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Sent on Tuesday, 2011 Oct 25Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | PLoS Negl Trop Dis. 2011 Oct;5(10):e1344. Epub 2011 Oct 11.Canine Antibody Response to Phlebotomus perniciosus Bites Negatively Correlates with the Risk of Leishmania infantum Transmission.Vlkova M, Rohousova I, Drahota J, Stanneck D, Kruedewagen EM, Mencke N, Otranto D, Volf P.SourceDepartment of Parasitology, Faculty of Science, Charles University in Prague, Prague, Czech Republic. AbstractBACKGROUND:Phlebotomine sand flies are blood-sucking insects that can transmit Leishmania parasites. Hosts bitten by sand flies develop an immune response against sand fly salivary antigens. Specific anti-saliva IgG indicate the exposure to the vector and may also help to estimate the risk of Leishmania spp. transmission. In this study, we examined the canine antibody response against the saliva of Phlebotomus perniciosus, the main vector of Leishmania infantum in the Mediterranean Basin, and characterized salivary antigens of this sand fly species. METHODOLOGY/PRINCIPAL FINDINGS:Sera of dogs bitten by P. perniciosus under experimental conditions and dogs naturally exposed to sand flies in a L. infantum focus were tested by ELISA for the presence of anti-P. perniciosus antibodies. Antibody levels positively correlated with the number of blood-fed P. perniciosus females. In naturally exposed dogs the increase of specific IgG, IgG1 and IgG2 was observed during sand fly season. Importantly, Leishmania-positive dogs revealed significantly lower anti-P. perniciosus IgG2 compared to Leishmania-negative ones. Major P. perniciosus antigens were identified by western blot and mass spectrometry as yellow proteins, apyrases and antigen 5-related proteins. CONCLUSIONS:Results suggest that monitoring canine antibody response to sand fly saliva in endemic foci could estimate the risk of L. infantum transmission. It may also help to control canine leishmaniasis by evaluating the effectiveness of anti-vector campaigns. Data from the field study where dogs from the Italian focus of L. infantum were naturally exposed to P. perniciosus bites indicates that the levels of anti-P. perniciosus saliva IgG2 negatively correlate with the risk of Leishmania transmission. Thus, specific IgG2 response is suggested as a risk marker of L. infantum transmission for dogs. |
| 2. | PLoS One. 2011;6(10):e26218. Epub 2011 Oct 14.Identification of intracellular and plasma membrane calcium channel homologues in pathogenic parasites.Prole DL, Taylor CW.SourceDepartment of Pharmacology, University of Cambridge, Cambridge, United Kingdom. AbstractCa(2+) channels regulate many crucial processes within cells and their abnormal activity can be damaging to cell survival, suggesting that they might represent attractive therapeutic targets in pathogenic organisms. Parasitic diseases such as malaria, leishmaniasis, trypanosomiasis and schistosomiasis are responsible for millions of deaths each year worldwide. The genomes of many pathogenic parasites have recently been sequenced, opening the way for rational design of targeted therapies. We analyzed genomes of pathogenic protozoan parasites as well as the genome of Schistosoma mansoni, and show the existence within them of genes encoding homologues of mammalian intracellular Ca(2+) release channels: inositol 1,4,5-trisphosphate receptors (IP(3)Rs), ryanodine receptors (RyRs), two-pore Ca(2+) channels (TPCs) and intracellular transient receptor potential (Trp) channels. The genomes of Trypanosoma, Leishmania and S. mansoni parasites encode IP(3)R/RyR and Trp channel homologues, and that of S. mansoni additionally encodes a TPC homologue. In contrast, apicomplexan parasites lack genes encoding IP(3)R/RyR homologues and possess only genes encoding TPC and Trp channel homologues (Toxoplasma gondii) or Trp channel homologues alone. The genomes of parasites also encode homologues of mammalian Ca(2+)influx channels, including voltage-gated Ca(2+) channels and plasma membrane Trp channels. The genome of S. mansoni also encodes Orai Ca(2+) channel and STIM Ca(2+) sensor homologues, suggesting that store-operated Ca(2+) entry may occur in this parasite. Many anti-parasitic agents alter parasite Ca(2+) homeostasis and some are known modulators of mammalian Ca(2+) channels, suggesting that parasite Ca(2+) channel homologues might be the targets of some current anti-parasitic drugs. Differences between human and parasite Ca(2+) channels suggest that pathogen-specific targeting of these channels may be an attractive therapeutic prospect. |
| 3. | Proteins. 2011 Sep 15. doi: 10.1002/prot.23196. [Epub ahead of print]Target highlights in CASP9: Experimental target structures for the critical assessment of techniques for protein structure prediction.Kryshtafovych A, Moult J, Bartual SG, Bazan JF, Berman H, Casteel DE, Christodoulou E, Everett JK, Hausmann J, Heidebrecht T, Hills T, Hui R, Hunt JF, Seetharaman J, Joachimiak A, Kennedy MA, Kim C, Lingel A, Michalska K, Montelione GT, Otero JM, Perrakis A, Pizarro JC, van Raaij MJ, Ramelot TA, Rousseau F, Tong L, Wernimont AK, Young J, Schwede T.SourceGenome Center, University of California, Davis, 451 Health Sciences Drive, Davis, California 95616. AbstractOne goal of the CASP community wide experiment on the critical assessment of techniques for protein structure prediction is to identify the current state of the art in protein structure prediction and modeling. A fundamental principle of CASP is blind prediction on a set of relevant protein targets, that is, the participating computational methods are tested on a common set of experimental target proteins, for which the experimental structures are not known at the time of modeling. Therefore, the CASP experiment would not have been possible without broad support of the experimental protein structural biology community. In this article, several experimental groups discuss the structures of the proteins which they provided as prediction targets for CASP9, highlighting structural and functional peculiarities of these structures: the long tail fiber protein gp37 from bacteriophage T4, the cyclic GMP-dependent protein kinase Iβ dimerization/docking domain, the ectodomain of the JTB (jumping translocation breakpoint) transmembrane receptor, Autotaxin in complex with an inhibitor, the DNA-binding J-binding protein 1 domain essential for biosynthesis and maintenance of DNA base-J (β-D-glucosyl-hydroxymethyluracil) in Trypanosoma and Leishmania, an so far uncharacterized 73 residue domain from Ruminococcus gnavus with a fold typical for PDZ-like domains, a domain from the phycobilisome core-membrane linker phycobiliprotein ApcE from Synechocystis, the heat shock protein 90 activators PFC0360w and PFC0270w from Plasmodium falciparum, and 2-oxo-3-deoxygalactonate kinase from Klebsiella pneumoniae. Proteins 2011; © 2011 Wiley-Liss, Inc. Copyright © 2011 Wiley-Liss, Inc. |
| 4. | Mol Cell Biochem. 2011 Oct 22. [Epub ahead of print]Diverse viscerotropic isolates of Leishmania all express a highly conserved secretory nuclease during human infections.Joshi MB, Hernandez Y, Owings JP, Dwyer DM.SourceCell Biology Section, Laboratory of Parasitic Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892-0425, USA. AbstractPreviously, we characterized a gene encoding the unique nuclease (LdNuc(s)) from a Sudanese isolate of the human pathogen Leishmania donovani. This parasite secretory enzyme is involved in the salvage of host-derived purines and is constitutively expressed by both developmental forms of the parasite. Currently, we assessed whether an LdNuc(s)-like nuclease was conserved among other geographically disparate isolates of L. donovani and whether this enzyme was produced by intracellular amastigotes during human infections. Using RT-PCR and Southern blotting, we showed that LdNuc (s) gene homologs were present in each of the viscerotropic Leishmania tested (i.e., L. donovani isolates from the Sudan, Ethiopia and India as well as L. infantum). Further results of in situ enzyme activity gel analyses showed that each of these parasite isolates also expressed a released/secreted LdNuc (s)-like nuclease activity. In Western blots, our anti-LdNuc(s) (Sudan) peptide-specific antibody reacted with only a single ~35 kDa protein in each of the viscerotropic Leishmania isolates. Further, the ~35 kDa nuclease secreted by each of these isolates was specifically immunoprecipitated by the anti-LdNuc(s) antibody above. In situ gel analyses showed that each of these immunoprecipitates had LdNuc(s)-like nuclease activity. Moreover, sera from acute visceral leishmaniasis patients from India, Sudan and Brazil all immunoprecipitated an LdNuc(s)-HA expressed nuclease demonstrating, that these patients possessed antibodies against this parasite secretory enzyme. Cumulatively, these results showed that the LdNuc (s) homologs were functionally conserved among geographically disparate visceral Leishmania spp. and that amastigotes of these parasites must produce this nuclease enzyme during the course of human disease. |
| 5. | Exp Parasitol. 2011 Oct 12. [Epub ahead of print]Lack of signaling by IL-4 or by IL-4/IL-13 has more attenuating effects on Leishmania amazonensis dorsal skin - than on footpad-infected mice.Felizardo TC, Gaspar-Elsas MI, Lima GM, Abrahamsohn IA.SourceDepartamento de Imunologia, Instituto de Ciências Biomédicas IV, Universidade de São Paulo, Av. Prof. Lineu Prestes 1730, 05508-900 São Paulo, SP, Brazil. AbstractLesion development in tegumentary leishmaniasis is markedly influenced by the inoculation site and the type and number of injected infective forms. This and the yet unclear contribution of Th2 cytokines as susceptibility factors to Leishmania amazonensis infection prompted us to investigate the roles of IL-4, IL-13 and IL-10 on C57BL/6 and BALB/c mice infected in the footpad (paw) or rump with low-dose L. amazonensis purified-metacyclics. Wild-type (WT) mice of either strain developed, in the rump, a single large ulcerated lesion whereas paw lesions never ulcerated and were much smaller in C57BL/6 than in BALB/c mice. However, rump-inoculated IL-4-deficient (IL-4(-/-)) C57BL/6 mice did not develop any visible lesions although parasites remained in the dermis and lymph nodes, even after systemic IL-10-receptor blocking. By comparison, all IL-4(-/-) BALB/c mice developed rump ulcers. Strikingly, only 30% of rump-infected IL-4Rα(-/-) BALB/c mice developed lesions. IL-4(-/-) mice had higher IFN-γ and lower IL-10 and IL-13 levels than WT mice. Paw-infected IL-4Rα(-/-) BALB/c mice developed minimal paw lesions. While other factors contributing to L. amazonensis susceptibility cannot be discounted, our results indicate that absent signalling by IL-4 or by IL-4/IL-13 have more intense attenuating effects on rump than on paw lesions but do not eradicate parasitism. Copyright © 2011 Elsevier Inc. All rights reserved. |
| 6. | Exp Parasitol. 2011 Oct 12. [Epub ahead of print]Radio-attenuated leishmanial parasites as immunoprophylactic agent against experimental murine visceral leishmaniasis.Datta S, Adak R, Chakraborty P, Haldar AK, Bhattacharjee S, Chakraborty A, Roy S, Manna M.SourceDepartment of Zoology, Bethune College, 181, Bidhan Sarani, Kolkata 700 006, India. AbstractThe present study intends to evaluate the role of radio-attenuated leishmania parasites as immunoprophylactic agents for experimental murine visceral leishmaniasis. BALB/c mice were immunized with gamma (γ)-irradiated Leishmania donovani. A second immunization was given after 15days of first immunization. After two immunizations, mice were infected with virulent L. donovani promastigotes. Protection against Kala-azar (KA) was estimated from spleen and liver parasitic burden along with the measurement of nitrite and superoxide anion generation by isolation of splenocytes and also by T-lymphocyte helper 1(Th1) and T-lymphocyte helper 2(Th2) cytokines release from the experimental groups. It was observed that BALB/c mice having prior immunization with radio-attenuated parasites showed protection against L. donovani infection through higher expression of Th1 cytokines and suppression of Th2 cytokines along with the generation of protective free radicals. The group of mice without prior priming with radio-attenuated parasites surrendered to the disease. Thus it can be concluded that radio-attenuated L. donovani may be used for. Copyright © 2011 Elsevier Inc. All rights reserved. |
| 7. | Exp Parasitol. 2011 Oct 12. [Epub ahead of print]The opioid antagonist naloxone inhibits Leishmania major infection in BALB/c mice.Karaji AG, Hamzavi Y.SourceDepartment of Immunology School of Medicine, Kermanshah University of Medical Sciences, Iran. AbstractBALB/c mice are susceptible to develop non-healing, progressive infection with Leishmania major (L. major) due to the development of a non-protective Th2 response. Resistance to L. major infection is dependent to Th1 response. Treatment of mice with the opioid antagonist naloxone can promote the activation of Th1 responses. Here we study the effect of chronic administration of various doses of naloxone on susceptibility of BALB/c mice to L. major infection. Our results showed that naloxone has dose-dependent biphasic effect on L. major infection in BALB/c mice. While administration of 1mg/kg×2/day tends to exacerbate the local reaction to L. major infection, treatment with 10mg/kg×2/day of naloxone suppresses the local reaction and progress of infection. On the other hand treatment of mice with middle dose (5mg/kg whether 1 or 2 times per day) does not have significant effect on the infection. This study demonstrates that administration of high dose of naloxone could improve protection against L. major infection in BALB/c mice, presumably by modulation in Th1/Th2 balance or by affecting macrophages through binding to Toll-like receptors. Copyright © 2011 Elsevier Inc. All rights reserved. |
| 8. | Mol Biochem Parasitol. 2011 Oct 13. [Epub ahead of print]Developmental regulation of gene expression in the absence of transcriptional control: The case of kinetoplastids.Kramer S.SourceDepartment of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK. AbstractKinetoplastids, including the human pathogens Trypanosoma brucei, Trypanosoma cruzi and Leishmania, are the only known organisms that do not regulate the transcription of protein coding genes transcribed by RNA polymerase II. Yet, profound changes in gene expression are induced by many different external stimuli and stresses, the extreme example are cascades of changes in gene expression initiated by differentiation triggers that ultimately and irreversibly result in the massive morphological and metabolic changes observed during life-cycle progression. This review explores how kinetoplastids change gene expression by looking at life-cycle stage specific changes in chromatin, mRNA processing, mRNA stability, mRNA translation, protein stability and protein modifications. Copyright © 2011 Elsevier B.V. All rights reserved. |
| 9. | Eur J Med Chem. 2011 Sep 16. [Epub ahead of print]Anti-tumoral activities of dioncoquinones B and C and related naphthoquinones gained from total synthesis or isolation from plants.Bringmann G, Zhang G, Hager A, Moos M, Irmer A, Bargou R, Chatterjee M.SourceInstitute of Organic Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany. AbstractDioncoquinones belong to a family of natural naphthoquinone products of interest due to their promising anti-tumoral and anti-infective activities. In particular, dioncoquinones A (5) and B (6) have been shown to be highly active against Leishmania major and multiple myeloma cells without any significant toxicity toward normal blood cells. Their effective concentrations against multiple myeloma cell lines were similar to those of melphalan, a well known DNA-alkylating agent used in a standard therapy against B cell lymphoma and multiple myeloma. We report on the first total synthesis of the highly oxygenated anti-tumoral agent dioncoquinone B (6) and the isolation of its new, even higher-oxygenated analogs, dioncoquinones C (7), D (8), and E (9), from cell cultures of Triphyophyllum peltatum. In addition, several derivatives of these compounds were synthesized, including dioncoquinone C (7), and a small library of naphthoquinones was created. Furthermore, the first structure-activity relationship (SAR) study on this class of compounds was conducted, showing that each of the three hydroxy groups, at C-3, C-5, and C-6, is required for improved anti-tumoral activities and decreased cytotoxicities. Copyright © 2011 Elsevier Masson SAS. All rights reserved. |
| 10. | J Am Mosq Control Assoc. 2011 Sep;27(3):333-5.Sticky bottle traps: a simple and effective method for collecting adult phlebotomine sand flies from rodent burrows in a Leishmania-endemic region of Egypt.Obenauer PJ, Villinski JT, Zayed A, Watany N, El-Hossary SS.SourceUS Naval Medical Research Unit No. 3, Cairo, Egypt. AbstractWe describe a simple, economic, and effective method for constructing sticky bottle traps that can be used to capture adult sand flies from rodent burrows. Although sand fly surveillance activities often employ light- or CO2-baited traps, sticky papers secured to a post or placed on the ground can also be used. However, in arid environments, sand and other debris often collect on the sticky surface, reducing trap effectiveness, capacity, and a means for rapid discrimination and enumeration of adult specimens. Herein, a procedure for constructing sticky bottle traps is provided, as well as preliminary results from a recent sand fly field survey utilizing this device. |
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