46 research outputs found

    Phosphorylation of MCPH1 isoforms during mitosis followed by isoform‐specific degradation by APC/C‐CDH1

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    Microcephalin‐1 (MCPH1) exists as 2 isoforms that regulate cyclin‐dependent kinase‐1 activation and chromosome condensation during mitosis, with MCPH1 mutations causing primary microcephaly. MCPH1 is also a tumor suppressor protein, with roles in DNA damage repair/checkpoints. Despite these important roles, there is little information on the cellular regulation of MCPH1. We show that both MCPH1 isoforms are phosphorylated in a cyclin‐dependent kinase‐1–dependent manner in mitosis and identify several novel phosphorylation sites. Upon mitotic exit, MCPH1 isoforms were degraded by the anaphase‐promoting complex/cyclosome–CDH1 E3 ligase complex. Anaphase‐promoting complex/cyclosome–CDH1 target proteins generally have D‐Box or KEN‐Box degron sequences. We found that MCPH1 isoforms are degraded independently, with the long isoform degradation being D‐Box dependent, whereas the short isoform was KEN‐Box dependent. Our research identifies several novel mechanisms regulating MCPH1 and also highlights important issues with several commercial MCPH1 antibodies, with potential relevance to previously published data.—Meyer, S. K., Dunn, M., Vidler, D. S., Porter, A., Blain, P. G., Jowsey, P. A. Phosphorylation of MCPH1 isoforms during mitosis followed by isoform‐specific degradation by APC/C‐CDH1. FASEB J. 33, 2796–2808 (2019). www.fasebj.or

    "Outside, it is snowing": Experience and finitude in the nonrepresentational landscapes of Alain Robbe-Grillet

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    Copyright © 2008 PionRomanillos J L, 2008. The definitive, peer-reviewed and edited version of this article is published in Environment and Planning D: Society and Space 26(5) 795 – 822 DOI: 10.1068/d6207This paper presents and explicates the anonymous and impersonal spatialities tentatively mapped in the novels of Alain Robbe-Grillet. Emerging from the kinds of landscapes and visualities articulated, these spatialities are at odds with the kind of anthropocentrism characteristic of phenomenological narratives of spatial experience that would start from an apparently stable human-subject position. It is argued that his body of literature dismantles the anthropocentric narratives and biographies that would produce in both the space of the world and the ‘phenomenological subject’ an unwarranted depth and naturalism. Importantly, and reflecting the theoretical turn towards the being of language, Robbe-Grillet questions the legitimacy of linguistic subjects to capture the spaces of the visible. As such, it is argued that his literature reflects an experience of the critiques of phenomenology. Importantly, this ‘critique’ goes hand in hand with the kinds of spatialities and landscapes that are rendered in the novels—the indefinite perspectives they open up, the paradoxical visualities they sustain or deny, and the disorientation they inject into the heart of spatial experience. These literary effects produce a nonanthropocentric and nonpersonal spatiality which, although contributing to an erasure of the ‘subject’, at the same time expose and open up a sociospatiality based on singularities, intensities, and finitude

    Le nouveau Bulletin mensuel du département des imprimés de la Bibliothèque nationale

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    Vidier Alexandre. Le nouveau Bulletin mensuel du département des imprimés de la Bibliothèque nationale. In: Bibliothèque de l'école des chartes. 1910, tome 71. pp. 471-476

    Collection de documents inédits sur l'histoire économique de la Révolution française, publiés par le ministère de l'Instruction publique. Paris, E. Leroux, 1906-1909.

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    Vidier Alexandre. Collection de documents inédits sur l'histoire économique de la Révolution française, publiés par le ministère de l'Instruction publique. Paris, E. Leroux, 1906-1909. In: Bibliothèque de l'école des chartes. 1910, tome 71. pp. 139-152

    Collection de documents inédits sur l'histoire économique de la Révolution française, publiés par le ministère de l'Instruction publique. Paris, E. Leroux, 1906-1909.

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    Vidier Alexandre. Collection de documents inédits sur l'histoire économique de la Révolution française, publiés par le ministère de l'Instruction publique. Paris, E. Leroux, 1906-1909. In: Bibliothèque de l'école des chartes. 1910, tome 71. pp. 139-152

    Ermitages orléanais établis au XIIe siècle

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    Vidier Alexandre. Ermitages orléanais établis au XIIe siècle. In: Comptes rendus des séances de l'Académie des Inscriptions et Belles-Lettres, 50ᵉ année, N. 2, 1906. pp. 156-157

    Évolution paléogéographique en Europe du Nord-Ouest au Cénozoïque supérieur

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    Les formations littorales et fluviatiles sableuses du Néogène et du Quaternaire ancien sont réétudiées dans les régions encadrant le Sud de la mer du Nord et la Manche, en prenant en compte leur contexte géodynamique. Deux domaines sont définis au sein d\u27une zone limitée au Nord par le front varisque et au Sud par la branche nord du cisaillement sud-armoricain. Les régions situées respectivement au Nord et au Sud de ces limites sont subsidentes depuis le Paléogène. Le secteur interne est soumis à des épisodes de soulèvement temporaires de grande longueur d\u27onde, légèrement diachroniques du Sud au Nord, qui vont contrôler la géométrie des littoraux et l\u27ouverture du Pas-de-Calais, vers la fin du Zancléen. Le maximum d\u27espace disponible pour la sédimentation sableuse est enregistré au Tortonien supérieur et au Piacenzien final, en correspondance avec les épisodes de relâchement des contraintes tectoniques. Les relations fauniques entre la Manche et la mer du Nord se trouvent ainsi expliquées.A re-analysis of the stratigraphy based on recent dating of palaeo-shores of Neogene to early Pleistocene ages is proposed within a geodynamic context in the Channel and Dover Strait areas. This sector of Europe is controlled by two main geological boundaries: to the North, the Variscan Overthrust and, to the South, the northern branch of the southern Armorican Shearing Zone. These two boundaries border a domain that seems to behave rather homogeneously on a large scale controlled by plate tectonics. Since the Paleogene shorelines have been subsiding North and South of this "Channel" region. Episodic uplift largely controlled the opened or closed status of the Dover Strait during late Zanclean, by reactivating Variscan structures. Re-analysis of post-Oligocene sandy formations shows that these regions have suffered long wavelength deformations during the Neogene. These deformations, slightly diachronous from South to North, affect the limits of the Miocene and Pliocene transgressions. The periods of maximum accommodation space for sedimentation are the late Tortonian and the late Piacenzian, both coinciding with tectonic relaxation events. They explain the micropalaeontological evolution of the micropalaeontological fauna of the Channel and southern North Sea during the considered time span.</p

    D-penicillamine Chemical Quality

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    Un XI e

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