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 14

1.	Eur J Immunol. 2010 Aug 3. [Epub ahead of print] Human mucosal leishmaniasis: Neutrophils infiltrate areas of tissue damage that express high levels of Th17-related cytokines. Boaventura VS, Santos CS, Cardoso CR, de Andrade J, Dos Santos WL, Clarêncio J, Silva JS, Borges VM, Barral-Netto M, Brodskyn CI, Barral A. Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil. Abstract Mucosal leishmaniasis (ML) is characterised by severe tissue destruction. Herein, we evaluated the involvement of the IL-17-type response in the inflammatory infiltrate of biopsy specimens from 17 ML patients. IL-17 and IL-17-inducing cytokines (IL-1beta, IL-23, IL-6 and TGF-beta) were detected by immunohistochemistry in ML patients. IL-17(+) cells exhibited CD4(+), CD8(+) or CD14(+) phenotypes, and numerous IL-17(+) cells co-expressed the CC chemokine receptor 6 (CCR6). Neutrophils, a hallmark of Th17-mediated inflammation, were regularly detected in necrotic and perinecrotic areas and stained positive for neutrophil elastase, myeloperoxidase and MMP-9. Taken together, these observations demonstrate the existence of Th17 cells in ML lesions associated with neutrophils in areas of tissue injury and suggest that IL-17 is involved in ML pathogenesis.
	PMID: 20812234 [PubMed - as supplied by publisher]
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2.	Am J Trop Med Hyg. 2010 Sep;83(3):515-8. Mucosal leishmaniasis and abnormalities on computed tomographic scans of paranasal sinuses. Camargo RA, Tuon FF, Sumi DV, Gebrim EM, Imamura R, Nicodemo AC, Cerri GG, Amato VS. Department of Infectious Diseases, Institute of Radiology, and Infectious and Parasitic Diseases Clinic, Hospital das Clínicas, University of São Paulo, Medical School, São Paulo, Brazil; Division of Infectious and Parasitic Diseases, Hospital Universitário Evangélico de Curitiba, Curitiba, Paraná, Brazil. Abstract Studies evaluating radiologic aspects, local complications, and structural alterations of the paranasal sinus in patients with mucosal leishmaniasis (ML) are lacking. The aim of this study was to analyze alterations of the paranasal sinuses in patients with ML by using computed tomography (CT) scans. This prospective study evaluated 26 patients in Brazil with ML from December 2008 through June 2009. All patients underwent CT scans of the paranasal sinuses. Paranasal thickening was observed in 25 patients (96%). Nasal perforation was observed in 17 patients (65%). Those patients who received re-treatment showed more abnormalities on CT scan than cured patients (P < 0.05). Complications of ML are not limited to the nasal mucosa but extend to the paranasal sinuses. Mucosal thickening, opacified air cells, bony remodeling, and bony thickening caused by inflammatory osteitis of the sinus cavity walls are CT findings suggestive of chronic sinusitis.
	PMID: 20810813 [PubMed - in process]
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3.	Am J Trop Med Hyg. 2010 Sep;83(3):512-4. Lack of Protection of Pre-Immunization with Saliva of Long-Term Colonized Phlebotomus papatasi against Experimental Challenge with Leishmania major and Saliva of Wild-Caught P . papatasi. Ahmed SB, Kaabi B, Chelbi I, Derbali M, Cherni S, Laouini D, Zhioua E. Laboratory of Vector Ecology, Laboratory of Epidemiology and Ecology of Parasites, and Laboratory of Immuno-Pathology, Vaccinology, and Molecular Genetics, Institut Pasteur de Tunis, Tunis, Tunisia; Department of Biology, University of Gafsa, Gafsa, Tunisia. Abstract Immunity to saliva of Phlebotomus papatasi protects against Leishmania major infection as determined by co-inoculation of parasites with salivary gland homogenates (SGHs) of this vector. These results were obtained with long-term colonized female P. papatasi. We investigated the effect of pre-immunization with SGH of long-term colonized P. papatasi against L. major infection co-inoculated with SGH of wild-caught P. papatasi. Our results showed that pre-exposure to SGH of long-term, colonized P. papatasi do not confer protection against infection with L. major co-inoculated with SGH of wild-caught P. papatasi. These preliminary results strongly suggest that the effectiveness of a vector saliva-based vaccine derived from colonized sand fly populations may be affected by inconsistent immune response after natural exposure.
	PMID: 20810812 [PubMed - in process]
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4.	Am J Trop Med Hyg. 2010 Sep;83(3):507-511. Effectiveness and Feasibility of Active and Passive Case Detection in the Visceral Leishmaniasis Elimination Initiative in India, Bangladesh, and Nepal. Hirve S, Singh SP, Kumar N, Banjara MR, Das P, Sundar S, Rijal S, Joshi A, Kroeger A, Varghese B, Thakur CP, Huda MM, Mondal D. KEM Hospital Research Center, Rasta Peth, Pune 411011 India; Institute of Medical Sciences, Benares Hindu University, Varanasi, India; Rajendra Memorial Research Institute of Medical Sciences, Patna, India; Institute of Medicine, Tribhuvan University, Kathmandu, Nepal; BP Koirala Institute of Health Sciences, Dharan, Nepal; World Health Organization, Special Programme for Research and Training in Tropical Diseases, WHO, Geneva, Switzerland; School of Tropical Medicine, Liverpool, United Kingdom; Public Health Foundation of India, New Delhi, India; Balaji Utthan Sanstha, Patna, India; International Center for Diarrheal Diseases Research, Bangladesh, Dhaka, Bangladesh. Abstract This study analyzed the effectiveness of active case detection (ACD) for new visceral leishmaniasis (VL) cases. ACD detection was carried out using house to house screening in Bangladesh and India and by neighborhood screening around index cases in Nepal. The percent increase of new VL cases through ACD compared to PCD was 6.7-17.1% in India; 38.8% in Nepal; and 60% in Bangladesh. The screening effort was high in India and Bangladesh (house to house screening) compared to Nepal (index case screening). The additional cost per new VL case detected varied: $50 to $106 in India; $172 in Bangladesh; $262 in Nepal depending on the type of screening staff, transport and training costs. The estimated annual VL incidence in the ACD arm ranged from 315-383 in India; 109 in Bangladesh, and 43 per 100,000 in Nepal. The additional effort and cost rises as disease incidence declines or PCD improves.
	PMID: 20810811 [PubMed - as supplied by publisher]
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5.	Am J Trop Med Hyg. 2010 Sep;83(3):502-6. Asymptomatic infection with visceral leishmaniasis in a disease-endemic area in bihar, India. Topno RK, Das VN, Ranjan A, Pandey K, Singh D, Kumar N, Siddiqui NA, Singh VP, Kesari S, Kumar N, Bimal S, Kumar AJ, Meena C, Kumar R, Das P. Rajendra Memorial Research Institute of Medical Science, Agamkuan Patna, Bihar, India. Abstract A prospective study was carried out in a cohort of 355 persons in a leishmaniasis-endemic village of the Patna District in Bihar, India, to determine the prevalence of asymptomatic persons and rate of progression to symptomatic visceral leishmaniasis (VL) cases. At baseline screening, 50 persons were positive for leishmaniasis by any of the three tests (rK39 strip test, direct agglutination test, and polymerase chain reaction) used. Point prevalence of asymptomatic VL was 110 per 1,000 persons and the rate of progression to symptomatic cases was 17.85 per 1,000 person-months. The incidence rate ratio of progression to symptomatic case was 3.36 (95% confidence interval [CI] = 0.75-15.01, P = 0.09) among case-contacts of VL compared with neighbors. High prevalence of asymptomatic persons and clinical VL cases and high density of Phlebotomus argentipes sand flies can lead to transmission of VL in VL-endemic areas.
	PMID: 20810810 [PubMed - in process]
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6.	Vet Parasitol. 2010 Aug 6. [Epub ahead of print] Comparison between ELISA using total antigen and immunochromatogr aphy with antigen rK39 in the diagnosis of canine visceral leishmaniasis. de Lima VM, Fattori KR, Michelin AD, Neto LD, Vasconcelos RD. Departamento de Clínica, Cirurgia e Reprodução Animal, Faculdade de Odontologia de Araçatuba, Curso de Medicina Veterinária, Universidade Estadual Paulista, Rua Clóvis Pestana, 793, Jardim Dona Amélia, 16050-680 - Araçatuba, SP, Brazil. Abstract In this study, an enzyme-linked immunosorbent assay using crude total antigen (CTA-ELISA) and immunochromatography with antigen rK39 were compared in the diagnosis of canine visceral leishmaniasis (CVL). Fifty-two total blood samples from symptomatic dogs obtained from a location endemic for leishmaniasis and 52 blood samples from healthy dogs from a nonendemic region were tested. Polymerase chain reaction (PCR) was used to detect DNA from Leishmania spp. in both groups. Symptomatic dogs with positive PCR were considered infected by Leishmania spp. and the PCR technique was chosen as a gold standard test. The sensitivity determined for CTA-ELISA was 100%, with specificity of 91.2%, while the immunochromatographic assay with the antigen rK39 showed sensitivity of 91.5%, with specificity of 94.7%. A strong correlation was verified between CTA-ELISA and immunochromatography with antigen rK39, with a kappa coefficient of agreement of 0.88. Analysis of the results suggested that both assays presented good sensitivity and specificity for diagnosing CVL; however, immunochromatography with the antigen rK39 may be more advantageous when a fast field test is required.
	PMID: 20810216 [PubMed - as supplied by publisher]
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7.	Eur J Immunol. 2010 Sep;40(9):2356-7. In this issue. [No authors listed] Abstract COVER IMAGE: This issue's cover consists of a collage of images taken from Mönnich et al. (pp. 2379-2384). In this elegant study, the authors describe the identification and characterization of two deleterious mutations in the zebrafish topoisomerase III alpha (top3a) gene that reveal an unexpected tissue-specific requirement of top3a function in developing thymocytes. In the forefront, the structure of the E. coli Top3 protein in complex with ssDNA substrate is depicted. In the background, the image depicts a lateral view of rag1-specific RNA in situ hybridization in a 5-day post-fertilization zebrafish embryo, allowing for the detection of differentiating thymocytes. THE UPSIDE AND DOWNSIDE OF ESTROGEN POWER: INDUCTION OF IL-17: Estrogen, a natural immunomodulator, is thought to contribute to well known sex-differences in immune capabilities and to influence female-predominant autoimmune diseases. In this issue, Khan et al. show that splenocytes from estrogen-exposed C57BL/6 mice respond robustly to IL-6+TGF-beta+anti-CD3, resulting in the vigorous induction of the powerful proinflammatory cytokine IL-17. Estrogen-promotion of IL-17 can be both bane and boon, as IL-17 plays a key role in triggering inflammation that counter extracellular pathogens, but aberrant regulation of IL-17 levels can also promote autoimmune or inflammatory diseases. In this study, the authors also demonstrate that exposure of splenocytes to IL-27 or IFN-gamma prior to their commitment to IL-17-secreting cells suppresses the induction of IL-17, in part, by inhibiting the expression of the IL-17-specific transcription factor RORgammat. However, delaying IL-27 or IFN-gamma exposure diminishes the two cytokines' effectiveness as "natural brakes" of IL-17 induction. Together, these findings reveal new facets of immune regulation by estrogen.pp. 2549-2556 VACCINES THAT CHANGE HOST IMMUNE RESPONSES TO PATHOGENS: THE ROLE OF TH17 CELLS IN LEISHMANIASIS: Leishmaniasis caused by Leishmania major is a neglected, emerging disease that produces open sores, scarring and disfigurement. A paradigmatic skin infection, it is an excellent model for the study of dermal immunity. Mendez and colleagues previously reported that vaccination of C57BL/6 mice with live L. major plus CpG DNA (Lm/CpG) prevents disease and provides long-term immunity. In this issue, Wu et al. further characterize the components of adaptive immunity that are unique to this successful live vaccine. The authors demonstrate that Lm/CpG induces the proliferation of Th17 cells, which contrasts with the highly polarized Th1 response caused by the infection alone, and that neutralization of IL-17 results in increased parasite burdens in Lm/CpG-vaccinated, but not in L. major-infected, mice. Furthermore, the authors show that IL-17 receptor-deficient Lm/CpG-vaccinated mice develop larger lesions and greater parasite burdens, as well as decreased neutrophil accumulation and increased regulatory T cell numbers, compared with their WT counterparts. Taken together, these findings suggest that vaccines combining live pathogens with immunomodulatory molecules may strikingly modify immunity to infection in a different manner to killed or subunit vaccines.pp. 2517-2527 B-CELL FATE CHOICE: BTK LACKS DECISION-MAKING CAPACITIES: Seventeen years after the identification of Bruton's tyrosine kinase (Btk) as the signaling molecule defective in the primary immunodeficiency disease X-linked agammaglobulinemia, the exact function of Btk in B cells remains unclear. Btk mediates B-cell receptor signals that provide the basis for the differentiation of B cells in the bone marrow, and subsequently into the follicular, marginal zone or B-1 B-cell subsets. In this issue, Kersseboom et al. report that transgenic mice expressing low levels of the constitutively active BtkE41K mutant, have reduced numbers of follicular and marginal zone B-cells, and increased B-1 B-cells, in the spleen. Residual B cells were shown to be hyperresponsive and spontaneously driven into germinal center-independent autoreactive IgM plasma cell differentiation. Interestingly, the authors demonstrate that constitutively active Btk expression did not change follicular, marginal zone or B-1 B-cell differentiation, but rather resulted in selective expansion or survival of B-1 cells. Together, these findings suggest that BCR signaling strength may not be responsible for B-cell differentiation, in contrast to previous postulates.pp. 2643-2654 HIGH CD127 EXPRESSION ON ACTIVATED TREG: A ROLE FOR IL-7 IN TREG BIOLOGY?: Treg (CD25(+)Foxp3(+)CD4(+) T cells) are crucial for the regulation of immune responses, and in preventing autoimmunity and inflammation. Treg have been characterized by a specific cytokine receptor expression profile, i.e. high expression of CD25 (IL-2Ralpha) and low expression of CD127 (IL-7Ralpha), both in mice and humans. In this issue, Simonetta et al. show that murine Treg up-regulate CD127 upon activation, both in vitro and in vivo, whereas Foxp3(-) conventional CD4(+) T cells down-regulate CD127. These findings thus demonstrate that low CD127 expression is not an intrinsic characteristic of Treg, and identify activated Treg as a novel target of endogenous and therapeutic IL-7. These data may have important clinical implications, both for Treg quantification in pathological conditions, and for the clinical development of IL-7-based therapies. The exact role of IL-7 on Treg biology remains to be further assessed: is IL-7 a survival factor, competition factor during suppression and/or modulator of Treg function?pp. 2528-2538 SUBOPTIMAL TCRalphabeta PAIRS OPERATE EFFECTIVELY AT THE SITE OF INFECTION: The extent of T-cell receptor (TCR) alphabeta diversity is thought to influence the efficacy of CD8(+) T-cell populations. In this issue, Valkenburg et al. challenge transgenic mice expressing a single, ovalbumin-specific TCRalpha chain with influenza A virus to investigate the mechanisms underlying this effect. The authors report that mandating the use of an "irrelevant" TCRValpha decreases both the response magnitude and the diversity of TCRVbeta selection for the two prominent influenza-specific CD8(+) T-cell sets. The effect was more pronounced for the particular epitope that normally generates a less diverse TCRbeta repertoire, reflecting the reduced availability of appropriate Vbeta chains that can pair with the fixed Valpha. Interestingly, although the IFN-gamma, TNF-alpha and IL-2 cytokine profiles were diminished for the cells recovered from the spleen of the transgenic, as compared with the control mice, this measure of polyfunctionality was equivalent for the cells that had localized to the infected lungs. Thus, these findings suggest that even "suboptimal" TCRalphabeta pairs can operate effectively when exposed to an inflammatory environment with high viral load.pp. 2470-2481.
	PMID: 20809488 [PubMed - in process]
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8.	PLoS One. 2010 Aug 17;5(8). pii: e12235. The impact of mRNA structure on guide RNA targeting in kinetoplastid RNA editing. Reifur L, Yu LE, Cruz-Reyes J, Vanhartesvelt M, Koslowsky DJ. Comparative Medicine and Integrative Biology Program, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, United States of America. Abstract Mitochondrial mRNA editing in Trypanosoma brucei requires the specific interaction of a guide RNA with its cognate mRNA. Hundreds of gRNAs are involved in the editing process, each needing to target their specific editing domain within the target message. We hypothesized that the structure surrounding the mRNA target may be a limiting factor and involved in the regulation process. In this study, we selected four mRNAs with distinct target structures and investigated how sequence and structure affected efficient gRNA targeting. Two of the mRNAs, including the ATPase subunit 6 and ND7-550 (5' end of NADH dehydrogenase subunit 7) that have open, accessible anchor binding sites show very efficient gRNA targeting. Electrophoretic mobility shift assays indicate that the cognate gRNA for ND7-550 had 10-fold higher affinity for its mRNA than the A6 pair. Surface plasmon resonance studies indicate that the difference in affinity was due to a four-fold faster association rate. As expected, mRNAs with considerable structure surrounding the anchor binding sites were less accessible and had very low affinity for their cognate gRNAs. In vitro editing assays indicate that efficient pairing is crucial for gRNA directed cleavage. However, only the A6 substrate showed gRNA-directed cleavage at the correct editing site. This suggests that different gRNA/mRNA pairs may require different "sets" of accessory factors for efficient editing. By characterizing a number of different gRNA/mRNA interactions, we may be able to define a "bank" of RNA editing substrates with different putative chaperone and other co-factor requirements. This will allow the more efficient identification and characterization of transcript specific RNA editing accessory proteins.
	PMID: 20808932 [PubMed - in process]
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9.	PLoS One. 2010 Aug 17;5(8). pii: e12211. Linking In Vitro and In Vivo Survival of Clinica l Leishmania donovani Strains. Vanaerschot M, Maes I, Ouakad M, Adaui V, Maes L, De Doncker S, Rijal S, Chappuis F, Dujardin JC, Decuypere S. Unit of Molecular Parasitology, Department of Parasitology, Institute of Tropical Medicine, Antwerp, Belgium. Abstract BACKGROUND: Leishmania donovani is an intracellular protozoan parasite that causes a lethal systemic disease, visceral leishmaniasis (VL), and is transmitted between mammalian hosts by phlebotomine sandflies. Leishmania expertly survives in these 'hostile' environments with a unique redox system protecting against oxidative damage, and host manipulation skills suppressing oxidative outbursts of the mammalian host. Treating patients imposes an additional stress on the parasite and sodium stibogluconate (SSG) was used for over 70 years in the Indian subcontinent. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated whether the survival capacity of clinical L. donovani isolates varies significantly at different stages of their life cycle by comparing proliferation, oxidative stress tolerance and infection capacity of 3 Nepalese L. donovani strains in several in vitro and in vivo models. In general, the two strains that were resistant to SSG, a stress encountered in patients, attained stationary phase at a higher parasite density, contained a higher amount of metacyclic parasites and had a greater capacity to cause in vivo infection in mice compared to the SSG-sensitive strain. CONCLUSIONS/SIGNIFICANCE: The 2 SSG-resistant strains had superior survival skills as promastigotes and as amastigotes compared to the SSG-sensitive strain. These results could indicate that Leishmania parasites adapting successfully to antimonial drug pressure acquire an overall increased fitness, which stands in contrast to what is found for other organisms, where drug resistance is usually linked to a fitness cost. Further validation experiments are under way to verify this hypothesis.
	PMID: 20808916 [PubMed - in process]
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10.	PLoS Pathog. 2010 Aug 19;6(8). pii: e1001050. Functional Characterisation and Drug Target Validation of a Mitotic Kinesin-13 in Trypanosoma brucei. Chan KY, Matthews KR, Ersfeld K. Department of Biological Sciences, University of Hull, Hull, United Kingdom. Abstract Mitotic kinesins are essential for faithful chromosome segregation and cell proliferation. Therefore, in humans, kinesin motor proteins have been identified as anti-cancer drug targets and small molecule inhibitors are now tested in clinical studies. Phylogenetic analyses have assigned five of the approximately fifty kinesin motor proteins coded by Trypanosoma brucei genome to the Kinesin-13 family. Kinesins of this family have unusual biochemical properties because they do not transport cargo along microtubules but are able to depolymerise microtubules at their ends, therefore contributing to the regulation of microtubule length. In other eukaryotic genomes sequenced to date, only between one and three Kinesin-13s are present. We have used immunolocalisation, RNAi-mediated protein depletion, biochemical in vitro assays and a mouse model of infection to study the single mitotic Kinesin-13 in T. brucei. Subcellular localisation of all five T. brucei Kinesin-13s revealed distinct distributions, indicating that the expansion of this kinesin family in kinetoplastids is accompanied by functional diversification. Only a single kinesin (TbKif13-1) has a nuclear localisation. Using active, recombinant TbKif13-1 in in vitro assays we experimentally confirm the depolymerising properties of this kinesin. We analyse the biological function of TbKif13-1 by RNAi-mediated protein depletion and show its central role in regulating spindle assembly during mitosis. Absence of the protein leads to abnormally long and bent mitotic spindles, causing chromosome mis-segregation and cell death. RNAi-depletion in a mouse model of infection completely prevents infection with the parasite. Given its essential role in mitosis, proliferation and survival of the parasite and the availability of a simple in vitro activity assay, TbKif13-1 has been identified as an excellent potential drug target.
	PMID: 20808899 [PubMed - in process]
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