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mRNA-Abbau ist ein essentieller Prozess der Genexpression, der den Zellen ermöglicht, die Qualität und die Quantität der mRNA zu kontrollieren. Besonders unter Stressbedingungen könnte der mRNA-Abbau eine bedeutende Rolle neben der Speicherung von mRNAs sowie der Regulation der Proteinhomöostase zum Schutz vor schädigenden Einflüssen spielen. Studien mit Hefen und Säugerzellen zeigten, dass dem 5'-3'mRNA-Abbau ein wichtige Rolle sowohl unter normalen Bedingungen als auch unter Stressbedingungen zukommt und dieser in zytoplasmatischen Processing bodies (P-bodies) stattfindet. Im Rahmen dieser Arbeit sollten Erkenntnisse über den 5'-3'mRNA-Abbau erhalten werden. Im Vordergrund stand die Frage nach der Existenz von P-bodies in Arabidopsis thaliana und die Identifikation und Charakterisierung deren Komponenten. Weiterhin sollten Erkenntnisse über die Rolle der P-bodies unter Stressbedingungen gewonnen werden. Dabei sollten besonders Informationen über die Beziehungen zwischen den P-bodies und RNA Stressgranula (mRNA Speicherkompartimente) und Hitzestressgranula (Regulation der Proteinhomöostase) erhalten werden. Das komplette sequenzierte Genom von Arabidopsis thaliana eignete sich zur Identifikation von mRNA-Abbauproteine kodierender Gene. Unter Verwendung von Aminosäuresequenzen bereits bekannter mRNA-Abbauproteine aus Hefe und Säugerzellen konnten Homologe für die Decappingproteine Dcp1 und Dcp2 sowie für die Proteine LSm1,2,5,8 als Untereinheiten des LSm1-7 Komplexes, welcher an der Regulation der Decappingreaktion beteiligt ist, identifiziert werden. Über Hefe-Zwei-Hybrid Analysen konnten anschließend Protein-Protein-Interaktionen zwischen den untersuchten Proteinen identifiziert werden. Weiterhin konnte unter Einsatz der BIFC-Analyse gezeigt werden, dass die Interaktionen zwischen den untersuchten Proteinen hauptsächlich in zytoplasmatischen Strukturen stattfanden. Aufbauend auf diesen Befunden wurde ein Antikörper gegen Dcp1 als Marker für die zytoplasmatischen Strukturen erstellt. Dieser ermöglichte erstmals die Detektion der endogenen Strukturen in Arabidopsis thaliana. Die weitere Charakterisierung über Immunofluoreszenzanalysen zeigten, dass diese P-bodies sind. Wie die P-bodies anderer Organismen sind sie hochdynamisch und benötigen untranslatierte mRNA für die Assemblierung. Die Größe und Anzahl der P-bodies hängt dabei vom Verhältniss des Zuflusses von mRNA und der mRNA-Abbaurate ab. Weiterhin konnte beobachtet werden, das die P-bodies besonders groß unter Stressbedingungen sind und deuten eine wichtige Funktion des mRNA-Abbaus unter Stress an. Dies führte zu der Frage nach der Beziehung der P-bodies zu RNA Stressgranula, die der Speicherung von mRNA unter Stressbedingungen dienen, sowie zu Hitzestressgranula, die an der Aufrechterhaltung der Proteinhomöostase beteiligt sind. Durch Kolokalisationsanalysen mit Markern der RNA Stressgranula, der Hitzestressgranula und der P-bodies konnte erstmals gezeigt werden, dass es sich um voneinander unabhängige Mikrokompartimente handelt, und dass unter Stressbedingungen die zellulären Prozesse mRNA-Abbau, mRNA-Speicherung und Aufrechterhaltung der Proteinhomöostase auf einzelne Mikrkompartimente beschränkt sind. Allerdings konnte zwischen P-bodies und RNA Stressgranula häufig eine räumliche Nähe beobachtet werden. Dies deutet auf einen Austausch von Komponenten zwischen diesen Strukturen hin. Zusammen zeigen die erhaltenen Ergebnisse, dass die identifizierten Proteine Komponenten des 5'-3'mRNA-Abbaus darstellen, und dass der 5'-3'mRNA-Abbau in Pflanzen auch in P-bodies stattfindet. Die Identifizierung und Charakterisierung der pflanzlichen P-bodies bildet eine Grundlage für zukünftige Untersuchungen. Vor allem die massive Bildung von P-bodies unter Stressbedingungen und die Interaktion der P-bodies mit RNA Stressgranula zeigen neue Aspekte der pflanzlichen Hitzestressantwort auf.
Weber, H. ; Ernst, Christoph ; Bleicher, Marcus ; Bravina, Larissa ; Stöcker, Horst ; Greiner, Walter ; Spieles, Christian ; Bass, Steffen A.
We estimate the energy density epsilon pile-up at mid-rapidity in central Pb+Pb collisions from 2 200 GeV/nucleon. epsilon is decomposed into hadronic and partonic contributions. A detailed analysis of the collision dynamics in the framework of a microscopic transport model shows the importance of partonic degrees of freedom and rescattering of leading (di)quarks in the early phase of the reaction for Elab 30 GeV/nucleon. In Pb+Pb collisions at 160 GeV/nucleon the energy density reaches up to 4 GeV/fm3, 95% of which are contained in partonic degrees of freedom.
Weber, Heike ; Scholz, Claus Jürgen ; Domschke, Katharina ; Baumann, Christian ; Klauke, Benedikt ; Jacob, Christian P. ; Maier, Wolfgang ; Fritze, Jürgen ; Bandelow, Borwin ; Zwanzger, Peter M. ; Lang, Thomas ; Fehm, Lydia ; Ströhle, Andreas ; Hamm, Alfons ; Gerlach, Alexander ; Alpers, Georg W. ; Kircher, Tilo ; Wittchen, Hans-Ulrich ; Arolt, Volker ; Pauli, Paul ; Deckert, Jürgen ; Reif, Andreas
Background: Panic disorder is common (5% prevalence) and females are twice as likely to be affected as males. The heritable component of panic disorder is estimated at 48%. Glutamic acid dehydrogenase GAD1, the key enzyme for the synthesis of the inhibitory and anxiolytic neurotransmitter GABA, is supposed to influence various mental disorders, including mood and anxiety disorders. In a recent association study in depression, which is highly comorbid with panic disorder, GAD1 risk allele associations were restricted to females.
Methodology/Principal Findings: Nineteen single nucleotide polymorphisms (SNPs) tagging the common variation in GAD1 were genotyped in two independent gender and age matched case-control samples (discovery sample n = 478; replication sample n = 584). Thirteen SNPs passed quality control and were examined for gender-specific enrichment of risk alleles associated with panic disorder by using logistic regression including a genotype×gender interaction term. The latter was found to be nominally significant for four SNPs (rs1978340, rs3762555, rs3749034, rs2241165) in the discovery sample; of note, the respective minor/risk alleles were associated with panic disorder only in females. These findings were not confirmed in the replication sample; however, the genotype×gender interaction of rs3749034 remained significant in the combined sample. Furthermore, this polymorphism showed a nominally significant association with the Agoraphobic Cognitions Questionnaire sum score.
Conclusions/Significance: The present study represents the first systematic evaluation of gender-specific enrichment of risk alleles of the common SNP variation in the panic disorder candidate gene GAD1. Our tentative results provide a possible explanation for the higher susceptibility of females to panic disorder.
Der eine gibt nur wenige Cents, der nächste lässt beim Trinkgeld etwas mehr springen. Am Extra-Obolus, der Rechnung plus X, scheiden sich die Geister. Ein Forschungsseminar an der Goethe-Universität hat zum Thema Trinkgeld ein Semester lang Gäste und Kellner/innen befragt – mit überraschenden Ergebnissen.
Winckelmann, Luke Andreas ; Bass, Steffen A. ; Bleicher, Marcus ; Brandstetter, Mathias ; Dumitru, Adrian Bogdan ; Ernst, Christoph ; Gerland, Lars ; Konopka, Jens ; Soff, Sven ; Spieles, Christian ; Weber, Henning ; Hartnack, Christoph ; Aichelin, Jörg ; Amelin, Nikolai ; Stöcker, Horst ; Greiner, Walter
The behavior of hadronic matter at high baryon densities is studied within Ultrarelativistic Quantum Molecular Dynamics (URQMD). Baryonic stopping is observed for Au+Au collisions from SIS up to SPS energies. The excitation function of flow shows strong sensitivities to the underlying equation of state (EOS), allowing for systematic studies of the EOS. Effects of a density dependent pole of the rho-meson propagator on dilepton spectra are studied for different systems and centralities at CERN energies.
Winckelmann, Luke Andreas ; Ernst, Christoph ; Gerland, Lars ; Konopka, Jens ; Soff, Sven ; Bass, Steffen A. ; Bleicher, Marcus ; Brandstetter, Mathias ; Dumitru, Adrian Bogdan ; Spieles, Christian ; Weber, Henning ; Hartnack, Christoph ; Aichelin, Jörg ; Amelin, Nikolai ; Stöcker, Horst ; Greiner, Walter
The behavior of hadronic matter at high baryon densities is studied within Ultrarelativistic Quantum Molecular Dynamics (URQMD). Baryonic stopping is observed for Au+Au collisions from SIS up to SPS energies. The excitation function of flow shows strong sensitivities to the underlying equation of state (EOS), allowing for systematic studies of the EOS. Dilepton spectra are calculated with and without shifting the rho pole. Except for S+Au collisions our calculations reproduce the CERES data.
Wolf, Kerstin ; Galeano Weber, Elena M. ; Bosch, Jasper J. F. van den ; Volz, Steffen ; Nöth, Ulrike ; Deichmann, Ralf ; Naumer, Marcus Johannes ; Pfeiffer, Till ; Fiebach, Christian
Our ability to select relevant information from the environment is limited by the resolution of attention – i.e., the minimum size of the region that can be selected. Neural mechanisms that underlie this limit and its development are not yet understood. Functional magnetic resonance imaging (fMRI) was performed during an object tracking task in 7- and 11-year-old children, and in young adults. Object tracking activated canonical fronto-parietal attention systems and motion-sensitive area MT in children as young as 7 years. Object tracking performance improved with age, together with stronger recruitment of parietal attention areas and a shift from low-level to higher-level visual areas. Increasing the required resolution of spatial attention – which was implemented by varying the distance between target and distractors in the object tracking task – led to activation increases in fronto-insular cortex, medial frontal cortex including anterior cingulate cortex (ACC) and supplementary motor area, superior colliculi, and thalamus. This core circuitry for attentional precision was recruited by all age groups, but ACC showed an age-related activation reduction. Our results suggest that age-related improvements in selective visual attention and in the resolution of attention are characterized by an increased use of more functionally specialized brain regions during the course of development.
Zschiesche, Detlef ; Bass, Steffen A. ; Bleicher, Marcus ; Brachmann, Jörg ; Gerland, Lars ; Paech, Kerstin ; Scherer, Stefan ; Soff, Sven ; Spieles, Christian ; Weber, Henning ; Stöcker, Horst ; Greiner, Walter
Compelling evidence for the creation of a new form of matter has been claimed to be found in Pb+Pb collisions at SPS. We discuss the uniqueness of often proposed experimental signatures for quark matter formation in relativistic heavy ion collisions. It is demonstrated that so far none of the proposed signals like J/psi meson production/suppression, strangeness enhancement, dileptons, and directed flow unambigiously show that a phase of deconfined matter has been formed in SPS Pb+Pb collisions. We emphasize the need for systematic future measurements to search for simultaneous irregularities in the excitation functions of several observables in order to come close to pinning the properties of hot, dense QCD matter from data.
Öztürk, Fatma Cagla ; Akkuş, Baki ; Atanasov, Dinko ; Beyer, Heinrich F. ; Bosch, Fritz ; Boutin, David ; Brandau, Carsten ; Bühler, Paul ; Çakirli Mutlu, Rabia Burcu ; Chen, Ruijiu ; Chen, Weidong ; Chen, Xiangcheng ; Dillmann, Iris ; Dimopoulou, Christina ; Enders, Wolfgang ; Essel, Hans G. ; Faestermann, Thomas ; Forstner, Oliver ; Gao, Bing-Shui ; Geissel, Hans ; Gernhäuser, Roman ; Grisenti, Robert Evaristo ; Gumberidze, Alexandre ; Hagmann, Siegbert ; Heftrich, Tanja ; Heil, Michael ; Herdrich, Marc Oliver ; Hillenbrand, Pierre-Michel ; Izumikawa, Takuji ; Kienle, Paul ; Klaushofer, Christoph ; Kleffner, Carl-Michael ; Kozhuharov, Christophor ; Knöbel, Ronja ; Kovalenko, Oleksandr ; Kreim, Susanne ; Kühl, Thomas ; Lederer-Woods, Claudia ; Lestinsky, Michael ; Litvinov, Sergey A. ; Litvinov, Yuri A. ; Liu, Zhong ; Ma, Xinwen ; Maier, Ludwig W. ; Mei, Bo ; Miura, Hiroshi ; Mukha, Ivan ; Najafi, Mohammad Ali ; Nagae, Daisuke ; Nishimura, Takuro ; Nociforo, Chiara ; Nolden, Fritz ; Ohtsubo, Takashi ; Öktem, Yeşim ; Omika, Shunichiro ; Ozawa, Akira ; Petridis, Nikolaos ; Piotrowski, Jeremi ; Reifarth, René ; Roßbach, Jörg ; Sánchez Alarcón, Rodolfo Marcelo ; Sanjari, Mohammad Shahab ; Scheidenberger, Christoph ; Sidhu, Ragandeep Singh ; Simon, Haik ; Spillmann, Uwe ; Steck, Markus ; Stöhlker, Thomas ; Sun, Baohua ; Susam, Lidya Amon ; Suzaki, Fumi ; Suzuki, Takeshi ; Torilov, Sergey Yu. ; Trageser, Christian ; Trassinelli, Martino ; Trotsenko, Sergiy ; Tu, Xiaolin ; Walker, Philip M. ; Wang, M. ; Weber, Günter ; Weick, Helmut ; Winckler, Nicolas ; Winters, Danyal Ferdinant Alexander ; Woods, Philip John ; Yamaguchi, Takayuki ; Xu, X.D. ; Yan, X.L. ; Yang, Jiancheng ; Yuan, You-Jin ; Zhang, Yuhu ; Zhou, Xiaohong
An experiment addressing electron capture (EC) decay of hydrogen-like 142Pm60+ions has been conducted at the experimental storage ring (ESR) at GSI. The decay appears to be purely exponential and no modulations were observed. Decay times for about 9000 individual EC decays have been measured by applying the single-ion decay spectroscopy method. Both visually and automatically analysed data can be described by a single exponential decay with decay constants of 0.0126(7)s−1 for automatic analysis and 0.0141(7)s−1 for manual analysis. If a modulation superimposed on the exponential decay curve is assumed, the best fit gives a modulation amplitude of merely 0.019(15), which is compatible with zero and by 4.9 standard deviations smaller than in the original observation which had an amplitude of 0.23(4).