Thursday, September 24, 2009

What's new for 'Trypanosomatids' in PubMed

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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 -8 of 8

1: Bioorg Med Chem Lett. 2009 Sep 3. [Epub ahead of print]

Novel non-peptidic vinylsulfones targeting the S2 and S3 subsites of parasite cysteine proteases.

Bryant C, Kerr ID, Debnath M, Ang KK, Ratnam J, Ferreira RS, Jaishankar P, Zhao D, Arkin MR, McKerrow JH, Brinen LS, Renslo AR.

Small Molecule Discovery Center, University of California, San Francisco, CA 94158, United States; Sandler Center for Basic Research on Parasitic Disease, University of California, San Francisco, CA 94158, United States.

We describe here the identification of non-peptidic vinylsulfones that inhibit parasite cysteine proteases in vitro and inhibit the growth of Trypanosoma brucei brucei parasites in culture. A high resolution (1.75A) co-crystal structure of 8a bound to cruzain reveals how the non-peptidic P2/P3 moiety in such analogs bind the S2 and S3 subsites of the protease, effectively recapitulating important binding interactions present in more traditional peptide-based protease inhibitors and natural substrates.

PMID: 19773167 [PubMed - as supplied by publisher]

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2: Rev Bras Parasitol Vet. 2009 Abr-Jun;18(3):46-51.

[Allochthonous cases of canine visceral leishmaniasis in Paraná, Brazil: epidemiological implications.]

[Article in Portuguese]

Tomaz-Soccol V, Castro EA, Navarro IT, de Farias MR, de Souza LM, Carvalho Y, Bispo S, Membrive NA, Minozzo JC, Truppel J, Bueno W, Luz E.

Laboratório Parasitologia Molecular, Setor de Ciências Biológicas, Centro Politécnico, Universidade Federal do Paraná - UFPR, Rua Cel. Francisco H. dos Santos, s/n, Jardim das Américas, CEP 81531-990 Curitiba - PR, Brasil. vasoccol@ufpr.br.

The south region is the only area in Brazil that does not present autochthonous cases of visceral leishmaniasis (VL), however, in the state of Paraná, dogs and humans have been found showing a VL compatible clinical profle. In view of this problem, the present work aimed at isolating and identifying the parasite and determining the cases autochthony. All animals clinically suspect of VL were clinically evaluated, and had samples of their blood collected for hemoculture (NNN culture medium), serology, PCR and RAPD-PCR, hemogram, and biochemical assays. The dogs presenting VL clinical profle had their lymph nodes and/or bone marrow punctured and their content inoculated in NNN culture medium. The protozoan isolated was identifed by PCR and PCR-RAPD. Strains of Leishmania were isolated in 19 out of the 24 studied animals. Fourteen isolates were identifed as L. (Leishmania) infantum, and fve were L. (Viannia) braziliensis. In the epidemiological analysis, it was possible to determine that all dogs with L. (L.) infantum being allochthonous cases. Leishmaniasis is a zoonose that has the domestic dog as reservoir, the migration of such animals can disseminate the parasite to other regions, provided the agent fnds an adequate ecotope and a specifc vector (Lutzomyia longipalpis).

PMID: 19772775 [PubMed - as supplied by publisher]

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3: Rev Bras Parasitol Vet. 2009 Jul-Sep;18(3):24-40.

Epidemiological profle of cutaneous leishmaniasis in an endemic region in the State of Rio de Janeiro, Brazil.

de Bustamante MC, Pereira MJ, Schubach Ade O, da Fonseca AH.

Departamento de Parasitologia Animal, Instituto de Veterinária - IV, Universidade Federal Rural do Rio de Janeiro - UFRRJ, BR 465, km 7, CEP 2389-000 Seropédica - RJ, Brazil. m.salim@ufrrj.br.

The objective of the present study was to investigate the dynamics and profle of American Cutaneous Leishmaniasis (ACL) in an old colonization area in the State of Rio de Janeiro. Health departments of municipalities in the Central-Southern region that had notifed cases to the Ministry of Health's Notifable Diseases Information System between 1997 and 2002 were contacted to obtain data. Out of the 119 cases recorded, 51 patients were visited for an interview and inspection of the environment. The cases of ACL exhibited a profle similar to that observed in other Brazilian cities, afecting individuals of both genders, all age groups and diferent occupational categories, especially students. Risk activities were reported by 56.9% of the interviewees and 84.3% had never left their homeland. Water courses, chicken coops, bamboo plantations and diferent fruit trees including banana plants and mango trees were frequently observed in the surrounding environment. Most of the interviewees had not noted any environmental changes prior to becoming sick. Domestic animals were present in all homes, but only dogs presented lesions suggestive of the disease. These were on diferent occasions that rarely preceded or coincided with the human cases. The possible existence of distinct transmission cycles, i.e. one for canines and another for humans, was discussed.

PMID: 19772772 [PubMed - in process]

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4: BMC Cell Biol. 2009 Sep 21;10(1):68. [Epub ahead of print]

CRK9 contributes to regulation of mitosis and cytokinesis in the procyclic form of Trypanosoma brucei.

Gourguechon S, Wang CC.

ABSTRACT: BACKGROUND: The Trypanosoma brucei cell cycle is regulated by combinations of cyclin/CRKs (cdc2 related kinases). Recently, two additional cyclins (CYC10, CYC11) and six new CRK (CRK7-12) homologues were identified in the T. brucei genome database [1, 2]. RESULTS: Individual RNAi knockdowns of these new proteins in the procyclic form of T. brucei showed no apparent phenotype except for the CRK9 depletion, which enriched the cells in G2/M phase. But a similar CRK9 knockdown in the bloodstream form caused no apparent phenotype. CRK9 lacks the typical PSTAIRE motif for cyclin binding and the phenylalanine "gatekeeper" but binds to cyclin B2 in vitro and localizes to the nucleus in both forms of T. brucei. CRK9-depleted procyclic-form generated no detectable anucleate cells, suggesting an inhibition of cytokinesis by CRK9 depletion as well. The knockdown enriched cells with one nucleus, one kinetoplast and two closely associated basal bodies with an average distance of 1.08 mum in between, which was shorter than the control value of 1.36 mum, and the cells became morphologically deformed and rounded with time. CONCLUSIONS: CRK9 may play a role in mediating the segregation between the two kinetoplast/basal body pairs prior to cytokinetic initiation. Since such a segregation over a relatively significant distance is essential for cytokinetic initiation only in the procyclic but may not be in the bloodstream form, CRK9 could be specifically involved in regulating cytokinetic initiation in the procyclic form of T. brucei.

PMID: 19772588 [PubMed - as supplied by publisher]

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5: Parasit Vectors. 2009 Sep 21;2(1):43. [Epub ahead of print]

Intraclonal mating occurs during tsetse transmission of Trypanosoma brucei.

Peacock L, Ferris V, Bailey M, Gibson W.

ABSTRACT: BACKGROUND: Mating in Trypanosoma brucei is a non-obligatory event, triggered by the co-occurrence of different strains in the salivary glands of the vector. Recombinants that result from intra- rather than interclonal mating have been detected, but only in crosses of two different trypanosome strains. This has led to the hypothesis that when trypanosomes recognize a different strain, they release a diffusible factor or pheromone that triggers mating in any cell in the vicinity whether it is of the same or a different strain. This idea assumes that the trypanosome can recognize self and non-self, although there is as yet no evidence for the existence of mating types in T. brucei. RESULTS: We investigated intraclonal mating in T. b. brucei by crossing red and green fluorescent lines of a single strain, so that recombinant progeny can be detected in the fly by yellow fluorescence. For strain 1738, seven flies had both red and green trypanosomes in the salivary glands and, in three, yellow trypanosomes were also observed, although they could not be recovered for subsequent analysis. Nonetheless, both red and non-fluorescent clones from these flies had recombinant genotypes as judged by microsatellite and karyotype analyses, and some also had raised DNA contents, suggesting recombination or genome duplication. Strain J10 produced similar results indicative of intraclonal mating. In contrast, trypanosome clones recovered from other flies showed that genotypes can be transmitted with fidelity. When a yellow hybrid clone expressing both red and green fluorescent protein genes was transmitted, the salivary glands contained a mixture of fluorescent-coloured trypanosomes, but only yellow and red clones were recovered. While loss of the GFP gene in the red clones could have resulted from gene conversion, some of these clones showed loss of heterozygosity and raised DNA contents as in the other single strain transmissions. Our observations suggest that many recombinants are non-viable after intraclonal mating. CONCLUSIONS: We have demonstrated intraclonal mating during fly transmission of T. b. brucei, contrary to previous findings that recombination occurs only when another strain is present. It is thus no longer possible to assume that T. b. brucei remains genetically unaltered after fly transmission.

PMID: 19772562 [PubMed - as supplied by publisher]

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6: Trop Med Int Health. 2009 Oct;14(10):1272-7.

Susceptibility to chemical insecticides of two Brazilian populations of the visceral leishmaniasis vector Lutzomyia longipalpis (Diptera: Psychodidae).

Alexander B, Barros VC, de Souza SF, Barros SS, Teodoro LP, Soares ZR, Gontijo NF, Reithinger R.

Departamento de Parasitologia, Instituto de Ciências Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerias, Brazil. bruce.alexander@.xeroshield.co.uk

OBJECTIVES: To investigate the insecticide susceptibility of two geographically separated Lutzomyia longipalpis populations (Lapinha and Montes Claros) with different histories of insecticide exposure (i.e. no exposure and repeated exposure, respectively). METHODS: (i) Bioassay monitoring of sand fly survival over time when exposed to a range of insecticides; and (ii) analysis of the level of insecticide detoxification enzymes in individual sand flies caught at both study sites. Insecticides tested were the organophosphates malathion and fenitrothion and the pyrethroids lambda-cyhalothrin, permethrin and deltamethrin. RESULTS: Survival analyses showed that whilst there was no overall significant difference in susceptibility of both populations to organophosphates, Lapinha sand flies were significantly more susceptible to pyrethroids than those from Montes Claros. Multiple regression analyses also showed that insecticide susceptibility in both locations varied with sand fly sex. The relative susceptibilities of the two sand fly populations to tested insecticides were also compared. Thus, Montes Claros sand flies were most susceptible to malathion, followed by fenitrothion, deltamethrin and permethrin. Those from Lapinha were most susceptible to lambda-cyhalothrin, followed by malathion, permethrin, deltamethrin and fenitrothion. Biochemical analyses demonstrated that Montes Claros sand flies had significantly lower insecticide detoxification enzyme activity than Lapinha sand flies. CONCLUSIONS: Our results are the first record of significantly reduced susceptibility to the insecticides used in control of wild populations of Lu. longipalpis. They demonstrate the importance of evaluating chemicals against this species by conventional bioassay and microplate assays before and during spraying programmes.

PMID: 19772549 [PubMed - in process]

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  • Permethrin (Elimite®, Nix® Creme Rinse)

    Permethrin kills parasites and their eggs. It is used to treat scabies (a skin infestation) and lice infestations of the head, body, and pubic area ('crabs'). Permethrin does not prevent these infestations.

  • Source: AHFS Consumer Medication Information
7: J Immunol. 2009 Sep 15;183(6):4103-8. Epub 2009 Aug 19.Click here to read LinkOut

Chronic human infection with Trypanosoma cruzi drives CD4+ T cells to immune senescence.

Albareda MC, Olivera GC, Laucella SA, Alvarez MG, Fernandez ER, Lococo B, Viotti R, Tarleton RL, Postan M.

Instituto Nacional de Parasitología Dr M Fatala Chaben, Buenos Aires, Argentina.

Previously we found that the frequency of IFN-gamma-producing CD8(+) T cells specific for Trypanosoma cruzi inversely correlates with disease severity in chronic human Chagas disease along with low levels of IL-2-secreting CD8(+) T cells in all clinical stages. This impairment of the parasite-specific T cell responses was associated with phenotypic features of immune senescence of the CD8(+) T cell compartment. These data prompted us to address the question of whether the CD4(+) T cell compartment also experiences signs of exhaustion. Thus, we performed a functional and phenotypical characterization of T. cruzi-specific and overall CD4(+) T cells in chronically infected subjects with different degrees of cardiac dysfunction. The results show an inverse association between disease severity and the frequency of T. cruzi-specific IFN-gamma-producing CD4(+) T cells. The high expression of CD27 and CD28 with a relative low expression of CD57 found on CD4(+)IFN-gamma(+) T cells suggests that the effector T cell pool in chronic T. cruzi infection includes a high proportion of newly recruited T cells, but a low frequency of long-term memory cells. The total CD4(+) T cell compartment shows signs of senescence and later stages of differentiation associated with more severe stages of the disease. These findings support the hypothesis that long-term T. cruzi infection in humans might exhaust long-lived memory T cells.

PMID: 19692645 [PubMed - indexed for MEDLINE]

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8: J Proteome Res. 2009 Jul;8(7):3642-52.Click here to read LinkOut

Proteomic analysis of detergent-solubilized membrane proteins from insect-developmental forms of Trypanosoma cruzi.

Cordero EM, Nakayasu ES, Gentil LG, Yoshida N, Almeida IC, da Silveira JF.

Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, UNIFESP, Rua Botucatu, 862, CEP 04023-062, São Paulo, Brazil.

The cell surface of Trypanosoma cruzi, the etiologic agent of Chagas disease, is covered by a dense layer of glycosylphosphatidylinositol (GPI)-anchored molecules. These molecules are involved in a variety of interactions between this parasite and its mammalian and insect hosts. Here, using the neutral detergent Triton X-114, we obtained fractions rich in GPI-anchored and other membrane proteins from insect developmental stages of T. cruzi. These fractions were analyzed by two-dimensional liquid chromatography coupled to tandem mass spectrometry (2D-LC-MS/MS), resulting in the identification of 98 proteins of metacyclic trypomastigotes and 280 of epimastigotes. Of those, approximately 65% (n=245) had predicted lipid post-translational modification sites (i.e., GPI-anchor, myristoylation, or prenylation), signal-anchor sequence, or transmembrane domains that could explain their solubility in detergent solution. The identification of some of these modified proteins was also validated by immunoblotting. We also present evidence that, in contrast to the noninfective proliferative epimastigote forms, the infective nonproliferative metacyclic trypomastigote forms express a large repertoire of surface glycoproteins, such as GP90 and GP82, which are involved in adhesion and invasion of host cells. Taken together, our results unequivocally show stage-specific protein profiles that appear to be related to the biology of each T. cruzi insect-derived developmental form.

PMID: 19374451 [PubMed - indexed for MEDLINE]

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