We evaluated the effects of dihydroxyacetone (DHA) on Trypanosoma brucei bloodstream forms. DHA is considered an energy source for many different cell types. T. brucei takes up DHA readily due to the presence of aquaglyceroporins. However, the parasi
The dissociation of histone proteins a-d from the chromatin ofTrypanosoma brucei brucei procyclic culture forms was investigated by removing the proteins f
BACKGROUND: Protozoan parasites of the genus Trypanosoma cause disease in a wide range of mammalian hosts. Trypanosoma brucei brucei, transmitted by tsetse fly to cattle, causes a disease (Nagana) of great economic importance in parts of Africa. T. b. brucei also serves as a model for related Trypanosoma species, which cause human sleeping sickness. MATERIALS AND METHODS: Chalcone and acyl hydrazide derivatives are known to retard the growth of Plasmodium falciparum in vitro and inhibit the malarial cysteine proteinase, falcipain. We tested the effects of these compounds on the growth of bloodstream forms of T. b. brucei in cell culture and in a murine trypanosomiasis model, and investigated their ability to inhibit trypanopain-Tb, the major cysteine proteinase of T. b. brucei. RESULTS: Several related chalcones, acyl hydrazides, and amides killed cultured bloodstream forms of T. b. brucei, with the most effective compound reducing parasite numbers by 50% relative to control populations at a
The flagellum is attached along the length of the cell body in the protozoan parasite Trypanosoma brucei and is a defining morphological feature of this parasite. The flagellum attachment zone (FAZ) is a complex structure and has been characterised morphologically as comprising a FAZ filament struct …
A procyclic acidic repetitive protein (PARP) fraction was purified from long-term cultures of Trypanosoma brucei procyclic forms by a solvent-extraction and reverse phase chromatography procedure. The PARP fraction yielded small quantities of a single N-linked oligosaccharide with the structure Man alpha1-6(Man alpha1-3)Man alpha1-6(Man alpha1-3)Manbeta1-4GlcNAcbeta1-4GlcNAc (Man5GlcNAc2). Fractionation of PARP on Con A-Sepharose revealed that the majority (80 to 90%) of the PARP fraction did not bind to Con A and was composed of the parpA alpha gene product that contains repeats of -Glu-Pro-Pro-Thr- (GPEET-PARP) and that lacks an N-glycosylation site. This form of PARP has not been previously identified at the protein-level. The minor Con-A-binding fraction was shown to be rich in the previously described form of PARP, encoded by the parpAbeta and/or parpB alpha genes, that contains a -Glu-Pro- repeat domain (EP-PARP) and an N-glycosylation site. Analysis of longer and shorter-term cultures suggested
article{4d1c267f-cfe4-4d9a-8850-1fed2b5343ec, author = {Sternberg, J M and McGuigan, F}, issn = {0014-4894}, keyword = {Animals,Culture Media,Epidermal Growth Factor,Humans,Mice,Recombinant Proteins,Regression Analysis,Trypanosoma brucei brucei,Journal Article,Research Support, Non-U.S. Govt}, language = {eng}, number = {4}, pages = {4--422}, publisher = {Elsevier}, series = {Experimental Parasitology}, title = {Trypanosoma brucei : mammalian epidermal growth factor promotes the growth of the African trypanosome bloodstream form}, url = {http://dx.doi.org/10.1006/expr.1994.1047}, volume = {78}, year = {1994 ...
Author Summary African trypanosomiasis (AT) is a disease caused by the single-celled protozoan parasite Trypanosoma brucei. In humans, AT causes neurological problems including sleep disturbances, which give the disease its colloquial name of
(2010) Cristodero et al. Molecular Microbiology. The parasitic protozoa Trypanosoma brucei has a complex life cycle. Oxidative phosphorylation is highly active in the procyclic form but absent from bloodstream cells. The mitochondrial genome enco...
The procyclic acidic repetitive protein is the major cell-surface glycoprotein of the insect-dwelling procyclic forms of the Trypanosoma brucei species of African trypanosomes. The glycoprotein contains an acidic Glu-Pro repeat domain, a glycosyl-phosphatidylinositol membrane anchor and a putative asparagine glycosylation site. In this paper we describe a rapid purification scheme for this glycoprotein, using solvent extraction and hydrophobic interaction chromatography, and a partial characterization of the glycosylphosphatidylinositol membrane anchor. The carbohydrate composition of the anchor is extremely unusual; it contains on average nine GlcNAc, nine Gal, and five sialic acid residues. This is the first description of such a heavily substituted and negatively charged anchor. A comparison between the trypanosome procyclic surface and the Leishmania promastigote surface is also presented. ...
2017. Franco J, Sardi F, Szilágyi L, Kövér K, Fehér K, Comini MA (2017) Diglycosyl diselenides alter redox homeostasis and glucose consumption of infective African trypanosomes. Int. J. Parasitol. Drugs & Drug Resist. 7: 303-313.. Ornithine decarboxylase or gamma-glutamylcysteine synthetase overexpression protects Leishmania (Vianna) guyanensis against antimony (2017) Fonseca MS, Comini M, Resende BV, Santi AMM, Zoboli AP, Moreira DS, Monte-Neto RL and Murta SMF. Exp. Parasitol. 175: 36-43.. Franco J, Medeiros A, Benítez D, Perelmuter K, Serra G, Comini MA, Scarone L (2017) In vitro activity and mode of action of Distamycin analogues against African trypanosomes. Eu. J. Med. Chem. 126: 776-788.. 2016. Orban OCF, Korn RS, Benítez D, Medeiros A, Preu L, Loaëc N, Meijer L, Koch O, Comini MA, and Kunick C (2016) 5-Substituted 3-chlorokenpaullone derivatives are potent inhibitors of Trypanosoma brucei bloodstream forms. Bioorg Med Chem. 24(16):3790-800.. Benítez D, Medeiros A, Fiestas L, ...
Work in my laboratory is focused on the clinically relevant trypanosomatid parasites, primarily the African trypanosome Trypanosoma brucei, the closely related American trypanosome Trypanosoma cruzi, and Leishmania species. These parasites are the causative agents of neglected tropical diseases that produce a substantial health and economic burden in endemic areas, and improved therapeutics are urgently needed. By examining the biology of these parasites we may uncover differences between the host and parasite biology that can be exploited to develop therapeutic treatments.. We are particularly interested in how T. brucei is able to sense and respond to its host environment, which is essential for its survival and virulence. The African trypanosome has a complex lifecycle requiring transmission by the insect vector the tsetse fly, propagation in a mammalian host, and reinfection of the tsetse fly. Trypanosomes are evolutionarily divergent eukaryotes and use exclusively post-transcriptional ...
Trypanosoma brucei Procyclin GPEET, 0.5 ml. GPEET and EP procyclins are the major surface glycoproteins of Trypanosoma brucei while it lives in the midgut (procyclic form) of tsetse flies (Glossina spp.
TY - JOUR. T1 - Investigation of Trypanothione Reductase as a Drug Target in Trypanosoma brucei. AU - Spinks, Daniel. AU - Shanks, Emma J.. AU - Cleghorn, Laura A. T.. AU - McElroy, Stuart. AU - Jones, Deuan. AU - James, Daniel. AU - Fairlamb, Alan H.. AU - Frearson, Julie A.. AU - Wyatt, Paul G.. AU - Gilbert, Ian H.. PY - 2009/12. Y1 - 2009/12. N2 - There is an urgent need for new drugs for the treatment of tropical parasitic diseases such as human African trypanosomiasis, which is caused by Trypanosoma brucei. The enzyme trypanothione reductase (TryR) is a potential drug target within these organisms. Herein we report the screening of a 62000 compound library against T brucei TryR. Further work was undertaken to optimise potency and selectivity of two novel-compound series arising from the enzymatic and whole parasite screens and mammalian cell counterscreens. Both of these series, containing either a quinoline or pyrimidinopyrazine scaffold, yielded low micromolar inhibitors of the enzyme ...
Trypanosoma brucei is the causative agent of human African sleeping sickness and Nagana in cattle. In addition to being an important pathogen T. brucei has developed into a model system in cell biology. Using Stable Isotope Labelling of Amino acids in Cell culture (SILAC) in combination with mass spectrometry we determined the abundance of |1600 proteins in the long slender (LS), short stumpy (SS) mammalian bloodstream form stages relative to the procyclic (PC) insect-form stage. In total we identified 2645 proteins, corresponding to ~30% of the total proteome and for the first time present a comprehensive overview of relative protein levels in three life stages of the parasite. We can show the extent of pre-adaptation in the SS cells, especially at the level of the mitochondrial proteome. The comparison to a previously published report on monomorphic in vitro grown bloodstream and procyclic T. brucei indicates a loss of stringent regulation particularly of mitochondrial proteins in these cells when
TY - JOUR. T1 - A Conserved DNA Repeat Promotes Selection of a Diverse Repertoire of Trypanosoma brucei Surface Antigens from the Genomic Archive. AU - Hovel-Miner, Galadriel. AU - Mugnier, Monica. AU - Goldwater, Benjamin. AU - Cross, George A M. AU - Papavasiliou, F. Nina. PY - 2016/5/1. Y1 - 2016/5/1. N2 - African trypanosomes are mammalian pathogens that must regularly change their protein coat to survive in the host bloodstream. Chronic trypanosome infections are potentiated by their ability to access a deep genomic repertoire of Variant Surface Glycoprotein (VSG) genes and switch from the expression of one VSG to another. Switching VSG expression is largely based in DNA recombination events that result in chromosome translocations between an acceptor site, which houses the actively transcribed VSG, and a donor gene, drawn from an archive of more than 2,000 silent VSGs. One element implicated in these duplicative gene conversion events is a DNA repeat of approximately 70 bp that is found in ...
Kinetoplastid parasites, including Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp., are transmitted by insect vectors and infect 20 million people, mainly in the most impoverished regions of the world. T. brucei is the causative agent of human African trypanosomiasis, which is a health threat to millions in sub-Saharan Africa and is 100% fatal if left untreated (1). Investigations into the novel biology of kinetoplastids may provide new chemotherapeutic avenues. Indeed, these early-branching eukaryotes utilize unusual processes for gene expression regulation and metabolic organization, and a large number of predicted kinetoplastid proteins lack any homology to proteins in their mammalian hosts.. Kinetoplastids are named for their distinctive mitochondrial DNA network, known as a kinetoplast, or kDNA, localized within their single mitochondrion. In T. brucei, kDNA is a giant catenated network of circular molecules comprised of a few dozen copies of a maxicircle (∼23 to 40 kb) and ...
At the end of ones tether with the NCBI database the following proteins were identified: isoform 1 of serum albumin (ALB1), HSP70, dihydropyrimidinase-related protein 2 (DPYSL2), isoforms of myelin root protein (MBP1), isoform 3 of spectrin alpha chain (SPTAN1), proton ATPase catalytic subunit A (ATP6V1A), glutathione S-transferase P (GSTP1), pro- tein DJ-1 (PUT7), and dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex (DLAT). Although subject to involuntary hydrolysis and detoxication away glutathione, successive 6 Target-Organ Toxicity: Liver and Kidney The using software is irritation version. WordPress: Free blogs managed by the developers of the WordPress package buy cabgolin 0.5 mg low price treatment arthritis. Chamber 31:11В-24 Montagna G, Cremona ML, Paris G, Amaya MF, Buschiazzo A, Alzari PM, Frasch ACC (2002) The trans-sialidase from the African trypanosome Trypanosoma brucei. This letter triggers the nomination of the Rapporteur and ...
We recently presented a model for site-specific protein N-glycosylation in Trypanosoma brucei whereby the TbSTT3A oligosaccharyltransferase (OST) first selectively transfers biantennary Man(5)GlcNAc(2) from the lipid-linked oligosaccharide (LLO) donor Man(5)GlcNAc(2)-PP-Dol to N-glycosylation sequons in acidic to neutral peptide sequences and TbSTT3B selectively transfers triantennary Man(9)GlcNAc(2) to any remaining sequons. In this paper, we investigate the specificities of the two OSTs for their preferred LLO donors by glycotyping the variant surface glycoprotein (VSG) synthesized by bloodstream-form T. brucei TbALG12 null mutants. The TbALG12 gene encodes the alpha 1-6-mannosyltransferase that converts Man(7)GlcNAc(2)-PP-Dol to Man(8)GlcNAc(2)-PP-Dol. The VSG synthesized by the TbALG12 null mutant in the presence and the absence of alpha-mannosidase inhibitors was characterized by electrospray mass spectrometry both intact and as pronase glycopetides. The results show that TbSTT3A is able to ...
Trypanosoma brucei survives in mammals through antigenic variation, which is driven by RAD51-directed homologous recombination of Variant Surface Glycoproteins (VSG) genes, most of which reside in a subtelomeric repository of |1000 silent genes. A key regulator of RAD51 is BRCA2, which in T. brucei contains a dramatic expansion of a motif that mediates interaction with RAD51, termed the BRC repeats. BRCA2 mutants were made in both tsetse fly-derived and mammal-derived T. brucei, and we show that BRCA2 loss has less impact on the health of the former. In addition, we find that genome instability, a hallmark of BRCA2 loss in other organisms, is only seen in mammal-derived T. brucei. By generating cells expressing BRCA2 variants with altered BRC repeat numbers, we show that the BRC repeat expansion is crucial for RAD51 subnuclear dynamics after DNA damage. Finally, we document surprisingly limited co-localization of BRCA2 and RAD51 in the T. brucei nucleus, and we show that BRCA2 mutants display aberrant
In general, the cellular structure of T. brucei is similar to all other eukaryotes. There are however, a few differences. T. bruceis cell surface has, (in addition to its surface antigens), a thick layer of proteins, called Variant Surface Glycoprotein (VSGs) genes. These allow the surface antigens to mutate, by switching variants.(2) Having over 1000 VSG genes and psuedogenes, T. brucei is able to switch variants frequently. Trascription occurs one gene at a time, from one of many telomeric VSG expression sites.(3) In order to switch an active VSG gene, DNA rearrangements must occur, to switch the old VSG gene with a new one. Using the bloodstream form of T. brucei, scientists in the Netherlands discovered that telomere exchange, thought to be rare, was indeed occuring. The scientists marked a VSG gene with a hygromycin resistance gene, allowed the gene to undergo variation, and selected switched Trypanosomes. The drug sensitivity and polymerase chain reactions (PCR), revealed that telomere ...
TY - JOUR. T1 - Killing of Trypanosoma brucei by Concanavalin A. T2 - Structural basis of resistance in glycosylation mutants. AU - Acosta-Serrano, Alvaro. AU - Cole, Robert N. AU - Englund, Paul T.. PY - 2000/12/8. Y1 - 2000/12/8. N2 - Concanavalin A (Con A) kills procyclic (insect) forms of Trypanosoma brucei by binding to N-glycans on EP-procyclin, a major surface glycosyl phosphatidylinositol (GPI)-anchored protein which is rich in Glu-Pro repeats. We have previously isolated and studied two procyclic mutants (ConA 1-1 and ConA 4-1) that are more resistant than wild-type (WT) to Con A killing. Although both mutants express the same altered oligosaccharides compared to WT cells, ConA 4-1 is considerably more resistant to lectin killing than is ConA 1-1. Thus, we looked for other alterations to account for the differences in sensitivity. Using mass spectrometry, together with chemical and enzymatic treatments, we found that both mutants express types of EP-procyclin that are either poorly ...
Dr. Elisabetta Ullu, professor of internal medicine and cell biology at Yale University, presented the new biology of Trypanosoma brucei, a one-celled parasite that causes sleeping sickness in humans and in animals, at Cleveland State on Friday, March 29.. Professor Ullu is a leader in Trypanosoma genetics and molecular biology, and has been recognized for her labs work with the protozoan parasite - Trypanosoma brucei, which causes African sleeping sickness. African sleeping sickness is a potentially fatal parasitic disease that infects 500,000 people per year, and is a major public health concern in Sub-Saharan Africa. The disease is transmitted by the tsetse fly - a large, brown, biting fly that injects metacyclic trypomastigotes into the skin tissue during a blood meal with a mammalian host.. Professors and students who had come to hear Ullu speak were impressed by her talk and her research on this obligate parasite. "She has screened the entire genome for different mRNAs that are expressed ...
TY - PAT. T1 - Synthesis and Antiprotozoal Activity of Dicationic 3.5 Diphenylisoxazoles. AU - Tidwell,Richard R.. AU - Bakunova,Svetlana M.. AU - Bakunov,Stanislav. AU - Patrick,Donald A.. N1 - Status: published applicationnumber: 11/415,982 usclass: 514/378 ; 548/247 applicationnumber: 11/415,982. PY - 1800. Y1 - 1800. N2 - Novel dicationic 3,5-diphenylisoxazole compounds are described. Synthetic routes to these novel compounds are provided. Several of the compounds displayed in vitro activity versus Trypanosoma brucei brucei and Plasmodium falciparum comparable to that of furamidine. A majority of the novel compounds also were less toxic to VERO cells than furamidine.. AB - Novel dicationic 3,5-diphenylisoxazole compounds are described. Synthetic routes to these novel compounds are provided. Several of the compounds displayed in vitro activity versus Trypanosoma brucei brucei and Plasmodium falciparum comparable to that of furamidine. A majority of the novel compounds also were less toxic to ...
cytosolic large ribosomal subunit, rRNA binding, structural constituent of ribosome, ribosomal large subunit assembly, translation
Opens the Highlight Feature Bar and highlights feature annotations from the FEATURES table of the record. The Highlight Feature Bar can be used to navigate to and highlight other features and provides links to display the highlighted region separately. Links in the FEATURES table will also highlight the corresponding region of the sequence. More... ...
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Trypanosoma brucei MARP-1 protein: from Trypanosoma brucei; high molecular weight, repetitive protein; amino acid has sequence has been determined
Trypanosoma brucei is a protozoan parasite of major public health and economic importance in sub-Saharan Africa, where it is the causative agent of sleeping sickness in man and Nagana in cattle. The complete genome sequence of T.brucei is now available and the diploid genetic system has recently been demonstrated to be Mendelian. This opens up the possibility of using a classical genetic approach to identify genetic loci that determine important phenotypic traits in this parasite, such as host specificity, drug resistance, and pathogenicity. A genetic map of the non human-infective subspecies, T.b.brucei, has already been assembled and successfully used in quantitative trait analysis of a number of traits specific to this pathogen. This thesis describes the construction of a separate genetic map for the sub-species responsible for , 90% of human African trypanosomiasis infections, T.b.gambiense, which differs significantly from T.b.brucei in many key phenotypes. The genetic linkage map was ...
Author Summary Trypanosomes are single-celled organisms that are transmitted between animal hosts by the tsetse fly. These parasites infect a wide range of mammals and in sub-Saharan Africa are extensively debilitating to livestock, and some species are also able to infect humans causing a disease, sleeping sickness, that is usually fatal unless treated. Some trypanosome strains cause more severe disease than others, and studying these differences may allow the identification of how serious disease is caused. We approached this problem by looking at how differences in disease symptoms (enlarged spleen and liver, and reduced blood cell numbers) that are caused in infections in mice with two strains of Trypanosoma brucei, TREU927 and STIB247. These disease manifestations are clinically relevant in human and livestock trypanosome infections. Examining how the symptoms are inherited in infections with offspring of a cross between the two strains allowed the identification of a region of the T. brucei genome
Endocytosis by African trypanosomes. I. Three dimensional structure of the endocytic organelles in Trypanosoma brucei and Trypanosoma ...
The parasite Trypanosoma brucei is the causative agent of human African sleeping sickness. T. brucei genes are constitutively transcribed in polycistronic units that are processed by trans-splicing and polyadenylation. All mRNAs are trans-spliced to generate mRNAs with a common 5′ exon derived from the spliced leader RNA (SL RNA). Persistent endoplasmic reticulum (ER) stress induces the spliced leader silencing (SLS) pathway, which inhibits trans-splicing by silencing SL RNA transcription, and correlates with increased programmed cell death. We found that during ER stress induced by SEC63 silencing or low pH, the serine-threonine kinase PK3 translocated from the ER to the nucleus, where it phosphorylated the TATA-binding protein TRF4, leading to the dissociation of the transcription preinitiation complex from the promoter of the SL RNA encoding gene. PK3 loss of function attenuated programmed cell death induced by ER stress, suggesting that SLS may contribute to the activation of programmed ...
Cell division is regulated by intricate and interconnected signal transduction pathways that precisely coordinate, in time and space, the complex series of events involved in replicating and segregating the component parts of the cell. In Trypanosoma brucei, considerable progress has been made over recent years in identifying molecular regulators of the cell cycle and elucidating their functions, although many regulators undoubtedly remain to be identified, and there is still a long way to go with respect to determining signal transduction pathways. However, it is clear that cell cycle regulation in T. brucei is unusual in many respects. Analyses of trypanosome orthologues of conserved eukaryotic cell cycle regulators have demonstrated divergence of their function in the parasite, and a number of other key regulators are missing from T. brucei. Cell cycle regulation differs in different parasite life cycle stages, and T. brucei appears to use different checkpoint control strategies compared to model
There is an urgent need for new drugs for the treatment of tropical parasitic diseases such as human African trypanosomiasis, which is caused by Trypanosoma brucei. The enzyme trypanothione reductase (TryR) is a potential drug target within these organisms. Herein we report the screening of a 62,000 compound library against T. brucei TryR. Further work was undertaken to optimise potency and selectivity of two novel-compound series arising from the enzymatic and whole parasite screens and mammalian cell counterscreens. Both of these series, containing either a quinoline or pyrimidinopyrazine scaffold, yielded low micromolar inhibitors of the enzyme and growth of the parasite. The challenges of inhibiting TryR with druglike molecules is discussed.
In this paper we describe an analysis of the mRNA expression profile of trypanosomes from two discrete bloodstream form stages of the parasite (slender and stumpy forms), as well as during the transition of the stumpy population to the procyclic life-cycle stage. Although previous analyses have compared either cultured or rodent derived bloodstream form parasites with cultured procyclic forms [37, 38], our analysis represents the first comparison of in vivo derived pleomorphic slender cells with genetically identical stumpy forms, and a first analysis of the dynamic changes in mRNA profile that accompany the transition to procyclic forms. Previous analyses of the differentiation from stumpy to procyclic forms have established that this transition follows a defined and highly reproducible temporal programme, with progression through the major events of differentiation occurring with great synchrony in the population [33]. This provides a considerable power to the analysis of regulated mRNA ...
weight loss pills for women best appetite suppressant best weight loss products best weight loss supplementPosted February 17th, 18:36 by Dorothycoitycheap essays application essays help with writing a narrative essay write essays for me Posted February 17th, 16:59 by Pay For Essay Online Trends Parasitol 22:485-491 Clarckson AB Jr, Bienen EJ, Pollakis G et al (1989) Respiration of bloodstream forms of the parasite Trypanosoma brucei brucei is dependent on a plant-like choice oxidase. I created a standardized size for distinct files where reference developers can stipulate metadata close to their tools, and de- swell what size (denominate and transcribe) input evidence has to have, as shown in Listing 4. Thither are umpteen contiguous threats too generic kamagra soft 100 mg without prescription erectile dysfunction treatment machine. Notwithstanding how, understanding incision and sharing rates are at rest not satisfying, so that extra efforts appearance of to be neces- sary to optimize ...
The detergent-insoluble T. brucei cytoskeleton consists of several morphologically distinct regions and organelles, many of which are detectable only by electron microscopy. We have produced a set of monoclonal antibodies that define each structural component of this highly ordered cytoskeleton. The monoclonal antibodies were selected by cloning of hybridomas produced from mice injected with complex mixtures of proteins of either the cytoskeleton itself or salt extracts thereof. Four antibodies define particular tubulin isotypes and locate the microtubules of the axoneme and sub-pellicular array; two antibodies recognize the flagellum attachment zone; one recognizes the paraflagellar rod and another the basal bodies. Finally, one antibody defines a detergent-insoluble component of the nucleus. The antigens detected by each monoclonal antibody have been analysed by immunofluorescence microscopy, immunogold electron microscopy and Western blotting. ...
for: The role of the subpellicular microtubule array in Trypanosoma brucei cytokinesis Microtubules are essential cytoskeletal filaments in eukaryotic cells. Th...
Research - original articles and review articles. Morriswood B, Engstler M. Lets get fISSical: fast in silico synchronization as a new tool for cell division cycle analysis. (2017) Parasitology. Feb 7:1-14.. Cicova Z, Dejung M, Skalicky T, Eisenhuth N, Hanselmann S, Morriswood B, Figueiredo LM, Butter F, Janzen CJ. (2016) Two flagellar BAR domain proteins in Trypanosoma brucei with stage-specific regulation. Sci Rep. 6:35826.. Vidilaseris K, Lesigang J, Morriswood B, Dong G. Assembly mechanism of Trypanosoma brucei BILBO1 at the flagellar pocket collar. (2015) Commun Integr Biol.8(1):e992739.. Morriswood B. Form, Fabric, and Function of a Flagellum-Associated Cytoskeletal Structure. (2015) Cells. 4(4):726-47.. Morriswood B, Schmidt K. A MORN Repeat Protein Facilitates Protein Entry into the Flagellar Pocket of Trypanosoma brucei. (2015) Eukaryot Cell. 14(11):1081-93.. Vidilaseris K, Shimanovskaya E, Esson HJ, Morriswood B, Dong G. Assembly mechanism of Trypanosoma brucei BILBO1, a multidomain ...
Metacaspase (MCA) is an important enzyme in Trypanosoma brucei, absent from humans and differing significantly from the orthologous human caspases. Therefore MCA constitutes a new attractive drug target for antiparasitic chemotherapeutics, which needs further characterization to support the discovery of innovative drug candidates. A first series of inhibitors has been prepared on the basis of known substrate specificity and the predicted catalytic mechanism of the enzyme. In this Letter we present the first inhibitors of TbMCA2 with low micromolar enzymatic and antiparasitic activity in vitro combined with low cytotoxicity.. ...
mRNA maturation in Trypanosoma brucei depends upon trans splicing, and variations in trans-splicing efficiency could be an important step in controlling the levels of individual mRNAs. RNA splicing requires specific sequence elements, including conserved 5′ splice sites, branch points, pyrimidine-rich regions [poly(Y) tracts],3′ splice sites (3′SS), and sometimes enhancer elements. To analyze sequence requirements for efficient trans splicing in the poly(Y) tract and around the 3′SS, we constructed a luciferase-β-galactosidase double-reporter system. By testing ∼90 sequences, we demonstrated that the optimum poly(Y) tract length is ∼25 nucleotides. Interspersing a purely undine-containing poly(Y) tract with cytidine resulted in increased ironssplicing efficiency, whereas purines led to a large decrease. The position of the poly(Y) tract relative to the 3′SS is important, and an AC dinucleotide at positions -3 and -4 can lead to a 20-fold decrease in irons splicing. However, ...
Lysates from logarithmic growth phase T. brucei (2.5 × 108 cells) isolated from infected rats and from the logarithmic growth and late stationary phase (8.3 and 5.4 × 107 cells, respectively) organisms isolated from bloodstream-form cultures were prepared by hypotonic lysis using double-distilled water containing a cocktail of reversible and irreversible inhibitors (one tablet in 25 ml) of pancreas extract, pronase, thermolysin, chemotrypsin, trypsin, and papain (Complete™; Roche Diagnostics). For PG production from AA, we used the reaction mixture described by Ujihara et al. (21) with the following modifications: 100 mM sodium phosphate, pH 7.0, 2 μM hematin, 5 mM tryptophan, 1 mM AA, and 300 μl of the respective T. brucei lysates in a final volume of 500 μl. The mixture was incubated at 37°C for 30 min, and then the reaction was stopped by addition of 100 μl of 1 M HCl and 6 vol of cold ethyl acetate.. For PGF2α synthesis from PGH2, a standard reaction mixture that contained 100 mM ...
Using video fluorescence microscopy and Golgi proteins tagged with variants of GFP, it has been possible to follow the duplication of the Golgi apparatus in the protozoan parasite T. brucei. A matrix protein and a putative enzyme were chosen for study because in mammals there is evidence that these two types of Golgi protein can behave differently during certain phases of the Golgi life cycle (Seemann et al., 2000, 2002). The GRASP family of matrix proteins has been implicated in cisternal stacking and other signaling events. A single homologue was identified by searching the T. brucei genome that was most similar to mammalian GRASP55 and had the same domain structure: a predicted NH2-terminal myristic acid that aids membrane binding; a highly homologous NH2-terminal region (50% identity) that in mammals binds to the coiled-coil matrix protein GM130 (Barr et al., 1998); and a poorly conserved COOH-terminal region, rich in serines and prolines, which in mammals is thought to mediate mitotic ...
By Zandile Nare, University of EdinburghTrypanosoma brucei is a parasite which is responsible for causing African sleeping sickness and nagana in cattle in sub-Saharan Africa. Cell differentiation in T. brucei is associated with the upregulation and downregulation of several genes some of which seem to be regulated by epigenetic mechanisms. T. brucei could therefore be a…
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Our research is aimed at understanding the molecular mechanisms of RNA editing in kinetoplastid parasites, which cause African sleeping sickness, Chagasdisease...
Mitochondrial RNA-binding proteins, molecular model. This complex consists of two mitochondrial RNA-binding proteins MRP1 and MRP2. These act together to bind to RNA (ribonucleic acid). Here, they here form a heteromeric complex, specifically a heterotetramer, with fourfold symmetry. These two proteins are from the protozoan Trypanosoma brucei. - Stock Image C015/4586
Mitochondrial RNA-binding proteins, molecular model. This complex consists of two mitochondrial RNA-binding proteins MRP1 and MRP2. These act together to bind to RNA (ribonucleic acid). Here, they here form a heteromeric complex, specifically a heterotetramer, with fourfold symmetry. These two proteins are from the protozoan Trypanosoma brucei. - Stock Image C015/4007
Department of Infectious Disease and Microbiology, Graduate School of Public Health. University of Pittsburgh, 421 Parran Hall, 130 Desoto St., Pittsburgh, PA 15213. Cell Phone: [412] 268-0319. Office Phone: [412] 624-5915. Email: [email protected] [email protected] Website : http://www.idm.pitt.edu/directory/bios/tarunsal.asp. Expertise: Infectious diseases, molecular and biochemical parasitology, molecular models of eukaryotic translational regulation, in vitro systems of protein synthesis in yeast, translation initiation factors required for cell cycle in the African sleeping sickness parasite (Trypanosoma brucei) ...
Üks põhilik küsimus trypanosoma uurimisel on see, kuidas enamikku VSG geene hoitakse nii "vaikselt", ja kuidas neid geene ümber lülitatakse. Ekspresseeritud VSG on alati paigutatud ekspressioonitsooni - leidub suurte ja keskmiste kromosoomide telomeeridel. Sel ajal kui on vähemalt 20 tuntud ekspressioonitsooni, aktiivseks võib olla ainult üks neist. Selle protsessiga kaasuvad mitmed mehhanismid, kuid täpne geenide vaigistamise olemus ei ole veel selge.[9] VSG-d on võimalik ümber lülitada kas aktiivse ekspressiooni muutmisel (aktiivse kohta vahetamine varem vaiksele kohale) või VSG geeni vahetamisel aktiivses kohas. Genoom sisaldab palju võimalikke VSG geenide koopiaid, nii minikromosoomidel kui ka korduvates sektsioonides kromosoomide sisemuses. Need on peamiselt vaiksed, tüüpiliselt vahelejäänud sektorid või enneaegsed stoppkoodonid, kuid need on olulised uute VSG geenide evolutsioonis. Umbes 10% T. brucei genoomist võib koosneda VSG geenidest või pseudogeenidest. Igaüks ...
The effects of Prozyme knockout on blood form T. brucei.(A) Cell growth curves. Log cell number versus days in culture. Triangle, Flag-tagged prozyme Expressed