Epstein-Barr virus nuclear antigen 3A protein regulates CDKN2B transcription via interaction with MIZ-1

The Epstein-Barr virus (EBV) nuclear antigen 3 family of protein is critical for the EBV-induced primary B-cell growth transformation process. Using a yeast two-hybrid screen we identified 22 novel cellular partners of the EBNA3s. Most importantly, among the newly identified partners, five are known to play direct and important roles in transcriptional regulation. Of these, the Myc-interacting zinc finger protein-1 (MIZ-1) is a transcription factor initially characterized as a binding partner of MYC. MIZ-1 activates the transcription of a number of target genes including the cell cycle inhibitor CDKN2B. Focusing on the EBNA3A/MIZ-1 interaction we demonstrate that binding occurs in EBV-infected cells expressing both proteins at endogenous physiological levels and that in the presence of EBNA3A, a significant fraction of MIZ-1 translocates from the cytoplasm to the nucleus. Moreover, we show that a trimeric complex composed of a MIZ-1 recognition DNA element, MIZ-1 and EBNA3A can be formed, and that interaction of MIZ-1 with nucleophosmin (NPM), one of its coactivator, is prevented by EBNA3A. Finally, we show that, in the presence of EBNA3A, expression of the MIZ-1 target gene, CDKN2B, is downregulated and repressive H3K27 marks are established on its promoter region suggesting that EBNA3A directly counteracts the growth inhibitory action of MIZ-1

Absence of Complex I Is Associated with Diminished Respiratory Chain Function in European Mistletoe

Parasitism is a life history strategy found across all domains of life whereby nutrition is obtained from a host. It is often associated with reductive evolution of the genome, including loss of genes from the organellar genomes [1, 2]. In some unicellular parasites, the mitochondrial genome (mitogenome) has been lost entirely, with far-reaching consequences for the physiology of the organism [3, 4]. Recently, mitogenome sequences of several species of the hemiparasitic plant mistletoe (Viscum sp.) have been reported [5, 6], revealing a striking loss of genes not seen in any other multicellular eukaryotes. In particular, the nad genes encoding subunits of respiratory complex I are all absent and other protein-coding genes are also lost or highly diverged in sequence, raising the question what remains of the respiratory complexes and mitochondrial functions. Here we show that oxidative phosphorylation (OXPHOS) in European mistletoe, Viscum album, is highly diminished. Complex I activity and protein subunits of complex I could not be detected. The levels of complex IV and ATP synthase were at least 5-fold lower than in the non-parasitic model plant Arabidopsis thaliana, whereas alternative dehydrogenases and oxidases were higher in abundance. Carbon flux analysis indicates that cytosolic reactions including glycolysis are greater contributors to ATP synthesis than the mitochondrial tricarboxylic acid (TCA) cycle. Our results describe the extreme adjustments in mitochondrial functions of the first reported multicellular eukaryote without complex I

FIRST RESULTS OF THE NEW BUNCH-BY-BUNCH FEEDBACK SYSTEM AT ANKA

Abstract A new digital three dimensional fast bunch-by-bunch feedback system has been installed and commissioned at ANKA. Immediate improvements to stored current and lifetime were achieved for normal user operation. For this, the feedback has to be running during the injection and the energy ramp to 2.5 GeV. Additionally, the feedback system was also incorporated into the diagnostic tool-set at ANKA and opened up new possibilities of automated and continuous measurement of certain beam parameters. The system can operate in different modes such as the low alpha operation mode, which has different requirements on the feedback system compared to normal user operation. Results on the various aspects will be presented as well as future improvements

Electro-optical bunch length monitor for flute: Layout and simulations

A new compact linear accelerator FLUTE is currently under construction at Karlsruhe Institute of Technology (KIT) in collaboration with DESY and PSI. It aims at obtaining femtosecond electron bunches (~1fs - 300 fs) with a wide charge range (1 pC - 3 nC) and requires a precise bunch length diagnostic system. Here we present the layout of a bunch length monitor based on the electro-optic technique of spectral decoding using an Yb-doped fiber laser system (central wavelength 1030 nm) and a GaP crystal. Simulations of the electro-optic signal for different operation modes of FLUTE were performed and main challenges are discussed in this talk. This work is funded by the European Union under contract PITN-GA-2011-28919