What's new for 'Trypanosomatids' in PubMed

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 Friday, 2011 Jan 07
Search 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

Items 1 - 10 of 13

1.	PLoS One. 2010 Dec 31;5(12):e15807. Classification and regression tree and spatial analyses reveal geographic heterogeneity in genome wide linkage study of Indian visceral leishmaniasis. Fakiola M, Mishra A, Rai M, Singh SP, O'Leary RA, Ball S, Francis RW, Firth MJ, Radford BT, Miller EN, Sundar S, Blackwell JM. Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom. Abstract BACKGROUND: Genome wide linkage studies (GWLS) have provided evidence for loci controlling visceral leishmaniasis on Chromosomes 1p22, 6q27, 22q12 in Sudan and 6q27, 9p21, 17q11-q21 in Brazil. Genome wide studies from the major focus of disease in India have not previously been reported. METHODS AND FINDINGS: We undertook a GWLS in India in which a primary ∼10 cM (515 microsatellites) scan was carried out in 58 multicase pedigrees (74 nuclear families; 176 affected, 353 total individuals) and replication sought in 79 pedigrees (102 nuclear families; 218 affected, 473 total individuals). The primary scan provided evidence (≥2 adjacent markers allele-sharing LOD≥0.59; nominal P≤0.05) for linkage on Chromosomes 2, 5, 6, 7, 8, 10, 11, 20 and X, with peaks at 6p25.3-p24.3 and 8p23.1-p21.3 contributed to largely by 31 Hindu families and at Xq21.1-q26.1 by 27 Muslim families. Refined mapping confirmed linkage across all primary scan families at 2q12.2-q14.1 and 11q13.2-q23.3, but only 11q13.2-q23.3 replicated (combined LOD = 1.59; P = 0.0034). Linkage at 6p25.3-p24.3 and 8p23.1-p21.3, and at Xq21.1-q26.1, was confirmed by refined mapping for primary Hindu and Muslim families, respectively, but only Xq21.1-q26.1 replicated across all Muslim families (combined LOD 1.49; P = 0.0045). STRUCTURE and SMARTPCA did not identify population genetic substructure related to religious group. Classification and regression tree, and spatial interpolation, analyses confirm geographical heterogeneity for linkages at 6p25.3-p24.3, 8p23.1-p21.3 and Xq21.1-q26.1, with specific clusters of families contributing LOD scores of 2.13 (P = 0.0009), 1.75 (P = 0.002) and 1.84 (P = 0.001), respectively. CONCLUSIONS: GWLS has identified novel loci that show geographical heterogeneity in their influence on susceptibility to VL in India.
	PMID: 21209823 [PubMed - in process]

2.	Kathmandu Univ Med J (KUMJ). 2010 Jan-Mar;8(29):73-9. Kala azar in Nepal: Estimating the effects of socioeconomic factors on disease incidence. Adhikari SR, Supakankunti S, Khan MM. Faculty of Economics, Chulalongkorn University, Thailand. Abstract Background: The incidence of Kala Azar (KA), a neglected tropical infectious disease, describes the pattern of disease, but is not principally concerned with explaining its causes. The transmission of the infectious diseases is determined by the complex interactions between environmental and socioeconomic factors. Environmental factors are predicted to have a significant impact on disease transmission; moreover, socioeconomic factors modify the magnitude and direction of these impacts. A number of studies have examined possible determinants of KA in endemic countries of the world; however, most of them appear to have used either qualitative approaches or subjective speculations. None of the studies indicates in quantitative terms the potential effects of poverty-alleviation programs on the incidence of KA. Materials and methods: Data related to charecteristics of community were collected from primary as well as secondary sources. Underlying socioeconomic determints on KA incidence were estimated by exploiting a linear multiple regression. Results: The multivariate analysis has confirmed that burden of KA is disproportionately borne by vulnerable and marginalized groups. KA is most entrenched in the poorest communities. Elimination of KA is directly related to poverty alleviation because if the poverty incidence reduces by10 percent, it will lead to reduction of KA incidence by 16 percent. The strategy for disease control or elimination should shift from traditional disease-centered approaches to a holistic approach that can break the links between poverty and KA. Conclusions: To achieve the target of elimination of KA in Nepal by 2015, the poverty incidence should be reduced from existing poverty 27 percent to at least 16 percent in KA endemic areas. The association between poverty and KA reflects causality running in both directions: poverty multiplies KA incidence and KA pushes poor into marginal poor or further poverty. Key words: Kala azar, Socioeconomic factors, Leishmaniasis.
	PMID: 21209511 [PubMed - in process]

3.	J Biol Chem. 2011 Jan 5. [Epub ahead of print] Post-transcriptional repair of a split heat shock protein 90 gene by mRNA trans-splicing. Nageshan RK, Roy N, Hehl AB, Tatu U. Indian Institute of Science, India; Abstract Heat shock protein 90 participates in diverse biological processes ranging from protein folding, cell cycle, signal transduction, development to evolution in all eukaryotes. It is also critically involved in regulating growth of protozoa such as Dictyostelium discoideum, Leishmania donovani, Plasmodium falciparum, Trypanosoma cruziand Trypanosoma evansi. Selective inhibition of Hsp90 has also been explored as an intervention strategy against important human diseases such as cancer, malaria or trypanosomiasis. Giardia lamblia, a simple protozoan parasite of humans and animals is an important cause of diarrheal disease with significant morbidity and some mortality in tropical countries. Here we show that the G. lamblia cytosolic Hsp90 (GlHsp90) is split in two similar sized fragments located 777 kb apart on the same scaffold. Intrigued by this unique arrangement which appears to be specific for the Giardiinae, we have investigated the biosynthesis of GlHsp90. We used genome sequencing to confirm the split nature of the giardial Hsp90. However, a specific antibody raised against the peptide detected a single product with a mass of about 80 kDa, suggesting a post transcriptional rescue of the genomic defect. We show evidence for the joining of the two independent Hsp90 transcripts in trans to one long mature mRNA presumably by RNA splicing. The splicing junction carries hallmarks of classical cis spliced introns suggesting that the regular cis splicing machinery may be sufficient for the repair of the open reading frame. A complementary 26 nt sequence in the intron regions adjacent to the splice sites may assist in positioning the two pre mRNAs for processing. This is the first example of post transcriptional rescue of a split gene by trans splicing.
	PMID: 21209094 [PubMed - as supplied by publisher]
	Related citations

4.	J Infect Dis. 2011 Feb;203(3):418-29. Epub 2010 Dec 14. Intradermal infections of mice by low numbers of african trypanosomes are controlled by innate resistance but enhance susceptibility to reinfection. Wei G, Bull H, Zhou X, Tabel H. Department of Veterinary Microbiology. Abstract Antibodies are required to control blood-stage forms of African trypanosomes in humans and animals. Here, we report that intradermal infections by low numbers of African trypanosomes are controlled by innate resistance but prime the adaptive immune response to increase susceptibility to a subsequent challenge. Mice were found 100 times more resistant to intradermal infections by Trypanosoma congolense or Trypanosoma brucei than to intraperitoneal infections. B cell-deficient and RAG2(-/-) mice are as resistant as wild-type mice to intradermal infections, whereas inducible nitric oxide synthase (iNOS)(-/-) mice and wild-type mice treated with antibody to tumor necrosis factor (TNF) α are more susceptible. We conclude that primary intradermal infections with low numbers of parasites are controlled by innate defense mediated by induced nitric oxide (NO). CD1d(-/-) and major histocompatibility complex (MHC) class II(-/-) mice are more resistant than wild-type mice to primary intradermal infections. Trypanosome-specific spleen cells, as shown by cytokine production, are primed as early as 24 h after intradermal infection. Infecting mice intradermally with low numbers of parasites, or injecting them intradermally with a trypanosomal lysate, makes mice more susceptible to an intradermal challenge. We suggest that intradermal infections with low numbers of trypanosomes or injections with trypanosomal lysates prime the adaptive immune system to suppress protective immunity to an intradermal challenge.
	PMID: 21208931 [PubMed - in process]
	Related citations

5.	Hum Pathol. 2011 Jan 3. [Epub ahead of print] Enteroglial cells act as antigen-p resenting cells in chagasic megacolon. Barcelos Morais da Silveira A, de Oliveira EC, Neto SG, Luquetti AO, Toshio Fujiwara R, Correa Oliveira R, Brehmer A. Human Anatomy Sector, ICBIM, Universidade Federal de Uberlândia, 38.400-902, Minas Gerais, Brazil; Research Center René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, 30.190-002, Brazil. Abstract Chagas disease is one of the most serious parasitic diseases of Latin America, with a social and economic impact far outweighing the combined effects of other parasitic diseases such as malaria, leishmaniasis, and schistosomiasis. In the chronic phase of this disease, the destruction of enteric nervous system components leads to megacolon development. Besides neurons, the enteric nervous system is constituted by enteric glial cells, representing an extensive but relatively poorly described population within the gastrointestinal tract. Several lines of evidence suggest that enteric glial cells represent an equivalent of central nervous system astrocytes. Previous data suggest that enteric glia and neurons are active in the enteric nervous system during intestinal inflammatory and immune responses. To evaluate whether these cells act as antigen-presenting cells, we investigated the expression of molecules responsible for activation of T cells, such as HLA-DR complex class II and costimulatory molecules (CD80 and CD86), by neurons and enteric glial cells. Our results indicate that only enteric glial cells of chagasic patients with megacolon express HLA-DR complex class II and costimulatory molecules, and hence they present the attributes necessary to act as antigen-presenting cells. Copyright © 2010 Elsevier Inc. All rights reserved.
	PMID: 21208643 [PubMed - as supplied by publisher]
	Related citations

6.	BMC Microbiol. 2011 Jan 6;11(1):4. [Epub ahead of print] The exopolyphosphatase TbrPPX1 OF Trypanosoma brucei. Luginbuehl E, Kunz S, Wentzinger L, Freimoser F, Seebeck T. Abstract ABSTRACT: BACKGROUND: Exopolyphosphatases and pyrophosphatases play important but still incompletely understood roles in energy metabolism, and also in other aspects of cell biology such as osmoregulation or signal transduction. Earlier work has suggested that a human exopolyphosphatase, Prune, might exhibit cyclic nucleotide phosphodiesterase activity. RESULTS: The kinetoplastida, a large order of unicellular eukaryotes that contains many important pathogens such as Trypanosoma brucei (human sleeping sickness), Trypanosoma cruzi (Chagas disease) or Leishmania ssp (several clinically dinstinct leishmaniases) all contain several exo- and pyrophosphatases. The current study provides a systematic classification of these enzymes, which now allows to situate the information that is already available on some of these enzymes. It then analyses the exopolyphosphatase TbrTPPX1 of T. brucei in detail, using RNA interference and genetic knockouts in an attempt to define its function, and immunofluorescence microscopy to study its subcellular localization. TbrPPX1 is an exopolyphosphatase that does hydrolyze pentasodium triphosphate, but not organic triphosphates such as ATP, pyrophosphate or long-chain polyphosphates. Finally, the study investigates the potential cyclic nucleotide phosphodiesterase activity of TbrPPX1. CONCLUSIONS: All kinetoplastid genomes that are currently available contain genes for one class of an exopolyphosphatase and two classes of pyrophosphatases, one associated with the acidocalcisomes and one cytoplasmic. TbrPPX1 represents the T. brucei exopolyphosphatase. It is located throughout the cytoplasm, and its genetic ablation does not produce a dramatic phenotype. Importantly, TbrPPX1 does not exhibit any cyclic nucleotide specific phosphodiesterase activity, which definitively eliminates it as an additional player in cAMP signalling of the kinetoplastida.
	PMID: 21208463 [PubMed - as supplied by publisher]
	Related citations

7.	BMC Evol Biol. 2011 Jan 5;11(1):4. [Epub ahead of print] Phylogenomics of Phosphoinositide Lipid Kinases: Perspectives on the Evolution of Second Messenger Signaling and Drug Discovery. Brown JR, Auger KR. Abstract ABSTRACT: BACKGROUND: Phosphoinositide lipid kinases (PIKs) generate specific phosphorylated variants of phosatidylinositols (PtdIns) that are critical for second messenger signaling and cellular membrane remodeling. Mammals have 19 PIK isoforms spread across three major families: the PtIns 3-kinases (PI3Ks), PtdIns 4-kinases (PI4Ks), and PtdIns-P (PIP) kinases (PIPKs). Other eukaryotes have fewer yet varying PIK complements. PIKs are also an important, emerging class of drug targets for many therapeutic areas including cancer, inflammatory and metabolic diseases and host-pathogen interactions. Here, we report the genomic occurrences and evolutionary relationships or phylogenomics of all three PIK families across major eukaryotic groups and suggest potential ramifications for drug discovery. RESULTS: Our analyses reveal four core eukaryotic PIKs which are type III PIK4A and PIK4B, and at least one homolog each from PI3K (possibly PIK3C3 as the ancestor) and PIP5K families. We also applied evolutionary analyses to PIK disease ontology and drug discovery. Mutated PIK3CA are known to be oncogenic and several inhibitors are in anti-cancer clinical trials. We found conservation of activating mutations of PIK3CA in paralogous isoforms suggesting specific functional constraints on these residues. By mapping published compound inhibition data (IC50s) onto a phylogeny of PI3Ks, type II PI4Ks and distantly related, MTOR, ATM, ATR and PRKDC kinases, we also show that compound polypharmacology corresponds to kinase evolutionary relationships. Finally, we extended the rationale for drugs targeting PIKs of malarial Plasmodium falciparum, and the parasites, Leishmania sp. and Trypanosoma sp. by identifying those PIKs highly divergent from human homologs. CONCLUSION: Our phylogenomic analysis of PIKs provides new insights into the evolution of second messenger signaling. We postulate two waves of PIK diversification, the first in metazoans with a subsequent expansion in cold-blooded vertebrates that was post-emergence of Deutrostomia\Chordata but prior to the appearance of mammals. Reconstruction of the evolutionary relationships among these lipid kinases also adds to our understanding of their roles in various diseases and assists in their development as potential drug targets.
	PMID: 21208444 [PubMed - as supplied by publisher]
	Related citations

8.	Biochem Soc Trans. 2010 Oct;38(5):1294-301. Systems biology from micro-organisms to human metabolic diseases: the role of detailed kinetic models. Bakker BM, van Eunen K, Jeneson JA, van Riel NA, Bruggeman FJ, Teusink B. Department of Liver, Digestive and Metabolic Diseases, University Medical Centre Groningen, University of Groningen, The Netherlands. b.m.bakker@med.umcg.nl Abstract Human metabolic diseases are typically network diseases. This holds not only for multifactorial diseases, such as metabolic syndrome or Type 2 diabetes, but even when a single gene defect is the primary cause, where the adaptive response of the entire network determines the severity of disease. The latter may differ between individuals carrying the same mutation. Understanding the adaptive responses of human metabolism naturally requires a systems biology approach. Modelling of metabolic pathways in micro-organisms and some mammalian tissues has yielded many insights, qualitative as well as quantitative, into their control and regulation. Yet, even for a well-known pathway such as glycolysis, precise predictions of metabolite dynamics from experimentally determined enzyme kinetics have been only moderately successful. In the present review, we compare kinetic models of glycolysis in three cell types (African trypanosomes, yeast and skeletal muscle), evaluate their predictive power and identify limitations in our understanding. Although each of these models has its own merits and shortcomings, they also share common features. For example, in each case independently measured enzyme kinetic parameters were used as input. Based on these 'lessons from glycolysis', we will discuss how to make best use of kinetic computer models to advance our understanding of human metabolic diseases.
	PMID: 20863302 [PubMed - indexed for MEDLINE]
	Related citations

9.	Parasitol Res. 2010 Oct;107(5):1193-204. Epub 2010 Aug 3. Croton cajucara crude extract and isolated terpenes: activity on Trypanoso ma cruzi. Campos MC, Salomão K, Castro-Pinto DB, Leon LL, Barbosa HS, Maciel MA, de Castro SL. Laboratório de Biologia de Tripanosomatídeos, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil 4365, Manguinhos, 21045-900 Rio de Janeiro, Rio de Janeiro, Brazil. Abstract Croton cajucara is a plant found in the Amazon region and is known for its medicinal properties. The effects of the methanolic extract of the stem bark of C. cajucara (MCC) and of the isolated terpenes, trans-dehydrocrotonin (t-DCTN) and acetyl aleuritolic acid (AAA), were investigated using four isolates of Trypanosoma cruzi. In assays with trypomastigotes, the extract was more active than the isolated compounds, presenting IC(50) in the range of 10 to 50 μg/mL. The trypanocidal effect of MCC, AAA and benznidazole was significantly higher in the GLT291 and C45 strains, which were recently isolated from wild animals. MCC and AAA caused a dose-dependent inhibition of epimastigote proliferation. In assays using intracellular amastigotes, AAA and MCC reduced the percent of infection and the endocytic index after 96 h of treatment, at concentrations that were non-toxic to the host cells. MCC inhibited the trypanothione reductase pathway in both epimastigotes and trypomastigotes of all the subpopulations. The absence of AAA activity on the trypanothione reductase pathway in epimastigotes of Dm28c suggests heterogeneity of the biochemical profile between this clone and the three strains. Epimastigotes and trypomastigotes (GLT291) were treated for 24 h with MCC or AAA, and both induced alterations of the plasma membrane, while AAA-treated epimastigotes also displayed mitochondrial damage.
	PMID: 20680342 [PubMed - indexed for MEDLINE]
	Related citations

10.	Parasitol Res. 2010 Oct;107(5):1279-83. Epub 2010 Aug 3. Association of clomipramine and allopurinol for the treatment of the experimental infe ction with Trypanosoma cruzi. Gobbi P, Baez A, Lo Presti MS, Fernández AR, Enders JE, Fretes R, Gea S, Paglini-Oliva PA, Rivarola HW. Cátedra de Física Biomédica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, PC 5000 Córdoba, Argentina. Abstract We have previously shown that clomipramine and allopurinol used separately are effective in preventing chronic chagasic cardiomyopathy. The aim of the present study was to evaluate the effect of the association of clomipramine (Clo--5 mg/kg/day/90 days) and allopurinol (Allo--5, 10, or 15 mg/kg/day/90 days) for the treatment of experimental Chagas disease in the acute stage. Treatment effectiveness was evaluated through parasitemia, survival, electrocardiography, serology, and cardiac histopathology. Groups treated showed no electrocardiographic abnormalities, in contrast to those untreated which presented 25% of mice with conduction alterations. The myocardium of treated mice (Clo, Allo10+Clo, and Allo15+Clo) presented no structural alterations. Cardiac b-receptor affinity was preserved in mice treated with Clo or Clo+Allo at the different doses; receptor density of the Clo and Allo15+Clo groups did not differ from the non-infected group. Anti-cruzipain antibody levels were similar in treated and untreated groups. Survival was significantly increased in the treated groups (p < 0.05), with Clo and all the Clo+Allo groups presenting the highest rates. These results show that the association of clomipramine + allopurinol is effective for Chagas disease treatment and has the same effect as clomipramine alone.
	PMID: 20680335 [PubMed - indexed for MEDLINE]
	Related citations