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Sent on Friday, 2010 Dec 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. | Parasitol Res. 2010 Dec 2. [Epub ahead of print]Immunization against leishmaniasis by PLGA nanospheres encapsulated with autoclaved Leishmania major (ALM) and CpG-ODN.Tafaghodi M, Khamesipour A, Jaafari MR.Nanotechnology and Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. AbstractVarious adjuvants and delivery systems have been evaluated for increasing the protective immune responses against leishmaniasis and mostly have been shown not to be effective enough. In this study, poly(D: ,L: -lactide-co-glycolide) (PLGA) nanospheres as an antigen delivery system and CpG-ODN as an immunoadjuvant have been used for the first time to enhance the immune response against autoclaved Leishmania major (ALM). PLGA nanospheres were prepared by a double-emulsion (W/O/W) technique. Particulate characteristics were studied by scanning electron microscopy and particle size analysis. Mean diameter of ALM + CpG-ODN-loaded nanospheres was 300 ± 128 nm. BALB/c mice were immunized three times in 3-week intervals using ALM plus CpG-ODN-loaded nanospheres [(ALM + CpG-ODN)(PLGA)], ALM encapsulated PLGA nanospheres [(ALM)(PLGA)], (ALM)(PLGA) + CpG, ALM + CpG, ALM alone, or phosphate buffer solution (PBS). The intensity of infection induced by L. major challenge was assessed by measuring size of footpad swelling. The strongest protection, showed by significantly (P < 0.05) smaller footpad, was observed in mice immunized with (ALM + CpG-ODN)(PLGA). The (ALM)(PLGA), (ALM)(PLGA) + CpG, and ALM + CpG were also showed a significantly (P < 0.05) smaller footpad swelling compared to the groups received either PBS or ALM alone. The mice immunized with (ALM + CpG-ODN)(PLGA), (ALM)(PLGA) + CpG, and ALM + CpG showed the highest IgG2a/IgG1 ratio, interferon-γ production, and lowest interleukin-4 production compared to the other groups. It is concluded that when both PLGA nanospheres and CpG-ODN adjuvants were used simultaneously, it induce stronger immune response and enhance protection rate against Leishmania infection. |
| PMID: 21125294 [PubMed - as supplied by publisher] | |
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| 2. | PLoS One. 2010 Nov 23;5(11):e15020.The Expanded Kinesin-13 Repertoire of Trypanosomes Contains Only One Mitotic Kinesin Indicating Multiple Extra-Nuclear Roles.Wickstead B, Carrington JT, Gluenz E, Gull K.Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom. AbstractBACKGROUND: Kinesin-13 proteins have a critical role in animal cell mitosis, during which they regulate spindle microtubule dynamics through their depolymerisation activity. Much of what is known about Kinesin-13 function emanates from a relatively small sub-family of proteins containing MCAK and Kif2A/B. However, recent work on kinesins from the much more widely distributed, ancestral Kinesin-13 family, which includes human Kif24, have identified a second function in flagellum length regulation that may exist either alongside or instead of the mitotic role. METHODOLOGY/PRINCIPAL FINDINGS: The African trypanosome Trypanosoma brucei encodes 7 distinct Kinesin-13 proteins, allowing scope for extensive specialisation of roles. Here, we show that of all the trypanosomal Kinesin-13 proteins, only one is nuclear. This protein, TbKIN13-1, is present in the nucleoplasm throughout the cell cycle, but associates with the spindle during mitosis, which in trypanosomes is closed. TbKIN13-1 is necessary for the segregation of both large and mini-chromosomes in this organism and reduction in TbKIN13-1 levels mediated by RNA interference causes deflects in spindle disassembly with spindle-like structures persisting in non-mitotic cells. A second Kinesin-13 is localised to the flagellum tip, but the majority of the Kinesin-13 family members are in neither of these cellular locations. CONCLUSIONS/SIGNIFICANCE: These data show that the expanded Kinesin-13 repertoire of trypanosomes is not associated with diversification of spindle-associated roles. TbKIN13-1 is required for correct spindle function, but the extra-nuclear localisation of the remaining paralogues suggests that the biological roles of the Kinesin-13 family is wider than previously thought. |
| PMID: 21124853 [PubMed - as supplied by publisher] | |
| 3. | PLoS Pathog. 2010 Nov 24;6(11):e1001204.A Molecular Mechanism for Eflornithine Resistance in African Trypanosomes.Vincent IM, Creek D, Watson DG, Kamleh MA, Woods DJ, Wong PE, Burchmore RJ, Barrett MP.Faculty of Biomedical and Life Science and Wellcome Trust Centre for Molecular Parasitology, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, United Kingdom. AbstractHuman African trypanosomiasis, endemic to sub-Saharan Africa, is invariably fatal if untreated. Its causative agent is the protozoan parasite Trypanosoma brucei. Eflornithine is used as a first line treatment for human African trypanosomiasis, but there is a risk that resistance could thwart its use, even when used in combination therapy with nifurtimox. Eflornithine resistant trypanosomes were selected in vitro and subjected to biochemical and genetic analysis. The resistance phenotype was verified in vivo. Here we report the molecular basis of resistance. While the drug's target, ornithine decarboxylase, was unaltered in resistant cells and changes to levels of metabolites in the targeted polyamine pathway were not apparent, the accumulation of eflornithine was shown to be diminished in resistant lines. An amino acid transporter gene, TbAAT6 (Tb927.8.5450), was found to be deleted in two lines independently selected for resistance. Ablating expression of this gene in wildtype cells using RNA interference led to acquisition of resistance while expression of an ectopic copy of the gene introduced into the resistant deletion lines restored sensitivity, confirming the role of TbAAT6 in eflornithine action. Eflornithine resistance is easy to select through loss of a putative amino acid transporter, TbAAT6. The loss of this transporter will be easily identified in the field using a simple PCR test, enabling more appropriate chemotherapy to be administered. |
| PMID: 21124824 [PubMed - as supplied by publisher] | |
| 4. | Acta Crystallogr D Biol Crystallogr. 2010 Dec 1;66(Pt 12):1334-1340. Epub 2010 Nov 16.High-resolution structures of Trypanosoma brucei pteridine reductase ligand complexes inform on the placement of new molecular entities in the active site of a potential drug target.Dawson A, Tulloch LB, Barrack KL, Hunter WN.Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland. AbstractPteridine reductase (PTR1) is a potential target for drug development against parasitic Trypanosoma and Leishmania species. These protozoa cause serious diseases for which current therapies are inadequate. High-resolution structures have been determined, using data between 1.6 and 1.1 Å resolution, of T. brucei PTR1 in complex with pemetrexed, trimetrexate, cyromazine and a 2,4-diaminopyrimidine derivative. The structures provide insight into the interactions formed by new molecular entities in the enzyme active site with ligands that represent lead compounds for structure-based inhibitor development and to support early-stage drug discovery. |
| PMID: 21123874 [PubMed - as supplied by publisher] | |
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| 5. | Emerg Infect Dis. 2010 Dec;16(12):2017-2019.Imported Leishmaniasis in Dogs, US Military Bases, Japan.Kawamura Y, Yoshikawa I, Katakura K.Hokkaido University Graduate School of Veterinary Medicine, Sapporo, Hokkaido, Japan (Y. Kawamura, K. Katakura); and US Army Japan District Veterinary Command-Zama Branch Kangawa, Japan (I. Yoshikawa). AbstractTo the Editor: Leishmaniasis is found in canids in ≈50 of the 88 countries where leishmaniases are found in humans (1). In Japan, 2 cases of imported canine leishmaniasis have been documented in dogs from Spain (2,3). We report 2 cases of leishmaniasis in dogs in which dermatitis developed mainly on the face. Leishmaniasis was diagnosed from results of a serologic rk39 test, followed by PCR of skin lesion specimens for the Leishmania spp.-specific small subunit (SSU) rRNA gene. Because the dogs had lived on a US military base in Sicily, Italy, for 3 years before their owners were transfered to Japan, the animals were likely infected with L. infantum in Italy. |
| PMID: 21122254 [PubMed - as supplied by publisher] | |
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| 6. | Emerg Infect Dis. 2010 Dec;16(12):1973-1975.Leishmania tropica Infection in Golden Jackals and Red Foxes, Israel.Talmi-Frank D, Kedem-Vaanunu N, King R, Bar-Gal GK, Edery N, Jaffe CL, Baneth G.Hebrew University, Rehovot, Israel (D. Talmi-Frank, N. Kedem-Vaanunu, G. Kahila Bar-Gal, G. Baneth); Israel Nature and Parks Authority, Jerusalem, Israel (R. King); Kimron Veterinary Institute, Bet-Dagan, Israel (N. Edery); and Hebrew University-Hadassah Medical School, Jerusalem (C.L. Jaffe). AbstractDuring a survey of wild canids, internal transcribed spacer 1 real-time PCR and high-resolution melt analysis identified Leishmania tropica in samples from jackals and foxes. Infection was most prevalent in ear and spleen samples. Jackals and foxes may play a role in the spread of zoonotic L. tropica. |
| PMID: 21122235 [PubMed - as supplied by publisher] | |
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| 7. | BMC Infect Dis. 2010 Dec 1;10(1):342. [Epub ahead of print]A canine leishmaniasis pilot survey in an emerging focus of visceral leishmaniasis: Posadas (Misiones, Argentina).Cruz I, Acosta L, Gutierrez MN, Nieto J, Canavate C, Deschutter J, Bornay-Llinares FJ.AbstractABSTRACT: BACKGROUND: An increasing number of reports are calling our attention to the worldwide spread of leishmaniasis. The urbanization of zoonotic visceral leishmaniasis (VL) has been observed in different South American countries, due to changes in demographic and ecological factors. In May 2006, VL was detected for the first time in the city of Posadas (Misiones, Argentina). This event encouraged us to conduct a clinical and parasitological pilot survey on domestic dogs from Posadas to identify their potential role as reservoirs for the disease. METHODS: One hundred and ten dogs from the city of Posadas were included in the study. They were selected based on convenience and availability. All dogs underwent clinical examination. Symptomatology related to canine leishmaniasis was recorded, and peripheral blood and lymph node aspirates were collected. Anti-Leishmania antibodies were detected using rK39-immunocromatographic tests and IFAT. Parasite detection was based on peripheral blood and lymph node aspirate PCR targeting the SSUrRNA gene. Molecular typing was addressed by DNA sequence analysis of the PCR products obtained by SSUrRNA and ITS-1 PCR. RESULTS: According to clinical examination, 69.1% (76/110) of the dogs presented symptoms compatible with canine leishmaniasis. Serological analyses were positive for 43.6% (48/110) of the dogs and parasite DNA was detected in 47.3% (52/110). A total of 63 dogs (57.3%) were positive by serology and/or PCR. Molecular typing identified Leishmania infantum (syn. Leishmania chagasi) as the causative agent. CONCLUSIONS: This work confirms recent findings which revealed the presence of Lutzomyia longipalpis, the vector of L. infantum in this area of South America. This new VL focus could be well established, and further work is needed to ascertain its magnitude and to prevent further human VL cases. |
| PMID: 21122107 [PubMed - as supplied by publisher] | |
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