What Can We Learn from FGF-2 Isoform-Specific Mouse Mutants? Differential Insights into FGF-2 Physiology In Vivo

Fibroblast growth factor 2 (FGF-2), ubiquitously expressed in humans and mice, is functionally involved in cell growth, migration and maturation in vitro and in vivo. Based on the same mRNA, an 18-kilo Dalton (kDa) FGF-2 isoform named FGF-2 low molecular weight (FGF-2LMW) isoform is translated in humans and rodents. Additionally, two larger isoforms weighing 21 and 22 kDa also exist, summarized as the FGF-2 high molecular weight (FGF-2HMW) isoform. Meanwhile, the human FGF-2HMW comprises a 22, 23, 24 and 34 kDa protein. Independent studies verified a specific intracellular localization, mode of action and tissue-specific spatiotemporal expression of the FGF-2 isoforms, increasing the complexity of their physiological and pathophysiological roles. In order to analyze their spectrum of effects, FGF-2LMW knock out (ko) and FGF-2HMWko mice have been generated, as well as mice specifically overexpressing either FGF-2LMW or FGF-2HMW. So far, the development and functionality of the cardiovascular system, bone formation and regeneration as well as their impact on the central nervous system including disease models of neurodegeneration, have been examined. This review provides a summary of the studies characterizing the in vivo effects modulated by the FGF-2 isoforms and, thus, offers a comprehensive overview of its actions in the aforementioned organ systems.     

A DNA Methyltransferase Modulator Inspired by Peyssonenyne Natural Product Structures

A novel epigenetic modulator that displays a DNMT1 inhibition and DNMT3A activation profile was characterized (compound 8 ). This compound is a derivative of palmitic acid that incorporates the putative reactive functional group (diynone) of the peyssonenyne natural products. Other analogues containing the diynone or an acetoxyenediyne did not show the same biological profile. In U937 human leukemia cells, diynone 8 induced cell differentiation and apoptosis, which correlated with the expression of Fas protein. Very surprisingly, diynone 8 was toxic to normal human fibroblasts (BJ) and mouse embryo fibroblasts (MEF), but not to immortalized human fibroblasts (BJEL); this unique effect was not observed with the classical DNMT inhibitor 5‐azacytidine. Therefore, compound 8 interferes in a very specific manner with signaling pathways, the activities of which differ between normal and immortalized cell types. This toxicity is reminiscent of the effects of Dnmt1 ablation on mouse fibroblasts. In fact, some of the genes deregulated by the loss of Dnmt1 are similarly deregulated by 8 , but not by the DNMT inhibitor SGI‐1027.     

Die patentierten Erfindungen von Wolfgang Gaede aus der Zeit von 1905 bis 1945

The Patented Inventions from Wolfgang Gaede from 1905 to 1945 The collection of Gaede's patents shows how successfully cooperation between science and industry could bee. Several up to now important inventions in vacuum technique have been made and this in sometimes hard and difficult circumstances. Even when Gaede has lost his chair at the university of Karlsruhe from illegal intrigues by the Nazis.     

Towards an optimised lab procedure for long-term oxidative ageing of asphalt mix specimen

Ageing of bitumen leads to increased stiffness and brittleness. Thus, bituminous bound pavements become more prone to failure by low-temperature and fatigue cracking. Therefore, the ageing behaviour of bitumen has a crucial impact on durability, as well as recyclability of pavements. To assess ageing of bitumen, the rolling thin film oven test and pressure ageing vessel are standardised methods for short-term and long-term ageing in the lab. For lab-ageing of hot mix asphalt (HMA), various methods have been developed in the last decades. This paper presents a study on the potential of employing a highly oxidant gas for simulating the long-term oxidative ageing of asphalt mix specimens in the lab. Based on the results, an optimised lab-ageing procedure (Viennese Ageing Procedure – VAPro) for compacted HMA specimens to assess mix performance of long-term lab-aged specimens is developed. Thus, it is possible to optimise mix design not only for short-term performance but to take into account effects of oxidative ageing during its in-service life. VAPro is based on a triaxial cell with forced flow of a gaseous oxidant agent through the specimen. The oxidant agent is enriched in ozone and nitric oxides to increase the rate of oxidation. It is shown by stiffness tests of unaged and lab-aged specimens, as well as by Dynamic Shear Rheometer tests of recovered binder from aged specimens that asphalt mixes can be long-term aged at moderate temperatures (+60°C) and within 4 days and a flow rate of 1 l/min by applying VAPro. Thus, an ageing procedure is at hand that can simulate long-term ageing at conditions that are representative of conditions that occur in the field within an efficient amount of time.     

Thioether Analogues of Disulfide‐Bridged Cyclic Peptides Targeting Death Receptor 5: Conformational Analysis,Dimerisation and Consequences for Receptor Activation

Cyclic peptides containing redox‐stable thioether bridges might provide a useful alternative to disulfide‐bridged bioactive peptides. We report the effect of replacing the disulfide bridge with a lanthionine linkage in a 16‐mer cyclic peptide that binds to death receptor 5 (DR5, TRAIL‐R2). Upon covalent oligomerisation, the disulfide‐bridged peptide has previously shown similar behaviour to that of TNF‐related apoptosis inducing ligand (TRAIL), by selectively triggering the DR5 cell death pathway. The structural and biological properties of the DR5‐binding peptide and its desulfurised analogue were compared. Surface plasmon resonance (SPR) data suggest that these peptides bind DR5 with comparable affinities. The same holds true for dimeric versions of these peptides: the thioether is able to induce DR5‐mediated apoptosis of BJAB lymphoma and tumorigenic BJELR cells, albeit to a slightly lower extent compared to its disulfide homologue. NMR analysis revealed subtle variation in the conformations of the two peptides and suggests that the thioether peptide is slightly less folded than its disulfide homologue. These observations could account for the different capability of the two dimers to cluster DR5 receptors on the cell surface and to trigger apoptosis. Nevertheless, our results suggest that the thioether peptide is a potential candidate for evaluation in animal models.     

High-Resolution Infrared Fourier-Transform Spectroscopy and Rotational Constants of the nu4 Band of BrNO2

In this study, we assessed the influence of three analgesic techniques on postoperative knee rehabilitation after total knee arthroplasty (TKA). Forty-five patients scheduled for elective TKA under general anesthesia were randomly divided into three groups. Postoperative analgesia was provided with i.v. patient-controlled analgesia (PCA) with morphine in Group A, continuous 3-in-1 block in Group B, and epidural analgesia in Group C. Immediately after surgery, the three groups started identical physical therapy regimens. Pain scores, supplemental analgesia, side effects, degree of maximal knee flexion, day of first walk, and duration of hospital stay were recorded. Patients in Groups B and C reported significantly lower pain scores than those in Group A. Supplemental analgesia was comparable in the three groups. Compared with Groups A and C, a significantly lower incidence of side effects was noted in Group B. Significantly better knee flexion (until 6 wk after surgery), faster ambulation, and shorter hospital stay were noted in Groups B and C. However, these benefits did not affect outcome at 3 mo. We conclude that, after TKA, continuous 3-in-1 block and epidural analgesia provide better pain relief and faster knee rehabilitation than i.v. PCA with morphine. Because it induces fewer side effects, continuous 3-in-1 block should be considered the technique of choice. Implications: In this study, we determined that, after total knee arthroplasty, loco-regional analgesic techniques (epidural analgesia or continuous 3-in-1 block) provide better pain relief and faster postoperative knee rehabilitation than i.v. patient-controlled analgesia with morphine. Because it causes fewer side effects than epidural analgesia, continuous 3-in-1 block is the technique of choice.     

Efficiency of Light Outcoupling Structures in Organic Light‐Emitting Diodes: 2D TiO2 Array as a Model System

Organic light‐emitting diodes (OLEDs) are widely used in research and are established in the industry. The building block nature of organic compounds enables a vast variety of materials. On top of that, there exist many strategies to improve the light outcoupling of OLEDs making a direct comparison of outcoupling technologies difficult. Here, a novel approach is introduced for the evaluation of light outcoupling structures. The new defined “efficiency of light outcoupling structures” (ELOS) clearly determines the effectiveness of the light outcoupling structure by weighting the experimental efficiency enhancement over the theoretical outcoupling gain. It neither depends on cavity design nor on the chosen organic material. The methodology is illustrated for red phosphorescent OLEDs comprising internal and external light outcoupling structures. Assumptions and further uses are discussed with respect to experimental and theoretical handling. In addition, the ELOS is calculated for various outcoupling techniques from literature to demonstrate the universality. Finally, most suitable reference OLEDs are discussed for application of light outcoupling structures. The presented approach enables new possibilities for studying light outcoupling structures and improves their comparability in a highly material‐driven research field.