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  • Proceedings of the National Academy of Sciences  (5)
  • Biology  (5)
  • 1
    Online Resource
    Online Resource
    The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies
    Proceedings of the National Academy of Sciences ; 2022
    In:  Proceedings of the National Academy of Sciences Vol. 119, No. 21 ( 2022-05-24)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 119, No. 21 ( 2022-05-24)
    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged 〈 70 y and in 〉 4% of those 〉 70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals 〈 70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals 〈 40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2200413119
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2022
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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  • 2
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    Online Resource
    Observation of a multiferroic critical end point
    Proceedings of the National Academy of Sciences ; 2009
    In:  Proceedings of the National Academy of Sciences Vol. 106, No. 37 ( 2009-09-15), p. 15573-15576
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 106, No. 37 ( 2009-09-15), p. 15573-15576
    Abstract: The study of abrupt increases in magnetization with magnetic field known as metamagnetic transitions has opened a rich vein of new physics in itinerant electron systems, including the discovery of quantum critical end points with a marked propensity to develop new kinds of order. However, the electric analogue of the metamagnetic critical end point, a “metaelectric” critical end point, has been rarely studied. Multiferroic materials wherein magnetism and ferroelectricity are cross-coupled are ideal candidates for the exploration of this novel possibility using magnetic-field ( H ) as a tuning parameter. Herein, we report the discovery of a magnetic-field-induced metaelectric transition in multiferroic BiMn 2 O 5 , in which the electric polarization ( P ) switches polarity along with a concomitant Mn spin–flop transition at a critical magnetic field H c . The simultaneous metaelectric and spin–flop transitions become sharper upon cooling but remain a continuous cross-over even down to 0.5 K. Near the P = 0 line realized at μ 0 H c ≈ 18 T below 20 K, the dielectric constant (ɛ) increases significantly over wide field and temperature ( T ) ranges. Furthermore, a characteristic power-law behavior is found in the P ( H ) and ɛ( H ) curves at T = 0.66 K. These findings indicate that a magnetic-field-induced metaelectric critical end point is realized in BiMn 2 O 5 near zero temperature.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0907589106
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2009
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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  • 3
    Online Resource
    Online Resource
    Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation
    Proceedings of the National Academy of Sciences ; 2008
    In:  Proceedings of the National Academy of Sciences Vol. 105, No. 45 ( 2008-11-11), p. 17414-17419
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 105, No. 45 ( 2008-11-11), p. 17414-17419
    Abstract: The mammalian translational initiation machinery is a tightly controlled system that is composed of eukaryotic initiation factors, and which controls the recruitment of ribosomes to mediate cap-dependent translation. Accordingly, the mTORC1 complex functionally controls this cap-dependent translation machinery through the phosphorylation of its downstream substrates 4E-BPs and S6Ks. It is generally accepted that rapamycin, a specific inhibitor of mTORC1, is a potent translational repressor. Here we report the unexpected discovery that rapamycin's ability to regulate cap-dependent translation varies significantly among cell types. We show that this effect is mechanistically caused by rapamycin's differential effect on 4E-BP1 versus S6Ks. While rapamycin potently inhibits S6K activity throughout the duration of treatment, 4E-BP1 recovers in phosphorylation within 6 h despite initial inhibition (1–3 h). This reemerged 4E-BP1 phosphorylation is rapamycin-resistant but still requires mTOR, Raptor, and mTORC1's activity. Therefore, these results explain how cap-dependent translation can be maintained in the presence of rapamycin. In addition, we have also defined the condition by which rapamycin can control cap-dependent translation in various cell types. Finally, we show that mTOR catalytic inhibitors are effective inhibitors of the rapamycin-resistant phenotype.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0809136105
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2008
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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  • 4
    Online Resource
    Online Resource
    A nontransferring dry adhesive with hierarchical polymer nanohairs
    Proceedings of the National Academy of Sciences ; 2009
    In:  Proceedings of the National Academy of Sciences Vol. 106, No. 14 ( 2009-04-07), p. 5639-5644
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 106, No. 14 ( 2009-04-07), p. 5639-5644
    Abstract: We present a simple yet robust method for fabricating angled, hierarchically patterned high-aspect-ratio polymer nanohairs to generate directionally sensitive dry adhesives. The slanted polymeric nanostructures were molded from an etched polySi substrate containing slanted nanoholes. An angled etching technique was developed to fabricate slanted nanoholes with flat tips by inserting an etch-stop layer of silicon dioxide. This unique etching method was equipped with a Faraday cage system to control the ion-incident angles in the conventional plasma etching system. The polymeric nanohairs were fabricated with tailored leaning angles, sizes, tip shapes, and hierarchical structures. As a result of controlled leaning angle and bulged flat top of the nanohairs, the replicated, slanted nanohairs showed excellent directional adhesion, exhibiting strong shear attachment (≈26 N/cm 2 in maximum) in the angled direction and easy detachment (≈2.2 N/cm 2 ) in the opposite direction, with a hysteresis value of ≈10. In addition to single scale nanohairs, monolithic, micro-nanoscale combined hierarchical hairs were also fabricated by using a 2-step UV-assisted molding technique. These hierarchical nanoscale patterns maintained their adhesive force even on a rough surface (roughness 〈 20 μm) because of an increase in the contact area by the enhanced height of hierarchy, whereas simple nanohairs lost their adhesion strength. To demonstrate the potential applications of the adhesive patch, the dry adhesive was used to transport a large-area glass (47.5 × 37.5 cm 2 , second-generation TFT-LCD glass), which could replace the current electrostatic transport/holding system with further optimization.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0900323106
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2009
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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    Online Resource
  • 5
    Online Resource
    Online Resource
    Notch1 confers a resistance to glucocorticoid-induced apoptosis on developing thymocytes by down-regulating SRG3 expression
    Proceedings of the National Academy of Sciences ; 2001
    In:  Proceedings of the National Academy of Sciences Vol. 98, No. 18 ( 2001-08-28), p. 10267-10272
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 18 ( 2001-08-28), p. 10267-10272
    Abstract: We previously have reported that SRG3 is required for glucocorticoid (GC)-induced apoptosis in the S49.1 thymoma cell line. Activation of Notch1 was shown to induce GC resistance in thymocytes. However, the specific downstream target of Notch1 that confers GC resistance on thymocytes is currently unknown. We found that the expression level of SRG3 was critical in determining GC sensitivity in developing thymocytes. The expression of SRG3 also was down-regulated by the activated form of Notch1 (NotchIC). The promoter activity of the SRG3 gene also was down-regulated by NotchIC. Expression of transgenic SRG3 resulted in the restoration of GC sensitivity in thymocytes expressing transgenic Notch1. These results suggest that SRG3 is the downstream target of Notch1 in regulating GC sensitivity of thymocytes.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.181076198
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2001
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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    Online Resource
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