| depletion of mitochondrial acyl carrier protein in bloodstream-form trypanosoma brucei causes a kinetoplast segregation defect. | like other eukaryotes, trypanosomes have an essential type ii fatty acid synthase in their mitochondrion. we have investigated the function of this synthase in bloodstream-form parasites by studying the effect of a conditional knockout of acyl carrier protein (acp), a key player in this fatty acid synthase pathway. we found that acp depletion not only caused small changes in cellular phospholipids but also, surprisingly, caused changes in the kinetoplast. this structure, which contains the mitoc ... | 2011 | 21239625 |
| biased cellular locations of tandem repeat antigens in african trypanosomes. | trypanosoma brucei subspecies cause african trypanosomiasis in humans and animals. these parasites possess genes encoding proteins with large tandem repeat (tr) domains as do the other trypanosomatid parasites. we have previously demonstrated that tr protein of leishmania infantum and trypanosoma cruzi are often targets of b-cell responses. however, african trypanosomes are susceptible to antibody-mediated immunity, and it may be detrimental for the parasites to have such b-cell antigens on the ... | 2011 | 21241659 |
| a novel member of the rnase d exoribonuclease family functions in mitochondrial guide rna metabolism in trypanosoma brucei. | rna turnover and rna editing are essential for regulation of mitochondrial gene expression in trypanosoma brucei. rna turnover is controlled in part by rna 3' adenylation and uridylation status, with trans-acting factors also impacting rna homeostasis. however, little is known about the mitochondrial degradation machinery or its regulation in t. brucei. we have identified a mitochondrial exoribonuclease, tbrnd, whose expression is highly up-regulated in the insect proliferative stage of the para ... | 2011 | 21252235 |
| crystal structures of three protozoan homologs of tryptophanyl-trna synthetase. | tryptophanyl-trna synthetase (trprs) is an essential enzyme that is recognizably conserved across all forms of life. it is responsible for activating and attaching tryptophan to a cognate trna(trp) molecule for use in protein synthesis. in some eukaryotes this original core function has been supplemented or modified through the addition of extra domains or the expression of variant trprs isoforms. the three trprs structures from pathogenic protozoa described here represent three illustrations of ... | 2011 | 21255615 |
| trypanosoma brucei brucei: endocytic recycling is important for mouse infectivity. | endocytosis in the african trypanosome, trypanosoma brucei, is intimately involved in maintaining homeostasis of the cell surface proteome, morphology of the flagellar pocket and has recently been demonstrated as a bona fide drug target. rnai-mediated knockdown of many factors required for endocytic transport, including several small gtpases, the major coat protein clathrin and a clathrin-associated receptor, epsinr, results in rapid cell death in vitro. rapid loss of viability in vitro preclude ... | 2011 | 21256128 |
| a second mitochondrial dna primase is essential for cell growth and kinetoplast minicircle dna replication in trypanosoma brucei. | the mitochondrial dna of trypanosomes contains two types of circular dnas, minicircles and maxicircles. both minicircles and maxicircles replicate from specific replication origins by unidirectional theta-type intermediates. initiation of the minicircle leading strand and also that of at least the first okazaki fragment involve rna priming. the trypanosoma brucei genome encodes two mitochondrial dna primases, pri1 and pri2, related to the primases of eukaryotic nucleocytoplasmic large dna viruse ... | 2011 | 21257796 |
| induction of er stress response leading to programmed cell death in trypanosoma brucei. | trypanosomes are parasitic protozoans that include several medically and a variety of economically important parasites, such as trypanosoma brucei, the causative agent of sleeping sickness. this parasite cycles between the insect host (procyclic form) and mammalian host (bloodstream form). these parasites lack transcription regulation, including factors that govern the unfolded protein response (upr) in other eukaryotes. gene expression is controlled posttranscriptionally by unique mechanisms su ... | 2011 | 21266231 |
| potent and selective inhibition of cysteine proteases from plasmodium falciparum and trypanosoma brucei. | | 2010 | 21275051 |
| what is a functional locus? understanding the genetic basis of complex phenotypic traits. | a multitude of results from genome-wide association studies have been published in recent years in relation to different human diseases and phenotypic traits. however, the identified polymorphisms explain just a small fraction of the variability of the traits and they are poor predictors of occurrence of disease. although part of the missing variability may be found in still to be identified rare genetic variants, the present work proposes that a major part of the problem is due to our conceptua ... | 2011 | 21277686 |
| selective inhibitors of methionyl-trna synthetase have potent activity against trypanosoma brucei infection in mice. | human african trypanosomiasis continues to be an important public health threat in extensive regions of sub-saharan africa. treatment options for infected patients are unsatisfactory due to toxicity, difficult administration regimes, and poor efficacy of available drugs. the aminoacyl-trna synthetases were selected as attractive drug targets due to their essential roles in protein synthesis and cell survival. comparative sequence analysis disclosed differences between the trypanosome and mammali ... | 2011 | 21282428 |
| snrna-specific role of smn in trypanosome snrnp biogenesis in vivo. | pre-mrna splicing in trypanosomes requires the smn-mediated assembly of small nuclear ribonucleoproteins (snrnps). in contrast to higher eukaryotes, the cellular localization of snrnp biogenesis and the involvement of nuclear-cytoplasmic trafficking in trypanosomes are controversial. by using rnai knockdown of smn in t. brucei to investigate its functional role in snrnp assembly, we found dramatic changes in the steady-state levels of snrnas and snrnps: the sl rna accumulates, whereas u1, u4, an ... | 2011 | 21282982 |
| magnetic resonance imaging to assess blood-brain barrier damage in murine trypanosomiasis. | the ability of trypanosomes to invade the brain and induce an inflammatory reaction is well-recognized. this study uses magnetic resonance imaging (mri) in conjunction with a murine model of central nervous system (cns) stage trypanosomiasis to investigate this phenomenon at the level of the blood-brain barrier (bbb). mice were scanned before and after administration of the contrast agent. signal enhancement maps were generated, and the percentage signal change was calculated. the severity of th ... | 2011 | 21292912 |
| peptide aptamer mimicking rad51-binding domain of brca2 inhibits dna damage repair and survival in trypanosoma brucei. | the eukaryotic dna recombination repair protein brca2 is functional in the parasitic protozoan trypanosoma brucei. the mechanism of the involvement of brca2 in homologous recombination includes its interaction with the dna recombinase proteins of the rad51 family. brca2 is known to interact with rad51 through its unique and essential brc sequence motifs. t. brucei brca2 homolog (tbbrca2) has fifteen repeating brc motifs as compared to mammalian brca2 that has only eight. we report here our yeast ... | 2011 | 21296653 |
| requirement for acetyl-coa carboxylase in trypanosoma brucei is dependent upon the growth environment. | trypanosoma brucei, the causative agent of human african trypanosomiasis, possesses two fatty acid synthesis pathways: a major de novo synthesis pathway in the er and a mitochondrial pathway. the 2-carbon donor for both pathways is malonyl-coa, which is synthesized from acetyl-coa by acetyl-coa carboxylase (acc). here, we show that t. brucei acc shares the same enzyme architecture and moderate ~ 30% identity with yeast and human accs. acc is cytoplasmic and appears to be distributed throughout t ... | 2011 | 21306439 |
| synthesis and biological evaluation of 1,4-benzodiazepin-2-ones with antitrypanosomal activity. | a library of 1,4-benzodiazepines has been synthesized and evaluated against trypanosoma brucei, a causative parasite of human african trypanosomiasis. benzodiazepines possessing a p2- transporter motif were found to have mic values as low as 0.78 µm. | 2011 | 21306904 |
| examination of the telomere g-overhang structure in trypanosoma brucei. | the telomere g-overhang structure has been identified in many eukaryotes including yeast, vertebrates, and trypanosoma brucei. it serves as the substrate for telomerase for de novo telomere dna synthesis and is therefore important for telomere maintenance. t. brucei is a protozoan parasite that causes sleeping sickness in humans and nagana in cattle. once infected mammalian host, t. brucei cell regularly switches its surface antigen to evade the host's immune attack. we have recently demonstrate ... | 2011 | 21307825 |
| huprines as a new family of dual acting trypanocidal-antiplasmodial agents. | a series of 19 huprines has been evaluated for their activity against cultured bloodstream forms of trypanosoma brucei and plasmodium falciparum. moreover, cytotoxicity against rat myoblast l6 cells was assessed for selected huprines. all the tested huprines are moderately potent and selective trypanocidal agents, exhibiting ic(50) values against t. brucei in the submicromolar to low micromolar range and selectivity indices for t. brucei over l6 cells of approximately 15, thus constituting inter ... | 2011 | 21315611 |
| identification of the meiotic life cycle stage of trypanosoma brucei in the tsetse fly. | elucidating the mechanism of genetic exchange is fundamental for understanding how genes for such traits as virulence, disease phenotype, and drug resistance are transferred between pathogen strains. genetic exchange occurs in the parasitic protists trypanosoma brucei, t. cruzi, and leishmania major, but the precise cellular mechanisms are unknown, because the process has not been observed directly. here we exploit the identification of homologs of meiotic genes in the t. brucei genome and demon ... | 2011 | 21321215 |
| trypanosome reh1 is an rna helicase involved with the 3'-5' polarity of multiple grna-guided uridine insertion/deletion rna editing. | uridine insertion/deletion rna editing in kinetoplastid mitochondria corrects encoded frameshifts in mrnas. the genetic information for editing resides in small guide rnas (grnas), which form anchor duplexes just downstream of an editing site and mediate editing within a single editing "block." many mrnas require multiple grnas; the observed overall 3' to 5' polarity of editing is determined by the formation of upstream mrna anchors by downstream editing. hel61, a mitochondrial dead-box protein, ... | 2011 | 21321231 |
| design, synthesis, and structure-activity relationship of trypanosoma brucei leucyl-trna synthetase inhibitors as antitrypanosomal agents. | african trypanosomiasis, caused by the proto zoal pathogen trypanosoma brucei (t. brucei), is one of the most neglected tropical diseases that are in great need of new drugs. we report the design and synthesis of t. brucei leucyl-trna synthetase (tbleurs) inhibitors and their structure--activity relationship. benzoxaborole was used as the core structure and c(6) was modified to achieve improved affinity based on docking results that showed further binding space at this position. indeed, compound ... | 2011 | 21322634 |
| quantitative real time polymerase chain reaction assays for the sensitive detection of besnoitia besnoiti infection in cattle. | bovine besnoitiosis, an economically important disease in cattle in some countries of africa and asia, is emerging in europe. the definitive host of besnoitia besnoiti, the causative agent of bovine besnoitiosis, is unknown and the transmission of the parasite is not completely understood. sensitive and quantitative dna detection methods are needed to determine whether serologically positive animals are infectious and to examine the role of vectors (e.g. haematophagous insects) in the transmissi ... | 2011 | 21324596 |
| a newly discovered role of telomeres in an ancient organism. | trypanosoma brucei expresses variant surface glycoprotein (vsg) genes in a strictly monoallelic fashion in its mammalian hosts, and the regulation of this important virulence mechanism has been the research focus for decades. telomere position effect (tpe), an epigenetic phenomenon, has been proposed to play a critical role in vsg regulation, yet no telomeric protein was identified whose disruption led to vsg derepression. we recently identified tbrap1 as an intrinsic component of the t. brucei ... | 2010 | 21327073 |
| the serum of rabbitfish (siganus oramin) has antimicrobial activity to some pathogenic organisms and a novel serum l-amino acid oxidase is isolated. | the serum of rabbitfish (siganus oramin) has been confirmed previously to have killing effect to cryptocaryon irritans, an important marine ciliate protozoan that causes a disease referred to as "marine white spot disease". herein, we find the serum of the rabbitfish also shows antibacterial activity against both gram-positive and gram-negative bacteria and has killing effect on two other parasites: trypanosoma brucei brucei, ichthyophthirius multifiliis. results of scanning electron microscopy ... | 2011 | 21333741 |
| comparative histopathology of the lymph nodes, spleen, liver and kidney in experimental ovine trypanosomosis. | the infection of yankassa rams with three important trypanosome species affecting livestock, namely, trypanosoma congolense, t. vivax and t. bruceiproduced both acute and chronic fatal conditions. chronic infections were induced in the three infections by the application of subcurative doses of diaminazene aceturate (berenil). pathological changes in the infected animals included splenomegaly and hepatomegaly which were more pronounced in acute than in chronic t. congolense infection. however, t ... | 2009 | 21344787 |
| nifurtimox activation by trypanosomal type i nitroreductases generates cytotoxic nitrile metabolites. | the prodrug nifurtimox has been used for more than 40 years to treat chagas disease and forms part of a recently approved combinational therapy that targets west african trypanosomiasis. despite this, its mode of action is poorly understood. detection of reactive oxygen and nitrogen intermediates in nifurtimox-treated extracts led to the proposal that this drug induces oxidative stress in the target cell. here, we outline an alternative mechanism involving reductive activation by a eukaryotic ty ... | 2011 | 21345801 |
| 2,4-diaminopyrimidines as potent inhibitors of trypanosoma brucei and identification of molecular targets by a chemical proteomics approach. | there is an urgent need to develop new, safe and effective treatments for human african trypanosomiasis (hat) because current drugs have extremely poor safety profiles and are difficult to administer. here we report the discovery of 2,4-diaminopyrimidines, exemplified by 4-[4-amino-5-(2-methoxy-benzoyl)-pyrimidin-2-ylamino]-piperidine-1-carboxylic acid phenylamide (scyx-5070), as potent inhibitors of trypanosoma brucei and the related trypanosomatid protozoans leishmania spp. | 2011 | 21347454 |
| differential effects of trypanosoma brucei gambiense and trypanosoma brucei brucei on rat macrophages. | mammalian immune responses to trypanosoma brucei infection are important to control of the disease. in rats infected with t. brucei gambiense (wellcome strain; ws) or t. brucei brucei (interleukin-tat 1.4 strain [ils]), a marked increase in the number of macrophages in the spleen can be observed. however, the functional repercussions related to this expansion are not known. to help uncover the functional significance of macrophages in the context of trypanosome infection, we determined the mrna ... | 2010 | 21348606 |
| effect of trypanosoma brucei brucei on erythropoiesis in infected rats. | anemia generated from african trypanosome infection is considered an important symptom in humans and in domestic animals. in order to recover from anemia, the process of erythropoiesis is essential. erythropoiesis is affected by erythropoietin (epo), an erythropoietic hormone, supplying iron and inflammatory and proinflammatory cytokines. however, the role of these factors in erythropoiesis during african trypanosome infection remains unclear. in the present study, we analyze how erythropoiesis ... | 2010 | 21348612 |
| in silico identification of novel protective vsg antigens expressed by trypanosoma brucei and an effort for designing a highly immunogenic dna vaccine using il-12 as adjuvant. | african trypanosomiasis continues to be a major health problem, with more adults dying from this disease world-wide. as the sequence diversity of trypanosoma brucei is extreme, with vsgs having 15-25% identity with most other vsgs, hence it displays a huge diversity of adaptations and host specificities. therefore the need for an improved vaccine has become an international priority. the highly conserved and specific epitopes acting as both cd8+ and cd4+ t-cell epitopes (flinkkpal and ftalctlaa) ... | 2011 | 21349321 |
| the trypanosoma brucei zinc finger protein zc3h18 is involved in differentiation. | in mammalian cells, the degradation of mrnas that have au-rich elements in their 3'-untranslated regions is accelerated by the binding of proteins that contain two ccch-zinc-finger-domains. three ccch zinc-finger proteins, tbzfp1, tbzfp2, and tbzfp3, have been shown to have roles in trypanosome differentiation. we here studied another protein, zc3h18, which has two ccch zinc finger domains. the zc3h18 gene is not essential in bloodstream forms, but in an in vitro model of differentiation, deplet ... | 2011 | 21354218 |
| elongator protein 3b negatively regulates ribosomal dna transcription in african trypanosomes. | eukaryotic cells limit ribosomal dna (rdna) transcription by rna polymerase i (rnap-i) to maintain genome integrity. african trypanosomes present an excellent model for studies on rnap-i regulation because they possess a bifunctional rnap-i and because rnap-ii transcription appears unregulated. since elp3, the catalytic component of elongator, controls rnap-ii transcription in yeast and human cells, we predicted a role for a trypanosome elp3-related protein, elp3a or elp3b, in rnap-i regulation. ... | 2011 | 21357738 |
| high-throughput phenotyping using parallel sequencing of rna interference targets in the african trypanosome. | african trypanosomes are major pathogens of humans and livestock and represent a model for studies of unusual protozoal biology. we describe a high-throughput phenotyping approach termed rna interference (rnai) target sequencing, or rit-seq that, using illumina sequencing, maps fitness-costs associated with rnai. we scored the abundance of >90,000 integrated rnai targets recovered from trypanosome libraries before and after induction of rnai. data are presented for 7435 protein coding sequences, ... | 2011 | 21363968 |
| parasite-driven pathogenesis in trypanosoma brucei infections. | trypanosomes are protozoan parasites of medical and veterinary importance. it is well established that different species, subspecies and strains of trypanosome can cause very different disease in the mammalian host, exemplified by the two human-infective subspecies of trypanosoma brucei that cause either acute or chronic disease. we are beginning to understand how the host response shapes the course of the disease and how genetic variation in the host can be a factor in disease severity, particu ... | 2011 | 21366624 |
| three-dimensional reconstruction of trypanosoma brucei editosomes using single-particle electron microscopy. | rna editing within the mitochondria of kinetoplastid protozoa is performed by a multicomponent -macromolecular machine known as the editosome. editosomes are high molecular mass protein assemblies that consist of about 15-25 individual polypeptides. they bind pre-edited transcripts and convert them into translation-competent mrnas through a biochemical reaction cycle of enzyme-catalyzed steps. at steady-state conditions, several distinct complexes can be purified from mitochondrial detergent lys ... | 2011 | 21370039 |
| icoda: rnai-based inducible knock-in system in trypanosoma brucei. | in vivo mutational analysis is often required to characterize enzymes that function as subunits of the u-insertion/deletion rna editing core complex (recc) in mitochondria of trypanosoma brucei. the mutations may skew phenotypic manifestation of a dominant negative overexpression if complex association is disrupted. conditional knockouts and knock-ins of essential mitochondrial genes are time consuming and restricted to the bloodstream form parasites, thus limiting biochemical analysis. we have ... | 2011 | 21370040 |
| analysis of trna editing in native and synthetic substrates. | the primary sequence of all nucleic acids in a cell contain 4 canonical nucleotides (g, a, t, and c for dna and g, a, u, and c for rna). however, post-transcriptionally, nucleic acids can undergo a number of chemical modifications, which may change their structure and function. trnas contain the most diverse array of post-transcriptionally added chemical groups that involve both editing and modification. because editing and modification events can serve vital roles in cell function, it is import ... | 2011 | 21370051 |
| trypanosoma brucei brucei: a comparison of gene expression in the liver and spleen of infected mice utilizing cdna microarray technology. | trypanosoma brucei brucei, the infectious agent of the disease known as nagana, is a pathogenic trypanosome occurring in africa, where it causes significant economic loss to domesticated livestock. although many studies on the histopathology of organs of mice infected with t. b. brucei have been reported, little work has been done regarding gene expression in these organs in infected mice. in this paper, we describe the use of cdna microarray to determine gene expression profiles in the liver an ... | 2011 | 21376043 |
| trypanosoma brucei s.l.: microsatellite markers revealed high level of multiple genotypes in the mid-guts of wild tsetse flies of the fontem sleeping sickness focus of cameroon. | to identify trypanosoma brucei genotypes which are potentially transmitted in a sleeping sickness focus, microsatellite markers were used to characterize t. brucei found in the mid-guts of wild tsetse flies of the fontem sleeping sickness focus in cameroon. for this study, two entomological surveys were performed during which 2685 tsetse flies were collected and 1596 (59.2%) were dissected. microscopic examination revealed 1.19% (19/1596) mid-gut infections with trypanosomes; the pcr method iden ... | 2011 | 21376044 |
| synthesis of potential metal-binding group compounds to examine the zinc dependency of the gpi de-n-acetylase metalloenzyme in trypanosoma brucei. | a small zinc-binding group (zbg) library of deoxy-2-c-branched-monosaccharides, for example, 1,5-anhydroglucitols, consisting of either monodentate ligand binding carboxylic acids or bidentate ligand binding hydroxamic acids, were prepared to assess the zinc affinity of the putative metalloenzyme 2-acetamido-2-deoxy-a-d-glucopyranosyl-(1?6)-phosphatidylinositol de-n-acetylase (ec 3.5.1.89) of glycosylphosphatidylinositol biosynthesis. the n-ureido thioglucoside was also synthesised and added to ... | 2011 | 21377660 |
| naphthalene-based rna editing inhibitor blocks rna editing activities and editosome assembly in trypanosoma brucei. | rna editing, catalyzed by the multiprotein editosome complex, is an essential step for the expression of most mitochondrial genes in trypanosomatid pathogens. it has been shown previously that trypanosoma brucei rna editing ligase 1 (tbrel1), a core catalytic component of the editosome, is essential in the mammalian life stage of these parasitic pathogens. because of the availability of its crystal structure and absence from human, the adenylylation domain of tbrel1 has recently become the focus ... | 2011 | 21378165 |
| structure-function analysis of dynein light chain 1 identifies viable motility mutants in bloodstream-form trypanosoma brucei. | the flagellum of trypanosoma brucei is an essential and multifunctional organelle that is receiving increasing attention as a potential drug target and as a system for studying flagellum biology. rna interference (rnai) knockdown is widely used to test the requirement for a protein in flagellar motility and has suggested that normal flagellar motility is essential for viability in bloodstream-form trypanosomes. however, rnai knockdown alone provides limited functional information because the con ... | 2011 | 21378260 |
| experimental examination of efl and matx eukaryotic horizontal gene transfers: coexistence of mutually exclusive transcripts predates functional rescue. | many eukaryotic genes do not follow simple vertical inheritance. elongation factor 1+¦ (ef-1+¦) and methionine adenosyl transferase (mat) are enzymes with complicated evolutionary histories and, interestingly, the two cases have several features in common. these essential enzymes occur as two relatively divergent paralogs (ef-1+¦/efl, mat/matx) that have patchy distributions in eukaryotic lineages that are nearly mutually exclusive. to explain such distributions, we must invoke either multiple e ... | 2011 | 21385829 |
| nuclear architecture, genome and chromatin organisation in trypanosoma brucei. | the nucleus of the human pathogen trypanosoma brucei not only has unusual chromosomal composition, characterised by the presence of megabase, intermediate and minichromosomes, but also chromosome and gene organisation that is unique amongst eukaryotes. here i provide an overview of current knowledge of nuclear structure, chromatin organisation and chromosome dynamics during interphase and mitosis. new technologies such as chromatin immunoprecipitation, in combination with new generation sequenci ... | 2011 | 21392575 |
| trypanosoma brucei: two mitogen activated protein kinase kinases are dispensable for growth and virulence of the bloodstream form. | mitogen activated protein kinase cascades function in eukaryotic responses to the environment and stress. trypanosomatid parasites possess protein kinases with sequences characteristic of kinases in such cascades. in this report we use gene knockouts to demonstrate that two mitogen activated kinase kinase genes, mkk1 (tb927.3.4860) and mkk5 (tb927.10.5270), are not essential in the pathogenic bloodstream stage of trypanosoma brucei, either in vitro or in vivo. bloodstream forms lacking mkk1 show ... | 2011 | 21396364 |
| trypanocidal furamidine analogues: influence of pyridine nitrogens on trypanocidal activity, transport kinetics, and resistance patterns. | current therapies for human african trypanosomiasis (hat) are unsatisfactory and under threat from emerging drug resistance linked to the loss of transporters, e.g., the p2 aminopurine transporter (tbat1). here we compare the uptake and trypanocidal properties of furamidine (db75), recently evaluated in clinical trials against stage 1 (haemolymphatic) hat, and two aza analogues, db820 and cpd0801 (db829), which are candidate compounds for treatment of stage 2 (neurological) disease. values of 50 ... | 2011 | 21402852 |
| cerebral changes occurring in arginase and dimethylarginine dimethylaminohydrolase (ddah) in a rat model of sleeping sickness. | involvement of nitric oxide (no) in the pathophysiology of human african trypanosomiasis (hat) was analyzed in a hat animal model (rat infected with trypanosoma brucei brucei). with this model, it was previously reported that trypanosomes were capable of limiting trypanocidal properties carried by no by decreasing its blood concentration. it was also observed that brain no concentration, contrary to blood, increases throughout the infection process. the present approach analyses the brain impair ... | 2011 | 21408057 |
| generation of anti-trypanosomal agents through concise synthesis and structural diversification of sesquiterpene analogues. | to access high-quality small-molecule libraries to screen lead candidates for neglected diseases exemplified by human african trypanosomiasis, we sought to develop a synthetic process that would produce collections of cyclic scaffolds relevant to an assortment of natural products exhibiting desirable biological activities. by extracting the common structural features among several sesquiterpenes, including artemisinin, anthecularin, and transtaganolides, we designed six types of scaffolds with s ... | 2011 | 21413715 |
| assembling fe/s-clusters and modifying trnas: ancient co-factors meet ancient adaptors. | trypanosoma brucei undergoes two clearly distinct develomental stages: in the insect vector (procyclic stage) the cells generate the bulk of their energy through respiration, whereas in the bloodstream of the mammalian host (bloodstream stage) they grow mostly glycolytically. several mitochondrial respiratory proteins require iron-sulfur clusters for activity, and their activation coincides with developmental changes. likewise some trna modification enzymes either require iron-sulfur clusters or ... | 2011 | 21419700 |
| a gateway® compatible vector for gene silencing in bloodstream form trypanosoma brucei. | rna interference is the most rapid method for generation of conditional knockdown mutants in trypanosoma brucei. the dual t7 promoter (pzjm) and the stem-loop vectors have been widely used to generate stable inducible rnai cell lines with the latter providing tighter regulatory control. however, the steps for cloning stem-loop constructs are cumbersome requiring either multiple cloning steps or multi-fragment ligation reactions. we report the development of a vector (ptryprnaigate) derived from ... | 2011 | 21420443 |
| novel compounds to combat trypanosomatid infections: a medicinal chemical perspective. | introduction: the current therapeutic arsenal against the kinetoplastids trypanosoma brucei, trypanosoma cruzi and leishmania spp. is clearly inadequate and underscores the urgent need to develop new effective, safe and cost-effective drugs. areas covered: accordingly, this review of patented products and processes using anti-kinetoplastid agents provides insight into the identification of novel or more refined drugs. in this review, we describe products developed in recent years for the treatme ... | 2011 | 21428846 |
| the diamidine diminazene aceturate is a substrate for the high-affinity pentamidine transporter: implications for the development of high resistance levels in trypanosomes. | african trypanosomiasis is a disease of humans and livestock in many areas south of the sahara. resistance to the few existing drugs is a major impediment to the control of these diseases, and we investigated how resistance to the main veterinary drug diminazene aceturate correlates with changes in drug transport in resistant strains. the strain tbat1(-/-), lacking the tbat1/p2 aminopurine transporter implicated previously in diminazene transport, was adapted to higher levels of diminazene resis ... | 2011 | 21436312 |
| synthetic glycosylphosphatidylinositol (gpi) anchors: how these complex molecules have been made. | | 2011 | 21448495 |
| mrb3010 is a core component of the mrb1 complex that facilitates an early step of the kinetoplastid rna editing process. | gene expression in the mitochondria of the kinetoplastid parasite trypanosoma brucei is regulated primarily post-transcriptionally at the stages of rna processing, editing, and turnover. the mitochondrial rna-binding complex 1 (mrb1) is a recently identified multiprotein complex containing components with distinct functions during different aspects of rna metabolism, such as guide rna (grna) and mrna turnover, precursor transcript processing, and rna editing. in this study we examined the functi ... | 2011 | 21451155 |
| trypanocidal activity of peptidyl vinyl ester derivatives selective for inhibition of mammalian proteasome trypsin-like activity. | nine vinyl ester tripeptides selective for inhibition of mammalian proteasome trypsin-like activity were tested for in vitro activity against trypanosoma brucei. interestingly, two compounds showed trypanocidal activity in the low micromolar range without displaying cytotoxicity against human cells. however, the compounds did not inhibit the trypsin-like activity of the trypanosome proteasome although their effect correlates with inactivation of the chymotrypsin-like activity. this finding shows ... | 2011 | 21458452 |
| a zinc finger protein, tbzc3h20, stabilizes two developmentally regulated mrnas in trypanosomes. | ccch zinc finger proteins (zc3hs) are a novel class of rna-binding protein involved in post-transcriptional mechanisms controlling gene expression. we show tbzc3h20 from trypanosoma brucei, the causative agent of sleeping sickness and other diseases, stabilizes two developmentally regulated transcripts encoding a mitochondrial carrier protein (mcp12) and trans-sialidase (ts-like e). tbzc3h20 is shown to be an rna-binding protein that is enriched in insect procyclic form t. brucei and is the firs ... | 2011 | 21467035 |
| functional characterization of three aquaglyceroporins from trypanosoma brucei in osmoregulation and glycerol transport. | previous studies using bloodstream form trypanosoma brucei have shown that glycerol transport in this parasite occurs via specific membrane proteins, namely a glycerol transporter and glycerol channels [1]. later, we cloned, expressed and characterized the transport properties of all three aquaglyceroporins (aqp1-3) [2], which were found permeable for water, glycerol and other small uncharged solutes like dihydroxyacetone [3]. here, we report on the cellular localization of tbaqp1 and tbaqp3 in ... | 2011 | 21471730 |
| pentatricopeptide repeat proteins stimulate mrna adenylation/uridylation to activate mitochondrial translation in trypanosomes. | the majority of trypanosomal mitochondrial pre-mrnas undergo massive uridine insertion/deletion editing, which creates open reading frames. although the pre-editing addition of short 3' a tails is known to stabilize transcripts during and after the editing, the processing event committing the fully edited mrnas to translation remained unknown. here, we show that a heterodimer of pentatricopeptide repeat-containing (ppr) proteins, termed kinetoplast polyadenylation/uridylation factors (kpafs) 1 a ... | 2011 | 21474072 |
| potent antiprotozoal activity of a novel semi-synthetic berberine derivative. | treatment of diseases such as african sleeping sickness and leishmaniasis often depends on relatively expensive or toxic drugs, and resistance to current chemotherapeutics is an issue in treating these diseases and malaria. in this study, a new semi-synthetic berberine analogue, 5,6-didehydro-8,8-diethyl-13-oxodihydroberberine chloride (1), showed nanomolar level potency against in vitro models of leishmaniasis, malaria, and trypanosomiasis as well as activity in an in vivo visceral leishmaniasi ... | 2011 | 21474310 |
| endonuclease associations with three distinct editosomes in trypanosoma brucei. | three distinct editosomes, typified by mutually exclusive kren1, kren2, or kren3 endonucleases, are essential for mitochondrial rna editing in trypanosoma brucei. the three editosomes differ in substrate endoribonucleolytic cleavage specificity, which may reflect the vast number of editing sites that need insertion or deletion of uridine nucleotides (us). each editosome requires the single rnase iii domain in each endonuclease for catalysis. studies reported here show that the editing endonuclea ... | 2011 | 21474442 |
| composition, and antimicrobial and remarkable antiprotozoal activities of the essential oil of rhizomes of aframomum sceptrum k. schum. (zingiberaceae). | the essential oil from the rhizomes of aframomum sceptrum (zingiberaceae) was analyzed by gc/ms, and its major constituents were found to be β-pinene (12.7%), caryophyllene oxide (10.0%), and cyperene (6.0%). the oil was also evaluated for antimicrobial activities, in comparison with β-pinene, caryophyllene oxide, and the leaf essential oil of melaleuca alternifolia (myrtaceae). the a. sceptrum essential oil exhibited bacteriostatic activity against the gram-positive bacteria bacillus subtilis, ... | 2011 | 21480511 |
| trypanosoma brucei glycogen synthase kinase-3, a target for anti-trypanosomal drug development: a public-private partnership to identify novel leads. | trypanosoma brucei, the causative agent of human african trypanosomiasis (hat), expresses two proteins with homology to human glycogen synthase kinase 3β (hsgsk-3) designated tbrugsk-3 short and tbrugsk-3 long. tbrugsk-3 short has previously been validated as a potential drug target and since this enzyme has also been pursued as a human drug target, a large number of inhibitors are available for screening against the parasite enzyme. a collaborative industrial/academic partnership facilitated by ... | 2011 | 21483717 |
| the cell cycle regulated transcriptome of trypanosoma brucei. | progression of the eukaryotic cell cycle requires the regulation of hundreds of genes to ensure that they are expressed at the required times. integral to cell cycle progression in yeast and animal cells are temporally controlled, progressive waves of transcription mediated by cell cycle-regulated transcription factors. however, in the kinetoplastids, a group of early-branching eukaryotes including many important pathogens, transcriptional regulation is almost completely absent, raising question ... | 2011 | 21483801 |
| transmission stages dominate trypanosome within-host dynamics during chronic infections. | sleeping sickness is characterized by waves of the extracellular parasite trypanosoma brucei in host blood, with infections continuing for months or years until inevitable host death. these waves reflect the dynamic conflict between the outgrowth of a succession of parasite antigenic variants and their control by the host immune system. although a contributor to these dynamics is the density-dependent differentiation from proliferative "slender forms" to transmissible "stumpy forms," an absence ... | 2011 | 21501830 |
| evolutionary reconstruction of the retromer complex and its function in trypanosoma brucei. | intracellular trafficking and protein sorting are mediated by various protein complexes, with the retromer complex being primarily involved in retrograde traffic from the endosome or lysosome to the golgi complex. here, comparative genomics, cell biology and phylogenetics were used to probe the early evolution of retromer and its function. retromer subunits vps26, vps29 and vps35 are near universal, and, by inference, the complex was an ancient feature of eukaryotic cells. surprisingly, we found ... | 2011 | 21502137 |
| an evolutionary analysis of trypanosomatid gp63 proteases. | the trypanosomatid gp63 proteases are known to be involved in parasite-host interaction and exhibit strong sequence and structural similarities to those of their hosts and insect vectors. based on genome sequences of the three trypanosomatids, trypanosoma brucei, trypanosoma cruzi, and leishmania spp., we annotated all their gp63 proteases and divided highly duplicated t. cruzi gp63 proteases into four novel groups according to sequence features. in leishmania spp., we studied the evolutionary d ... | 2011 | 21503641 |
| sar of 2-amino and 2,4-diamino pyrimidines with in vivo efficacy against trypanosoma brucei. | a series of 2,4-diaminopyrimidines was investigated and compounds were found to have in vivo efficacy against trypanosoma brucei in an acute mouse model. however, in vitro permeability data suggested the 2,4-diaminopyrimidenes would have poor permeability through the blood brain barrier. consequently a series of 4-desamino analogs were synthesized and found to have improved in vitro permeability. | 2011 | 21507639 |
| a single zinc ion is sufficient for an active trypanosoma brucei trna editing deaminase. | editing of adenosine (a) to inosine (i) at the first anticodon position in trna is catalyzed by adenosine deaminases acting on trna (adats). this essential reaction in bacteria and eukarya permits a single trna to decode multiple codons. bacterial adata is a homodimer with two bound essential zn(2+). the adata crystal structure revealed residues important for substrate binding and catalysis; however, such high resolution structural information is not available for eukaryotic trna deaminases. des ... | 2011 | 21507956 |
| (1)h, (13)c and (15)n resonance assignments for a putative adf/cofilin from trypanosoma brucei. | actin-depolymerizing factor (adf)/cofilin proteins are a family of actin-binding proteins expressed in almost all eukaryotic cells, and play a significant role in regulating actin-filament dynamics. here we report the resonance assignments of a putative adf/cofilin from trypanosoma brucei for further understanding of the relationship between its structure and function. | 2011 | 21523437 |
| characterization, localization, essentiality and high-resolution crystal structure of glucosamine 6-phosphate n-acetyltransferase from trypanosoma brucei. | a gene predicted to encode trypanosoma brucei glucosamine 6-phosphate n-acetyltransferase (ec 2.3.1.4, tbgna1) was cloned and expressed in escherichia coli. the recombinant protein was enzymatically active and its high-resolution crystal structure obtained at 1.86 å. endogenous tbgna1 protein was localized to the peroxisome-like microbody, the glycosome. a bloodstream form t. brucei gna1 conditional null mutant was constructed and shown to be unable to sustain growth in vitro under non-permissiv ... | 2011 | 21531872 |
| three mitochondrial dna polymerases are essential for kinetoplast dna replication and survival of bloodstream form trypanosoma brucei. | trypanosoma brucei, the causative agent of human african trypanosomiasis, has a complex life cycle that includes multiple life cycle stages and metabolic changes as the parasite switches between insect vector and mammalian host. the parasite's single mitochondrion contains a unique catenated mitochondrial dna network called kinetoplast dna (kdna) that is composed of minicircles and maxicircles. long-standing uncertainty about the requirement of kdna in bloodstream form (bf) t. brucei has recentl ... | 2011 | 21531873 |
| pseudogene-derived small interference rnas regulate gene expression in african trypanosoma brucei. | pseudogenes have been shown to acquire unique regulatory roles from more and more organisms. we report the observation of a cluster of sirnas derived from pseudogenes of african trypanosoma brucei using high through-put analysis. we show that these pseudogene-derived sirnas suppress gene expression through rna interference. the discovery that sirnas may originate from pseudogenes and regulate gene expression in a unicellular eukaryote provides insights into the functional roles of pseudogenes an ... | 2011 | 21531904 |
| novel lipophilic acetohydroxamic acid derivatives based on conformationally constrained spiro carbocyclic 2,6-diketopiperazine scaffolds with potent trypanocidal activity. | we describe novel acetohydroxamic acid derivatives with potent activity against cultured bloodstream-form trypanosoma brucei, and selectivity indices of >1000. these analogues were derived from conformationally constrained, lipophilic, spiro carbocyclic 2,6-diketopiperazine (2,6-dkp) scaffolds by attaching acetohydroxamic acid moieties to the imidic nitrogen. optimal activity was achieved by placing benzyl groups adjacent to the basic nitrogen of the 2,6-dkp core. s-enantiomer 2d was the most ac ... | 2011 | 21542562 |
| wildtype and engineered monomeric triosephosphate isomerase from trypanosoma brucei: partitioning of reaction intermediates in d(2)o and activation by phosphite dianion. | product yields for the reactions of (r)-glyceraldehyde 3-phosphate (gap) in d(2)o at pd 7.9 catalyzed by wildtype triosephosphate isomerase from trypanosoma brucei brucei (tbb tim) and a monomeric variant (monotim) of this wildtype enzyme were determined by (1)h nmr spectroscopy and were compared with the yields determined in earlier work for the reactions catalyzed by tim from rabbit and chicken muscle [ o'donoghue , a. c. , amyes , t. l. , and richard , j. p. ( 2005 ) , biochemistry 44 , 2610 ... | 2011 | 21553855 |
| transketolase in trypanosoma brucei. | a single copy gene, encoding a protein highly similar to transketolase from other systems, was identified in the trypanosoma brucei genome. the gene was expressed in e. coli and the purified protein demonstrated transketolase activity with k(m) values of 0.2mm and 0.8mm respectively for xylulose 5-phosphate and ribose 5-phosphate. a peroxisomal targeting signal (pts-1) present at the c-terminus of the protein suggested a glycosomal localisation. however, subcellular localisation experiments reve ... | 2011 | 21570429 |
| ubiquitylation and developmental regulation of invariant surface protein expression in trypanosomes. | the cell surface of trypanosoma brucei is dominated by the gpi-anchored variant surface glycoprotein (vsg), which is essential for immune evasion. vsg biosynthesis, trafficking and turnover are well documented but trans-membrane domain (tmd) proteins, including the invariant surface glycoproteins (isgs), are less well characterized. internalization and degradation of isg65 depends on ubiquitylation of conserved cytoplasmic lysines. using epitope-tagged isg75 and reporter chimeric proteins bearin ... | 2011 | 21571921 |
| tbiswi regulates multiple pol i transcribed loci and is present at pol ii transcription boundaries in trypanosoma brucei. | the unicellular eukaryote trypanosoma brucei is unusual in having very little transcriptional control. the bulk of the t. brucei genome is constitutively transcribed by rna polymerase ii (pol ii) as extensive polycistronic transcription units. exceptions to this rule include several rna polymerase i (pol i) transcription units such as the vsg expression sites (ess), which are mono-allelically expressed. tbiswi, a member of the swi2/snf2 related chromatin remodelling atpases, plays a role in repr ... | 2011 | 21571922 |
| genome sequencing gets func-y. | this month, genome watch highlights new strategies for revealing the functions of uncharacterized genes through high-throughput sequencing coupled with phenotypic assays. | 2011 | 21572456 |
| mining a cathepsin inhibitor library for new antiparasitic drug leads. | the targeting of parasite cysteine proteases with small molecules is emerging as a possible approach to treat tropical parasitic diseases such as sleeping sickness, chagas' disease, and malaria. the homology of parasite cysteine proteases to the human cathepsins suggests that inhibitors originally developed for the latter may be a source of promising lead compounds for the former. we describe here the screening of a unique ∼2,100-member cathepsin inhibitor library against five parasite cysteine ... | 2011 | 21572521 |
| genital lesions in male red fronted gazelles (gazella rufifrons) experimentally infected with trypanosoma brucei and the effect of melarsamine hydrochloride (cymelarsan(®)) and diminazene aceturate (berenil(®)) in its treatment. | thirty red fronted gazelles (gazella rufifrons) were used to assess the genital lesions associated with trypanosomosis and the efficacy of melarsamine hydrochloride (cymelarsan(®)) and diminazene aceturate (berenil(®)) in the treatment of the condition. the animals were divided into 6 equal groups (a-f). animals in groups a-e were infected with trypanosoma brucei, and later treated on day 8 post infection (p.i.) with either melarsamine hydrochloride (cymelarsan(®)) at 0.3 mg/kg (group a) and 0.6 ... | 2011 | 21601916 |
| the c-terminal end of the trypanosoma brucei editing deaminase plays a critical role in trna binding. | adenosine to inosine editing at the wobble position allows decoding of multiple codons by a single trna. this reaction is catalyzed by adenosine deaminases acting on trna (adats) and is essential for viability. in bacteria, the anticodon-specific enzyme is a homodimer that recognizes a single trna substrate (trna(arg)(acg)) and can efficiently deaminate short anticodon stem-loop mimics of this trna in vitro. the eukaryal enzyme is composed of two nonidentical subunits, adat2 and adat3, which upo ... | 2011 | 21602302 |
| consensus models of activity landscapes with multiple chemical, conformer and property representations. | we report consensus structure-activity similarity (sas) maps that address the dependence of activity landscapes on molecular representation. as a case study, we characterized the activity landscape of 54 compounds with activities against human cathepsin b (hcatb), human cathepsin l (hcatl), and <i>trypanosoma brucei</i> cathepsin b (tbcatb). starting from an initial set of 28 descriptors we selected ten representations that capture different aspects of the chemical structures. these included fou ... | 2011 | 21609014 |
| trypanosoma brucei mitochondrial respiratome: composition and organization in procyclic form. | the mitochondrial respiratory chain is comprised of four different protein complexes (i-iv), which are responsible for electron transport and generation of proton gradient in the mitochondrial intermembrane space. this proton gradient is then used by fof1-atp synthase (complex v) to produce atp by oxidative phosphorylation. in this study, the respiratory complexes i, ii and iii were affinity purified from trypanosoma brucei procyclic form cells and their composition was determined by mass spectr ... | 2011 | 21610103 |
| interactions among trypanosoma brucei rad51 paralogues in dna repair and antigenic variation. | homologous recombination in trypanosoma brucei is used for moving variant surface glycoprotein (vsg) genes into expression sites during immune evasion by antigenic variation. a major route for such vsg switching is gene conversion reactions in which rad51, a universally conserved recombinase, catalyses homology-directed strand exchange. in any eukaryote, rad51-directed strand exchange in vivo is mediated by further factors, including rad51-related proteins termed rad51 paralogues. these appear t ... | 2011 | 21615552 |
| antitrypanosomal and cytotoxic activities of 22-hydroxyclerosterol, a new sterol from allexis cauliflora (violaceae). | in the search for new antiparasitic natural compounds from the medicinal plants from cameroon, the new 22-hydroxyclerosterol, established as such on the basis of detailed chemical and spectroscopic analysis, was isolated from the hexane extract of the stem bark of allexis cauliflora together with the known clerosterol. 22-hydroxyclerosterol inhibited the growth of trypanosoma brucei brucei cells with an ed(50) value of 1.56 μm. the compound was also established as an uncompetitive inhibitor of t ... | 2011 | 21617778 |
| trypanocidal activity of nitroaromatic prodrugs: current treatments and future perspectives. | chagas disease and african sleeping sickness are trypanosomal infections that represent important public health problems in latin america and africa, respectively. the restriction of these diseases to the poorer parts of the world has meant that they have been largely neglected and limited progress has been made in their treatment. the nitroheterocyclic prodrugs nifurtimox and benznidazole, in use against chagas disease for >40 years, remain the only agents available for this infection. in the c ... | 2011 | 21619510 |
| sterol 14alpha-demethylase (cyp51) as a therapeutic target for human trypanosomiasis and leishmaniasis. | pathogenic protozoa threaten lives of several hundred million people throughout the world and are responsible for large numbers of deaths globally. the parasites are transmitted to humans by insect vectors, more than a hundred of infected mammalian species forming reservoir. with human migrations, hiv-coinfections, and blood bank contamination the diseases are now spreading beyond the endemic tropical countries, being found in all parts of the world including the usa, canada and europe. in spite ... | 2011 | 21619513 |
| medical microbiology | resistance to parasitic protozoa appears to be similar to resistance against other
infectious agents, although the mechanisms of resistance in protozoan infections are
not yet as well understood. resistance can be divided into two main groups of
mechanisms: (1) nonspecific mechanism(s) or factor(s) such as the presence of a
nonspecific serum component that is lethal to the parasite; and (2) specific
mechanism(s) invo ... | 1996 | 21413293 |
| genetic reconstruction of protozoan rrna decoding sites provides a rationale for paromomycin activity against leishmania and trypanosoma. | aminoglycoside antibiotics target the ribosomal decoding a-site and are active against a broad spectrum of bacteria. these compounds bind to a highly conserved stem-loop-stem structure in helix 44 of bacterial 16s rrna. one particular aminoglycoside, paromomycin, also shows potent antiprotozoal activity and is used for the treatment of parasitic infections, e.g. by leishmania spp. the precise drug target is, however, unclear; in particular whether aminoglycoside antibiotics target the cytosolic ... | 2011 | 21629725 |
| lipoamide dehydrogenase is essential for both bloodstream and procyclic trypanosoma brucei. | lipoamide dehydrogenase (lipdh) is a component of four mitochondrial multienzyme complexes. rna-interference or the deletion of both alleles in bloodstream trypanosoma brucei resulted in an absolute requirement for exogenous thymidine. in the absence of thymidine, lipdh-/- parasites showed a severely altered morphology and cell cycle distribution. most probably, in bloodstream cells with their only rudimentary mitochondrion, lipdh is required as component of the glycine cleavage complex which ge ... | 2011 | 21631607 |
| substrate preferences and catalytic parameters determined by structural characteristics of sterol 14{alpha}-demethylase (cyp51) from leishmania infantum. | leishmaniasis is a major health problem that affects populations of 88 countries worldwide, with no vaccine and only a few moderately effective drugs. here we report structure/function characterization of sterol 14α-demethylase (cyp51) from leishmania infantum. the enzyme catalyzes removal of the 14α-methyl group from sterol precursors. the reaction is essential for membrane biogenesis and therefore has great potential to become a target for antileishmanial chemotherapy. although l. infantum cyp ... | 2011 | 21632531 |
| a tryparedoxin-dependent peroxidase protects african trypanosomes from membrane damage. | hydroperoxide detoxification in african trypanosomes is achieved by 2-cys-peroxiredoxin (txnpx)- and non-selenium glutathione peroxidase (px)-type enzymes which both obtain their reducing equivalents from the unique trypanothione/tryparedoxin system. previous rna interference approaches revealed that the cytosolic txnpx and the px-type enzymes are essential for trypanosoma brucei. because of partially overlapping in vitro substrate specificities and subcellular localisation the physiological fun ... | 2011 | 21640819 |
| rab11 function in trypanosoma brucei; identification of conserved and novel interaction partners. | the ras-like gtpase rab11 is implicated in multiple aspects of intracellular transport, including maintenance of plasma membrane composition and cytokinesis. in metazoa these functions are mediated in part via coiled-coil rab11-interacting proteins (fips) acting as rab11 effectors. additional interaction between rab11 and the exocyst subunit sec15 connects rab11 with exocytosis. we find that fips are metazoan-specific, suggesting that other factors mediate rab11 functions in non-metazoa. we exam ... | 2011 | 21642507 |
| trypanosoma brucei infection in a hiv positive ugandan male. | human african trypanosomiasis, or african sleeping sickness, is a parasitic infection caused by trypanosoma brucei (gambiense or rhodesiense), and one of the declared neglected tropical diseases. sleeping sickness has high fatality rates and is a continued threat in several african countries. we present characteristic clinical and microbiologic features of a fatal case of african sleeping sickness in an hiv-infected individual. | 2011 | 21657140 |
| genetic control of resistance to trypanosoma brucei brucei infection in mice. | trypanosoma brucei brucei infects livestock, with severe effects in horses and dogs. mouse strains differ greatly in susceptibility to this parasite. however, no genes controlling these differences were mapped. | 2011 | 21666791 |
| langevin dynamics deciphers the motility pattern of swimming parasites. | the parasite african trypanosome swims in the bloodstream of mammals and causes the highly dangerous human sleeping sickness. cell motility is essential for the parasite's survival within the mammalian host. we present an analysis of the random-walk pattern of a swimming trypanosome. from experimental time-autocorrelation functions for the direction of motion we identify two relaxation times that differ by an order of magnitude. they originate from the rapid deformations of the cell body and a s ... | 2011 | 21668266 |
| high-throughput analysis of an rnai library identifies novel kinase targets in trypanosoma brucei. | new drugs are needed to treat human african trypanosomiasis because the currently approved treatments are toxic or limited in efficacy. one strategy for developing new drugs involves discovering novel genes whose products can be targeted for modulation by small-molecule chemotherapeutic agents. the trypanosoma brucei genome contains many genes with the potential to become such targets. kinases represent one group of genes that regulate many important cell functions and can be modulated by small ... | 2011 | 21668652 |
| glycerol-3-phosphate alters trypanosoma brucei hexokinase activity in response to environmental change. | the african trypanosome, trypanosoma brucei, compartmentalizes some metabolic enzymes within peroxisome-like organelles, glycosomes. the amounts, activities, and types of glycosomal enzymes are modulated coincident with developmental and environmental changes. pexophagy, fusion of glycosomes with acidic lysosomes, has been proposed to facilitate this glycosome remodeling. here, we report that while the glycosome-resident enzyme t. brucei hexokinase 1 (tbhk1) protein levels are maintained during ... | 2011 | 21813651 |
| alba-domain proteins of trypanosoma brucei are cytoplasmic rna-binding proteins that interact with the translation machinery. | trypanosoma brucei and related pathogens transcribe most genes as polycistronic arrays that are subsequently processed into monocistronic mrnas. expression is frequently regulated post-transcriptionally by cis-acting elements in the untranslated regions (utrs). gpeet and ep procyclins are the major surface proteins of procyclic (insect midgut) forms of t. brucei. three regulatory elements common to the 3' utrs of both mrnas regulate mrna turnover and translation. the glycerol-responsive element ... | 2011 | 21811616 |
| guide rna biogenesis involves a novel rnase iii family endoribonuclease in trypanosoma brucei. | the mitochondrial genome of kinetoplastids, including species of trypanosoma and leishmania, is an unprecedented dna structure of catenated maxicircles and minicircles. maxicircles represent the typical mitochondrial genome encoding components of the respiratory complexes and ribosomes. however, most mrna sequences are cryptic, and their maturation requires a unique u insertion/deletion rna editing. minicircles encode hundreds of small guide rnas (grnas) that partially anneal with unedited mrnas ... | 2011 | 21810935 |
| the cdc45/mcm2-7/gins complex in trypanosomes regulates dna replication and interacts with two orc1-like proteins in the origin recognition complex. | accurate dna replication requires a complex interplay of many regulatory proteins at replication origins. the cmg (cdc45/mcm2-7/gins) complex, which is composed of cdc45, mcm2-7, and the gins complex consisting of sld5 and psf1 to psf3, is recruited by cdc6 and cdt1 onto origins bound by the heterohexameric origin recognition complex (orc) and functions as a replicative helicase. trypanosoma brucei, an early branched microbial eukaryote, appears to express an archaea-like orc consisting of a sin ... | 2011 | 21799014 |