Architecture of coatomer: Molecular characterization of delta-COP and protein interactions within the complex

Copyright © 2011 by The Rockefeller University Press.Coatomer is a cytosolic protein complex that forms the coat of COP I-coated transport vesicles. In our attempt to analyze the physical and functional interactions between its seven subunits (coat proteins, [COPs] alpha-zeta), we engaged in a program to clone and characterize the individual coatomer subunits. We have now cloned, sequenced, and overexpressed bovine alpha-COP, the 135-kD subunit of coatomer as well as delta-COP, the 57-kD subunit and have identified a yeast homolog of delta-COP by cDNA sequence comparison and by NH2-terminal peptide sequencing. delta-COP shows homologies to subunits of the clathrin adaptor complexes AP1 and AP2. We show that in Golgi-enriched membrane fractions, the protein is predominantly found in COP I-coated transport vesicles and in the budding regions of the Golgi membranes. A knock-out of the delta-COP gene in yeast is lethal. Immunoprecipitation, as well as analysis exploiting the two-hybrid system in a complete COP screen, showed physical interactions between alpha- and epsilon-COPs and between beta- and delta-COPs. Moreover, the two-hybrid system indicates interactions between gamma- and zeta-COPs as well as between alpha- and beta' COPs. We propose that these interactions reflect in vivo associations of those subunits and thus play a functional role in the assembly of coatomer and/or serve to maintain the molecular architecture of the complex.This work was supported by The Deutsche Forschungsgemeinschaft (SFB 352), the Human Frontier Science Program, and the Swiss National Science Foundation No. 31-43366.95

Hochschulisches Lernen – eine analytische Perspektive

Dieser Beitrag betrachtet hochschulisches Lernen unter einer analytischen Perspektive: Danach artikuliert sich hochschulisches Lernen im institutionellen Kontext der Hochschule mit ihren studiengangstrukturellen Rahmenbedingungen in einer je spezifischen, dabei stets kontingenten und polymorphen Koppelung zwischen Wissenschaft als Ort der Wissensproduktion einerseits und Studium als Ort der Erschliesung von Sinn- und Handlungsressourcen andererseits. Hochschulisches Lernen lasst sich als Moglichkeitsraum von Figurationen dieser Bezugnahmen rekonstruieren. Die Analyse des Lernens an Hochschulen erschliest auserdem Forschungsperspektiven einer bildungswissenschaftlichen Hochschulforschung und einer theoretischen Hochschuldidaktik, zu denen die Erwachsenenbildungswissenschaft substanzielle Beitrage liefern kann

Dynamic generation of maximally entangled photon multiplets by adiabatic passage

The adiabatic passage scheme for quantum state synthesis, in which atomic Zeeman coherences are mapped to photon states in an optical cavity, is extended to the general case of two degenerate cavity modes with orthogonal polarization. Analytical calculations of the dressed-state structure and Monte Carlo wave-function simulations of the system dynamics show that, for a suitably chosen cavity detuning, it is possible to generate states of photon multiplets that are maximally entangled in polarization. These states display nonclassical correlations of the type described by Greenberger, Horne, and Zeilinger (GHZ). An experimental scheme to realize a GHZ measurement using coincidence detection of the photons escaping from the cavity is proposed. The correlations are found to originate in the dynamics of the adiabatic passage and persist even if cavity decay and GHZ state synthesis compete on the same time scale. Beyond entangled field states, it is also possible to generate entanglement between photons and the atom by using a different atomic transition and initial Zeeman state.Comment: 22 pages (RevTeX), including 23 postscript figures. To be published in Physical Review

Rezensionen

Rezension zu: 1) Arnold, Rolf: Selbstbildung - oder: Wer kann ich werden und wenn ja wie? Baltmannsweiler: Schneider Verl. Hohengehren 2010. ISBN 978-3-8340-0801-5. 2) Hadjar, Andreas (Hrsg.): Geschlechtsspezifische Bildungsungleichheiten. Wiesbaden: VS Verl. f. Sozialwissenschaften 2011. ISBN 978-3-531-17288-0. 3) Hartz, Stefanie: Qualität in Organisationen der Weiterbildung: eine Studie zur Akzeptanz und Wirkung der Lernorientierten Qualitätstestierung in der Weiterbildung. Wiesbaden: VS Verl. f. Sozialwissenschaften 2011. ISBN 978-3-531-17485-3. 4) Ioannidou, Alexandra: Steuerung im transnationalen Bildungsraum: Internationales Bildungsmonitoring zum Lebenslangen Lernen. Reihe Theorie und Praxis der Erwachsenenbildung. Bielefeld: W. Bertelsmann Verl. 2010. ISBN 978-3-7639-1991-8. 5) Münk, Dieter; Severing, Eckart (Hrsg.): Theorie und Praxis der Kompetenzfeststellung im Betrieb - Status quo und Entwicklungsbedarf. Berichte zur beruflichen Bildung - Schriftenreihe des Bundesinstituts für Berufsbildung Bonn. Bielefeld: W. Bertelsmann Verl. 2009. ISBN 978-3-7639-1130-1. 6) Nühlen, Maria: Erwachsenenbildung und die Philosophie: historischer Rückblick und die Herausforderung für die Zukunft. Berlin: LIT Verl. 2010. ISBN 978-3-643-10110-5. 7) Schrader, Josef; Hohmann, Reinhard; Hartz, Stefanie (Hrsg.): Mediengestützte Fallarbeit: Konzepte, Erfahrungen und Befunde zur Kompetenzentwicklung von Erwachsenenbildnern. Bielefeld: W. Bertelsmann Verl. 2010. ISBN 978-3-7639-4659-4

Screening of depression in adolescents through the Internet: Sensitivity and specificity of two screening questionnaires.

.001). The scores on both instruments were significantly increased in all subjects with a mood disorder, whether current or lifetime, except for lifetime minor depression. In the ROC analyses, high areas under the curve were found for the MDI (0.89) and CESD (0.90). The best cut-off point for the MDI was 19 (sensitivity: 90.48; specificity: 71.53), and for the CES-D it was 22 (sensitivity: 90.48; specificity: 74.31). We conclude that the MDI and CES-D are reliable and valid instruments that can be used for this screening

Impact of Rheumatic Musculoskeletal Disease on Psychological Development in Adolescents and Young Adults

Adolescents and young adults (AYAs) undergo significant physiological and psychological transformations. When developmental milestones are combined with additional challenges of growing up with a chronic rheumatic musculoskeletal disease (RMD), it can increase AYA's susceptibility to psychological problems. Emotional issues in adolescence can often persist into adulthood and negatively impact future health, social, and work outcomes. This chapter summarises psychological challenges for AYAs and recommends ways for healthcare professionals (HCPs) to promote mental wellbeing in AYAs with RMD

Hypoxia Alters Cell Cycle Regulatory Protein Expression and Induces Premature Maturation of Oligodendrocyte Precursor Cells

Periventricular white matter injury (PWMI) is a common form of brain injury sustained by preterm infants. A major factor that predisposes to PWMI is hypoxia. Because oligodendrocytes (OLs) are responsible for myelination of axons, abnormal OL development or function may affect brain myelination. At present our understanding of the influences of hypoxia on OL development is limited. To examine isolated effects of hypoxia on OLs, we examined the influences of hypoxia on OL development in vitro.Cultures of oligodendrocyte precursor cells (OPCs) were prepared from mixed glial cultures and were 99% pure. OPCs were maintained at 21% O(2) or hypoxia (1% or 4% O(2)) for up to 7 days. We observed that 1% O(2) lead to an increase in the proportion of myelin basic protein (MBP)-positive OLs after 1 week in culture, and a decrease in the proportion of platelet-derived growth factor receptor alpha (PDGFRalpha)-positive cells suggesting premature OL maturation. Increased expression of the cell cycle regulatory proteins p27(Kip1) and phospho-cdc2, which play a role in OL differentiation, was seen as well.These results show that hypoxia interferes with the normal process of OL differentiation by inducing premature OPC maturation

Invasion of ovarian cancer cells is induced by PITX2-mediated activation of TGF-β and Activin-A

Background:Most ovarian cancers are highly invasive in nature and the high burden of metastatic disease make them a leading cause of mortality among all gynaecological malignancies. The homeodomain transcription factor, PITX2 is associated with cancer in different tissues. Our previous studies demonstrated increased PITX2 expression in human ovarian tumours. Growing evidence linking activation of TGF-β pathway by homeodomain proteins prompted us to look for the possible involvement of this signalling pathway in PITX2-mediated progression of ovarian cancer. Methods: The status of TGF-β signalling in human ovarian tissues was assessed by immunohistochemistry. The expression level of TGFB/INHBA and other invasion-associated genes was measured by quantitative-PCR (Q-PCR) and Western Blot after transfection/treatments with clones/reagents in normal/cancer cells. The physiological effect of PITX2 on invasion/motility was checked by matrigel invasion and wound healing assay. The PITX2- and activin-induced epithelial-mesenchymal transition (EMT) was evaluated by Q-PCR of respective markers and confocal/phase-contrast imaging of cells. Results: Human ovarian tumours showed enhanced TGF-β signalling. Our study uncovers the PITX2-induced expression of TGFB1/2/3 as well as INHBA genes (p < 0.01) followed by SMAD2/3-dependent TGF-β signalling pathway. PITX2-induced TGF-β pathway regulated the expression of invasion-associated genes, SNAI1, CDH1 and MMP9 (p < 0.01) that accounted for enhanced motility/invasion of ovarian cancers. Snail and MMP9 acted as important mediators of PITX2-induced invasiveness of ovarian cancer cells. PITX2 over-expression resulted in loss of epithelial markers (p < 0.01) and gain of mesenchymal markers (p < 0.01) that contributed significantly to ovarian oncogenesis. PITX2-induced INHBA expression (p < 0.01) contributed to EMT in both normal and ovarian cancer cells. Conclusions: Overall, our findings suggest a significant contributory role of PITX2 in promoting invasive behaviour of ovarian cancer cells through up-regulation of TGFB/INHBA. We have also identified the previously unknown involvement of activin-A in promoting EMT. Our work provides novel mechanistic insights into the invasive behavior of ovarian cancer cells. The extension of this study have the potential for therapeutic applications in future