Das Buch in der nationalsozialistischen Propagandapolitik

Diese Studie untersucht die Buchpolitik der NS-Zeit im Kontext der modernen Massenmedien. Gestützt auf zahlreiche veröffentlichte und unveröffentlichte Quellen, rekonstruiert sie die Buchförderungspolitik im Spannungsfeld von politischen Interessen und langfristig wirksamen Traditionsbindungen, von ideologischen Imperativen und marktwirtschaftlichen Konditionen, von totalitären Ansprüchen und einer modernen, ausdifferenzierten Gesellschaft. Zugleich dokumentiert die Analyse die Auswirkungen dieser Spannungen in den z.T. widersprüchlichen literaturpolitischen Diskursen über das auch zwischen 1933 und 1945 diversifizierte literarische Feld

Cardiac Extracellular Vesicles (EVs) Released in the Presence or Absence of Inflammatory Cues Support Angiogenesis in Different Manners

Cells release extracellular vesicles (EVs) to communicate in a paracrine manner with other cells, and thereby influence processes, such as angiogenesis. The conditioned medium of human cardiac-derived adherent proliferating (CardAP) cells was recently shown to enhance angiogenesis. To elucidate whether their released EVs are involved, we isolated them by differential centrifugation from the conditioned medium derived either in the presence or absence of a pro-inflammatory cytokine cocktail. Murine recipient cells internalized CardAP-EVs as determined by an intracellular detection of human proteins, such as CD63, by a novel flow cytometry method for studying EV-cell interaction. Moreover, endothelial cells treated for 24 h with either unstimulated or cytokine stimulated CardAP-EVs exhibited a higher tube formation capability on Matrigel. Interestingly, unstimulated CardAP-EVs caused endothelial cells to release significantly more vascular endothelial growth factor and interleukin (IL)-6, while cytokine stimulated CardAP-EVs significantly enhanced the release of IL-6 and IL-8. By nCounter® miRNA expression assay (NanoString Technologies) we identified microRNA 302d-3p to be enhanced in unstimulated CardAP-EVs compared to their cytokine stimulated counterparts, which was verified by quantitative polymerase chain reaction. This study demonstrates that both CardAP-EVs are pro-angiogenic by inducing different factors from endothelial cells. This would allow to select potent targets for a safe and efficient therapeutic application

Extracellular vesicles from regenerative human cardiac cells act as potent immune modulators by priming monocytes

Background: Nano-sized vesicles, so called extracellular vesicles (EVs), from regenerative cardiac cells represent a promising new therapeutic approach to treat cardiovascular diseases. However, it is not yet sufficiently understood how cardiac-derived EVs facilitate their protective effects. Therefore, we investigated the immune modulating capabilities of EVs from human cardiac-derived adherent proliferating (CardAP) cells, which are a unique cell type with proven cardioprotective features. Results: Differential centrifugation was used to isolate EVs from conditioned medium of unstimulated or cytokinestimulated (IFNγ, TNFα, IL-1β) CardAP cells. The derived EVs exhibited typical EV-enriched proteins, such as tetraspanins, and diameters mostly of exosomes (< 100 nm). The cytokine stimulation caused CardAP cells to release smaller EVs with a lower integrin ß1 surface expression, while the concentration between both CardAP-EV variants was unaffected. An exposure of either CardAP-EV variant to unstimulated human peripheral blood mononuclear cells (PBMCs) did not induce any T cell proliferation, which indicates a general low immunogenicity. In order to evaluate immune modulating properties, PBMC cultures were stimulated with either Phytohemagglutin or anti-CD3. The treatment of those PBMC cultures with either CardAP-EV variant led to a significant reduction of T cell proliferation, pro-inflammatory cytokine release (IFNγ, TNFα) and increased levels of active TGFβ. Further investigations identified CD14+ cells as major recipient cell subset of CardAP–EVs. This interaction caused a significant lower surface expression of HLA-DR, CD86, and increased expression levels of CD206 and PD-L1. Additionally, EV-primed CD14+ cells released significantly more IL-1RA. Notably, CardAP-EVs failed to modulate anti-CD3 triggered T cell proliferation and pro-inflammatory cytokine release in monocultures of purified CD3+ T cells. Subsequently, the immunosuppressive feature of CardAPEVs was restored when anti-CD3 stimulated purified CD3+ T cells were co-cultured with EV-primed CD14+ cells. Beside attenuated T cell proliferation, those cultures also exhibited a significant increased proportion of regulatory T cells. Conclusions: CardAP-EVs have useful characteristics that could contribute to enhanced regeneration in damaged cardiac tissue by limiting unwanted inflammatory processes. It was shown that the priming of CD14+ immune cells by CardAP-EVs towards a regulatory type is an essential step to attenuate significantly T cell proliferation and proinflammatory cytokine release in vitro

Speckle-tracking echocardiography combined with imaging mass spectrometry assesses region-dependent alterations

Left ventricular (LV) contraction is characterized by shortening and thickening of longitudinal and circumferential fibres. To date, it is poorly understood how LV deformation is altered in the pathogenesis of streptozotocin (STZ)-induced type 1 diabetes mellitus-associated diabetic cardiomyopathy and how this is associated with changes in cardiac structural composition. To gain further insights in these LV alterations, eight-week-old C57BL6/j mice were intraperitoneally injected with 50 mg/kg body weight STZ during 5 consecutive days. Six, 9, and 12 weeks (w) post injections, echocardiographic analysis was performed using a Vevo 3100 device coupled to a 30-MHz linear-frequency transducer. Speckle-tracking echocardiography (STE) demonstrated impaired global longitudinal peak strain (GLS) in STZ versus control mice at all time points. 9w STZ animals displayed an impaired global circumferential peak strain (GCS) versus 6w and 12w STZ mice. They further exhibited decreased myocardial deformation behaviour of the anterior and posterior base versus controls, which was paralleled with an elevated collagen I/III protein ratio. Additionally, hypothesis-free proteome analysis by imaging mass spectrometry (IMS) identified regional- and time-dependent changes of proteins affecting sarcomere mechanics between STZ and control mice. In conclusion, STZ-induced diabetic cardiomyopathy changes global cardiac deformation associated with alterations in cardiac sarcomere proteins

Apolipoprotein A-I gene transfer exerts immunomodulatory effects and reduces vascular inflammation and fibrosis in ob/ob mice

Background Obesity is associated with vascular inflammation, fibrosis and reduced high-density lipoproteins (HDL)-cholesterol. We aimed to investigate whether adenoviral gene transfer with human apolipoprotein (apo) A-I (Ad.A-I), the main apo of HDL, could exert immunomodulatory effects and counteract vascular inflammation and fibrosis in ob/ob mice. Methods Ad.A-I transfer was performed in 8 weeks (w) old ob/ob mice, which were sacrificed 7 w later. The aorta was excised for mRNA analysis and the spleen for splenocyte isolation for subsequent flow cytometry and co-culture with murine fibroblasts. HDL was added to mononuclear cells (MNC) and fibroblasts to assess their impact on adhesion capacity and collagen deposition, respectively. Results Ad.A-I led to a 1.8-fold (p < 0.05) increase in HDL-cholesterol versus control ob/ob mice at the day of sacrifice, which was paralleled by a decrease in aortic TNF-α and VCAM-1 mRNA expression. Pre-culture of MNC with HDL decreased their adhesion to TNF-α-activated HAEC. Ad.A-I exerted immunomodulatory effects as evidenced by a downregulation of aortic NOD2 and NLRP3 mRNA expression and by a 12 %, 6.9 %, and 15 % decrease of the induced proliferation/activity of total splenic MNC, CD4+, and CD8+ cells in ob/ob Ad.A-I versus control ob/ob mice, respectively (p < 0.05). Ad.A-I further reduced aortic collagen I and III mRNA expression by 62 % and 66 %, respectively (p < 0.0005), and abrogated the potential of ob/ob splenocytes to induce the collagen content in murine fibroblasts upon co-culture. Finally, HDL decreased the TGF-ß1-induced collagen deposition of murine fibroblasts in vitro

Literary translation from Flemish into German during the Nazi regime

. During the Nazi regime and, more specifically, the Second World War, literary translation was eyed with suspicion by the controlling instances as it inevitably involved the import of foreign thought as well as economic exchange with foreign states. Against this backdrop, Flanders represents an interesting case. On the one hand, since it was considered a ‘kindred’ source-language nation, the translation of Flemish literature into German was encouraged within the constraints of the totalitarian system. On the other hand, persisting literary traditions, the private market logic, the agency of mediators, and the prevailing Catholic tone and idyllic nature of much Flemish literature caused significant disparities between translation policy and practice. Starting from the publishing figures of translated Flemish literature in Nazi Germany and their evolution during the twelve-year period, this article confronts official attitudes and discourses regarding Flemish translated fiction with the actual situation within the translated fiction market

Proteomic diversity of high-density lipoprotein explains its association with clinical outcome in patients with heart failure

Aims: Previously, low high-density lipoprotein (HDL) cholesterol was found to be one of the strongest predictors of mortality and/or heart failure (HF) hospitalisation in patients with HF. We therefore performed in-depth investigation of the multifunctional HDL proteome to reveal underlying pathophysiological mechanisms explaining the association between HDL and clinical outcome. Methods and results: We selected a cohort of 90 HF patients with 1:1 cardiovascular death/survivor ratio from BIOSTAT-CHF. A novel optimised protocol for selective enrichment of lipoproteins was used to prepare plasma. Enriched lipoprotein content of samples was analysed using high resolution nanoscale liquid chromatography-mass spectrometry-based proteomics, utilising a label free approach. Within the HDL proteome, 49 proteins significantly differed between deaths and survivors. An optimised model of 12 proteins predicted death with 76% accuracy (Nagelkerke R2=0.37, P &lt; 0.001). The strongest contributors to this model were filamin-A (related to crosslinking of actin filaments) [odds ratio (OR) 0.31, 95% confidence interval (CI) 0.15–0.61, P = 0.001] and pulmonary surfactant-associated protein B (related to alveolar capillary membrane function) (OR 2.50, 95% CI 1.57–3.98, P &lt; 0.001). The model predicted mortality with an area under the curve of 0.82 (95% CI 0.77–0.87, P &lt; 0.001). Internal cross validation resulted in 73.3 ± 7.2% accuracy. Conclusion: This study shows marked differences in composition of the HDL proteome between HF survivors and deaths. The strongest differences were seen in proteins reflecting crosslinking of actin filaments and alveolar capillary membrane function, posing potential pathophysiological mechanisms underlying the association between HDL and clinical outcome in HF