Publications

structure of the la motif: a winged helix domain mediates rna binding via a conserved aromatic patch.	the la protein is a ubiquitous nuclear phosphoprotein that recognizes the 3' uridylates found in all newly synthesized rna polymerase iii transcripts. la binding stabilizes these transcripts from exonucleases and may also assist their folding. here we present the first structural insights into how the la protein specifically interacts with its rna substrates. the most conserved region of the la protein is the la motif, a domain also found in several other rna-binding proteins. we have determined ...	2004	14976553
scanning electron microscopy of cells and tissues under fully hydrated conditions.	a capability for scanning electron microscopy of wet biological specimens is presented. a membrane that is transparent to electrons protects the fully hydrated sample from the vacuum. the result is a hybrid technique combining the ease of use and ability to see into cells of optical microscopy with the higher resolution of electron microscopy. the resolution of low-contrast materials is approximately 100 nm, whereas in high-contrast materials the resolution can reach 10 nm. standard immunogold t ...	2004	14988502
p75 tumor necrosis factor-receptor shedding occurs as a protective host response during african trypanosomiasis.	in experimental murine trypanosomiasis, resistance is often scored as the capacity to control peak parasitemia levels, which results in prolonged survival. infection-induced pathology has not systematically been used as a resistance criterion. because this parameter could be the most relevant for comparative analysis of natural and experimental infections, as well as for understanding of pathology-associated immune alterations, we analyzed trypanosoma brucei infections in 4 different established ...	2004	14745712
the transmission of mixed trypanosoma brucei brucei/t. congolense infections by tsetse (glossina morsitans morsitans).	laboratory experiments and field observations clearly show that tsetse flies can be carriers of mixed trypanosome infections. question remains how easy it is for the tsetse fly to acquire such a mixed infection during the first bloodmeal. this is of particular importance in the epidemiology of trypanosoma brucei s.l., often a cryptic infection and difficult to transmit to non-teneral tsetse flies. to determine the transmission rate of t. brucei as part of a mixed infection, teneral glossina mors ...	2004	14746974
enhanced survival of rats concurrently infected with trypanosoma brucei and strongyloides ratti.	the interaction between the blood protozoan parasite, trypanosoma brucei and the gastrointestinal nematode parasite, strongyloides ratti was studied in outbred white albino rats. rats were grouped and given either single infection with t. brucei or s. ratti or concurrently infected with both parasites. blood parasitaemia and packed cell volume, faecal egg/larva output, adult worm burden and survivability were monitored in order to assess the interactive effects of the infections. all trypanosome ...	2004	14746976
integration of pzjm library plasmids into unexpected locations in the trypanosoma brucei genome.		2004	14747155
the trypanosoma brucei spliced leader rna and rrna gene promoters have interchangeable tbsnap50-binding elements.	in the protist parasite trypanosoma brucei, the small nuclear spliced leader (sl) rna and the large rrnas are key molecules for mrna maturation and protein synthesis, respectively. the sl rna gene (slrna) promoter recruits rna polymerase ii and consists of a bipartite upstream sequence element (use) and an element close to the transcription initiation site. here, we analyzed the distal part of the ribosomal (rrna) promoter and identified two sequence blocks which, in reverse orientation, closely ...	2004	14757834
splenic denervation suppresses mrna gene expression and protein production of il-1beta and il-6 by peritoneal macrophages in both trypanosoma brucei brucei-infected and non-infected rats.	to test the hypothesis that the nervous system participates in modulating the immune response during experimental african trypanosomiasis caused by trypanosoma brucei brucei.	2004	14758057
transformation of monomorphic and pleomorphic trypanosoma brucei.	african trypanosomes, such as trypanosoma brucei, are protozoan parasites of mammals that were first described over 100 hundred years ago. they have long been the subjects of biological investigation, which has yielded insights into a number of fundamental, as well as novel, cellular processes in all organisms. in the last decade or so, genetic manipulation of trypanosomes has become possible through dna transformation, allowing yet more detailed analysis of the biology of the parasite. one face ...	2004	14769956
smd1 is required for spliced leader rna biogenesis.	the sm-binding site of the kinetoplastid spliced leader rna has been implicated in accurate spliced leader rna maturation and trans-splicing competence. in trypanosoma brucei, rna interference-mediated knockdown of smd1 caused defects in spliced leader rna maturation, displaying aberrant 3'-end formation, partial formation of cap 4, and overaccumulation in the cytoplasm; u28 pseudouridylation was unaffected.	2004	14871954
a differential role for actin during the life cycle of trypanosoma brucei.	actin is expressed at similar levels but in different locations in bloodstream and procyclic forms of trypanosoma brucei. in bloodstream forms actin colocalizes with the highly polarized endocytic pathway, whereas in procyclic forms it is distributed throughout the cell. rna interference demonstrated that in bloodstream forms, actin is an essential protein. depletion of actin resulted in a rapid arrest of cell division, termination of vesicular traffic from the flagellar pocket membrane leading ...	2004	14963487
human african trypanosomiasis of the cns: current issues and challenges.	human african trypanosomiasis (hat), also known as sleeping sickness, is a major cause of mortality and morbidity in sub-saharan africa. current therapy with melarsoprol for cns hat has unacceptable side-effects with an overall mortality of 5%. this review discusses the issues of diagnosis and staging of cns disease, its neuropathogenesis, and the possibility of new therapies for treating late-stage disease.	2004	14966556
temporal dissection of bax-induced events leading to fission of the single mitochondrion in trypanosoma brucei.	the protozoan trypanosoma brucei has a single mitochondrion and lacks an apoptotic machinery. here we show that expression of the proapoptotic protein bax in t. brucei causes the release of cytochrome c, the depolarization of the mitochondrial membrane potential and mitochondrial fission. however, in contrast to mammalian cells, the three events are temporally well separated. the release of cytochrome c from the intermembrane space precedes mitochondrial fission, showing that it does not depend ...	2004	14968134
identification and functional characterization of lsm proteins in trypanosoma brucei.	rna interference of sm proteins in trypanosoma brucei demonstrated that the stability of the small nuclear rnas (u1, u2, u4, u5) and the spliced leader rna, but not u6 rna, were affected upon sm depletion (mandelboim, m., barth, s., biton, m., liang, x. h., and michaeli, s. (2003) j. biol. chem. 278, 51469-51478), suggesting that lsm proteins that bind and stabilize u6 rna in other eukaryotes should exist in trypanosomes. in this study, we identified seven lsm proteins (lsm2p to lsm8p) and exami ...	2004	14990572
kinetics of endocytosis and recycling of the gpi-anchored variant surface glycoprotein in trypanosoma brucei.	the dense coat of glycosylphosphatidylinositol (gpi)-anchored variant surface glycoprotein (vsg) covering parasitic african trypanosomes is essential for survival in mammalian hosts. vsg is internalised and recycled exclusively via a specialised part of the plasma membrane, the flagellar pocket. direct measurement of the kinetics of vsg endocytosis and recycling shows that the vsg cell-surface pool is turned over within 12 minutes. correspondingly, the turnover of the intracellular pool (9+/-4% ...	2004	14996937
protein conformer selection by sequence-dependent packing contacts in crystals of 3-phosphoglycerate kinase.	in several crystal structures of 3-phosphoglycerate kinase (pgk), the two domains occupy different relative positions. it is intriguing that the two extreme (open and closed) conformations have never been observed for the enzyme from the same species. furthermore, in certain cases, these different crystalline conformations represent the enzyme-ligand complex of the same composition, such as the ternary complex containing either the substrate 3-phosphoglycerate (3-pg) and beta,gamma-imido-adenosi ...	2004	14997553
twenty-four-hour disruption of the sleep-wake cycle and sleep-onset rem-like episodes in a rat model of african trypanosomiasis.	patients with human african trypanosomiasis (sleeping sickness) due to the inoculation of trypanosoma brucei gambiense or rhodesiense show a major disruption of the 24-hour sleep-wake distribution, accompanied by the occurrence of sleep-onset rapid-eye-movement (rem) sleep episodes, proportional to the severity of the illness. although animal models of human african trypanosomiasis have been developed to understand the pathogenic mechanisms leading to immune alterations, the development of an an ...	2004	14998236
mathematical and statistical analysis of the trypanosoma brucei slender to stumpy transition.	we propose a new model for the stumpy induction factor-induced slender to stumpy transformation of trypanosoma brucei gambiense cells in immunosuppressed mice. the model is a set of delay differential equations that describe the time-course of the infection. we fit the model, using a maximum-likelihood method, to previously published data on parasitaemia in four mice. the model is shown to be a good fit and parameter estimates and confidence intervals are derived. our estimated parameter values ...	2004	15002904
gene synteny and evolution of genome architecture in trypanosomatids.	the trypanosomatid protozoa trypanosoma brucei, trypanosoma cruzi and leishmania major are related human pathogens that cause markedly distinct diseases. using information from genome sequencing projects currently underway, we have compared the sequences of large chromosomal fragments from each species. despite high levels of divergence at the sequence level, these three species exhibit a striking conservation of gene order, suggesting that selection has maintained gene order among the trypanoso ...	2004	15003838
endocytosis, membrane recycling and sorting of gpi-anchored proteins: trypanosoma brucei as a model system.	in the flagellated protozoon trypanosoma brucei, endo- and exocytosis are restricted to a small area of the plasma membrane, the flagellar pocket. all endosomal compartments and the single golgi complex are located within the posterior part of the cell between the flagellar pocket and the nucleus. the use of reverse genetic tools, including rna interference, in combination with quantitative 3d-fluorescence and electron microscopic techniques has provided an insight into endosomal membrane traffi ...	2004	15255888
factors affecting the level and localization of the transferrin receptor in trypanosoma brucei.	transfer of bloodstream-form trypanosoma brucei variant 221a from calf serum to dog serum-based medium induces acute iron starvation, as the transferrin receptor (tf-r) of variant 221a binds dog tf poorly. we show here that transfer to dog serum induces a 3-5-fold increase in tf-r mrna and protein within one doubling time (8 h). because iron stores are still high 8 h after transfer, we infer that the signal for tf-r overproduction is the decreased availability of cytosolic iron when cellular iro ...	2004	15263009
the efficacy of inhibitors involved in spermidine metabolism in plasmodium falciparum, anopheles stephensi and trypanosoma evansi.	in the present study, we have tested the effect of different polyamine inhibitors of the spermidine metabolizing enzymes deoxyhypusine synthase and homospermidine synthase in different chloroquine resistant plasmodium falciparum strains, in the mosquito anopheles stephensi (diptera: culicidae) and in a trypanosoma evansi clone i from strain stib 806 k china. recent experiments have shown that agmatine is a growth inhibitor of the malaria parasite p. falciparum (kaiser et al. 2001) in vitro. a co ...	2004	15278440
rab4 is an essential regulator of lysosomal trafficking in trypanosomes.	rapid endocytosis and recycling of surface proteins are important processes common to most nucleated eukaryotic cells. the best characterized membrane recycling routes are mediated by the small gtpases rab4 and rab11, but the precise roles that these pathways play have not been fully elucidated. the protozoan trypanosoma brucei has a highly developed endocytic system that is similar to that found in metazoans, albeit with an accelerated rate of membrane turnover. we have used this organism to in ...	2004	15284229
the trypanosoma brucei reference strain treu927/4 contains t. brucei rhodesiense-specific sra sequences, but displays a distinct phenotype of relative resistance to human serum.	the trypanosoma brucei reference strain treu927/4 exhibits some resistance to lysis by normal human serum (nhs), but this resistance is never complete even after selection. the genome of this strain contains a minimum of eight sequences related to the t. brucei rhodesiense-specific serum resistance-associated gene (sra), which encodes a truncated variant surface glycoprotein (vsg) conferring full resistance to lysis by nhs. we selected two sequences showing the highest similarity to sra and also ...	2004	15287585
purification and identification of a fatty acyl-coa synthetase from trypanosoma brucei.		2004	15287596
rna interference for analysis of gene function in trypanosomatids.	gene-specific silencing by rna interference is a valuable tool for analysis of gene function in the protozoan parasite trypanosoma brucei. the development of tetracycline-regulated vectors for production of double-stranded rna has facilitated its widespread use. rna interference provides a fast and efficient method for determining whether a gene is essential for growth and viability, reveals mechanistic information on gene function, and has greatly enhanced our understanding of complex biologica ...	2004	15288622
antigenic variation in trypanosoma brucei: facts, challenges and mysteries.	antigenic variation allows african trypanosomes to develop chronic infections in mammalian hosts. this process results from the alternative occurrence of transcriptional switching and dna recombination targeted to a telomeric locus that contains the gene of the variant antigen and is subjected to mono-allelic expression control. so far, the identification of mechanisms and factors involved still resists technological developments and genome sequencing.	2004	15288623
cloning, heterologous expression, and characterization of three aquaglyceroporins from trypanosoma brucei.	trypanosoma brucei, causative for african sleeping sickness, relies exclusively on glycolysis for atp production. under anaerobic conditions, glucose is converted to equimolar amounts of glycerol and pyruvate, which are both secreted from the parasite. as we have shown previously, glycerol transport in t. brucei occurs via specific membrane proteins (wille, u., schade, b., and duszenko, m. (1998) eur. j. biochem. 256, 245-250). here, we describe cloning and biochemical characterization of the th ...	2004	15294911
activities of pt(ii) and ru(iii) triazole-pyrimidine complexes against trypanosoma cruzi and t. brucei brucei.	we studied the biological activity of three newly synthesized metal complexes of triazole-pyrimidine derivatives that were previously observed to inhibit in vitro growth of epimastigotes of trypanosoma cruzi and procyclic forms of trypanosoma brucei brucei. we analyzed the possible inhibitory effect of these compounds on the synthesis of dna, rna and protein, ultrastructure and excretion of metabolites by these parasites. rna synthesis was inhibited by all three complexes assayed. these complexe ...	2004	14685011
the ingi and rime non-ltr retrotransposons are not randomly distributed in the genome of trypanosoma brucei.	the ingi (long and autonomous) and rime (short and nonautonomous) non--long-terminal repeat retrotransposons are the most abundant mobile elements characterized to date in the genome of the african trypanosome trypanosoma brucei. these retrotransposons were thought to be randomly distributed, but a detailed and comprehensive analysis of their genomic distribution had not been performed until now. to address this question, we analyzed the ingi/rime sequences and flanking sequences from the ongoin ...	2004	14694076
the 6-phosphogluconate dehydrogenase from trypanosoma cruzi: the absence of two inter-subunit salt bridges as a reason for enzyme instability.	the third enzyme of the pentose phosphate pathway (ppp), 6-phosphogluconate dehydrogenase (6pgdh), is present in the four major stages of trypanosoma cruzi, cl brener clone. the enzyme was too unstable to be purified from epimastigote cell-free extracts. two genes encoding 6pgdh were cloned and sequenced; the predicted amino acid sequences differ only in five non-essential residues. since southern blots suggested the presence of a single copy per haploid genome, the two genes found are probably ...	2004	14698432
trypanosome apoptotic factor mediates apoptosis in human brain vascular endothelial cells.	human african trypanosomiasis (hat, sleeping sickness) is a devastating disease caused by infection with trypanosoma brucei ssp. these hemoflagellates invade the central nervous system (cns) and induce meningo-encephalitis, neuronal demyelination, blood-brain-barrier (bbb) dysfunction, peri-vascular infiltration, astrocytosis and apoptosis. the molecular basis of these manifestations is unclear. we previously reported t. brucei-induced apoptosis in cerebella and brain-stem nuclei in mice at peak ...	2004	14698435
base j, found in nuclear dna of trypanosoma brucei, is not a target for dna glycosylases.	base excision repair (ber) is an evolutionarily conserved system which removes altered bases from dna. the initial step in ber is carried out by dna glycosylases which recognize altered bases and cut the n-glycosylic bond between the base and the dna backbone. in kinetoplastid flagellates, such as trypanosoma brucei, the modified base beta-d-glucosyl-hydroxymethyluracil (j) replaces a small percentage of thymine residues, predominantly in repetitive telomeric sequences. base j is synthesized at ...	2004	14706348
design and synthesis of peptidomimetic protein farnesyltransferase inhibitors as anti-trypanosoma brucei agents.	on the basis of the structure of the cvim tetrapeptide substrate of mammalian protein farnesyltransferase, a series of imidazole-containing peptidomimetics was designed and synthesized, and their inhibition activity against trypanosoma brucei protein farnesyltransferase (tbpft) was evaluated. peptidomimetics where the 5-position of the imidazole ring was linked to the hydrophobic scaffold showed over 70% inhibition activity at 50 nm in the enzyme assay, whereas the corresponding c-4 regioisomers ...	2004	14711313
trypanosoma brucei plasma membrane-type ca(2+)-atpase 1 (tbpmc1) and 2 (tbpmc2) genes encode functional ca(2+)-atpases localized to the acidocalcisomes and plasma membrane, and essential for ca(2+) homeostasis and growth.	trypanosoma brucei adaptation and survival in its host involve integrated regulation of ca(2+) pumps (ca(2+)-atpases), which are essential in calcium ion homeostasis. here we report the cloning and sequencing of two genes (tbpmc1 and tbpmc2) encoding plasma membrane-type ca(2+)-atpases (pmcas) of t. brucei, an agent of african trypanosomiasis. indirect immunofluorescence analysis using antibodies against the proteins and against epitope tags introduced into each protein showed that tbpmc1 co-loc ...	2004	14724285
bloodstream form-specific up-regulation of silent vsg expression sites and procyclin in trypanosoma brucei after inhibition of dna synthesis or dna damage.	the african trypanosome trypanosoma brucei transcribes the active variant surface glycoprotein (vsg) gene from one of about 20 vsg expression sites (ess). in order to study es control, we made reporter lines with a green fluorescent protein gene inserted behind the promoter of different ess. we attempted to disrupt the silencing machinery, and we used fluorescence-activated cell sorter analysis for the rapid and sensitive detection of es up-regulation. we find that a range of treatments that eit ...	2004	14726511
molecular profiles of trypanosoma brucei, t. evansi and t. equiperdum stocks revealed by the random amplified polymorphic dna method.	a total of 20 random primers (10-mers) were used to amplify rapd markers from the genomic dna of four trypanosoma brucei stocks from east and west africa, four t. evansi stocks from africa, asia and south america and one t. equiperdum stock from asia. between 65 and 88 reproducible fragments ranging from 0.25 to 2.15 kb were generated from these stocks depending on the stock/primer combination. the similarity coefficient (sc) among the stocks of t. brucei from kenya, nigeria, tanzania and zambia ...	2004	14727188
megazol combined with suramin improves a new diagnosis index of the early meningo-encephalitic phase of experimental african trypanosomiasis.	in human african trypanosomiasis (hat), the parasites invade the central nervous system (cns), leading to the development of meningo-encephalitis and an irreversible demyelinating process, which kills the patient unless specific treatment is undertaken. among the experimental trypanocides, the nitroimidazole derivative megazol alone at optimal doses does not cure late-stage disease tested in mouse models, however the combination of suramin and megazol is able to cure infected mice without cns in ...	2004	14728611
tbpde1, a novel class i phosphodiesterase of trypanosoma brucei.	cyclic nucleotide specific phosphodiesterases (pdes) are important components of all camp signalling networks. in humans, 11 different pde families have been identified to date, all of which belong to the class i pdes. pharmacologically, they have become of great interest as targets for the development of drugs for a large variety of clinical conditions. pdes in parasitic protozoa have not yet been extensively investigated, despite their potential as antiparasitic drug targets. the current study ...	2004	14728691
successful design and synthesis of a polarity-triggered beta-->alpha conformational switch using the side chain interaction index (scii) as a measure of local structural stability.	certain sequences within proteins have the ability to undergo an abrupt cooperative conformational switch from beta-strand to helix in response to decreasing polarity of the environment. this behavior was first observed at the cd4 binding site of the envelope glycoprotein gp120 of hiv-1, but evidence has accumulated that polarity-driven beta --> alpha switches may be widespread, serving both to facilitate binding on protein/membrane or protein/protein contact and to signal that docking has occur ...	2004	14730964
the single dynamin-like protein of trypanosoma brucei regulates mitochondrial division and is not required for endocytosis.	members of the evolutionarily conserved dynamin-related gtpase family mediate numerous cellular membrane remodeling events. dynamin family functions include the scission of clathrin-coated pits from the plasma membrane, mitochondrial fission, and chloroplast division. here we report that the divergent eukaryote trypanosoma brucei possesses a single dynamin family gene, which we have designated tbdlp. furthermore, a single dynamin family gene is also found in the leishmania major and trypanosoma ...	2004	14670954
argonaute protein in the early divergent eukaryote trypanosoma brucei: control of small interfering rna accumulation and retroposon transcript abundance.	members of the argonaute protein family have been linked through a combination of genetic and biochemical studies to rna interference (rnai) and related phenomena. here, we describe the characterization of the first argonaute protein (ago1) in trypanosoma brucei, the earliest divergent eukaryote where rnai has been described so far. ago1 is predominantly cytoplasmic and is found in a ribonucleoprotein particle with small interfering rnas (sirnas), and this particle is present in a soluble form, ...	2004	14673174
the effect of rna interference down-regulation of rna editing 3'-terminal uridylyl transferase (tutase) 1 on mitochondrial de novo protein synthesis and stability of respiratory complexes in trypanosoma brucei.	inhibition of rna editing by down-regulation of expression of the mitochondrial rna editing tutase 1 by rna interference had profound effects on kinetoplast biogenesis in trypanosoma brucei procyclic cells. de novo synthesis of the apocytochrome b and cytochrome oxidase subunit i proteins was no longer detectable after 3 days of rnai. the effect on protein synthesis correlated with a decline in the levels of the assembled mitochondrial respiratory complexes iii and iv, and also cyanide-sensitive ...	2004	14681226
effects of depletion and overexpression of the trypanosoma brucei ribonuclease l inhibitor homologue.		2004	14668021
functional expression and characterization of a purine nucleobase transporter gene from leishmania major.	leishmania major, like all the other kinetoplastid protozoa, are unable to synthesize purines and rely on purine nucleobase and nucleoside acquisition across the parasite plasma membrane by specific permeases. although, several genes have been cloned that encode nucleoside transporters in leishmania and trypanosoma brucei, much less progress has been made on nucleobase transporters, especially at the molecular level. the studies reported here have cloned and expressed the first gene for a l. maj ...	2004	14668134
characterization of components of the mismatch repair machinery in trypanosoma brucei.	mismatch repair is one of a number of dna repair pathways that cells possess to deal with damage to their genome. mismatch repair is concerned with the recognition and correction of incorrectly paired bases, which can be base-base mismatches or insertions or deletions of a few bases, and appears to have been conserved throughout evolution. primarily, this is concerned with increasing the fidelity of dna replication, but also has important roles in the regulation of homologous recombination and t ...	2004	14651619
heme oxygenase in candida albicans is regulated by hemoglobin and is necessary for metabolism of exogenous heme and hemoglobin to alpha-biliverdin.	candida albicans is an opportunistic pathogen that has adapted uniquely to life in mammalian hosts. one of the host factors recognized by this yeast is hemoglobin, which binds to a specific cell surface receptor. in addition to its regulating the expression of adhesion receptors on the yeast, we have found that hemoglobin induces the expression of a c. albicans heme oxygenase (cahmx1p). hemoglobin transcriptionally induces the cahmx1 gene independent of the presence of inorganic iron in the medi ...	2004	14615478
a pyrophosphatase regulating polyphosphate metabolism in acidocalcisomes is essential for trypanosoma brucei virulence in mice.	we report the functional characterization of a soluble pyrophosphatase (tbvsp1), which localizes to acidocalcisomes, a vesicular acidic compartment of trypanosoma brucei. depending on the ph and the cofactors mg(2+) or zn(2+), both present in the compartment, the enzyme hydrolyzes either inorganic pyrophosphate (pp(i)) (k(cat) = 385 s(-1)) or tripolyp (polyp(3)) and polyphosphate (polyp) of 28 residues (polyp(28)) with k(cat) values of 52 and 3.5 s(-1), respectively. an unusual n-terminal domain ...	2004	14615483
non-canonical eukaryotic glutaminyl- and glutamyl-trna synthetases form mitochondrial aminoacyl-trna in trypanosoma brucei.	glutaminyl-trna synthetase is thought to be absent from organelles. instead, gln-trna is formed via the transamidation pathway, the other route to this essential compound in protein biosynthesis. however, it was previously shown that glutaminyl-trna synthetase activity is present in leishmania mitochondria. this work identifies genes encoding glutaminyl- and glutamyl-trna synthetase in the closely related organism trypanosoma brucei. down-regulation of their respective gene products by rna inter ...	2004	14563839
multiple triclosan targets in trypanosoma brucei.	trypanosoma brucei genes encoding putative fatty acid synthesis enzymes are homologous to those encoding type ii enzymes found in bacteria and organelles such as chloroplasts and mitochondria. it was therefore not surprising that triclosan, an inhibitor of type ii enoyl-acyl carrier protein (enoyl-acp) reductase, killed both procyclic forms and bloodstream forms of t. brucei in culture with 50% effective concentrations (ec(50)s) of 10 and 13 microm, respectively. triclosan also inhibited cell-fr ...	2004	15302818
an intragenic guide rna location suggests a complex mechanism for mitochondrial gene expression in trypanosoma brucei.	in trypanosoma brucei, two classes of transcripts are produced from two distinct mitochondrial genome components. guide rnas (grnas) are usually minicircle encoded and exist as primary transcripts, while the maxicircle-encoded rrnas and mrnas are processed from a polycistronic precursor. the genes for the grnas gmurf2-ii and gcyb(560) each have uncommon kinetoplast dna (kdna) locations that are not typically associated with transcription initiation events. we demonstrate that the conserved maxic ...	2004	15302819
role of a 300-kilodalton nuclear complex in the maturation of trypanosoma brucei initiator methionyl-trna.	trnas are transcribed as precursors containing 5' leader and 3' extensions that are removed by a series of posttranscriptional processing reactions to yield functional mature trnas. here, we examined the maturation pathway of trna(met) in trypanosoma brucei, an early divergent unicellular eukaryote. we identified an approximately 300-kda complex located in the nucleus of t. brucei that is required for trimming the 5' leader of initiator trna(met) precursors. one of the subunits of the complex (t ...	2004	15302822
clathrin-dependent targeting of receptors to the flagellar pocket of procyclic-form trypanosoma brucei.	in trypanosomatids, endocytosis and exocytosis occur exclusively at the flagellar pocket, which represents about 0.43% of the pellicle membrane and is a deep invagination of the plasma membrane where the flagellum extends from the cell. receptor molecules are selectively retained at the flagellar pocket. we studied the function of clathrin heavy chain (tbclh) in the trafficking of the flagellar pocket receptors in trypanosoma brucei by using the double-stranded rna interference approach. it appe ...	2004	15302833
multiple terminal uridylyltransferases of trypanosomes.	the transferase activities that add uridylyl residues to rna have been reported in several unicellular and metazoan organisms. thus far, the two terminal uridylyltransferases (tutases) involved in uridine insertion/deletion mrna editing in mitochondria of trypanosomes were the only known enzymes with confirmed utp specificity. here, we demonstrate that protein sequences of editing tutases may be used to predict novel utp-specific enzymes by data mining. the highest-scoring open reading frame fro ...	2004	15304317
why trypanosomes cause sleeping sickness.	african trypanosomiasis or sleeping sickness is hallmarked by sleep and wakefulness disturbances. in contrast to other infections, there is no hypersomnia, but the sleep pattern is fragmented. this overview discusses that the causative agents, the parasites trypanosoma brucei, target circumventricular organs in the brain, causing inflammatory responses in hypothalamic structures that may lead to dysfunctions in the circadian-timing and sleep-regulatory systems.	2004	15304634
cyp51 from trypanosoma brucei is obtusifoliol-specific.	new isoforms of cyp51 (sterol 14alpha-demethylase), an essential enzyme in sterol biosynthesis and primary target of azole antimycotic drugs, are found in pathogenic protists, trypanosoma brucei(tb), t. vivax, t. cruzi, and leishmania major. the sequences share approximately 80% amino acid identity and are approximately 25% identical to sterol 14alpha-demethylases from other biological kingdoms. differences of residues conserved throughout the rest of the cyp51 family that align with the bc-loop ...	2004	15311940
trypanocidal effect of alpha',beta'-epoxyketones indicates that trypanosomes are particularly sensitive to inhibitors of proteasome trypsin-like activity.	previous studies have shown that the proteasome of trypanosoma brucei is a candidate for novel chemotherapy of african sleeping sickness. in this study, two potent and highly selective alpha',beta'-epoxyketones peptide proteasome inhibitors, epoxomicin and yu101, have been tested for their trypanocidal activities in vitro using culture-adapted bloodstream forms of t. brucei. both inhibitors displayed promising anti-trypanosomal activities with ed(50) and ed(90) values in the low to mid nanomolar ...	2004	15325434
a cathepsin b-like protease is required for host protein degradation in trypanosoma brucei.	identification and analysis of clan ca (papain) cysteine proteases in primitive protozoa and metazoa have suggested that this enzyme family is more diverse and biologically important than originally thought. the protozoan parasite trypanosoma brucei is the etiological agent of african sleeping sickness. the cysteine protease activity of this organism is a validated drug target as first recognized by the killing of the parasite with the diazomethane inhibitor z-phe-ala-chn(2) (where z is benzylox ...	2004	15326171
acetyl:succinate coa-transferase in procyclic trypanosoma brucei. gene identification and role in carbohydrate metabolism.	acetyl:succinate coa-transferase (asct) is an acetate-producing enzyme shared by hydrogenosomes, mitochondria of trypanosomatids, and anaerobically functioning mitochondria. the gene encoding asct in the protozoan parasite trypanosoma brucei was identified as a new member of the coa transferase family. its assignment to asct activity was confirmed by 1) a quantitative correlation of protein expression and activity upon rna interference-mediated repression, 2) the absence of activity in homozygou ...	2004	15326192
tcrrms and tcp28 genes are intercalated and differentially expressed in trypanosoma cruzi life cycle.	the identification and characterization of rna binding proteins in trypanosoma cruzi are particularly relevant as they play key roles in the regulatory mechanisms of gene expression. in this work, we have identified coding sequences for the proteins, named tcrrm1 and tcrrm2, in the est database generated by the t. cruzi genomic initiative. tcrrm1 and tcrrm2 contain two rna binding domains (rrm) and are very similar to two trypanosoma brucei rna binding proteins previously reported, tbp34 and tbp ...	2004	15336561
cytoplasmic targeting signals in transmembrane invariant surface glycoproteins of trypanosomes.	protein targeting mechanisms in flagellated protozoan parasites have received considerable interest because of a huge bias in these organisms toward the glycosylphosphatidylinositol anchor as a mechanism for the membrane attachment of cell surface macromolecules. in this study, the trafficking of invariant surface glycoprotein 65 (isg65), a family of type i transmembrane proteins, was examined. analysis of the c-terminal domains of isg65 family members demonstrated a high level of conservation a ...	2004	15342636
cerebral vessel laminins and ifn-gamma define trypanosoma brucei brucei penetration of the blood-brain barrier.	subspecies of trypanosoma brucei cause severe brain diseases after penetration of the blood-brain barrier. we investigated whether cytokines that modulate inflammatory cell infiltration into the brain also influence t. brucei neuroinvasion. migration of a rodent pathogenic t. brucei strain from the cerebral blood vessels into the brain parenchyma was impeded in ifn-gamma(-/-), ifn-gamma receptor(-/-) (ifn-gammar(-/-)), il-12p40(-/-), and recombinant activating gene-1(-/-) (rag-1(-/-)) mice as co ...	2004	15343387
differential effects of interferon-gamma on production of trypanosome-derived lymphocyte-triggering factor by trypanosoma brucei gambiense and trypanosoma brucei brucei.	trypanosome-derived lymphocyte-triggering factor (tltf) produced by trypanosoma brucei brucei stimulates production of interferon-gamma (ifn-gamma) by cd8+ t cells, and it is reported that, in turn, ifn-gamma stimulates proliferation of t. b. brucei. we studied the role of tltf in trypanosome proliferation using the wellcome strain (ws) of trypanosoma brucei gambiense and the iltat 1.4 strain (il) of t. b. brucei. increase in the number of ws in infected rats is more rapid than il and correspond ...	2004	15357062
the molecular control of antigenic variation in trypanosoma brucei.	the african trypanosome, trypanosoma brucei, is a protozoan that causes sleeping sickness in humans and n'gana in livestock. these flagellated parasites are directly exposed to immune defences as they circulate in the mammalian host bloodstream but they maintain persistent infections by undergoing antigenic variation. central to this process is mono-allelic transcription and switching of the expressed variant-surface glycoprotein (vsg) gene which encodes the vast majority of their dense surface ...	2004	15357208
camp signalling in the kinetoplastid protozoa.	several species of kinetoplastid protozoa cause major human infectious diseases. trypanosoma cruzi is responsible for the fatal chagas disease in large parts of south america, the various species of leishmania cause a number of different human diseases with millions of patients world-wide, and the african trypanosome trypanosoma brucei is the agent of human sleeping sickness, a disastrously re-emerging epidemic of fatal infections in sub-saharan africa. chemotherapy of all of these infections is ...	2004	15357210
anthranoid compounds with antiprotozoal activity from vismia orientalis.	a phytochemical investigation of the 80% ethanolic extract of stem bark of vismia orientalis engl. (guttiferae or clusiaceae), a plant used in traditional medicine in tanzania, resulted in the isolation and spectroscopic characterisation of 3-geranyloxy-6-methyl-1,8-dihydroxyanthraquinone, emodin, vismione d and bianthrone a1. vismione d exhibited a broad range of antiprotozoal activities against trypanosoma brucei rhodesiense and t. cruzi (ic50 < 10 micrograms/ml), leishmania donovani (ic50 0.3 ...	2004	15368649
high resolution crystal structure of a key editosome enzyme from trypanosoma brucei: rna editing ligase 1.	trypanosomatids are causative agents of several devastating tropical diseases such as african sleeping sickness, chagas' disease and leishmaniasis. there are no effective vaccines available to date for treatment of these protozoan diseases, while current drugs have limited efficacy, significant toxicity and suffer from increasing resistance. trypanosomatids have several remarkable and unique metabolic and structural features that are of great interest for developing new anti-protozoan therapeuti ...	2004	15465048
molecular cloning and characterization of trypanosoma vivax alternative oxidase (aox) gene, a target of the trypanocide ascofuranone.	trypanosoma vivax causes nagana disease in cattle. since t. vivax is transmitted not only by tsetse flies but also by other biting flies (non-cyclic transmission), the parasite has been distributed to and has had a significant economic impact on wide geographical areas, including africa and south america. our previous study on trypanosoma brucei brucei showed that the trypanosome alternative oxidase (tao, tbaox) is a promising target of chemotherapy. for this reason, we also have cloned the t vi ...	2004	15468531
tbdss-1, an essential trypanosoma brucei exoribonuclease homolog that has pleiotropic effects on mitochondrial rna metabolism.	mitochondrial gene expression in trypanosomes is controlled primarily at the levels of rna processing and rna stability. this regulation undoubtedly involves numerous ribonucleases. here we characterize the trypanosoma brucei homolog of the yeast dss-1 mitochondrial exoribonuclease, which we term tbdss-1. biochemical fractionation indicates that tbdss-1 is mitochondrially localized, as predicted by its n-terminal sequence. in contrast to its yeast homolog, tbdss-1 does not appear to be associate ...	2004	15470249
multiple active site conformations revealed by distant site mutation in ornithine decarboxylase.	ornithine decarboxylase (odc) is an obligate homodimer that catalyzes the pyridoxal 5'-phosphate-dependent decarboxylation of l-ornithine to putrescine, a vital step in polyamine biosynthesis. a previous mutagenic analysis of the odc dimer interface identified several residues that were distant from the active site yet had a greater impact on catalytic activity than on dimer stability [myers, d. p., et al. (2001) biochemistry 40, 13230-13236]. to better understand the basis of this phenomenon, t ...	2004	15476392
molecular and phylogenetic characterization of syntaxin genes from parasitic protozoa.	vesicular transport is an integral process in eukaryotic cells and the syntaxins, a member of the snare protein superfamily, are a critical piece of the vesicular transport machinery. we have obtained syntaxin homologues from diverse protozoan parasites (including entamoeba, giardia, trichomonas and trypanosoma), determined the paralogue affinity of the homologues by molecular phylogenetics and compared functionally critical amino acid sites identified in other syntaxins. surprisingly, three seq ...	2004	15478792
rna interference of trypanosoma brucei topoisomerase ib: both subunits are essential.	type ib topoisomerases are enzymes essential for the orderly synthesis of nucleic acids and are the molecular target for antitumor camptothecins. in dozens of organisms, including eukaryotes, bacteria, and viruses, this enzyme is monomeric. however, we previously found that topoisomerase ib in trypanosomes is a heteromultimer, comprised of two distinct subunits encoded by separate genes. a large 90 kda subunit contains the dna binding domain and a small 36 kda subunit contains the catalytic doma ...	2004	15478803
a novel purine nucleoside transporter whose expression is up-regulated in the short stumpy form of the trypanosoma brucei life cycle.	purine nucleoside and nucleobase transporters play a vital role in the metabolism and survival of trypanosoma brucei because this parasitic protozoan is unable to synthesize purines de novo and thus must acquire preformed purines from its hosts. these parasites express a variety of nucleoside and nucleobase permeases with diverse substrate specificities and distinct patterns of expression during the trypanosome life cycle. we report here that expression of the newly characterized t. brucei nucle ...	2004	15478805
tbrab23; a nuclear-associated rab protein from trypanosoma brucei.		2004	15478808
functional characterization of a trypanosoma brucei tata-binding protein-related factor points to a universal regulator of transcription in trypanosomes.	transcriptional mechanisms remain poorly understood in trypanosomatid protozoa. in particular, there is no knowledge about the function of basal transcription factors, and there is an apparent rarity of promoters for protein-coding genes transcribed by rna polymerase (pol) ii. here we describe a trypanosoma brucei factor related to the tata-binding protein (tbp). although this tbp-related factor (tbp-related factor 4 [trf4]) has about 31% identity to the tbp core domain, several key residues inv ...	2004	15485927
the n-glycan glucosidase system in trypanosoma brucei.	reactions involving removal and addition of glucose to n-glycans in the er (endoplasmic reticulum) are performed in higher eukaryotes by glucosidases i and ii and the udp-glucose:glycoprotein glucosyltransferase respectively. monoglucosylated n-glycan structures have been implicated in glycoprotein folding or er quality control. components of the system appear across a range of organisms; however, the precise combination differs between organisms. we have identified putative components of the sy ...	2004	15494010
maturation of the unusual single-cysteine (xxxch) mitochondrial c-type cytochromes found in trypanosomatids must occur through a novel biogenesis pathway.	the c-type cytochromes are characterized by the covalent attachment of haem to the polypeptide via thioether bonds formed from haem vinyl groups and, normally, the thiols of two cysteines in a cxxch motif. intriguingly, the mitochondrial cytochromes c and c1 from two euglenids and the trypanosomatidae contain only a single cysteine within the haem-binding motif (xxxch). there are three known distinct pathways by which c-type cytochromes are matured post-translationally in different organisms. th ...	2004	15500440
characterization of primate trypanosome lytic factors.	humans are one of the few species that resist infection by trypanosoma brucei brucei because the parasites are killed by lytic factors found in human serum. trypanosome lytic factors (tlfs) are protein/lipid complexes that contain apolipoprotein a-i (apoa-i), and are therefore a class of high density lipoproteins (hdls). haptoglobin-related protein (hpr) is a unique protein component of tlfs, and its expression has only been demonstrated in humans. trypanolytic activity has only been found in th ...	2004	15500911
both of the rab5 subfamily small gtpases of trypanosoma brucei are essential and required for endocytosis.	endocytosis is an essential process in trypanosoma brucei and all evidence suggests it is exclusively clathrin-mediated. the trypanosome genome encodes two rab5 proteins, small gtpases that play a role in very early stages of endocytosis. in the mammalian bloodstream stage tbrab5a localises to compartments containing internalised antibody, variant surface glycoprotein (vsg) and transferrin, whilst tbrab5b localises to compartments containing the transmembrane protein isg(100). dominant-active fo ...	2004	15500917
role of the n-terminal domains of ep and gpeet procyclins in membrane targeting and the establishment of midgut infections by trypanosoma brucei.		2004	15383295
tbrab1 and tbrab2 mediate trafficking through the early secretory pathway of trypanosoma brucei.	the african trypanosome possesses a total of 16 small gtpases of the rab family, which are involved in control of various membrane transport events. recently the roles of these proteins in the endocytosis and recycling of the major surface antigen of the bloodstream form, the variant surface glycoprotein (vsg), have been described but little has been reported on the roles of rab proteins in exocytic pathways in trypanosomatids. whilst phylogenetic analysis based on sequence similarity indicates ...	2004	15383296
failure to detect binding of trypanosoma brucei snapc to u2 and u6 snrna gene sequences by in vitro transcription competition and pull-down assays.	the small nuclear rna (snrna)-activating protein complex (snap(c)) is a multi-subunit transcription factor characterized in humans and drosophila melanogaster. it binds to an upstream sequence element (use) of snrna gene promoters and activates both rna polymerase (pol) ii and iii-mediated transcription of snrna genes. the first identified and partially characterized transcription factor in a trypanosomatid organism appears to be a snap(c) homologue. it was identified in leptomonas seymouri and ...	2004	15383299
function of the trypanosome argonaute 1 protein in rna interference requires the n-terminal rgg domain and arginine 735 in the piwi domain.	argonaute proteins are central components of rna interference (rnai) and related phenomena in a wide variety of eukaryotes, including the early diverging protozoan trypanosoma brucei. the single t. brucei argonaute protein (tbago1) is in a complex with small interfering rnas (sirnas), and a fraction of this ribonucleoprotein particle is associated with polyribosomes. in this study, we generated a panel of insertion, deletion, and single point mutants of tbago1 and assayed them in vivo for their ...	2004	15383544
a novel erk-like, crk-like protein kinase that modulates growth in trypanosoma brucei via an autoregulatory c-terminal extension.	the protozoan parasite trypanosoma brucei undergoes a complex developmental cycle coordinated with cell cycle control. these processes in eukaryotes are frequently regulated through mitogen-activated protein kinases (mapks) and cyclin-dependent protein kinases (cdks), respectively. we have discovered a novel protein kinase which shares features of both erk-type mapks and cdks (t. brucei erk-like, cdk-like protein kinase). this molecule, named tbeck1, is similar to the unusual mammalian kkiamre p ...	2004	15387824
crystallization and preliminary x-ray diffraction study of the farnesyl diphosphate synthase from trypanosoma brucei.	farnesyl diphosphate synthase (fpps) catalyses the formation of farnesyl diphosphate from dimethylallyl diphosphate and isopentenyl diphosphate and is an rnai-validated drug target in trypanosoma brucei, the causative agent of african sleeping sickness. a t. brucei fpps (390 amino acids) has been expressed in escherichia coli and the recombinant protein has been crystallized in the absence and presence of the bisphosphonate inhibitor minodronate. diffraction data were collected at 100 k using sy ...	2004	15388934
ultrastructure in cell biology: do we still need it?	john heuser is being honored in this special issue for his enormous contributions to cell biology using morphological approaches. foremost in this context is his ability to use light and electron microscopy to visualize structures and processes such that the information has both scientific and artistic value. the beauty of his images helps to focus the observer more intensely on the scientific messages, which have been numerous and important. his recent studies of living cells using state-of-the ...	2004	15511081
isolation of the repertoire of vsg expression site containing telomeres of trypanosoma brucei 427 using transformation-associated recombination in yeast.	trypanosoma brucei switches between variant surface glycoproteins (vsgs) allowing immune escape. the active vsg is in one of many telomeric bloodstream form vsg expression sites (bess), also containing expression site-associated genes (esags) involved in host adaptation. the role of bes sequence diversity in parasite virulence can best be understood through analysis of the full repertoire of bess from a given t. brucei strain. however, few bess have been cloned, as telomeres are highly underrepr ...	2004	15520294
human infectivity trait in trypanosoma brucei: stability, heritability and relationship to sra expression.	some trypanosoma brucei lines infect humans whereas others do not because the parasites are lysed by human serum. we have developed a robust, quantitative in vitro assay based on differential uptake of fluorescent dyes by live and dead trypanosomes to quantify the extent and kinetics of killing by human serum. this method has been used to discriminate between 3 classes of human serum resistance; sensitive, resistant and intermediate. treu 927/4, the parasite used for the t. brucei genome project ...	2004	15521633
tsetseep, a gut protein from the tsetse glossina morsitans, is related to a major surface glycoprotein of trypanosomes transmitted by the fly and to the products of a drosophila gene family.	african trypanosomes live in the lumen of the gut of tsetse (glossina) and may have to face an immune response. as yet, it is unclear whether they are sensitive to antimicrobial peptides in vivo, but for some years there has been indirect evidence that one or more lectins can influence the infection. we have purified a protein complex from midgut extracts that, by sds-page, is a doublet of 37 and 38 kda in a ratio of 3:1. through prediction from corresponding cdna clones, the full-length protein ...	2004	15522612
a variant histone h3 is enriched at telomeres in trypanosoma brucei.	variant histones play critical roles in transcriptional activation and repression, dna repair and chromosome segregation. we have identified htv, a single-copy gene in trypanosoma brucei encoding a variant form of histone h3 (h3v). h3v is present at discrete nuclear foci that shift over the course of the cell cycle and associate with the mitotic spindle, a pattern of localization reminiscent of that described previously for both mini-chromosomes and telomeres. by combining fluorescence in situ h ...	2004	15522895
new approaches to the microscopic imaging of trypanosoma brucei.	protozoan parasites are fearsome pathogens responsible for a substantial proportion of human mortality, morbidity, and economic hardship. the principal disease agents are members of the orders apicomplexa (plasmodium, toxoplasma, eimeria) and kinetoplastida (trypanosomes, leishmania). the majority of humans are at risk from infection from one or more of these organisms, with profound effects on the economy, social structure and quality of life in endemic areas; plasmodium itself accounts for ove ...	2004	15525435
selective transport of a new class of purine antimetabolites by the protozoan parasite trypanosoma brucei.	purine antimetabolites have been very successful therapeutic agents against a host of infectious diseases and malignancies. success of the treatment relies as much on the efficient accumulation by the target cell or organism as it does on selective action on a vital biochemical pathway of the target cell. here we compare the ability of a new class of tricyclic purine antimetabolites to interact with transporters from human erythrocytes or trypanosoma brucei. we show that these compounds display ...	2004	15571273
the 3'-untranslated region of cytochrome oxidase ii mrna functions in rna editing of african trypanosomes exclusively as a cis guide rna.	rna editing in trypanosomes is a post-transcriptional process responsible for correcting the coding sequences of many mitochondrial mrnas. uridines are specifically added or deleted from mrna by an enzymatic cascade in which a pre-edited mrna is specifically cleaved, uridines are added or removed, and the corrected mrna is ligated. the process is directed by rna molecules, termed guide rnas (grna). the ability of this class of small, noncoding rna to function in rna editing is essential for thes ...	2004	15574518
trypanocidal activities of trileucine methyl vinyl sulfone proteasome inhibitors.	previous studies have shown that proteasome inhibitors are novel agents for chemotherapy of human african trypanosomiasis or sleeping sickness. in this study, five peptide trileucine methyl vinyl sulfones with different n-terminal substituents were tested for their trypanocidal activities in vitro using culture-adapted bloodstream forms of trypanosoma brucei. two inhibitors displayed promising anti-trypanosomal activities with ed50 values in the sub-micromolar range. higher trypanocidal activity ...	2004	15578221
protective efficacy of isometamidium chloride and diminazene aceturate against natural trypanosoma brucei, trypanosoma congolense and trypanosoma vivax infections in cattle under a suppressed tsetse population in uganda.	the protective efficacy of isometamidium chloride (ismm) and diminazene aceturate (dim) against trypanosoma brucei, trypanosoma congolense and trypanosoma vivax infections in cattle under a suppressed tsetse population was assessed in southeast uganda. a total of 66 and 57 trypanosome-infected cattle were treated with ismm and dim, respectively together with 177 trypanosome-free animals not treated were followed for 12 months, checked every 4 weeks. there was no statistical difference in the mea ...	2004	15580773
trypanosomatid flagellum biogenesis: arl-3a is involved in several species.	overexpression in leishmania amazonensis promastigotes of the gtpase-deficient small g protein ldarl-3a-q70l specifically provokes the loss of the flagella without affecting cell viability and body size. however, motility is lost and, remarkably, cells do not survive in the insect vector lutzomyia longipalpis gut, leading to interruption of parasite transmission. we report here that overexpression of the same protein in leishmania major, leishmania donovani, and crithidia fasciculata also led to ...	2004	15582509
inhibition of both trypanosoma brucei bloodstream form and related glycolytic enzymes by a new kolavic acid derivative isolated from entada abyssinica.	a new kolavic acid derivative known from spectroscopic analyses as monomethyl ester-15-kolavic acid was isolated from the stem bark of entada abyssinica, a plant traditionally used in west and east africa for the management of sleeping sickness. the new derivative showed a strong and selective inhibitory activity on the gapdh enzyme of trypanosoma brucei with an ic50 value of 0.012 mm.	2004	15587590
macrophage galactose-type c-type lectins as novel markers for alternatively activated macrophages elicited by parasitic infections and allergic airway inflammation.	molecular markers, especially surface markers associated with type ii, cytokine-dependent, alternatively activated macrophages (aamf), remain scarce. besides the earlier documented markers, macrophage mannose receptor and arginase 1, we demonstrated recently that murine aamf are characterized by increased expression of found in inflammatory zone 1 (fizz1) and the secretory lectin ym. we now document that expression of the two members of the mouse macrophage galactose-type c-type lectin gene fami ...	2004	15591125
telomere length regulation and transcriptional silencing in ku80-deficient trypanosoma brucei.	ku is a heterodimer, consisting of approximately 70 and approximately 80 kda subunits (ku70 and ku80, respectively), which is involved in a variety of nuclear functions. we generated tbku80-deficient trypanosomes to explore the potential role of the tbku complex in telomere maintenance and transcriptional regulation of variant surface glycoprotein (vsg) genes in trypanosoma brucei. using real-time pcr, we demonstrated that the expression of several different vsg genes remains tightly regulated i ...	2004	15602000
kola acuminata proanthocyanidins: a class of anti-trypanosomal compounds effective against trypanosoma brucei.	human african trypanosomiasis is undergoing an alarming rate of recrudescence in many parts of sub-saharan africa. yet, there is no successful chemotherapy for the disease due to a limited number of useful drugs, side effects and drawbacks of the existing medication, as well as the development of drug resistance by the parasite. here we describe a new lead anti-trypanosomal compound isolated from kola acuminata (makasu). we purified a proanthocyanidin by chromatographic procedures and confirmed ...	2004	15619520