How Good are Present Analytical QCD-Predictions on Fluctuations in Angular Intervals ?

Results on two-particle angular correlations in jet cones and on multiplicity fluctuations in one- and two- dimensional angular intervals, delivered by three experiments (DELPHI, L3 and ZEUS, at $\sqrt{s}$ from few to 183 GeV) are compared to present existing analytical QCD calculations, using the LPHD hypothesis. Two different types of functions have been tested. While the differentially normalized correlation functions show substantial deviations from the predictions, a globally normalized correlation function agrees surprisingly well. The role of the QCD parameters $\alpha_s$, $\Lambda$ and $n_f$ is discussed. The necessity to include full energy-momentum conservation into the analytical calculations is stressed.Comment: 13 pages (LaTeX), 11 figures, uses sprocl.sty. Miniraporteur-talk given at the Internat. Symposium of Multiparticle Dynamics, Delphi, Greece, 6-11 Sept. 1998 (to appear in Proceedings

Study of gluon fragmentation and colour octet neutralization in DELPHI

Using the full statistics of the DELPHI experiment at $\sqrt{s}=91 GeV$ 3-jet events are selected and gluon respectively quark jet enriched subsamples are defined. The leading systems of the two kinds of jets are determined using rapidity gaps. The sum of charges of the leading systems is studied. It is found that for gluon-jets there is a significant excess of leading systems with total charge zero when compared to Monte Carlo simulations with JETSET. The corresponding leading systems of quark-jets do not exhibit such an excess. The mass spectra of the leading systems with total charge zero are studied.Comment: 8 pages, 6 figures (in eps) talk given at XXXI International Symposium on Multiparticle Dynamics, Sep. 1-7, 2001, Datong China URL http://ismd31.ccnu.edu.cn

Investigation of Bose-Einstein Correlations in 3 jet events with the DELPHI detector

A preliminary investigation of Bose-Einstein correlations in 3 jet events has been made by analysing the collected data at the $Z^0$ peak from '94 and '95 and the calibration runs during the LEP2 period from '97 to 2000. Three methods were used to extract two-particle correlation functions. No significant difference was found between quark and gluon jets for all three methods.Comment: 6 pages, 2 figures in ps and 1 in eps, talk given at XXXI International Symposium on Multiparticle Dynamics, Sept 1-7, 2001, Datong China. see http://ismd31.ccnu.edu.cn

Untersuchungen zur Regulierung und Funktion der Mitogen-aktivierten Proteinkinase ERK5 = Regulation and Function of the Mitogen-activated Protein Kinase ERK5

Mitogen activated protein kinases (MAPKs) are found in all eukaryotic cells and represent crucial elements in the signal transduction from the plasma membrane to the nucleus. Although a broad variety of extracellular stimuli activate MAPKs, they evoke very distinct cellular responses. The amplitude and duration of MAPK activation determine signal identity and ultimately cell fate. A tight and finely tuned regulation is therefore critical for a specific cellular response. The role and the regulation of extracellular signal-regulated kinase 5 (ERK5), a MAPK with a large and unique C-terminal tail, were studied in different cellular systems. The study highlights two aspects of ERK5 regulation: control of the phosphorylation state and regulated protein stability. In analogy to other MAPKs ERK5 is activated by dual phosphorylation of threonine and tyrosine residues in its activation motif. A first part of the study concentrates on whether and how the protein tyrosine phosphatase PTP-SL is involved in the downregulation of the ERK5 signal. The direct interaction of both proteins is shown to result in mutual modulation of their enzymatic activities. PTP-SL is a substrate of ERK5 and, independent of its phosphorylation, binding to the kinase enhances its catalytic phosphatase activity. On the other hand, interaction with PTP-SL does not only downregulate enzymatic ERK5 activity but also effectively impedes its translocation to the nucleus. The second part of this study focuses on the interaction of ERK5 with c-Abl and its oncogenic variants Bcr/Abl and v-Abl. In this study these tyrosine kinases are demonstrated to regulate ERK5 by two mechanisms: first, by induction of kinase activity and secondly, by stabilisation of the ERK5 protein. Stabilisation involves the direct interaction of unique ERK5 domains with Abl kinases and is independent of MAPK cascade activation. The level of ERK5 and its intrinsic basal activity – rather than its activation – are essential for v-Abl-induced transformation as well as for survival of Bcr/Abl-positive leukaemia cells. Stabilisation of ERK5 thus contributes to cell survival and should therefore be considered as an additional aspect in therapy of chronic myeloid leukaemia. Taken together, the results obtained in this study demonstrate that diverse pathways regulate ERK5 signalling by affecting kinase activity, localisation and protein stability. While the phosphatase PTP-SL is involved in negative regulation of ERK5, Abl kinases potently activate ERK5 and increase its half-life. Protein stabilisation thus is presented as a novel mechanism in the regulation of MAPKs.Mitogen-aktivierte Proteinkinasen (MAPKn) werden in allen eukaryontischen Zellen exprimiert und spielen eine bedeutende Rolle in der Weiterleitung von Signalen von der Plasmamembran zum Zellkern. Obwohl eine Vielzahl von unterschiedlichsten Stimulanzien MAPKn aktiveren, rufen diese doch sehr spezifische und vor allem adequate Reaktionen der Zelle hervor. Die molekularen Grundlagen für dieses Pradoxon sind weitgehend unbekannt. Es ist allerdings klar, daß die Amplitude und die Dauer der MAPKn-Aktivierung zwei entscheidende Parameter sind, die den weiteren Signalweg definieren und somit das Schicksal der Zelle festlegen. Daher müssen MAPKn einer sehr stringenten und fein regulierbaren Kontrolle unterliegen. In der vorliegenden Arbeit wurde die Funktion und die Regulierung der durch extrazelluläre Signale regulierten Kinase 5 (ERK5), einer MAPK mit einem außergewöhnlich langen und strukturell einzigartigen C-Terminus, in unterschiedlichen Zellsystemen untersucht. Zwei Aspekte der Regulierung von ERK5 werden insbesonders hervorgehoben: die Kontrolle des Phosphorilierungsstatus und die beeinflußbare Proteinstabilität. In Analogie zu anderen MAPKs wird ERK5 durch die Phosphorilierung eines Threonin und eines Tyrosinrestes aktiviert. Der erste Teil dieser Studie konzentriert sich auf die Frage ob und wie die Phosphatase PTP-SL und der Regulierung der ERK5 beteiligt sein könnte. Es konnte gezeigt werden, daß die direkte Interaktion dieser beiden Proteine zur gegenseitigen Beeinflussung ihrer enzymatischen Aktivitäten führt. PTP-SL ist nicht nur ein Substrat für die ERK5 sondern besitzt auch im Komplex mit ERK5 eine höhere Aktivität. Andererseits ist PTP-SL in der Lage, die Aktivität von ERK5 runterzuregulieren und darüber hinaus auch die Translokation von ERK5 in den Nucleus zu inhibieren. Der zweite Scherpunkt dieser Arbeit liegt auf der Wechselwirkung von ERK5 mit der Tyrosinkinasen c-Abl und ihren onkogenen Varianten Bcr/Abl und v-Abl. Es konnte gezeigt werden, daß diese Tyrosinkinasen ERK5 in zweierlei Weise beeinflussen: Erstens führen sie zur klassischen Aktivierung von ERK5 und zweitens stabilisieren sie das ERK5-Protein. Die Bedeutung der Proteinstabilisierung wurde durch die Untersuchung der Funktion von ERK5 bei von Abl-Kinase vermittelten Prozessen veranschaulicht. Sowohl für die Vestärkung Transformierung von Nagerfibroblasten durch v-Abl als auch für das Überleben von Bcr/Abl-positiven Leukämiezellen waren die Proteinmenge und die Basalaktivität und nicht etwa die Aktivierung von ERK5 ausschlaggebend. Zusammengenommen zeigen die Ergebnisse dieser Arbeit, daß die ERK5-vermittelte Signale durch Beeinflussung der Kinaseaktivität, der zellulären Lokalisation und der Proteinstabilität von ERK5 reguliert werden können. Während die Phosphatase PTP-SL an der Negativregulierung der ERK5 beteiligt ist, verstärken Abl-Kinasen ihre Aktivität und verlängern darüberhinaus die Halbwertszeit des Proteines in der Zelle. Proteinstabilisierung stellt somit einen neuen Aspekt in der Kontrolle von MAPKn dar

Intermittency in a single event

The possibility to study intermittency in a single event of high multiplicity is investigated in the framework of the $\alpha-$model. It is found that, for cascade long enough, the dispersion of intermittency exponents obtained from individual events is fairly small. This fact opens the possibility to study the distribution of the intermittency parameters characterizing the cascades seen (by observing intermittency) in particle spectra.Comment: 7 pages, latex, 2 figures available on request by e-mai

Elongator: An Ancestral Complex Driving Transcription and Migration through Protein Acetylation

Elongator is an evolutionary highly conserved complex. At least two of its cellular functions rely on the intrinsic lysine acetyl-transferase activity of the Elongator complex. Its two known substrates—Histone H3 and α-Tubulin—reflect the different roles of Elongator in the cytosol and the nucleus. A picture seems to emerge in which nuclear Elongator could regulate the transcriptional elongation of a subset of stress-inducible genes through acetylation of Histone H3 in the promoter-distal gene body. In the cytosol, Elongator-mediated acetylation of α-Tubulin contributes to intracellular trafficking and cell migration. Defects in both functions of Elongator have been implicated in neurodegenerative disorders

Post-Translational Modifications of H2A Histone Variants and Their Role in Cancer

Altres ajuts: Research leading to inventions at the IJC is supported by the 'La Caixa' Foundation, the Fundació Internacional Josep Carreras, Celgene Spain and the CERCA Programme/Generalitat de Catalunya.Histone variants are chromatin components that replace replication-coupled histones in a fraction of nucleosomes and confer particular characteristics to chromatin. H2A variants represent the most numerous and diverse group among histone protein families. In the nucleosomal structure, H2A-H2B dimers can be removed and exchanged more easily than the stable H3-H4 core. The unstructured N-terminal histone tails of all histones, but also the C-terminal tails of H2A histones protrude out of the compact structure of the nucleosome core. These accessible tails are the preferential target sites for a large number of post-translational modifications (PTMs). While some PTMs are shared between replication-coupled H2A and H2A variants, many modifications are limited to a specific histone variant. The present review focuses on the H2A variants H2A.Z, H2A.X, and macroH2A, and summarizes their functions in chromatin and how these are linked to cancer development and progression. H2A.Z primarily acts as an oncogene and macroH2A and H2A.X as tumour suppressors. We further focus on the regulation by PTMs, which helps to understand a degree of context dependency