The effect of microgravity on skeletal muscles has so far been examined in rat and mice only after short-term (5–20 day) spaceflights. The mice drawer system (MDS) program, sponsored by Italian Space Agency, for the first time aimed to investigate the consequences of long-term (91 days) exposure to microgravity in mice within the International Space Station. Muscle atrophy was present indistinctly in all fiber types of the slow-twitch soleus muscle, but was only slightly greater than that observed after 20 days of spaceflight. Myosin heavy chain analysis indicated a concomitant slow-to-fast transition of soleus. In addition, spaceflight induced translocation of sarcolemmal nitric oxide synthase-1 (NOS1) into the cytosol in soleus but not in the fast-twitch extensor digitorum longus (EDL) muscle. Most of the sarcolemmal ion channel subunits were up-regulated, more in soleus than EDL, whereas Ca 2+ -activated K + channels were down-regulated, consistent with the phenotype transition. Gene expression of the atrophy-related ubiquitin-ligases was up-regulated in both spaceflown soleus and EDL muscles, whereas autophagy genes were in the control range. Muscle-specific IGF-1 and interleukin-6 were down-regulated in soleus but up-regulated in EDL. Also, various stress-related genes were up-regulated in spaceflown EDL, not in soleus. Altogether, these results suggest that EDL muscle may resist to microgravity-induced atrophy by activating compensatory and protective pathways. Our study shows the extended sensitivity of antigravity soleus muscle after prolonged exposition to microgravity, suggests possible mechanisms accounting for the resistance of EDL, and individuates some molecular targets for the development of countermeasures.

The coordination of copper to the amyloid-β (1-16) (Aβ) peptide has been investigated because of its relevance for understanding Cu redox activity when the ion is embedded in peptides involved in neurodegenerative diseases. In this work, several reasonable models of Cu(+) coordination were built on the basis of experimental information and investigated by first-principles molecular dynamics simulations in the Car-Parrinello scheme. The propensity of a linear Nδ (His)-Cu-Nδ (His) coordination for Cu(+) is shown by all the models investigated here, with distortions due to weak interactions with the carbonyl O of His 6 and His 13 and with the amide N of His 14. Though the His 6-Cu-His 14 linear coordination is favored in truncated models, the His 13-Cu-His 14 linear coordination is favored by interactions present in the complete solvated and in vacuo models of Cu-Aβ (1-16). These interactions include steric hindrance for the expulsion of His 13, hydrogen bonds between Asp and His side chains and a network of electrostatic interactions stabilizing two separated 1-10 and 11-16 peptide regions. The role of linear His 13-Cu-His 14 coordination in stabilizing Cu(I) and in increasing the Cu(II)/Cu(I) reorganization energy can be therefore modulated by boundary conditions acting on the Aβ (1-16) ligand.