Deubiquitinating Enzyme USP8 Is Essential for Skeletogenesis by Regulating Wnt Signaling

Disturbance in a differentiation program of skeletal stem cells leads to indecorous skeletogenesis. Growing evidence suggests that a fine-tuning of ubiquitin-mediated protein degradation is crucial for skeletal stem cells to maintain their stemness and osteogenic potential. Here, we demonstrate that the deubiquitinating enzyme (DUB) ubiquitin-specific protease 8 (USP8) stabilizes the Wnt receptor frizzled 5 (FZD5) by preventing its lysosomal degradation. This pathway is essential for Wnt/β-catenin signaling and the differentiation of osteoprogenitors to mature osteoblasts. Accordingly, deletion of USP8 in osteoprogenitors (Usp8^Osx) resulted in a near-complete blockade in skeletal mineralization, similar to that seen in mice with defective Wnt/β-catenin signaling. Likewise, transplanting USP8-deficient osteoprogenitors under the renal capsule in wild-type secondary hosts did not to induce bone formation. Collectively, this study unveils an essential role for the DUB USP8 in Wnt/β-catenin signaling in osteoprogenitors and osteogenesis during skeletal development.     

Modifiziertes Fibrillierverhalten von lösungsgesponnenen Cellulosefasern durch Umsetzungen mit Reaktivfarbstoffen

The macroscopic symptoms of the high crystallinity of solvent-spun cellulosic fibres appear as a specific tendency to fibrillation, if the swollen fibres are exposed to mechanical stress. The method of proving such fibrillations is the wet abrasion. An increase of the binding forces between the fibril structural elements of the solvent-spun cellulosic fibres results in a reduction of fibrillation. The reinforced bonds are also reflected in increased wet abrasion numbers. By reaction with solvent-spun cellulosic fibres, mono- as well as bi(poly)functional reactive dyestuffs can increase the wet abrasion number. This fact could indicate crosslinking processes between cellulosic chains. The effect of monofunctional reactive dyestuffs with two reactive centres in one reactive group is imaginable as a partial crosslinking realised by covalent and hydrogen bridge bonds. Essentially higher wet abrasion numbers can be achieved with bifunctional reactive dyestuffs. By means of the wet abrasion test it was found that there is a relation between the structural characteristics of the dyestuff and its ability to form crosslinking bridges. In this case the arrangement of the reactive groups on the chromophore and the constitution of the chromophore play an important role. Furthermore, the wet abrasion number is influenced by the concentration of the reactive dyestuff and by the dyeing conditions, for example electrolyte quantity, pH-value and dyeing temperature.     

Untersuchungen zur Naßvernetzung von Lyocell-Fasern

The high wet fibrillation tendency of Lyocell fibres forms the background to this investigation. The wet abrasion behaviour can be improved by crosslinking reactions. Substances containing sulfato ethyl sulfonyl groups but different bridging groups were synthesised and optimised regarding to their application. The wet fibrillation tendency can be reduced clearly with these selected substances. If the concentration of the crosslinking agent on the fibre is the basis of comparisons the different structures have a similar effect on the fibrillation tendency. So the swollen Lyocell fibre permits a crosslinking reaction with curing agents of different size.     

Age-related differences in warning symbol comprehension and training effectiveness: effects of familiarity, complexity, and comprehensibility

Age-related changes in selective attention, inhibitory efficiency, and the ability to form new associations suggest that older adults may have greater difficulty with more complex and less comprehensible symbols. We examined comprehension of symbols varying in terms of ratings of familiarity, complexity, and comprehensibility, by younger (aged 18-35) and older (aged 55-70) adults. It was found that older adults have greater difficulty than younger adults in comprehending warning symbols and that accident scenario training improves comprehension. Regression analyses indicated that familiarity and comprehensibility were important in determining performance on the pre-training comprehension test by both younger and older adults. However, training eliminated the effects of stimulus characteristics for younger adults, while older adults' comprehension continued to be significantly influenced by comprehensibility. We suggest that symbol design incorporates cues to knowledge to facilitate the linkage between new knowledge (i.e. the warning symbol) and relevant knowledge in long-term memory. Statement of Relevance: Symbol characteristics play an important role in age-related differences in warning symbol comprehension. To optimise comprehension by older adults, symbols should have a clear relationship with areal-world referent. Alternatively, symbol design could incorporate cues to knowledge to facilitate the linkage between new knowledge and relevant knowledge in long-term memory.     

Development of a specially tailored local drug delivery system for the prevention of fibrosis after insertion of cochlear implants into the inner ear

A cochlear implant (CI)-associated local drug delivery system based on dexamethasone (DMS) was developed with the purpose to inhibit the growth of fibrotic tissue which influences the signal transmission from the CI to the neurons of the inner ear. For the realization of a targeted DMS delivery the following concepts were combined: modification of the silicone-based electrode carrier by incorporation of DMS and a DMS-containing polymeric coating chemically attached on the surface of the electrode carrier. It was demonstrated that the coated CI showed a high coating stability in a simulated implantation procedure. The in vitro drug release studies in a quasi-stationary model revealed a faster DMS release in the initial phase originating from the DMS-containing coatings and then a lower and sustained DMS release originating from the DMS-loaded silicone carrier. The performed in vitro biocompatibility study confirmed that the released DMS was non-toxic for cultured spiral ganglion cells.     

Warning symbols as reminders of hazards: impact of training

Prior research indicates that many warning symbols are poorly understood. However Lesch [Lesch, M.F., 2003. Comprehension and memory for warning symbols: Age-related differences and impact of training. J. Safety Res. 34, 495–505] found that accident scenarios could be used to improve comprehension of warning symbols. The current study further investigated the potential benefits of accident scenario training. During training, warning symbols with verbal labels corresponding to the meaning of the symbol were paired with accident scenarios which expanded on the nature of the hazard, the required/prohibited actions, as well as the possible consequences of failing to comply. A number of measures were obtained prior to, and following (immediately and 2 weeks later), the accident scenario training: comprehension across three knowledge types (verbal label, required/prohibited actions, potential consequences of failure to comply), ratings of agreement with statements reflecting perceived control, and ratings of hazard and intent to comply. Benefits of training were observed on all dependent measures: Comprehension improved from 43 to 82% correct, reaction times were reduced by about 2 s, and level of confidence in correct responses increased by 23%. Ratings of perceived hazard, intent to comply, and perceived control over accident/injury involvement also increased. It is suggested that accident scenario training can be used to help prevent accidents and injuries by ensuring that responses to warnings are “sure and swift”.     

Remembering to be afraid: applications of theories of memory to the science of safety communication

Since it is not always possible to design-out hazards, safety communications take on the critical roles of warning about potential hazards, informing how to avoid injury, and revealing the possible consequences of failing to take appropriate action. Failures to adequately communicate, comprehend, or remember safety information may result in serious injury or death. While one goal of safety communications is to persuade, the focus here is on their role as reminders of hazards. It is suggested that psychological research in the area of memory can provide pointers as to how to improve a warning's ability to communicate safety information such that it is adequately understood and remembered. Towards this end, selected psychological theories and findings in the area of memory and their application to the study of warning processing are reviewed. Based on the studies reviewed, recommendations are made for improving memory for warning information and areas for future research are suggested. It is concluded that increased communication and collaboration among researchers from different disciplines, as well as professionals in the field, will more rapidly advance the science of safety communication.