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Sent on Tuesday, 2009 Nov 03Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Eur J Ophthalmol. 2009 Jul 24. [Epub ahead of print]Proliferative vitreoretinopathy in a child with visceral leishmaniasis.Salvanos P, Kabanarou SA, Xirou T, Kourentis C, Feretis E.Ophthalmic Department, Ullevål University Hospital, Oslo - Norway. Purpose. We present a rare case of ocular leishmaniasis complicated by proliferative vitreoretinopathy in a child with active visceral leishmaniasis. Methods. A 10-year-old boy with active visceral leishmaniasis presented with a 5- day history of redness, photophobia, and blurred vision in his left eye. Visual acuity was measured and the child had a complete ocular examination. Results. Snellen best-corrected visual acuity (BCVA) was 10/10 in the right eye and 7/10 in the left eye at presentation. Ophthalmic examination of the right eye was normal but the left eye showed clinical signs of panuveitis. Laboratory investigations were negative. Treatment with systemic and local steroids was initiated and clinical improvement achieved. Eight months later, the patient had a relapse of systemic and ocular disease with severe panuveitis in both eyes. A combined tractional-rhegmatogenous retinal detachment was present in the left eye. Pars plana vitrectomy was undertaken in the left eye and the patient was started on systemic and local steroid treatment. Retinal reattachment was achieved postoperatively but visual acuity in the left eye remained poor. Conclusions. Early diagnosis, prompt systemic and ocular treatment, as well as close ophthalmic examination are essential in such cases. |
| PMID: 19882533 [PubMed - as supplied by publisher] | |
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| 2. | Saudi Med J. 2009 Nov;30(11):1480-2.Coping with visceral leishmaniasis in Turkey.Cakan HS, Iscan MY, Oz V, Aslan M, Karayel TM, Cakir I, Uner HB.Institute of Forensic Sciences, Istanbul University, Istanbul, Turkey. Tel. +90 (212) 4143000 Ext. 22824. Fax. +90 (212) 5880011. E-mail: hcakan@istanbul.edu.tr. |
| PMID: 19882066 [PubMed - in process] | |
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| 3. | Proc Natl Acad Sci U S A. 2009 Oct 30. [Epub ahead of print]Propulsion of African trypanosomes is driven by bihelical waves with alternating chirality separated by kinks.Rodríguez JA, Lopez MA, Thayer MC, Zhao Y, Oberholzer M, Chang DD, Kisalu NK, Penichet ML, Helguera G, Bruinsma R, Hill KL, Miao J.Molecular Biology Institute, Department of Surgery, Division of Surgical Oncology, and Department of Microbiology Immunology and Molecular Genetics, The David Geffen School of Medicine, and Department of Physics and Astronomy, University of California, Los Angeles, CA 90095. Trypanosoma brucei, a parasitic protist with a single flagellum, is the causative agent of African sleeping sickness. Propulsion of T. brucei was long believed to be by a drill-like, helical motion. Using millisecond differential interference-contrast microscopy and analyzing image sequences of cultured procyclic-form and bloodstream-form parasites, as well as bloodstream-form cells in infected mouse blood, we find that, instead, motility of T. brucei is by the propagation of kinks, separating left-handed and right-handed helical waves. Kink-driven motility, previously encountered in prokaryotes, permits T. brucei a helical propagation mechanism while avoiding the large viscous drag associated with a net rotation of the broad end of its tapering body. Our study demonstrates that millisecond differential interference-contrast microscopy can be a useful tool for uncovering important short-time features of microorganism locomotion. |
| PMID: 19880745 [PubMed - as supplied by publisher] | |
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| 4. | J Biol Chem. 2009 Oct 30. [Epub ahead of print]RNA interference in Trypanosoma brucei: the role of the amino-terminal RGG domain and the polyribosome association of Argonaute1.Shi H, Chamond N, Djikeng A, Tschudi C, Ullu E.Yale University, United States. Argonaute proteins (AGO) are central to RNA interference (RNAi) and related silencing pathways. At the core of the RNAi pathway in the ancient parasitic eukaryote Trypanosoma brucei is a single Argonaute protein, TbAGO1, with an established role in the destruction of potentially harmful retroposon transcripts. One notable feature of TbAGO1 is that a fraction sediments with polyribosomes and this association is facilitated by an arginine/glycine-rich domain (RGG domain) at the N-terminus of the protein. Here we report that reducing the size of the RGG domain and in particular mutating all arginine residues, severely reduced the association of TbAGO1 with polyribosomes and RNAi-induced cleavage of mRNA. However, these mutations did not change the cellular localization of Argonaute and did not affect the accumulation of single-stranded siRNAs, an essential step in the activation of the RNA-induced silencing complex. We further show that mRNA on polyribosomes can be targeted for degradation, although this alliance is not a pre-requisite. Finally, sequestering tubulin mRNAs from translation with antisense morpholino oligonucleotides reduced the RNAi response indicating that mRNAs not engaged in translation may be less accessible to the RNAi machinery. We conclude that the association of the RNAi machinery and target mRNA on polyribosomes promotes an efficient RNAi response. This mechanism may represent an ancient adaptation to insure that retroposon transcripts are efficiently destroyed, if they become associated with the translational apparatus. |
| PMID: 19880512 [PubMed - as supplied by publisher] | |
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| 5. | J Biol Chem. 2009 Oct 30. [Epub ahead of print]Identification and characterization of a novel deoxyhypusine synthase in Leishmania donovani.Chawla B, Jhingran A, Singh S, Tyagi N, Park MH, Srinivasan N, Roberts SC, Madhubala R.Jawaharlal Nehru University, India; Deoxyhypusine synthase, an NAD+-dependent enzyme, catalyzes the first step in the post-translational synthesis of an unusual amino acid, hypusine [N epsilon-(4-amino-2-hydroxybutyl)lysine], in the eukaryotic initiation factor 5A (eIF5A) precursor protein. Two putative deoxyhypusine synthase (DHS) sequences have been identified in the Leishmania donovani genome, which are present on chromosomes 20 (DHS-like-gene, DHSL20) and 34 (DHS34). Although both sequences exhibit an overall conservation of key residues, DHSL20 protein lacks a critical lysine residue and the recombinant protein showed no DHS activity in vitro. However, DHS34 contains the critical lysine residue and the recombinant DHS34 effectively catalyzed deoxyhypusine synthesis. Furthermore, in vivo labeling confirmed that hypusination of eIF5A occurs in intact Leishmania parasites. Interestingly, the DHS34 is much longer with 601 amino acids compared to the human DHS enzyme (369 amino acids) and contains several unique insertions. To study the physiological role of DHS34 in Leishmania, gene deletion mutations were attempted via targeted gene replacement. However, chromosomal null mutants of DHS34 could only be obtained in the presence of a DHS34-containing episome. The present data provide evidence that DHS34 is essential for L. donovani and that structural differences in the human and leishmanial DHS enzyme may be exploited for designing selective inhibitors against the parasite. |
| PMID: 19880510 [PubMed - as supplied by publisher] | |
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| 6. | Vaccine. 2009 Oct 29. [Epub ahead of print]Safety and immunogenicity of a defined vaccine for the prevention of cutaneous leishmaniasis.Vélez ID, Gilchrist K, Martίnez S, Ramírez-Pineda JR, Ashman JA, Alves FP, Coler RN, Bogatzki LY, Kahn SJ, Beckmann AM, Cowgill KD, Reed SG, Piazza FM.Programa de Estudio y Control de Enfermedades Tropicales, PECET, Universidad de Antioquia, Medellín, Colombia. Healthy Colombian adult volunteers with no history of leishmaniasis were evaluated for evidence of previous subclinical infection with Leishmania based on the Montenegro skin test (MST). Twelve MST-positive subjects were enrolled in an open-label, uncontrolled clinical trial (the "MST-positive trial") and received three injections of the LEISH-F1+MPL-SE vaccine (consisting of 10mug recombinant Leishmania polyprotein LEISH-F1 antigen [TSA+LmSTI1+LeIF]+25mug MPL((R))-SE adjuvant). Sixty-eight MST-negative subjects were enrolled in a randomized, double-blind, controlled trial (the "MST-negative trial") and were randomly assigned to receive three injections of either the vaccine (n=34), 10mug LEISH-F1 protein-alone (n=17), or saline placebo (n=17). In both trials, the study injections were given subcutaneously on Days 0, 28, and 56, and subjects were followed for safety and immunological endpoints. The LEISH-F1+MPL-SE vaccine was safe and well tolerated in MST-positive and MST-negative subjects. In both trials, an IFN-gamma response to the LEISH-F1 antigen at Day 84 was observed in more than half of the vaccine recipients. In the MST-negative trial, the IFN-gamma response was significantly more frequent and of greater magnitude in vaccine recipients than in protein-alone or placebo recipients. An IgG antibody response to LEISH-F1 was observed in all vaccine recipients. In both trials, delayed-type hypersensitivity (DTH) to LEISH-F1 was observed in most of the vaccine recipients. In the MST-negative trial, DTH was significantly higher in vaccine than placebo recipients. These clinical trials of the first defined vaccine for leishmaniasis show that the LEISH-F1+MPL-SE vaccine is safe and immunogenic in healthy subjects with and without evidence of previous subclinical infection with Leishmania. |
| PMID: 19879995 [PubMed - as supplied by publisher] | |
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| 7. | Mol Biochem Parasitol. 2009 Oct 29. [Epub ahead of print]Isolation of Toxoplasma gondii development mutants identifies a potential proteophosphogylcan that enhances cyst wall formation.Craver MP, Rooney PJ, Knoll LJ.Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, 1550 Linden Drive, Madison, WI 53706. Within warm-blooded animals, Toxoplasma gondii switches from an actively replicating form called a tachyzoite into a slow growing encysted form called a bradyzoite. To uncover the genes involved in bradyzoite development, we screened over 8000 T. gondii insertional mutants by immunofluorescence microscopy. We identified nine bradyzoite development mutants that were defective in both cyst wall formation and expression of a bradyzoite specific heat shock protein. One of these mutants, named 42F5, contained an insertion into the predicted gene TGME49_097520. The disrupted protein is serine/proline-rich with homology to proteophosphoglycans from Leishmania. T. gondii proteophosphoglycan (TgPPG1) expressed from the native promoter was undetectable in tachyzoites, but bradyzoites show punctate spots within the parasite and staining around the parasitophorous vacuole. Complementation of the 42F5 mutant with TgPPG1 expressed from either the alpha-tubulin or native promoter restores cyst wall formation. Overall, TgPPG1 is upregulated in bradyzoites and enhances cyst wall component expression and assembly. |
| PMID: 19879901 [PubMed - as supplied by publisher] | |
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| 8. | Int J Parasitol. 2009 Oct 29. [Epub ahead of print]The paraflagellar rod of kinetoplastid parasites: From structure to components and function.Portman N, Gull K.Sir William Dunn School of Pathology, University of Oxford, Oxford, UK OX1 3RE. The role of the eukaryotic flagellum in cell motility is well established but its importance in many other aspects of cell biology, from cell signaling to developmental regulation, is becoming increasingly apparent. In addition to this diversity of function the core structure of the flagellum, which has been inherited from the earliest ancestor of all eukaryotes, is embellished with a range of extra-axonemal structures in many organisms. One of the best studied of these structures is the paraflagellar rod of kinetoplastid protozoa in which the morphological characteristics have been well defined and some of the major protein constituents have been identified. Here we discuss recent advances in the identification of further molecular components of the paraflagellar rod,, how these impact on our understanding of its function and regulation and the implications for therapeutic intervention in a number of devastating human pathologies. |
| PMID: 19879876 [PubMed - as supplied by publisher] | |
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| 9. | Acta Trop. 2009 Oct 29. [Epub ahead of print]Comparative study of kala-azar vector control measures in eastern Nepal.Das ML, Roy L, Rijal S, Paudel IS, Picado A, Kroeger A, Petzold M, Davies C, Boelaert M.B.P. Koirala Institute of Health Sciences, Dharan, Nepal. This study was conducted to explore the most effective vector control tool among indoor residual spraying (IRS), long lasting insecticidal nets (LLINs) and ecological vector management (EVM) as a part of the regional visceral leishmaniasis elimination initiative. Alpha-cypermethrin as IRS, PermaNet(R) as LLINs and plastering the inner walls of houses with lime as EVM were the interventions. One baseline and three follow up entomological surveys were carried out in all arms using CDC miniature light traps (LT) and mouth aspirators. Comparisons were made between intervention arms and control arms with pre intervention and post intervention vector densities. Light traps were found more efficient in the collection of P. argentipes in comparison to aspiration. Vector densities were significantly low in both IRS arm (p=0.009 in LT and p<0.001 in aspirator collections) and LLIN arm (p=0.019 in LT and p=0.023 in aspirator collections) in comparison to control arm. However, in EVM arm, there was no significant difference in P. argentipes sand fly density in comparison to control arm (p=0.785) in LT collections in follow-up surveys. Hence, IRS was found most effective control measure to decrease vector density. LLINs was also found effective and can be considered as a promising alternative vector control tool in VL elimination initiative. |
| PMID: 19879851 [PubMed - as supplied by publisher] | |
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| 10. | Eur J Med Chem. 2009 Sep 30. [Epub ahead of print]Alkyl and dialkylaminoethyl derivatives of 5-ami no-2-azabicyclo[3.2.2]nonanes and their antiplasmodial and antitrypanosomal activities.Faist J, Seebacher W, Kaiser M, Brun R, Saf R, Weis R.Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl-Franzens-University, Universitätsplatz 1, A-8010 Graz, Austria. N-Alkyl and N-(2-dialkylaminoethyl) derivatives of 5-amino-2-azabicyclo-nonanes were prepared and tested in vitro for their activities against the multidrug-resistant K(1) strain of Plasmodium falciparum and Trypanosoma brucei rhodesiense (STIB 900). Most of the new compounds showed lower antitrypanosomal activity than their parent compounds. With respect to their activity against P. falciparum the N-alkyl derivatives exhibited worse selectivity due to decreased antiplasmodial activity or higher cytotoxicity. In comparison all of the new N-(2-dialkylaminoethyl) analogues possessed a much better selectivity and a single of these compounds showed even better antiplasmodial activity and selectivity than chloroquine. |
| PMID: 19879671 [PubMed - as supplied by publisher] | |
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