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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.
Previously, [1,3]dioxolo[4,5-f][1,3]benzodioxole (DBD)-based fluorophores used as highly sensitive fluorescence lifetime probes reporting on their microenvironmental polarity have been described. Now, a new generation of DBD dyes has been developed. Although they are still sensitive to polarity, in contrast to the former DBD dyes, they have extraordinary spectroscopic properties even in aqueous surroundings. They are characterized by long fluorescence lifetimes (10-20ns), large Stokes shifts (approximate to 100nm), high photostabilities, and high quantum yields (>0.56). Here, the spectroscopic properties and synthesis of functionalized derivatives for labeling biological targets are described. Furthermore, thio-reactive maleimido derivatives of both DBD generations show strong intramolecular fluorescence quenching. This mechanism has been investigated and is found to undergo a photoelectron transfer (PET) process. After reaction with a thiol group, this fluorescence quenching is prevented, indicating successful bonding. Being sensitive to their environmental polarity, these compounds have been used as powerful fluorescence lifetime probes for the investigation of conformational changes in the maltose ATP-binding cassette transporter through fluorescence lifetime spectroscopy. The differing tendencies of the fluorescence lifetime change for both DBD dye generations promote their combination as a powerful toolkit for studying microenvironments in proteins.
The majority of cases of community-acquired pneumonia are caused by Streptococcus pneumoniae and most studies on pneumococcal host interaction are based on cell culture or animal experiments. Thus, little is known about infections in human lung tissue.
Cyclooxygenase-2 and its metabolites play an important regulatory role in lung inflammation. Therefore, we established a pneumococcal infection model on human lung tissue demonstrating mitogen-activated protein kinase (MAPK)-dependent induction of cyclooxygenase-2 and its related metabolites.
In addition to alveolar macrophages and the vascular endothelium, cyclooxygenase-2 was upregulated in alveolar type II but not type I epithelial cells, which was confirmed in lungs of patients suffering from acute pneumonia. Moreover, we demonstrated the expression profile of all four E prostanoid receptors at the mRNA level and showed functionality of the E prostanoid(4) receptor by cyclic adenosine monophosphate production. Additionally, in comparison to previous studies, cyclooxygenase-2/prostaglandin E-2 related pro- and anti-inflammatory mediator regulation was partly confirmed in human lung tissue after pneumococcal infection.
Overall, cell type-specific and MAPK-dependent cyclooxygenase-2 expression and prostaglandin E-2 formation in human lung tissue may play an important role in the early phase of pneumococcal infections.
Aus dem Inhalt dieser Ausgabe: BEITRÄGE: Hanna Sonkajärvi: Soldaten als Fremde in Straßburg im 18. Jahrhundert, Jörg Rogge: Das Kriegswesen im späten Mittelalter und seine Erforschung: neuere englische und deutsche Arbeiten zu Krieg, Staat und Gesellschaft, PROJEKTE: Shin Demura: Allso hiebe der innere krieg schon an, der vil Erger dann der eüssere war : die Stadt als Zufluchtsort für Flüchtlinge : Erfahrungsformen des Dreißigjährigen Krieges in der Reichsstadt Ulm und ihrer Region, Robby Fichte: Zur Entwicklungsgeschichte des öffentlich-rechtlichen Vertrages anhand der Begründung des Militärdienstverhältnisses 1650-1914, Urte Christine Allkämper: Die Braut des Soldaten : symbolische Kommunikation mit der Waffe von der Frühen Neuzeit bis zur Gegenwart, Anuschka Tischer: Offizielle Kriegsbegründungen in der frühen Neuzeit - Funktionen, Formen, Inhalte, Thomas Wollschläger: Die Military Revolution und der deutsche Territorialstaat unter besonderer Berücksichtigung Brandenburg-Preußens und Sachsens : Determinanten der Staatskonsolidierung im europäischen Kontext 1670-1740, BERICHTE: Reiner Prass: Tagungsbericht Gewalt in der Frühen Neuzeit : 5. Tagung der Arbeitsgemeinschaft Frühe Neuzeit vom 18. bis 20. September 2003 an der Freien Universität Berlin, Andreas Helmedach, Thomas Kubetzky, Heidi Mehrkens: Tilly ist nur eine Chiffre, die es aufzulösen gilt ... - Jahrestagung des Arbeitskreises Militärgeschichte: Soldat und Gesellschaft : Biographien und Selbstzeugnisse in der Militärgeschichte 10.-11. Oktober 2003, Thomas Kater: Bericht über die Jahrestagung des Arbeitskreises Historische Friedensforschung : Der Friede ist keine leere Idee ... - Bilder und Vorstellungen vom Frieden im langen 19. Jahrhundert, 31.10. bis 2.11.2003, Stiftung Adam von Trott, Imshausen, Jan Marco Sawilla: Religion und Krieg - Bericht über die Hamburger Gespräche zur Geschichtswissenschaft (V III.) WS 2003/ 2004, Dorit Schneider: Kriegsbegründungen in der Geschichte. Strategien der Legitimierung und Legalisierung militärischer Gewalt - 30.-31.01.2004, Deutscher Bundestag, Berlin, REZENSIONEN: Ellen Ueberschär: Das Strafgericht Gottes : Kriegserfahrungen und Religion im Heiligen Römischen Reich Deutscher Nation im Zeitalter des Dreißigjährigen Krieges, hrsg. von Matthias Asche und Anton Schindling, Münster 2001, Jürgen Angelow: Jutta Nowosadtko: Krieg, Gewalt und Ordnung : Einführung in die Militärgeschichte, Tübingen 2002, Jörg Muth: John A. Lynn: Battle - A History of Combat and Culture from Ancient Greece to Modern Amerika, Boulder 2003, Heinrich Lang: Del Treppo, Mario (H g.): Condottieri e uomini d arme nell Italia del Rinascimento. Acura e con un saggio introduttivo di Mario Del Treppo, Napoli 2001, Stefan Kroll: Jörg Muth, Flucht aus dem militärischen Alltag : Ursachen und individuelle Ausprägung der Desertion in der Armee Friedrichs des Großen. Mit besonderer Berücksichtigung der Infanterie-Regimenter der Potsdamer Garnison, Freiburg i. Br. 2003, ANKÜNDIGUNGEN: Bernhard R. Kroener, Ralf Pröve: Tempi passati! Der Arbeitskreis Militär und Gesellschaft in der Frühen Neuzeit : ein Zwischenbericht nach einem Jahrzehnt, Mitgliederversammlung 2004, AMG-Tagung 2007, Cecilie Hollberg: Glaube & Macht : Sachsen im Europa der Reformationszeit ; die 2. Sächsische Landesausstellung ; die Schlacht bei Mühlberg : Ausgang und Folgen
Degradable polymers with a tailorable degradation rate might be promising candidate materials for biomaterial-based cartilage repair. In view of the poor intrinsic healing capability of cartilage, implantation of autologous chondrocytes seeded on a biocompatible slow degrading polymer might be an encouraging approach to improve cartilage repair in the future. This study was undertaken to test if the fiber orientation (random versus aligned) of two different degradable polymers and a polymer intended for long term applications could influence primary articular chondrocytes growth and ultrastructure.
A degradable copoly(ether) esterurethane (PDC) was synthesized via co-condensation of poly(p-dioxanone) diol and poly(epsilon-caprolactone) diol using an aliphatic diisocyanate as linker. Poly(p-dioxanone) (PPDO) was applied as commercially available degradable polymer, while polyetherimide (PEI) was chosen as biomaterial enabling surface functionalization. The fibrous scaffolds of PDC and PPDO were obtained by electrospinning using 1,1,1,3,3,3 hexafluoro-2-propanol (HFP), while for PEI dimethyl acetamide (DMAc) was applied as solvent. Primary porcine articular chondrocytes were seeded at different cell densities on the fibrous polymer scaffolds and analyzed for viability (fluorescein diacetate/ethidiumbromide staining), for type II collagen synthesis (immunolabelling), ultrastructure and orientation on the fibers (SEM: scanning electron microscopy).
Vital chondrocytes adhered on all electrospun scaffolds irrespective of random and aligned topologies. In addition, the chondrocytes produced the cartilage-specific type II collagen on all tested polymer topologies suggesting their differentiated functions. SEM revealed an almost flattened chondrocytes shape on scaffolds with random fiber orientation: whereby chondrocytes growth remained mainly restricted to the scaffold surface. On aligned fibers the chondrocytes exhibited a more spindle-shaped morphology with rougher cell surfaces but only a minority of the cells aligned according to the fibers. As a next step the reduction of the fiber diameter of electrospun scaffolds should be addressed as an important parameter to mimic cartilage ECM structure.
The article describes the surface modification of 3D printed poly(lactic acid) (PLA) scaffolds with calcium phosphate (CP)/gelatin and CP/chitosan hybrid coating layers. The presence of gelatin or chitosan significantly enhances CP co-deposition and adhesion of the mineral layer on the PLA scaffolds. The hydrogel/CP coating layers are fairly thick and the mineral is a mixture of brushite, octacalcium phosphate, and hydroxyapatite. Mineral formation is uniform throughout the printed architectures and all steps (printing, hydrogel deposition, and mineralization) are in principle amenable to automatization. Overall, the process reported here therefore has a high application potential for the controlled synthesis of biomimetic coatings on polymeric biomaterials.
The article describes the surface modification of 3D printed poly(lactic acid) (PLA) scaffolds with calcium phosphate (CP)/gelatin and CP/chitosan hybrid coating layers. The presence of gelatin or chitosan significantly enhances CP co-deposition and adhesion of the mineral layer on the PLA scaffolds. The hydrogel/CP coating layers are fairly thick and the mineral is a mixture of brushite, octacalcium phosphate, and hydroxyapatite. Mineral formation is uniform throughout the printed architectures and all steps (printing, hydrogel deposition, and mineralization) are in principle amenable to automatization. Overall, the process reported here therefore has a high application potential for the controlled synthesis of biomimetic coatings on polymeric biomaterials.
The article describes a systematic investigation of the effects of an aqueous NaOH treatment of 3D printed poly(lactic acid) (PLA) scaffolds for surface activation. The PLA surface undergoes several morphology changes and after an initial surface roughening, the surface becomes smoother again before the material dissolves. Erosion rates and surface morphologies can be controlled by the treatment. At the same time, the bulk mechanical properties of the treated materials remain unaltered. This indicates that NaOH treatment of 3D printed PLA scaffolds is a simple, yet viable strategy for surface activation without compromising the mechanical stability of PLA scaffolds.
The article describes a systematic investigation of the effects of an aqueous NaOH treatment of 3D printed poly(lactic acid) (PLA) scaffolds for surface activation. The PLA surface undergoes several morphology changes and after an initial surface roughening, the surface becomes smoother again before the material dissolves. Erosion rates and surface morphologies can be controlled by the treatment. At the same time, the bulk mechanical properties of the treated materials remain unaltered. This indicates that NaOH treatment of 3D printed PLA scaffolds is a simple, yet viable strategy for surface activation without compromising the mechanical stability of PLA scaffolds.
The article describes a systematic investigation of the effects of an aqueous NaOH treatment of 3D printed poly(lactic acid) (PLA) scaffolds for surface activation. The PLA surface undergoes several morphology changes and after an initial surface roughening, the surface becomes smoother again before the material dissolves. Erosion rates and surface morphologies can be controlled by the treatment. At the same time, the bulk mechanical properties of the treated materials remain unaltered. This indicates that NaOH treatment of 3D printed PLA scaffolds is a simple, yet viable strategy for surface activation without compromising the mechanical stability of PLA scaffolds.