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CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation.
Musik und Dichtung sind spätestens seit dem Hohelied Salomos und den bacchantischen Hymnen an Dionysos engstens verbunden. Der gregorianische Gesang des Mittelalters benutzte die lateinischen Texte der Liturgie, Liedkomponisten seit Schubert nehmen ihre Libretti von literarischen Texten her, und Debussys Prélude à l'après-midi d'un faune setzt eine Bekanntschaft mit Mallarmés Gedicht voraus. Die Form der Sonate unterliegt Thomas Manns 'Tonio Kröger' (1903) sowie auch Hermann Hesses 'Der Steppenwolf' (1927), und andere musikalische Formen werden häufig mit raffinierter Bewusstheit angewendet, wie etwa in Robert Pingets 'Passacaille' (1969), Herbert Rosendorfers 'Deutsche Suite' (1972) oder Anthony Burgess' 'Napoleon Symphony' (1974). Thomas Bernhard in 'Der Untergeher' (1983) sowie französische, englische, und amerikanische Schriftsteller derselben Jahre nahmen Bachs Goldberg Variationen als Grundlage für Thema und/oder Struktur ihrer Romane. Und mehrere Komponisten haben versucht, die Musikstücke, die in Thomas Manns 'Doktor Faustus' (1947) so ausführlich beschrieben werden, zu realisieren. So verwundert es kaum, wenn gewisse Motive, die mit der Musik eng verwoben sind auch in Dichtungen auftauchen.
Drei Wellen der Bach-Begeisterung lassen sich seit Mitte des 20. Jahrhunderts deutlich unterscheiden. In der dritten Welle der Bachbegeisterung, erschienen im Jahr 2000 neben der maßgeblichen Biographie des Musikwissenschaftlers Christoph Wolff auch solche popularisierenden Lebensdarstellungen wie Malte Korffs 'Johann Sebastian Bach' in der Reihe DTVPortraits oder RuthAnn Ridleys Roman 'Bach's Passion' (1999), in der Bachs 'Leidenschaften' - vor allem sexuell und religiös - die Hauptrolle spielen. In 'Evening in the Palace of Reason' (2005) präsentiert James R. Gaines eine faszinierende und gut informierte Doppelbiographie von Bach und Friedrich II., die in der Begegnung der beiden Aufklärungs-Genies 1747 in Potsdam und der Komposition von Bachs Musikalischem Opfer kulminiert. (Bereits 2003 wurde im Schweizer Film 'Mein Name ist Bach' [Regie von Dominique de Rivaz] dieselbe Begegnung unter Betonung des sexuellen Lebens beider Männer dargestellt.) Der große Dirigent John Eliot Gardiner lokalisierte seinen Bach (2013) im Kontext der Familie Bach, seiner Altersgenossen Scarlatti und Händel, sowie der gesellschaftlichen und musikalischen Kultur des Jahrhunderts und diskutierte vor allem seine Vokalwerke mit einer Einsicht, die sich nur nach Jahren der persönlichen Praxis und Erfahrung ergibt.
Die literarischen Werke dieser dritten Welle, die nun genauer betrachtet werden sollen, lassen sich wiederum in drei Gruppen unterteilen, von denen die erste und dritte eine theologische Dimension aufweisen, die sich von der rein strukturellen Verwendung von Bachs Goldberg Variationen wie sie sich in der zweiten Welle finden ließ, differenziert.
Das Licht gilt uns als "das" Signum von Humanität, Aufklärung, Erkenntnis und Fortschritt, aber im Theater "übersehen" wir das Licht meist oder reduzieren seinen Einsatz auf eine technische Dienstleistung, die mit "hoher Kunst" scheinbar nichts zu tun hat. Woher kommt das? Und welche Gründe sprechen dafür, dem Licht im Theater mehr Aufmerksamkeit zu schenken, als es viele Zuschauer, Theaterwissenschaftler und Theaterschaffende derzeit tun? Antworten lassen sich unter anderem bei Michel Foucault, Friedrich Schiller und Adolphe Appia finden.
Using the MAXENT algorithm, we developed risk maps for eight invasive plant species in southern Transylvania, Romania, a region undergoing drastic land-use changes. Our findings show that invasion risk increased with landscape heterogeneity. Roads and agricultural areas were most prone to invasion, whereas forests were least at risk.
Seed production varies from year-to-year in most species. Factors influencing this variation can include pollination and dispersal mechanisms, seed predation and resource availability. Here we examine a long-term (12– year) photographic record of seed cone production for the Australian endemic conifer Wollemia nobilis (Araucariaceae). Coefficient of variation (a commonly used measure of variation in seed production) was low for the two trees analysed, compared with published values for other polycarpic plants. Nevertheless, cone production decreased with increasing spring minimum temperatures (during pollination) and increased with summer total rainfall (during cone initiation). Hence, Wollemia nobilis cone production was correlated with weather, in line with the resource-matching hypothesis. Impacts of variation in cone production on the Wollemia nobilis population are likely to be buffered by the shade-tolerant, slow-growing juvenile life stage of Wollemia nobilis.
The advent of improved experimental and theoretical techniques has brought a lot of attention to the electric dipole (E1) response of atomic nuclei in the last decade. The extensive studies have led to the observation and interpretation of a concentration of E1 strength energetically below the Giant Dipole Resonance in many nuclei. This phenomenon is commonly denoted as Pygmy Dipole Resonance (PDR). This contribution will summarize the most important results obtained using different experimental probes, define the challenges to gain a deeper understanding of the excitations, and discuss the newest experimental developments.
Proton-pumping complex I of the mitochondrial respiratory chain is among the largest and most complex membrane protein complexes. The enzyme contributes substantially to oxidative energy-conversion in eukaryotic cells. Its malfunctions are implicated in many hereditary and degenerative disorders. Here, we report the X-ray structure of mitochondrial complex I at 3.6- 3.9 Å resolution describing in detail the central subunits that execute the bioenergetic function. A continuous axis of basic and acidic residues running centrally through the membrane arm connects the ubiquinone reduction site in the hydrophilic arm to four putative proton-pumping units. The binding position for a substrate analogous inhibitor and blockage of the predicted ubiquinone binding site provide a model for the ‘deactive’ form of the enzyme. The proposed transition into the active form is based on a concerted structural rearrangement at the ubiquinone reduction site rendering support for a two-state stabilization-change mechanism of protonpumping.
We investigate charmonium production in Pb + Pb collisions at LHC beam energy Elab=2.76A TeV at fixed-target experiment (√sNN = 72 GeV). In the frame of a transport approach including cold and hot nuclear matter effects on charmonium evolution, we focus on the antishadowing effect on the nuclear modification factors RAA and rAA for the J/ψ yield and transverse momentum. The yield is more suppressed at less forward rapidity (ylab ≃ 2) than that at very forward rapidity (ylab ≃ 4) due to the shadowing and antishadowing in different rapidity bins.
"Die Strahlen der Sonne vertreiben die Nacht" : Licht und Schatten im (Musik-)Theater der Vormoderne
(2015)
Bis zur Mitte des 18. Jahrhunderts waren Akteure und Zuschauer in einem geschlossenen Theaterraum gleich stark beleuchtet, wenn auch nur mit Kerzen und Öllampen. Erst danach geriet die Bühne – nicht ohne Protest der Besucher – ins Zentrum der Beleuchtung. Auf der Opernbühne führte der Einsatz der Kohlenbogenlampe, auch "Prophetensonne" genannt, im 19. Jahrhundert zu einem radikalen Umbruch: Endlich konnten Übergänge vom Dunkel zum Licht musikalisch und szenisch realisiert werden.