Neurofilaments: Properties, Functions, and Regulation - Springer

Neuronal intermediate filaments are the most prominent cytoskeleton component of adult neurons in both central and peripheral nervous system. They include neurofilament triplet proteins, peripherin, α-internexin, nestin, and synemin. Although it was initially thought that neuronal intermediate filaments serve a primarily structural function, it has since been demonstrated that they constitute a dynamic network involved in neuronal differentiation, axon outgrowth, and regeneration. Finally, they emerged as a primary cause of some neurodegenerative diseases. Here, we focus on the properties, function, and regulation of neuronal intermediate filaments as well as their relationship to different neurodegenerative diseases

Integration of the Forward Detectors inside the LHC Machine

Several forward detectors have been installed in the LHC long straight sections located on each side of the experimental caverns. Most of these detectors have been designed by the LHC experiments to study the forward physics while some of them are dedicated to the measurement of the LHC luminosity. The integration and the installation of the forward detectors have required an excellent coordination between the experiments and the different CERN groups involved into the design and the installation of the LHC accelerator. In some cases the integration of these detectors has required a modification of the standard beam lines in order to maximise their physics potential. Finally, additional systems have been installed in the LHC tunnel to ensure the operation of the forward detectors in a high radiation environment

Efficacy of targeting bone-specific GIP receptor in ovariectomy-induced bone loss

Glucose-dependent insulinotropic polypeptide (GIP) has been recognized in the last decade as an important contributor of bone remodeling and is necessary for optimal bone quality. However, GIP receptors are expressed in several tissues in the body and little is known about the direct versus indirect effects of GIP on bone remodeling and quality. The aims of the present study were to validate two new GIP analogues, called [D-Ala2]-GIP-Tag and [D-Ala2]-GIP1-30, that specifically target either bone or whole body GIP receptors, respectively; and to ascertain the beneficial effects of GIP therapy on bone in a mouse model of ovariectomy-induced bone loss. Both GIP analogues exhibited similar binding capacities at the GIP receptor and intracellular responses as full-length GIP1-42. Furthermore, only [D-Ala2]-GIP-Tag, but not [D-Ala2]-GIP1-30, was undoubtedly found exclusively in the bone matrix and released at acidic pH. In ovariectomized animals, [D-Ala2]-GIP1-30 but not [D-Ala2]-GIP-Tag ameliorated bone stiffness at the same magnitude than alendronate treatment. Only [D-Ala2]-GIP1-30 treatment led to significant ameliorations in cortical microarchitecture. Although alendronate treatment increased the hardness of the bone matrix and the type B carbonate substitution in the hydroxyapatite crystals, none of the GIP analogues modified bone matrix composition. Interestingly, in ovariectomy-induced bone loss, [D-Ala²]-GIP-Tag failed to alter bone strength, microarchitecture and bone matrix composition. Overall, this study shows that the use of a GIP analogue that target whole body GIP receptors might be useful to improve bone strength in ovariectomized animals