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  • Proceedings of the National Academy of Sciences  (4)
  • 1
    Online-Ressource
    Online-Ressource
    Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes
    Proceedings of the National Academy of Sciences ; 2023
    In:  Proceedings of the National Academy of Sciences Vol. 120, No. 36 ( 2023-09-05)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 36 ( 2023-09-05)
    Kurzfassung: Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1 *04 subtypes best accounted for the association, strongest with HLA-DRB1 *04:04 and HLA-DRB1 *04:07, and intermediary with HLA-DRB1 *04:01 and HLA-DRB1 *04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1 *04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1 *04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2302720120
    RVK:
    TA 1000
    RVK:
    WA 15000
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 2023
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Online-Ressource
  • 2
    Online-Ressource
    Online-Ressource
    The Leader Sequence from the 5′-Terminus to the A-Protein Initiation Codon in MS2-Virus RNA
    Proceedings of the National Academy of Sciences ; 1971
    In:  Proceedings of the National Academy of Sciences Vol. 68, No. 3 ( 1971-03), p. 585-589
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 68, No. 3 ( 1971-03), p. 585-589
    Kurzfassung: RNA fragments of different chain length, each containing the 5′-terminal guanosine tetraphosphate (pppGp) of bacteriophage-MS2 RNA, have been isolated from partial ribonuclease digests of the viral RNA. The longest fragment overlaps with the ribosomalbinding site of the A-protein cistron. The base sequence has been established for the major part. The results directly confirm that the A-protein cistron is closest to the 5′-terminus. Its initiating (AUG) codon starts at position 130, being preceded by an untranslated sequence of 129 nucleotides.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.68.3.585
    RVK:
    TA 1000
    RVK:
    WA 15000
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 1971
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Online-Ressource
  • 3
    Online-Ressource
    Online-Ressource
    A motion area in human visual cortex.
    Proceedings of the National Academy of Sciences ; 1995
    In:  Proceedings of the National Academy of Sciences Vol. 92, No. 4 ( 1995-02-14), p. 993-997
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 92, No. 4 ( 1995-02-14), p. 993-997
    Kurzfassung: We have localized an area in the human brain involved in the processing of contours defined by motion differences (kinetic contours) by comparing with positron emission tomography the regional cerebral blood flow in tasks performed with kinetic and luminance-defined gratings. These tasks included passive viewing, counting the total number of grating stimuli, and counting the number of gratings of a given orientation. Comparison between the counting tasks and passive viewing with a given type of contour revealed a set of active areas that were similar for both luminance-defined and kinetic contours. Comparisons between these two types of contours revealed a single focus in the right hemisphere that did not overlap with the many regions activated by uniform motion. In particular this "kinetic focus" was clearly separated from the area previously defined as the human homologue of V5/middle temporal. Activity in this kinetic focus was stronger when orientation had to be processed than in the other two tasks. These results and control experiments with uniformly moving random dot patterns suggest the existence of an area in the human visual system that is activated much more by kinetic contours than by luminance contours or uniformly moving random dots. Up to now, such an area has not been described in the monkey visual system.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.92.4.993
    RVK:
    TA 1000
    RVK:
    WA 15000
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 1995
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Online-Ressource
  • 4
    Online-Ressource
    Online-Ressource
    Adeno-associated viruses undergo substantial evolution in primates during natural infections
    Proceedings of the National Academy of Sciences ; 2003
    In:  Proceedings of the National Academy of Sciences Vol. 100, No. 10 ( 2003-05-13), p. 6081-6086
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 100, No. 10 ( 2003-05-13), p. 6081-6086
    Kurzfassung: Adeno-associated viruses (AAVs) are single-stranded DNA viruses that are endemic in human populations without known clinical sequelae and are being evaluated as vectors for human gene therapy. To better understand the biology of this virus, we examined a number of nonhuman primate species for the presence of previously uncharacterized AAVs and characterized their structure and distribution. AAV genomes were widely disseminated throughout multiple tissues of a variety of nonhuman primate species. Surprising diversity of sequence, primarily localized to hypervariable regions of the capsid protein, was detected. This diversity of sequence is caused, in part, by homologous recombination of co-infecting parental viruses that modify the serologic reactivity and tropism of the virus. This is an example of rapid molecular evolution of a DNA virus in a way that was formerly thought to be restricted to RNA viruses.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0937739100
    RVK:
    TA 1000
    RVK:
    WA 15000
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 2003
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Online-Ressource
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