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Sent on Tuesday, 2010 Nov 16Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Nucleic Acids Res. 2010 Nov 13. [Epub ahead of print]NLP is a novel transcription regulator involved in VSG expression site control in Trypanosoma brucei.Narayanan MS, Kushwaha M, Ersfeld K, Fullbrook A, Stanne TM, Rudenko G.Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London, South Kensington, London SW7 2AZ, Department of Biochemistry, University of Oxford, Oxford OX1 3QU and Department of Biological Sciences and Hull York Medical School, University of Hull, Cottingham Road, Hull HU6 7RX, UK. AbstractTrypanosoma brucei mono-allelically expresses one of approximately 1500 variant surface glycoprotein (VSG) genes while multiplying in the mammalian bloodstream. The active VSG is transcribed by RNA polymerase I in one of approximately 15 telomeric VSG expression sites (ESs). T. brucei is unusual in controlling gene expression predominantly post-transcriptionally, and how ESs are mono-allelically controlled remains a mystery. Here we identify a novel transcription regulator, which resembles a nucleoplasmin-like protein (NLP) with an AT-hook motif. NLP is key for ES control in bloodstream form T. brucei, as NLP knockdown results in 45- to 65-fold derepression of the silent VSG221 ES. NLP is also involved in repression of transcription in the inactive VSG Basic Copy arrays, minichromosomes and procyclin loci. NLP is shown to be enriched on the 177- and 50-bp simple sequence repeats, the non-transcribed regions around rDNA and procyclin, and both active and silent ESs. Blocking NLP synthesis leads to downregulation of the active ES, indicating that NLP plays a role in regulating appropriate levels of transcription of ESs in both their active and silent state. Discovery of the unusual transcription regulator NLP provides new insight into the factors that are critical for ES control. |
| PMID: 21076155 [PubMed - as supplied by publisher] | |
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| 2. | Mol Biochem Parasitol. 2010 Nov 10. [Epub ahead of print]The VSG C-termina l domain is inaccessible to antibodies on live trypanosomes.Schwede A, Jones N, Engstler M, Carrington M.Department of Biochemistry, 80 Tennis Court Road, Cambridge CB2 1GA, UK. AbstractIn the mammalian host, the Trypanosoma brucei cell surface is covered with a densely packed protein coat of a single protein, the variant surface glycoprotein (VSG). The VSG is believed to shield invariant surface proteins from host antibodies but there is limited information on how far antibodies can penetrate into the VSG monolayer. Here, the VSG surface coat was probed to determine whether it acts as a barrier to binding of antibodies to the membrane proximal VSG C-terminal domain. The binding of C-terminal domain antibodies to VSG221 or VSG118 was compared with antibodies recognising the cognate whole VSGs. The C-terminal VSG domain was inaccessible to antibodies on live cells but not on fixed cells. This provides further evidence that the VSG coat acts as a barrier and protects the cell from antibodies that would otherwise bind to some of the other externally disposed proteins. Copyright © 2010. Published by Elsevier B.V. |
| PMID: 21074579 [PubMed - as supplied by publisher] | |
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| 3. | Mol Biochem Parasitol. 2010 Nov 10. [Epub ahead of print]Complex I (NADH:ubiquinone oxidoreductase) is active in but non-essential for procyclic Trypanosoma brucei.Verner Z, Cermáková P, Skodová I, Kriegová E, Horváth A, Lukeš J.Biology Centre, Institute of Parasitology, Czech Academy of Sciences, České Budějovice (Budweis), Czech Republic; Faculty of Sciences, University of South Bohemia, České Budějovice (Budweis), Czech Republic. AbstractThe requirement of complex I (NADH:ubiquionone oxidoreductase) for respiration in Trypanosoma brucei is controversial. Recent identification of homologues of its subunits in mitochondrial proteome resolved a question of its presence or absence. However, with one exception, no data has been available concerning the function(s) of complex I or its subunits. Here we present a functional RNAi study of three (NUBM, NUKM, NUEM) putative subunits of this complex. Although no changes were detected in growth, mitochondrial membrane potential or reactive oxygen species production in cell lines depleted for target transcript,the NUBM and NUKM RNAi knock-downs showed decreased specific NADH:ubiquinone oxidoreductase activity. Moreover, glycerol gradients of all cell lines revealed the presence of two distinct peaks of NADH dehydrogenase activity, with shifted sensitivity to inhibitors of complex I upon RNAi induction. Thus complex I is not only present in the procyclic stage of T. brucei 29-13 strain, but it does participate in electron transport chain. Copyright © 2010. Published by Elsevier B.V. |
| PMID: 21074578 [PubMed - as supplied by publisher] | |
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| 4. | Trans R Soc Trop Med Hyg. 2010 Nov 10. [Epub ahead of print]Diagnosis of visceral leishmaniasis.Srivastava P, Dayama A, Mehrotra S, Sundar S.Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. AbstractLeishmaniasis is a vector-borne disease with up to 350 million people at risk of infection worldwide. Among its different clinical manifestations, visceral is the most severe form. Since clinical features of visceral leishmaniasis (VL) mimic several other common diseases, accurate diagnosis is crucial as the treatment is associated with significant toxicity. Invasive and risky techniques involving demonstration of the parasites in stained preparations from splenic and bone marrow aspirate is still the gold standard for VL diagnosis. Serological tests using rK39 in ELISA or rapid immunochromatographic format, Direct Agglutination Test (DAT), immunoblotting have issues related to a significant proportion of asymptomatic individuals being positive with these tests and their inability to diagnose relapses as these remain positive for several months to years after cure. PCR is the most common molecular technique successfully used for diagnosis and differentiation of species. Through this review we focus extensively on the comparative utilities of the various diagnostic tools currently available for VL, describing in depth their advantages and disadvantages, addressing the recent advances attained in the field. A simple, rapid, non invasive, accurate and cost effective marker of active VL, which can be used in field conditions, is necessary to improve diagnosis of VL. Copyright © 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved. |
| PMID: 21074233 [PubMed - as supplied by publisher] | |
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| 5. | Mol Biochem Parasitol. 2010 Nov 9. [Epub ahead of print]Trypanosoma cruzi MSH2: functional analyses on different parasite strains provide evidences for a role on the oxidativ e stress response.Campos PC, Silva VG, Furtado C, Machado-Silva A, Darocha WD, Peloso EF, Gadelha FR, Medeiros MH, Lana GD, Chen Y, Barnes RL, Silva DP, McCulloch R, Machado CR, Teixeira SM.Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. AbstractComponents of the DNA Mismatch Repair (MMR) pathway are major players in processes known to generate genetic diversity, such as mutagenesis and DNA recombination. Trypanosoma cruzi, the protozoan parasite that causes Chagas disease has a highly heterogeneous population, composed of a pool of strains with distinct characteristics. Studies with a number of molecular markers identified up to six groups in the T. cruzi population, which showed distinct levels of genetic variability. To investigate the molecular basis for such differences, we analyzed the T. cruzi MSH2 gene, which encodes a key component of MMR, and showed the existence of distinct isoforms of this protein. Here we compared cell survival rates after exposure to genotoxic agents and levels of oxidative stress-induced DNA in different parasite strains. Analyses of msh2 mutants in both T. cruzi and T. brucei were also used to investigate the role of Tcmsh2 in the response to various DNA damaging agents. The results suggest that the distinct MSH2 isoforms have differences in their activity. More importantly, they also indicate that, in addition to its role in MMR, TcMSH2 acts in the parasite response to oxidative stress through a novel mitochondrial function that may be conserved in T. brucei. Copyright © 2010. Published by Elsevier B.V. |
| PMID: 21073906 [PubMed - as supplied by publisher] | |
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| 6. | J Mol Biol. 2010 Nov 9. [Epub ahead of print]Structural basis for the broad substrate range of the UDP-sugar pyrophosphorylase from Leishmania major.Dickmanns A, Damerow S, Neumann P, Schulz EC, Lamerz AC, Routier FH, Ficner R.Abteilung für Molekulare Strukturbiologie, Institut für Mikrobiologie und Genetik and GZMB, Georg-August-Universität Göttingen, Justus-von-Liebig-Weg 11, D-37077 Göttingen, Germany. AbstractNucleotide sugars and the enzymes that are responsible for their synthesis are indispensable for the production of complex carbohydrates and thus for elaboration of a protective cellular coat for many organisms like protozoan parasite Leishmania. These activated sugars are synthesized de novo or derived from salvaged monosaccharides. In addition to the UDP-glucose pyrophosphorylase (UGP) that catalyzes the formation of UDP-glucose from substrates UTP and glucose-1-phosphate, Leishmania major and plants express an UDP-sugar pyrophosphorylase (USP), which exhibits a broad substrate specificity in vitro. The enzyme, likely involved in monosaccharide salvage, preferentially generates UDP-glucose and UDP-galactose but it may also activate other hexose- or pentose-1-phosphates such as galacturonic acid-1-phosphate or arabinose-1-phosphate. In order to gain insight into structural features governing the differences in substrate specificity we determined the crystal structure of the L. major UDP-sugar pyrophosphorylase in the APO-, UTP- and UDP-sugar bound conformations. The overall tripartite structure of USP exhibits a significant structural homology to other nucleotidyldiphosphate-glucose pyrophosphorylases. The obtained USP structures reveal the structural rearrangements occurring during the stepwise binding process of the substrates. Moreover, the different product complexes explain the broad substrate specificity of USP, which is enabled by structural changes in the sugar binding region of the active site. Copyright © 2010. Published by Elsevier Ltd. |
| PMID: 21073876 [PubMed - as supplied by publisher] | |
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| 7. | Med Vet Entomol. 2010 Nov 14. doi: 10.1111/j.1365-2915.2010.00919.x. [Epub ahead of print]Evaluation of juvenile hormone analogues as rodent feed-through insecticides for control of immature phleb otomine sandflies.Mascari TM, Mitchell MA, Rowton ED, Foil LD.Department of Entomology, Louisiana State University Agricultural Center, Baton Rouge, LA, U.S.A. Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL, U.S.A. Department of Entomology, Walter Reed Army Institute of Research, Silver Spring, MD, U.S.A. AbstractThe juvenile hormone analogues methoprene and pyriproxyfen were evaluated as rodent feed-through insecticides for control of immature stages of the sandfly Phlebotomus papatasi Scopoli (Diptera: Psychodidae). The development and survival of P. papatasi second-instar larvae fed faeces from Syrian hamsters, Mesocricetus auratus, that had been fed a diet containing methoprene (0, 9.788, 97.88 or 978.8 p.p.m.) or pyriproxyfen (0, 9.82, 98.2 or 982 p.p.m.) were evaluated. The faeces of methoprene-treated hamsters greatly reduced the percentage of larvae that pupated at all concentrations tested and prevented adult emergence at all but the lowest concentration (9.788 p.p.m.). Pyriproxyfen prevented both pupation and adult emergence at all concentrations tested. The results of this study suggest that a control strategy using rodent baits containing juvenile hormone analogues to control phlebotomine sandflies that live in rodent burrows and feed on rodent faeces may be possible. As rodent reservoirs and vectors of Leishmania major live in close association in many parts of the Middle East, control of the transmission of the agent of zoonotic cutaneous leishmaniasis may also be possible. © 2010 The Authors. Medical and Veterinary Entomology © 2010 The Royal Entomological Society. |
| PMID: 21073493 [PubMed - as supplied by publisher] | |
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| 8. | Parasite. 2010 Sep;17(3):257-65.The prevalence of African animal trypanosomoses and tsetse presence in Western Senegal.Seck MT, Bouyer J, Sall B, Bengaly Z, Vreysen MJ.Institut Sénégalais de Recherches Agricoles, Laboratoire National d'Elevage et de Recherches Vétérinaires, Service de Parasitologie, BP 2057 Dakar - Hann, Sénégal. mtseck@hotmail.fr AbstractIn 2005, the Government of Senegal initiated a tsetse eradication campaign in the Niayes and La Petite Côte aiming at the removal of African Animal Trypanosomosis (AAT), which is one of the main constraints to the development of more effective cattle production systems. The target area has particular meteorological and ecological characteristics that provide great potential for animal production, but it is unfortunately still infested by the riverine tsetse species Glossina palpalis gambiensis Vanderplank (Diptera: Glossinidae). The tsetse project in Senegal has adopted an area-wide integrated pest management (AW-IPM) approach that targets the entire tsetse population within a delimited area. During the first phase of the programme, a feasibility study was conducted that included the collection of entomological, veterinary, population genetics, environmental and socioeconomic baseline data. This paper presents the parasitological and serological prevalence data of AAT in cattle residing inside and outside the tsetse-infested areas of the target zone prior to the control effort. At the herd level, a mean parasitological prevalence of 2.4% was observed, whereas a serological prevalence of 28.7%, 4.4%, and 0.3% was obtained for Trypanosoma vivax, T. congolense and T. brucei brucei, respectively. The observed infection risk was 3 times higher for T. congolense and T. vivax in the tsetse-infested than in the assumed tsetse-free areas. Moreover, AAT prevalence decreased significantly with distance from the nearest tsetse captured which indicated that cyclical transmission of the parasites by tsetse was predominant over mechanical transmission by numerous other biting flies present. The importance of these results for the development of a control strategy for the planned AW-IPM campaign is discussed. |
| PMID: 21073148 [PubMed - in process] | |
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| 9. | Redox Rep. 2010;15(4):185-90.Increase of reactive oxygen species by desferrioxamine during experimental Chagas' disease.Francisco AF, de Abreu Vieira PM, Arantes JM, Silva M, Pedrosa ML, Elói-Santos SM, Martins-Filho OA, Teixeira-Carvalho A, Araújo MS, Tafuri WL, Carneiro CM.Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Brazil. AbstractOxidative stress is common in inflammatory processes associated with many diseases including Chagas' disease. The aim of the present study was to evaluate, in a murine model, biomarkers of oxidative stress together with components of the antioxidant system in order to provide an overview of the mechanism of action of the iron chelator desferrioxamine (DFO). The study population comprised 48 male Swiss mice, half of which were treated daily by intraperitoneal injection of DFO over a 35-day period, while half were administered sterile water in a similar manner. On the 14th day of the experiment, 12 DFO-treated mice and an equal number of untreated mice were experimentally infected with Trypanosoma cruzi. Serum concentrations of nitric oxide and superoxide dismutase and hepatic levels of total glutathione, thiobarbituric acid reactive species and protein carbonyl, were determined on days 0, 7, 14 and 21 post-infection. The results obtained revealed that DFO enhances antioxidant activity in the host but also increases oxidative stress, indicating that the mode of action of the drug involves a positive contribution to the host together with an effect that is not beneficial to the parasite. |
| PMID: 20663295 [PubMed - indexed for MEDLINE] | |
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| 10. | Clin Infect Dis. 2010 Sep 1;51(5):485-95.Molecular identification of Trypanosoma cruzi discrete typing units in end-stage chronic Chagas heart disease and reactivation after heart transplantation.Burgos JM, Diez M, Vigliano C, Bisio M, Risso M, Duffy T, Cura C, Brusses B, Favaloro L, Leguizamon MS, Lucero RH, Laguens R, Levin MJ, Favaloro R, Schijman AG.Laboratorio de Biología Molecular de la Enfermedad de Chagas, Instituto de Ingeniería Genética y Biología Molecular, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina. AbstractBACKGROUND: One hundred years after the discovery of Chagas disease, it remains a major neglected tropical disease. Chronic Chagas heart disease (cChHD) is the most severe manifestation. Heart transplantation is the proper treatment for end-stage heart failure, although reactivation of disease may result after receipt of immunosuppressive therapy. T. cruzi strains cluster into 6 discrete typing units (DTUs; I-VI) associated with different geographical distribution, transmission cycles and varying disease symptoms. In the southern cone of South America, T. cruzi II, V, and VI populations appear to be associated with Chagas disease and T. cruzi I with sylvatic cycles. METHODS: Molecular characterization of DTUs, T. cruzi I genotypes (on the basis of spliced-leader gene polymorphisms), and minicircle signatures was conducted using cardiac explant specimens and blood samples obtained from a cohort of 16 Argentinean patients with cChHD who underwent heart transplantation and from lesion samples obtained from 6 of these patients who presented with clinical reactivation of Chagas disease. RESULTS: Parasite persistence was associated with myocarditis progression, revealing T. cruzi I (genotype Id) in 3 explant samples and T. cruzi II, V, or VI in 5 explant samples. Post-heart transplantation follow-up examination of bloodstream DTUs identified T. cruzi I in 5 patients (genotypes Ia or Id) and T. cruzi II, V, or VI in 7 patients. T. cruzi I, V, and VI were detected in skin chagoma specimens, and T. cruzi V and VI were detected in samples obtained from patients with myocarditis reactivations. Multiple DTUs or genotypes at diverse body sites and polymorphic minicircle signatures at different cardiac regions revealed parasite histotropism. T. cruzi I infections clustered in northern Argentina (latitude, 23 degrees S-27 degrees S), whereas T. cruzi II, V, or VI DTUs were more ubiquitous. CONCLUSIONS: Multiple DTUs coexist in patients with Chagas disease. The frequent finding of T. cruzi I associated with cardiac damage was astounding, revealing its pathogenic role in cChHD at the southern cone. |
| PMID: 20645859 [PubMed - indexed for MEDLINE] | |
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