Microsolvation and sp²-stereoinversion of monomeric α-(2, 6-di-tert-butylphenyl)vinyllithium as measured by NMR

The beta-unsubstituted title compound dissolves in THF as a uniformly trisolvated monomer, whereas it forms exclusively disolvated monomers in tert-butyl methyl ether, Et2O, TMEDA, or toluene with TMEDA (1.4 equiv). This was established at low temperatures through the observation of separated NMR signals for free and lithium-coordinated ligands and/or through the patterns and magnitudes of C-13, Li-6 NMR coupling constants. An aggregated form was observed only with Et2O (2 equiv) in toluene as the solvent. The olefinic geminal interproton coupling constants of the H2C= part can be used as a secondary criterion to differentiate between these differently solvated ground-states (3, 2, or <2 coordinated ligands per Li). Due to a kinetic trisolvation privilege of THF, the cis/trans sp(2)-stereoinversion rates could be measured through analyses of H-1 NMR line broadening and coalescence only in THF as the solvent: The pseudomonomolecular (because THF-catalyzed),ionic mechanism is initialized by a C-Li bond heterolysis with the transient immobilization of one additional THF ligand, followed by stereoinversion of the quasi-sp(2)-hybridized carbanionic center in cooperation with a "conducted tour" migration of Li+(THF)(4) along the alpha-aryl group within the solvent-separated ion pair

Verantwortungsdarstellung und Verantwortungswahrnehmung in der 1. Welle der COVID-19-Pandemie: Ein mehrmethodischer Ansatz

Zu Beginn der COVID-19-Pandemie reagierte der Großteil der betroffenen Länder mit Maßnahmen, die das öffentliche Leben weitgehend einschränkten. Gleichzeitig baten Politiker:innen und andere gesellschaftliche Akteur:innen die Menschen, Abstand zu halten und zu Hause zu bleiben. Vor diesem Hintergrund stellt sich die Frage, wer für Ursachen und Lösungen der Pandemie als verantwortlich wahrgenommen wurde. Maßgeblich geprägt wird eine solche Verantwortungswahrnehmung durch deren Darstellung in der medialen Berichterstattung mittels Responsibility Frames. Entsprechend setzt sich der vorliegende Beitrag mit den Responsibility Frames in der Berichterstattung zu COVID-19 sowie der Verantwortungswahrnehmung seitens der Bevölkerung in der ersten Welle der Pandemie in Deutschland auseinander. Zu diesem Zweck wurden eine teilstandardisierte Inhaltsanalyse der Printberichterstattung sowie eine bevölkerungsrepräsentative Online-Panelbefragung im Zeitraum Januar bis Mai 2020 durchgeführt. Die Ergebnisse zeigen, dass die Medien insbesondere gesellschaftliche Verantwortung hervorhoben, während die Bevölkerung komplexere Verantwortungsattributionen aufwies. Insgesamt aber waren, anders als in der Berichterstattung, individuelle Verantwortungszuschreibungen in der Bevölkerung am stärksten ausgeprägt. Dies ist angesichts der Bedeutung der Verantwortungswahrnehmung für das individuelle Gesundheitsverhalten und die Bereitschaft, politische Maßnahmen zu unterstützen, ein zentraler Befund.At the beginning of the COVID-19 pandemic, most of the affected countries responded with measures that largely restricted public life. At the same time, politicians and other social actors repeatedly asked people to keep their distance and stay at home. Against this backdrop, the question arises as to who was perceived as responsible for causing and fixing the pandemic. Such a perception of responsibility is decisively shaped by its portrayal in media coverage. Accordingly, this article examines the responsibility frames in the reporting on COVID-19 and the perception of responsibility on the part of the population in the first wave of the pandemic in Germany (January to May 2020). For this purpose, a partially standardized content analysis of print coverage and a population-representative online panel survey were conducted. The results indicate that the media mostly emphasized societal responsibilities, while the population showed more complex attributions of responsibility. Overall, however, in contrast to the reporting, attributions of individual responsibility were strongest among the population. This is an important finding, given the importance of the perception of responsibility for individuals’ health behavior and the willingness to support political measures

CXCR2-Blocking Has Context-Sensitive Effects on Rat Glioblastoma Cell Line Outgrowth (S635) in an Organotypic Rat Brain Slice Culture Depending on Microglia-Depletion (PLX5622) and Dexamethasone Treatment

In glioblastoma (GBM), the interplay of different immune cell subtypes, cytokines, and/or drugs shows high context-dependencies. Interrelations between the routinely applied dexamethasone (Dex) and microglia remain elusive. Here, we exploited rat organotypic brain slice co-cultures (OBSC) to examine the effects on a rat GBM cell line (S635) outgrowth resulting from the presence of Dex and pretreatment with the colony-stimulating factor receptor 1 (CSF1-R) inhibitor PLX5622: in native OBSC (without PLX5622-pretreatment), a diminished S635 spheroid outgrowth was observable, whereas Dex-treatment enhanced outgrowth in this condition compared to PLX5622-pretreated OBSC. Screening the supernatants of our model with a proteome profiler, we found that CXCL2 was differentially secreted in a Dex- and PLX5622-dependent fashion. To analyze causal interrelations, we interrupted the CXCL2/CXCR2-axis: in the native OBSC condition, CXCR2-blocking resulted in increased outgrowth, in combination with Dex, we found potentiated outgrowth. No effect was found in the PLX5622-pretreated. Our method allowed us to study the influence of three different factors—dexamethasone, PLX5622, and CXCL2—in a well-controlled, simplified, and straight-forward mechanistic manner, and at the same time in a more realistic ex vivo scenario compared to in vitro studies. In our model, we showed a GBM outgrowth enhancing synergism between CXCR2-blocking and Dex-treatment in the native condition, which was levelled by PLX5622-pretreatment

Structural Optimization and De Novo Design of Dengue Virus Entry Inhibitory Peptides

Viral fusogenic envelope proteins are important targets for the development of inhibitors of viral entry. We report an approach for the computational design of peptide inhibitors of the dengue 2 virus (DENV-2) envelope (E) protein using high-resolution structural data from a pre-entry dimeric form of the protein. By using predictive strategies together with computational optimization of binding “pseudoenergies”, we were able to design multiple peptide sequences that showed low micromolar viral entry inhibitory activity. The two most active peptides, DN57opt and 1OAN1, were designed to displace regions in the domain II hinge, and the first domain I/domain II beta sheet connection, respectively, and show fifty percent inhibitory concentrations of 8 and 7 µM respectively in a focus forming unit assay. The antiviral peptides were shown to interfere with virus:cell binding, interact directly with the E proteins and also cause changes to the viral surface using biolayer interferometry and cryo-electron microscopy, respectively. These peptides may be useful for characterization of intermediate states in the membrane fusion process, investigation of DENV receptor molecules, and as lead compounds for drug discovery

Targets for immune mediated killing of tumor cells and T cell functions in B-CLL

There is a great need for developing and improving treatment alternatives in B-cell chronic lymphocytic leukemia (B-CLL). New therapeutical approaches based on the manipulation of the immune system enable establishment of enhanced control over the malignant clone. Exploitation of molecular defects of leukemic cells causing apoptotic failure and tumor immune escape mechanisms might have impact on a deeper understanding of the pathophysiology of B-CLL and targets for the development of novel therapy modalities of this disease. Analyses of CD95 receptor expression showed a downregulation on the leukemic cells. These B-CLL cells exhibited various functional abnormalities. A weak proliferation of B-CLL cells were induced upon activation with both anti-CD40 and anti-CD95 monoclonal antibodies (mAbs) and stimulation with anti-CD95 mAb did not induce apoptosis. Cross-linking of CD40 and CD95 molecules led to delayed protein tyrosine signals of weak intensities and transient signaling, respectively. Unspecific stimulation of B-CLL cells led to induction of apoptosis, but with a large variation between the different clones. The apoptosis induced was independent on the CD95 receptor expression and the stage of differentiation. Each leukemic clone investigated, upregulated the ex vivo undetectable p53 upon culture with CD40/IL4. No relation between the p53 expression and apoptosis of leukemic cells was noted. There was an inter-individual variation in the expression of Bcl-2 and phosphotyrosine proteins. These proteins were up- or downregulated by both activation manners. The relative expression of Bcl-2 was found to correlate with the degree of apoptosis. Potential target structures for monoclonal antibody therapy i.e. CD20, CD22 and CD52 have been estimated quantitatively by flow cytometry. A considerably lower expression of the CD20 and CD22 antigens was found on leukemic cells compared to control B cells. Furthermore, a substantial variability over the time was seen and most pronounced for CD20. No upregulation of CD20 was observed upon in vivo IL-4 therapy. Highly significant correlations were obtained between antigen receptor numbers on lymphocytes from control donors and B-CLL patients estimated with three different calibrator standards available for quantitative flow cytometry. Furthermore, methodological aspects on the technique are discussed. Estimation of cytokine production in ex vivo T cells revealed higher numbers of IL-2, IL-4 and GM-CSF producing cells in progressive disease than in patients with nonprogressive disease and controls. A well preserved functional capacity to produce Th1 (IL-2, TNF-alpha, IFN- gamma and GM-CSF) and Th2 (IL-4) cytokines was noted. A relative increase of IL-2 and TNF-alpha producing T cells was observed upon unspecific in vitro activation in both non-progressive and progressive disease stages. CD4+ T cells from patients with progressive disease expressed in higher proportions CD54, surface(s) and cytoplasmic(c) CTLA-4 antigens as compared to patients with non-progressive disease and control donors. Lower frequencies of zeta chain and CD28 expressing T cells were found within the CD4 subset in progressive as well as non-progressive disease stages than in controls. The proportions of CD8+/zeta chain+ and CD4+/CD28+ T cells decreased by advancing stage. In opposite, increasing proportions of CD4+/CD54+, CD4+/sCTLA- 4+, CD4+/cCTLA-4+ as well as CD8+/sCTLA-4+ and CD8+/cCTLA-4+ T lymphocytes were noted by advancing stage

Kommunikationswissenschaftliche Grundlagen der Gesundheitskommunikation

Rossmann C, Hastall MR, Baumann E. Kommunikationswissenschaftliche Grundlagen der Gesundheitskommunikation. In: Hurrelmann K, Baumann E, eds. Handbuch Gesundheitskommunikation. Bern: Hans Huber; 2014: 81-94

Riskant oder gefährlich? Dimensionen und Herausforderungen einer rezipientenzentrierten gesundheitsbezogenen Risikokommunikation

Früh H, Baumann E. Riskant oder gefährlich? Dimensionen und Herausforderungen einer rezipientenzentrierten gesundheitsbezogenen Risikokommunikation. In: Rossmann C, Hastall M, eds. Medien und Gesundheitskommunikation: Befunde, Entwicklungen, Herausforderungen. Baden-Baden: Nomos; 2013: 147--165

Gemeinsam aktiver? Der Einfluss von Gruppenbildern auf die körperliche Aktivität

Reifegerste D, Rossmann C. Gemeinsam aktiver? Der Einfluss von Gruppenbildern auf die körperliche Aktivität. In: Schäfer M, Quiring O, Rossmann C, Hastall MR, Baumann E, eds. Gesundheitskommunikation im gesellschaftlichen Wandel. Gesundheitskommunikation/Health Communication. Vol 10. Baden-Baden: Nomos; 2015: 179-188