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Gender differences in associations of glutamate decarboxylase 1 gene (GAD1) variants with panic disorder
(2012)
- 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.
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Identifizierung und Charakterisierung der mRNA processing bodies von Arabidopsis thaliana
(2007)
- 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.
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Nucleus-nucleus collisions at highest energies
(1996)
- The microscopic phasespace approach URQMD is used to investigate the stopping power and particle production in heavy systems at SPS and RHIC energies. We find no gap in the baryon rapidity distribution even at RHIC. For CERN energies URQMD shows a pile up of baryons and a supression of multi-nucleon clusters at midrapidity.
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Fluctuations and inhomogenities of energy density and isospin in Pb + Pb at the SPS
(1998)
- The main goal of heavy ion physics in the last fifteen years has been the search for the quark-gluon-plasma(QGP). Until now, unambigous experimental evidence for the QGP is missing.
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Can momentum correlations proof kinetic equilibration in heavy ion collisions at 160/A-GeV?
(1998)
- We perform an event-by-event analysis of the transverse momentum distribution of final state particles in central Pb(160AGeV)+Pb collisions within a microscopic non-equilibrium transport model (UrQMD). Strong influence of rescattering is found. The extracted momentum distributions show less fluctuations in A+A collisions than in p+p reactions. This is in contrast to simplified p+p extrapolations and random walk models.
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Excitation function of energy density and partonic degrees of freedom in relativistic heavy ion collisions
(1998)
- 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.
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Equilibrium and nonequilibrium effects in nucleus nucleus collisions
(1999)
- Abstract: Local thermal and chemical equilibration is studied for central AqA collisions at 10.7 160 AGeV in the Ultrarelativis- . tic Quantum Molecular Dynamics model UrQMD . The UrQMD model exhibits strong deviations from local equilibrium at the high density hadron string phase formed during the early stage of the collision. Equilibration of the hadron resonance matter is established in the central cell of volume Vs125 fm3 at later stages, tG10 fmrc, of the resulting quasi-isentropic expansion. The thermodynamical functions in the cell and their time evolution are presented. Deviations of the UrQMD quasi-equilibrium state from the statistical mechanics equilibrium are found. They increase with energy per baryon and lead to a strong enhancement of the pion number density as compared to statistical mechanics estimates at SPS energies. PACS: 25.75.-q; 24.10.Lx; 24.10.Pa; 64.30.qt
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Critical review of quark gluon plasma signatures
(1999)
- Noneequilibrium models (three-fluid hydrodynamics and UrQMD) use to discuss the uniqueness of often proposed experimental signatures for quark matter formation in relativistic heavy ion collisions. It is demonstrated that these two models - although they do treat the most interesting early phase of the collisions quite differently(thermalizing QGP vs. coherent color fields with virtual particles) - both yields a reasonable agreement with a large variety of the available heavy ion data.
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Relativistic hadron-hadron collisions in the ultra-relativistic quantum molecular dynamics model
(1999)
- Hadron-hadron collisions at high energies are investigated in the Ultra- relativistic-Quantum-Molecular-Dynamics approach. This microscopic trans- port model describes the phenomenology of hadronic interactions at low and intermediate energies ( s < 5 GeV) in terms of interactions between known hadrons and their resonances. At higher energies, s > 5 GeV, the excitation of color strings and their subsequent fragmentation into hadrons dominates the multiple production of particles in the UrQMD model. The model shows a fair overall agreement with a large body of experimental h-h data over a wide range of h-h center-of-mass energies. Hadronic reaction data with higher precision would be useful to support the use of the UrQMD model for relativistic heavy ion collisions.
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Physics opportunities at RHIC and LHC
(1999)
- Nonequilibrium models (three-fluid hydrodynamics, UrQMD, and quark molecular dynamics) are used to discuss the uniqueness of often proposed experimental signatures for quark matter formation in relativistic heavy ion collisions from the SPS via RHIC to LHC. It is demonstrated that these models - although they do treat the most interesting early phase of the collisions quite differently (thermalizing QGP vs. coherent color fields with virtual particles) -- all yield a reasonable agreement with a large variety of the available heavy ion data. Hadron/hyperon yields, including J/Psi meson production/suppression, strange matter formation, dileptons, and directed flow (bounce-off and squeeze-out) are investigated. Observations of interesting phenomena in dense matter are reported. However, 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. The role of future experiments with the STAR and ALICE detectors is pointed out.
