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  • 1
    Online Resource
    Online Resource
    DOCK2 is involved in the host genetics and biology of severe COVID-19
    Springer Science and Business Media LLC ; 2022
    In:  Nature Vol. 609, No. 7928 ( 2022-09-22), p. 754-760
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 609, No. 7928 ( 2022-09-22), p. 754-760
    Abstract: Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge 1–5 . Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene ( DOCK2 ), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis ( n  = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-022-05163-5
    RVK:
    TA 1000
    RVK:
    UA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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    SSG: 11
    Location Call Number Limitation Availability
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  • 2
    Online Resource
    Online Resource
    Radiation dose rates now and in the future for residents neighboring restricted areas of the Fukushima Daiichi Nuclear Power Plant
    Proceedings of the National Academy of Sciences ; 2014
    In:  Proceedings of the National Academy of Sciences Vol. 111, No. 10 ( 2014-03-11)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 10 ( 2014-03-11)
    Abstract: Radiation dose rates were evaluated in three areas neighboring a restricted area within a 20- to 50-km radius of the Fukushima Daiichi Nuclear Power Plant in August–September 2012 and projected to 2022 and 2062. Study participants wore personal dosimeters measuring external dose equivalents, almost entirely from deposited radionuclides (groundshine). External dose rate equivalents owing to the accident averaged 1.03, 2.75, and 1.66 mSv/y in the village of Kawauchi, the Tamano area of Soma, and the Haramachi area of Minamisoma, respectively. Internal dose rates estimated from dietary intake of radiocesium averaged 0.0058, 0.019, and 0.0088 mSv/y in Kawauchi, Tamano, and Haramachi, respectively. Dose rates from inhalation of resuspended radiocesium were lower than 0.001 mSv/y. In 2012, the average annual doses from radiocesium were close to the average background radiation exposure (2 mSv/y) in Japan. Accounting only for the physical decay of radiocesium, mean annual dose rates in 2022 were estimated as 0.31, 0.87, and 0.53 mSv/y in Kawauchi, Tamano, and Haramachi, respectively. The simple and conservative estimates are comparable with variations in the background dose, and unlikely to exceed the ordinary permissible dose rate (1 mSv/y) for the majority of the Fukushima population. Health risk assessment indicates that post-2012 doses will increase lifetime solid cancer, leukemia, and breast cancer incidences by 1.06%, 0.03% and 0.28% respectively, in Tamano. This assessment was derived from short-term observation with uncertainties and did not evaluate the first-year dose and radioiodine exposure. Nevertheless, this estimate provides perspective on the long-term radiation exposure levels in the three regions.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1315684111
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2014
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    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    FD, a bZIP Protein Mediating Signals from the Floral Pathway Integrator FT at the Shoot Apex
    American Association for the Advancement of Science (AAAS) ; 2005
    In:  Science Vol. 309, No. 5737 ( 2005-08-12), p. 1052-1056
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 309, No. 5737 ( 2005-08-12), p. 1052-1056
    Abstract: FLOWERING LOCUS T ( FT ) is a conserved promoter of flowering that acts downstream of various regulatory pathways, including one that mediates photoperiodic induction through CONSTANS ( CO ), and is expressed in the vasculature of cotyledons and leaves. A bZIP transcription factor, FD, preferentially expressed in the shoot apex is required for FT to promote flowering. FD and FT are interdependent partners through protein interaction and act at the shoot apex to promote floral transition and to initiate floral development through transcriptional activation of a floral meristem identity gene, APETALA1 ( AP1 ). FT may represent a long-distance signal in flowering.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1115983
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2005
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    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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