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Sent on Wednesday, 2011 Aug 10Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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1. | Gene. 2011 Jul 28. [Epub ahead of print]Comparative genomic analysis of dinucleotide repeats in Tritryps.Duhagon MA, Smircich P, Forteza D, Naya H, Williams N, Garat B.SourceLaboratorio de Interacciones Moleculares, Facultad de Ciencias, 11400 Montevideo, Uruguay; Departamento de Genética, Facultad de Medicina, 11800 Montevideo, Uruguay. AbstractThe protozoans Trypanosoma cruzi, Trypanosoma brucei and Leishmania major (Tritryps), are evolutionarily ancient eukaryotes which cause worldwide human parasitosis. They present unique biological features. Indeed, canonical DNA/RNA cis-acting elements remain mostly elusive. Repetitive sequences, originally considered as selfish DNA, have been lately recognized as potentially important functional sequence elements in cell biology. In particular, the dinucleotide patterns have been related to genome compartmentalization, gene evolution and gene expression regulation. Thus, we perform a comparative analysis of the occurrence, length and location of dinucleotide repeats (DRs) in the Tritryp genomes and their putative associations with known biological processes. We observe that most types of DRs are more abundant than would be expected by chance. Complementary DRs usually display asymmetrical strand distribution, favoring TT and GT repeats in the coding strands. In addition, we find that GT repeats are among the longest DRs in the three genomes. We also show that specific DRs are non-uniformly distributed along the polycistronic unit, decreasing toward its boundaries. Distinctive non-uniform density patterns were also found in the intergenic regions, with predominance at the vicinity of the ORFs. These findings further support that DRs may control genome structure and gene expression. Copyright © 2011. Published by Elsevier B.V. |
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2. | Lipids Health Dis. 2011 Aug 8;10(1):135. [Epub ahead of print]Tropically stable novel oral lipid formulation of amphoter icin B (iCo-010): Biodistribution and toxicity in a mouse model.Sivak O, Gershkovich P, Lin M, Wasan EK, Zhao J, Owen D, Clement JG, Wasan KM.AbstractABSTRACT: BACKGROUND:The purpose of this study was to evaluate the biodistribution and toxicity of amphotericin B (AmB) following multiple oral administrations of a novel tropically stable lipid-based formulation (iCo-010). METHODS:BALB/c mice were allocated into six groups: oral iCo-010 twice daily for 5 days in the dose of 20, 10, 5 and 2.5 mg/kg; vehicle control; and intravenous boluses of Fungizone(R) 2mg/kg once daily for 5 days. The animals were sacrificed 12h following the last administration and blood and tissues were collected. RESULTS:The plasma concentrations of AmB were similar to previously reported after administration of iCo-009. Somewhat lower concentrations of AmB were detected in reticulo-endothelial system in the case of iCo-010 when compared with iCo-009. The concentration in kidney was higher with iCo-010 than with iCo-009. The creatinine levels in all oral treatment groups were in a normal range as in the case of iCo-009. Administration of Fungizone(R) resulted in elevated plasma creatinine levels. Histopathology analysis detected no GI, liver or kidney toxicity following multiple dose oral administration of iCo-010. Fungizone(R) treatment induced necrotic changes in hepatic and kidney tissues. CONCLUSIONS:Given the tropical stability of iCo-010, near identical activity against visceral leishmaniasis and significant concentrations in target organs this formulation has a potential to become a treatment of choice in tropical developing countries. |
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3. | BMC Immunol. 2011 Aug 8;12(1):44. [Epub ahead of print]In silico predicted epitopes from the COOH-terminal extension of cysteine proteinase B inducing distinct immune responses during Leishmania (Leishmania) amazonensis experimental murine infection.Pereira BA, Silva FS, Rebello KM, Marin-Villa M, Traub-Cseko YM, Andrade TC, Bertho AL, Caffarena ER, Alves CR.AbstractABSTRACT: BACKGROUND:Leishmania parasites have been reported to interfere and even subvert their host immune responses to enhance their chances of survival and proliferation. Experimental Leishmania infection in mice has been widely used in the identification of specific parasite virulence factors involved in the interaction with the host immune system. Cysteine-proteinase B (CPB) is an important virulence factor in parasites from the Leishmania (Leishmania) mexicana complex: it inhibits lymphocytes Th1 and/or promotes Th2 responses either through proteolytic activity or through epitopes derived from its COOH-terminal extension. In the present study we analyzed the effects of Leishmania (Leishmania) amazonensis CPB COOH-terminal extension-derived peptides on cell cultures from murine strains with distinct levels of susceptibility to infection: BALB/c, highly susceptible, and CBA, mildly resistant. RESULTS:Predicted epitopes, obtained by in silico mapping, displayed the ability to induce cell proliferation and expression of cytokines related to Th1 and Th2 responses. Furthermore, we applied in silico simulations to investigate how the MHC/epitopes interactions could be related to the immunomodulatory effects on cytokines, finding evidence that specific interaction patterns can be related to in vitro activities. CONCLUSIONS:Based on our results, we consider that some peptides from the CPB COOH-terminal extension may influence host immune responses in the murine infection, thus helping Leishmania survival. |
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4. | Zoonoses Public Health. 2011 May 6. doi: 10.1111/j.1863-2378.2011.01407.x. [Epub ahead of print]Sonographical and Serological Survey of Human Cystic Echinococcosis and Analysis of Risk Factors Associated with Seroconversion in Rural Communities of Kerman, Iran.Harandi MF, Moazezi SS, Saba M, Grimm F, Kamyabi H, Sheikhzadeh F, Sharifi I, Deplazes P.SourceLeishmaniasis Research Center and Department of Parasitology School of Medicine, Kerman University of Medical Sciences, Kerman, Iran Department of Radiology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran WHO Collaborating Centre for Parasitic Zoonoses, Institute of Parasitology, University of Zurich, Zurich, Switzerland Kerman county Health Center, Kerman University of Medical Sciences, Kerman, Iran. AbstractCystic echinococcosis (CE) caused by larval stage of Echinococcus granulosus, is an endemic zoonosis in Iran particularly in rural regions. The objective of this study was to determine the prevalence of CE among rural communities in Kerman using ultrasonography (US) and serology. Kerman Province, in southeastern Iran, is the largest province, with 2.9 million inhabitants. A sample of 1140 individuals (200 males and 940 females) was selected by randomized cluster sampling in 2006-2008. After acquiring informed consent for each participant a questionnaire was filled, complete abdominal US in supine position was carried out and 5 ml blood was collected for ELISA test. Two hydatid cases (0.2%) were detected by ultrasound. Serological results showed 7.3% seropositivity, and females (8.3%) were significantly more positive than males (2.1%). There were significant difference between CE seropositivity and sex, age and occupation. Residents of desert regions (Shahdad, Andouhjerd and Golbaf) were 2.5 times more likely to be seropositive than mountainous regions with better socioeconomic status (OR = 2.5; 95% CI = 1.09-5.95). Dog ownership does not appear to be a significant risk factor for CE in the region. Only about 10% of households own dogs, usually only one dog. However, the stray dog population of Kerman province is estimated at 145 000-480 000 (3.5-11.5 times the owned dog population). Infection in humans and animals would appear to come mostly from infected stray dogs. Management of stray dog population could make major progress in control of hydatid disease. In addition, proper washing of vegetables decreased probability of infection by 53% (OR = 0.47; 95% CI = 0.26-0.84). The serological study showed that many people, especially women, had been exposed to Echinococcus eggs and had seroconverted but were not infected. © 2011 Blackwell Verlag GmbH. |
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5. | Cell Cycle. 2011 Apr 1;10(7):1132-43. Epub 2011 Apr 1.Microarray analysis of the mammalian thromboxane receptor-Trypanosoma cruzi interaction.Tanowitz HB, Mukhopadhyay A, Ashton AW, Lisanti MP, Machado FS, Weiss LM, Mukherjee S.SourceDepartment of Pathology, Albert Einstein College of Medicine, Bronx, NY USA. herbert.tanowitz@einstein.yu.edu AbstractTrypanosoma cruzi, the etiological agent of Chagas disease, causes vasculopathy and cardiomyopathy in humans and is associated with elevated levels of several vasoactive molecules such as nitric oxide, endothelin-1 and thromboxane A 2 (TXA 2). Parasite derived TXA 2 modulates vasculopathy and other pathophysiological features of Chagasic cardiomyopathy. Previously, we demonstrated that in response to infection with T. cruzi, TXA 2 receptor (TP) null mice displayed increased parasitemia; mortality and cardiac pathology compared with wild type (WT) and TXA 2 synthase null mice. In order to further study the role of TXA 2-TP signaling in the development of Chagas disease, GeneChip microarrays were used to detect transcriptome changes in rat fat pad endothelial cells (RFP-ECs) which is incapable of TXA 2 signaling (TP null) to that of control (wild type) and RFP-EC with reconstituted TP expression. Genes that were significantly regulated due to infection were identified using a time course of 2, 18 and 48 hrs post infection. We identified several key genes such as suppressor of cytokine signaling (SOCS-5), several cytokines (CSF-1, CXCF ligands), and MAP kinases (MAPK-1, Janus kinase) that were upregulated in the absence of TP signaling. These data underscore the importance of the interaction of the parasite with mammalian TP and may explain the increased mortality and cardiovascular pathology observed in infected TP null mice. |
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6. | Med Hypotheses. 2011 May;76(5):638-42. Epub 2011 Feb 1.What is a functional locus? Understanding the genetic basis of complex phenotypic traits.Ruiz-Narváez EA.SourceSlone Epidemiology Center at Boston University, 1010 Commonwealth Avenue, Boston, MA 02215, USA. eruiznar@bu.edu AbstractA multitude of results from genome-wide association studies have been published in recent years in relation to different human diseases and phenotypic traits. However, the identified polymorphisms explain just a small fraction of the variability of the traits and they are poor predictors of occurrence of disease. Although part of the missing variability may be found in still to be identified rare genetic variants, the present work proposes that a major part of the problem is due to our conceptual limitations regarding functional loci and its variants. Functional variants are currently defined in absolute positional terms; they are just sequence variations in fixed positions along the DNA molecule. In the present study is postulated that functional loci may include different positions in the DNA sequence. As consequence, variants of the same functional locus may be located in different physical positions along the genome and, the observed effect of any particular genetic variant will be then reduced compared to its true effect. The differential use of regulatory regions such as gene promoters and enhancers would be a particular case of the proposed hypothesis. The hypothesis makes predictions that can be tested, offering potential paths of research to elucidate the genetic basis of complex human traits. Copyright © 2011 Elsevier Ltd. All rights reserved. |
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