What's new for 'Trypanosomatids' in PubMed

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Sent on Tuesday, 2012 March 06
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 18

1.	Lancet Infect Dis. 2012 Feb;12(2):106-7. Drug donated for treatment of visceral leishmaniasis. Burki T.
	PMID: 22389914 [PubMed - in process]
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2.	PLoS Negl Trop Dis. 2012 Feb;6(2):e1543. Epub 2012 Feb 28. Glycoinositolphospholipids from Leishmania braziliensis and L. infantum: Modulation of Innate Immune System and Variations in Carbohydrate Structure. Assis RR, Ibraim IC, Noronha FS, Turco SJ, Soares RP. Source Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz - FIOCRUZ, Belo Horizonte, Brazil. Abstract The essential role of the lipophosphoglycan (LPG) of Leishmania in innate immune response has been extensively reported. However, information about the role of the LPG-related glycoinositolphospholipids (GIPLs) is limited, especially with respect to the New World species of Leishmania. GIPLs are low molecular weight molecules covering the parasite surface and are similar to LPG in sharing a common lipid backbone and a glycan motif containing up to 7 sugars. Critical aspects of their structure and functions are still obscure in the interaction with the vertebrate host. In this study, we evaluated the role of those molecules in two medically important South American species Leishmania infantum and L. braziliensis, causative agents of visceral (VL) and cutaneous Leishmaniasis (CL), respectively. GIPLs derived from both species did not induce NO or TNF-α production by non-primed murine macrophages. Additionally, primed macrophages from mice (BALB/c, C57BL/6, TLR2-/- and TLR4-/-) exposed to GIPLs from both species, with exception to TNF-α, did not produce any of the cytokines analyzed (IL1-β, IL-2, IL-4, IL-5, IL-10, IL-12p40, IFN-γ) or p38 activation. GIPLs induced the production of TNF-α and NO by C57BL/6 mice, primarily via TLR4. Pre incubation of macrophages with GIPLs reduced significantly the amount of NO and IL-12 in the presence of IFN-γ or lipopolysaccharide (LPS), which was more pronounced with L. braziliensis GIPLs. This inhibition was reversed after PI-specific phospholipase C treatment. A structural analysis of the GIPLs showed that L. infantum has manose rich GIPLs, suggestive of type I and Hybrid GIPLs while L. braziliensis has galactose rich GIPLs, suggestive of Type II GIPLs. In conclusion, there are major differences in the structure and composition of GIPLs from L. braziliensis and L. infantum. Also, GIPLs are important inhibitory molecules during the interaction with macrophages.
	PMID: 22389743 [PubMed - in process]
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3.	PLoS Negl Trop Dis. 2012 Feb;6(2):e1542. Epub 2012 Feb 28. Predictive models for the diagnostic of human visceral leishmaniasis in Brazil. Machado de Assis TS, Rabello A, Werneck GL. Source Laboratório de Pesquisas Clínicas, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz (FIOCRUZ), Belo Horizonte, Minas Gerais, Brazil. Abstract BACKGROUND AND OBJECTIVES: In Brazil, as in many other affected countries, a large proportion of visceral leishmaniasis (VL) occurs in remote locations and treatment is often performed on basis of clinical suspicion. This study aimed at developing predictive models to help with the clinical management of VL in patients with suggestive clinical of disease. METHODS: Cases of VL (n = 213) had the diagnosis confirmed by parasitological method, non-cases (n = 119) presented suggestive clinical presentation of VL but a negative parasitological diagnosis and a firm diagnosis of another disease. The original data set was divided into two samples for generation and validation of the prediction models. Prediction models based on clinical signs and symptoms, results of laboratory exams and results of five different serological tests, were developed by means of logistic regression and classification and regression trees (CART). From these models, clinical-laboratory and diagnostic prediction scores were generated. The area under the receiver operator characteristic curve, sensitivity, specificity, and positive predictive value were used to evaluate the models' performance. RESULTS: Based on the variables splenomegaly, presence of cough and leukopenia and on the results of five serological tests it was possible to generate six predictive models using logistic regression, showing sensitivity ranging from 90.1 to 99.0% and specificity ranging from 53.0 to 97.2%. Based on the variables splenomegaly, leukopenia, cough, age and weight loss and on the results of five serological tests six predictive models were generated using CART with sensitivity ranging from 90.1 to 97.2% and specificity ranging from 68.4 to 97.4%. The models composed of clinical-laboratory variables and the rk39 rapid test showed the best performance. CONCLUSION: The predictive models showed to be a potential useful tool to assist healthcare systems and control programs in their strategical choices, contributing to more efficient and more rational allocation of healthcare resources.
	PMID: 22389742 [PubMed - in process]
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4.	PLoS Negl Trop Dis. 2012 Feb;6(2):e1514. Epub 2012 Feb 28. Molecular mechanisms of drug resistance in natural leishmania populations vary with genetic background. Decuyp ere S, Vanaerschot M, Brunker K, Imamura H, Müller S, Khanal B, Rijal S, Dujardin JC, Coombs GH. Source Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. Abstract The evolution of drug-resistance in pathogens is a major global health threat. Elucidating the molecular basis of pathogen drug-resistance has been the focus of many studies but rarely is it known whether a drug-resistance mechanism identified is universal for the studied pathogen; it has seldom been clarified whether drug-resistance mechanisms vary with the pathogen's genotype. Nevertheless this is of critical importance in gaining an understanding of the complexity of this global threat and in underpinning epidemiological surveillance of pathogen drug resistance in the field. This study aimed to assess the molecular and phenotypic heterogeneity that emerges in natural parasite populations under drug treatment pressure. We studied lines of the protozoan parasite Leishmania (L.) donovani with differential susceptibility to antimonial drugs; the lines being derived from clinical isolates belonging to two distinct genetic populations that circulate in the leishmaniasis endemic region of Nepal. Parasite pathways known to be affected by antimonial drugs were characterised on five experimental levels in the lines of the two populations. Characterisation of DNA sequence, gene expression, protein expression and thiol levels revealed a number of molecular features that mark antimonial-resistant parasites in only one of the two populations studied. A final series of in vitro stress phenotyping experiments confirmed this heterogeneity amongst drug-resistant parasites from the two populations. These data provide evidence that the molecular changes associated with antimonial-resistance in natural Leishmania populations depend on the genetic background of the Leishmania population, which has resulted in a divergent set of resistance markers in the Leishmania populations. This heterogeneity of parasite adaptations provides severe challenges for the control of drug resistance in the field and the design of molecular surveillance tools for widespread applicability.
	PMID: 22389733 [PubMed - in process]
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5.	PLoS Negl Trop Dis. 2012 Feb;6(2):e1475. Epub 2012 Feb 28. Neglected tropical diseases of the middle East and north Africa: review of their prevalence, distribution, and opportunities for control. Hotez PJ, Savioli L, Fenwick A. Source Departments of Pediatrics and Molecular Virology & Microbiology, and National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of America. Abstract The neglected tropical diseases (NTDs) are highly endemic but patchily distributed among the 20 countries and almost 400 million people of the Middle East and North Africa (MENA) region, and disproportionately affect an estimated 65 million people living on less than US$2 per day. Egypt has the largest number of people living in poverty of any MENA nation, while Yemen has the highest prevalence of people living in poverty. These two nations stand out for having suffered the highest rates of many NTDs, including the soil-transmitted nematode infections, filarial infections, schistosomiasis, fascioliasis, leprosy, and trachoma, although they should be recognized for recent measures aimed at NTD control. Leishmaniasis, especially cutaneous leishmaniasis, is endemic in Syria, Iran, Iraq, Libya, Morocco, and elsewhere in the region. Both zoonotic (Leishmania major) and anthroponotic (Leishmania tropica) forms are endemic in MENA in rural arid regions and urban regions, respectively. Other endemic zoonotic NTDs include cystic echinococcosis, fascioliasis, and brucellosis. Dengue is endemic in Saudi Arabia, where Rift Valley fever and Alkhurma hemorrhagic fever have also emerged. Great strides have been made towards elimination of several endemic NTDs, including lymphatic filariasis in Egypt and Yemen; schistosomiasis in Iran, Morocco, and Oman; and trachoma in Morocco, Algeria, Iran, Libya, Oman, Saudi Arabia, Tunisia, and the United Arab Emirates. A particularly noteworthy achievement is the long battle waged against schistosomiasis in Egypt, where prevalence has been brought down by regular praziquantel treatment. Conflict and human and animal migrations are key social determinants in preventing the control or elimination of NTDs in the MENA, while local political will, strengthened international and intersectoral cooperative efforts for surveillance, mass drug administration, and vaccination are essential for elimination.
	PMID: 22389729 [PubMed - in process]
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6.	Mol Biochem Parasitol. 2012 Feb 25. [Epub ahead of print] In silico identification of conserved intercoding sequences in Leishmania genomes: Unraveling putative cis-regulatory elements. Vasconcelos EJ, Terrão MC, Ruiz JC, Vêncio RZ, Cruz AK. Source Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil. Abstract In silico analyses of Leishmania spp. genome data are a powerful resource to improve the understanding of these pathogens' biology. Trypanosomatids such as Leishmania spp. have their protein-coding genes grouped in long polycistronic units of functionally unrelated genes. The control of gene expression happens by a variety of posttranscriptional mechanisms. The high degree of synteny among Leishmania species is accompanied by highly conserved coding sequences (CDS) and poorly conserved intercoding untranslated sequences. To identify the elements involved in the control of gene expression, we conducted an in silico investigation to find conserved intercoding sequences (CICS) in the genomes of L. major, L. infantum, and L. braziliensis. We used a combination of computational tools, such as Linux-Shell, PERL and R languages, BLAST, MSPcrunch, SSAKE, and Pred-A-Term algorithms to construct a pipeline which was able to: (i) search for conservation in target-regions, (ii) eliminate CICS redundancy and mask repeat elements, (iii) predict the mRNA's extremities, (iv) analyze the distribution of orthologous genes within the generated LeishCICS-clusters, (v) assign GO terms to the LeishCICS-clusters, and (vi) provide statistical support for the gene-enrichment annotation. We associated the LeishCICS-cluster data, generated at the end of the pipeline, with the expression profile of L. donovani genes during promastigoteamastigote differentiation, as previously evaluated by others (GEO accession: GSE21936). A Pearson's correlation coefficient greater than 0.5 was observed for 730 LeishCICS-clusters containing from 2 to 17 genes. The designed computational pipeline is a useful tool and its application identified potential regulatory cis elements and putative regulons in Leishmania. Copyright © 2012. Published by Elsevier B.V.
	PMID: 22387760 [PubMed - as supplied by publisher]
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7.	Microbes Infect. 2012 Feb 18. [Epub ahead of print] Genetic characterization of Trypanosoma brucei circulating in domestic animals of the Fontem sleeping sickness of Cameroon. Simo G, Njitchouang GR, Njiokou F, Cuny G, Asonganyi T. Source Department of Biochemistry, Faculty of Science, P.O. Box 67, University of Dschang, Dschang, Cameroon. Abstract To improve our knowledge on the transmission dynamics of trypanosomes, Trypanosoma brucei was identified in domestic animals of the Fontem sleeping sickness focus of Cameroon and their genetic characterizations were performed using seven polymorphic microsatellite markers. About 397 domestic animals including 225 pigs, 87 goats, 65 sheep and 20 dogs were sampled. The card agglutination test for trypanosomiasis was positive for 254 (63.98%) animals while the parasitological examinations (thin blood film and capillary tube centrifugation) revealed 86 (21.66%) trypanosome infections. The PCR based method revealed 140 (35.26%) infections of trypanosomes of the subgenus Trypanozoon. The genetic characterization of these 140 positive samples revealed 89 different alleles: 82 in pigs, 72 in goat, 60 in sheep and 48 in dog. Whatever the microsatellite marker used, most of positive samples were amplified. However, the sensitivity (percentage of samples amplified for each marker) of these markers varies significantly between them (χ(2) = 120.32; P < 0.0001). This study showed a high level (80.00%) of mixed genotypes as well as a wide range of T. brucei genotypes circulating in domestic animals of the Fontem sleeping sickness focus of Cameroon. This indicates that several T. brucei genotypes can naturally be transmitted simultaneously to tsetse flies during a single blood meal. Copyright © 2012. Published by Elsevier Masson SAS.
	PMID: 22387499 [PubMed - as supplied by publisher]
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8.	Biochem Biophys Res Commun. 2012 Feb 21. [Epub ahead of print] Regulation and spatial organization of PCNA in Trypanosoma brucei. Kaufmann D, Gassen A, Maiser A, Leonhardt H, Janzen CJ. Source University of Munich (LMU), Department Biology I, Genetics, Großhaderner Str. 2-4, 82152 Martinsried, Germany. Abstract As in most eukaryotic cells, replication is regulated by a conserved group of proteins in the early-diverged parasite Trypanosoma brucei. Only a few components of the replication machinery have been described in this parasite and regulation, sub-nuclear localization and timing of replication are not well understood. We characterized the proliferating cell nuclear antigen in T. brucei (TbPCNA) to establish a spatial and temporal marker for replication. Interestingly, PCNA distribution and regulation is different compared to the closely related parasites Trypanosoma cruzi and Leishmania donovani. TbPCNA foci are clearly detectable during S phase of the cell cycle but in contrast to T. cruzi they are not preferentially located at the nuclear periphery. Furthermore, PCNA seems to be degraded when cells enter G2 phase in T. brucei suggesting different modes of replication regulation or functions of PCNA in these closely related eukaryotes. Copyright © 2012. Published by Elsevier Inc.
	PMID: 22387477 [PubMed - as supplied by publisher]
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9.	Arch Biochem Biophys. 2012 Feb 29. [Epub ahead of print] Low resolution structural characterization o f the Hsp70-interacting protein - Hip - from Leishmania braziliensis emphasizes its high asymmetry. Dores-Silva PR, Silva ER, Gomes FE, Silva KP, Barbosa LR, Borges JC. Source Grupo de Biologia Molecular e Bioquímica, Instituto de Química de São Carlos, USP, São Carlos, SP, 13560-970, Brasil. Abstract The Hsp70 is an essential molecular chaperone in protein metabolism since it acts as a pivot with other molecular chaperone families. Several co-chaperones act as regulators of the Hsp70 action cycle, as for instance Hip (Hsp70-interacting protein). Hip is a tetratricopeptide repeat protein (TPR) that interacts with the ATPase domain in the Hsp70-ADP state, stabilizing it and preventing substrate dissociation. Molecular chaperones from protozoans, which can cause some neglected diseases, are poorly studied in terms of structure and function. Here, we investigated the structural features of Hip from the protozoa Leishmania braziliensis (LbHip), one of the causative agents of the leishmaniasis disease. LbHip was heterologously expressed and purified in the folded state, as attested by circular dichroism and intrinsic fluorescence emission techniques. LbHip forms an elongated dimer, as observed by analytical gel filtration chromatography, analytical ultracentrifugation and small angle X-ray scattering (SAXS). With the SAXS data a low resolution model was reconstructed, which shed light on the structure of this protein, emphasizing its elongated shape and suggesting its domain organization. We also investigated the chemical-induced unfolding behavior of LbHip and two transitions were observed. The first transition was related to the unfolding of the TPR domain of each protomer and the second transition of the dimer dissociation. Altogether, LbHip presents a similar structure to mammalian Hip, despite their low level of conservation, suggesting that this class of eukaryotic protein may use a similar mechanism of action. Copyright © 2012 Elsevier Inc. All rights reserved.
	PMID: 22387434 [PubMed - as supplied by publisher]
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10.	Rev Clin Esp. 2012 Mar 2. [Epub ahead of print] [Oriental sore due to Leishmania infantum (L. chagasi).] [Article in Spanish] García-Lozano T, Kindem Gómez S, Serra Guillén C, Aznar Oroval E. Source Servicio de Análisis Clínicos y Microbiología, Fundación Instituto Valenciano de Oncología (FIVO), Valencia, España.
	PMID: 22386680 [PubMed - as supplied by publisher]
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