Nucleotide-, chemotactic peptide- and phorbol ester-induced exocytosis in HL-60 leukemic cells

Undifferentiated and differentiated HL-60 leukemic cells possess nucleotide receptors which functionally couple to phospholipase C via pertussis toxin-sensitive guanine nucleotide-binding proteins (G-proteins). We investigated the role of extracellular nucleotides in the regulation of beta-glucuronidase release in HL-60 cells. In dibutyryl cyclic AMP (Bt2cAMP)-differentiated HL-60 cells, the chemotactic peptide, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe), the phosphorothioate analogue of ATP, adenosine 5'-O-[3-thio]triphosphate (ATP[gamma S]), and UTP increased cytosolic Ca2+ from 100 nM up to 1.2 microM with EC50 values of 4 nM, 1 microM and 100 nM, respectively. In these cells, ATP[gamma S] induced exocytosis with an EC50 of 4 microM and an effectiveness amounting to 50-70% of that of fMet-Leu-Phe. ATP, ITP, UTP, CTP, and uridine 5'-O-[2-thio]diphosphate activated exocytosis as well. Phorbol myristate acetate (PMA) induced exocytosis with an EC50 of 115 ng/ml and an effectiveness similar to that of ATP[gamma S]. Cytochalasin B (CB) differently potentiated exocytosis induced by ATP[gamma S], fMet-Leu-Phe and PMA. Treatment of Bt2cAMP-differentiated HL-60 cells with pertussis toxin (500 ng/ml) for 24 h resulted in ADP-ribosylation of more than 97.5% of the G-proteins. Under these conditions, pertussis toxin almost completely inhibited the increase in cytosolic Ca2+ and beta-glucuronidase release induced by fMet-Leu-Phe but only partially inhibited the effects of ATP[gamma S] and UTP. fMet-Leu-Phe at a non-stimulatory concentration (1 nM) potentiated ATP[gamma S]-induced beta-glucuronidase release in the presence but not in the absence of CB. In contrast, ATP[gamma S] and fMet-Leu-Phe synergistically activated superoxide formation in the absence of CB. PMA potentiated superoxide formation induced by ATP[gamma S] or fMet-Leu-Phe and did not affect exocytosis induced by ATP[gamma S] or fMet-Leu-Phe. In undifferentiated HL-60 cells, fMet-Leu-Phe, ATP[gamma S], UTP and PMA did not induce beta-glucuronidase release. fMet-Leu-Phe did not increase cytosolic Ca2+ in undifferentiated HL-60 cells, whereas ATP[gamma S] and UTP were similarly potent and effective as in Bt2cAMP-differentiated cells. In differentiated HL-60 cells, fMet-Leu-Phe induced aggregation, and ATP[gamma S] induced a transient shape change. Our results show (I) that exocytosis in HL-60 cells does not obligatorily depend on CB. (II) Purine and pyrimidine nucleotides activate exocytosis via pertussis toxin-sensitive and -insensitive signal transduction pathways.(ABSTRACT TRUNCATED AT 400 WORDS

Dynamical Component Analysis (DyCA) and its application on epileptic EEG

Dynamical Component Analysis (DyCA) is a recently-proposed method to detect projection vectors to reduce the dimensionality of multi-variate deterministic datasets. It is based on the solution of a generalized eigenvalue problem and therefore straight forward to implement. DyCA is introduced and applied to EEG data of epileptic seizures. The obtained eigenvectors are used to project the signal and the corresponding trajectories in phase space are compared with PCA and ICA-projections. The eigenvalues of DyCA are utilized for seizure detection and the obtained results in terms of specificity, false discovery rate and miss rate are compared to other seizure detection algorithms.Comment: 5 pages, 4 figures, accepted for IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP) 201

Impact of Mistletoe Triterpene Acids on the Uptake of Mistletoe Lectin by Cultured Tumor Cells

Complementary treatment possibilities for the therapy of cancer are increasing in demand due to the severe side effects of the standard cytostatics used in the first-line therapy. A common approach as a complementary treatment is the use of aqueous extracts of Viscum album L. (Santalaceace). The therapeutic activity of these extracts is attributed to Mistletoe lectins which are Ribosome-inactivating proteins type II. Besides these main constituents the extract of Viscum album L. comprises also a mixture of lipophilic ingredients like triterpene acids of the oleanane, lupane and ursane type. However, these constituents are not contained in commercially available aqueous extracts due to their high lipophilicity and insolubility in aqueous extraction media. To understand the impact of the extract ingredients in cancer therapy, the intracellular uptake of the mistletoe lectin I (ML) by cultured tumor cells was investigated in relation to the mistletoe triterpene acids, mainly oleanolic acid. Firstly, these hydrophobic triterpene acids were solubilized using cyclodextrins ("TT" extract). Afterwards, the uptake of either single compounds (isolated ML and the aqueous "viscum" extract) or in combination with the TT extract (ML+TT, viscumTT), was analyzed. The uptake of ML was studied inTHP-1-, HL-60-, 143B- and Ewing TC-71-cells and determined after 30, 60 and 120 minutes by an enzyme linked immunosorbent assay which quantifies the A-chain of the hololectin. It could be shown that the intracellular uptake after 120 minutes amounted to 20 % in all cell lines after incubation with viscumTT. The studies further revealed that the uptake in THP-1-, HL-60- and Ewing TC-71-cells was independent of the addition of TT extract. Interestingly, the uptake of ML by 143B-cells could only be measured after addition of triterpenes pointing to resistance to mistletoe lectin

Geld nachhaltig investieren: Was sollte man wissen und wie steht es um dieses Wissen in Österreich?

The promotion of green and sustainable private investments is an important part of the European Union's Green Deal. An increasing number of investors also wants to invest money sustainably. In this policy brief, we present a learning tool of 30 questions. This tool was developed together with experts from nine Austrian institutions, and it provides relevant information about sustainable investing in a simple way to self-study. In addition, we present a measurement tool to assess sustainable finance knowledge which can be used by practitioners and academics to develop and evaluate financial education measures. Finally, we report the results of an online survey of over 1000 people in Austria. The results show that on average only half of the questions on sustainable financial knowledge can be answered correctly by a representative sample (concerning age and gender) of the population. Die Förderung von grünen und nachhaltigen privaten Investitionen ist ein wichtiger Bestandteil des Green Deals der Europäischen Union. Auch immer mehr Investor:innen wollen ihr Geld nachhaltig anlegen. In diesem Policy Brief präsentieren wir 30 Fragen und Antworten, die gemeinsam mit Expert:innen aus neun österreichischen Institutionen entwickelt wurden. Darin sind die wichtigsten Informationen rund um nachhaltiges Investieren fürs Selbststudium aufbereitet. Zudem wird ein Messinstrument zur Erfassung von nachhaltigem Finanzwissen präsentiert, welches Praktiker:innen und Wissenschaftler:innen zur Entwicklung und Evaluation von Finanzbildungsmaßnahmen dienen kann. Schließlich werden die Ergebnisse einer Online-Befragung von über 1000 Personen in Österreich berichtet. Die Stichprobe ist für Alter und Geschlecht repräsentativ. Die Ergebnisse zeigen, dass im Durchschnitt nur die Hälfte der Fragen zu nachhaltigem Finanzwissen korrekt beantwortet werden

Neurometabolic correlates of depression and disability in episodic cluster headache

A close association between pain, depression and disability has been shown. However, the neurometabolic correlates of this association have been barely investigated in disease states. Episodic cluster headache is a severe headache syndrome and represents a suitable disease model for the investigation of episodic pain. The aim of this study was to explore the relationship between depression and disability as well as pain scores and brain metabolism in patients with cluster headache during the disease period with repetitive pain attacks, but outside an acute attack. Thirteen patients with cluster headache underwent 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission (FDG-PET) and completed questionnaires on depression and disability as well as a pain visual analogue rating scale (VAS). A positive correlation between the depression scores and glucose metabolism was observed in the insular cortex. A positive correlation between the pain disability scores and brain metabolism was detected in the amygdala. The same applied to the pain visual analogue rating scores. Our data underline the association between severe episodic pain, depression and disability. In addition to this clinical observation, our results stress the importance of the insula and amygdala in pain processing and suffering

Sauberkeit in Müllbereichen. Die Rolle von Naturbildern, Infrastruktur und der Eigeninitiative von BewohnerInnen

Littering, das achtlose Wegwerfen von Müll, in Müllbereichen von Wohnhausanlagen beeinträchtigt das Wohlbefinden und verursacht hohe Kosten. Ziel der vorliegenden Studie war es, zu überprüfen, ob kostengünstige Poster von Naturbildern langfristig die Sauberkeit verbessern können. Zudem war es Ziel, den Einfluss der Infrastruktur auf die Sauberkeit sowie die Bedeutung der Eigeninitiative von BewohnerInnen, fremden Müll aufzuheben, zu untersuchen. In einem Lokalaugenschein in zehn Müllbereichen wurden mittels Beobachtung und 55 BewohnerInnen-Interviews mögliche Ursachen für Littering und 40 Ideen für Maßnahmen zur Erhöhung der Sauberkeit exploriert. Darauf aufbauend wurde ein Feldexperiment in 182 Müllbereichen durchgeführt, die vorab als besonders schmutzig identifiziert wurden. Der Effekt der Naturbilder auf die Sauberkeit im Vergleich zu einer Kontrollgruppe wurde nach einem, drei und 13 Monaten untersucht. Die Messung der Sauberkeit erfolgte anhand der Bewertung von BewohnerInnen und OrdnungsberaterInnen (OBs) sowie auf Basis von Fotos. Die Ergebnisse zeigen, dass die Grundsauberkeit in den Müllbereichen hoch ist, diese aber von den BewohnerInnen subjektiv als niedriger angesehen wird als die Sauberkeit, die durch die OBs oder auf Basis der Fotos festgestellt wurde. Die Ergebnisse geben außerdem Hinweise darauf, dass über die Dauer der Studie die Sauberkeit abnimmt, was im Zusammenhang mit einem Anstieg an Sperrmüll steht. Die Naturbilder haben nach einem Monat die durch die Be-wohnerInnen wahrgenommene Sauberkeit in den Müllräumen im Vergleich zur Kontrollgruppe verbessert. Für die Müllplätze zeigt sich kein Effekt. Kurz-, mittel- und langfristig über den Zeitraum von über einem Jahr ist kein Effekt der Naturbilder auf die Sauberkeit, gemessen durch OBs und Fotos, feststellbar. Weiters zeigen die Ergebnisse den starken Einfluss von infrastrukturellen Faktoren auf die Sauberkeit. In größeren Wohnhausanla-gen mit hoher Fluktuation und jungen MieterInnen ist die Sauberkeit geringer als bei kleineren Anlagen mit vielen AltmieterInnen. Außerdem ist es beispielsweise in Müllräumen schmutziger als auf Müllplätzen. Die Haustürbefragung zeigt, dass rund 35 Prozent der befragten 739 BewohnerInnen tendenziell Eigeninitiative zeigen und fremden Müll aufheben. Je höher diese Eigeninitiative, desto höher ist auch die Sauberkeit, subjektiv und gemessen durch OBs und Fotos. Der Bericht endet mit einer Diskussion von 13 Maßnahmen, die aufgrund der Ergebnisse die Sauberkeit verbessern könnten. Diese betreffen beispielweise die Fokussierung auf große Wohnhausanlagen, junge BewohnerInnen, gezielte Information zum Umgang mit Sperrmüll für (junge) BewohnerInnen, die ein- oder ausziehen, eine Generalreinigung der Müllbereiche, Errichtung von Müllplätzen im Neubau, mehr Container und Aschenbecher sowie die Stärkung der Eigeninitiative durch Maßnahmen, die soziale Normen und das Gemeinschaftsgefühl fördern

Individual health services

Background: The German statutory health insurance (GKV) reimburses all health care services that are deemed sufficient, appropriate, and efficient. According to the German Medical Association (BÄK), individual health services (IGeL) are services that are not under liability of the GKV, medically necessary or recommendable or at least justifiable. They have to be explicitly requested by the patient and have to be paid out of pocket. Research questions: The following questions regarding IGeL in the outpatient health care of GKV insurants are addressed in the present report: What is the empirical evidence regarding offers, utilization, practice, acceptance, and the relation between physician and patient, as well as the economic relevance of IGeL? What ethical, social, and legal aspects are related to IGeL? For two of the most common IGeL, the screening for glaucoma and the screening for ovarian and endometrial cancer by vaginal ultrasound (VUS), the following questions are addressed: What is the evidence for the clinical effectiveness? Are there sub-populations for whom screening might be beneficial? Methods: The evaluation is divided into two parts. For the first part a systematic literature review of primary studies and publications concerning ethical, social and legal aspects is performed. In the second part, rapid assessments of the clinical effectiveness for the two examples, glaucoma and VUS screening, are prepared. Therefore, in a first step, HTA-reports and systematic reviews are searched, followed by a search for original studies published after the end of the research period of the most recent HTA-report included. Results: 29 studies were included for the first question. Between 19 and 53% of GKV members receive IGeL offers, of which three-quarters are realised. 16 to 19% of the insurants ask actively for IGeL. Intraocular tension measurement is the most common single IGeL service, accounting for up to 40% of the offers. It is followed by ultrasound assessments with up to 25% of the offers. Cancer screening and blood or laboratory services are also frequent and represent a major proportion of the demand. The ethical, social, and legal aspects discussed in the context of IGeL concern eight subject areas: 1. autonomous patient decisions versus obtrusion, 2. commercialization of medicine, 3. duty of patient information, 4. benefit, evidence, and (quality) control, 5. role and relation of physicians and patients, 6. relation to the GKV, 7. social inequality, 8. formally correct performance. For glaucoma screening, no randomized controlled trial (RCT) is identified that shows a patient relevant benefit. For VUS three RCT are included. However, they do not yet present mortality data concerning screened and non-screened persons. VUS screening shows a high degree of over-diagnosis in turn leading to invasive interventions. To diagnose one invasive carcinoma, 30 to 35 surgical procedures are necessary. Conclusion: IGeL are a relevant factor in the German statutory health care system. To provide more transparency, the requests for evidence-based and independent patient information should be considered. Whether official positive and negative-lists could be an appropriate instrument to give guidance to patients and physicians, should be examined. Generally, IGeL must be seen in the broader context of the discussions about the future design and development of the German health care system

Financial or environmental-impact information promote ESG investments: Evidence from a large incentivized online-experiment

Effective stimulation of investments in Environmental, Social, and Governance (ESG) requires reliable knowledge of motives that drive investors’ decisions. We investigate how information on financial return and environmental impact as well as the combination of both affect the decision to invest sustainably. Moreover, we test whether offering a general or granular choice on sustainability preferences affects investment decisions. An incentivized online experiment with experienced retail investors and a representative sample of the Austrian population (N = 2254) shows that information on financial impact as well as on environmental impact stimulates sustainable investments. However, the combination of both types of information yields no additional positive effect. Information has no strong effect on investor satisfaction. Also, the difference in choice options on sustainability preferences has no large impact on investment decisions or satisfaction. An explorative analysis suggests that women and investors holding high biospheric values as well as investors with high financial literacy, and trust in ESG products are more likely to invest sustainably. Additional results on the revision and stability of investment decisions are discussed

Energiekrise – was tun? Verhaltenswissenschaftliche Empfehlungen

Die aktuelle Energiekrise verlangt nach einer Änderung unseres täglichen Verhaltens, als Individuen und als Gesellschaft. Erkenntnisse aus der verhaltenswissenschaftlichen Forschung liefern Hinweise, wie Haushalte, öffentliche Institutionen und Unternehmen beim Senken des Energieverbrauchs und der Nutzung erneuerbarer Energiequellen unterstützt werden können. In diesem Policy Brief werden diese Erkenntnisse entlang von drei zentralen Punkten vorgestellt. Zunächst wird diskutiert, wie durch gezielten Aufbau von Kompetenz Einzelner eine Verhaltensänderung erreicht werden kann. Danach wird dargestellt, wie durch Eingriffe in situative Gegebenheiten Energiesparen bzw. der Ausbau von nachhaltiger Energie einfacher gemacht werden kann. Besonders relevant ist auch die Motivation: Klassische Motivatoren wie Gesetze oder finanzielle Anreize können auf Basis neuer Forschungsergebnisse optimiert, und verhaltenswissenschaftliche Motivatoren wie konkrete Zielsetzungen, Kosten-Nutzen-Wahrnehmung, sozialer Einfluss und Identität können gezielt eingesetzt werden. Bei allen Vorschlägen gilt: Voraussetzung für erfolgreiche Maßnahmen sind breite Akzeptanz und Vertrauen, die durch transparente und wertschätzende Diskussion zwischen verschiedenen Interessensgruppen gefördert werden können