This message contains My NCBI what's new results from the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).
Do not reply directly to this message.
Sender's message:
Sent on Tuesday, 2011 Jul 26Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
Click here to view complete results in PubMed. (Results may change over time.)
To unsubscribe from these e-mail updates click here.
| PubMed Results |
| 1. | J Biol Chem. 2011 Jul 22. [Epub ahead of print]Molecular determinants of ciliary membrane localization of trypanosoma cruzi flagellar calcium-binding protein.Maric D, McGwire BS, Buchanan KT, Olson CL, Emmer BT, Epting CL, Engman DM.SourceNorthwestern University, United States; AbstractThe flagellar calcium binding protein (FCaBP)(4) of Trypanosoma cruzi is localized to the flagellar membrane in all life cycle stages of the parasite. Myristoylation and palmitoylation of the N-terminus of FCaBP are necessary for flagellar membrane targeting. Not all dually acylated proteins in T. cruzi are flagellar, however. Other determinants of FCaBP therefore likely contribute to flagellar specificity. We generated T. cruzi transfectants expressing the N-terminal 24 or 12 amino acids of FCaBP fused to GFP. Analysis of these mutants revealed that while amino acids 1-12 are sufficient for dual acylation and membrane binding, amino acids 13-24 are required for flagellar specificity and lipid raft association. Mutagenesis of several conserved lysine residues in the latter peptide demonstrated that these residues are essential for flagellar targeting and lipid raft association. Finally, FCaBP was expressed in the protozoan Leishmania amazonensis, which lacks FCaBP. The flagellar localization and membrane association of FCaBP in L. amazonensis suggest that the mechanisms for flagellar targeting, including a specific palmitoyl acyltransferase, are conserved in this organism. |
| Related citations | |
| 2. | Int J Antimicrob Agents. 2011 Jul 21. [Epub ahead of print]Uptake and antileishmanial activity of meglumine antimoniate-containing liposomes in Leishmania (Leishmania) major-infected macrophages.Treiger Borborema SE, Schwendener RA, Osso Junior JA, de Andrade Junior HF, do Nascimento N.SourceInstituto de Pesquisas Energéticas e Nucleares-CNEN/SP, Centro de Biotecnologia, Av. Lineu Prestes 2242, CEP: 05508-000, São Paulo, SP, Brazil. AbstractLeishmaniasis is a parasitic disease caused by the intramacrophage protozoa Leishmania spp. and may be fatal if left untreated. Although pentavalent antimonials are toxic and their mechanism of action is unclear, they remain the first-line drugs for treatment of leishmaniasis. An effective therapy could be achieved by delivering antileishmanial drugs to the site of infection. Compared with free drugs, antileishmanial agent-containing liposomes are more effective, less toxic and have fewer adverse side effects. The aim of this study was to develop novel meglumine antimoniate (MA)-containing liposome formulations and to analyse their antileishmanial activity and uptake by macrophages. Determination of the 50% inhibitory concentration (IC(50)) values showed that MA-containing liposomes were ≥10-fold more effective than the free drug, with a 5-fold increase in selectivity index, higher activity and reduced macrophage toxicity. The concentration required to kill 100% of intracellular amastigotes was ≥40-fold lower when MA was encapsulated in liposomes containing phosphatidylserine compared with the free drug. Fluorescence microscopy analysis revealed increased uptake of fluorescent liposomes in infected macrophages after short incubation times compared with non-infected macrophages. In conclusion, these data suggest that MA encapsulated in liposome formulations is more effective against Leishmania-infected macrophages than the non-liposomal drug. Development of liposome formulations is a valuable approach to the treatment of infectious diseases involving the mononuclear phagocyte system. Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. |
| Related citations | |
| 3. | J Ethnopharmacol. 2011 Jul 18. [Epub ahead of print]In vitro antitrypanosomal and antileishmanial activity of plants used in Benin in traditional medicine and bio-guided fractionation of the most active extract.Bero J, Hannaert V, Gabrielle C, Marie-France H, Quetin-Leclercq J.SourceUniversité catholique de Louvain, Louvain Drug Research Institute, Pharmacognosy Research Group, Avenue E. Mounier, 72, B-1200 Brussels, Belgium. AbstractETHNOPHARMACOLOGICAL RELEVANCE:The aim of the study was to evaluate the in vitro antitrypanosomal and antileishmanial activity of crude extracts of 10 plant species traditionally used in Benin to treat parasitic infections. MATERIALS AND METHODS:For each species, dichloromethane, methanol and aqueous extracts were tested. Their antitrypanosomal and antileishmanial activities were evaluated in vitro on Trypanosoma brucei brucei (strain 427) (Tbb) and on promastigotes of Leishmania mexicana mexicana (MHOM/BZ/84/BEL46) (Lmm). RESULTS:The best growth inhibition was observed with the dichloromethane extracts of aerial parts of Acanthospermum hispidum DC. (Asteraceae) (IC(50)=14.5μg/ml on Tbb and 11.1μg/ml on Lmm), twigs of Keetia leucantha (K. Krause) Bridson (syn. Plectronia leucantha Krause) (IC(50)=5.8μg/ml on Tbb), aerial parts of Byrsocarpus coccineus Schumach. & Thonn (syn. Rourea coccinea (Schumach. & Thonn.) Hook.f.) (IC(50)=14.7μg/ml on Tbb) and aerial parts of Carpolobia lutea G.Don. (IC(50)=18.3μg/ml on Tbb). All these extracts had a low cytotoxicity. It is not the case for the methanolic and water extracts of roots of Anchomanes difformis (Blume) Engl. (IC(50)=14.7 and 13.8μg/ml on Tbb) which were toxic at the same concentration range on WI38, human cells. A bio-guided fractionation of the most active extract of Keetia leucantha allowed to identify oleanolic acid and ursolic acid as responsible for the observed activities. CONCLUSION:Our study gives some justification for antiparasitic activity of some investigated plants. Copyright © 2011. Published by Elsevier Ireland Ltd. |
| Related citations | |
| 4. | Nanomedicine. 2011 Jul 20. [Epub ahead of print]Investigations on Alternate Approach to Target Mannose Receptors on Macrophages using 4-Sulfated N-Acetyl Galactosamine more Efficiently as Compared to Mannose Decorated Liposomes : An Application in Drug Delivery.Singodia D, Verma A, Verma RK, Mishra PR.AbstractIn the present study the targeting potential of two different ligands i.e palmitoyl mannose (Man-Lip) and 4-SO(4)GalNAc (Sulf-Lip) to resident macrophages have been investigated after having decorated on the surface of Amphotericin B (AmB) loaded liposomes. In case of Sulf-Lip, the 4-SO(4)GalNAc was adsorbed through electrostatic interaction on cationic liposomes, which was confirmed by change in zeta potential from +48.2 ± 3.7 mV for Lip to +12.2 ± 1.3 mV for Sulf-Lip. The mean particle size of Sulf-Lip and Man-Lip was found to be 139.4 ± 7.4 nm and 147.4 ± 8.6 nm respectively. Flow cytometric data reveals enhanced uptake of Sulf-Lip in both J774 and RAW cell lines as compared to Man-Lip. Intracellular localization studies indicate that the fluorescence intensity of Sulf-Lip was much higher as compared to Man-Lip and Lip formulations. Sulf-Lip and Man-Lip showed significantly higher localization of AmB at all time points compared to Lip (P < .05) after i.v. administration. The studies provides evidences that 4-SO(4)GalNAc possess promising feature for targeting resident macrophages and its application in the conditions of leishmaniasis is in offing. Copyright © 2011. Published by Elsevier Inc. |
| Related citations | |
| 5. | Parasite Immunol. 2011 Jul 22. doi: 10.1111/j.1365-3024.2011.01318.x. [Epub ahead of print]Co-administration of rectal BCG and Autoclaved Leishmania major (ALM) induce protection in susceptible BALB/c mice.Soudi S, Hosseini AZ, Hashemi SM.SourceDepartment of Immunology, Faculty of Medical sciences, Tarbiat Modares University, PO Box 14115-331, Tehran, Iran. AbstractWe examined the protective effect of autoclaved Leishmania major (ALM) vaccine in combination of either rectal or subcutaneous BCG on susceptible BALB/c mice. One month after BCG vaccination, BALB/c mice were immunized subcutaneously twice with ALM + alum at three weeks intervals. Three weeks after booster injection, 5 × 10(5) stationary phase L.major promastigotes were inoculated subcutaneously in one footpad. Immunological evaluation at before and post infectious challenge, showed strong proliferative responses in the spleen cells of the rectal immunized group after stimulating with parasite lysate. High level of interferon gamma was induced in the spleen and significant increase in the serum ratio of IgG2a/IgG1was observed only in rectal immunized group. Rectal immunized mice showed comparable nitric oxide production and iNOS induction in peritoneal macrophages (p ≤ 0.05). The obtained results in rectal BCG vaccinated group showed no mortality but low parasite burden in the liver and spleen. In conclusion, the results of the our study indicated that co-administration of rectal BCG and ALM induced protective type 1 immune responses against L. major infection. This safe and effective mucosal vaccine could be useful in prevention of human leishmaniasis infections. Copyright © 2011 Blackwell Publishing Ltd. |
| Related citations | |
| 6. | Mol Biochem Parasitol. 2011 Jun;177(2):116-25. Epub 2011 Feb 24.Differential protein expression throughout the life cycle of Trypanosoma congolense, a major parasite of cattle in Africa.Eyford BA, Sakurai T, Smith D, Loveless B, Hertz-Fowler C, Donelson JE, Inoue N, Pearson TW.SourceDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada. AbstractTrypanosoma congolense is an important pathogen of livestock in Africa. To study protein expression throughout the T. congolense life cycle, we used culture-derived parasites of each of the three main insect stages and bloodstream stage parasites isolated from infected mice, to perform differential protein expression analysis. Three complete biological replicates of all four life cycle stages were produced from T. congolense IL3000, a cloned parasite that is amenable to culture of major life cycle stages in vitro. Cellular proteins from each life cycle stage were trypsin digested and the resulting peptides were labeled with isobaric tags for relative and absolute quantification (iTRAQ). The peptides were then analyzed by tandem mass spectrometry (MS/MS). This method was used to identify and relatively quantify proteins from the different life cycle stages in the same experiment. A search of the Wellcome Trust's Sanger Institute's semi-annotated T. congolense database was performed using the MS/MS fragmentation data to identify the corresponding source proteins. A total of 2088 unique protein sequences were identified, representing 23% of the ∼9000 proteins predicted for the T. congolense proteome. The 1291 most confidently identified proteins were prioritized for further study. Of these, 784 yielded annotated hits while 501 were described as "hypothetical proteins". Six proteins showed no significant sequence similarity to any known proteins (from any species) and thus represent new, previously uncharacterized T. congolense proteins. Of particular interest among the remainder are several membrane molecules that showed drastic differential expression, including, not surprisingly, the well-studied variant surface glycoproteins (VSGs), invariant surface glycoproteins (ISGs) 65 and 75, congolense epimastigote specific protein (CESP), the surface protease GP63, an amino acid transporter, a pteridine transporter and a haptoglobin-hemoglobin receptor. Several of these surface disposed proteins are of functional interest as they are necessary for survival of the parasites. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved. |
| Related citations | |
 |
| 7. | Mol Biochem Parasitol. 2011 Jun;177(2):152-5. Epub 2011 Feb 24.TcNDPK2, a Trypanosoma cruzi microtubule-associated nucleoside diphosphate kinase.Miranda MR, Camara Mde L, Bouvier LA, Pereira CA.SourceLaboratorio de BiologÃa Molecular de Trypanosoma cruzi (LBMTC), Instituto de Investigaciones Médicas Alfredo Lanari, Universidad de Buenos Aires and CONICET, Buenos Aires, Argentina. AbstractNucleoside diphosphate kinases (NDPKs) are enzymes required to preserve the intracellular nucleoside phosphate equilibrium. Trypanosoma cruzi has four putative nucleoside diphosphate kinases with unidentified biological roles and subcellular localization. TcNDPK2 has an N-terminal domain (DM10) with unknown function, which defines a subgroup of NDPKs distributed in a wide variety of organisms. Digitonin extraction demonstrated that this isoform is distributed in detergent soluble and insoluble fractions. Fluorescence microscopy showed that TcNDPK2 alone or fused to GFP was localized in cytoskeleton and flagella. TcNDPK2 was also detected by Western blot in purified polymerized tubulin and flagellar samples. In parasites expressing DM10 fused with GFP, the fluorescence was localized in cytoskeleton and flagellum with an identical pattern to TcNDPK2. This constitutes the first report that could give insights on the role of DM10 domains in NDPKs and also the identification of the first T. cruzi peptide that contains a microtubule association domain. Copyright © 2011 Elsevier B.V. All rights reserved. |
| Related citations | |
| |
| 8. | Mol Biochem Parasitol. 2011 Jun;177(2):83-99. Epub 2011 Feb 21.Autophagy in parasitic protists: unique features and drug targets.< /h1>Brennand A, Gualdrón-López M, Coppens I, Rigden DJ, Ginger ML, Michels PA.SourceResearch Unit for Tropical Diseases, de Duve Institute, Brussels, Belgium. ana.paesbarreto@uclouvain.be AbstractEukaryotic cells can degrade their own components, cytosolic proteins and organelles, using dedicated hydrolases contained within the acidic interior of their lysosomes. This degradative process, called autophagy, is used under starvation conditions to recycle redundant or less important macromolecules, facilitates metabolic re-modeling in response to environmental cues, and is also often important during cell differentiation. In this review, we discuss the role played by autophagy during the life cycles of the major parasitic protists. To provide context, we also provide an overview of the different forms of autophagy and the successive steps in the autophagic processes, including the proteins involved, as revealed in recent decades by studies using the model organism Saccharomyces cerevisiae, methylotrophic yeasts and mammalian cells. We describe for trypanosomatid parasites how autophagy plays a role in the differentiation from one life cycle stage to the next one and, in the case of the intracellular parasites, for virulence. For malarial parasites, although only a limited repertoire of canonical autophagy-related proteins can be detected, autophagy seems to play a role in the removal of redundant organelles important for cell invasion, when sporozoites develop into intracellular trophozoites inside the hepatocytes. The complete absence of a canonical autophagy pathway from the microaerophile Giardia lamblia is also discussed. Finally, the essential role of autophagy for differentiation and pathogenicity of some pathogenic protists suggests that the proteins involved in this process may represent new targets for drug development. Opportunities and strategies for drug design targeting autophagy proteins are discussed. Copyright © 2011 Elsevier B.V. All rights reserved. |
| Related citations | |
| |
| 9. | Int J Antimicrob Agents. 2011 May;37(5):449-56. Epub 2011 Feb 2.Effect of topoisomerase inhibitors and DNA-binding drugs on the cell p roliferation and ultrastructure of Trypanosoma cruzi.Zuma AA, Cavalcanti DP, Maia MC, de Souza W, Motta MC.SourceLaboratório de Ultraestrutura Celular Hertha Meyer, Instituto de BiofÃsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-590 Rio de Janeiro, RJ, Brazil. AbstractTrypanosomatids present unusual organelles, such as the kinetoplast that contains the mitochondrial DNA arranged in catenated circles. The nucleus of these protozoa presents distinct domains during interphase as well as a closed mitosis. DNA topoisomerases modulate the topological state of DNA by regulating supercoiling of the double-stranded DNA during replication, transcription, recombination and repair. Because topoisomerases play essential roles in cellular processes, they constitute a potential target for antitumour and antimicrobial drugs. In this study, the effects of various topoisomerase inhibitors and DNA-binding drugs were tested on the cellular proliferation and ultrastructure of the Trypanosoma cruzi epimastigote form Blastocrithidia culicis was used as a comparative model, which has a more relaxed kinetoplast DNA (kDNA) organization. The results showed that the eukaryotic topoisomerase I inhibitors camptothecin and rebeccamycin were the most effective compounds in the arrest of T. cruzi proliferation. Of the eukaryotic topoisomerase II inhibitors, mitoxantrone, but not merbarone, was effective against cell proliferation. The prokaryotic topoisomerase II inhibitors norfloxacin and enoxacin targeted the kinetoplast specifically, thus promoting ultrastructural kDNA rearrangement in B. culicis. Of the DNA-binding drugs, berenil caused remarkable kDNA disorganization. With the exception of camptothecin, there have been no previous evaluations of the compounds tested here on trypanosomatid ultrastructure. In conclusion, inhibitors of the same class may have different effects on trypanosomatid proliferation and ultrastructure. The results obtained in this work may help to reveal the mechanism of action of different topoisomerase inhibitors in trypanosomatids. Copyright © 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. |
| Related citations | |
| |
No comments:
Post a Comment