NIPA Defines an SCF-Type Mammalian E3 Ligase that Regulates Mitotic Entry

SummaryThe regulated oscillation of protein expression is an essential mechanism of cell cycle control. The SCF class of E3 ubiquitin ligases is involved in this process by targeting cell cycle regulatory proteins for degradation by the proteasome, with the F-box subunit of the SCF specifically recruiting a given substrate to the SCF core. Here we identify NIPA (nuclear interaction partner of ALK) as a human F-box-containing protein that defines an SCF-type E3 ligase (SCFNIPA) controlling mitotic entry. Assembly of this SCF complex is regulated by cell-cycle-dependent phosphorylation of NIPA, which restricts substrate ubiquitination activity to interphase. We show nuclear cyclin B1 to be a substrate of SCFNIPA. Inactivation of NIPA by RNAi results in nuclear accumulation of cyclin B1 in interphase, activation of cyclin B1-Cdk1 kinase activity, and premature mitotic entry. Thus, SCFNIPA-based ubiquitination may regulate S-phase completion and mitotic entry in the mammalian cell cycle

APC/CCdh1-Mediated Degradation of the F-Box Protein NIPA Is Regulated by Its Association with Skp1

NIPA (Nuclear Interaction Partner of Alk kinase) is an F-box like protein that targets nuclear Cyclin B1 for degradation. Integrity and therefore activity of the SCFNIPA E3 ligase is regulated by cell-cycle-dependent phosphorylation of NIPA, restricting substrate ubiquitination to interphase. Here we show that phosphorylated NIPA is degraded in late mitosis in an APC/CCdh1-dependent manner. Binding of the unphosphorylated form of NIPA to Skp1 interferes with binding to the APC/C-adaptor protein Cdh1 and therefore protects unphosphorylated NIPA from degradation in interphase. Our data thus define a novel mode of regulating APC/C-mediated ubiquitination

Cold atoms in space: community workshop summary and proposed road-map

We summarise the discussions at a virtual Community Workshop on Cold Atoms in Space concerning the status of cold atom technologies, the prospective scientific and societal opportunities offered by their deployment in space, and the developments needed before cold atoms could be operated in space. The cold atom technologies discussed include atomic clocks, quantum gravimeters and accelerometers, and atom interferometers. Prospective applications include metrology, geodesy and measurement of terrestrial mass change due to, e.g., climate change, and fundamental science experiments such as tests of the equivalence principle, searches for dark matter, measurements of gravitational waves and tests of quantum mechanics. We review the current status of cold atom technologies and outline the requirements for their space qualification, including the development paths and the corresponding technical milestones, and identifying possible pathfinder missions to pave the way for missions to exploit the full potential of cold atoms in space. Finally, we present a first draft of a possible road-map for achieving these goals, that we propose for discussion by the interested cold atom, Earth Observation, fundamental physics and other prospective scientific user communities, together with the European Space Agency (ESA) and national space and research funding agencies

Cold atoms in space: community workshop summary and proposed road-map

We summarise the discussions at a virtual Community Workshop on Cold Atoms in Space concerning the status of cold atom technologies, the prospective scientific and societal opportunities offered by their deployment in space, and the developments needed before cold atoms could be operated in space. The cold atom technologies discussed include atomic clocks, quantum gravimeters and accelerometers, and atom interferometers. Prospective applications include metrology, geodesy and measurement of terrestrial mass change due to, e.g., climate change, and fundamental science experiments such as tests of the equivalence principle, searches for dark matter, measurements of gravitational waves and tests of quantum mechanics. We review the current status of cold atom technologies and outline the requirements for their space qualification, including the development paths and the corresponding technical milestones, and identifying possible pathfinder missions to pave the way for missions to exploit the full potential of cold atoms in space. Finally, we present a first draft of a possible road-map for achieving these goals, that we propose for discussion by the interested cold atom, Earth Observation, fundamental physics and other prospective scientific user communities, together with the European Space Agency (ESA) and national space and research funding agencies.publishedVersio

Cold atoms in space: community workshop summary and proposed road-map

We summarise the discussions at a virtual Community Workshop on Cold Atoms in Space concerning the status of cold atom technologies, the prospective scientific and societal opportunities offered by their deployment in space, and the developments needed before cold atoms could be operated in space. The cold atom technologies discussed include atomic clocks, quantum gravimeters and accelerometers, and atom interferometers. Prospective applications include metrology, geodesy and measurement of terrestrial mass change due to, e.g., climate change, and fundamental science experiments such as tests of the equivalence principle, searches for dark matter, measurements of gravitational waves and tests of quantum mechanics. We review the current status of cold atom technologies and outline the requirements for their space qualification, including the development paths and the corresponding technical milestones, and identifying possible pathfinder missions to pave the way for missions to exploit the full potential of cold atoms in space. Finally, we present a first draft of a possible road-map for achieving these goals, that we propose for discussion by the interested cold atom, Earth Observation, fundamental physics and other prospective scientific user communities, together with the European Space Agency (ESA) and national space and research funding agencies

Folgen von Misshandlung im Kindes- und Jugendalter

von Klitzing K, Goldbeck L, Brunner R, et al. Folgen von Misshandlung im Kindes- und Jugendalter. Trauma & Gewalt. 2015;9(2):122-133.Kindesmisshandlung und -vernachlässigung stellt ein bedeutsames Risiko für die gesunde körperliche und emotionale Entwicklung eines Kindes bis zum Erwachsenenalter dar. Dennoch überstehen manche Kinder Misshandlungserfahrlungen relativ unbeschadet, wohingegen andere eine große Bandbreite an psychischen oder körperlichen Symptomen offenbaren. Warum welches Kind welche Folgen entwickelt, ist bisher jedoch noch unzureichend erforscht. In diesem Beitrag werden fünf deutsche Forschungsverbünde vorgestellt, die sich in ihrer kürzlich begonnenen Arbeit den zentralen psychosozialen und neurobiologischen Folgen und Einflussfaktoren auf die unterschiedliche Entwicklung von Kindern nach erlebter Misshandlung widmen. Mithilfe dieser Studien wird ein wichtiges Fundament für weitere unverzichtbare Längsschnittuntersuchungen geschaffen, die nun folgen müssen. Erst längsschnittliche Designs werden uns in eine bessere Lage versetzen, ätiopathologische Mechanismen zu identifizieren, die als mögliche Ansatzpunkte für gezieltere und wirksamere Interventionen bei Kindesmisshandlung dienen können

Exploring the Foundations of the Universe with Space Tests of the Equivalence Principle

We present the scientific motivation for future space tests of the equivalence principle, and in particular the universality of free fall, at the $10^{-17}$ level or better. Two possible mission scenarios, one based on quantum technologies, the other on electrostatic accelerometers, that could reach that goal are briefly discussed

Exploring the Foundations of the Physical Universe with Space Tests of the Equivalence Principle

We present the scientific motivation for future space tests of the equivalence principle, and in particular the universality of free fall, at the 10− 17 level or better. Two possible mission scenarios, one based on quantum technologies, the other on electrostatic accelerometers, that could reach that goal are briefly discussed. This publication is a White Paper written in the context of the Voyage 2050 ESA Call for White Papers