Sonderforschungsbereiche / Forschungskollegs
Refine
Year of publication
Document Type
- Article (112)
- Review (17)
- Part of a Book (2)
- Book (1)
- Conference Proceeding (1)
Has Fulltext
- yes (133)
Is part of the Bibliography
- no (133)
Keywords
- inflammation (8)
- macrophage (6)
- Biophysical chemistry (4)
- macrophage polarization (4)
- rna (4)
- Macrophages (3)
- Membrane proteins (3)
- RNA (3)
- cancer (3)
- mitochondria (3)
Institute
- Sonderforschungsbereiche / Forschungskollegs (133)
- Medizin (57)
- Biochemie und Chemie (48)
- Exzellenzcluster Makromolekulare Komplexe (31)
- Zentrum für Biomolekulare Magnetische Resonanz (BMRZ) (25)
- Exzellenzcluster Die Herausbildung normativer Ordnungen (10)
- Geschichtswissenschaften (9)
- Center for Membrane Proteomics (CMP) (8)
- Biowissenschaften (7)
- Kulturwissenschaften (7)
Für die Erforschung der spätantiken Herrscherideologie hat Andreas Alföldi (1895-1981) Grundlegendes geleistet. Ihm gelang es, bildliche Darstellungen zum Sprechen zu bringen und ihre Bedeutung für die Repräsentation der Kaiser zu verdeutlichen. In dieser Tradition bewegt sich der Tübinger Althistoriker (und zeitweilige Assistent Alföldis) Frank Kolb mit seinem hier anzuzeigenden Buch. Darin führt er die verstreuten, von verschiedenen altertumswissenschaftlichen Disziplinen vorangetriebenen Forschungen zur spätantiken Herrscherideologie zusammen, die er durch eigene Beiträge wesentlich beeinflußt hat. ...
Es war eine heißer, schwüler Sommerabend, als John Rawls im Hörsaal H der Frankfurter Universität einen Vortrag hielt. Er sprach leise, fast schleppend, und er hatte sich vorgenommen, den Text in einer deutschen Übersetzung vorzulesen, was für einen amerikanischen Professor ungewöhnlich war und deshalb Bewunderung verdiente. Doch war die angespannte Konzentration spürbar, die Rawls aufbringen musste, um deutscheWorte mit so wenig amerikanischer Phonetik wiemöglich zu sprechen, und der Vortrag wurde dadurch noch langsamer, die Stimme noch leiser. Außerdem funktionierte das Mikrofon nicht richtig. Deshalb wurde es ihm von seinem Übersetzer, Wilfried Hinsch, mit ausgestrecktem Arm so nahe an denMund gehalten, dass wenigstens ein paar Worte zu verstehen waren. Nach kurzer Zeit verließen die ersten Zuhörer den Hörsaal. Der ausgestreckte Arm des Helfers wurde sichtbar schwerer; Anstrengung und Hitze ließen Schweißbäche rinnen und das Oberhemd nass werden.Der Vortragwar nicht einfach. Rawls machte, wie gewohnt, keinerlei Konzessionen, sondern diktierte einen komplexen Satz nach dem anderen. Wer etwas verstehen wollte, musste von der komischen Situation absehen, alle Kräfte gegen die von der schwülen Hitze geführten Ermüdungsattacken aufbieten und sich irgendwie konzentrieren. Der einzige, der sich davon nicht beirren ließ, sondern hartnäckig Satz für Satz in den schwülen Sommerabend hämmerte, war der kleine, schmächtige, blasse, sein Gesicht hinter einer riesigen Brille verbergende, aber Respekt heischende Professor Rawls. Wenn Geist so unmittelbar präsent ist, wird eben alles andere banal. ...
Zeichen der Herrschaftsausübung, der Gerichtsbarkeit und der Marktfreiheit, öffentlich angebrachte Maße und Gewichte zur Kontrolle des Wirtschaftslebens, mittelalterliche und frühneuzeitliche Gerichtsstätten, Orte und Gegenstände des Strafvollzugs, die der Rechtshistoriker Karl Frölich in den dreißiger bis fünfziger Jahren des 20. Jahrhunderts auf große Glasplatten gebannt hat, berichten anschaulich von der Rechtsausübung vergangener Epochen, indem sie "Sachzeugen des Rechtslebens" abbilden. Die Platten dieser umfangreichen Fotosammlung werden derzeit durch die Bibliothek des Max- Planck-Instituts für europäische Rechtsgeschichte eingescannt, um die Bilder der Forschung zu erhalten und zur Verfügung zu stellen. Ein Teil der "Sammlung Frölich" befindet sich heute in der Obhut von Prof. Dr. Gerhard Dilcher, Frankfurt am Main. Ein weiterer, größerer Teil, ist nach München ins Leopold-Wenger-Institut gelangt (Prof. Dr. Hermann Nehlsen); auch diese Bilder werden nun durch Scannen mit der "Frankfurter Partie" virtuell zusammengeführt. ...
Die Podiumsdiskussion fand als öffentliche Abendveranstaltung im Rahmen des sozialwissenschaftlichen Workshops "Krise der 'Arbeitsgesellschaft' - Transformation zur 'Grundeinkommensgesellschaft'? Diskurse, Deutungsmuster und Habitusformen im Wandel" statt, der vom 14. bis 15. Juli 2006 an der Goethe-Universität in Frankfurt am Main abgehalten wurde. Veranstalter war das soziologische Forschungsprojekt "Praxis als Erzeugungsquelle von Wissen" (Leiter: Prof. Dr. Ulrich Oevermann) im Forschungskolleg und Sonderforschungsbereich 435 "Wissenskultur und gesellschaftlicher Wandel" der Deutschen Forschungsgemeinschaft an der Goethe-Universität Frankfurt am Main. Initiiert und organisiert wurde der Workshop von Manuel Franzmann mit Unterstützung zahlreicher Kollegen und Förderer.
Oral presentations Background: We selected peptide ligands for the HIV-1 packaging signal PSI by screening phage displayed peptide libraries. Peptide ligands were optimized by screening spot synthesis peptide membranes. The aim of this study is the functional characterization of these peptide ligands with respect to inhibition of HIV-1 replication. Methods: Phage displayed peptide libraries were screened with PSI-RNA structures. The Trp-rich peptide motifs were optimized for specific binding on spot synthesis peptide membranes. The best binding peptide was expressed intracellularly in fusion with RFP or linked to a protein transduction domain (PTD) for intracellular delivery. The effects on virion production were analyzed using pseudotyped lentiviral particles. Results: After positive and negative selection rounds, phages binding specifically to PSI-RNA were identified by ELISA. Peptide inserts contained conserved motifs of aromatic amino acids known to be implicated in binding of PSI-RNA by the natural Gag ligand. The filter assay identified HKWPWW as the best binding ligand for PSI-RNA, which is delivered into several cell lines by addition of a PTD. Compared to a control peptide, the HKWPWW peptide inhibited HIV-1 replication as deduced from reduced titers of culture supernatants. As HKWPWW also binds to the TAR-RNA like the natural nucleocapsid PSI-RNA ligand, the effect on Tat-TAR inhibition will also be analyzed. Currently T-cell lines are established which stably express HKWPWW as well as a control peptide, which will be infected with HIV-1 to monitor the ability of HKWPWW to inhibit wild type HIV-1 replication. Conclusion: The selection of a peptide ligand for PSI-RNA able to inhibit HIV-1 replication proves the suitability of the phage display technology for the selection of peptides binding to RNA-structures. This enables the indentification of peptides serving as leads to interfere with additional targets in the HIV-1 replication cycle.
Ribosomal proteins are assumed to stabilize specific RNA structures and promote compact folding of the large rRNA. The conformational dynamics of the protein between the bound and unbound state play an important role in the binding process. We have studied those dynamical changes in detail for the highly conserved complex between the ribosomal protein L11 and the GTPase region of 23S rRNA. The RNA domain is compactly folded into a well defined tertiary structure, which is further stabilized by the association with the C-terminal domain of the L11 protein (L11ctd). In addition, the N-terminal domain of L11 (L11ntd) is implicated in the binding of the natural thiazole antibiotic thiostrepton, which disrupts the elongation factor function. We have studied the conformation of the ribosomal protein and its dynamics by NMR in the unbound state, the RNA bound state and in the ternary complex with the RNA and thiostrepton. Our data reveal a rearrangement of the L11ntd, placing it closer to the RNA after binding of thiostrepton, which may prevent binding of elongation factors. We propose a model for the ternary L11–RNA–thiostrepton complex that is additionally based on interaction data and conformational information of the L11 protein. The model is consistent with earlier findings and provides an explanation for the role of L11ntd in elongation factor binding.
Metal-ion binding and metal-ion induced folding of the adenine-sensing riboswitch aptamer domain
(2007)
Divalent cations are important in the folding and stabilization of complex RNA structures. The adenine-sensing riboswitch controls the expression of mRNAs for proteins involved in purine metabolism by directly sensing intracellular adenine levels. Adenine binds with high affinity and specificity to the ligand binding or aptamer domain of the adenine-sensing riboswitch. The X-ray structure of this domain in complex with adenine revealed an intricate RNA-fold consisting of a three-helix junction stabilized by long-range base-pairing interactions and identified five binding sites for hexahydrated Mg2+-ions. Furthermore, a role for Mg2+-ions in the ligand-induced folding of this RNA was suggested. Here, we describe the interaction of divalent cations with the RNA–adenine complex in solution as studied by high-resolution NMR spectroscopy. Paramagnetic line broadening, chemical shift mapping and intermolecular nuclear Overhauser effects (NOEs) indicate the presence of at least three binding sites for divalent cations. Two of them are similar to those in the X-ray structure. The third site, which is important for the folding of this RNA, has not been observed previously. The ligand-free state of the RNA is conformationally heterogeneous and contains base-pairing patterns detrimental to ligand binding in the absence of Mg2+, but becomes partially pre-organized for ligand binding in the presence of Mg2+. Compared to the highly similar guanine-sensing riboswitch, the folding pathway for the adenine-sensing riboswitch aptamer domain is more complex and the influence of Mg2+ is more pronounced.
In a combined NMR/MD study, the temperature-dependent changes in the conformation of two members of the RNA YNMG-tetraloop motif (cUUCGg and uCACGg) have been investigated at temperatures of 298, 317 and 325 K. The two members have considerable different thermal stability and biological functions. In order to address these differences, the combined NMR/MD study was performed. The large temperature range represents a challenge for both, NMR relaxation analysis (consistent choice of effective bond length and CSA parameter) and all-atom MD simulation with explicit solvent (necessity to rescale the temperature). A convincing agreement of experiment and theory is found. Employing a principle component analysis of the MD trajectories, the conformational distribution of both hairpins at various temperatures is investigated. The ground state conformation and dynamics of the two tetraloops are indeed found to be very similar. Furthermore, both systems are initially destabilized by a loss of the stacking interactions between the first and the third nucleobase in the loop region. While the global fold is still preserved, this initiation of unfolding is already observed at 317 K for the uCACGg hairpin but at a significantly higher temperature for the cUUCGg hairpin.
Introduction: Immune paralysis with massive T-cell apoptosis is a central pathogenic event during sepsis and correlates with septic patient mortality. Previous observations implied a crucial role of peroxisome proliferator-activated receptor gamma (PPARγ) during T-cell apoptosis.
Methods: To elucidate mechanisms of PPARγ-induced T-cell depletion, we used an endotoxin model as well as the caecal ligation and puncture sepsis model to imitate septic conditions in wild-type versus conditional PPARγ knockout (KO) mice.
Results: PPARγ KO mice showed a marked survival advantage compared with control mice. Their T cells were substantially protected against sepsis-induced death and showed a significantly higher expression of the pro-survival factor IL-2. Since PPARγ is described to repress nuclear factor of activated T cells (NFAT) transactivation and concomitant IL-2 expression, we propose inhibition of NFAT as the underlying mechanism allowing T-cell apoptosis. Corroborating our hypothesis, we observed up-regulation of the pro-apoptotic protein BIM and downregulation of the anti-apoptotic protein Bcl-2 in control mice, which are downstream effector proteins of IL-2 receptor signaling. Application of a neutralizing anti-IL-2 antibody reversed the pro-survival effect of PPARγ-deficient T cells and confirmed IL-2-dependent apoptosis during sepsis.
Conclusion: Apparently antagonizing PPARγ in T cells might improve their survival during sepsis, which concomitantly enhances defence mechanisms and possibly provokes an increased survival of septic patients.