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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.
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.
Prokaryotic solute binding protein-dependent ATP-binding cassette import systems are divided into type land type II and mechanistic differences in the transport process going along with this classification are under intensive investigation. Little is known about the conformational dynamics during the catalytic cycle especially concerning the transmembrane domains. The type I transporter for positively charged amino acids from Salmonella enterica serovar Typhimurium (1A0-Hi5QMP2) was studied by limited proteolysis in detergent solution in the absence and presence of co-factors including ATP, ADP, LAO/arginine, and Mg2+ ions. Stable peptide fragments could be obtained and differentially susceptible cleavage sites were determined by mass spectrometry as Lys-258 in the nucleotide-binding subunit, HisP, and Arg-217/Arg-218 in the transmembrane subunit, HisQ In contrast, transmembrane subunit HisM was gradually degraded but no stable fragment could be detected. HisP and HisQ were equally resistant under pre- and post-hydrolysis conditions in the presence of arginine-loaded solute-binding protein LAO and ATP/ADP. Some protection was also observed with LAO/arginine alone, thus reflecting binding to the transporter in the apo-state and transmembrane signaling. Comparable digestion patterns were obtained with the transporter reconstituted into proteoliposomes and nanodiscs. Fluorescence lifetime spectroscopy confirmed the change of HisQ(R218) to a more apolar microenvironment upon ATP binding and hydrolysis. Limited proteolysis was subsequently used as a tool to study the consequences of mutations on the transport cycle. Together, our data suggest similar conformational changes during the transport cycle as described for the maltose ABC transporter of Escherichia coli, despite distinct structural differences between both systems.
Throughfall, that is, the fraction of rainfall that passes through the forest canopy, is strongly influenced by rainfall and forest stand characteristics which are in turn both subject to seasonal dynamics. Disentangling the complex interplay of these controls is challenging, and only possible with long-term monitoring and a large number of throughfall events measured in parallel at different forest stands. We therefore based our analysis on 346 rainfall events across six different forest stands at the long-term terrestrial environmental observatory TERENO Northeast Germany. These forest stands included pure stands of beech, pine and young pine, and mixed stands of oak-beech, pine-beech and pine-oak-beech. Throughfall was overall relatively low, with 54-68% of incident rainfall in summer. Based on the large number of events it was possible to not only investigate mean or cumulative throughfall but also its statistical distribution. The distributions of throughfall fractions show distinct differences between the three types of forest stands (deciduous, mixed and pine). The distributions of the deciduous stands have a pronounced peak at low throughfall fractions and a secondary peak at high fractions in summer, as well as a pronounced peak at higher throughfall fractions in winter. Interestingly, the mixed stands behave like deciduous stands in summer and like pine stands in winter: their summer distributions are similar to the deciduous stands but the winter peak at high throughfall fractions is much less pronounced. The seasonal comparison further revealed that the wooden components and the leaves behaved differently in their throughfall response to incident rainfall, especially at higher rainfall intensities. These results are of interest for estimating forest water budgets and in the context of hydrological and land surface modelling where poor simulation of throughfall would adversely impact estimates of evaporative recycling and water availability for vegetation and runoff.
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.
Reflexion ist eine Schlüsselkategorie für die professionelle Entwicklung von Lehrkräften, welche als Ausbildungsziel in den Bildungsstandards für die Lehrkräftebildung verankert ist. Eine Verstetigung universitär geprägter Forschung und Modellierung in der praxisnahen Anwendung im schulischen Kontext bietet Potentiale nachhaltiger Professionalisierung. Die Stärkung reflexionsbezogener Kompetenzen durch Empirie und Anwendung scheint eine phasenübergreifende Herausforderung der Lehrkräftebildung zu sein, die es zu bewältigen gilt. Ziele des Tagungsbandes Reflexion in der Lehrkräftebildung sind eine theoretische Schärfung des Konzeptes „Reflexive Professionalisierung“ und der Austausch über Fragen der Einbettung wirksamer reflexionsbezogener Lerngelegenheiten in die Lehrkräftebildung. Forschende und Lehrende der‚ drei Phasen (Studium, Referendariat sowie Fort- und Weiterbildung) der Lehrkräftebildung stellen Lehrkonzepte und Forschungsprojekte zum Thema Reflexion in der Lehrkräftebildung vor und diskutieren diese. Gemeinsam mit Teilnehmenden aller Phasen und von verschiedenen Standorten der Lehrkräftebildung werden zukünftige Herausforderungen identifiziert und Lösungsansätze herausgearbeitet.
Transmission of measles virus (MV) from dendritic to airway epithelial cells is considered as crucial to viral spread late in infection. Therefore, pathways and effectors governing this process are promising targets for intervention. To identify these, we established a 3D respiratory tract model where MV transmission by infected dendritic cells (DCs) relied on the presence of nectin-4 on H358 lung epithelial cells. Access to recipient cells is an important prerequisite for transmission, and we therefore analyzed migration of MV-exposed DC cultures within the model. Surprisingly, enhanced motility toward the epithelial layer was observed for MV-infected DCs as compared to their uninfected siblings. This occurred independently of factors released from H358 cells indicating that MV infection triggered cytoskeletal remodeling associated with DC polarization enforced velocity. Accordingly, the latter was also observed for MV-infected DCs in collagen matrices and was particularly sensitive to ROCK inhibition indicating infected DCs preferentially employed the amoeboid migration mode. This was also implicated by loss of podosomes and reduced filopodial activity both of which were retained in MV-exposed uninfected DCs. Evidently, sphingosine kinase (SphK) and sphingosine-1-phosphate (S1P) as produced in response to virus-infection in DCs contributed to enhanced velocity because this was abrogated upon inhibition of sphingosine kinase activity. These findings indicate that MV infection promotes a push-and-squeeze fast amoeboid migration mode via the SphK/S1P system characterized by loss of filopodia and podosome dissolution. Consequently, this enables rapid trafficking of virus toward epithelial cells during viral exit.
Das 12. Herbsttreffen Patholinguistik mit dem Schwerpunktthema »Weg(e) mit dem Stottern: Therapie und Selbsthilfe für Kinder und Erwachsene« fand am 24.11.2018 in Potsdam statt. Das Herbsttreffen wird seit 2007 jährlich vom Verband für Patholinguistik e.V. (vpl) durchgeführt. Der vorliegende Tagungsband beinhaltet die Vorträge zum Schwerpunktthema sowie Beiträge der Posterpräsentationen zu weiteren Themen aus der sprachtherapeutischen Forschung und Praxis.
An der Universität Potsdam wurden im Rahmen des Qualitätspakt Lehre-Projekts „Qualität etablieren in Lehre und Lernen (QueLL)“ Maßnahmen für eine Verbesserung der Studienbedingungen und eine Weiterentwicklung der Lehre und des Lernens durchgeführt. Die während der neunjährigen Projektlaufzeit thematisierten Fragestellungen, erarbeiteten Lösungsansätze und entsprechenden Erfahrungen werden im vorliegenden Sammelband in Form von wissenschaftlichen Auseinandersetzungen und Werkstattberichten dargestellt und diskutiert.
Die Beiträge spiegeln in ihrer thematischen Vielfalt unterschiedliche universitäre Übergangsphasen wider, wie in diesem Fall den Übergang in die Hochschule, Übergänge innerhalb der Hochschule (im Kontext der Organisationsentwicklung, der Weiterbildung akademischer Statusgruppen oder der Entwicklung einer digitalen Lehr-Lernkultur) und schließlich den Übergang in die Berufspraxis. Denn während der Projektlaufzeit hat sich gezeigt, dass die Gestaltung von Lehre und Lernen letztlich immer eine Gestaltung solcher Übergänge ist: sowohl zwischen den innerinstitutionellen Ebenen und Bereichen als auch zwischen Akteur/innen der Hochschule und schließlich ebenso innerhalb des Student Life Cycle. Weiterhin wird anhand der Beiträge deutlich, dass die Entwicklung von Lehre und Studium nicht als isolierte Aufgabe verstanden werden kann, sondern in die Strukturen und Prozesse der Universität hineinwirken und Formen der Zusammenarbeit etablieren sollte, die es braucht, um Projekte nachhaltig zu gestalten.
Ziel dieses Bandes ist es, zur Diskussion über Gelingensbedingungen einer nachhaltigen Entwicklung von Lehre und Lernen beizutragen. Damit richtet er sich an Akteur/innen aus der Hochschulleitung, an Lehrende und Forschende sowie Mitarbeitende des Third Space.