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 - 10 of 19

1.	Nucleic Acids Res. 2010 Jul 3. [Epub ahead of print] Small nucleolar RNA interference in Trypanosoma brucei: mechanism and utilization for elucidating the function of snoRNAs. Gupta SK, Hury A, Ziporen Y, Shi H, Ullu E, Michaeli S. The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900 Israel, Department of Internal Medicine and Department of Cell Biology, Yale University Medical School, New Haven, CT 06536-0812, USA. Abstract Expression of dsRNA complementary to small nucleolar RNAs (snoRNAs) in Trypanosoma brucei results in snoRNA silencing, termed snoRNAi. Here, we demonstrate that snoRNAi requires the nuclear TbDCL2 protein, but not TbDCL1, which is involved in RNA interference (RNAi) in the cytoplasm. snoRNAi depends on Argonaute1 (Slicer), and on TbDCL2, suggesting that snoRNA dicing and slicing takes place in the nucleus, and further suggesting that AGO1 is active in nuclear silencing. snoRNAi was next utilized to elucidate the function of an abundant snoRNA, TB11Cs2C2 (92 nt), present in a cluster together with the spliced leader associated RNA (SLA1) and snR30, which are both H/ACA RNAs with special nuclear functions. Using AMT-UV cross-linking and RNaseH cleavage, we provide evidence for the interaction of TB11Cs2C2 with the small rRNAs, srRNA-2 and srRNA-6, which are part of the large subunit (LSU) rRNA. snoRNAi of TB11Cs2C2 resulted in defects in generating srRNA-2 and LSUbeta rRNA. This is the first snoRNA described so far to engage in trypanosome-specific processing events.
	PMID: 20601683 [PubMed - as supplied by publisher]
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2.	J Immunol. 2010 Jul 2. [Epub ahead of print] Applying TLR Synergy in Immunotherapy: Implications in Cutan eous Leishmaniasis. Raman VS, Bhatia A, Picone A, Whittle J, Bailor HR, O'Donnell J, Pattabhi S, Guderian JA, Mohamath R, Duthie MS, Reed SG. Infectious Disease Research Institute, Seattle, WA 98104. Abstract Therapy of intracellular pathogens can be complicated by drug toxicity, drug resistance, and the need for prolonged treatment regimens. One approach that has shown promise is immunotherapy. Leishmaniasis, a vector-borne disease ranked among the six most important tropical infectious diseases by the World Health Organization, has been treated clinically with crude or defined vaccine preparations or cytokines, such as IFN-gamma and GM-CSF, in combination with chemotherapy. We have attempted to develop an improved and defined immunotherapeutic using a mouse model of cutaneous leishmaniasis. We hypothesized that immunotherapy may be improved by using TLR synergy to enhance the parasite-specific immune response. We formulated L110f, a well-established Leishmania poly-protein vaccine candidate, in conjunction with either monophosphoryl lipid A, a TLR4 agonist, or CpG, a TLR9 agonist, or a combination of these, and evaluated anti-Leishmania immune responses in absence or presence of active disease. Only mice treated with L110f plus monophosphoryl lipid A-CpG were able to induce a strong effective T cell response during disease and subsequently cured lesions and reduced parasite burden when compared with mice treated with L110f and either single adjuvant. Our data help to define a correlate of protection during active infection and indicate TLR synergy to be a potentially valuable tool in treating intracellular infections.
	PMID: 20601594 [PubMed - as supplied by publisher]
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3.	J Biol Chem. 2010 Jul 2. [Epub ahead of print] A glucose transporter can mediate ribose uptake: Definition of residues that confer substrate specificity in a sugar transporter. Naula CM, Logan FJ, Wong PE, Barrett MP, Burchmore RJ. University of Glasgow, United Kingdom. Abstract Sugars, the major energy source for many organisms, must be transported across biological membranes. Glucose is the most abundant sugar in human plasma, and in many other biological systems, and has been the primary focus of sugar transporter studies in eukaryotes. We have previously cloned and characterised a family of glucose transporter genes from the protozoan parasite Leishmania. These transporters, called LmGT1, LmGT2 and LmGT3, are homologous to the well-characterised GLUT family of mammalian glucose transporters. We have demonstrated that LmGT proteins are important for parasite viability. Here we show that one of these transporters, LmGT2, is a more effective carrier of the pentose sugar D-ribose than LmGT3, which has a 6-fold lower relative specificity (Vmax/Km) for ribose. A pair of threonine residues, located in the putative extracellular loops joining transmembrane helices 3 to 4, and 7 to 8, define a filter that limits ribose approaching the exofacial substrate binding pocket in LmGT3. When these threonines are substituted by alanine residues, as found in LmGT2, the LmGT3 permease acquires ribose-permease activity that is similar to that of LmGT2. The location of these residues in hydrophilic loops supports recent suggestions that substrate recognition is separated from substrate binding and translocation in this important group of transporters.
	PMID: 20601430 [PubMed - as supplied by publisher]
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4.	Infect Genet Evol. 2010 Jun 22. [Epub ahead of print] Genotypically distinct strains of Leishmania major display diverse clinical and immunological patterns in BALB/c mice. Alimohammadian MH, Darabi H, Ajdary S, Khaze V, Torkabadi E. Department of Immunology, Pasteur Institute of Iran, Pasteur Avenue 69, Tehran, Iran. Abstract Infection with Leishmania major species is endemic in many provinces of Iran. Isolates from four endemic areas located in north (Damghan), center (Kashan), west (Dehloran), and south (Shiraz) of country which showed major distinctive polymorphism by RAPD-PCR method were evaluated. Isolates were inoculated to different groups of BALB/c mice and their clinical and immunological status was compared. Lesion size, parasite burden and T cell phenotype in lymph node (LN), and cytokine secretion in the culture of LN mononuclear cells were determined. The results showed the lowest and highest lesion sizes in mice infected by Shiraz strain (3.02+/-0.52mm) and Kashan strain (5.20+/-0.45), respectively, 8 weeks after inoculation. No significant difference was observed between other strains. The parasite burden was significantly lower in lymph node of mice infected with strain of Damghan (1.51x10(7)) than Kashan (3.60x10(9)) and Shiraz (7.08x10(9)) strains, 8 weeks post-infection. However, Dehloran strain showed intermediate load of viable parasites (1.51x10(9)) in LN, 8 weeks post-infection. High ratios of IFN-gamma/IL-4 were shown in mice inoculated by strain of Dehloran (3.17) and Damghan (2.66), but not in mice infected by other strains, 8 weeks post-infection. The highest and lowest ratios of CD4(+)/CD8(+) T cells were found in LN cells of mice infected with Kashan (1.82) and Dehloran (1.00) strains, respectively. Results indicate that the lowest and intermediate loads of parasites induced by Damghan and Dehloran strains along with higher ratio of IFN-gamma/IL-4 produced by both strains in LN of inoculated mice suggest that these strains have the capacity to shift the immune responses to a predominant Th1 response after 8 weeks infection in BALB/c mice and might be the ideal strains for vaccine studies and development of candidate vaccine against leishmaniasis. Copyright © 2010. Published by Elsevier B.V.
	PMID: 20601170 [PubMed - as supplied by publisher]
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5.	Int J Biochem Cell Biol. 2010 Jun 22. [Epub ahead of print] Cell homeostasis in a Leishmania major mutant overexpressing the spliced leader RNA is maintained by an increased proteolytic activity. Toledo JS, Ferreira TR, Defina TP, Dossin FD, Beattie KA, Lamont DJ, Cloutier S, Papadopoulou B, Schenkman S, Cruz AK. Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade Medicina de Ribeirão Preto - Universidade de São Paulo, São Paulo, Brasil. Abstract Although several stage-specific genes have been identified in Leishmania, the molecular mechanisms governing developmental gene regulation in this organism are still not well understood. We have previously reported an attenuation of virulence in Leishmaniamajor and Leishmania braziliensis carrying extra-copies of the spliced leader RNA gene. Here, we surveyed the major differences in proteome and transcript expression profiles between the spliced leader RNA overexpressor and control lines using two-dimensional gel electrophoresis and differential display reverse transcription PCR, respectively. Thirty nine genes related to stress response, cytoskeleton, proteolysis, cell cycle control and proliferation, energy generation, gene transcription, RNA processing and post-transcriptional regulation have abnormal patterns of expression in the spliced leader RNA overexpressor line. The evaluation of proteolytic pathways in the mutant revealed a selective increase of cysteine protease activity and an exacerbated ubiquitin-labeled protein population. Polysome profile analysis and measurement of cellular protein aggregates showed that protein translation in the spliced leader RNA overexpressor line is increased when compared to the control line. We found that Leishmania major promastigotes maintain homeostasis in culture when challenged with a metabolic imbalance generated by spliced leader RNA surplus through modulation of intracellular proteolysis. However, this might interfere with a fine-tuned gene expression control necessary for the amastigote multiplication in the mammalian host. Copyright © 2010 Elsevier Ltd. All rights reserved.
	PMID: 20601086 [PubMed - as supplied by publisher]
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6.	Microbes Infect. 2010 Jul 2. [Epub ahead of print] Vaccination with the Leishmania infantum ribosomal proteins induces protection in BALB/c mice a gainst Leishmania chagasi and Leishmania amazonensis challenge. Chávez-Fumagalli MA, Costa MA, Oliveira DM, Ramírez L, Costa LE, Duarte MC, Martins VT, Oliveira JS, Olortegi CC, Bonay P, Alonso C, Tavares CA, Soto M, Coelho EA. Departamento de Bioquímica e Imunologia Universidade Federal de Minas Gerais, 31.270-901, Belo Horizonte, Minas Gerais, Brazil. Abstract Leishmania chagasi and Leishmania amazonensis are the etiologic agents of different clinical forms of human leishmaniasis in South America. In an attempt to select candidate antigens for a vaccine protecting against different Leishmania species, the efficacy of vaccination using Leishmania ribosomal proteins and saponin as adjuvant was examined in BALB/c mice against challenge infection with both parasite species. Mice vaccinated with parasite ribosomal proteins purified from L. infantum plus saponin showed a specific production of IFN-gamma, IL-12 and GM-CSF after in vitro stimulation with L. infantum ribosomal proteins. Vaccinated mice showed a reduction in the liver and spleen parasite burdens after L. chagasi infection. After L. amazonensis challenge, vaccinated mice showed a decrease of the dermal pathology and a reduction in the parasite loads in the footpad and spleen. In both models, protection was correlated to an IL-12-dependent production of IFN-gamma by CD4(+) and CD8(+) T cells that activate macrophages for the synthesis of NO. In the protected mice a decrease in the parasite-mediated IL-4 and IL-10 responses was also observed. In mice challenged with L. amazonensis, lower levels of anti-parasite specific antibodies were detected. Thus, Leishmania ribosomal proteins plus saponin fits the requirements to compose a pan-Leishmania vaccine. Copyright © 2010. Published by Elsevier SAS.
	PMID: 20601076 [PubMed - as supplied by publisher]
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7.	J Ethnopharmacol. 2010 Jun 22. [Epub ahead of print] Investigation of plant extracts in traditional medicine of the Brazilian Cerrado against protozoans and yeasts. Albernaz LC, Paula JE, Romero GA, Silva MD, Grellier P, Mambu L, Espindola LS. Laboratório de Farmacognosia, Universidade de Brasília, Brasília, Brasil. Abstract AIM OF THE STUDY: To investigate the activities of the 217 plant extracts in traditional medicine of the Brazilian Cerrado against protozoans and yeasts. MATERIALS AND METHODS: Plant extracts were prepared by the method of maceration using solvents of different polarities. The growth inhibition of chloroquine-resistant Plasmodium falciparum strain (FcB1) was determined by measuring the radioactivity of the tritiated hypoxanthine incorporated. Activity against Leishmania (Leishmania) chagasi and Trypanosomacruzi was measured by the MTT colorimetric assay. The antifungal tests were carried out by using the CLSI method. The active extracts were tested also by cytotoxicity assay using NIH-3T3 cells of mammalian fibroblasts. RESULTS: Two hundred and seventeen extracts of plants were tested against P. falciparum. The eleven active extracts, belonging to eight plant species were evaluated against L. (L.) chagasi, T. cruzi, yeasts and in NIH-3T3 cells. The results found in these biological models are consistent with the ethnopharmacological data of these plants. The ethyl acetate extract of Diospyros hispida root showed IC(50) values of 1mug/mL against P. falciparum. This extract demonstrated no toxicity against mammalian cells, resulting in a significant selectivity index (SI) of 435.8. The dichloromethane extract of Calophyllum brasiliense root wood was active against Cryptococcusgattii LMGO 01 with MIC of 1.95mug/mL; and C. albicans ATCC 10231 and C. krusei LMGO 174, both with MIC of 7.81mug/mL. The same extract was also active against P. falciparum and L. (L.) chagasi with IC(50) of 6.7 and 27.6mug/mL respectively. The ethyl acetate extract of S. odoratissima leaves was active against C. gattii LMGO 01 with MIC of 31.25mug/mL, and against P. falciparum with IC(50) of 9.2mug/mL and T. cruzi with IC(50) of 56.3mug/mL. CONCLUSION: The active extracts for protozoans and human pathogenic yeasts are considered promising to continue the search for the identification and development of leading compounds. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
	PMID: 20600775 [PubMed - as supplied by publisher]
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8.	Mol Biochem Parasitol. 2010 Jun 19. [Epub ahead of print] Transcriptomic analyses of the avirulent protozoan parasite Trypanosoma rangeli(1). Grisard EC, Stoco PH, Wagner G, Sincero TC, Rotava G, Rodrigues JB, Snoeijer CQ, Koerich LB, Sperandio MM, Bayer-Santos E, Fragoso SP, Goldenberg S, Triana O, Vallejo GA, Tyler KM, Dávila AM, Steindel M. Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil, 88040-970; University of East Anglia, Norwich, Norfolk, United Kingdom. Abstract Two species of the genus Trypanosoma infective to humans have been extensively studied at a cell and molecular level, but study of the third, Trypanosoma rangeli, remains in relative infancy. T. rangeli is non-pathogenic, but is frequently mistaken for the related Chagas disease agent T. cruzi with which it shares vectors, hosts, significant antigenicity and a sympatric distribution over a wide geographical area. In this study, we present the T. rangeli gene expression profile as determined by the generation of ESTs (Expressed Sequence Tags) and ORESTES (Open Reading Frame ESTs). A total of 4,208 unique high quality sequences were analyzed, composed from epimastigote and trypomastigote forms of SC-58 and Choachí strains, representing the two major phylogenetic lineages of this species. Comparative analyses with T. cruzi and other parasitic kinetoplastid species allowed the assignment of putative biological functions to most of the sequences generated and the establishment of an annotated T. rangeli gene expression database. Even though T. rangeli is apathogenic to mammals, genes associated with virulence in other pathogenic kinetoplastids were found. Transposable elements and genes associated mitochondrial gene expression, specifically RNA editing components, are also described for the first time. Our studies confirm the close phylogenetic relationship between T. cruzi and T. rangeli and enable us to make an estimate for the size of the T. rangeli genome repertoire ( approximately 8,500 genes). Copyright © 2010. Published by Elsevier B.V.
	PMID: 20600354 [PubMed - as supplied by publisher]
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9.	Exp Parasitol. 2010 Jun 18. [Epub ahead of print] Trypanosoma brucei: Immunisation with plasmid DNA encoding Invariant Surface Glycoprotein gene is able to induce partial protection in experimental African trypanosomiasis. Lança AS, de Sousa KP, Atouguia J, Prazeres DM, Monteiro GA, Silva MS. Unidade de Ensino e Investigação de Clínica das Doenças Tropicais - Centro de Malária e Outras Doenças Tropicais (CMDT) - Instituto de Higiene e Medicina Tropical. Abstract Trypanosoma brucei is the etiological agent responsible for African trypanosomiasis, an infectious pathology which represents a serious problem of public health and economic losses in sub-Saharan Africa. As one of the foremost neglected illnesses, few resources have been available for the development of vaccines or new drugs, in spite of the current therapeutical drugs showing little efficiency and high toxicity. Hence, it is obviously important to widen effective therapeutics and preventive strategies against African trypanosomiasis. In this work, we use the DNA vaccine model to evaluate immunisation effectiveness in mice challenged with Trypanosoma brucei brucei. We demonstrate that Balb/C mice immunised intramuscularly with a single dose of a DNA plasmid encoding a bloodstream stage specific invariant surface glycoprotein (ISG) are partially protected from a lethal dose of Trypanosoma brucei brucei. Interestingly, the surviving animals show high levels of IgG2a anti-trypanosoma antibodies, suggesting that the Th1 response profile seems important for the induced mechanisms of immune protection. Copyright © 2010. Published by Elsevier Inc.
	PMID: 20599996 [PubMed - as supplied by publisher]
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10.	Exp Parasitol. 2010 Jun 22. [Epub ahead of print] Evaluation and improvement of two PCR targets in molecular typing of clinical samples of Leishmania patients. Roelfsema JH, Nozari N, Herremans T, Kortbeek LM, Pinelli E. National Institute of Public Health and the Environment Centre for Infectious Disease Control Netherlands. Abstract Leishmaniasis is a disease caused by the unicellular Leishmania parasite. World wide millions of people are affected by this vector born disease. The disease presents itself in different clinical manifestations which are caused by specific Leishmania species. The therapeutic strategy depends on the Leishmania species involved. It is important to detect Leishmania and subsequently type the infecting species in a sensitive way using PCR. Various targets have been proposed but two seem to be best suited, the ITS1 region and the mini-exon. There is, however, no consensus as to which of these two is best. The aim of this study was to compare both targets with our current method, a PCR on the 18S ribosomal RNA gene. The ITS1 PCR proved to be slightly more sensitive and more practical than the mini-exon. Nevertheless, the mini-exon is more polymorphic and is needed in subtyping Leishmania species belonging to the L. (Viannia) subgenus. The ITS1 method was adapted to use as a real-time PCR for diagnostic purposes. In addition, designing and testing a new primer set improved sensitivity of the PCR on the mini-exon. Copyright © 2010. Published by Elsevier Inc.
	PMID: 20599989 [PubMed - as supplied by publisher]
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