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Sent on Saturday, 2011 May 14Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Med Microbiol Immunol. 2011 May 13. [Epub ahead of print]mTOR signaling pathway regulates the IL-12/IL-10 axis in Leishmania donovani infection.Cheekatla SS, Aggarwal A, Naik S.SourceDepartment of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India. AbstractLeishmania-induced interleukin-12 (IL-12) expression is negatively regulated by the phosphatidylinositol 3-kinase (PI3K) and extracellular signal regulated kinase (ERK) 1/2 pathways in human monocyte derived macrophages (MDMs). To extend these studies, we examined the pathways downstream from PI3K in L. donovani-induced reciprocal regulation of IL-12/IL-10 axis in THP-1-derived macrophages. We show for the first time that in THP-1-derived macrophages and human monocytes, mTOR inhibition by rapamycin reversed L. donovani-induced IL-12 and IL-10 modulation. L. donovani-induced phosphorylation of P70S6K, a correlate of mTOR activity, in TLR-stimulated THP-1 derived macrophages. This increase in P70S6K phosphorylation was completely blocked by rapamycin (mTOR inhibitor) and partially by wortmannin (PI3K inhibitor). These observations suggest that a PI3K independent pathway is operative in the modulation of IL-12 and IL-10. Blocking of TLR2 significantly attenuated IL-10 induced by the parasite, but did not affect IL-12 production. Thus, our data suggests that intracellular network of PI3K and mTOR pathway control IL-12/IL-10 modulation by L. donovani. mTOR inhibitors may be attractive molecules to reverse this modulation and may result in control of disease. |
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| 2. | Virulence. 2011 May 1;2(3). [Epub ahead of print]Trypanosomatid apoptosis: 'Apoptos is' without the canonical regulators.Smirlis D, Soteriadou K.SourceLaboratory of Molecular Parasitology; Department of Microbiology; Hellenic Pasteur Institute; Athens, Greece. AbstractApoptosis is a regulated process of cell death originally described in multicelullar organisms contributing to their development and functionality. There is now increasing experimental evidence that a similar form of cell death is operative in unicellular eukaryotes, including trypanosomatids of the genera Trypanosoma and Leishmania. The determination of ancestral executors and regulators of 'apoptosis' in these protozoa belonging to the most primitive eukaryotes that appeared on earth 1.5 billion years ago, provide an exciting challenge in the understanding of the evolution of apoptosis-regulating processes. A review of the present knowledge of trypanosomatid apoptosis points to the fact that these dying protozoa acquire common apoptotic morphological features as metazoan cells, although they lack many of the molecules accepted today as canonical apoptosis mediators (Bcl-2 family members, caspases, TNF related family of receptors). Herein, we discuss how the knowledge of regulators and executors of trypanosomatid apoptosis may provide answers to the gaps concerning the origin of apoptosis. The aim of this addendum is to emphasize the need for classifying the ancestral death program and to discuss how this relates to the complex death programs in multicellular lineages, with the hope to stimulate further enquiry and research into this area. |
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| 3. | J Biol Chem. 2011 May 12. [Epub ahead of print]The crystal structure of Leishmania major peroxidase and characterization of the compound I tryptophan radical.Jasion VS, Polanco JA, Meharenna YT, Li H, Poulos TL.SourceUniversity of California-Irvine, United States. AbstractThe parasitic protozoa, Leishmania major, produces a peroxidase (abbreviated LmP) that exhibits activities characteristic of both yeast cytochrome c peroxidase (CCP) and plant cytosolic ascorbate peroxidase (APX). One common feature is a key Trp residue, Trp208 in LmP and Trp191 in CCP, that is situated adjacent to the proximal His heme ligand in CCP, APX and LmP. In CCP Trp191 forms a stable cationic radical after reaction with H2O2 to form Compound I; in APX the radical is located on the porphyrin ring. In order to clarify the role of Trp208 in LmP and to further probe peroxidase structure-function relationships we have determined the crystal structure of LmP and have studied the role of Trp208 using electron paramagnetic resonance spectroscopy (EPR), mutagenesis, and enzyme kinetics. Both CCP and LmP have an extended section of beta structure near Trp191 and 208, respectively, which is absent in APX. This region provides stability to the Trp191 radical in CCP. EPR of LmP Compound I exhibits an intense and stable signal similar to CCP Compound I. In the LmP Trp208Phe mutant this signal disappears indicating that Trp208 forms a stable cationic radical. In LmP conversion of the Cys197 to Thr significantly weakens the Compound I EPR signal and dramatically lowers enzyme activity. These results further support the view that modulation of the local electrostatic environment controls the stability of the Trp radical in peroxidases. Our results also suggest that the biological role of LmP is to function as a cytochrome c peroxdase. |
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| 4. | Vet Parasitol. 2011 Apr 19. [Epub ahead of print]Canine vector-borne disease in travelled dogs in Germany-A retrospective evaluation of laboratory data from the years 2004-2008.Hamel D, Röhrig E, Pfister K.SourceInstitute of Comparative Tropical Medicine and Parasitology, Veterinary Faculty, Ludwig-Maximilians-Universität, Leopoldstr. 5, 80802 Munich, Germany. AbstractWhen importing dogs from various Mediterranean countries into Western Europe canine vector-borne infections are often considered as a major issue. Several diseases including babesiosis, leishmaniosis, hepatozoonosis, canine heartworm disease or ehrlichiosis can potentially be endemic in this region and pose a potential health risk for travelling dogs. Information on such infections in travelled dogs is scarce and therefore this study has been undertaken to examine the frequency of vector-borne infections in travelled dogs from the years 2004-2008. A total of 997 samples were screened by direct and/or indirect methods. Total seroprevalence was 7.5% with individual seroprevalence for the 3 species Leishmania spp., Ehrlichia canis and Babesia canis spp. ranging from 3.1 to 4.9%. Total detection rate for pathogens by direct methods was 3.5%. Ninteen Giemsa-stained blood smears were positive for large Babesia. None of the samples screened for microfilariae by Knott's test or for Dirofilaria immitis antigen by DiroChek(®) were positive. Using PCR methods Leishmania-DNA was detected in 1/42 samples but none of 59 animals screened for E. canis-DNA was positive. The prevalence values as established by indirect and direct pathogen detection are considered as rather low. Copyright © 2011. Published by Elsevier B.V. |
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| 5. | Biotech Histochem. 2010 Dec;85(6):341-54.Dyes, trypanosomiasis and DNA: a historical and critical review.Wainwright M.SourceSchool of Pharmacy & Biomolecular Science, Liverpool John Moores University, Liverpool, United Kingdom. mark_wainwright@hotmail.com AbstractTrypanosomiasis, a group of diseases including sleeping sickness in humans and Nagana in cattle in Africa, and Chagas' disease in South America, remains a considerable problem in the 21(st) century. The therapies that are available, however, usually have their roots in the "dye therapy" of a century ago, knowledge gained at the microscope from parasite staining procedures and converted to chemotherapy based on compounds closely related to the laboratory reagents. Dyes such as trypan red and trypan blue led to the development of suramin, while cationic nitrogen heterocyclic dyes furnished examples of the phenanthridinium class, such as ethidium (homidium) and isometamidium. Both suramin and isometamidium remain in use. Owing to mutagenicity issues, the presence of ethidium among the phenanthridinium dyes has led to concerns over the clinical use of related derivatives. There are several mechanisms for dye-DNA interaction, however, including possible hydrogen bonding of dye to the polymer, and these are discussed together with structure-activity relations and cellular localization of the phenanthridine and isomeric acridines involved. Better understanding of nucleic acid binding properties has allowed the preparation of more effective phenanthridinium analogues intended for use as anticancer/antiviral therapy. |
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