, but also because these protozoa contain several very unusual biological features, such as their specially adapted mitochondrion and the compartmentalization of glycolytic enzymes in glycosomes. the energy metabolism of trypanosoma brucei differs significantly from that of their hosts and changes drastically during the life cyc ...	2005	16246022
the myo-inositol-1-phosphate synthase gene is essential in trypanosoma brucei.	the de novo synthesis of myo-inositol occurs via a two-step process: first, glucose 6-phosphate is converted into inositol 1-phosphate by an ino1 (myo-inositol-1-phosphate synthase; ec 5.5.1.4); then, it is dephosphorylated by an inositol monophosphatase. the myo-inositol can then be incorporated into pi (phosphatidylinositol), which is utilized in a variety of cellular functions, including the biosynthesis of gpi (glycosylphosphatidylinositol) anchors. a putative ino1 was identified in the tryp ...	2005	16246027
il-1 type i receptor plays a key role in mediating the recruitment of leukocytes into the central nervous system.	this study investigates the role of type i il-1 receptor (il-1r1) in mediating the recruitment of leukocytes into the brain parenchyma in mice. intracerebroventricular (icv) injection of interleukin il-1beta induced infiltration of leukocytes between 8 and 72 h after the injection. leukocytes were rarely found in the brain tissue of saline-injected animals. at 8h after il-1beta injection, leukocytes were seen lining the blood vessels of the brain and sparsely scattered infiltration of leukocytes ...	2005	15664785
the transcriptomes of trypanosoma brucei lister 427 and treu927 bloodstream and procyclic trypomastigotes.	we describe developmentally regulated genes in two strains of trypanosoma brucei: the monomorphic strain lister 427 and the pleomorphic strain treu927. expression patterns were obtained using an array of 24,567 genomic fragments. probes were prepared from bloodstream-form or procyclic-form trypanosomes. fourteen procyclic-specific and 77 bloodstream-specific signals were obtained from sequences matching variant surface glycoprotein or associated genes, and a further 17 regulated sequences were r ...	2005	15664651
the effect of over-expression of the alternative oxidase in the procyclic forms of trypanosoma brucei.	trypanosome alternative oxidase (tao) is the cyanide-resistant but sham-sensitive terminal oxidase of the mitochondrial electron transport chain in african trypanosomes. the bloodstream forms of trypanosoma brucei lack cytochromes and respire exclusively via tao. on the other hand, the insect, or procyclic form possesses a fully developed cytochrome system, and down regulates tao several folds by reducing the stability of the tao transcript. we expressed an ectopic copy of tao in the procyclic f ...	2005	15664650
characterization of two protein disulfide isomerases from the endocytic pathway of bloodstream forms of trypanosoma brucei.	proteins from the endocytic pathway in bloodstream forms of trypanosome brucei are modified by the addition of linear poly-n-acetyllactosamine side chains, which permits their isolation by tomato lectin affinity chromatography. antibodies against this tomato lectin binding fraction were employed to screen a cdna expression library from bloodstream forms of t. brucei. two cdnas were prominent among those selected. these cdnas coded for two putative protein disulfide isomerases (pdis) that respect ...	2005	15642735
parsing parasites.		2005	16196248
in vitro and in vivo analysis of the major type i protein arginine methyltransferase from trypanosoma brucei.	in mammals and yeasts, arginine methylation, catalyzed by protein arginine methyltransferases (prmts), has been implicated in regulation of diverse processes such as protein-protein interaction, protein localization, signal transduction, rna processing, and transcription. a large number of prmt substrates are rna binding proteins. in trypanosomes, gene regulation is controlled primarily at the levels of rna processing, stability, and translation, and likely involves numerous rna binding proteins ...	2005	16198009
trypanosome lytic factor, a subclass of high-density lipoprotein, forms cation-selective pores in membranes.	trypanosome lytic factor 1 (tlf1) is a subclass of human high-density lipoprotein that kills some african trypanosomes thereby protecting humans from infection. we have shown that tlf1 is a 500 kda hdl complex composed of lipids and at least seven different proteins. here we present evidence outlining a new paradigm for the mechanism of lysis; tlf1 forms cation-selective pores in membranes. we show that the replacement of external na+ (23 da) with the larger tetramethylammonium+, choline+ and te ...	2005	16202458
treatment of african trypanosomiasis with cordycepin and adenosine deaminase inhibitors in a mouse model.	there is an urgent need to discontinue the use of highly toxic compounds still in use for treatment of the encephalitic stage of human african trypanosomiasis (hat). we show here that intraperitoneal injection of the adenosine analogue cordycepin (3'-deoxyadenosine), together with an adenosine deaminase (ada) inhibitor (coformycin or deoxycoformycin), cures trypanosoma brucei brucei infection in mice. treatment was also effective at a stage when the trypanosomes had penetrated into the brain par ...	2005	16206083
columbin inhibits cholesterol uptake in bloodstream forms of trypanosoma brucei-a possible trypanocidal mechanism.	the diterpenoid furanolactone (columbin) from aristolochia albida inhibited growth of culture forms of trypanosoma brucei. in vitro analysis of the compound at 5-250 microg/ml showed complete lysis of the parasites within 10-20 minutes post incubation. at 50 microg/ml, columbin killed about 50% of the parasites which initially appeared swollen under phase contrast microscopy. also the total amount of cholesterol diminished dose-dependently in the presence of 10-100 microg/ml of columbin after a ...	2005	16206831
tropolysin, a new oligopeptidase from african trypanosomes.	oligopeptidases are emerging as important pathogenic factors and therapeutic targets in trypanosome infections. we describe here the purification, cloning, and biochemical analysis of a new oligopeptidase from two pathogenic african trypanosomes. this oligopeptidase, which we have called tropolysin (encoded by the trn gene), represents an evolutionarily distant member of the m3a subfamily of metallopeptidases, ancestral to thimet oligopeptidase, neurolysin, and saccharolysin. the trn gene was pr ...	2005	16262265
gpi valence and the fate of secretory membrane proteins in african trypanosomes.	progression of gpi-anchored proteins in bloodstream african trypanosomes correlates with gpi-valence: homodimeric vsg (2 gpi) is a surface protein; heterodimeric transferrin receptor (1 gpi) localizes in the flagellar pocket; homodimeric gpi-minus vsg (0 gpi) is rapidly degraded in the lysosome. we test this relationship using three native secretory/endocytic proteins as monomeric gpi-plus and -minus reporters. gpi-minus procyclin trafficks to the lysosome and is degraded. gpi-plus procyclin tra ...	2005	16291721
an essential rnase iii insertion editing endonuclease in trypanosoma brucei.	rna editing adds and deletes uridine nucleotides in many preedited mrnas to create translatable mrnas in the mitochondria of the parasite trypanosoma brucei. kinetoplastid rna editing protein b3 (krepb3, formerly tbmp61) is part of the multiprotein complex that catalyzes editing in t. brucei and contains an rnase iii motif that suggests nuclease function. repression of krepb3 expression, either by rna interference in procyclic forms (pfs) or by conditional inactivation of an ectopic krepb3 allel ...	2005	16269544
diminazene aceturate resistance on the virulence of trypanosoma brucei for rats.	four groups (a, b, c and d) of 10 naïve rats were used to compare the virulence of isolates of a strain of trypanosoma brucei before and after the development of diminazene aceturate resistance. group a rats were uninfected (controls). group b rats were infected with a trypanosome isolate unexposed to the drug, while groups c and d rats were infected with two different drug-resistant isolates of the same strain. rats in the three infected groups each received 10(6) trypanosomes intraperitoneally ...	2005	16271938
purification and analysis of recombinant 11s activators of the 20s proteasome: trypanosoma brucei pa26 and human pa28 alpha, pa28 beta, and pa28 gamma.	proteasomes perform the bulk of nonlysosomal degradation of aberrant, damaged, misfolded, and naturally short-lived regulatory proteins in eukaryotic cells. they are approximately 700-kda assemblies whose hollow architecture sequesters the proteolytic sites inside a central chamber, thereby ensuring that the activity of isolated proteasomes is repressed. in vivo, proteasomes are activated by protein complexes, including the 11s activators (pa28 and pa26), which bind to one or both ends of the ba ...	2005	16275338
expression of procyclin mrnas during cyclical transmission of trypanosoma brucei.	trypanosoma brucei, the parasite causing human sleeping sickness, relies on the tsetse fly for its transmission. in the insect, ep and gpeet procyclins are the major surface glycoproteins of procyclic (midgut) forms of the parasite, with gpeet predominating in the early procyclic form and two isoforms of ep in the late procyclic form. ep procyclins were previously detected on salivary gland trypanosomes, presumably epimastigotes, by immunoelectron microscopy. however, no procyclins could be dete ...	2005	16276404
the parkin co-regulated gene product, pacrg, is an evolutionarily conserved axonemal protein that functions in outer-doublet microtubule morphogenesis.	eukaryotic cilia and flagella are highly conserved structures composed of a canonical 9+2 microtubule axoneme. comparative genomics of flagellated and non-flagellated eukaryotes provides one way to identify new putative flagellar proteins. we identified the parkin co-regulated gene, or pacrg, from such a screen. male mice deficient in pacrg are sterile, but its function has been little explored. the flagellated protozoan parasite trypanosoma brucei possesses two homologues of pacrg. we performed ...	2005	16278296
highly efficient tandem affinity purification of trypanosome protein complexes based on a novel epitope combination.	tandem affinity purification (tap) allows for rapid and efficient purification of epitope-tagged protein complexes from crude extracts under native conditions. the method was established in yeast and has been successfully applied to other organisms, including mammals and trypanosomes. however, we found that the original method, which is based on the tap tag, consisting of a duplicate protein a epitope, a tobacco etch virus protease cleavage site, and the calmodulin-binding peptide (cbp), did not ...	2005	16278461
structural basis for utp specificity of rna editing tutases from trypanosoma brucei.	trypanosomatids are pathogenic protozoa that undergo a unique form of post-transcriptional rna editing that inserts or deletes uridine nucleotides in many mitochondrial pre-mrnas. editing is catalyzed by a large multiprotein complex, the editosome. a key editosome enzyme, rna editing terminal uridylyl transferase 2 (tutase 2; ret2) catalyzes the uridylate addition reaction. here, we report the 1.8 a crystal structure of the trypanosoma brucei ret2 apoenzyme and its complexes with uridine nucleot ...	2005	16281058
a deletion site editing endonuclease in trypanosoma brucei.	rna editing in trypanosoma brucei inserts and deletes uridines in mitochondrial mrnas by a series of enzymatic steps that are catalyzed by a multiprotein complex, the editosome. krepb1 and two related editosome proteins krepb2 and krepb3 contain motifs that suggest endonuclease and rna/protein interaction functions. repression of krepb1 expression in procyclic forms by rnai inhibited growth, in vivo editing, and in vitro endoribonucleolytic cleavage of deletion substrates. however, cleavage of i ...	2005	16285922
histone h2az dimerizes with a novel variant h2b and is enriched at repetitive dna in trypanosoma brucei.	h2az is a widely conserved histone variant that is implicated in protecting euchromatin from the spread of heterochromatin. h2az is incorporated into nucleosomes as a heterodimer with h2b, by the swr1 atp-dependent chromatin-remodeling complex. we have identified a homolog of h2az in the protozoan parasite trypanosoma brucei, along with a novel variant of histone h2b (h2bv) that shares approximately 38% sequence identity with major h2b. both h2az and h2bv are essential for viability. h2az locali ...	2005	16303849
interaction of monobenzamidine-linked trypanocides with the trypanosoma brucei p2 aminopurine transporter.	single benzamidine group-carrying compounds were shown to interact with the trypanosoma brucei p2 aminopurine transporter. replacement of the amidine with a guanidine group decreased affinity. trypanocidal activity was evident, but compounds were equally toxic against trypanosomes lacking the p2 transporter, which indicates additional uptake routes for monobenzamidine-derived compounds.	2005	16304196
minimal pre-mrna substrates with natural and converted sites for full-round u insertion and u deletion rna editing in trypanosomes.	trypanosome rna editing by uridylate insertion or deletion cycles is a mitochondrial mrna maturation process catalyzed by multisubunit complexes. a full-round of editing entails three consecutive steps directed by partially complementary guide rnas: pre-mrna cleavage, u addition or removal, and ligation. the structural and functional composition of editing complexes is intensively studied, but their molecular interactions in and around editing sites are not completely understood. in this study, ...	2005	16306234
the genetic map and comparative analysis with the physical map of trypanosoma brucei.	trypanosoma brucei is the causative agent of african sleeping sickness in humans and contributes to the debilitating disease 'nagana' in cattle. to date we know little about the genes that determine drug resistance, host specificity, pathogenesis and virulence in these parasites. the availability of the complete genome sequence and the ability of the parasite to undergo genetic exchange have allowed genetic investigations into this parasite and here we report the first genetic map of t.brucei fo ...	2005	16314301
evolutionary relationships and protein domain architecture in an expanded calpain superfamily in kinetoplastid parasites.	employing whole-genome analysis we have characterized a large family of genes coding for calpain-related proteins in three kinetoplastid parasites. we have defined a total of 18 calpain-like sequences in trypanosoma brucei, 27 in leishmania major, and 24 in trypanosoma cruzi. sequence characterization revealed a well-conserved protease domain in most proteins, although residues critical for catalytic activity were frequently altered. many of the proteins contain a novel n-terminal sequence motif ...	2005	16315106
antileishmanial and trypanocidal activities of new miltefosine liposomal formulations.	liposomes composed of hexadecylphosphocholine/egg phosphatidylcholine/stearylamine (hepc/epc/sa) 10:10:0.1, 10:10:0.5 and 10:10:1 (molar ratio) (1-3) were prepared and lyophilized. the liposomes were physicochemically characterized (size and zeta-potential) and they were found stable at 4 degrees c over a period of 4 weeks. in vitro, liposomes 1 and 2 were about twice more active than hepc against leishmania donovani wt whereas liposomes 3 were about three times more active than hepc on hepc-res ...	2005	16325367
distinct roles for two rad51-related genes in trypanosoma brucei antigenic variation.	in trypanosoma brucei, dna recombination is crucial in antigenic variation, a strategy for evading the mammalian host immune system found in a wide variety of pathogens. t.brucei has the capacity to encode >1000 antigenically distinct variant surface glycoproteins (vsgs). by ensuring that only one vsg is expressed on the cell surface at one time, and by periodically switching the vsg gene that is expressed, t.brucei can evade immune killing for prolonged periods. much of vsg switching appears to ...	2005	16326865
rna-binding domain proteins in kinetoplastids: a comparative analysis.	rna-binding proteins are important in many aspects of rna processing, function, and destruction. one class of such proteins contains the rna recognition motif (rrm), which consists of about 90 amino acid residues, including the canonical rnp1 octapeptide: (k/r)g(f/y)(g/a)fvx(f/y). we used a variety of homology searches to classify all of the rrm proteins of the three kinetoplastids trypanosoma brucei, trypanosoma cruzi, and leishmania major. all three organisms have similar sets of rrm-containin ...	2005	16339728
[analysis of molecular profiles among trypanozoon species and subspecies by mge-pcr method].	to analyze the relationship between genetic variability and evolution among trypanosoma brucei (including t. b. brucei, t. b. rhodesiense and t. b. gambiense), t. evansi and t. equiperdum isolates.	2005	16562478
comprehensive mass spectrometric analysis of the 20s proteasome complex.	the 20s proteasome is a multicatalytic protein complex that plays an important role in intracellular protein degradation from archaebacteria to eukaryotes. this complex is made up of two copies each of seven different alpha (alpha) and seven different beta (beta) subunits arranged into four stacked rings (alpha7beta7beta7alpha7). although the proteasome's cylindrical structure is conserved, the subunit composition of the 20s protein complex varies during the evolution, and the number of subunits ...	2005	16413316
a preliminary crystallographic analysis of the putative mevalonate diphosphate decarboxylase from trypanosoma brucei.	mevalonate diphosphate decarboxylase catalyses the last and least well characterized step in the mevalonate pathway for the biosynthesis of isopentenyl pyrophosphate, an isoprenoid precursor. a gene predicted to encode the enzyme from trypanosoma brucei has been cloned, a highly efficient expression system established and a purification protocol determined. the enzyme gives monoclinic crystals in space group p2(1), with unit-cell parameters a = 51.5, b = 168.7, c = 54.9 a, beta = 118.8 degrees. ...	2005	16511101
ability of trypanosome-infected tsetse flies (diptera: glossinidae) to acquire an infection with a second trypanosome species.	the epidemiology of human and animal trypanosomiasis is determined to a large extent by the number of infected tsetse flies in a specific area. in the field, a substantial proportion of infected flies carry mixed trypanosome infections. the way in which these tsetse flies acquire a mixed infection is not fully understood. in particular, the susceptibility of tsetse flies to sequential infection with trypanosomes is not well understood. accordingly, laboratory studies were made of the effects of ...	2005	16465745
the f1-atp synthase complex in bloodstream stage trypanosomes has an unusual and essential function.	survival of bloodstream form trypanosoma brucei, the agent of african sleeping sickness, normally requires mitochondrial gene expression, despite the absence of oxidative phosphorylation in this stage of the parasite's life cycle. here we report that silencing expression of the alpha subunit of the mitochondrial f(1)-atp synthase complex is lethal for bloodstream stage t. brucei as well as for t. evansi, a closely related species that lacks mitochondrial protein coding genes (i.e. is dyskinetopl ...	2005	16270030
development of an adaptive tsetse population management scheme for the luke community, ethiopia.	since 1996, tsetse (glossina spp.) control operations, using odor-baited traps, have been carried out in the luke area of gurage zone, southwestern ethiopia. glossina morsitans submorsitans newstead was identified as the dominant species in the area, but the presence of glossina fuscipes newstead and glossina pallidipes austen also was recorded. here, we refer to the combined number of these three species and report the work undertaken from october 2002 to october 2004 to render the control syst ...	2005	16465742
rapid identification of isometamidium-resistant stocks of trypanosoma b. brucei by pcr-rflp.	analyses were made on the adenosine transporter-1 gene in trypanosoma brucei (tbat1), encoding a p2-like nucleoside transporter, from t. brucei brucei field stocks to investigate a possible link between the presence of mutations in this gene and isometamidium resistance. we have analysed the gene from 11 isometamidium-sensitive field stocks isolated from cattle in uganda, two sensitive reference clones and two resistant reference clones. a sequence alignment showed that the isometamidium-sensiti ...	2006	16541260
programmed cell death in african trypanosomes.	until recently it had generally been assumed that apoptosis and other forms of programmed cell death evolved during evolution of the metazoans to regulate growth and development in these multicellular organisms. however, recent research is adding strength to the original phenotypic observations described almost a decade ago which indicated that some parasitic protozoa may have evolved a cell death pathway analogous to the process described as apoptosis in metazoa. here we explore the implication ...	2006	17018168
the mitochondrial fad-dependent glycerol-3-phosphate dehydrogenase of trypanosomatidae and the glycosomal redox balance of insect stages of trypanosoma brucei and leishmania spp.	the genes for the mitochondrial fad-dependent glycerol-3-phosphate dehydrogenase were identified in trypanosoma brucei and leishmania major genomes. we have expressed the l. major gene in saccharomyces cerevisiae and confirmed the subcellular localization and activity of the produced enzyme. using cultured t. brucei procyclic and leishmania mexicana promastigote cells with a permeabilized plasma membrane and containing intact glycosomes, it was shown that dihydroxyacetone phosphate is converted ...	2006	16806528
consequences of telomere shortening at an active vsg expression site in telomerase-deficient trypanosoma brucei.	trypanosoma brucei evades the host immune response by sequential expression of a large family of variant surface glycoproteins (vsg) from one of approximately 20 subtelomeric expression sites (es). vsg transcription is monoallelic, and little is known about the regulation of antigenic switching. to explore whether telomere length could affect antigenic switching, we created a telomerase-deficient cell line, in which telomeres shortened at a rate of 3 to 6 bp at each cell division. upon reaching ...	2006	17071826
rna editing complex interactions with a site for full-round u deletion in trypanosoma brucei.	trypanosome u insertion and u deletion rna editing of mitochondrial pre-mrnas is catalyzed by multisubunit editing complexes as directed by partially complementary guide rnas. the basic enzymatic activities and protein composition of these high-molecular mass complexes have been under intense study, but their specific protein interactions with functional pre-mrna/grna substrates remains unknown. we show that editing complexes purified through extensive ion-exchange chromatography and immunopreci ...	2006	16690999
ethanolaminephosphate side chain added to glycosylphosphatidylinositol (gpi) anchor by mcd4p is required for ceramide remodeling and forward transport of gpi proteins from endoplasmic reticulum to golgi.	glycosylphosphatidylinositol (gpi) anchors of mammals as well as yeast contain ethanolaminephosphate side chains on the alpha1-4- and the alpha1-6-linked mannoses of the anchor core structure (protein-co-nh-(ch(2))(2)-po(4)-6manalpha1-2manalpha1-6manalpha1-4glcnh(2)-inositol-po(4)-lipid). in yeast, the ethanolaminephosphate on the alpha1-4-linked mannose is added during the biosynthesis of the gpi lipid by mcd4p. mcd4 is essential because gpi10p, the mannosyltransferase adding the subsequent alp ...	2006	16704983
role of p38 in replication of trypanosoma brucei kinetoplast dna.	trypanosomes have an unusual mitochondrial genome, called kinetoplast dna, that is a giant network containing thousands of interlocked minicircles. during kinetoplast dna synthesis, minicircles are released from the network for replication as theta-structures, and then the free minicircle progeny reattach to the network. we report that a mitochondrial protein, which we term p38, functions in kinetoplast dna replication. rna interference (rnai) of p38 resulted in loss of kinetoplast dna and accum ...	2006	16809774
analysis of neutral glycosphingolipids from trypanosoma brucei.	neutral glycosphingolipids (gsls) were isolated from trypanosoma brucei and analyzed by thin-layer chromatography (tlc), tlc/secondary ion mass spectrometry (tlc/sims), and liposome immune lysis assay (lila). three species of neutral gsls, designated as n-1, -2, and -3 were separated on tlc. n-1 gsl migrated very close to glucosylceramide (glccer) and n-2 gsl showed the same mobility as lactosylceramide (laccer). on the other hand, the mobility of n-3 gsl on the tlc plate was slower than globote ...	2006	16806714
the role of trypanosoma brucei mrpa in melarsoprol susceptibility.	we previously showed that over-expression of trypanosoma brucei mrpa, a member of the multidrug resistance protein family in t. brucei, reproducibly resulted in resistance to the anti-trypanosomal drug melarsoprol in vitro. mrpa is predicted to mediate efflux of melarsoprol as a conjugate with trypanothione, a glutathione-spermidine conjugate which is the major small thiol in trypanosomes. here, we show that depletion of mrpa by rna interference resulted in moderate hypersensitivity to both mela ...	2006	16343658
structure and reactivity of trypanosoma brucei pteridine reductase: inhibition by the archetypal antifolate methotrexate.	the protozoan trypanosoma brucei has a functional pteridine reductase (tbptr1), an nadph-dependent short-chain reductase that participates in the salvage of pterins, which are essential for parasite growth. ptr1 displays broad-spectrum activity with pterins and folates, provides a metabolic bypass for inhibition of the trypanosomatid dihydrofolate reductase and therefore compromises the use of antifolates for treatment of trypanosomiasis. catalytic properties of recombinant tbptr1 and inhibition ...	2006	16968221
changing roles of aurora-b kinase in two life cycle stages of trypanosoma brucei.	aurora-b kinase is a chromosomal passenger protein essential for chromosome segregation and cytokinesis. in the procyclic form of trypanosoma brucei, depletion of an aurora-b kinase homologue tbauk1 inhibited spindle formation, mitosis, cytokinesis, and organelle replication without altering cell morphology. in the present study, an rna interference knockdown of tbauk1 or overexpression of inactive mutant tbauk1-k58r in the bloodstream form also resulted in defects in spindle formation, chromoso ...	2006	16835447
the glycosylphosphatidylinositol (gpi) biosynthetic pathway of bloodstream-form trypanosoma brucei is dependent on the de novo synthesis of inositol.	in bloodstream-form trypanosoma brucei (the causative agent of african sleeping sickness) the glycosylphosphatidylinositol (gpi) anchor biosynthetic pathway has been validated genetically and chemically as a drug target. the conundrum that gpi anchors could not be in vivo labelled with [3h]-inositol led us to hypothesize that de novo synthesis was responsible for supplying myo-inositol for phosphatidylinositol (pi) destined for gpi synthesis. the rate-limiting step of the de novo synthesis is th ...	2006	16824097
alternative editing of cytochrome c oxidase iii mrna in trypanosome mitochondria generates protein diversity.	trypanosomes use rna editing to produce most functional mitochondrial messenger rna. precise insertion and deletion of hundreds of uridines is necessary to make full-length cytochrome c oxidase iii (coxiii) mrna. we show that coxiii mrna can be alternatively edited by a mechanism using an alternative guide rna to make a stable mrna. this alternatively edited mrna is translated to produce a unique protein that fractionates with mitochondrial membranes and colocalizes with mitochondrial proteins i ...	2006	17008930
preferential interaction of a 25kda protein with an a6 pre-mrna substrate for rna editing in trypanosoma brucei.	mitochondrial gene expression in kinetoplastids is controlled after transcription, potentially at the levels of rna maturation, stability and translation. among these processes, rna editing by u-insertion/deletion catalysed by multi-subunit editing complexes is best characterised at the molecular level. nevertheless, mitochondrial rna metabolism overall remains poorly understood, including the potential regulatory factors that may interact with the relevant catalytic molecular machines and/or rn ...	2006	16860325
sorting signals required for trafficking of the cysteine-rich acidic repetitive transmembrane protein in trypanosoma brucei.	in trypanosomatids, endocytosis and exocytosis are restricted to the flagellar pocket (fp). the cysteine-rich acidic repetitive transmembrane (cram) protein is located at the fp of trypanosoma brucei and potentially functions as a receptor or an essential component for lipoprotein uptake. we characterized sorting determinants involved in efficient trafficking of cram to and from the fp of t. brucei. previous studies indicated the presence of signals in the cram c terminus, specific for its local ...	2006	16896208
conserved and specific functions of axoneme components in trypanosome motility.	the trypanosoma brucei flagellum is unusual as it is attached along the cell body and contains, in addition to an apparently conventional axoneme, a structure called the paraflagellar rod, which is essential for cell motility. here, we investigated flagellum behaviour in normal and mutant trypanosome cell lines where expression of genes encoding various axoneme proteins (pf16, pf20, dnai1, lc2) had been silenced by rnai. first, we show that the propulsive wave (normally used for forward motility ...	2006	16882690
phosphatidylinositol synthesis is essential in bloodstream form trypanosoma brucei.	pi (phosphatidylinositol) is a ubiquitous eukaryotic phospholipid which serves as a precursor for messenger molecules and gpi (glycosylphosphatidylinositol) anchors. pi is synthesized either de novo or by head group exchange by a pis (pi synthase). the synthesis of gpi anchors has previously been validated both genetically and chemically as a drug target in trypanosoma brucei, the causative parasite of african sleeping sickness. however, nothing is known about the synthesis of pi in this organis ...	2006	16475982
characterization and selective inhibition of myristoyl-coa:protein n-myristoyltransferase from trypanosoma brucei and leishmania major.	the eukaryotic enzyme nmt (myristoyl-coa:protein n-myristoyltransferase) has been characterized in a range of species from saccharomyces cerevisiae to homo sapiens. nmt is essential for viability in a number of human pathogens, including the fungi candida albicans and cryptococcus neoformans, and the parasitic protozoa leishmania major and trypanosoma brucei. we have purified the leishmania and t. brucei nmts as active recombinant proteins and carried out kinetic analyses with their essential fa ...	2006	16480339
structural differences in triosephosphate isomerase from different species and discovery of a multitrypanosomatid inhibitor.	we examined the interfaces of homodimeric triosephosphate isomerase (tim) from eight different species. the crystal structures of the enzymes showed that a portion of the interface is markedly similar in tims from trypanosoma cruzi (tctim), trypanosoma brucei, and leishmania mexicana and significantly different from that of tims from human, yeast, chicken, plasmodium falciparum, and entamoeba histolytica. since this interfacial region is central in the stability of tctim, we hypothesized that it ...	2006	16489748
bloodstream form trypanosoma brucei depend upon multiple metacaspases associated with rab11-positive endosomes.	trypanosoma brucei possesses five metacaspase genes. of these, mca2 and mca3 are expressed only in the mammalian bloodstream form of the parasite, whereas mca5 is expressed also in the insect procyclic form. triple rnai analysis showed mca2, mca3 and mca5 to be essential in the bloodstream form, with parasites accumulating pre-cytokinesis. nevertheless, triple null mutants (deltamca2/3deltamca5) could be isolated after sequential gene deletion. thereafter, deltamca2/3deltamca5 mutants were found ...	2006	16507595
selective irreversible inhibition of fructose 1,6-bisphosphate aldolase from trypanosoma brucei.	an irreversible competitive inhibitor hydroxynaphthaldehyde phosphate was synthesized that is highly selective against the glycolytic enzyme fructose 1,6-bisphosphate aldolase from trypanosoma brucei (causative agent of sleeping sickness). inhibition involves schiff base formation by the inhibitor aldehyde with lys116 followed by reaction of the resultant schiff base with a second residue. molecular simulations indicate significantly greater molecular geometries conducive for nucleophilic attack ...	2006	16509566
removal or maintenance of inositol-linked acyl chain in glycosylphosphatidylinositol is critical in trypanosome life cycle.	the protozoan parasite trypanosoma brucei is coated by glycosylphosphatidylinositol (gpi)-anchored proteins. during gpi biosynthesis, inositol in phosphatidylinositol becomes acylated. inositol is deacylated prior to attachment to variant surface glycoproteins in the bloodstream form, whereas it remains acylated in procyclins in the procyclic form. we have cloned a t. brucei gpi inositol deacylase (gpideac2). in accordance with the acylation/deacylation profile, the level of gpideac2 mrna was 6- ...	2006	16510441
toward a rational design of selective multi-trypanosomatid inhibitors: a computational docking study.	compound v7, a benzothiazole which was recently found as selective inhibitor of trypanosomal tims, was docked into tims from trypanosoma cruzi, trypanosoma brucei, entamoeba histolytica, plasmodium falciparum, yeast, and human. structural analyses revealed the importance of the accessibility to the two aromatic clusters located at the dimer's interface for the selective inhibition of trypanosomal tims. thus, it was found that different accessibilities of the protein interface of tims plays an im ...	2006	16997551
blood-brain barrier traversal by african trypanosomes requires calcium signaling induced by parasite cysteine protease.	in this study we investigated why bloodstream forms of trypanosoma brucei gambiense cross human brain microvascular endothelial cells (bmecs), a human blood-brain barrier (bbb) model system, at much greater efficiency than do t. b. brucei. after noting that t. b. gambiense displayed higher levels of cathepsin l-like cysteine proteases, we investigated whether these enzymes contribute to parasite crossing. first, we found that t. b. gambiense crossing of human bmecs was abrogated by n-methylpiper ...	2006	16998589
using fragment cocktail crystallography to assist inhibitor design of trypanosoma brucei nucleoside 2-deoxyribosyltransferase.	the 1.8 a resolution de novo structure of nucleoside 2-deoxyribosyltransferase (ec 2.4.2.6) from trypanosoma brucei (tbndrt) has been determined by sada phasing in an unliganded state and several ligand-bound states. this enzyme is important in the salvage pathway of nucleoside recycling. to identify novel lead compounds, we exploited "fragment cocktail soaks". out of 304 compounds tried in 31 cocktails, four compounds could be identified crystallographically in the active site. in addition, we ...	2006	17004709
effect of isometamidium chloride treatment on susceptibility of tsetse flies (diptera: glossinidae) to trypanosome infections.	experiments were conducted to determine the effect of a single isometamidium chloride treatment of teneral tsetse flies, glossina morsitans morsitans westwood (diptera: glossinidae), on the subsequent susceptibility to an infection with trypanosoma congolense or trypanosoma brucei brucei. flies were offered a first bloodmeal on sterile gamma-irradiated defibrinated bovine blood that contained either 10 or 100 microg ofisometamidium chloride/ml. treated flies were subsequently infected with t. co ...	2006	16739416
evidence for a sliding-resistance at the tip of the trypanosome flagellum.	motility in trypanosomes is achieved through the undulating behaviour of a single "9 + 2" flagellum; normally the flagellar waves begin at the flagellar tip and propagate towards the base. for flagella in general, however, propagation is from base-to-tip and it is believed that bend formation, and sustained regular oscillation, depend upon a localised resistance to inter-doublet sliding - which is normally conferred by structures at the flagellar base, typically the basal body. we therefore pred ...	2006	17009329
post-transcriptional control of nuclear-encoded cytochrome oxidase subunits in trypanosoma brucei: evidence for genome-wide conservation of life-cycle stage-specific regulatory elements.	trypanosomes represent an excellent model for the post-transcriptional regulation of gene expression because their genome is organized into polycistronic transcription units. however, few signals governing developmental stage-specific expression have been identified, with there being no compelling evidence for widespread conservation of regulatory motifs. as a tool to search for common regulatory sequences we have used the nuclear-encoded components of the cytochrome oxidase (cox) complex of the ...	2006	17012283
the thiol-based redox networks of pathogens: unexploited targets in the search for new drugs.	hydroperoxide metabolism in diverse pathogens is reviewed under consideration of involved enzymes as potential drug targets. the common denominator of the peroxidase systems of trypanosoma, leishmania, plasmodium, and mycobacterium species is the use of nad(p)h to reduce hydroperoxides including peroxynitrite via a flavin-containing disulfide reductase, a thioredoxin (trx)-related protein and a peroxidase that operates with thiol catalysis. in plasmodium falciparum, thioredoxin- and glutathione ...	2006	17012768
basal body and flagellum mutants reveal a rotational constraint of the central pair microtubules in the axonemes of trypanosomes.	productive beating of eukaryotic flagella and cilia requires a strict regulation of axonemal dynein activation. fundamental to any description of axonemal beating is an understanding of the significance of the central pair microtubules and the degree to which central pair rotation has a role. however, for the majority of organisms, it is unclear whether the central pair actually rotates. using an extra-axonemal structure as a fixed reference, we analysed the orientation of the central pair in af ...	2006	16720646
metabolic functions of glycosomes in trypanosomatids.	protozoan kinetoplastida, including the pathogenic trypanosomatids of the genera trypanosoma and leishmania, compartmentalize several important metabolic systems in their peroxisomes which are designated glycosomes. the enzymatic content of these organelles may vary considerably during the life-cycle of most trypanosomatid parasites which often are transmitted between their mammalian hosts by insects. the glycosomes of the trypanosoma brucei form living in the mammalian bloodstream display the h ...	2006	17023066