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  • 1
    Online Resource
    Online Resource
    The Orientia tsutsugamushi genome reveals massive proliferation of conjugative type IV secretion system and host–cell interaction genes
    Proceedings of the National Academy of Sciences ; 2007
    In:  Proceedings of the National Academy of Sciences Vol. 104, No. 19 ( 2007-05-08), p. 7981-7986
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 104, No. 19 ( 2007-05-08), p. 7981-7986
    Abstract: Scrub typhus is caused by the obligate intracellular rickettsia Orientia tsutsugamushi (previously called Rickettsia tsutsugamushi ). The bacterium is maternally inherited in trombicuid mites and transmitted to humans by feeding larvae. We report here the 2,127,051-bp genome of the Boryong strain, which represents the most highly repeated bacterial genome sequenced to date. The repeat density of the scrub typhus pathogen is 200-fold higher than that of its close relative Rickettsia prowazekii , the agent of epidemic typhus. A total of 359 tra genes for components of conjugative type IV secretion systems were identified at 79 sites in the genome. Associated with these are 〉 200 genes for signaling and host–cell interaction proteins, such as histidine kinases, ankyrin-repeat proteins, and tetratrico peptide-repeat proteins. Additionally, the O. tsutsugamushi genome contains 〉 400 transposases, 60 phage integrases, and 70 reverse transcriptases. Deletions and rearrangements have yielded unique gene combinations as well as frequent pseudogenization in the tra clusters. A comparative analysis of the tra clusters within the genome and across strains indicates sequence homogenization by gene conversion, whereas complexity, diversity, and pseudogenization are acquired by duplications, deletions, and transposon integrations into the amplified segments. The results suggest intragenomic duplications or multiple integrations of a massively proliferating conjugative transfer system. Diversifying selection on host–cell interaction genes along with repeated population bottlenecks may drive rare genome variants to fixation, thereby short-circuiting selection for low complexity in bacterial genomes.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0611553104
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2007
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  • 2
    Online Resource
    Online Resource
    Molecular Characterization of a Group of Proteins Containing Ankyrin Repeats in Orientia tsutsugamushi
    Wiley ; 2005
    In:  Annals of the New York Academy of Sciences Vol. 1063, No. 1 ( 2005-12), p. 100-101
    Details
    In: Annals of the New York Academy of Sciences, Wiley, Vol. 1063, No. 1 ( 2005-12), p. 100-101
    Abstract: A bstract : Orientia tsutsugamushi , an obligate intracellular bacterium, is the causative agent of scrub typhus. The sequencing and analysis of full genomic DNA of O. tsutsugamushi has revealed at least 19 genes thus far encoding proteins with different numbers of ankyrin repeat domains. We have cloned several genes containing ankyrin repeats from the genome and produced fusion proteins to characterize their functions in host cells. It is likely that the proteins with ankyrin repeat domains expressed in O. tsutsugamushi ‐infected cells may control the synthesis or stability of host proteins to modulate the various cellular functions after infection. The exploitation of host factors by ankyrin repeat proteins of O. tsutsugamushi may also play a critical role in its pathogenesis.
    Type of Medium: Online Resource
    ISSN: 0077-8923 , 1749-6632
    URL: Article
    DOI: 10.1196/annals.1355.016
    RVK:
    TD 7650
    Language: English
    Publisher: Wiley
    Publication Date: 2005
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  • 3
    Online Resource
    Online Resource
    Patient-Specific Embryonic Stem Cells Derived from Human SCNT Blastocysts
    American Association for the Advancement of Science (AAAS) ; 2005
    In:  Science Vol. 308, No. 5729 ( 2005-06-17), p. 1777-1783
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 308, No. 5729 ( 2005-06-17), p. 1777-1783
    Abstract: Patient-specific, immune-matched human embryonic stem cells (hESCs) are anticipated to be of great biomedical importance for studies of disease and development and to advance clinical deliberations regarding stem cell transplantation. Eleven hESC lines were established by somatic cell nuclear transfer (SCNT) of skin cells from patients with disease or injury into donated oocytes. These lines, nuclear transfer (NT)âhESCs, grown on human feeders from the same NT donor or from genetically unrelated individuals, were established at high rates, regardless of NT donor sex or age. NT-hESCs were pluripotent, chromosomally normal, and matched the NT patient's DNA. The major histocompatibility complex identity of each NT-hESC when compared to the patient's own showed immunological compatibility, which is important for eventual transplantation. With the generation of these NT-hESCs, evaluations of genetic and epigenetic stability can be made. Additional work remains to be done regarding the development of reliable directed differentiation and the elimination of remaining animal components. Before clinical use of these cells can occur, preclinical evidence is required to prove that transplantation of differentiated NT-hESCs can be safe, effective, and tolerated.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1112286
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2005
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  • 4
    Online Resource
    Online Resource
    Integrated one- and two-photon imaging platform reveals clonal expansion as a major driver of mutation load
    Proceedings of the National Academy of Sciences ; 2008
    In:  Proceedings of the National Academy of Sciences Vol. 105, No. 30 ( 2008-07-29), p. 10314-10319
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 105, No. 30 ( 2008-07-29), p. 10314-10319
    Abstract: The clonal expansion of mutant cells is hypothesized to be an important first step in cancer formation. To understand the earliest stages of tumorigenesis, a method to identify and analyze clonal expansion is needed. We have previously described transgenic Fluorescent Yellow Direct Repeat (FYDR) mice in which cells that have undergone sequence rearrangements (via homologous recombination events) express a fluorescent protein, enabling fluorescent labeling of phenotypically normal cells. Here, we develop an integrated one- and two-photon imaging platform that spans four orders of magnitude to permit rapid quantification of clonal expansion in the FYDR pancreas in situ . Results show that as mice age there is a significant increase in the number of cells within fluorescent cell clusters, indicating that pancreatic cells can clonally expand with age. Importantly, 〉 90% of fluorescent cells in aged mice result from clonal expansion, rather than de novo sequence rearrangements at the FYDR locus. The spontaneous frequency of sequence rearrangements at the FYDR locus is on par with that of other classes of mutational events. Therefore, we conclude that clonal expansion is one of the most important mechanisms for increasing the burden of mutant cells in the mouse pancreas.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0804346105
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2008
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    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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