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Multiple Sclerosis (MS) is a neuroinflammatory disorder, which is histopathologically characterized by multifocal inflammatory demyelinating lesions affecting both the central nervous system's white and grey matter. Especially during the progressive phases of the disease, immunomodulatory treatment strategies lose their effectiveness. To develop novel progressive MS treatment options, pre-clinical animal models are indispensable. Among the various different models, the cuprizone de- and remyelination model is frequently used. While most studies determine tissue damage and repair at the histological and ultrastructural level, functional readouts are less commonly applied. Among the various overt functional deficits, gait and coordination abnormalities are commonly observed in MS patients. Motor behavior is mediated by a complex neural network that originates in the cortex and terminates in the skeletal muscles. Several methods exist to determine gait abnormalities in small rodents, including the rotarod testing paradigm. In this review article, we provide an overview of the validity and characteristics of the rotarod test in cuprizone-intoxicated mice.

Two full-length analogs of the anticancer peptide yaku'amide A (1a) and four partial structures have been synthesized. These analogs were identified by computational studies in which the three E - and Z -ΔIle residues of the natural product were replaced by the more accessible dehydroamino acids ΔVal and ΔEnv. Of the eight possible analogs, modeling showed that the targeted structures 2a and 2b most closely resembled the three-dimensional structure of 1a. Synthesis of 2a and 2b followed a convergent route that was streamlined by the absence of ΔIle in the targets. Screening of the compounds against various cancer cell lines revealed that 2a and 2b mimic the potent anticancer activity of 1a, thereby validating the computational studies., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Total synthesis of the anticancer peptide natural product yaku'amide A is reported. Its β-tert-hydroxy amino acids were prepared by regioselective aminohydroxylation involving a chiral mesyloxycarbamate reagent. Stereospecific construction of the E- and Z-ΔIle residues was accomplished through a one-pot reaction featuring anti dehydration, azide reduction, and O→N acyl transfer. Alkene isomerization was negligible during this process. These methods enabled a highly convergent and efficient synthetic route to the natural product., (© 2020 Wiley-VCH GmbH.)

The synthesis of functionalized nitriles via microwave-promoted radical fragmentations of cyclic O-phenyl oxime ethers is reported. A variety of radical traps can be employed, permitting the generation of diverse adducts via C-O, C-C, C-N, or C-X bond formation. Other salient features include a simple and practical protocol, very short reaction times, and the avoidance of metal catalysts and toxic cyanide reagents. The utility of this method is demonstrated by the ring-distortion of a steroid-derived substrate., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The key idea underlying many Ambient Intelligence (AmI) projects and applications is context awareness, which is based mainly on their capacity to identify users and their locations. The actual computing capacity should remain in the background, in the periphery of our awareness, and should only move to the center if and when necessary. Computing thus becomes 'invisible', as it is embedded in the environment and everyday objects. The research project described herein aims to realize an Ambient Intelligence-based environment able to improve users' quality of life by learning their habits and anticipating their needs. This environment is part of an adaptive, context-aware framework designed to make today's incompatible heterogeneous domotic systems fully interoperable, not only for connecting sensors and actuators, but for providing comprehensive connections of devices to users. The solution is a middleware architecture based on open and widely recognized standards capable of abstracting the peculiarities of underlying heterogeneous technologies and enabling them to co-exist and interwork, without however eliminating their differences. At the highest level of this infrastructure, the Ambient Intelligence framework, integrated with the domotic sensors, can enable the system to recognize any unusual or dangerous situations and anticipate health problems or special user needs in a technological living environment, such as a house or a public space.