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1. The GATA-Type Transcription Factor Csm1 Regulates Conidiation and Secondary Metabolism in

Author

Niehaus, E.M., Schumacher, J., Burkhardt, I., Rabe, P., Spitzer, E., Münsterkötter, M., Güldener, U., Sieber, C.M.K., Dickschat, J.S., and Tudzynski, B.

Subjects
0301 basic medicine, Microbiology (medical), 030106 microbiology, Mutant, lcsh:QR1-502, Conidiation, Repressor, conidiation, Microbiology, lcsh:Microbiology, Csm1, 03 medical and health sciences, Aspergillus nidulans, Original Research, Genetics, secondary metabolism, biology, Wild type, Fusarium Fujikuroi, Gata Transcription Factor, Gene Expression, Nsdd, Secondary Metabolism, Stc, biology.organism_classification, GATA transcription factor, Complementation, 030104 developmental biology, gene expression, NsdD, Heterologous expression, Erratum, Fusarium fujikuroi, STC
Abstract

GATA-type transcription factors (TFs) such as the nitrogen regulators AreA and AreB, or the light-responsive TFs WC-1 and WC-2, play global roles in fungal growth and development. The conserved GATA TF NsdD is known as an activator of sexual development and key repressor of conidiation in Aspergillus nidulans, and as light-regulated repressor of macroconidia formation in Botrytis cinerea. In the present study, we functionally characterized the NsdD ortholog in Fusarium fujikuroi, named Csm1. Deletion of this gene resulted in elevated microconidia formation in the wild-type (WT) and restoration of conidiation in the non-sporulating velvet mutant Δvel1 demonstrating that Csm1 also plays a role as repressor of conidiation in F. fujikuroi. Furthermore, biosynthesis of the PKS-derived red pigments, bikaverin and fusarubins, is de-regulated under otherwise repressing conditions. Cross-species complementation of the Δcsm1 mutant with the B. cinerea ortholog LTF1 led to full restoration of WT-like growth, conidiation and pigment formation. In contrast, the F. fujikuroi CSM1 rescued only the defects in growth, the tolerance to H2O2 and virulence, but did not restore the light-dependent differentiation when expressed in the B. cinerea Δltf1 mutant. Microarray analysis comparing the expression profiles of the F. fujikuroi WT and the Δcsm1 mutant under different nitrogen conditions revealed a strong impact of this GATA TF on 19 of the 47 gene clusters in the genome of F. fujikuroi. One of the up-regulated silent gene clusters is the one containing the sesquiterpene cyclase-encoding key gene STC1. Heterologous expression of STC1 in Escherichia coli enabled us to identify the product as the volatile bioactive compound (-)-germacrene D.

Published
2017

2. Histochemical localization of heart-type fatty-acid binding protein in human and murine tissues

Author

Zschiesche, W., Kleine, M.J. de, Spitzer, E., Veerkamp, J.H., and Glatz, J.F.C.

Subjects
Structure and function of fatty acid binding protein of human muscles, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Structuur en functie van humaan spier vetzuurbindend eiwit
Abstract

Contains fulltext : 22186___.PDF (Publisher’s version ) (Open Access)

Published
1995

3. Sushi syncope schusser gets wedeler's valve at Vail

Author

Spitzer E

Subjects
medicine.medical_specialty, Ventricular size, medicine.diagnostic_test, biology, business.industry, Syncope (genus), Regurgitation (circulation), General Medicine, Tricuspid insufficiency, medicine.disease, biology.organism_classification, Surgery, Internal medicine, Angiography, cardiovascular system, medicine, Cardiology, Medical history, cardiovascular diseases, business, human activities
Abstract

To the Editor. — A 68-year-old man was involved in a severe frontal impact with another skier while "wedeling" at a high rate of speed in Vail, Colo. Medical history was unremarkable, other than having developed "sushi syncope" at 63 years of age. 1 While prior to the accident he had experienced no difficulty skiing expert trails at an elevation of over 3600 m (10000 ft), afterward he became dyspneic while walking at the base of the mountain. On returning to sea level, he noted continued dyspnea on exertion; examination revealed V waves in the jugulars evident at 30° and a prominent murmur of tricuspid insufficiency. Transesophageal echocardiography demonstrated a flail tricuspid leaflet, and angiography revealed wide-open tricuspid regurgitation. Fortunately, his dyspnea gradually resolved, and by 3 months after the event he had returned to playing tennis without difficulty. Serial echocardiograms reveal that his right ventricular size has remained stable

Published
1994

4. Is the Sarcolemmal Na+ −K+ ATPase Involved in Active Calcium Transport?

Author

V.V. Kupriyanov, Spitzer E, Grosse R, and Preobrazhensky An

Subjects
biology, Sodium, ATPase, Vesicle, Cardiac muscle, chemistry.chemical_element, Calcium, Ouabain, Calcium ATPase, medicine.anatomical_structure, chemistry, biology.protein, medicine, Biophysics, Na+/K+-ATPase, medicine.drug
Abstract

Sarcolemmal preparations from rat and guinea pig cardiac muscle consisting mostly of inside-out vesicles were found to accumulate Ca2+ in the presence of ATP. The normalized rate of calcium uptake (the rate of calcium accumulation divided by its initial content in vesicles) correlated with the Na+ -K+ ATPase activity of the preparation. ATP-dependent calcium uptake by sarcolemmal vesicles was inhibited by 40-50% by cardenolids, digitoxigenin and ouabain, when the latter was included inside the vesicles. The Ca2+ gradient formed in the presence of ATP was dissipated by the addition of external sodium; Li+ was found to be ineffective in this process. External sodium also caused calcium release from vesicles pre-equilibrated with calcium in the medium. In the energy-dependent calcium uptake, the membrane-bound creatine kinase ATP-regenerating system was found to be the most effective energy source for active calcium transport. The results obtained may be interpreted to show that either the cardiac sarcolemma contains an energy-dependent calcium transport system or the sarcolemmal Na+ -K+ ATPase is able to transport calcium instead of sodium.

Published
1982

5. Hautkrankheiten

Author

Winkler, Max, Juliusberg, Fritz, Joseph, Max, Baer, Theodor, Ullmann, J., Leiner, Schwab, Theodor, Pick, Walther, Oppenheim, M., Münchheimer, F., Arzt, Leopold, Weiler, Zweig, Ludwig, Roth, Alfred, Lion, V., Stern, Marg, Hannes, Spitzer, Ernest, Krzysztalowicz, F., Leibkind, Max, Hanf, H., Fuchs, H., Odstrčil, Starke, Spitzer, E., Spitzer, Ernst, Bandler, Viktor, and Lewandowsky, F.

Abstract

n/a

Published
1915

7. Mammary-derived growth inhibitor (MDGI)

Author

Grosse, R., Böhmer, F. D., Binas, B., Andreas Kurtz, Spitzer, E., Müller, T., and Zschiesche, W.

Subjects
Molecular Sequence Data, Sequence Homology, Nerve Tissue Proteins, Arachidonic Acids, Fatty Acid-Binding Proteins, Epithelium, Mice, Mammary Glands, Animal, Pregnancy, Receptors, Adrenergic, beta, Animals, Amino Acid Sequence, Carcinoma, Ehrlich Tumor, Cell Nucleus, Stem Cells, Cell Differentiation, Lipid Metabolism, Growth Inhibitors, Neoplasm Proteins, Rats, Gene Expression Regulation, Organ Specificity, Multigene Family, Cattle, Female, Carrier Proteins, Fatty Acid-Binding Protein 7, Peptides, Fatty Acid Binding Protein 3, Sequence Alignment, Cell Division

8. Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial

Author

Pascal Vranckx, Marco Valgimigli, Peter Jüni, Christian Hamm, Philippe Gabriel Steg, Dik Heg, Gerrit Anne van Es, Eugene P McFadden, Yoshinobu Onuma, Cokky van Meijeren, Ply Chichareon, Edouard Benit, Helge Möllmann, Luc Janssens, Maurizio Ferrario, Aris Moschovitis, Aleksander Zurakowski, Marcello Dominici, Robert Jan Van Geuns, Kurt Huber, Ton Slagboom, Patrick W Serruys, Stephan Windecker, Mohamed Abdellaoui, David Adlam, Ibrahim Akin, Agustin Albarran Gonzalez-Trevilla, Manuel Almeida, Pedro Alves Lemos Neto, Adel Aminian, Richard Anderson, Rick Andreae, Michael Angioi, Taku Asano, Emanuele Barbato, Peter Barlis, Pascal Barraud, Olivier Bertrand, Farzin Beygui, Leonardo Bolognese, Roberto Botelho, Coby Bouwman, Marco Bressers, Philippe Brunel, Pawel Buszman, Ian Buysschaert, Pedro Canas da Silva, Didier Carrie, Angel Cequier, Chun Chin Chang, Saqib Chowdhary, Carlos Collet, Antonio Colombo, James Cotton, Rui Cruz Ferreira, Salvatore Curello, Nick Curzen, Judith de Bot, Tone de Vreede, Georg Delle Karth, Lynn Dijksma, István Édes, Eric Eeckhout, Ingo Eitel, József Faluközy, Farzin Fath-Ordoubadi, Geza Fontos, Jose Francisco Diaz, Edgard Freitas Quintella, Bernhard Frey, Guy Friedrich, Gavin Galasko, Grzegorz Galuszka, Vasco Gama Ribeiro, Scot Garg, Giuseppe Gargiulo, Tobias Geisler, Valeri Gelev, Art Ghandilyan, Javier Goicolea, Tommaso Gori, Felice Gragnano, Ana Guimarães, Michael Haude, Pieter Heijke, Rosa Ana Hernández Antolin, David Hildick-Smith, Dorien Hillen, Ina Hoekman, Sjoerd Hofma, Lene Holmvang, Stephen Hoole, Iván Horváth, Annemarie Hugense, Karim Ibrahim, Andres Iñiguez, Karl Isaaz, Zoltán Jambrik, Pawel Jasionowicz, Judith Jonk, Werner Jung, Yuki Katagiri, Norihiro Kogame, Tian Hai Koh, René Koning, Mariana Konteva, Zsolt Kőszegi, Florian Krackhardt, Yvonne Kreuger, Neville Kukreja, Boudijn Ladan, Pierre Lantelme, Sergio Leandro, Gregor Leibundgut, Christoph Liebetrau, Wietze Lindeboom, Carlos Macaya Miguel, François Mach, Michael Magro, Luc Maillard, Negar Manavifar, Laura Mauri, Eugene McFadden, Bela Merkely, Yosuke Miyazaki, Adam Młodziankowski, Tiziano Moccetti, Rodrigo Modolo, Helge Möllman, Jean-François Morelle, Michael Munndt Ottesen, Martin Muurling, Christoph Kurt Naber, Franz-Josef Neumann, Keith Oldroyd, Paul Ong, Sanne Palsrok, Ivo Petrov, Sylvain Plante, Janusz Prokopczuk, Tessa Rademaker-Havinga, Christopher Raffel, Benno Rensing, Marco Roffi, Kees-Jan Royaards, Manel Sabate, Volker Schächinger, Tim Seidler, Antonio Serra Peñaranda, Patrick Serruys, Lali Sikarulidze, Osama I Soliman, Amanda Sousa, Ernest Spitzer, Rod Stables, Gabriel Steg, Clemens Steinwender, Eduardas Subkovas, Harry Suryapranata, Kuniaki Takahashi, Suneel Talwar, Emmanuel Teiger, Addy ter Weele, Eva Teurlings, Attila Thury, Jan Tijssen, Gincho Tonev, Diana Trendafilova-Lazarova, Carlo Tumscitz, Victor Umans, Imre Ungi, Veselin Valkov, Pim van der Harst, Robert Jan van Geuns, Dobrin Vassilev, Vasil Velchev, Esther Velthuizen, Freek Verheugt, Natalia Vlcek, Jürgen vom Dahl, Mathias Vrolix, Simon Walsh, Nikos Werner, Maarten Witsenburg, Azfar Zaman, Krzysztof Żmudka, Bernhard Zrenner, Robert Zweiker, University of Zurich, Serruys, Patrick W, Cardiology, Vranckx, P., Valgimigli, M., Juni, P., Hamm, C., Steg, P. G., Heg, D., van Es, G. A., Mcfadden, E. P., Onuma, Y., van Meijeren, C., Chichareon, P., Benit, E., Mollmann, H., Janssens, L., Ferrario, M., Moschovitis, A., Zurakowski, A., Dominici, M., Van Geuns, R. J., Huber, K., Slagboom, T., Serruys, P. W., Windecker, S., Abdellaoui, M., Adlam, D., Akin, I., Albarran Gonzalez-Trevilla, A., Almeida, M., Alves Lemos Neto, P., Aminian, A., Anderson, R., Andreae, R., Angioi, M., Asano, T., Barbato, E., Barlis, P., Barraud, P., Bertrand, O., Beygui, F., Bolognese, L., Botelho, R., Bouwman, C., Bressers, M., Brunel, P., Buszman, P., Buysschaert, I., Canas da Silva, P., Carrie, D., Cequier, A., Chin Chang, C., Chowdhary, S., Collet, C., Colombo, A., Cotton, J., Cruz Ferreira, R., Curello, S., Curzen, N., de Bot, J., de Vreede, T., Delle Karth, G., Dijksma, L., Edes, I., Eeckhout, E., Eitel, I., Falukozy, J., Fath-Ordoubadi, F., Fontos, G., Francisco Diaz, J., Freitas Quintella, E., Frey, B., Friedrich, G., Galasko, G., Galuszka, G., Gama Ribeiro, V., Garg, S., Gargiulo, G., Geisler, T., Gelev, V., Ghandilyan, A., Goicolea, J., Gori, T., Gragnano, F., Guimaraes, A., Haude, M., Heijke, P., Hernandez Antolin, R. A., Hildick-Smith, D., Hillen, D., Hoekman, I., Hofma, S., Holmvang, L., Hoole, S., Horvath, I., Hugense, A., Ibrahim, K., Iniguez, A., Isaaz, K., Jambrik, Z., Jasionowicz, P., Jonk, J., Jung, W., Katagiri, Y., Kogame, N., Koh, T. H., Koning, R., Konteva, M., Koszegi, Z., Krackhardt, F., Kreuger, Y., Kukreja, N., Ladan, B., Lantelme, P., Leandro, S., Leibundgut, G., Liebetrau, C., Lindeboom, W., Macaya Miguel, C., Mach, F., Magro, M., Maillard, L., Manavifar, N., Mauri, L., Mcfadden, E., Merkely, B., Miyazaki, Y., Mlodziankowski, A., Moccetti, T., Modolo, R., Mollman, H., Morelle, J. -F., Munndt Ottesen, M., Muurling, M., Naber, C. K., Neumann, F. -J., Oldroyd, K., Ong, P., Palsrok, S., Petrov, I., Plante, S., Prokopczuk, J., Rademaker-Havinga, T., Raffel, C., Rensing, B., Roffi, M., Royaards, K. -J., Sabate, M., Schachinger, V., Seidler, T., Serra Penaranda, A., Serruys, P., Sikarulidze, L., Soliman, O. I., Sousa, A., Spitzer, E., Stables, R., Steg, G., Steinwender, C., Subkovas, E., Suryapranata, H., Takahashi, K., Talwar, S., Teiger, E., ter Weele, A., Teurlings, E., Thury, A., Tijssen, J., Tonev, G., Trendafilova-Lazarova, D., Tumscitz, C., Umans, V., Ungi, I., Valkov, V., van der Harst, P., van Geuns, R. J., Vassilev, D., Velchev, V., Velthuizen, E., Verheugt, F., Vlcek, N., vom Dahl, J., Vrolix, M., Walsh, S., Werner, N., Witsenburg, M., Zaman, A., Zmudka, K., Zrenner, B., Zweiker, R., ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, Graduate School, ACS - Heart failure & arrhythmias, and ACS - Amsterdam Cardiovascular Sciences

Subjects
medicine.medical_specialty, Aspirin, Acute coronary syndrome, business.industry, medicine.medical_treatment, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Percutaneous coronary intervention, 610 Medicine & health, General Medicine, 2700 General Medicine, 030204 cardiovascular system & hematology, medicine.disease, Clopidogrel, 11171 Cardiocentro Ticino, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Drug-eluting stent, Internal medicine, medicine, 030212 general & internal medicine, Myocardial infarction, business, Ticagrelor, medicine.drug
Abstract

Background We hypothesised that ticagrelor, in combination with aspirin for 1 month, followed by ticagrelor alone, improves outcomes after percutaneous coronary intervention compared with standard antiplatelet regimens. Methods GLOBAL LEADERS was a randomised, open-label superiority trial at 130 sites in 18 countries. Patients undergoing percutaneous coronary intervention with a biolimus A9-eluting stent for stable coronary artery disease or acute coronary syndromes were randomly assigned (1:1) to 75-100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy, or standard dual antiplatelet therapy with 75-100 mg aspirin daily plus either 75 mg clopidogrel daily (for patients with stable coronary artery disease) or 90 mg ticagrelor twice daily (for patients with acute coronary syndromes) for 12 months, followed by aspirin monotherapy for 12 months. Randomisation was concealed, stratified by centre and clinical presentation (stable coronary artery disease vs acute coronary syndrome), and blocked, with randomly varied block sizes of two and four. The primary endpoint at 2 years was a composite of all-cause mortality or non-fatal centrally adjudicated new Q-wave myocardial infarction as assessed by a core lab in a blinded manner. The key secondary safety endpoint was site-reported bleeding assessed according to the Bleeding Academic Research Consortium criteria (grade 3 or 5). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01813435, and is closed to new participants, with followup completed. Findings Between July 1, 2013, and Nov 9, 2015, 15 968 participants were randomly assigned, 7980 to the experimental group and 7988 to the control group. At 2 years, 304 (3.81%) participants in the experimental group had died or had a non-fatal centrally adjudicated new Q-wave myocardial infarction, compared with 349 (4.37%) participants in the control group (rate ratio 0.87 [95% CI 0. 75-1. 01]; p=0.073]). There was no evidence for a difference in treatment effects for the primary endpoint across prespecified subgroups of acute coronary syndromes and stable coronary artery disease (p=0.93). Grade 3 or 5 bleeding occurred in 163 participants in the experimental group and 169 in the control group (2.04% vs 2.12%; rate ratio 0.97 [95% CI 0. 78-1. 20]; p=0.77). Interpretation Ticagrelor in combination with aspirin for 1 month followed by ticagrelor alone for 23 months was not superior to 12 months of standard dual antiplatelet therapy followed by 12 months of aspirin alone in the prevention of all-cause mortality or new Q-wave myocardial infarction 2 years after percutaneous coronary intervention. Copright (C) 2018 Elsevier Ltd. All rights reserved. European Clinical Research Institute; Biosensors International; AstraZeneca; Medicines Company; Canada Research Chairs Programme

Published
2018

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