What's new for 'Trypanosomatids' in PubMed

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Sent on Thursday, 2011 Jan 27
Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results

Items 1 - 5 of 5

1.	Eur J Immunol. 2011 Feb;41(2):537-548. doi: 10.1002/eji.201040989. Epub 2010 Dec 29. Serum and organ-associated anti-hemoglobin humoral autoreactivity: Association with anti-Sm responses and inflammation. Bhatnagar H, Kala S, Sharma L, Jain S, Kim KS, Pal R. National Institute of Immunology, Aruna Asaf Ali Marg, JNU Complex, New Delhi, India. Abstract The release of hemoglobin (Hb) occurs in some infectious and autoimmune diseases characterized by inflammation. As levels of haptoglobin (Hp) fall, free Hb can cause pathology. Humoral autoreactivity to human Hb was demonstrated in the sera of systemic lupus erythematosus (SLE), leishmania and malaria patients. Serum anti-murine Hb antibody levels in lupus-prone mice also exhibited an age-dependent increase, with progressive organ sequestration; significant isotypic correlation was observed with anti-dsDNA antibodies. A suggestive link between anti-Hb and anti-Sm responses was observed: Human lupus sera expressing anti-Sm antibody reactivity preferentially contained heightened levels of anti-Hb autoantibodies, and immunization of lupus-prone mice with Sm led to enhanced anti-murine Hb reactivity. Human and murine anti-Hb monoclonal antibodies were generated, some of which were preferentially reactive toward disease-associated methemoglobin. Epitope-mapping studies revealed evidence of intra-molecular cross-reactivity. One such autoantibody synergized with Hb to enhance the secretion of pro-inflammatory cytokines while eliciting the increased production of monocyte migratory signals from endothelial cells. Preferential usage of specific variable region gene segments was not observed, although somatic mutations were documented. These studies reveal that, while the etiology, specificity and sequences of anti-Hb autoreactive antibodies can vary, they occur quite frequently and can have inflammatory consequences. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
	PMID: 21268022 [PubMed - as supplied by publisher]

2.	Org Biomol Chem. 2011 Jan 26. [Epub ahead of print] Exploring Leishmania major Inositol Phosphorylceramide Synthase (LmjIPCS): Insights into the ceramide binding domain. Mina JG, Mosely JA, Ali HZ, Denny PW, Steel PG. Centre for Bioactive Chemistry, Biophysical Sciences Institute, Department of Chemistry and School of Biological Sciences, Durham University, Science Laboratories, South Road, Durham, UKDH1 3LE. p.w.denny@durham.ac.uk p.g.steel@durham.ac.uk. Abstract The synthesis of set of ceramide analogues exploring hydrophobicity in the acyl chains and the degree and nature of hydroxylation is described. These have been assayed against the parasitic protozoan enzyme LmjIPCS. These studies showed that whilst the C-3 hydroxyl group was not essential for turnover it provided enhanced affinity. Reflecting the membrane bound nature of the enzyme a long (C(13)) hydrocarbon ceramide tail was necessary for both high affinity and turnover. Whilst the N-acyl chain also contributed to affinity, analogues lacking the amide linkage functioned as competitive inhibitors in both enzyme and cell-based assays. A model that accounts for this observation is proposed.
	PMID: 21267500 [PubMed - as supplied by publisher]

3.	FASEB J. 2011 Jan 25. [Epub ahead of print] HIV proteinase inhibitors target the Ddi1-like protein of Leishmania parasites. White RE, Powell DJ, Berry C. *Cardiff School of Biosciences, Cardiff University, Cardiff, UK; and. Abstract HIV proteinase inhibitors reduce the levels of Leishmania parasites in vivo and in vitro, but their biochemical target is unknown. We have identified an ortholog of the yeast Ddi1 protein as the only member of the aspartic proteinase family in Leishmania parasites, and in this study we investigate this protein as a potential target for the drugs. To date, no enzyme assay has been developed for the Ddi1 proteins, but Saccharomyces cerevisiae lacking the DDI1 gene secrete high levels of protein into the medium. We developed an assay in which these knockout yeast were functionally complemented to low secretion by introduction of genes encoding Ddi1 orthologs from Leishmania major or humans. Plasmid alone controls gave no complementation. Treatment of the Ddi1 transformants with HIV proteinase inhibitors showed differential effects dependent on the origin of the Ddi1. Dose responses allowed calculation of IC(50) values; e.g., for nelfinavir, of 3.4 μ M (human Ddi1) and 0.44 μ M (Leishmania Ddi1). IC(50) values with Leishmania constructs mirror the potency of inhibitors against parasites. Our results show that Ddi1 proteins are targets of HIV proteinase inhibitors and indicates the Leishmania Ddi1 as the likely target for these drugs and a potential target for antiparasitic therapy.-White, R. E., Powell, D. J., Berry, C. HIV proteinase inhibitors target the Ddi1-Like protein of Leishmania parasites.
	PMID: 21266539 [PubMed - as supplied by publisher]

4.	Methods Enzymol. 2011;489C:189-205. Induction of ER Stress Response Leading to Programmed Cell Death in Trypanosoma brucei. Goldshmidt H, Michaeli S. The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel; Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan, Israel. Abstract Trypanosomes are parasitic protozoans that include several medically and a variety of economically important parasites, such as Trypanosoma brucei, the causative agent of sleeping sickness. This parasite cycles between the insect host (procyclic form) and mammalian host (bloodstream form). These parasites lack transcription regulation, including factors that govern the unfolded protein response (UPR) in other eukaryotes. Gene expression is controlled posttranscriptionally by unique mechanisms such as trans-splicing and RNA editing and by mRNA stability. In trans-splicing, a common exon, the spliced leader (SL) is donated to all mRNAs from a small RNA, the SL RNA. The SL RNA is transcribed from a defined promoter assisted by the tSNAP complex. Despite the lack of transcriptional regulation, induction of ER stress elicits changes in the transcriptome similar to those induced by conventional UPR found in other eukaryotes. The mechanism of upregulation under UPR is dependent on differential stabilization of mRNAs. The transcriptome changes result in ER expansion and elevation in the ER chaperone, BiP. Prolonged ER stress induces the spliced leader RNA silencing (SLS) pathway. SLS is the trypanosome-specific stress response mechanism that elicits the shut-off of SL RNA transcription by perturbing the binding of the transcription factor tSNAP42 to its cognate promoter, eliminating trans-splicing of all mRNAs. SLS was discovered in the RNAi silenced cells depleted for functions that mediate translocation of proteins to the ER such as the signal recognition particle receptor SRα, SEC63- a factor that participates in protein translocation across the ER membrane, or SEC61- the translocation channel. Induction of SLS, either by prolonged ER stress or silencing of the genes associated with the ER membrane that function in ER protein translocation led to programmed cell death (PCD), evident by the exposure of phosphatidyl serine, DNA laddering, increase in ROS production, increase in cytoplasmic Ca(2+), and decrease in mitochondrial membrane potential. Here, we describe the protocols to induce ER stress and to observe the resulting morphological changes by transmission electron microscopy (TEM), changes in cytoplasmic Ca(2+), and DNA fragmentation which are the hallmarks of programmed cell death. Copyright © 2011 Elsevier Inc. All rights reserved.
	PMID: 21266231 [PubMed - as supplied by publisher]

5.	Parasit Vectors. 2011 Jan 25;4(1):9. [Epub ahead of print] Distribution of Leishmania major zymodemes in relation to populations of Phlebotomus papatasi sand flies. Hamarsheh O. Abstract ABSTRACT: Phlebotomus papatasi is the principle vector of Leishmania major, the causative agent of zoonotic cutaneous leishmaniasis in the Old World. Multi locus enzyme electrophoresis (MLEE) was extensively used to type different L. major stocks allover the world. Multi locus microsatellite typing (MLMT) has been recently used to investigate P. papatasi sand flies at population and sub-population levels. The Association between geographical distribution of L. major zymodemes and the distribution of populations and subpopulations of L. major vector; P. papatasi were discussed.
	PMID: 21266079 [PubMed - as supplied by publisher]