β1-Syntrophin Modulation by miR-222 in mdx Mice

Background: In mdx mice, the absence of dystrophin leads to the deficiency of other components of the dystrophin-glycoprotein complex (DAPC), making skeletal muscle fibers more susceptible to necrosis. The mechanisms involved in the disappearance of the DAPC are not completely understood. The muscles of mdx mice express normal amounts of mRNA for the DAPC components, thus suggesting post-transcriptional regulation. Methodology/Principal Findings: We investigated the hypothesis that DAPC reduction could be associated with the microRNA system. Among the possible microRNAs (miRs) found to be upregulated in the skeletal muscle tissue of mdx compared to wt mice, we demonstrated that miR-222 specifically binds to the 3′-UTR of β1-syntrophin and participates in the downregulation of β1-syntrophin. In addition, we documented an altered regulation of the 3′-UTR of β1-syntrophin in muscle tissue from dystrophic mice. Conclusion/Significance: These results show the importance of the microRNA system in the regulation of DAPC components in dystrophic muscle, and suggest a potential role of miRs in the pathophysiology of dystrophy. © 2010 De Arcangelis et al

Adaptation of Mouse Skeletal Muscle to Long-Term Microgravity in the MDS Mission

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 Ca2+-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

Un caso di carcinoma del surrene sinistro con trombo cavale esteso all’atrio destro

We describe a case of cancer of the left adrenal gland with a thrombus of the vena cava that reached the right atrium which was treated with abdominal and cardiac surgery. The positive outcome and the current literature lead the Authors to sustain surgical intervention with the aim either of radical eradication or reduction of the neoplastic mass leading to a reduction of the ormonal effects and a better effectiveness of adjuvant therapy

On ground preflight studies on skeletal muscle from mice kept in the Mouse Drawer System (MDS)

The Mouse Drawer System (MDS) has been developed to individually accommodate mice on board the International Space Station. MDS size is 110 x 118 mm (floor area) and 85 mm height, which is several fold smaller than standard laboratory cages, and may affect mouse activity. The study was aimed at establish the effects of 20-day housing in MDS on 2-month-old male mice compared to age-matched controls individually housed in normal cages. After 20 days, body weight of MDS mice (n = 3) decreased by about 12% whereas that of controls (n = 3) increased by about 4.4%. The mean cross sectional area of EDL and soleus muscle fibers of MDS mice was slightly lower than that of controls. SDS-PAGE analysis of myosin heavy chain (MyHC) composition shows that type 2B MyHC was slightly reduced in MDS EDL compared to control. Expression of the activity-dependent gene PGC-1a and of IGF-1 isoforms was up-regulated in MDS soleus, whereas that of chloride channel-1 was unchanged. Expression of ubiquitin-ligases and autophagic genes was only slightly modified. The study shows that short-term housing in the MDS payload produces adaptive changes on hind limb skeletal muscle properties, known to disappear in prolonged housing