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Sent on Tuesday, 2011 Jun 21Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | PLoS One. 2011;6(6):e20730. Epub 2011 Jun 8.An essential nuclear protein in trypanosomes is a component of mRNA transcription/export pathway.Serpeloni M, Moraes CB, Muniz JR, Motta MC, Ramos AS, Kessler RL, Inoue AH, Duarte Darocha W, Yamada-Ogatta SF, Fragoso SP, Goldenberg S, Freitas-Junior LH, Avila AR.SourceDepartamento de Biologia Celular e Molecular, Universidade Federal do Paraná (UFPR), Curitiba, Brazil. AbstractIn eukaryotic cells, different RNA species are exported from the nucleus via specialized pathways. The mRNA export machinery is highly integrated with mRNA processing, and includes a different set of nuclear transport adaptors as well as other mRNA binding proteins, RNA helicases, and NPC-associated proteins. The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, a widespread and neglected human disease which is endemic to Latin America. Gene expression in Trypanosoma has unique characteristics, such as constitutive polycistronic transcription of protein-encoding genes and mRNA processing by trans-splicing. In general, post-transcriptional events are the major points for regulation of gene expression in these parasites. However, the export pathway of mRNA from the nucleus is poorly understood. The present study investigated the function of TcSub2, which is a highly conserved protein ortholog to Sub2/ UAP56, a component of the Transcription/Export (TREX) multiprotein complex connecting transcription with mRNA export in yeast/human. Similar to its orthologs, TcSub2 is a nuclear protein, localized in dispersed foci all over the nuclei -except the fibrillar center of nucleolus- and at the interface between dense and non-dense chromatin areas, proposing the association of TcSub2 with transcription/processing sites. These findings were analyzed further by BrUTP incorporation assays and confirmed that TcSub2 is physically associated with active RNA polymerase II (RNA pol II), but not RNA polymerase I (RNA pol I) or Spliced Leader (SL) transcription, demonstrating participation particularly in nuclear mRNA metabolism in T. cruzi. The double knockout of the TcSub2 gene is lethal in T. cruzi, suggesting it has an essential function. Alternatively, RNA interference assays were performed in Trypanosoma brucei. It allowed demonstrating that besides being an essential protein, its knockdown causes mRNA accumulation in the nucleus and decrease of translation levels, reinforcing that Trypanosoma-Sub2 (Tryp-Sub2) is a component of mRNA transcription/export pathway in trypanosomes. |
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| 2. | Enzyme Res. 2011;2011:415976. Epub 2011 May 25.Biosynthesis of galactofuranose in kinetoplastids: novel therapeutic targets for treating leishmaniasis and chagas' disease.Oppenheimer M, Valenciano AL, Sobrado P.SourceDepartment of Biochemistry, Virginia Tech, Blacksburg, VA 24061, USA. AbstractCell surface proteins of parasites play a role in pathogenesis by modulating mammalian cell recognition and cell adhesion during infection. β-Galactofuranose (Galf) is an important component of glycoproteins and glycolipids found on the cell surface of Leishmania spp. and Trypanosoma cruzi. β-Galf-containing glycans have been shown to be important in parasite-cell interaction and protection against oxidative stress. Here, we discuss the role of β-Galf in pathogenesis and recent studies on the Galf-biosynthetic enzymes: UDP-galactose 4' epimerase (GalE), UDP-galactopyranose mutase (UGM), and UDP-galactofuranosyl transferase (GalfT). The central role in Galf formation, its unique chemical mechanism, and the absence of a homologous enzyme in humans identify UGM as the most attractive drug target in the β-Galf-biosynthetic pathway in protozoan parasites. |
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| 3. | J Map Geogr Libr. 2011 Jan 1;7(1):87-113.Embracing the Open-Source Movement for the Management of Spatial Data: A Case Study of African Trypanosomiasis in Kenya.< /h1>Langley SA, Messina JP.SourceDepartment of Geography Michigan State University, East Lansing, Michigan, USA. AbstractThe past decade has seen an explosion in the availability of spatial data not only for researchers, but the public alike. As the quantity of data increases, the ability to effectively navigate and understand the data becomes more challenging. Here we detail a conceptual model for a spatially explicit database management system that addresses the issues raised with the growing data management problem. We demonstrate utility with a case study in disease ecology: to develop a multi-scale predictive model of African Trypanosomiasis in Kenya. International collaborations and varying technical expertise necessitate a modular open-source software solution. Finally, we address three recurring problems with data management: scalability, reliability, and security. |
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| 4. | Stud Health Technol Inform. 2011;162:17-37.Topological analysis of metabolic networks based on petri net theory.Zevedei-Oancea I, Schuster S.SourceMax Delbrück Center for Molecular Medicine, Department of Bioinformatics, Berlin-Buch, Germany. AbstractPetri net concepts provide additional tools for the modelling of metabolic networks. Here, the similarities between the counterparts in traditional biochemical modelling and Petri net theory are discussed. For example the stoichiometry matrix of a metabolic network corresponds to the incidence matrix of the Petri net. The flux modes and conservation relations have the T-invariants, respectively, P-invariants as counterparts. We reveal the biological meaning of some notions specific to the Petri net framework (traps, siphons, deadlocks, liveness). We focus on the topological analysis rather than on the analysis of the dynamic behaviour. The treatment of external metabolites is discussed. Some simple theoretical examples are presented for illustration. Also the Petri nets corresponding to some biochemical networks are built to support our results. For example, the role of triose phosphate isomerase (TPI) in Trypanosoma brucei metabolism is evaluated by detecting siphons and traps. All Petri net properties treated in this contribution are exemplified on a system extracted from nucleotide metabolism. |
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| 5. | Mol Cell Proteomics. 2011 Jun 19. [Epub ahead of print]Independent analysis of t he flagellum surface and matrix proteomes provides insight into flagellum signaling in mammalian-infectious Trypanosoma brucei.Oberholzer M, Langousis G, Nguyen HT, Saada EA, Shimogawa MM, Jonsson ZO, Nguyen SM, Wohlschlelgel JA, Hill KL.SourceULCA, United States; AbstractThe flagellum of African trypanosomes is an essential and multifunctional organelle that functions in motility, cell morphogenesis and host-parasite interaction. Previous studies of the trypanosome flagellum have been limited by the inability to purify flagella without first removing the flagellar membrane. This limitation is particularly relevant in the context of studying flagellum signaling, as signaling requires surface-exposed proteins in the flagellar membrane and soluble signaling proteins in the flagellar matrix. Here we employ a combination of genetic and mechanical approaches to purify intact flagella from the African trypanosome, Trypanosoma brucei, in its mammalian-infectious stage. We combined flagellum purification with affinity-purification of surface-exposed proteins to conduct independent proteomic analyses of the flagellum surface and matrix fractions. The proteins identified encompass a broad range of molecular functionalities, including many predicted to function in signaling. Immunofluorescence and RNAi knockdown studies demonstrate flagellum localization and function for proteins identified and provide insight into mechanisms of flagellum attachment and motility. The flagellum surface proteome includes many T. brucei-specific proteins and is enriched for proteins upregulated in the mammalian-infectious stage of the parasite life-cycle. The combined results indicate that the flagellum surface presents a diverse and dynamic host-parasite interface that is well-suited for host-parasite signaling. |
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| 6. | J Leukoc Biol. 2011 Jun 17. [Epub ahead of print]Lutzomyia longipalpis saliva drives apoptosis and enhances parasite burden in neutrophils.Prates DB, Araújo-Santos T, Luz NF, Andrade BB, França-Costa J, Afonso L, Clarêncio J, Miranda JC, Bozza PT, Dosreis GA, Brodskyn C, Barral-Netto M, Borges VD, Barral A.Source*Centro de Pesquisa Gonçalo Moniz (CPqGM)-Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil; AbstractNeutrophils are considered the host's first line of defense against infections and have been implicated in the immunopathogenesis of Leishmaniasis. Leishmania parasites are inoculated alongside vectors' saliva, which is a rich source of pharmacologically active substances that interfere with host immune response. In the present study, we tested the hypothesis that salivary components from Lutzomyia longipalpis, an important vector of visceral Leishmaniasis, enhance neutrophil apoptosis. Murine inflammatory peritoneal neutrophils cultured in the presence of SGS presented increased surface expression of FasL and underwent caspase-dependent and FasL-mediated apoptosis. This proapoptosis effect of SGS on neutrophils was abrogated by pretreatment with protease as well as preincubation with antisaliva antibodies. Furthermore, in the presence of Leishmania chagasi, SGS also increased apoptosis on neutrophils and increased PGE(2) release and decreased ROS production by neutrophils, while enhancing parasite viability inside these cells. The increased parasite burden was abrogated by treatment with z-VAD, a pan caspase inhibitor, and NS-398, a COX-2 inhibitor. In the presence of SGS, Leishmania-infected neutrophils produced higher levels of MCP-1 and attracted a high number of macrophages by chemotaxis in vitro assays. Both of these events were abrogated by pretreatment of neutrophils with bindarit, an inhibitor of CCL2/MCP-1 expression. Taken together, our data support the hypothesis that vector salivary proteins trigger caspase-dependent and FasL-mediated apoptosis, thereby favoring Leishmania survival inside neutrophils, which may represent an important mechanism for the establishment of Leishmania infection. |
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| 7. | Bioorg Med Chem. 2011 Jun 1. [Epub ahead of print]Design, synthesis and antileishmanial in vitro activity of new series of chalcones-like compounds: A molecular hybridization approach.Barbosa TP, Sousa SC, Amorim FM, Rodrigues YK, de Assis PA, Caldas JP, Oliveira MR, Vasconcellos ML.SourceLaboratório de Síntese Orgânica Medicinal da Paraíba (LASOM-PB), Departamento de Química, Universidade Federal da Paraíba, Campus I, João Pessoa, PB 58059-900, Brazil. AbstractThe chalcone-like series 1a-1g was efficiently synthesized from Morita-Baylis-Hillman reaction (52-74% yields). Compounds 1a-1g were designed by molecular hybridization based on the anti-inflammatory drug methyl salicylate (3) and the antileishmanial moiety of the Morita-Baylis-Hillman adducts 2a-2g. The 1a-1g compounds were much more actives than precursor series 2a-2g, for example, IC(50)=7.65μM on Leishmania amazonensis and 10.14μM on Leishmania chagasi (compound 1c) when compared to IC(50)=50.08μM on L. amazonensis and 82.29μM on L. chagasi (compound 2c). The IC(50) values of compound 3 (228.49μM on L. amazonensis and 261.45μM on L. chagasi) and acryloyl salicylate 4 (108.50μM on L. amazonensis and 118.83μM on L. chagasi) were determined here, by the first time, on Leishmania. Copyright © 2011 Elsevier Ltd. All rights reserved. |
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| 8. | Mol Biochem Parasitol. 2011 Jun 12. [Epub ahead of print]Ca(2+)-activated transbilayer movement of plasma membrane phospholipids in Leishmania donovani during ionomycin or thapsigargin stimulation.Weingärtner A, Dos Santos MG, Drobot B, Pomorski TG.SourceHumboldt-Universität zu Berlin, Faculty of Mathematics and Natural Science I, Institute of Biology, Invalidenstraße 42, 10115 Berlin, Germany. AbstractThe protozoan parasite Leishmania causes serious infections in humans all over the world. After being inoculated into the skin through the bite of an infected sandfly, Leishmania promastigotes must gain entry into macrophages to initiate a successful infection. Specific, surface exposed phospholipids have been implicated in Leishmania-macrophage interaction but the mechanisms controlling and regulating the plasma membrane lipid distribution remains to be elucidated. Here, we provide evidence for Ca(2+)-induced phospholipid scrambling in the plasma membrane of Leishmania donovani. Stimulation of parasites with ionomycin increases intracellular Ca(2+) levels and triggers exposure of phosphatidylethanolamine at the cell surface. We found that increasing intracellular Ca(2+) levels with ionomycin or thapsigargin induces rapid transbilayer movement of NBD-labelled phospholipids in the parasite plasma membrane that is bidirectional, independent of cellular ATP and not specific to the polar lipid head group. The findings suggest the presence of a Ca(2+)-dependent lipid scramblase activity in Leishmania parasites. Our studies further show that lipid scrambling is not activated by rapid exposure of promastigotes to higher physiological temperature that increases intracellular Ca(2+) levels. Copyright © 2011 Elsevier B.V. All rights reserved. |
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| 9. | Exp Parasitol. 2011 Jun 13. [Epub ahead of print]Use of a fluorescent stain for evaluating in vitro infection with Leishmania panamensis.Perez-Cordero JJ, Sánchez-Suárez J, Delgado G.SourceImmunotoxicology Research Group, Department of Pharmacy, Faculty of Science, Universidad Nacional de Colombia, Bogotá, Colombia. AbstractLeishmaniasis is a group of endemic diseases produced by infection with Leishmania parasites and affects tropical and subtropical regions of the world. Due to the severe problems related to the treatment of this condition (resistance and toxicity), further studies are needed to evaluate new antileishmanial compounds. The activity of antileishmanial prototypes should be analyzed in models that allow a better interpretation of the findings with respect to natural infection. In this sense, the use of an infection model with macrophages and dendritic cells is a better than using promastigotes alone, in order to establish the potential leishmanicidal activity of a prototype compound. For infection analysis, staining with polychromatic dyes such as Giemsa plus microscopic examination is the gold standard. However, it is common to find problems associated with color uniformity, expertise of the observer, sensitivity and specificity of the technique. For this reason, it necessary to develop tools and protocols to overcome such limitations. This study assessed the utility of the SYBR® Safe fluorescent dye, considering its affinity for nucleic acids as a useful property for staining the nucleus and kinetoplast of Leishmania parasites within an infected cell. Infection (and subsequent treatment) assays were performed in dendritic cells and macrophages infected with Leishmania panamensis parasites to compare SYBR® Safe and Giemsa stain for the same assay. Correlation coefficients were found to be above 0.9 for both techniques; however, unlike Giemsa, SYBR® Safe staining was easier and provided a clearer observation of internalized parasites. These results support the use of SYBR® Safe as a promising tool for evaluating potential antileishmanials given its advantages over the traditional technique. Copyright © 2011 Elsevier Inc. All rights reserved. |
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| 10. | Int J Infect Dis. 2011 Jun 15. [Epub ahead of print]Human African trypanosomiasis: a review of non-endemic cases in the past 20 years.Migchelsen SJ, Büscher P, Hoepelman AI, Schallig HD, Adams ER.SourceRoyal Tropical Institute - Biomedical Research, Parasitology, Meibergdreef 39, 1105 AZ Amsterdam, the Netherlands; Department of Internal Medicine and Infectious Disease, University Medical Centre, Universiteit Utrecht, Utrecht, the Netherlands. AbstractHuman African trypanosomiasis (HAT) is caused by sub-species of the parasitic protozoan Trypanosoma brucei and is transmitted by tsetse flies, both of which are endemic only to sub-Saharan Africa. Several cases have been reported in non-endemic areas, such as North America and Europe, due to travelers, ex-patriots or military personnel returning from abroad or due to immigrants from endemic areas. In this paper, non-endemic cases reported over the past 20 years are reviewed; a total of 68 cases are reported, 19 cases of Trypanosoma brucei gambiense HAT and 49 cases of Trypanosoma brucei rhodesiense HAT. Patients ranged in age from 19 months to 72 years and all but two patients survived. Physicians in non-endemic areas should be aware of the signs and symptoms of this disease, as well as methods of diagnosis and treatment, especially as travel to HAT endemic areas increases. We recommend extension of the current surveillance systems such as TropNetEurop and maintaining and promotion of existing reference centers of diagnostics and expertise. Important contact information is also included, should physicians require assistance in diagnosing or treating HAT. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. |
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