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Currently, no reliable genotype–phenotype correlation is available for pediatric Marfan patients in everyday clinical practice. We investigated correlations of FBN1 variants with the prevalence and age of onset of Marfan manifestations in childhood and differentiated three groups: missense/in-frame, splice, and nonsense/frameshift variants. In addition, we differentiated missense variants destroying or generating a cysteine (cys-missense) and alterations not affecting cysteine. We categorized 105 FBN1-positive pediatric patients. Patients with cys-missense more frequently developed aortic dilatation (p = 0.03) requiring medication (p = 0.003), tricuspid valve prolapse (p = 0.03), and earlier onset of myopia (p = 0.02) than those with other missense variants. Missense variants correlated with a higher prevalence of ectopia lentis (p = 0.002) and earlier onset of pulmonary artery dilatation (p = 0.03) than nonsense/frameshift, and dural ectasia was more common in the latter (p = 0.005). Pectus excavatum (p = 0.007) appeared more often in patients with splice compared with missense/in-frame variants, while hernia (p = 0.04) appeared earlier in the latter. Findings on genotype–phenotype correlations in Marfan-affected children can improve interdisciplinary therapy. In patients with cys-missense variants, early medical treatment of aortic dilatation seems reasonable and early regular ophthalmologic follow-up essential. Patients with nonsense/frameshift and splice variants require early involvement of orthopedic specialists to support the growing child.

Comets hold the key to the understanding of our solar system, its formation and its evolution, and to the fundamental plasma processes at work both in it and beyond it. A comet nucleus emits gas as it is heated by the sunlight. The gas forms the coma, where it is ionised, becomes a plasma and eventually interacts with the solar wind. Besides these neutral and ionised gases, the coma also contains dust grains, released from the comet nucleus. As a cometary atmosphere develops when the comet travels through the solar system, large-scale structures, such as the plasma boundaries, develop and disappear, while at planets such large-scale structures are only accessible in their fully grown, quasi-steady state. In situ measurements at comets enable us to learn both how such large-scale structures are formed or reformed and how small-scale processes in the plasma affect the formation and properties of these large scale structures. Furthermore, a comet goes through a wide range of parameter regimes during its life cycle, where either collisional processes, involving neutrals and charged particles, or collisionless processes are at play, and might even compete in complicated transitional regimes. Thus a comet presents a unique opportunity to study this parameter space, from an asteroid-like to a Mars- and Venus-like interaction. Fast flybys of comets have made many new discoveries, setting the stage for a multi-spacecraft mission to accompany a comet on its journey through the solar system. This white paper reviews the present-day knowledge of cometary plasmas, discusses the many questions that remain unanswered, and outlines a multi-spacecraft ESA mission to accompany a comet that will answer these questions by combining both multi-spacecraft observations and a rendezvous mission, and at the same time advance our understanding of fundamental plasma physics and its role in planetary systems.

Laser-induced acoustic desorption (LIAD) has recently been established as a tool for analytical chemistry. It is capable of launching intact, neutral, or low charged molecules into a high vacuum environment. This makes it ideally suited to mass spectrometry. LIAD can be used with fragile biomolecules and very massive compounds alike. Here, we apply LIAD time-of-flight mass spectrometry (TOF-MS) to the natural biochromophores chlorophyll, hemin, bilirubin, and biliverdin and to high mass fluoroalkyl-functionalized porphyrins. We characterize the variation in the molecular fragmentation patterns as a function of the desorption and the VUV postionization laser intensity. We find that LIAD can produce molecular beams an order of magnitude slower than matrix-assisted laser desorption (MALD), although this depends on the substrate material. Using titanium foils we observe a most probable velocity of 20 m/s for functionalized molecules with a mass m = 10 000 Da.

Hintergrund: Elektronische Prüfungen haben gegenüber papierbasierten Prüfungen den Vorteil, dass innovative kompetenzorientierte Aufgabenformate und -inhalte, wie z. B. Key-Feature-Aufgaben und Hot-Spot-Aufgaben, eingesetzt werden können. Bei der Einführung elektronischer Prüfungen,[zum vollständigen Text gelangen Sie über die oben angegebene URL], Gemeinsame Jahrestagung der Gesellschaft für Medizinische Ausbildung (GMA) und des Arbeitskreises zur Weiterentwicklung der Lehre in der Zahnmedizin (AKWLZ)

Hausaufgaben spielen in der Paartherapie unabhängig von deren theoretischer Ausrichtung eine bedeutende Rolle. Dabei variieren je nach therapeutischem Ansatz die Form der Inhalt die Häufigkeit und der Zeitpunkt im therapeutischen Prozess wann Hausaufgaben aufgegeben werden. Bezüglich Funktion der Hausaufgabe gibt es deutlich weniger Differenzen und die meisten Richtungen der Paartherapie anerkennen den Nutzen von Hausaufgaben zur Gewinnung neuer Einsichten oder zur Vertiefung und Festigung von neuen Verhaltensweisen Kognitionen oder Emotionen. Gerade in der Verhaltenstherapie mit Paaren spielen Hausaufgaben eine zentrale Rolle. Sie sind häufig inhaltlich und formal strukturiert und werden im Gegensatz zu anderen Ansätzen als verpflichtender Beitrag des Paares zum Gelingen der Therapie angesehen. Dieser Artikel versucht einen Überblick über den Einsatz und die Bedeutung von Hausaufgaben in der Paartherapie sowie über verschiedene Formen und Handhabungsmöglichkeiten zu geben. Schwierigkeiten mit Hausaufgaben im Rahmen der Paartherapie werden ebenfalls thematisiert.

Background: Human protein kinase CK2 represents a novel therapeutic target for neoplastic diseases. Inhibitors are in need to explore the druggability and the therapeutic options of this enzyme. A bottleneck in the search for new inhibitors is the availability of the target for testing. Therefore an assay was developed to provide easy access to CK2 for discovery of novel inhibitors. Results: Autodisplay was used to present human CK2 on the surface of Escherichia coli. Heterotetrameric CK2 consists of two subunits, α and β, which were displayed individually on the surface. Co-display of CK2α and CK2β on the cell surface led to the formation of functional holoenzyme, as demonstrated by NaCl dependency of enzymatic activity, which differs from that of the catalytic subunit CK2α without β. In addition interaction of CK2α and CK2β at the cell surface was confirmed by co-immunoprecipitation assays. Surface displayed CK2 holoenzyme enabled an easy IC50 value determination. The IC50 values for the known CK2 inhibitors TBB and Silmitasertib were determined to be 50 and 3.3 nM, respectively. Conclusion: Surface-displayed CK2α and CK2β assembled on the cell surface of E. coli to an active tetrameric holoenzyme. The whole-cell CK2 autodisplay assay as developed is suitable for inhibition studies. Furthermore, it can be used to determine quantitative CK2 inhibition data such as IC50 values. In summary, this is the first report on the functional surface display of a heterotetrameric enzyme on E. coli.

The upstream stimulatory factors (USFs) are regulators of important cellular processes. Both USF1 and USF2 are supposed to have major roles in metabolism, tissue protection and tumor development. However, the knowledge about the mechanisms that control the function of USFs, in particular in tissue protection and cancer, is limited. Phosphorylation is a versatile tool to regulate protein functions. Thereby, phosphorylation can positively or negatively affect different aspects of transcription factor function including protein stability, protein–protein interaction, cellular localization, or DNA binding. The present review aims to summarize the current knowledge about the regulation of USFs by direct phosphorylation and the consequences for USF functions in tissue protection and cancer. Correction article: Front. Pharmacol., 05 April 2016 | https://doi.org/10.3389/fphar.2016.00092