What's new for 'Trypanosomatids' in PubMed

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Sent on Tuesday, 2010 Jun 29
Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results

Items 1 - 7 of 7

1.	Eukaryot Cell. 2010 Jun 25. [Epub ahead of print] The pre-mRNA Splicing Machinery of Trypanosomes: Complex or Simplified? Günzl A. Department of Genetics and Developmental Biology and Department of Molecular, Microbial and Structural Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3301, USA. Abstract Trypanosomatids are early-diverged, protistan parasites of which Trypanosoma brucei, Trypanosoma cruzi, and several species of Leishmania cause severe, often lethal diseases in humans. To better combat these parasites, their molecular biology has been a research focus for more than three decades and the discovery of spliced leader (SL) trans splicing in T. brucei established a key difference between parasites and hosts. In SL trans splicing, the capped 5' terminal region of the small nuclear SL RNA is fused onto the 5' end of each mRNA. This process, in conjunction with polyadenylation, generates individual mRNAs from polycistronic precursors and creates functional mRNA by providing the cap structure. The reaction is a two step transesterification process analogous to intron removal by cis splicing which, in trypanosomatids, is confined to very few pre-mRNAs. Both types of pre-mRNA splicing are carried out by the spliceosome consisting of five U-rich small nuclear (sn)RNAs and, in humans, of up to approximately 170 different proteins. While trypanosomatids possess a full set of spliceosomal U snRNAs, only few splicing factors were identified by standard genome annotation because trypanosomatid amino acid sequences are among the most divergent in the eukaryotic kingdom. This review focuses on recent progress made in the characterization of the splicing factor repertoire in T. brucei which was achieved by tandem affinity purification of splicing complexes, by systematic analysis of proteins containing RNA recognition motifs, and by mining the genome database. In addition, recent findings about functional differences between trypanosome and human pre-mRNA splicing factors are discussed.
	PMID: 20581293 [PubMed - as supplied by publisher]

2.	Eukaryot Cell. 2010 Jun 25. [Epub ahead of print] Cellular and molecular remodelling of the endocytic pathway during differentiation of Trypanosoma brucei bloodstream forms. Vanhollebeke B, Uzureau P, Monteyne D, Pérez-Morga D, Pays E. Laboratory of Molecular Parasitology, Institute of Molecular Biology and Medicine, Université Libre de Bruxelles, 12 rue des Professeurs Jeener et Brachet, B-6041 Gosselies, Belgium; Department of Biochemistry & Biophysics, UCSF, 1550 Fourth Street, San Francisco CA 94158-2328, USA. Abstract During the course of mammalian infection, African trypanosomes undergo extensive cellular differentiation, as actively dividing long slender forms (SL) progressively transform into intermediate forms (I) and finally quiescent G1/G0-locked short stumpy forms (ST). ST forms maintain adaptations compatible with their survival in the mammalian bloodstream such as high endocytic activity, but they already show pre-adaptations to the insect midgut conditions. The nutritional requirements of ST forms must differ from those of SL forms because they do not multiply any longer. We report that in ST forms the uptake of several ligands was reduced as compared with SL forms. In particular, the haptoglobin-hemoglobin (Hp-Hb) complex was no longer taken up due to dramatic down-regulation of its cognate receptor TbHpHbR. As this receptor also allows uptake of trypanolytic particles from human serum, ST forms were resistant to trypanolysis by human serum lipoproteins. These observations allowed both flow cytometry analysis of SL to ST differentiation and the generation of homogeneous ST populations after positive selection upon exposure to trypanolytic particles. In addition, we observed that in ST forms the lysosome relocates anterior to the nucleus. Altogether, we identified novel morphological and molecular features that characterize SL to ST differentiation.
	PMID: 20581292 [PubMed - as supplied by publisher]

3.	Biochim Biophys Acta. 2010 May 22. [Epub ahead of print] Identification of an atypical peptidyl-prolyl cis/trans isomerase from trypanosomatids. Erben ED, Valguarnera E, Nardelli S, Chung J, Daum S, Potenza M, Schenkman S, Téllez-Iñón MT. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (INGEBI-CONICET) Buenos Aires, R. Argentina. Abstract The parvulin family of peptidyl-prolyl cis/trans isomerases (PPIases) catalyzes the cis/trans isomerization of the peptide bonds preceding Pro residues. Eukaryotic parvulin-type PPIases have been shown to be involved in cell proliferation and cell cycle progression. Here we present the biochemical and molecular characterization of a novel multi-domain parvulin-type PPIase from the human pathogenic Trypanosoma cruzi, annotated as TcPar45. Like most other parvulins, Par45 has an N-terminal extension, but, in contrast to human Pin1, it contains a forkhead-associated domain (FHA) instead of a WW domain at the N-terminal end. Par45 shows a strong preference for a substrate with the basic Arg residue preceding Pro (Suc-Ala-Arg-Pro-Phe-NH-Np: k(cat)/K(M)=97.1 /M/s), like that found for human Par14. In contrast to human Pin1, but similarly to Par14, Par45 does not accelerate the cis/trans interconversion of acidic substrates containing Glu-Pro bonds. It is preferentially located in the parasite nucleus. Single RNA interference (RNAi)-mediated knock-down showed that there was a growth inhibition in procyclic Trypanosoma brucei cells. These results identify Par45 as a phosphorylation-independent parvulin required for normal cell proliferation in a unicellular eukaryotic cell. Copyright © 2010. Published by Elsevier B.V.
	PMID: 20580912 [PubMed - as supplied by publisher]

4.	Int J Antimicrob Agents. 2010 Jun 25. [Epub ahead of print] Antipar asitic activity of alkaloids from plant species of Papua New Guinea and Australia. Fernandez LS, Sykes ML, Andrews KT, Avery VM. Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Australia; Griffith Medical Research College, A Joint Program of Griffith University and the Queensland Institute of Medical Research, QIMR, Herston, QLD 4006, Australia. Abstract New drugs are needed to help overcome the increasing problem of drug resistance in parasites that cause diseases such as malaria and trypanosomiasis. In this study, alkaloid compounds isolated from extracts of the plants Flindersia amboinensis, Stephania zippeliana and Voacanga papuana from Papua New Guinea and Flindersia acuminata from Australia were examined for their antiparasitic activity against Plasmodium falciparum strains and Trypanosoma brucei brucei as well as their cytotoxicity against the mammalian cell lines HEK 293 and HeLa. The most active compound, dimethylisoborreverine (DMIB), showed submicromolar activity, with 50% inhibitory concentration (IC(50)) values between 20nM and 810nM both against drug-sensitive and drug-resistant P. falciparum strains, along with moderate selectivity against T. b. brucei and mammalian cells. Stage specificity studies revealed that P. falciparum trophozoite-stage parasites were more susceptible to DMIB than ring- or schizont-stage parasites. DMIB-treated trophozoites showed changes in food vacuole morphology, with an apparent reduction in haemozoin formation that does not appear to be inhibited via the direct binding of haem. These findings suggest a potential for indole alkaloids from Flindersia spp. as new antiparasitic agents. Copyright © 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
	PMID: 20580535 [PubMed - as supplied by publisher]

5.	Bioorg Med Chem. 2010 Jun 4. [Epub ahead of print] A novel achiral seco-cyclopropylpyrido[e]indolone (CPyI) analog of CC-1065 and the duocarmycins: Synthesis, DNA interactions, in vivo anticancer and anti-parasitic evaluation. Chavda S, Babu B, Yanow SK, Jardim A, Spithill TW, Kiakos K, Kluza J, Hartley JA, Lee M. Division of Natural Sciences and Department of Chemistry, Hope College, 35 East 12th Street, Holland, MI 49423, USA. Abstract The synthesis of an achiral seco-hydroxy-aza-CBI-TMI analog (8) of the duocarmycins is reported. Its specificity for the DNA minor groove of AT-rich sequences and covalent bonding to adenine-N3 was ascertained by a thermal cleavage assay. Compound 8 was found to be cytotoxic in the nanomolar range against murine and human cancer cells. It was further demonstrated that compound 8 was active against murine melanoma (B16-F0) grown in C57BL/6 mice. Compound 8 was also shown to inhibit the growth of the protozoan parasites Leishmania donovani, Leishmania mexicana, Trypanosoma brucei, and Plasmodium falciparum in culture. Copyright © 2010 Elsevier Ltd. All rights reserved.
	PMID: 20579889 [PubMed - as supplied by publisher]

6.	J Enzyme Inhib Med Chem. 2010 Jun 28. [Epub ahead of print] Synthesis and antileishmanial activity of 5-(5-nitroaryl)-2-substituted-thio-1,3,4-thiadiazoles. Alipour E, Emami S, Yahya-Meymandi A, Nakhjiri M, Johari F, Ardestani SK, Poorrajab F, Hosseini M, Shafiee A, Foroumadi A. Department of Chemistry, Islamic Azad University, Tehran-North Branch, Zafar St, Tehran, Iran. Abstract A series of novel 2-substituted-thio-1,3,4-thiadiazoles bearing a 5-nitroaryl moiety including nitrofuran, nitrothiophene or nitroimidazole at the 5-position and a bulky residue attached to the 2-position of the thiadiazole ring were synthesised as potential antileishmanial agents. The target compounds were evaluated against the promastigote form of Leishmania major using the tetrazolium bromide salt (MTT) colorimetric assay. All test compounds exhibited high activity against L. major promastigotes with 50% inhibitory concentrations (IC(50)) ranging from 1.11 to 3.16 muM. The structure-activity relationship study indicated that the S-pendant group attached to the 2-position of the thiadiazole ring has a high flexibility for structural alteration therefore retaining good antileishmanial activity.
	PMID: 20578974 [PubMed - as supplied by publisher]

7.	Southeast Asian J Trop Med Public Health. 2009 Nov;40(6):1188-98. Evaluation of anti-leishmanial activity by induction of nitric oxide and inhibition of prostaglandin in Balb/c mice infected with Leishmania major. Nahrevanian H, Hajihosseini R, Arjmand M, Farahmand M, Ghasemi F. Department of Parasitology, Pasteur Institute of Iran, Tehran. mobcghn@yahoo.co.uk Abstract Cutaneous leishmaniasis is still one of the health problems in Iran and in the region. Nitric oxide (NO) has a key mechanism in the elimination of parasite from the body by its anti-leishmanial activity. Prostaglandin (PG) is a critical inhibitory factor of infected macrophage to decrease their anti-leishmanial activity. This study was designed to induce NO by L-arginine (L-Arg) precursor and inhibit PG production by anti-inflammatory Indomethacin (INDO) in Leishmania major infected Balb/c mice, in order to evaluate the effects of NO and PG on delay of lesion formation, size of lesion and proliferation of amastigotes inside macrophages. Liver, spleen and lymph nodes were also studied as target organs to detect amastigotes. Serum, liver and spleen suspensions were investigated for NO induction by using Griess microassay and serum PG was determined by ELISA. The results indicated that NO production was inhibited by Leishmania in infected Balb/c mice as compared with naive animals. Serum NO was inhibited by a combination therapy of L-Arg and INDO. Although NO was decreased in the liver by L-Arg, however it increased in the spleen after L-Arg and INDO application. A significant decline was observed in lesion size from Week 6 after infection by INDO. Both L-Arg and INDO had significant inhibitory effects on visceralization of leishmania in target organs. Only L-Arg decreased proliferation of promastigotes in macrophages. Pathophysiological signs including hepatomegaly, splenomegaly, survival rate and body weight all were affected in this experiment. Statistical analysis of data revealed an association between NO induction and PG inhibition in leishmaniasis. These data may indicate a possible candidatory for L-Arg and INDO as novel drugs for the treatment of leishmaniasis in mouse model.
	PMID: 20578452 [PubMed - in process]