What's new for 'Trypanosomatids' in PubMed

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Sent on Tuesday, 2010 Aug 03
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 - 6 of 6

1.	Eukaryot Cell. 2010 Jul 30. [Epub ahead of print] Functional Characterization of Three Leishmania PABP Homologues with Distinct Binding Properties to RNA and Protein Partners. da Costa Lima TD, Moura DM, Reis CR, Vasconcelos JR, Ellis L, Carrington M, Figueiredo RC, de Melo Neto OP. Departamento de Microbiologia, Centro de Pesquisas Aggeu Magalhães/Fiocruz, Av. Moraes Rego s/n, Campus UFPE, Recife, PE, Brazil, 50670-420; Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge UK CB2 1GA. Abstract Trypanosomatid protozoans are reliant on post-transcriptional processes to control gene expression. Regulation occurs at the level of mRNA processing, stability and translation, events that may require the participation of the poly(A) binding protein (PABP). Here, we have undertaken a functional study of the three distinct Leishmania major PABP homologues: the previously described LmPABP1; LmPABP2, orthologous to the PABP described from Trypanosoma species; and LmPABP3, unique to Leishmania. Sequence identity between the three PABPs is no greater than 40%. In assays measuring binding to A-rich sequences, LmPABP1 binding was poly(A) sensitive but heparin insensitive; LmPABP2 binding was heparin sensitive and less sensitive to poly(A), compatible with unique substitutions observed in residues implicated in poly(A) binding; and LmPABP3 displayed intermediate properties. All three homologues are simultaneously expressed as abundant cytoplasmic proteins in L. major promastigotes but only LmPABP1 is present as multiple isoforms. Upon transcription inhibition, LmPABP2 and 3 migrated to the nucleus whilst LmPABP1 remained predominantly cytoplasmic. Immunoprecipitation assays showed an association between LmPABP2 and 3. Although the three proteins bound to a Leishmania homologue of the translation initiation factor eIF4G (LmEIF4G3) in vitro, LmPABP1 was the only one to co-purify with native LmEIF4G3 from cytoplasmic extracts. Functionality was tested using RNAi in T. brucei where both orthologues to LmPABP1 and 2 are required for cellular viability. Our results indicate that these homologues have evolved divergent functions, some of which may be unique to the trypanosomatids, and reinforces a role for LmPABP1 in translation, through its interaction with the eIF4G homologue.
	PMID: 20675580 [PubMed - as supplied by publisher]

2.	J Biol Chem. 2010 Jul 30. [Epub ahead of print] Leishmania subtilisin is a maturase for the trypanothione reductase system and contributes to disease pathology. Swenerton RK, Knudsen GM, Sajid M, Kelly BL, McKerrow JH. UC San Francisco, United States; Abstract Proteases are a ubiquitous group of enzymes that play key roles in the life cycle of parasites, in the host-parasite relationship, and in the pathogenesis of parasitic diseases. Furthermore, proteases are druggable targets for the development of new anti-parasitic therapy. The subtilisin protease (SUB; Clan SB, family S8) of Leishmania donovani was cloned and found to possess a unique catalytic triad. This gene was then deleted by gene knockout, which resulted in reduced ability by the parasite to undergo promastigote to amastigote differentiation in vitro. Electron microscopy of SUB knockout amastigotes revealed abnormal membrane structures, retained flagella, and increased binucleation. SUB deficient Leishmania displayed reduced virulence in both hamster and murine infection models. Histology of spleens from SUB knockout-infected hamsters revealed the absence of psammoma body calcifications indicative of the granulomatous lesions that occur during Leishmania infection. To delineate the specific role of SUB in parasite physiology, two-dimensional gel electrophoresis was carried out on SUB -/- versus wildtype parasites. SUB knockout parasites showed altered regulation of the terminal peroxidases of the trypanothione reductase system. Leishmania and other trypanosomatids lack glutathione reductase, and therefore rely on the novel trypanothione reductase system to detoxify reactive oxygen intermediates and to maintain redox homeostasis. The predominant tryparedoxin peroxidases were decreased in SUB -/- parasites, and higher molecular weight isoforms were present, indicating altered processing. In addition, knockout parasites showed increased sensitivity to hydroperoxide. These data suggest that subtilisin is the maturase for tryparedoxin peroxidases and is necessary for full virulence.
	PMID: 20675366 [PubMed - as supplied by publisher]

3.	Environ Health Perspect. 2010 Aug 1. [Epub ahead of print] Artificial Lighting as a Vector Attractant and Cause of Disease Diffusion. Barghini A, de Medeiros BA. Universidade de São Paulo. Abstract Background Traditionally, epidemiologists have considered electrification to be a positive factor. In fact, electrification as well as plumbing are typical initiatives that represent the integration of an isolated population into modern society, ensuring the control of pathogens and promoting public health. Nonetheless, electrification is always accompanied by night lighting, which attracts insect vectors and changes people's behavior. Although this may lead to new modes of infection and increased transmission of insect-borne diseases, the role of night lighting is rarely considered in epidemiological surveys. Objectives This paper reviews evidence concerning the role of lighting in the spread of diseases as documented in epidemiological literature, in order to encourage other researchers to consider this element in future studies. Discussions We present three case studies of infectious vector-borne diseases (Chagas, leishmaniasis, and malaria) and discuss evidence which suggests that use of artificial lighting results in behavioral changes and changes in the prevalence of vector species and modes of transmission. Conclusion Despite a surprising lack of studies, we conclude that existing evidence supports our hypothesis that artificial lighting leads to a higher risk of infection with vector-borne diseases. We believe that this is not only related to the simple attraction of traditional vectors to light sources, but also to changes in the behavior of both humans and insects that result in new modes of disease transmission. Considering the ongoing expansion of night lighting in developing countries, additional research on this subject is urgently needed.
	PMID: 20675268 [PubMed - as supplied by publisher]

4.	Bioorg Med Chem. 2010 Jul 29. [Epub ahead of print] Design, synthesis, and in vitro antiprotozoal, antimycobacterial activities of N-{2-[(7-chloroquinolin-4-yl)amino]ethyl}ureas. Nava-Zuazo C, Estrada-Soto S, Guerrero-Álvarez J, León-Rivera I, Molina-Salinas GM, Said-Fernández S, Chan-Bacab MJ, Cedillo-Rivera R, Moo-Puc R, Mirón-López G, Navarrete-Vazquez G. Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico. Abstract We have synthesized a new series of quinoline tripartite hybrids from chloroquine, ethambutol, and isoxyl drugs, using a short synthetic route. Compounds 1-8 were tested in vitro against five protozoa (Giardia intestinalis, Trichomonas vaginalis,Entamoeba histolytica, Leishmania mexicana and Trypanosoma cruzi) and Mycobacterium tuberculosis. N-(4-Butoxyphenyl)-N'-{2-[(7-chloroquinolin-4-yl)amino]ethyl}urea (6) was the most active compound against all parasites tested. Compound 6 was 670 times more active than metronidazole, against G. intestinalis. It was as active as pentamidine against L. mexicana, and it was twofold more potent than ethambutol and isoxyl versus M. tuberculosis. This compound could be considered as a new broad spectrum antimicrobial agent. Copyright © 2010 Elsevier Ltd. All rights reserved.
	PMID: 20674375 [PubMed - as supplied by publisher]

5.	Med Hypotheses. 2010 Jul 29. [Epub ahead of print] Efficacy of photodynamic therapy in cutaneous leishmaniasis: A "hidden" local heat effect? Kluger N, Girard C, Debu A, Guillot B. Université Montpellier I, Service de dermatologie, Hôpital Saint-Eloi, CHU de Montpellier, 80, Avenue Augustin Fliche, FR-34295 Montpellier Cedex 5, France Tel.: +33 4 67 33 69 06; fax: +33 4 67 33 69 58.
	PMID: 20673703 [PubMed - as supplied by publisher]

6.	Immunology. 2010 Jul 28. [Epub ahead of print] Natural killer cells support the induction of protective immunity during dendritic cell-mediated vaccination against Leishmania major. Remer KA, Roeger B, Hambrecht C, Moll H. University of Würzburg, Institute for Molecular Infection Biology, Würzburg, Germany. Abstract Summary Dendritic cell (DC)-mediated vaccination against Leishmania major induces a parasite-specific T helper 1 (Th1) response and long-lasting protective immunity in susceptible mice. As the cytokine interleukin-12 required for induction of this Th1 response is not derived from the transferred DC, but has to be produced by the vaccinated host, we examined cross-presentation of transferred DC via resident DC of the host and cross-activation with natural killer (NK) cells as mechanisms supporting the induction of protective immunity after DC-mediated vaccination. Co-culture with DC that had been conditioned ex vivo by loading with L. major lysate and stimulation with CpG-containing oligodeoxynucleotides did not result in the activation of naive DC in vitro. Furthermore, L. major antigen from conditioned DC was not cross-presented to a significant extent in vivo. In contrast, co-culture of DC with NK cells led to cross-activation of both cell populations with induction of interferon-gamma, which was dependent on the activation status of the conditioned DC. Transient depletion of NK cells during vaccination of L. major-susceptible mice with conditioned DC resulted in reduced protection. Our findings indicate that cross-presentation of conditioned DC after DC-based vaccination against L. major plays a minor role in the induction of protective immunity. However, we demonstrated for the first time that the capacity of DC to mediate protection against L. major is supported by cross-activation with NK cells of the host and NK-cell-derived interferon-gamma.
	PMID: 20673238 [PubMed - as supplied by publisher]