What's new for 'Trypanosomatids' in PubMed

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Sent on Wednesday, 2010 Aug 11
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 11

1.	Appl Opt. 2010 Aug 10;49(23):4460-71. doi: 10.1364/AO.49.004460. Modeling and interpretation of extinction spectra of oriented nonspherical composite particles: application to biological cells. Serebrennikova YM, Garcia-Rubio LH. Abstract The majority of cells and microorganisms have a nonspherical shape and complex structure that challenge the interpretation of their spectral features. To address this issue, two approximations to the core-shell Mie theory were proposed. These included the approximation of light extinction by an ellipsoid with representation of the extinction by an equivalent sphere and representation of the extinction by a population of ellipsoidal particles with those of two weighted particle orientations. These hypotheses were first tested through numerical interpretation of the theoretical extinction spectra of prolate nucleated ellipsoids mimicking biological cells generated with anomalous diffraction approximation used as a reference method. Theoretical cases of fixed and random particle orientations demonstrated excellent capabilities of the proposed approach to retrieve the size, shape, and composition parameters of the model particles. Second, the UV-visible spectra of Leishmania species, promastigotes, elongated cells with prominent nuclei, were interpreted. The retrieved estimates of the protozoa size, shape, nucleus size, and nucleotide composition were in agreement with the corresponding microscopy estimates and literature values. Both theoretical tests and experimental results illustrated that the proposed approach can be successfully applied to estimate the structural and compositional parameters of cells from spectroscopic measurements.
	PMID: 20697450 [PubMed - in process]

2.	Infect Immun. 2010 Aug 9. [Epub ahead of print] Trypanosoma cruzi-induced activation of functionally distinct {alpha}{beta} and {gamma}{delta} CD4-CD8- (double negative) T cells in individuals with polar forms of Chagas disease.Villani FN, Rocha MO, Nunes MD, Antonelli LR, Magalhães LM, Santos JS, Gollob KJ, Dutra WO. Department of Morphology and INCT-DT, Institute of Biological Sciences, UFMG, Infectious Diseases and Tropical Medicine Graduate Course, School of Medicine, UFMG, Belo Horizonte, MG, Brazil; Instituto, FIOCRUZ, Belo Horizonte, MG, Brazil; SRI International, Biosciences Division, Center for Infectious Disease Research, Menlo Park, CA, USA. Abstract CD4-CD8- (double negative- DN) T-cells have recently been shown to display important immunological functions in human diseases. They express gammadelta or alphabeta T-cell receptors that recognize lipid/glycolipid antigens presented via the non-classical MHC molecules of the CD1 family. We recently demonstrated that while alphabeta DN T-cells are mainly committed to the expression of inflammatory cytokines, gammadelta DN T-cells express mainly IL-10 in patients with cutaneous leishmaniasis. We also demonstrated a correlation between DN T-cells and the expression of IFN-gamma in the acute phase of T. cruzi experimental infection. In this work, we sought to investigate whether alphabeta or gammadelta DN T-cells display distinct immunoregulatory potentials in patients with polar forms of human Chagas disease. Our data showed that in vitro infection with Trypanosoma cruzi leads to expansion of DN T-cells in patients of the indeterminate and severe cardiac clinical forms. However, while alphabeta DN T-cells are more committed to the production of inflammatory cytokines in both forms, gammadelta DN T-cells display a marked significant increase in antigen-specific IL-10 expression in indeterminate as compared to cardiac patients. Finally, higher frequencies of the IL-10-producing gammadelta DN T-cells were correlated with improved clinical measures of cardiac function in the patients, suggesting a protective role for these cells in Chagas disease. Taken together, these data show distinct functional characteristics for alphabeta and gammadelta DN T-cells associated with distinct morbidity and clinical forms in human Chagas disease.
	PMID: 20696836 [PubMed - as supplied by publisher]

3.	Vet Immunol Immunopathol. 2010 Jul 12. [Epub ahead of print] Time dependent expression of cytokines in Mycobacterium bovis infected cattle lymph nodes. Witchell J, Maddipatla SV, Wangoo A, Vordermeier M, Goyal M. School of Life Sciences, University of Hertfordshire, College Lane, Hatfield, Herts AL10 9AB, UK. Abstract Advancements in the current diagnostic and vaccination protocols employed against bovine tuberculosis rely heavily upon a sound knowledge of the bovine immunological response. Central to this is the importance of timing in the cellular immune profile and how this dynamic process evolves post-Mycobacterium bovis challenge. In the present study, we quantitatively analysed mRNA expression of interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha) and interleukins (IL) 4 and 10 within select thoracic lymph nodes of cattle infected with M. bovis for 5, 12 and 19 weeks as compared to non-infected bovine tissues. The M. bovis infected lymph nodes displayed significantly higher expression levels of IFN-gamma and TNF-alpha as compared to the non-infected lymph node tissues. This, in conjunction with undetectable levels of IL4, suggests a pro-inflammatory cytokine response. However a significant increase was also detected in IL10 mRNA which is consistent with a described aspect of T(H)1 type T cells in Leishmania infection, a 'self-limiting' process in which cells produced both IFN-gamma and IL10 with the aim of controlling the heightened immunopathological responses. This was further reflected when comparing the cytokine profiles of the individual lymph node types, as those displaying a higher IFN-gamma/IL10 ratio also had a greater level of gross pathology. This data highlights the important role of IL10 in the bovine response to M. bovis infection and supports its involvement as an immunological marker of disease progression. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.
	PMID: 20696483 [PubMed - as supplied by publisher]

4.	Biochem Pharmacol. 2010 Aug 6. [Epub ahead of print] Identification of a kappa-opioid agonist as a potent and selective lead for drug development against human African trypanosomiasis. Jones DC, Hallyburton I, Stojanovski L, Read KD, Frearson JA, Fairlamb AH. Division of Biological Chemistry & Drug Discovery, College of Life Sciences, University of Dundee, Dundee, UK. Abstract A resazurin-based cell viability assay was developed for phenotypic screening of the LOPAC 1280 'library of pharmacologically active compounds' against bloodstream forms of T. brucei in vitro identifying 33 compounds with EC(50) values<1muM. Counter-screening versus normal diploid human fibroblasts (MRC5 cells) was used to rank these hits for selectivity, with the most potent (< 70nM) and selective (> 700-fold) compounds being suramin and pentamidine. These are well known antitrypanosomal drugs which demonstrate the robustness of the resazurin cell viability assay. The most selective novel inhibitor was (+)-trans-(1R,2R)-U50,488 having an EC(50) value of 60nM against T. brucei and 270-fold selectivity over human fibroblasts. Interestingly, (-)-U50,488, a known CNS-active kappa-opioid receptor agonist and other structurally related compounds were>70-fold less active or inactive, as were several mu- and kappa-opioid antagonists. Although (+)-U50,488 was well tolerated by the oral route and displayed good pharmaceutical properties, including high brain penetration, the compound was not curative in the mouse model of infection. Nonetheless, the divergence of antinociceptive and antitrypanosomal activity represents a promising start point for further exploratory chemistry. Bioinformatic studies did not reveal any obvious candidate opioid receptors and the target of this cytostatic compound is unknown. Among the other potent, but less selective screening hits were compound classes with activity against protein kinases, topoisomerases, tubulin, as well as DNA and energy metabolism. Copyright © 2010. Published by Elsevier Inc.
	PMID: 20696141 [PubMed - as supplied by publisher]

5.	Acta Trop. 2010 Aug 6. [Epub ahead of print] Experimental canine leishmaniasis: clinical, parasitological and serological follow-up. Maia C, Nunes M, Cristóvão J, Campino L. Unidade de Leishmanioses. Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL). Rua da Junqueira 100, 1349-008 Lisboa, Portugal; Centro Malaria e Doenças Tropicais/IHMT/UNL. Abstract Canine leishmaniasis (CanL) caused by Leishmania infantum is transmitted by the bite of phlebotomine sand flies and affects millions of dogs in Europe, Asia, North Africa and South America. Canis familiaris is the major host for these parasites, and the main reservoir for human visceral infection. The development of effective molecules for therapy and immunoprophylaxis, would be an important tool in the control of this zoonosis. The aim of this study was to characterize an experimental CanL model in order to determine the best challenge model and which parameters are the most reliable to evaluate the efficacy of new drugs or vaccine candidates against L. infantum infection. The intravenous challenge with purified amastigotes used in this study allowed the development of infection in all animals inoculated (as confirmed by the detection of parasite in the different tissues and organs collected six months after inoculation). Molecular and serologic techniques were efficient methods for the follow up. Lymph node and bone marrow aspirates were suitable clinical samples to detect the presence of Leishmania parasites. Despite ELISA was highly sensitive in detecting specific anti-Leishmania antibodies the use of two tests can improve the sensitivity and specificity of serological diagnosis. Copyright © 2010. Published by Elsevier B.V.
	PMID: 20696122 [PubMed - as supplied by publisher]

6.	BMC Bioinformatics. 2010 Aug 9;11(1):417. [Epub ahead of print] FACT: Functional annotation transfer between proteins with similar feature architectures. Koestler T, von Haeseler A, Ebersberger I. Abstract ABSTRACT: BACKGROUND: The increasing number of sequenced genomes provides the basis for exploring the genetic and functional diversity within the tree of life. Only a tiny fraction of the encoded proteins undergoes a thorough experimental characterization. For the remainder, bioinformatics annotation tools are the only means to infer their function. Exploiting significant sequence similarities to already characterized proteins, commonly taken as evidence for homology, is the prevalent method to deduce functional equivalence. Such methods fail when homologs are too diverged, or when they have assumed a different function. Finally, due to convergent evolution, functional equivalence is not necessarily linked to common ancestry. Therefore complementary approaches are required to identify functional equivalents. RESULTS: We present the Feature Architecture Comparison Tool (http://www.cibiv.at/FACT) to search for functionally equivalent proteins. FACT uses the similarity between feature architectures of two proteins, i.e., the arrangements of functional domains, secondary structure elements and compositional properties, as a proxy for their functional equivalence. A scoring function measures feature architecture similarities, which enables searching for functional equivalents in entire proteomes. Our evaluation of 9,570 EC classified enzymes revealed that FACT, using the full feature, set outperformed the existing architecture-based approaches by identifying significantly more functional equivalents as highest scoring proteins. We show that FACT can identify functional equivalents that share no significant sequence similarity. However, when the highest scoring protein of FACT is also the protein with the highest local sequence similarity, it is in 99% of the cases functionally equivalent to the query. We demonstrate the versatility of FACT by identifying a missing link in the yeast glutathione metabolism and also by searching for the human GolgA5 equivalent in Trypanosoma brucei. CONCLUSIONS: FACT facilitates a quick and sensitive search for functionally equivalent proteins in entire proteomes. FACT is complementary to approaches using sequence similarity to identify proteins with the same function. Thus, FACT is particularly useful when functional equivalents need to be identified in evolutionarily distant species, or when functional equivalents are not homologous. The most reliable annotation transfers, however, are achieved when feature architecture similarity and sequence similarity are jointly taken into account.
	PMID: 20696036 [PubMed - as supplied by publisher]

7.	Australas J Dermatol. 2010 Aug;51(3):195-7. Cutaneous leishmaniasis in a child treated with oral fluconazole. Sklavos AV, Walls T, Webber MT, Watson AB. Royal Newcastle Centre Department of Dermatology, Rankin Park, NSW, Australia. Abstract We report a case of cutaneous leishmaniasis in a 3-year-old West African girl with a 3-month history of multiple disfiguring, infiltrated, ulcerating and variably necrotic granulomatous plaques on the limbs and face that occurred after swimming in a river approximately 6 weeks before arriving in Australia. A diagnosis of cutaneous leishmaniasis, a protozoal zoonosis usually transmitted by the Phlebotomus species of sandfly, was considered. The clinico-pathological features were consistent with Leishmania major infection, known to be the major endemic species causing cutaneous leishmaniasis in the country of origin. Because of the presence of lesions on the face, active treatment was instituted. Continuing resolution of all lesions over 6 weeks was noted to occur with cribiform scarring with the use of oral fluconazole 150 mg daily. Oral fluconazole appears to be emerging as a therapy for uncomplicated cutaneous leishmaniasis, with advantages particularly important in paediatrics.
	PMID: 20695859 [PubMed - in process]

8.	Expert Rev Anti Infect Ther. 2010 Aug;8(8):919-44. Current diagnosis and treatment of visceral leishmaniasis. Mondal S, Bhattacharya P, Ali N. Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, Kolkata, India. Abstract Human visceral leishmaniasis (VL), a potentially fatal disease, is most prevalent in the Indian subcontinent, East Africa and South America. Definite diagnosis and effective treatment are the primary needs for the control of VL. Diagnosis of VL has typically relied on microscopic examination of bone marrow/splenic aspirate, but serology and molecular methods are now better alternatives. The conventional drugs for treatment of VL have limitations including unresponsiveness, relapse, specific toxicities and parenteral administration lasting for long durations. Moreover, they are less effective in HIV-VL-coinfected patients. Registration of miltefosine and paromomycin, and preferential pricing of AmBisome has offered more choices for monotherapy and combination therapy for VL. Combination therapy will increase treatment efficacy and prevent the development of resistance. In addition, active case finding and vector control strategies will also have a positive impact in the control of VL. This article critically addresses the currently available diagnostic and treatment regimens for the control of VL.
	PMID: 20695748 [PubMed - in process]

9.	Am J Trop Med Hyg. 2010 Jul;83(1):164-70. Identification of a hyperendemic area for Trypanosoma cruzi infection in central Veracruz, Mexico. Ramos-Ligonio A, López-Monteon A, Guzmán-Gómez D, Rosales-Encina JL, Limón-Flores Y, Dumonteil E. LADISER Inmunología y Biología Molecular, Facultad de Ciencias Químicas, Universidad Veracruzana, Orizaba, Veracruz, Mexico. angramos@uv.mx Abstract The state of Veracruz, Mexico, is a well-recognized endemic region for Chagas disease, but the geographic distribution of the disease and its magnitude are still poorly documented. We evaluated the seroprevalence of Trypanosoma cruzi infection in the sanitary jurisdictions of Cordoba and Cosamaloapan in central Veracruz. A total of 654 serum samples from 19 rural localities were tested by using four tests: two enzyme-linked immunosorbent assays, an indirect immunofluorescent, and Western blotting. Overall, 110 (16.8%) of 654 samples were positive for T. cruzi by >/= 2 tests (95% confidence interval = 14.2-19.9%). The municipality of Tezonapa in the jurisdiction of Cordoba was identified as a potential hyperendemic region with seroprevalence rates </= 45% in young children. No cases were detected in the jurisdiction of Cosamaloapan. Further studies should help clarify T. cruzi transmission dynamics in Tezonapa. The magnitude of T. cruzi infection rate in this region calls for the urgent implementation of extensive epidemiologic surveillance and control programs.
	PMID: 20595496 [PubMed - indexed for MEDLINE]
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10.	J Immunol. 2010 Jul 15;185(2):1150-7. Epub 2010 Jun 18. IL-17 is necessary for host protection against acut e-phase Trypanosoma cruzi infection. Miyazaki Y, Hamano S, Wang S, Shimanoe Y, Iwakura Y, Yoshida H. Division of Molecular and Cellular Immunoscience, Department of Biomolecular Sciences, Saga University, Saga, Japan. miyazak4@cc.saga-u.ac.jp Abstract IL-17A is a key cytokine that induces inflammatory responses through the organized production of inflammatory cytokines, such as IL-6, TNF-alpha, and GM-CSF, and induces neutrophil migration. The roles of IL-17A in infection of intracellular protozoan parasites have not been elucidated, although augmented immune responses by IL-17A are important for the resolution of some bacterial and fungal infections. Therefore, we experimentally infected IL-17A-deficient (IL-17A(-/-)) mice with Trypanosoma cruzi. IL-17A(-/-) mice had a lower survival rate and prolonged worse parasitemia compared with control C57BL/6 wild-type (WT) mice postinfection. In the infected IL-17A(-/-) mice, multiple organ failure was observed compared with WT mice, as reflected by the marked increase in serologic markers of tissue injury, such as aspartate aminotransferase, which resulted in increased mortality of IL-17A(-/-) mice. Expression of cytokines, such as IFN-gamma, IL-6, and TNF-alpha, was lower in liver-infiltrating cells from the IL-17A(-/-) mice compared with WT mice. A similar defect was observed in the expression of neutrophil enzymes, such as myeloperoxidase and lipoxygenase, whereas cellular infiltration into the infected tissues was not affected by IL-17A deficiency. These results suggested that the efficient activation of immune-related cells critical for the killing of T. cruzi was impaired in the absence of IL-17A, resulting in the greater susceptibility of those mice to T. cruzi infection. From these results, we conclude that IL-17A is important for the resolution of T. cruzi infection.
	PMID: 20562260 [PubMed - indexed for MEDLINE]
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