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The amyloid precursor protein (APP) and its paralogs, amyloid precursor-like protein 1 (APLP1) and APLP2, are metalloproteins with a putative role both in synaptogenesis and in maintaining synapse structure. Here, we studied the effect of zinc on membrane localization, adhesion, and secretase cleavage of APP, APLP1, and APLP2 in cell culture and rat neurons. For this, we employed live-cell microscopy techniques, a microcontact printing adhesion assay and ELISA for protein detection in cell culture supernatants. We report that zinc induces the multimerization of proteins of the amyloid precursor protein family and enriches them at cellular adhesion sites. Thus, zinc facilitates the formation of de novo APP and APLP1 containing adhesion complexes, whereas it does not have such influence on APLP2. Furthermore, zinc-binding prevented cleavage of APP and APLPs by extracellular secretases. In conclusion, the complexation of zinc modulates neuronal functions of APP and APLPs by (i) regulating formation of adhesion complexes, most prominently for APLP1, and (ii) by reducing the concentrations of neurotrophic soluble APP/APLP ectodomains.
A simple way to prepare cucurbit[5]uril is described. The macrocycles of the cucurbituril type are nearly insoluble in water. The solubilities of cucurbit[5]uril, decamethylcucurbit[5]uril and cucurbit[6]uril in hydrochloric acid, formic acid and acetic acid of different concentrations have been investigated. Due to the formation of complexes between cucurbit[n]urils and protons the solubility increases in aqueous acids. The macrocyclic ligands are able to form complexes with several organic compounds. Thus, the complex formation of the cucurbituril macrocycles with different amines has beenstudied by means of calorimetric titrations. The reaction enthalpy gives noevidence of the formation of inclusion or exclusion complexes. 1H-NMR measurements show that in the case of cucurbit[5]uril and cucurbit[6]uril the organic guest compound is included within the hydrophobic cavity. Decamethylcucurbit[5]uril forms only exclusion complexes with organicamines. This was confirmed by the crystal structure of the decamethylcucurbit[5]uril-1,6- diaminohexane complex. complex formation - cucurbit[5]uril - cucurbit[6]uril - decamethylcucurbit[5]uril - solubility - synthesis
A new method is proposed for tracking individual motor units (MUs) across multiple experimental sessions on different days. The technique is based on a novel decomposition approach for high-density surface electromyography and was tested with two experimental studies for reliability and sensitivity. Experiment I (reliability): ten participants performed isometric knee extensions at 10, 30, 50 and 70% of their maximum voluntary contraction (MVC) force in three sessions, each separated by 1 week. Experiment II (sensitivity): seven participants performed 2 weeks of endurance training (cycling) and were tested pre-post intervention during isometric knee extensions at 10 and 30% MVC. The reliability (Experiment I) and sensitivity (Experiment II) of the measured MU properties were compared for the MUs tracked across sessions, with respect to all MUs identified in each session. In Experiment I, on average 38.3% and 40.1% of the identified MUs could be tracked across two sessions (1 and 2 weeks apart), for the vastus medialis and vastus lateralis, respectively. Moreover, the properties of the tracked MUs were more reliable across sessions than those of the full set of identified MUs (intra-class correlation coefficients ranged between 0.63-0.99 and 0.39-0.95, respectively). In Experiment II, similar to 40% of the MUs could be tracked before and after the training intervention and training-induced changes in MU conduction velocity had an effect size of 2.1 (tracked MUs) and 1.5 (group of all identified motor units). These results show the possibility of monitoring MU properties longitudinally to document the effect of interventions or the progression of neuromuscular disorders.
Objective: To assess the intra-and inter-session reliability of estimates of motor unit behavior and muscle fiber properties derived from high-density surface electromyography (HDEMG). Methods: Ten healthy subjects performed submaximal isometric knee extensions during three recording sessions (separate days) at 10%, 30%, 50% and 70% of their maximum voluntary effort. The discharge timings of motor units of the vastus lateralis and medialis muscles were automatically identified from HDEMG by a decomposition algorithm. We characterized the number of detected motor units, their discharge rates, the coefficient of variation of their inter-spike intervals (CoVisi), the action potential conduction velocity and peak-to-peak amplitude. Reliability was assessed for each motor unit characteristics by intra-class correlation coefficient (ICC). Additionally, a pulse-to-noise ratio (PNR) was calculated, to verify the accuracy of the decomposition. Results: Good to excellent reliability within and between sessions was found for all motor unit characteristics at all force levels (ICCs > 0.8), with the exception of CoVisi that presented poor reliability (ICC < 0.6). PNR was high and similar for both muscles with values ranging between 45.1 and 47.6 dB (accuracy > 95%). Conclusion: Motor unit features can be assessed non-invasively and reliably within and across sessions over a wide range of force levels. Significance: These results suggest that it is possible to characterize motor units in longitudinal intervention studies. (C) 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.