| 1. |
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| 2. |
- Andersson, Björn, et al.
(författare)
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Complete sequence of a 93.4 kb contig from chromosome 3 of Trypanosoma cruzi containing a strand switch region
- 1998
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 8:8, s. 809-816
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Tidskriftsartikel (refereegranskat)abstract
- We have initiated large-scale sequencing of the third smallest chromosome of the CL Brener strain of Trypanosoma cruzi and we report here the complete sequence of a contig consisting of three cosmids. This contig covers 93.4 kb and has been found to contain 20-30 novel genes and several repeat elements, including a novel chromosome 3-specific 400-bp repeat sequence. The intergenic sequences were found to be rich in di- and trinucleotide repeats of varying lengths and also contained several known T. cruzi repeat elements. The sequence contains 29 open reading frames (ORFs) longer than 700 bp, the longest being 5157 bp, and a large number of shorter ORFs. Of the long ORFs, seven show homology to known genes in parasites and other organisms, whereas four ORFs were confirmed by sequencing of cDNA clones. Two shorter ORFs were confirmed by a database homology and a cDNA clone, respectively, and one RNA gene was identified. The identified genes include two copies of the gene for alanine-aminotransferase as well as genes for glucose-6-phosphate isomerase, protein kinases and phosphatases, and an ATP synthase subunit. An interesting feature of the sequence was that the genes appear to be organized in two long clusters containing multiple genes on the same strand. The two clusters are transcribed in opposite directions and they are separated by an approximately 20-kb long, relatively GC-rich sequence, that contains two large repetitive elements as well as a pseudogene for cruzipain and a gene for U2snRNA. It is likely that this strand switch region contains one or more regulatory and promoter regions. The reported sequence provides the first insight into the genome organization of T. cruzi and shows the potential of this approach for rapid identification of novel genes. [The sequence data described in this paper have been submitted to the GenBank data library under accession nos. AF052831-AF052833.]
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| 3. |
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| 4. |
- Ferella, Marcela, et al.
(författare)
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A solanesyl-diphosphate synthase localizes in glycosomes of Trypanosoma cruzi
- 2006
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 281:51, s. 39339-39348
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Tidskriftsartikel (refereegranskat)abstract
- We report the cloning of a Trypanosoma cruzi gene encoding a solanesyl-diphosphate synthase, TcSPPS. The amino acid sequence ( molecular mass similar to 39 kDa) is homologous to polyprenyl-diphosphate synthases from different organisms, showing the seven conserved motifs and the typical hydrophobic profile. TcSPPS preferred geranylgeranyl diphosphate as the allylic substrate. The final product, as determined by TLC, had nine isoprene units. This suggests that the parasite synthesizes mainly ubiquinone-9 (UQ-9), as described for Trypanosoma brucei and Leishmania major. In fact, that was the length of the ubiquinone extracted from epimastigotes, as determined by high-performance liquid chromatography. Expression of TcSPPS was able to complement an Escherichia coli ispB mutant. A punctuated pattern in the cytoplasm of the parasite was detected by immunofluorescence analysis with a specific polyclonal antibody against TcSPPS. An overlapping fluorescence pattern was observed using an antibody directed against the glycosomal marker pyruvate phosphate dikinase, suggesting that this step of the isoprenoid biosynthetic pathway is located in the glycosomes. Co-localization in glycosomes was confirmed by immunogold electron microscopy and subcellular fractionation. Because UQ has a central role in energy production and in reoxidation of reduction equivalents, TcSPPS is promising as a new chemotherapeutic target.
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| 5. |
- Franzen, Oscar, et al.
(författare)
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The Short Non-Coding Transcriptome of the Protozoan Parasite Trypanosoma cruzi
- 2011
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Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 5:8, s. e1283-
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Tidskriftsartikel (refereegranskat)abstract
- The pathway for RNA interference is widespread in metazoans and participates in numerous cellular tasks, from gene silencing to chromatin remodeling and protection against retrotransposition. The unicellular eukaryote Trypanosoma cruzi is missing the canonical RNAi pathway and is unable to induce RNAi-related processes. To further understand alternative RNA pathways operating in this organism, we have performed deep sequencing and genome-wide analyses of a size-fractioned cDNA library (16-61 nt) from the epimastigote life stage. Deep sequencing generated 582,243 short sequences of which 91% could be aligned with the genome sequence. About 95-98% of the aligned data (depending on the haplotype) corresponded to small RNAs derived from tRNAs, rRNAs, snRNAs and snoRNAs. The largest class consisted of tRNA-derived small RNAs which primarily originated from the 3' end of tRNAs, followed by small RNAs derived from rRNA. The remaining sequences revealed the presence of 92 novel transcribed loci, of which 79 did not show homology to known RNA classes.
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| 6. |
- Hanke, J, et al.
(författare)
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Mapping the Trypanosoma cruzi genome : Analyses of representative cosmid libraries
- 1996
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Ingår i: BioTechniques. - 0736-6205 .- 1940-9818. ; 21:4, s. 686-688
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Tidskriftsartikel (refereegranskat)abstract
- In order to generate contiguous cosmid coverage of the genome of the protozoan parasite Trypanosoma cruzi for large-scale sequence analysis, a cosmid library of 36864 individual, primary clones was generated. Total genomic DNA of the reference strain CL Brener was fragmented both by partial digestion with MboI and by physical shearing. For cloning, a modified cosmid vector was used that simplifies analyses such as restriction mapping. The library's representation is about 25 genome equivalents, assuming a size of 55 Mb per haploid genome. No chimerism of inserts in the clones could be detected. The colinearity between cosmid inserts and genomic DNA was verified. Also, hybridizations to the gel-separated karyotype of the organism were carried out as a quality check. Gridded onto two nylon filters, the library was analyzed with a variety of probes. Apart from being used for combined physical and transcriptional mapping of the genome, library filters and clones are also available to interested parties.
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| 7. |
- Henriksson, Jan, et al.
(författare)
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Karyotype variability in Trypanosoma cruzi
- 1996
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Ingår i: Parasitology Today. - : Elsevier BV. - 0169-4758 .- 1873-1473. ; 12:3, s. 108-114
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Tidskriftsartikel (refereegranskat)abstract
- Like many other protozoam parasites, Trypanosoma cruzi (the causative agent of Chagas disease) has a plastic genome. Chromosome size polymorphisms occur in different strains of T. cruzi as well as among clones originating from the same strain, Despite this polymorphism, major interchromosomal rearrangements appear to be rare since several linkage groups of chromosomal markers are well conserved among different T. cruzi strains. In addition, some correlation has been found between karyotype variability and classification by multilocus enzyme electrophoresis. In this review, Jan Henriksson, Lena Åslund and Ulf Petterson discuss the genomic variability and suggest that amplication of repetitive sequences or members of gene families make a major contribution to the chromosomal size variation
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| 8. |
- Hensvik, Lena, 1981-
(författare)
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The effects of markets, managers and peers on worker outcomes
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Essay 1: This essay exploits the entry of private independent high schools in Sweden to examine how local school competition affects the wages and the mobility of teachers in a market with individual wage bargaining. Using rich matched employer-employee panel data covering all high school teachers over a period of 16 years, I show that the entry of private schools is associated with higher teacher salaries, including higher salaries for teachers in public schools. The wage returns from competition are highest for teachers entering the profession and for teachers trained in math and science. Private school entry has also increased wage dispersion between high- and low-skilled teachers within the same field. Several robustness checks support a causal interpretation of the results, which draw attention to the potential effects of school competition on teacher supply, through the more differentiated wage setting of teachers. Essay 2: (with Olof Åslund and Oskar Nordström Skans) We investigate how manager origin affects hiring patterns, job separations, and entry wages. The analysis, draws on a longitudinal matched employer-employee data including more than 100,000 workplaces during a nine year period. Immigrant managers are substantially more likely to hire immigrants, a result robust to comparisons within 5-digit industry and location as well as within firms across establishments. The finding holds also when we follow establishments that change management over time, even accounting for trends. Origin dissimilarity increases separations within the first year of employment, but there is no impact on entry wages. Several results point to information asymmetries as an important explanation to the patterns. Essay 3: The third essay examines whether women benefit from working under female management. I use matched employer-employee panel data for Sweden, which enables me to account for unobserved heterogeneity among both workers and firms. In line with existing work, I document a substantial negative correlation between the proportion of female managers and the establishment’s gender wage gap. However, most of this relationship reflects worker heterogeneity, suggesting that sorting is an important explanation for the lower gender wage difference in female-led firms. Further analysis supports this conclusion by showing that while female managers are not more likely to hire same-sex workers per se, they do indeed hire women with higher portable earnings capacity. Essay 4: (with Peter Nilsson) We analyze how peer effects among co‑workers affect fertility using population‑wide matched employer-employee panel data. We provide evidence on if, when, why and for whom co‑workers’ fertility decisions matter. Overall the impact of co-workers on own fertility is of the same magnitude as the effect of being one year older in the age span 20 to 30. “Same-type” co‑workers are particularly influential, although social status and own previous childbearing experiences modify the influence of peers in distinct ways. Peers’ fertility decisions matter most when the uncertainty about job-related costs of childbearing is low. The results provide insights to the sharp fluctuations in fertility rates observed in many countries, and give an indication of how social interactions affect important career related decisions.
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| 9. |
- Jazin, Elena, et al.
(författare)
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Trypanosoma cruzi exoantigen is a member of a 160 kDa gene family
- 1995
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Ingår i: Parasitology. - 0031-1820 .- 1469-8161. ; 110:Pt1, s. 61-69
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Tidskriftsartikel (refereegranskat)abstract
- During the chronic stage of Chagas disease a 160 kDa antigen appears in the blood of patients and remains detectable many years after the onset of the disease. This antigen is secreted by the trypomastigote form of the parasite while it is undetectable in the epimastigote form. We report here that the chronic 160 kDa exoantigen is encoded by a gene family (CEA 160 family). We describe the cloning and partial nucleotide sequence of a gene (CEA 160-1) belonging to the CEA160 family. Comparison of the gene sequence with other sequences present in the databases revealed homologies with several Trypanosoma cruzi surface antigens. Highest amino acid identity (59%) was with members of a family containing epitopes that mimic nervous tissues (Van Voorhis et al. 1993). Another related group (18-22% amino acid identity) comprises proteins of 85 or 160 kDa sharing an amino acid motif that is conserved among bacterial neuraminidases (Fouts et al. 1991; Pollevick et al. 1991; Kahn et al. 1991; Takle & Cross, 1991; Franco et al. 1993). The amino acid identities with the different antigens were not homogeneously distributed. Regions of higher identity (40-60%) were grouped in the central region of each protein.
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| 10. |
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| 11. |
- Ochaya, Stephen, et al.
(författare)
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Characterization of a Trypanosoma cruzi acetyltransferase : cellular location, activity and structure
- 2007
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Ingår i: Molecular and biochemical parasitology (Print). - : Elsevier BV. - 0166-6851 .- 1872-9428. ; 152:2, s. 123-131
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Tidskriftsartikel (refereegranskat)abstract
- Trypanosomatids are widespread parasites that cause three major tropical diseases. In trypanosomatids, as in most other organisms, acetylation is a common protein modification that is important in multiple, diverse processes. This paper describes a new member of the Trypanosoma cruzi acetyltransferase family. The gene is single copy and orthologs are also present in the other two sequenced trypanosomatids, Trypanosoma brucei and Leishmania major. This protein (TcAT-1) has the essential motifs present in members of the GCN5-related acetyltransferase (GNAT) family, as well as an additional motif also found in some enzymes from plant and animal species. The protein is evolutionarily more closely related to this group of enzymes than to histone acetyltransferases. The native protein has a cytosolic cellular location and is present in all three life-cycle stages of the parasite. The recombinant protein was shown to have autoacetylation enzymatic activity.
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| 12. |
- Parussini, Fabiola, et al.
(författare)
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Characterization of a lysosomal serine carboxypeptidase from Trypanosoma cruzi.
- 2003
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Ingår i: Mol Biochem Parasitol. - 0166-6851. ; 131:1, s. 11-23
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Tidskriftsartikel (refereegranskat)abstract
- Trypanosoma cruzi, the flagellate protozoan which is the causative agent of the American trypanosomiasis, Chagas disease has carboxypeptidase activity. The enzyme has been purified to protein homogeneity, and shown to be a lysosomal monomeric glycoprotein with a molecular mass of about 54kDa. The enzyme has an optimum acidic pH (4.5 with furyl acryloyl-Phe-Phe as substrate), is highly specific for hydrophobic C-terminal amino acid residues, and is strongly inhibited by 3,4-dichloroisocoumarin (IC(50) value 0.3 microM). The enzyme is encoded by a number of genes arrayed in head-to-tail tandems; one of these genes has been cloned and sequenced. Sequence comparisons indicate that the enzyme belongs to the C group of serine carboxypeptidases, within the S10 serine peptidase family, and shows the higher similarity to plant and yeast enzymes. The residues involved in catalysis and most of those involved in substrate binding are conserved in the T. cruzi enzyme as well as 8 out of 10 Cys residues known to be involved in disulfide bridges in the yeast enzyme. This is the first report of an S10 family enzyme in trypanosomatids. The presence of serine carboxypeptidases is not restricted to T. cruzi, being possibly a general character of trypanosomatids.
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| 13. |
- Porcel, Betina M., et al.
(författare)
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Gene survey of the pathogenic protozoan Trypanosoma cruzi
- 2000
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 10:8, s. 1103-1107
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Tidskriftsartikel (refereegranskat)abstract
- We have performed a survey of the active genes in the important human pathogen Trypanosoma cruzi by analyzing 5013 expressed sequence tags (ESTs) generated from a normalized epimastigote cDNA library. Clustering of all sequences resulted in 771 clusters, comprising 54% of the ESTs. In total, the ESTs corresponded to 3054 transcripts that might represent one-fourth of the total gene repertoire in T. cruzi. About 33% of the T. cruzi transcripts showed similarity to sequences in the public databases, and a large number of hitherto undiscovered genes predicted to be involved in transcription, cell cycle control, cell division, signal transduction, secretion, and metabolism were identified. More than 140 full-length gene sequences were derived from the ESTs. Comparisons with all open reading frames in yeast and in Caenorhabditis elegans showed that only 12% of the T. cruzi transcripts were shared among diverse eukaryotic organisms. Comparison with other kinetoplastid sequences identified 237 orthologous genes that are shared between these evolutionarily divergent organisms. The generated data are a useful resource for further studies of the biology of the parasite and for development of new means to combat Chagas' disease.
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| 14. |
- Porcel, Betina, et al.
(författare)
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Trypanosoma rangeli and Trypanosoma cruzi : molecular characterization of genes encoding putative calcium-binding proteins, highly conserved in typanosomatids
- 1996
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Ingår i: Experimental parasitology. - : Elsevier BV. - 0014-4894 .- 1090-2449. ; 84:3, s. 387-399
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Tidskriftsartikel (refereegranskat)abstract
- Genes encoding a 29-kDa flagellar calcium-binding protein (F29) in Trypanosoma cruzi, strongly homologous to EF-hand calcium-binding protein-encoding genes previously reported in this parasite, were isolated by immunoscreening. F29 is encoded by a number of very similar genes, highly conserved among different T. cruzi isolates. The genes are located on a pair of homologous chromosomes, arranged in one or two clusters of tandem repeats. PCR amplification of Trypanosoma rangeli genomic DNA, using primers derived from the T. cruzi F29 sequence made it possible to isolate the homologous gene in T. rangeli, encoding a 23-kDa protein called TrCaBP. Gene sequence comparisons showed homology to EF-hand calcium-binding proteins from T. cruzi (82.8%), Trypanosoma brucei brucei (60.2%), and Entamoeba histolytica (28.4%). Northern blot analysis revealed that the TrCaBP gene is expressed in T. rangeli as a polyadenylated transcript. The TrCaBP-encoding genes are present in at least 20 copies per cell, organized in tandem arrays, on large T. rangeli chromosomes in some isolates and on two smaller ones in others. This gene, however, seems to be absent from Leishmania.
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| 15. |
- Respuela, Patricia, 1977-, et al.
(författare)
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Characterization of a Trypanosoma cruzi polypyrimidine tract binding protein interacting with single-stranded forming DNA
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Although crucial to their biology, regulation of gene expression in trypanosomatid parasites is not fully understood. Our knowledge is limited to the fact that transcript levels are mainly determined post-transcriptionally. However, where and how transcription is initiated is largely unknown and few DNA and RNA binding proteins have been characterized. Therefore, identification of regulatory sequences and counteracting proteins will considerably improve our understanding of the parasite biology. In this work, we have characterized a novel protein in the protozoan parasite Trypanosoma cruzi named T. cruzi polypyrimidine tract binding protein (TcPTB) and investigated its potential role in transcription initiation. TcPTB shares structural and functional properties with mammalian PTB, a protein with multiple roles in mRNA metabolism and transcription initiation. We show that TcPTB is expressed in all parasite stages and is predominantly located in the nucleus. It binds in vitro to polypyrimidine-rich ssDNA including cis-regulatory elements implicated in transcription initiation in mammals and in the related parasite Leishmania major. Chromatin immunoprecipitation analysis associates TcPTB to the RNA pol II promoter of the spliced leader gene. Finally, we also show that T. cruzi polypyrimidine/polypurine sequences form triple helix, a condition necessary for the binding of mammalian PTB. These results suggest that TcPTB has a similar multifunctional role in gene regulation as in mammals.
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| 16. |
- Respuela, Patricia, 1977-, et al.
(författare)
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Distinct histone modification profiles at transcription start sites during development of the parasite Trypanosoma cruzi.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The parasite Trypanosoma cruzi is the etiological agent causing Chagas' disease in Central and South America. This protozoon presents a complex life cycle that comprises three major developmental stages as the parasite is transmitted from the invertebrate vector to a mammalian host. Such drastic environmental changes demand rapid adjustment of the parasite cellular processes. This adaptation appears to be mainly achieved by regulating gene expression levels through post-transcriptional processes. We have previously shown the important role of chromatin in regulating transcriptional initiation through histone modifications. Histones typically associated with active chromatin states (i.e. histone acetylation and histone H3 trimethylated K4) were preferentially enriched at sequences directly flanking transcription start sites in the intergenic region between divergently transcribed polycistronic gene clusters. In this study, we compare acetylated histone H3 profiles in replicative (i.e. logarithmic epimastigotes) and non-replicative (i.e. stationary epimastigotes and trypomastigotes) parasite stages. Histone acetylation was found less abundant in non-replicative stages consistent with previous observations of diminished transcriptional activity in these stages and suggesting potential links between transcription and replication. This was also accompanied by possible changes in nucleosome positioning. We also report the epigenetic profile of histone H3 trimethylated K36, a histone modification previously uncharacterized in T. cruzi . This histone mark was found enriched at regions of transcriptional initiation, suggesting a rather distinct function compared with its established roles in other organisms.
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| 17. |
- Respuela, Patricia, 1977-, et al.
(författare)
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DNA methylation patterns in the parasite Trypanosoma cruzi
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Although DNA methylation is found to be a major epigenetic regulator of vital cellular processes in most organisms, its role in the protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas' disease, remains largely unknown. In this study, we report detection of 5-methyl cytosine (m5C) in T. cruzi DNA and also determine the genomic distribution of m5C by methyl DNA immunoprecipitation (MeDIP). Some of the methylated genomic loci identified were within repetitive retrotransposons or pseudogenes, suggesting a probable role for DNA methylation in transcriptional silencing similar to what has been reported in various organisms. DNA methylation was also found at intergenic regions close to putative transcription start sites, as well as in regions of transcriptional termination, suggesting that these loci are characterized by a complex combination of activating (e.g. acH3, H3K4me3) and silencing (e.g. m5C) epigenetic modifications. Interestingly, both immunostaining and immunoprecipitation results clearly demonstrated that DNA methylation is especially abundant in kinetoplast minicircles DNA. Both global and locus-specific differences in DNA methylation were observed between non-replicative (i.e. trypomastigotes, stationary-phase epimastigotes) and replicative (i.e. logarithmic epimastigotes) stages of the parasite, suggesting a role for DNA methylation in T. cruzi development.
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| 18. |
- Respuela, Patricia, 1977-
(författare)
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Gene Regulation and Epigenetic Mechanisms in the Parasite Trypanosoma cruzi
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Trypanosomes are unicellular protozoan parasites responsible for several human diseases that affect millions of people and cause thousands of casualties every year. They also represent a primitive eukaryotic model system harboring unique processes and basic regulatory mechanisms such as RNA-editing, polycistronic transcription and trans-splicing, first described in these organisms. Unlike most eukaryotes where levels of gene expression are controlled at initiation of transcription, trypanosomes use post-transcriptional events as the main regulators. This thesis explores the epigenetic mechanisms involved in gene expression control in trypanosomes, providing the first evidences for a functional “histone-code” as well as the existence and location of DNA methylation in Trypanosoma cruzi. Chromatin immunoprecipitation (ChIP) was used for the profiling of acetylated and methylated histones in T. cruzi, showing that the modified histones were exclusively localized at bidirectional transcription start sites. In addition, promoters from highly transcribed genes were found depleted of nucleosomes, while DNA regions expected to be silent were not enriched in the investigated modified histones. Furthermore, we showed that the histone patterns were developmentally regulated. The first in depth characterization of the DNA methylation patterns in T. cruzi was presented in this work. We detected m5C in regions of transcriptional initiation and termination, retrotransposons, pseudogenes and the kinetoplast minicircle. We also showed that the amount of methylation changes during development, with an increase in non-replicative forms. We also characterized the DNA-interacting properties of a T. cruzi polypyrimidine-tract binding protein (TcPTB), and its potential role as a transcription factor. TcPTB was found to interact with single-stranded DNA present in promoters bound by its mammalian homologue as well as to the region of transcriptional initiation in Leishmania major. We also demonstrated that T. cruzi polypyrimidine stretches were able to confer ssDNA conformations. Overall, these results provide new insights into the biology of ancient pathogenic parasites, which might be exploited for drug development.
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| 19. |
- Respuela, Patricia, 1977-, et al.
(författare)
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Histone acetylation and methylation at sites initiating divergent polycistronic transcription in Trypanosoma cruzi
- 2008
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 283:23, s. 15884-15892
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Tidskriftsartikel (refereegranskat)abstract
- Trypanosomes are ancient eukaryotic parasites in which the protein-coding genes, organized in large polycistronic clusters on both strands, are transcribed from as yet unidentified promoters. In an effort to reveal transcriptional initiation sites, we examined the Trypanosoma cruzi genome for histone modification patterns shown to be linked to active genes in various organisms. Here, we show that acetylated and methylated histones were found to be enriched at strand switch regions of divergent gene arrays, not at convergent clusters or intra- and intergenic regions within clusters. The modified region showed a bimodular profile with two peaks centered over the 5'-regions of the gene pair flanking the strand switch region. This pattern, which demarcates polycistronic transcription units originating from bidirectional initiation sites, is likely to be common in kinetoplastid parasites as well as in other organisms with polycistronic transcription. In contrast, no acetylation was found at promoters of the highly expressed rRNA and spliced leader genes or satellite DNA or at tested retrotransposonal elements. These results reveal, for the first time, the presence of specific epigenetic marks in T. cruzi with potential implications for transcriptional regulation; they indicate that both histone modifications and bidirectional transcription are evolutionarily conserved.
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| 20. |
- Sabaj, V, et al.
(författare)
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Histone genes expression during the cell cycle in Trypanosoma cruzi
- 2001
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Ingår i: Journal of Cellular Biochemistry. - 0730-2312 .- 1097-4644. ; 80:4, s. 617-624
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Tidskriftsartikel (refereegranskat)abstract
- Histones, the basic proteins which compact DNA into the nucleosomal and solenoidal fibers are synthesized in correlation with DNA replication during the S-phase of the cell cycle. This behavior is controlled both at transcriptional and postranscriptional levels in higher eukaryotes and yeasts. We have found that histone synthesis in synchronized trypanosomes is controlled by fluctuations on the levels of their mRNAs. Though we cannot preclude the existence of a transcriptional regulatory mechanism, our results point to the participation of changes in the stability of histone mRNAs as a regulatory mechanism of their levels during the cell cycle in Trypanosoma. We have also found a postranscriptional regulatory mechanism which could be acting at the translational level. These results show both similarities and differences between Trypanosoma and higher eukaryotes regarding the expression of their histone genes.
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| 21. |
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| 22. |
- Tran, Anh-Nhi
(författare)
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A Genetic Survey of the Pathogenic Parasite Trypanosoma cruzi
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Trypanosoma cruzi, the causative agent of Chagas´ disease, is an evolutionarily ancient species with distinct biological and immunological characteristics. A fundamental understanding of the basic biology of the parasite is necessary in order to develop reliable therapeutic and prophylactic agents against T. cruzi. We have, as a part of the T. cruzi genome project launched by the WHO, generated ESTs corresponding to about one third of the functional genes in the parasite. Only about 1/3 of the unique ESTs could be assigned a function upon sequence comparison to all publicly available data. Comparative analysis of the ESTs to functional genes in S. cerevisiae and C. elegans as well as to sequence data from all other kinetoplastids provided primary insights into the evolutionary divergence of T. cruzi. A novel dispersed gene family (DGC3) was identified and shown to be present specifically on chromosome 3 and its homologue. Sequence analysis of ten isolated DGC3 genes revealed a high sequence similarity of almost 98% among copies. The DGC3 genes were transcribed, trans-spliced with the spliced leader and polyadenylated, but did not seem to have any protein-coding property. These data preliminary suggest that it encodes a novel family of functional RNA. In the T. cruzi CL Brener strain, the two alleles of a single copy gene encoding the trypanothione synthetase (TcTRS) enzyme appeared to be highly polymorphic. The divergence of the deduced protein sequence was 4%, almost ten-fold higher than another protein, trypanothione reductase, involved in the same pathway. The observed allelic divergence might influence the TcTRS activity thereby having implications for drug design. Moreover, the TcTRS gene was found to be flanked by a number of genes involved in diverse functions and located to a pair of homologous chromosomes with a size difference of about 2 Mbp. A gene potentially encoding the polypyrimidine-binding protein (TcPTB) was identified and characterised regarding its organisation and function. The deduced amino acid sequence was shown to comprise four RRM domains generally present in other PTBs. Interestingly, the TcPTB gene appeared to be expressed in a stage-specific manner implicating different functions during parasite development.
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| 23. |
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| 24. |
- Tran, Anh-Nhi, et al.
(författare)
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Trypanothione synthetase locus in Trypanosoma cruzi CL Brener strain shows an extensive allelic divergence
- 2003
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Ingår i: Acta Tropica. - 0001-706X .- 1873-6254. ; 87:2, s. 269-278
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Tidskriftsartikel (refereegranskat)abstract
- The protozoan parasite Trypanosoma cruzi, agent of Chagas' disease, displays an extensive genetic heterogeneity among strains and isolates. It is, therefore, important to determine the degree of polymorphism in potential candidates for drug design. Our studies on the organisation of the locus containing the gene encoding trypanothione synthetase (TcTRS) (an enzyme involved in the unique trypanothione pathway and hence a promising drug target) revealed a high degree of sequence polymorphism between the two alleles in the T. cruzi CL Brener strain, the reference clone for the genome project. The genes linked to the synthetase appeared to be involved in diverse cell-functions, not part of the trypanothione metabolism. The gene synteny was conserved at both allelic loci that were found to reside on a pair of homologous chromosomes with a size difference of about 2 Mb. The allelic polymorphism of TcTRS resulted in a protein sequence divergence of 4%, ten-times higher than in trypanothione reductase (TR), another key enzyme in the same pathway. Such allelic divergence observed in T. cruzi genes might have implications for drug design against Chagas' disease and the evolutional impact of the CL Brener strain.
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| 25. |
- Venegas, Juan A., et al.
(författare)
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Cloning and characterization of a DNA polymerase beta gene from Trypanosoma cruzi
- 2009
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Ingår i: Parasitology international. - : Elsevier BV. - 1383-5769 .- 1873-0329. ; 58:2, s. 187-192
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Tidskriftsartikel (refereegranskat)abstract
- A gene coding for a DNA polymerase beta from the Trypanosoma cruzi Miranda clone, belonging to the TcI lineage, was cloned (Miranda Tcpol beta), using the information from eight peptides of the T. cruzi beta-like DNA polymerase purified previously. The gene encodes for a protein of 403 amino acids which is very similar to the two T. cruzi CL Brener (TcIIe lineage) sequences published, but has three different residues in highly conserved segments. At the amino acid level, the identity of TcI-pol beta with mitochondrial pol beta and pol beta-PAK from other trypanosomatids was between 68-80% and 22-30%, respectively. Miranda Tc-pol beta protein has an N-terminal sequence similar to that described in the mitochondrial Crithidia fasciculata pol beta, which suggests that the TcI-pol beta plays a role in the organelle. Northern and Western analyses showed that this T. cruzi gene is highly expressed both in proliferative and non-proliferative developmental forms. These results suggest that, in addition to replication of kDNA in proliferative cells, this enzyme may have another function in non-proliferative cells, such as DNA repair role similar to that which has extensively been described in a vast spectrum of eukaryotic cells.
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| 26. |
- Zingales, Bianca, et al.
(författare)
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The Trypanosoma cruzi genome initiative
- 1997
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Ingår i: Parasitology Today. - 0169-4758 .- 1873-1473. ; 13:1, s. 16-22
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Tidskriftsartikel (refereegranskat)abstract
- An initiative was launched in 1994 by the Special Programme for Research and Training in Tropical Diseases (TDR) of the WHO to analyse the genomes of the parasites Filaria, Schistosoma, Leishmania, Trypanosoma brucei and Trypanosoma cruzi. Five networks were established through wide publicity, holding meetings of key laboratories and developing proposals which were then reviewed by the Steering Committee of Strategic Research for financial support. The aim of the Programme was to use the platform of these networks to: (1) train scientists from tropical disease-endemic countries; (2) transfer technology and share material and expertise, thereby reducing costs and increasing efficiency; and (3) provide an information system that is accessible globally as soon as the results become available. The initial target was to produce a low-resolution genome map for each of the parasites, but it soon became evident that by using rapidly developing technologies, it might be feasible to complete DNA-sequence analysis for some of the parasites in the next decade, as discussed here by Alberto Carlos Frasch and colleagues, with particular focus on the T. cruzi genome initiative.
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| 27. |
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| 28. |
- Åslund, Olof, et al.
(författare)
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Seeking Similarity : How Immigrants and Natives Manage in the Labor Market
- 2014
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Ingår i: Journal of Labor Economics. - : University of Chicago Press. - 0734-306X .- 1537-5307. ; 32:3, s. 405-441
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Tidskriftsartikel (refereegranskat)abstract
- We investigate how the interplay between manager and worker origin affects hiring patterns, job separations, and wages. Numerous specifications utilizing a longitudinal matched employer-employee database including 70,000 establishments consistently show that managers are substantially more likely to hire workers of their own origin. Workers who share an origin with their managers earn higher wages and have lower separation rates than dissimilar workers, but this pattern is driven by differences in unobserved worker characteristics. Our findings indicate that the sorting patterns are more likely to be explained by profit-maximizing concerns than by preference-based discrimination.
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