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  • 1
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    Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-11-05
    Description: Small molecules that perturb specific protein functions are valuable tools for dissecting complex processes in mammalian cells. A combination of two phenotype-based screens, one based on a specific posttranslational modification, the other visualizing microtubules and chromatin, was used to identify compounds that affect mitosis. One compound, here named monastrol, arrested mammalian cells in mitosis with monopolar spindles. In vitro, monastrol specifically inhibited the motility of the mitotic kinesin Eg5, a motor protein required for spindle bipolarity. All previously known small molecules that specifically affect the mitotic machinery target tubulin. Monastrol will therefore be a particularly useful tool for studying mitotic mechanisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mayer, T U -- Kapoor, T M -- Haggarty, S J -- King, R W -- Schreiber, S L -- Mitchison, T J -- CA78048/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1999 Oct 29;286(5441):971-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, and Institute of Chemistry and Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Thomas_Mayer@hms.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10542155" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/drug effects ; Animals ; Cattle ; Cell Line ; Cytoskeleton/drug effects ; Golgi Apparatus/drug effects ; Kinesin/*drug effects ; Microtubules/drug effects ; Mitosis/*drug effects ; Molecular Motor Proteins/drug effects ; Phenotype ; Phosphoproteins/metabolism ; Protein Processing, Post-Translational ; Pyrimidines/*pharmacology ; RNA-Binding Proteins/metabolism ; Spindle Apparatus/*drug effects ; Thiones/*pharmacology ; Tumor Cells, Cultured ; Xenopus ; *Xenopus Proteins
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    The APC/C inhibitor XErp1/Emi2 is essential for Xenopus early embryonic divisions (2012)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2012-09-29
    Description: Mitotic divisions result from the oscillating activity of cyclin-dependent kinase 1 (Cdk1). Cdk1 activity is terminated by the anaphase-promoting complex/cyclosome (APC/C), a ubiquitin ligase that targets cyclin B for destruction. In somatic divisions, the early mitotic inhibitor 1 (Emi1) and the spindle assembly checkpoint (SAC) regulate cell cycle progression by inhibiting the APC/C. Early embryonic divisions lack these APC/C-inhibitory components, which raises the question of how those cycles are controlled. We found that the APC/C-inhibitory activity of XErp1 (also known as Emi2) was essential for early divisions in Xenopus embryos. Loss of XErp1 resulted in untimely destruction of APC/C substrates and embryonic lethality. XErp1's APC/C-inhibitory function was negatively regulated by Cdk1 and positively by protein phosphatase 2A (PP2A). Thus, Cdk1 and PP2A operate at the core of early mitotic cell cycles by antagonistically controlling XErp1 activity, which results in oscillating APC/C activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tischer, Thomas -- Hormanseder, Eva -- Mayer, Thomas U -- New York, N.Y. -- Science. 2012 Oct 26;338(6106):520-4. doi: 10.1126/science.1228394. Epub 2012 Sep 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology and Konstanz Research School Chemical Biology, University of Konstanz, Universitatsstr. 10, 78457 Konstanz, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23019610" target="_blank"〉PubMed〈/a〉
    Keywords: Anaphase-Promoting Complex-Cyclosome ; Animals ; CDC2 Protein Kinase/metabolism ; Embryo, Nonmammalian/*cytology/enzymology ; F-Box Proteins/antagonists & inhibitors/genetics/*metabolism ; Mitosis/genetics/*physiology ; Phosphorylation ; Protein Phosphatase 2/metabolism ; Ubiquitin-Protein Ligase Complexes/antagonists & inhibitors/*metabolism ; Xenopus Proteins/antagonists & inhibitors/genetics/*metabolism ; Xenopus laevis/*embryology/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Full-scale 3D modelling of a nuclear waste repository in the Callovo-Oxfordian clay. Part 2: thermo-hydraulic two-phase transport of water, hydrogen, 14C and 129I (2014)
    Geological Society (of London)
    Details
    Publication Date: 2014-05-09
    Description: The development of deep geological repositories for nuclear waste requires a sound system understanding, to which performance analyses by means of numerical flow and transport simulations form an important contribution. In this context, we present modelling studies of the thermo-hydraulic two-phase transport of water and hydrogen in the planned French repository in part 1. This paper, part 2, uses the same modelling concept extended to include radionuclide transport. The numerical TOUGH2-MP-model encompasses the host rock from cap to bed rock including the repository in full 3D. We performed a series of single-phase and two-phase transport simulations of volatile radionuclides ( 14 C) and highly soluble ones ( 129 I). The sensitivity analyses concerned different conditions and scenarios, for example, early canister failure, varied hydrogen generation regimes and transport parameters. The results allow determination of the dominant radionuclide transport paths and transfer processes. They demonstrate that hydrogen generation inside the repository has a large impact on the transfer of 14 C, favouring its advective transfer in the gas phase along the backfilled tunnels, whereas it has only minor influence on the transfer of 129 I which is mainly transported by diffusion in the formation water of the host rock. The study demonstrates the feasibility of full-scale radionuclide transport simulations.
    Print ISSN: 0305-8719
    Electronic ISSN: 2041-4927
    Topics: Geosciences
    Published by Geological Society (of London)
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  • 4
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    Can argillaceous formations isolate nuclear waste? Insights from isotopic, noble gas, and geochemical profiles (2015)
    Wiley
    In: Geofluids
    Details
    Publication Date: 2015-02-25
    Description: There is considerable interest in the use of thick argillaceous geologic formations to contain nuclear waste. Here, we show that diffusion can be the controlling transport process in these formations and diffusional time scales for δ 18 O and δ 2 H in water, dissolved He, and Cl transport in shale-dominated aquitards are typically over 10 6 years, well exceeding the regulatory requirements for isolation in most countries. Our scientific understanding of diffusive solute transport processes through argillaceous formations would benefit from the application of additional isotopic tracers (e.g., using new 4 He sampling technology), multidimensional diffusive-dispersive modeling of groundwater flow and diffusive-dispersive solute transport over long geologic time scales, and an improved understanding of spatial heterogeneity as well as time-dependent changes in the subsurface conditions and properties of argillaceous formations in response to events such as glaciation. Based on our current isotopic and geochemical understanding of transport, we argue that argillaceous formations can provide favorable long-term conditions for isolating nuclear wastes.
    Print ISSN: 1468-8115
    Electronic ISSN: 1468-8123
    Topics: Geosciences
    Published by Wiley
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  • 5
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    Role of the proteasome in membrane extraction of a short-lived ER-transmembrane protein (1998)
    EMBO Press
    Details
    Publication Date: 1998-06-15
    Print ISSN: 0261-4189
    Electronic ISSN: 1460-2075
    Topics: Biology , Medicine
    Published by EMBO Press on behalf of European Molecular Biology Organization.
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