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Sent on Tuesday, 2009 Nov 17Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Eukaryot Cell. 2009 Nov 13. [Epub ahead of print]Active VSG expression sites in Trypanosoma brucei are depleted of nucleosomes.Stanne TM, Rudenko G.The Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford OX1 3SY, United Kingdom. African trypanosomes regulate transcription differently from other eukaryotes. Most of the trypanosome genome is constitutively transcribed by RNA polymerase II (Pol II) as large polycistronic transcription units, while the genes encoding the major surface proteins are transcribed by RNA polymerase I (Pol I). In bloodstream form Trypanosoma brucei the gene encoding the variant surface glycoprotein (VSG) coat is expressed in a mono-allelic fashion from one of about 15 VSG expression sites (ESs). Little is known about the chromatin structure of the trypanosome genome, and the chromatin state of active versus silent VSG ESs remains controversial. Here we determined histone H3 occupancy within the genome of T. brucei, focusing on active versus silent VSG ESs in the bloodstream form. We found that histone H3 was most enriched in the non-transcribed 50 bp and 177 bp repeats, and relatively depleted in Pol I, II and III transcription units, with particular depletion over promoter regions. Using two isogenic T. brucei lines containing marker genes in different VSG ESs, we determined that histone H3 is 11-40 fold depleted from active VSG ESs compared with silent VSG ESs. qPCR analysis of fractionated micrococcal nuclease digested chromatin revealed that the active VSG ES is depleted of nucleosomes. Therefore, in contrast to earlier views, nucleosome positioning appears to be involved in the mono-alleleic control of VSG ESs in T. brucei. This may provide a level of epigenetic regulation enabling bloodstream form trypanosomes to efficiently pass on the transcriptional state of active and silent ESs to daughter cells. |
| PMID: 19915073 [PubMed - as supplied by publisher] | |
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| 2. | J Immunol. 2009 Nov 13. [Epub ahead of print]Dynamic Regulation of Notch 1 and Notch 2 Surface Expression during T Cell Development and Activation Revealed by Novel Monoclonal Antibodies.Fiorini E, Merck E, Wilson A, Ferrero I, Jiang W, Koch U, Auderset F, Laurenti E, Tacchini-Cottier F, Pierres M, Radtke F, Luther SA, Macdonald HR.*Ludwig Institute for Cancer Research Ltd., Lausanne Branch, 1066 Epalinges, Switzerland; It is well established that Notch signaling plays a critical role at multiple stages of T cell development and activation. However, detailed analysis of the cellular and molecular events associated with Notch signaling in T cells is hampered by the lack of reagents that can unambiguously measure cell surface Notch receptor expression. Using novel rat mAbs directed against the extracellular domains of Notch1 and Notch2, we find that Notch1 is already highly expressed on common lymphoid precursors in the bone marrow and remains at high levels during intrathymic maturation of CD4(-)CD8(-) thymocytes. Notch1 is progressively down-regulated at the CD4(+)CD8(+) and mature CD4(+) or CD8(+) thymic stages and is expressed at low levels on peripheral T cells. Immunofluorescence staining of thymus cryosections further revealed a localization of Notch1(+)CD25(-) cells adjacent to the thymus capsule. Notch1 was up-regulated on peripheral T cells following activation in vitro with anti-CD3 mAbs or infection in vivo with lymphocytic chorio-meningitis virus or Leishmania major. In contrast to Notch1, Notch2 was expressed at intermediate levels on common lymphoid precursors and CD117(+) early intrathymic subsets, but disappeared completely at subsequent stages of T cell development. However, transient up-regulation of Notch2 was also observed on peripheral T cells following anti-CD3 stimulation. Collectively our novel mAbs reveal a dynamic regulation of Notch1 and Notch2 surface expression during T cell development and activation. Furthermore they provide an important resource for future analysis of Notch receptors in various tissues including the hematopoietic system. |
| PMID: 19915064 [PubMed - as supplied by publisher] | |
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| 3. | Nucleic Acids Res. 2009 Nov 13. [Epub ahead of print]EuPathDB: a portal to eukaryotic pathogen databases.Aurrecoechea C, Brestelli J, Brunk BP, Fischer S, Gajria B, Gao X, Gingle A, Grant G, Harb OS, Heiges M, Innamorato F, Iodice J, Kissinger JC, Kraemer ET, Li W, Miller JA, Nayak V, Pennington C, Pinney DF, Roos DS, Ross C, Srinivasamoorthy G, Stoeckert CJ Jr, Thibodeau R, Treatman C, Wang H.Center for Tropical & Emerging Global Diseases, University of Georgia, Athens, GA 30602, Penn Center for Bioinformatics, University of Pennsylvania, Philadelphia, PA 19104, Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, Center for Applied Genetic Technologies, University of Georgia, Athens, GA 30602, Department of Genetics, University of Georgia, Athens, GA 30602 and Department of Computer Science, University of Georgia, Athens, GA 30602, USA. EuPathDB (http://EuPathDB.org; formerly ApiDB) is an integrated database covering the eukaryotic pathogens of the genera Cryptosporidium, Giardia, Leishmania, Neospora, Plasmodium, Toxoplasma, Trichomonas and Trypanosoma. While each of these groups is supported by a taxon-specific database built upon the same infrastructure, the EuPathDB portal offers an entry point to all these resources, and the opportunity to leverage orthology for searches across genera. The most recent release of EuPathDB includes updates and changes affecting data content, infrastructure and the user interface, improving data access and enhancing the user experience. EuPathDB currently supports more than 80 searches and the recently-implemented 'search strategy' system enables users to construct complex multi-step searches via a graphical interface. Search results are dynamically displayed as the strategy is constructed or modified, and can be downloaded, saved, revised, or shared with other database users. |
| PMID: 19914931 [PubMed - as supplied by publisher] | |
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| 4. | Eur J Med Chem. 2009 Oct 23. [Epub ahead of print]Synthesis and antiprotozoal activity of 4-arylcoumarins.Piers on JT, Dumètre A, Hutter S, Delmas F, Laget M, Finet JP, Azas N, Combes S.UMR-CNRS 6264, Laboratoire Chimie Provence, Universités Aix-Marseille I, II and III, Faculté des Sciences de Saint-Jérôme, Avenue Escadrille-Normandie-Niemen, 13397 Marseille Cedex 20, France; UMR-MD 3, Relations Hôte-Parasites, Pharmacologie et Thérapeutique, Université Aix-Marseille II, Faculté de Pharmacie, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 5, France. A large series of 4-arylcoumarins was synthesized by Suzuki-Miyaura cross-coupling reaction and evaluated for antiprotozoal activity against Plasmodium falciparum and Leishmania donovani. Several compounds were found to strongly inhibit the proliferation of human cell line and/or parasites. The 4-(3,4-dimethoxyphenyl)-6,7-dimethoxycoumarin exhibit a potent activity on L. donovani amastigotes with a selectivity index (SI=265) twice than amphotericin B (SI=140) (c) 2009 Elsevier Science. All rights reserved. |
| PMID: 19914747 [PubMed - as supplied by publisher] | |
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| 5. | Gene. 2009 Nov 12. [Epub ahead of print]Analysis of ribosomal RNA transcription termination and 3' end processing in Leishmania amazonensis.Abreu-Blanco MT, Ramírez JL, Pinto-Santini DM, Papadopoulou B, Guevara P.Instituto de Biología Experimental. Universidad Central de Venezuela. Caracas, Venezuela. The control of gene expression in the human parasite Leishmania occurs mainly at the post-transcriptional level. Nevertheless, basic cell processes such as ribosome biogenesis seem to be conserved. Mature ribosomal RNAs (rRNAs) are synthesized from typical RNA polymerase I (Pol I) promoters and processed by pathways analogous to other eukaryotes. To further understand Pol I transcription control in these parasites, we have analyzed transcription termination and processing of the rDNA in Leishmania amazonensis. 3'-end S1 mapping of rRNA precursors identified three termini, one corresponding to the mature 28S rRNA and two to the rDNA intergenic spacer (IGS), termed T1 and T2, for precursors which are 185 and 576 nucleotides longer, respectively. Both T1 and T2 are associated with conserved G+C rich elements that have the potential to form hairpin structures and T-rich clusters. We found that two fragments of 423 bp and 233 bp, flanking sites T1 and T2 respectively when placed upstream of the green fluorescent protein gene (GFP), negatively affected the Pol I-driven transcription of this gene, which suggests the presence of a transcription terminator element in these regions. Deletion analysis pointed to a CCCTTTT heptamer as part of the putative terminator and suggested that the hairpins are processing signals. |
| PMID: 19914359 [PubMed - as supplied by publisher] | |
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| 6. | Bioorg Med Chem. 2009 Oct 27. [Epub ahead of print]Antimalarial and antileishma nial activities of histone deacetylase inhibitors with triazole-linked cap group.Patil V, Guerrant W, Chen PC, Gryder B, Benicewicz DB, Khan SI, Tekwani BL, Oyelere AK.School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA. Histone deacetylase inhibitors (HDACi) are endowed with plethora of biological functions including anti-proliferative, anti-inflammatory, anti-parasitic, and cognition-enhancing activities. Parsing the structure-activity relationship (SAR) for each disease condition is vital for long-term therapeutic applications of HDACi. We report in the present study specific cap group substitution patterns and spacer-group chain lengths that enhance the antimalarial and antileishmanial activity of aryltriazolylhydroxamates-based HDACi. We identified many compounds that are several folds selectively cytotoxic to the plasmodium parasites compared to standard HDACi. Also, a few of these compounds have antileishmanial activity that rivals that of miltefosine, the only currently available oral agent against visceral leishmaniasis. The anti-parasite properties of several of these compounds tracked well with their anti-HDAC activities. The results presented here provide further evidence on the suitability of HDAC inhibition as a viable therapeutic option to curb infections caused by apicomplexan protozoans and trypanosomatids. |
| PMID: 19914074 [PubMed - as supplied by publisher] | |
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| 7. | Bioorg Med Chem Lett. 2009 Oct 30. [Epub ahead of print]Synthesis of substituted aryloxy alkyl and aryloxy aryl alkyl imidazoles as antileishmanial agents.Bhandari K, Srinivas N, Marrapu VK, Verma A, Srivastava S, Gupta S.Medicinal and Process Chemistry Division, Central Drug Research Institute, CSIR, Lucknow 226 001, India. A series of aryloxy alkyl/aryl alkyl imidazoles were synthesized and evaluated in vitro as antileishmanials against Leishmania donovani. All the 19 compounds exhibited 94-100% inhibition at 10mug/mL against promastigotes and 12 compounds exhibited high inhibition with an IC(50) in the range of 0.47-4.85mug/mL against amastigotes. Promising compounds were tested further in vivo. Among all, compounds 4 and 23 with 4-CF(3) aryloxy moiety exhibited medium in vivo inhibition of 58-60%, thus providing new structural lead for antileishmanials. |
| PMID: 19913413 [PubMed - as supplied by publisher] | |
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| 8. | Infect Genet Evol. 2009 Nov 10. [Epub ahead of print]Sequence analysis and pcr-rflp profiling of the hsp70 Gene as a valuable tool for identifying Leishmania species associated with human leishmaniasis in Brazil.Silva LA, Sousa CD, Graça GC, Porrozzi R, Cupolillo E.Laboratório de Pesquisa em Leishmaniose, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil 4365, Manguinhos, 21045-900, Rio de Janeiro, RJ, Brazil. Since the first report of the genus Leishmania, many species have been described. In Brazil, human leishmaniasis has been associated with eight Leishmania species, of which seven are responsible for cutaneous leishmaniasis (CL). In some endemic areas, CL is associated with only one species; however, in other areas, such as the Amazon, the etiology of CL can be assigned to many species. The multitude of highly similar Leishmania species in Brazil makes it difficult to develop an appropriate method of typing them. Most Leishmania species were first described based on epidemiological and biological characteristics, and these were later corroborated by Multilocus Enzyme Electrophoresis (MLEE), the gold standard technique for identifying Leishmania species. In an attempt to overcome the limitations of MLEE, many PCR-based methods have been developed and used for parasite identification. In the present study, we analyzed the sequence of the hsp70 gene in Leishmania species associated with human leishmaniasis in Brazil. This analysis led to the identification of restriction enzymes that could be used for PCR-RFLP-based identification. The results obtained were in complete agreement with those obtained by MLEE, suggesting that PCR-RFLP analysis of hsp70 could soon replace MLEE for routine Leishmania typing. |
| PMID: 19913112 [PubMed - as supplied by publisher] | |
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| 9. | Infect Genet Evol. 2009 Nov 10. [Epub ahead of print]Identification of subspecies specific genes differentially expressed in procyclic forms of Trypanosoma brucei subspecies.Simo G, Queiroz R, Herder S, Cuny G, Hoheisel J.Deutsches Krebsforschungszentrum, Division of Functional Genome Analysis (B070), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany; Medical Research Centre, Institute of Medical Research and Medicinal Plant Studies (IMPM) Yaoundé, Cameroon. Trypanosoma brucei subspecies undergo establishment and maturation in tsetse flies mid-gut and salivary glands respectively. Successful establishment of trypanosomes in tsetse mid-gut as well as their migration to saliva gland depends on the ability of these parasites to adapt rapidly to new environmental conditions and to negotiate the physical barriers. To identify subspecies specific genes which are differentially regulated during the establishment of Trypanosoma brucei subspecies in tsetse flies mid gut, a comparative genomic analysis between different Trypanosoma brucei subspecies was performed using microarrays containing about 23 040 Trypanosoma brucei shotgun fragments. The whole genome analyses of RNA expression profiles revealed about 274 significantly differentially expressed genes between Trypanosoma brucei subspecies. About 7% of the differentially regulated clones did not match to any Trypanosoma brucei predicted genes. Most of the differentially regulated transcripts are involved in transport across cell membrane and also in the purines metabolism. The genes selectively up regulated in Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense (human infective Trypanosoma brucei) like snoRNA and HSP70 are expressed in response to stress. The high failure rate in the process of establishment and maturation of Trypanosoma brucei gambiense during cyclical transmission in tsetse flies may result from the incapacity of this parasite to regulate its growth due to the expression of a variety of chaperones or heat shock proteins. Genes selectively up regulated in Trypanosoma brucei brucei like NT8.1 nucleoside/nucleobase transporters and S-adenosylmethionine synthetase may favor the establishment of this subspecies in tsetse mid gut. These genes appear as potential targets for investigations on the development of vaccine blocking the transmission of trypanosomes in tsetse flies. |
| PMID: 19913111 [PubMed - as supplied by publisher] | |
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| 10. | Infect Genet Evol. 2009 Nov 10. [Epub ahead of print]Phylogeny of Leishmania species based on the heat-shock protein 70 gene.Fraga J, Montalvo AM, De Doncker S, Dujardin JC, Van der Auwera G.Parasitology Department, Institute of Tropical Medicine Pedro Kouri, La Havana, Cuba. Fraga J, Montalvo AM, De Doncker S, Dujardin J-C, Van der Auwera G, Phylogeny of Leishmania species based on the heat-shock protein 70 gene., Infection, Genetics and Evolution. The 70kDa heat-shock protein (HSP70) is conserved across prokaryotes and eukaryotes, and the protein as well as its encoding gene have been applied in phylogenetic studies of different parasites. In spite of the frequent use of New World Leishmania species identification on the basis of restriction fragment length polymorphisms (RFLP) in the hsp70 gene, it was never sequenced extensively for studying evolutionary relationships. To fill this void we determined the nucleotide sequence of an 1380bp fragment of the coding region commonly used in RFLP analysis, from 43 isolates and strains of different geographic origin. Combination with previously determined sequences amounted to a phylogenetic analysis including 52 hsp70 sequences representing 17 species commonly causing leishmaniasis both in the New and Old World. The genus Leishmania formed a monophyletic group with three distinct subgenera L. (Leishmania), L. (Viannia), and L. (Sauroleishmania). The obtained phylogeny supports the following eight species: L. (L.) donovani, L. (L.) major, L. (L.) tropica, L. (L.) mexicana, L. (V.) lainsoni, L. (V.) naiffi, L. (V.) guyanensis and L. (V.) braziliensis, in some of which subspecies can be recognized: L. (L.) donovani infantum, L. (V.) guyanensis panamensis, and L. (V.) braziliensis peruviana. The currently recognized L. (L.) aethiopica, L. (L.) garnhami, and L. (L.) amazonensis did not form monophyletic clusters. These findings are discussed in relation to results from other genes and proteins, which have to be integrated in order to build a genetically supported taxonomy for the entire genus. |
| PMID: 19913110 [PubMed - as supplied by publisher] | |
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