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  • 1
    Online Resource
    Online Resource
    Chelyabinsk Airburst, Damage Assessment, Meteorite Recovery, and Characterization
    American Association for the Advancement of Science (AAAS) ; 2013
    In:  Science Vol. 342, No. 6162 ( 2013-11-29), p. 1069-1073
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 342, No. 6162 ( 2013-11-29), p. 1069-1073
    Abstract: The asteroid impact near the Russian city of Chelyabinsk on 15 February 2013 was the largest airburst on Earth since the 1908 Tunguska event, causing a natural disaster in an area with a population exceeding one million. Because it occurred in an era with modern consumer electronics, field sensors, and laboratory techniques, unprecedented measurements were made of the impact event and the meteoroid that caused it. Here, we document the account of what happened, as understood now, using comprehensive data obtained from astronomy, planetary science, geophysics, meteorology, meteoritics, and cosmochemistry and from social science surveys. A good understanding of the Chelyabinsk incident provides an opportunity to calibrate the event, with implications for the study of near-Earth objects and developing hazard mitigation strategies for planetary protection.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1242642
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2013
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  • 2
    Online Resource
    Online Resource
    The pINDUCER lentiviral toolkit for inducible RNA interference in vitro and in vivo
    Proceedings of the National Academy of Sciences ; 2011
    In:  Proceedings of the National Academy of Sciences Vol. 108, No. 9 ( 2011-03), p. 3665-3670
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 108, No. 9 ( 2011-03), p. 3665-3670
    Abstract: The discovery of RNAi has revolutionized loss-of-function genetic studies in mammalian systems. However, significant challenges still remain to fully exploit RNAi for mammalian genetics. For instance, genetic screens and in vivo studies could be broadly improved by methods that allow inducible and uniform gene expression control. To achieve this, we built the lentiviral pINDUCER series of expression vehicles for inducible RNAi in vivo. Using a multicistronic design, pINDUCER vehicles enable tracking of viral transduction and shRNA or cDNA induction in a broad spectrum of mammalian cell types in vivo. They achieve this uniform temporal, dose-dependent, and reversible control of gene expression across heterogenous cell populations via fluorescence-based quantification of reverse tet-transactivator expression. This feature allows isolation of cell populations that exhibit a potent, inducible target knockdown in vitro and in vivo that can be used in human xenotransplantation models to examine cancer drug targets.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1019736108
    RVK:
    TA 1000
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2011
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  • 3
    Online Resource
    Online Resource
    Serum factors in older individuals change cellular clock properties
    Proceedings of the National Academy of Sciences ; 2011
    In:  Proceedings of the National Academy of Sciences Vol. 108, No. 17 ( 2011-04-26), p. 7218-7223
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 108, No. 17 ( 2011-04-26), p. 7218-7223
    Abstract: Human aging is accompanied by dramatic changes in daily sleep–wake behavior: Activity shifts to an earlier phase, and the consolidation of sleep and wake is disturbed. Although this daily circadian rhythm is brain-controlled, its mechanism is encoded by cell-autonomous circadian clocks functioning in nearly every cell of the body. In fact, human clock properties measured in peripheral cells such as fibroblasts closely mimic those measured physiologically and behaviorally in the same subjects. To understand better the molecular mechanisms by which human aging affects circadian clocks, we characterized the clock properties of fibroblasts cultivated from dermal biopsies of young and older subjects. Fibroblast period length, amplitude, and phase were identical in the two groups even though behavior was not, thereby suggesting that basic clock properties of peripheral cells do not change during aging. Interestingly, measurement of the same cells in the presence of human serum from older donors shortened period length and advanced the phase of cellular circadian rhythms compared with treatment with serum from young subjects, indicating that a circulating factor might alter human chronotype. Further experiments demonstrated that this effect is caused by a thermolabile factor present in serum of older individuals. Thus, even though the molecular machinery of peripheral circadian clocks does not change with age, some age-related circadian dysfunction observed in vivo might be of hormonal origin and therefore might be pharmacologically remediable.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1008882108
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2011
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
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  • 4
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    Online Resource
    Structural requirements for enzymatic activities of foamy virus protease‐reverse transcriptase
    Wiley ; 2014
    In:  Proteins: Structure, Function, and Bioinformatics Vol. 82, No. 3 ( 2014-03), p. 375-385
    Details
    In: Proteins: Structure, Function, and Bioinformatics, Wiley, Vol. 82, No. 3 ( 2014-03), p. 375-385
    Abstract: Reverse transcriptases (RTs) are pivotal in the life cycle of retroviruses and convert the genomic viral RNA into double‐stranded DNA. The RT polymerase domain is subdivided into fingers, palm, thumb, and the connection subdomain, which links the polymerase to the C‐terminal RNase H domain. In contrast to orthoretroviruses, mature RT of foamy viruses harbors the protease (PR) domain at its N‐terminus (PR‐RT). Therefore and due to low homology to other RTs, it is difficult to define the boundaries and functions of the (sub)domains. We introduced N‐ and C‐terminal deletions into simian foamy virus PR‐RT to investigate the impact of the truncations on the catalytic activities. Both, the RNase H domain and the connection subdomain contribute substantially to polymerase integrity and stability as well as to polymerase activity and substrate binding. The 42 amino acids long region C‐terminal of the PR is important for polymerase stability and activity. PR activation via binding of PR‐RT to viral RNA requires the presence of the full length PR‐RT including the RNase H domain. In vitro , the cleavage efficiencies of FV PR for the Gag and Pol cleavage site are comparable, even though in virus particles only the Pol site is cleaved to completion suggesting that additional factors control PR activity and that virus maturation needs to be strictly regulated. Proteins 2014; 82:375–385. © 2013 Wiley Periodicals, Inc.
    Type of Medium: Online Resource
    ISSN: 0887-3585 , 1097-0134
    URL: Issue
    URL: Article
    DOI: 10.1002/prot.v82.3
    DOI: 10.1002/prot.24394
    RVK:
    WA 15000
    Language: English
    Publisher: Wiley
    Publication Date: 2014
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  • 5
    Online Resource
    Online Resource
    Carbon Isotope Constraints on the Deglacial CO 2 Rise from Ice Cores
    American Association for the Advancement of Science (AAAS) ; 2012
    In:  Science Vol. 336, No. 6082 ( 2012-05-11), p. 711-714
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 336, No. 6082 ( 2012-05-11), p. 711-714
    Abstract: The stable carbon isotope ratio of atmospheric CO 2 (δ 13 C atm ) is a key parameter in deciphering past carbon cycle changes. Here we present δ 13 C atm data for the past 24,000 years derived from three independent records from two Antarctic ice cores. We conclude that a pronounced 0.3 per mil decrease in δ 13 C atm during the early deglaciation can be best explained by upwelling of old, carbon-enriched waters in the Southern Ocean. Later in the deglaciation, regrowth of the terrestrial biosphere, changes in sea surface temperature, and ocean circulation governed the δ 13 C atm evolution. During the Last Glacial Maximum, δ 13 C atm and atmospheric CO 2 concentration were essentially constant, which suggests that the carbon cycle was in dynamic equilibrium and that the net transfer of carbon to the deep ocean had occurred before then.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1217161
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2012
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    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 6
    Online Resource
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    Dickkopf-3, an immune modulator in peripheral CD8 T-cell tolerance
    Proceedings of the National Academy of Sciences ; 2012
    In:  Proceedings of the National Academy of Sciences Vol. 109, No. 5 ( 2012-01-31), p. 1631-1636
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 109, No. 5 ( 2012-01-31), p. 1631-1636
    Abstract: In healthy individuals, T cells react against incoming pathogens, but remain tolerant to self-antigens, thereby preventing autoimmune reactions. CD4 regulatory T cells are major contributors in induction and maintenance of peripheral tolerance, but a regulatory role has been also reported for several subsets of CD8 T cells. To determine the molecular basis of peripheral CD8 T-cell tolerance, we exploited a double transgenic mouse model in which CD8 T cells are neonatally tolerized following interaction with a parenchymal self-antigen. These tolerant CD8 T cells have regulatory capacity and can suppress T cells in an antigen-specific manner during adulthood. Dickkopf-3 (DKK3) was found to be expressed in the tolerant CD8 T cells and to be essential for the observed CD8 T-cell tolerance. In vitro, genetic deletion of DKK3 or blocking with antibodies restored CD8 T-cell proliferation and IL-2 production in response to the tolerizing self-antigen. Moreover, exogenous DKK3 reduced CD8 T-cell reactivity. In vivo, abrogation of DKK3 function reversed tolerance, leading to eradication of tumors expressing the target antigen and to rejection of autologous skin grafts. Thus, our findings define DKK3 as a immune modulator with a crucial role for CD8 T-cell tolerance.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1115980109
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2012
    detail.hit.zdb_id: 209104-5
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    SSG: 11
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  • 7
    Online Resource
    Online Resource
    PML promotes MHC class II gene expression by stabilizing the class II transactivator
    Rockefeller University Press ; 2012
    In:  Journal of Cell Biology Vol. 199, No. 1 ( 2012-10-01), p. 49-63
    Details
    In: Journal of Cell Biology, Rockefeller University Press, Vol. 199, No. 1 ( 2012-10-01), p. 49-63
    Abstract: Promyelocytic leukemia (PML) nuclear bodies selectively associate with transcriptionally active genomic regions, including the gene-rich major histocompatibility (MHC) locus. In this paper, we have explored potential links between PML and interferon (IFN)-γ–induced MHC class II expression. IFN-γ induced a substantial increase in the spatial proximity between PML bodies and the MHC class II gene cluster in different human cell types. Knockdown experiments show that PML is required for efficient IFN-γ–induced MHC II gene transcription through regulation of the class II transactivator (CIITA). PML mediates this function through protection of CIITA from proteasomal degradation. We also show that PML isoform II specifically forms a stable complex with CIITA at PML bodies. These observations establish PML as a coregulator of IFN-γ–induced MHC class II expression.
    Type of Medium: Online Resource
    ISSN: 1540-8140 , 0021-9525
    URL: Article
    DOI: 10.1083/jcb.201112015
    RVK:
    WA 15000
    Language: English
    Publisher: Rockefeller University Press
    Publication Date: 2012
    detail.hit.zdb_id: 1421310-2
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  • 8
    Online Resource
    Online Resource
    Testing mechanisms and context dependence of costs of plastic shade avoidance responses in Impatiens capensis (Balsaminaceae)
    Wiley ; 2011
    In:  American Journal of Botany Vol. 98, No. 10 ( 2011-10), p. 1602-1612
    Details
    In: American Journal of Botany, Wiley, Vol. 98, No. 10 ( 2011-10), p. 1602-1612
    Abstract: • Premise of the study: Many plant species elongate their shoots in response to neighbor proximity and neighbor height. Although these plastic responses may be beneficial in terms of enhancing light interception, they also may have costs in terms of increased risk of mechanical failure (i.e., lodging or breaking) because of thinner stems. This trade‐off between light acquisition and stability may shape the evolution of plastic elongation responses to foliage shade. • Methods: In a field experiment manipulating elongation phenotypes and densities, we tested two hypotheses. We predicted that the risks of mechanical failure depend on plastic elongation and/or on characteristics of the immediate neighborhood, such as density and neighbor height. Further, we predicted that plants that fail mechanically would have reduced fitness. • Key results: Mechanical failure was earlier and more frequent at high density and showed a complex interaction with neighborhood characteristics such as relative height of the neighbors and the expression of early plasticity. Plants that broke earlier had shorter lifespan and lower reproductive output. • Conclusions: Our results show that depending on the height and density of the group, plastic elongation responses can remain advantageous despite costs of increased risk of mechanical failure of the taller stems, as mechanical failure was not associated with strong costs in terms of reduced lifespan or seed production. The overall benefits of elongation outweigh the costs resulting in selection for elongation at the population level.
    Type of Medium: Online Resource
    ISSN: 0002-9122 , 1537-2197
    URL: Article
    DOI: 10.3732/ajb.1000439
    RVK:
    WA 15000
    Language: English
    Publisher: Wiley
    Publication Date: 2011
    detail.hit.zdb_id: 2053581-8
    SSG: 12
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