RNA-Mediated Gene Silencing in Hematopoietic Cells

In the past few years, the discovery of RNA-mediated gene silencing mechanisms, like RNA interference (RNAi), has revolutionized our understanding of eukaryotic gene expression. These mechanisms are activated by double-stranded RNA (dsRNA) and mediate gene silencing either by inducing the sequence-specific degradation of complementary mRNA or by inhibiting mRNA translation. RNAi now provides a powerful experimental tool to elucidate gene function in vitro and in vivo, thereby opening new exciting perspectives in the fields of molecular analysis and eventually therapy of several diseases such as infections and cancer. In hematology, numerous studies have described the successful application of RNAi to better define the role of oncogenic fusion proteins in leukemogenesis and to explore therapeutic approaches in hematological malignancies. In this review, we highlight recent advances and caveats relating to the application of this powerful new methodology to hematopoiesis

Transformation of Cognitive Assistance Systems into Augmented Reality

The field of Augmented Reality (AR) has received increasing attention in recent years, as AR can be applied to a wide range of problems. The use of AR offers great potential, especially in the industrial sector. Among many applications in this area, one promising application is the augmentation of cognitive assistance systems. Much research has already been done on the development of augmented support systems but it is still lacking on how to transform existing assistance systems into an AR application. This paper focuses on this transformation and presents a process model that intends to support the migration or digitalization of existing support systems into an AR application. An experimental study validates the proposed approach and derives recommendations for action

The seasonal dynamics of the stream sources and input flow paths of water and nitrogen of an Austrian headwater agricultural catchment

AbstractOur study examines the source aquifers and stream inputs of the seasonal water and nitrogen dynamics of a headwater agricultural catchment to determine the dominant driving forces for the seasonal dynamics in the surface water nitrogen loads and concentrations. We found that the alternating aquifer contributions throughout the year of the deep and shallow aquifers were the main cause for the seasonality of the nitrate concentration. The deep aquifer water typically contributed 75% of the total outlet discharge in the summer and 50% in the winter when the shallow aquifer recharges due to low crop evapotranspiration. The shallow aquifer supplied the vast majority of the nitrogen load to the stream due to the significantly higher total nitrogen concentration (11mg-N/l) compared to the deep aquifer (0.50mg-N/l). The main stream input pathway for the shallow aquifer nitrogen load was from the perennial tile drainages providing 60% of the total load to the stream outlet, while only providing 26% of the total flow volume. The diffuse groundwater input to the stream was the largest input to the stream (39%), but only supplied 27% to the total nitrogen load as the diffuse water was mostly composed of deep aquifer water

High-Speed imaging reveals opposing effects of chronic stress and antidepressants on neuronal activity propagation through the hippocampal trisynaptic circuit

Antidepressants (ADs) are used as first-line treatment for most stress-related psychiatric disorders. The alterations in brain circuit dynamics that can arise from stress exposure and underlie therapeutic actions of ADs remain, however, poorly understood. Here, enabled by a recently developed voltage-sensitive dye imaging assay in mouse brain slices, we examined the impact of chronic stress and concentration-dependent effects of eight clinically used ADs (belonging to different chemical/functional classes) on evoked neuronal activity propagations through the hippocampal trisynaptic circuitry (HTC: perforant path - dentate gyrus - area CA3 - area CA1). Exposure of mice to chronic social defeat stress led to markedly weakened activity propagations (HTC-Waves). In contrast, at concentrations in the low micromolar range, all ADs, which were bath applied to slices, caused an amplification of HTC-Waves in CA regions (invariably in area CA1). The fast-acting antidepressant ketamine, the mood stabilizer lithium, and brain-derived neurotrophic factor (BDNF) exerted comparable enhancing effects, whereas the antipsychotic haloperidol and the anxiolytic diazepam attenuated HTC-Waves. Collectively, we provide direct experimental evidence that chronic stress can depress neuronal signal flow through the HTC and demonstrate shared opposing effects of ADs. Thus, our study points to a circuit-level mechanism of ADs to counteract stress-induced impairment of hippocampal network function. However, the observed effects of ADs are impossible to depend on enhanced neurogenesis

Lentivirus-mediated antagomir expression for specific inhibition of miRNA function

Micro RNAs (miRNA) regulate gene expression by hybridization and recruitment of multi-protein complexes to complementary mRNA target sequences. miRNA function can transiently be antagonized by antagomirs—chemically modified oligonucleotides complementary to individual miRNAs. Here, we describe the induction of stable loss-of-function phenotypes for specific miRNAs by lentivirus-mediated antagomir expression. Lentivirally expressed antagomirs are transcribed from a H1-promoter located within the lentiviral 3′LTR and were directed against miRNAs encoded on the polycistronic miR17-92 transcript. Functional silencing of miR-18a, miR-19b and miR-20a by the corresponding antagomirs specifically relieves miRNA-mediated reporter gene repression. Inhibition of miRNA function correlates to reduction of ‘miRNA’ amplification by miRNA-specific quantitative RT-PCR. Furthermore, protein expression of E2F-1, a known miR-20 target, is enhanced by lentivirally expressed anti-miR-20 antagomirs in a dose-dependent manner, whereas over-expression of miR-20a reduces E2F-1 levels. Finally, combined over-expression of specific miRNAs and antagomirs reveals individual and complementary functions of miR-18a and miR-20a and demonstrates specific miRNA impact on cell proliferation in a cell culture model

Anaesthesia Monitoring by Recurrence Quantification Analysis of EEG Data

Appropriate monitoring of the depth of anaesthesia is crucial to prevent deleterious effects of insufficient anaesthesia on surgical patients. Since cardiovascular parameters and motor response testing may fail to display awareness during surgery, attempts are made to utilise alterations in brain activity as reliable markers of the anaesthetic state. Here we present a novel, promising approach for anaesthesia monitoring, basing on recurrence quantification analysis (RQA) of EEG recordings. This nonlinear time series analysis technique separates consciousness from unconsciousness during both remifentanil/sevoflurane and remifentanil/propofol anaesthesia with an overall prediction probability of more than 85%, when applied to spontaneous one-channel EEG activity in surgical patients

Match me, if you can – Zum Einfluss von persönlichkeitsbasierter Ähnlichkeit zwischen Marke und Testimonial auf die wahrgenommene Passung und die Kaufwahrscheinlichkeit

Die Match-up-Hypothese besagt, dass eine für ein Produkt werbende Person (Testimonial) dann besonders effektiv ist, wenn die Eigenschaften des Testimonials mit denen der Marke übereinstimmen (z. B. Till & Busler, 2000). Die spärliche Forschung hierzu hat sich bislang mit Attraktivität und Expertenwissen beschäftigt, das Image von Testimonial und Marke aber überraschenderweise nicht berücksichtigt. Ein hierfür geeigneter Ansatz ist die Analyse der Persönlichkeit von Testimonial und Marke. Drei kulturübergreifend stabile Markenpersönlichkeitsdimensionen (Aufrichtigkeit, Erregung und Kultiviertheit) aus der Brand Personality Scale (Aaker, 1997) wurden in einem experimentellen Design (N = 120) unter Verwendung zweier Testimonials untersucht. Die Versuchsteilnehmenden bewerteten die Marke und das Testimonial auf denselben Persönlichkeitsdimensionen. Die Ergebnisse zeigen, dass die wahrgenommene Passung zwischen Testimonial und Marke umso höher ist, je größer die Ähnlichkeit auf den Persönlichkeitsdimensionen ist. Zudem führt eine hohe wahrgenommene Passung zu einem Anstieg der Kaufwahrscheinlichkeit. Implikationen für die Anwendung in Werbekampagnen werden gegeben