Glycogen synthase kinase-3β negatively regulates group IIA phospholipase A2 expression in human aortic smooth muscle and HepG2 hepatoma cells

AbstractThe present study shows that the IFN-γ-mediated upregulation of secretory phospholipase A2 of group IIA (sPLA2-IIA) in HASMC and HepG2 cells is synergistically increased after simultaneous inhibition of glycogen synthase kinase-3β (GSK-3β) by indirubin-3′-monoxime, 5-iodo or AR-A014418. The effect of GSK-3β inhibition was dose- and time-dependent and can be further augmented by its concomitant incubation with Clostridium difficile toxin B, an inhibitor of small Rho proteins, or H-1152, an inhibitor of Rho-associated kinase. Using AG-490 and caffeic acid phenethyl ester (CAPE), it is further demonstrated that the effect of GSK-3β inhibition on sPLA2-IIA expression depends on Janus kinase-2 and NF-κB-signaling

Securing quality in public service television entertainment

The objective of this paper is twofold: First we discuss what can be regarded as quality in TV entertainment and how it’s promoted or regulated by different media systems. We argue that the public value of entertainment depends on its quality. Thus, there should be a difference between entertainment programming in public service and commercial broadcasts. A brief review of discussion on media quality is provided in order to distinguish the perspective of recipients, producers and regulators. We find three different types of quality criteria: Minimum standards apply to all broadcasters, while Public Service Broadcasters (PSB) must address rather fuzzy additional criteria derived from their respective mandates. Small states impose additional criteria to protect their market and culture. To fulfill our second objective, we present findings from a comparative study in five European countries with different media systems about the role perception of TV commissioners in the production process of entertainment programming and their commitment to quality content. We find that commissioners at PSBs have generally internalized their programming mandates. They allocate higher importance to quality dimensions that address a public value, however, when it comes to tangible commissioning decisions they generally use the same decision criteria in the same ranking as their counterparts in commercial broadcasting

Commercial communication in the digital age : information or disinformation?

In today’s digital age, online and mobile advertising are of growing importance, with advertising no longer bound to the traditional media industry. Although the advertising industry still has broader access to the different measures and channels, users and consumers today have more possibilities topublish, get informed or communicate – to “co-create” –, and toreach a bigger audience. There is a good chance thus that users and consumers are better informed about the objectives and persuasive tricks of the advertising industry than ever before. At the same time, advertisers can inform about products and services without the limitations of time and place faced by traditional mass media. But will there really be a time when advertisers and consumers have equal power, or does tracking users online and offline lead to a situation where advertisers have more information about the consumers than ever before? The volume discusses these questionsand related issues

Expression and shedding of endothelial protein C receptor in prostate cancer cells

<p>Abstract</p> <p>Background</p> <p>Increasing evidences show that beyond its role in coagulation, endothelial protein C receptor (EPCR) interferes with carcinogenesis. Pro-carcinogenic effects of EPCR were linked with a raised generation of activated protein C (aPC) and anti-apoptotic signalling. This study was carried out to analyze the expression, cell surface exposition, and shedding of EPCR in normal and malignant prostate cell lines.</p> <p>Results</p> <p>EPCR expression is up-regulated both at the mRNA and protein levels in invasive prostate DU-145 and PC-3 cells in comparison to normal prostate epithelial cells (PrEC) and less-invasive LNCaP cells. Release of soluble EPCR (sEPCR) is induced by 12-myristate 13-acetate, ionomycin, H₂O₂, and disruptor of lipid rafts in PrEC, DU-145, and PC-3 cells. Furthermore, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), but not interleukin-6 or interferon-γ increase sEPCR release. In LNCaP cells, neither pharmacological agents nor IL-1β or TNF-α result in a significant increase of sEPCR release. The effects of IL-1β and TNF-α on EPCR shedding in DU-145 cells are mediated by MEK/ERK 1/2, JNK, and p38 MAPK signalling cascades. In PC-3 cells, however, the MEK/ERK 1/2 pathway is down-regulated and incubation with cytokines did not elevate the phosphorylated ERK-1/2 fraction as in the case of DU-145 cells. Treatment with 4-aminophenylmercuric acetate (APMA), an activator of metalloproteases, causes a disproportionately large increase of sEPCR release in DU-145 and PC-3 cells, compared to PrEC and LNCaP cells. Finally, an increased release of sEPCR mediated by APMA treatment is shown to be connected with reduced generation of activated protein C indicating the functionality of EPCR in these cells.</p> <p>Conclusions</p> <p>The study demonstrates a number of substantial differences in expression and shedding of EPCR in prostate cancer cell lines in comparison with normal cells that may be relevant for understanding the role of this receptor in carcinogenesis.</p

Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment

Adeno-associated viruses (AAVs) are widely used to deliver genetic material in vivo to distinct cell types such as neurons or glial cells, allowing for targeted manipulation. Transduction of microglia is mostly excluded from this strategy, likely due to the cells’ heterogeneous state upon environmental changes, which makes AAV design challenging. Here, we established the retina as a model system for microglial AAV validation and optimization. First, we show that AAV2/6 transduced microglia in both synaptic layers, where layer preference corresponds to the intravitreal or subretinal delivery method. Surprisingly, we observed significantly enhanced microglial transduction during photoreceptor degeneration. Thus, we modified the AAV6 capsid to reduce heparin binding by introducing four point mutations (K531E, R576Q, K493S, and K459S), resulting in increased microglial transduction in the outer plexiform layer. Finally, to improve microglial-specific transduction, we validated a Cre-dependent transgene delivery cassette for use in combination with the Cx3cr1CreERT2 mouse line. Together, our results provide a foundation for future studies optimizing AAV-mediated microglia transduction and highlight that environmental conditions influence microglial transduction efficiency

Functional values and brand personality: The perception of consumers and media professionals in six European countries

The process of consolidation and concentration in the business of traditional media in Western countries was fed by the global financial crisis during the last three years. We argue that after the global financial crisis, branding and differentiation from competitors is becoming even more important. Traditional media need more effort in managing their brands. Our leading research question is: “What functional values and personality do different media brands represent in the minds of media consumers and media professionals in different European countries?” Useful theoretical background to further develop this research problem can be found in literature on journalism cultures and the functions of the media, as well as brand management in the media industry. To answer our research question, we conducted a survey in six big metropolitan areas: Berlin (N=741), Copenhagen (N=749), London (N=740), Paris (N=741), Rome (N=738), and Zurich (N=748). We asked media consumers what purpose their favourite newspaper and favourite TV news programme serves (functional value) and what personality items best fit the image they have of their favourite media brand. The same questions were asked media managers and senior editors (N=58) in the respective areas. ANOVA tests reveal significant differences among all six areas. Our results show that considerably more than consumers, media professionals see their brands in the light of traditional functions of journalism. Moreover, we found some evidence that the perception of functional values and brand personality in the UK is different from all other countries

Levodopa therapy in Parkinson’s disease: Influence on liquid chromatographic tandem mass spectrometricbased measurements of plasma and urinary normetanephrine, metanephrine and methoxytyramine

Background: Medication-related interferences with measurements of catecholamines and their metabolites represent important causes of false-positive results during diagnosis of phaeochromocytomas and paragangliomas (PPGLs). Such interferences are less troublesome with measurements by liquid chromatography with tandem mass-spectrometry (LC-MS/MS) than by other methods, but can still present problems for some drugs. Levodopa, the precursor for dopamine used in the treatment of Parkinson’s disease, represents one potentially interfering medication. Methods: Plasma and urine samples, obtained from 20 Parkinsonian patients receiving levodopa, were analysed for concentrations of catecholamines and their O-methylated metabolites by LC-MS/MS. Results were compared with those from a group of 120 age-matched subjects and 18 patients with PPGLs. Results: Plasma and urinary free and deconjugated (freeþconjugated) methoxytyramine, as well as urinary dopamine, showed 22- to 148-fold higher (P<0.0001) concentrations in patients receiving levodopa than in the reference group. In contrast, plasma normetanephrine, urinary noradrenaline and urinary free and deconjugated normetanephrine concentrations were unaffected. Plasma free metanephrine, urinary adrenaline and urinary free and deconjugated metanephrine all showed higher (P<0.05) concentrations in Parkinsonian patients than the reference group, but this was only a problem for adrenaline. Similar to normetanephrine, plasma and urinary metanephrine remained below the 97.5 percentiles of the reference group in almost all Parkinsonian patients. Conclusions: These data establish that although levodopa treatment confounds identification of PPGLs that produce dopamine, the therapy is not a problem for use of LC-MS/MS measurements of plasma and urinary normetanephrine and metanephrine to diagnose more commonly encountered PPGLs that produce noradrenaline or adrenaline

Smoking in Systemic Sclerosis: a Longitudinal European Scleroderma Trials and Research Group Study

Data on the role of tobacco exposure in systemic sclerosis (SSc) severity and progression are scarce. We aimed to assess the effects of smoking on the evolution of pulmonary and skin manifestations in the EUSTAR database