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Sent on Saturday, 2010 Feb 06Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Am J Trop Med Hyg. 2010 Feb;82(2):251-6.Leishmania infection: laboratory diagnosing in the absence of a "gold standard".Rodríguez-Cortés A, Ojeda A, Francino O, López-Fuertes L, Timón M, Alberola J.Unitat de Farmacologia Veterinària and LeishLAB-Servei d'Anàlisi de Fàrmacs, Departament de Farmacologia, de Terapèutica i de Toxicologia, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain; Servei Veterinari de Genètica Molecular, Departament de Ciència Animal i dels Aliments, Facultat de Veterinària, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain; Innoqua, Toxicology Consultants, Barcelona, Spain; Agencia Española del Medicamento, Madrid, Spain. There is no gold standard for diagnosing leishmaniases. Our aim was to assess the operative validity of tests used in detecting Leishmania infection using samples from experimental infections, a reliable equivalent to the classic definition of gold standard. Without statistical differences, the highest sensitivity was achieved by protein A (ProtA), immunoglobulin (Ig)G2, indirect fluorescenece antibody test (IFAT), lymphocyte proliferation assay, quantitative real-time polymerase chain reaction of bone marrow (qPCR-BM), qPCR-Blood, and IgG; and the highest specificity by IgG1, IgM, IgA, qPCR-Blood, IgG, IgG2, and qPCR-BM. Maximum positive predictive value was obtained simultaneously by IgG2, qPCR-Blood, and IgG; and maximum negative predictive value by qPCR-BM. Best positive and negative likelihood ratios were obtained by IgG2. The test having the greatest, statistically significant, area under the receiver operating characteristics curve was IgG2 enzyme-linked immunosorbent assay (ELISA). Thus, according to the gold standard used, IFAT and qPCR are far from fulfilling the requirements to be considered gold standards, and the test showing the highest potential to detect Leishmania infection is Leishmania-specific ELISA IgG2. |
| PMID: 20134001 [PubMed - in process] | |
| 2. | Am J Trop Med Hyg. 2010 Feb;82(2):243-50.Environmental risk factors for the incidence of american cutaneous leishmaniasis in a sub-andean zone of Colombia (chaparral, tolima).Valderrama-Ardila C, Alexander N, Ferro C, Cadena H, Marín D, Holford TR, Munstermann LE, Ocampo CB.Biology Department, Universidad Icesi, Cali, Colombia; Centro Internacional de Entrenamiento e Investigaciones Médicas, Cali, Colombia; Laboratorio de Entomología Médica, Instituto Nacional de Salud, Bogotá, Colombia; Biology Department, Universidad del Tolima, Tolima, Colombia; Department of Public Health, Yale University, New Haven, Connecticut. Environmental risk factors for cutaneous leishmaniasis were investigated for the largest outbreak recorded in Colombia. The outbreak began in 2003 in Chaparral, and in the following five years produced 2,313 cases in a population of 56,228. Candidate predictor variables were land use, elevation, and climatic variables such as mean temperature and precipitation. Spatial analysis showed that incidence of cutaneous leishmaniasis was higher in townships with mean temperatures in the middle of the county's range. Incidence was independently associated with higher coverage with forest or shrubs (2.6% greater for each additional percent coverage, 95% credible interval [CI] = 0.5-4.9%), and lower population density (22% lower for each additional 100 persons/km(2), 95% CI = 7-41%). The extent of forest or shrub coverage did not show major changes over time. These findings confirmed the roles of climate and land use in leishmaniasis transmission. However, environmental variables were not sufficient to explain the spatial variation in incidence. |
| PMID: 20134000 [PubMed - in process] | |
| 3. | Bioorg Med Chem. 2010 Jan 11. [Epub ahead of print]Antimalarial and antitubercular nostocarboline and eudistomin derivatives: Synthesis, in vitro and in vivo biological evaluation.Bonazzi S, Barbaras D, Patiny L, Scopelliti R, Schneider P, Cole ST, Kaiser M, Brun R, Gademann K.Chemical Synthesis Laboratory (SB-ISIC-LSYNC), Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland. The synthesis of nine nostocarboline derivatives with substitutions of the 2-methyl group by alkyl, aryl and functionalized residues, 10 symmetrical bis cationic dimers linking 6-Cl-norharmane through the 2-position and fifteen derivatives of the marine alkaloids eudistomin N and O is reported. These compounds were evaluated in vitro against four parasites (Trypanosoma brucei rhodesiense STIB 900, Trypanosoma cruzi Tulahuen C2C4, Leishmania donovani MHOM-ET-67/L82 axenic amastigotes, and Plasmodium falciparum K1 strain), against Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis mc(2)155 and Corynebacterium glutamicum ATCC13032, and cytotoxicity was determined against L6 rat myoblast cells. Nostocarboline and derivatives displayed potent and selective in vitro inhibition of P. falciparum with weak cytotoxicity. The dimers displayed submicromolar inhibition of L. donovani and T. brucei, and nanomolar activity against P. falciparum, albeit with pronounced cytotoxicity. One dimer showed a MIC(99) value against M. tuberculosis of 2.5mug/ml. The alkylated eudistomin N and O derivatives displayed activities down to 18nM against P. falciparum for N-Me Eudistomin N. Four dimers, nostocarboline and three eudostomin derivatives were evaluated in an in vivo Plasmodium berghei mouse model. No significant activity was observed for the dimers, but a 50% reduction in parasitaemia was observed at 4x50mg/kg ip for nostocarboline. Copyright © 2010 Elsevier Ltd. All rights reserved. |
| PMID: 20133138 [PubMed - as supplied by publisher] | |
| 4. | Vet Immunol Immunopathol. 2010 Jan 21. [Epub ahead of print]Diminished CD4+/CD25+ T cell and increased IFN-gamma levels occur in dogs vaccinated with Leishmune((R)) in an endemic area for visceral leishmaniasis.de Lima VM, Ikeda FA, Rossi CN, Feitosa MM, de Oliveira Vasconcelos R, Nunes CM, Goto H.Departamento de Clínica, Cirugia e Reproduçãp Animal, Faculdade de Odontologia, Curso de Medicina Veterinária, Universidade Estadual Paulista "Júlio de Mesquita Filho", Araçatuba Campus, SP, Brazil. The Leishmune((R)) vaccine has been used in endemic areas to prevent canine visceral leishmaniasis in Brazil, but cytokine production induced by vaccination has rarely been investigated in dogs. This study aimed to evaluate the immune response of dogs vaccinated with Leishmune FML vaccine (Fort Dodge) against total antigen of Leishmania (Leishmania) chagasi (TAg) and FML. Twenty healthy dogs from Araçatuba, São Paulo, Brazil, an endemic leishmaniasis area, received three consecutive subcutaneous injection of Leishmune vaccine at 21-day intervals. PBMC were isolated before and 10 days after completing vaccination and lymphoproliferative response and antibody production against FML or total promastigote antigen were tested. Cytokines IFN-gamma, IL-4 and TNF-alpha were measured in culture supernatant and CD4+/CD25+ and CD8+/CD25+ T cell presence was determined. Analysis of the data indicated that the vaccine conferred humoral responses (100%) against both antigens and cellular immunity to FML (85%) and total antigen (80%), the supernatant of cultured cells stimulated with TAg and FML showed an increase in IFN-gamma (P<0.05), and the vaccine reduced CD4+/CD25+ T cell presence compared to that observed before vaccination. These responses may constitute part of the immune mechanism induced by Leishmune. Copyright © 2010 Elsevier B.V. All rights reserved. |
| PMID: 20132994 [PubMed - as supplied by publisher] | |
| 5. | Parasitol Int. 2010 Feb 1. [Epub ahead of print]Momordicatin purified from fruits of momordica charantia is effective to act as a potent antileishmania agent.Gupta S, Raychaudhuri B, Banerjee S, Das B, Mukhopadhaya S, Datta SC.Department of Biological Chemistry, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata 700032, India. Aqueous extract of the green fruits of the Indian plant Momordica charantia and purified Momordicatin structurally established as 4- (o-carboethoxyphenyl) butanol were evaluated in vitro and in vivo against Kala-azar caused by Leishmania donovani. 50% inhibitory concentration (IC(50)) against Leishmania promastigotes in vitro for the crude extract and momordicatin were 0.6mg/L and 0.02mg/L, respectively. When administered in the hamster model of visceral leishmaniasis, 100% parasite clearance was achieved at a dose of 300mg/kg body weight of crude extract and 10mg/kg body weight of Momordicatin. Fe containing parasite superoxide dismutase (SOD) was totally inhibited when treated with 0.72mg/L crude extract and 0.20mg/L Momordicatin, respectively, whereas Cu-Zn containing SOD present in host remained unaffected. Results reveal that mode of action of these newly found antileishmanial agents is mediated through inhibiting parasite SOD which is one of the key enzymes of the oxidative burst. It may be proposed from the present study that both crude extract of Momordica charantia and Momordicatin obtained from the fruits of the said plant may be considered as potential candidates towards developing new chemotherapeutics against leishmaniasis. Copyright © 2009. Published by Elsevier Ireland Ltd. |
| PMID: 20132905 [PubMed - as supplied by publisher] | |
| 6. | J Mol Biol. 2010 Feb 1. [Epub ahead of print]Crystal structures of trypanosomal histidyl-tRNA synthetase illuminate differences between eukaryotic and prokaryotic homologs.Merritt EA, Arakaki TL, Gillespie JR, Larson ET, Kelley A, Mueller N, Napuli AJ, Kim J, Zhang L, Verlinde CL, Fan E, Zucker F, Buckner FS, Van Voorhis WC, Hol WG.Medical Structural Genomics of Pathogenic Protozoa http://www.msgpp.org; Department of Biochemistry, University of Washington, Seattle, WA 98195 USA. Crystal structures of histidyl-tRNA synthetase from the eukaryotic parasites Trypanosoma brucei and Trypanosoma cruzi provide a first structural view of a eukaryotic form of this enzyme, and reveal differences from bacterial homologs. Histidyl-tRNA synthetases in general contain an extra domain inserted between conserved motifs 2 and 3 of the Class II aminoacyl-tRNA synthetase catalytic core. The current structures show that the three dimensional topology of this domain is very different in bacterial and archaeal/eukaryotic forms of the enzyme. Comparison of apo and histidine-bound trypanosomal structures indicates substantial active site rearrangement upon histidine binding, but relatively little subsequent rearrangement after reaction of histidine with ATP to form the enzyme's first reaction product, histidyladenylate. The specific residues involved in forming the binding pocket for the adenine moiety differ substantially both from the previously characterized binding site in bacterial structures and from the homologous residues in human histidyl-tRNA synthetases. The essentiality of the single histidyl-tRNA synthetase gene in T. brucei is shown by a severe depression of parasite growth rate that results from even partial suppression of expression by RNA interference. Abbreviations HisRS, histidyl-tRNA synthetase; HAM, histidyl-adenosinemonophosphate (=histidyladenylate); aaRS, aminoacyl-tRNA synthetase. Copyright © 2010 Elsevier B.V. All rights reserved. |
| PMID: 20132829 [PubMed - as supplied by publisher] | |
| 7. | Mol Microbiol. 2010 Feb 1. [Epub ahead of print]Mitochondrial DNA polymerase POLIB is essential for minicircle DNA replication in African trypanosomes.Bruhn DF, Mozeleski B, Falkin L, Klingbeil MM.Department of Microbiology, University of Massachusetts, Amherst, Massachusetts 01003. SUMMARY The unique mitochondrial DNA of trypanosomes is a catenated network of minicircles and maxicircles called kinetoplast DNA (kDNA). The network is essential for survival, and requires an elaborate topoisomerase-mediated release and reattachment mechanism for minicircle theta structure replication. At least seven DNA polymerase (pols) are involved in kDNA transactions, including three essential proteins related to bacterial DNA pol I (POLIB, POLIC and POLID). How Trypanosoma brucei utilizes multiple DNA pols to complete to topologically complex task of kDNA replication is unknown. To fill this gap in knowledge we investigated the cellular role of POLIB using RNA interference (RNAi). POLIB silencing resulted in growth inhibition and progressive loss of kDNA networks. Additionally, unreplicated covalently closed precursors become the most abundant minicircle replication intermediate as minicircle copy number declines. Leading and lagging strand minicircle progeny similarly declined during POLIB silencing, indicating POLIB had no apparent strand preference. Interestingly, POLIB RNAi led to the accumulation of a novel population of free minicircles that is composed mainly of covalently closed minicircle dimers. Based these data, we propose that POLIB performs an essential role at the core of the minicircle replication machinery. |
| PMID: 20132449 [PubMed - as supplied by publisher] | |
| 8. | APMIS. 2010 Feb;118(2):108-14.Hypoxia modulates phenotype, inflammatory response, and leishmanial infection of human dendritic cells.Bosseto MC, Palma PV, Covas DT, Giorgio S.Department of Parasitology, Biology Institute, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil. Bosseto MC, Palma PVB, Covas DT, Giorgio S. Hypoxia modulates phenotype, inflammatory response, and leishmanial infection of human dendritic cells. APMIS 2010; 118: 108-14. Development of hypoxic areas occurs during infectious and inflammatory processes and dendritic cells (DCs) are involved in both innate and adaptive immunity in diseased tissues. Our group previously reported that macrophages exposed to hypoxia were infected with the intracellular parasite Leishmania amazonensis, but showed reduced susceptibility to the parasite. This study shows that although hypoxia did not alter human DC viability, it significantly altered phenotypic and functional characteristics. The expression of CD1a, CD80, and CD86 was significantly reduced in DCs exposed to hypoxia, whereas CD11c, CD14, CD123, CD49 and HLA-DR expression remained unaltered in DCs cultured in hypoxia or normoxia. DC secretion of IL-12p70, the bioactive interleukin-12 (IL-12), a cytokine produced in response to inflammatory mediators, was enhanced under hypoxia. In addition, phagocytic activity (Leishmania uptake) was not impaired under hypoxia, although this microenviroment induced infected DCs to reduce parasite survival, consequently controlling the infection rate. All these data support the notion that a hypoxic microenvironment promotes selective pressure on DCs to assume a phenotype characterized by pro-inflammatory and microbial activities in injured or inflamed tissues and contribute to the innate immune response. |
| PMID: 20132174 [PubMed - in process] | |
| 9. | Onderstepoort J Vet Res. 2009 Mar;76(1):35-40.Tsetse and trypanosomosis in Africa: the challenges, the opportunities.Ilemobade AA.Upline Resources Foundation, P.O. Box 1308, Akure, Ondo State 34001, Nigeria. Tsetse-fly and the disease it transmits, trypanosomosis, remain an enormous disease challenge in the 37 countries of sub-Saharan Africa where the impact continues to be manifest in disease burden, increased level of poverty and decreased agricultural productivity. The impact also extends over an estimated 10 million km2 (a third of the African continent) of land area, a third of which contains some well-watered part of the continent, thus denying humans and livestock of potentially rich arable and pastureland. The disease is a threat to an estimated 50 million people and 48 million cattle with estimated annual losses in cattle production alone of 1-1.2 billion US$. These losses are due to stock mortality and depressed productivity, which may be of meat, milk, reproduction or traction. Beyond its direct effects on humans and livestock is its impact on African agriculture and the livelihood of the rural population in the affected countries: the fly and the disease influence where people decide to live, how they manage their livestock, and the intensity and the mix of crop agriculture. The combined effects result in changes in land use and environment which may, in turn, affect human welfare and increase the vulnerability of agricultural activity. Trypanosomosis is, therefore, both a public health and an agricultural development constraint. The challenges that the elimination or control of tsetse fly and trypanosomosis pose as well as the opportunities to develop appropriate intervention technologies are discussed in this presentation. |
| PMID: 19967926 [PubMed - indexed for MEDLINE] | |
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| 10. | J Biol Chem. 2009 Dec 11;284(50):35015-28. Epub 2009 Oct 2.An RNA recognition motif mediates the nucleocytoplasmic transport of a trypanosome RNA-binding protein.Cassola A, Frasch AC.Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico Chascomús, UNSAM-CONICET, (1650) San Martín, Provincia de Buenos Aires, Argentina. RNA-binding proteins (RBPs) and RNA metabolism are considered to be important for modulating gene expression in trypanosomes, because these protozoan parasites mainly rely on post-transcriptional mechanisms to regulate protein levels. Previously, we have identified TcUBP1, a single RNA recognition motif (RRM)-type RBP from Trypanosoma cruzi. TcUBP1 is a cytoplasmic protein with roles in stabilization/degradation of mRNAs and in the protection of transcripts through their recruitment into cytoplasmic granules. We now show that TcUBP1, and the closely related protein TcUBP2, can be found in small amounts in the nucleus under normal conditions, and are able to accumulate in the nucleus under arsenite stress. The kinetics of nuclear accumulation, and export to the cytoplasm, are consistent with the shuttling of TcUBP1 between the nucleus and the cytoplasm. The sequence required for TcUBP1 nuclear accumulation was narrowed to the RRM, and point mutations affecting RNA binding abolished nuclear import. This RRM was also shown to be efficiently exported from the nucleus in unstressed parasites, a property that relied on the binding to RNA. TcUBP1 nuclear accumulation was dependent on active transcription, and colocalized with transcripts in the nucleus, suggesting nuclear binding of the mRNA. We propose that TcUBP1 could be linking the mRNA metabolism at both sides of the nuclear pore complex, using the RRM as a nuclear localization signal, and being exported as a cargo on mRNA. PMCID: PMC2787363 [Available on 2010/12/11] |
| PMID: 19801539 [PubMed - indexed for MEDLINE] | |
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