Long-Term Exercise Reduces Formation of Tubular Aggregates and Promotes Maintenance of Ca2+ Entry Units in Aged Muscle

Tubular aggregates (TAs) in skeletal muscle fibers are unusual accumulation of sarcoplasmic reticulum (SR) tubes that are found in different disorders including TA myopathy (TAM). TAM is a muscular disease characterized by muscle pain, cramping, and weakness that has been recently linked to mutations in STIM1 and ORAI1. STIM1 and ORAI1 are the two main proteins mediating store-operated Ca2+ entry (SOCE), a mechanism activated by depletion of intracellular Ca2+ stores (e.g., SR) that allows recovery of Ca2+ from the extracellular space during repetitive muscle activity. We have recently shown that exercise triggers the formation of unique intracellular junctions between SR and transverse tubules named Ca2+entry units (CEUs). CEUs promote colocalization of STIM1 with ORAI1 and improve muscle function in presence of external Ca2+. TAs virtually identical to those of TAM patients are also found in fast-twitch fibers of aging male mice. Here, we used a combination of electron and confocal microscopy, Western blotting, and ex vivo stimulation protocols (in presence or absence of external Ca2+) to evaluate the presence of TAs, STIM1-ORAI1 localization and expression and fatigue resistance of intact extensor digitorum longus (EDL) muscles in wild-type male adult (4-month-old) and aged (24-month-old) mice and in mice trained in wheel cages for 15 months (from 9 to 24 months of age). The results collected indicate that (i) aging causes STIM1 and ORAI1 to accumulate in TAs and (ii) long-term exercise significantly reduced formation of TAs. In addition, (iii) EDL muscles from aged mice exhibited a faster decay of contractile force than adult muscles, likely caused by their inability to refill intracellular Ca2+ stores, and (iv) exercise in wheel cages restored the capability of aged EDL muscles to use external Ca2+ by promoting maintenance of CEUs. In conclusion, exercise prevented improper accumulation of STIM1 and ORAI1 in TAs during aging, maintaining the capability of aged muscle to refill intracellular Ca2+ stores via SOCE.

Ferro-Self-Assembly: Magnetic and Electrochemical Adaptation of a Multiresponsive Zwitterionic Metalloamphiphile Showing a Shape-Hysteresis Effect

We report on a novel multi-stimuli-responsive amphiphile, 1-(<i>Z</i>)-heptenyl-1’-dimethylammonium-methyl-(3-sulfopropyl)ferrocene<b> </b>(<b>6</b>), whose self-assembly properties can be altered by three different stimuli, namely: (i) the addition of external salts which serve to unfold the sultone headgroup, thus triggering self-assembly of <b>6</b> into vesicles; (ii) oxidation to <b>6⁺</b>, which changes the lipophilic ferrocene to a hydrophilic ferrocenium entity, thereby broadening the size-distribution of the aggregates; and (iii) exposition of <b>6⁺ </b>to an external magnetic field of 0.8 T. Under thease conditions and at sufficient concentration, <b>6</b>^<b>+</b>forms large, tubular aggregates with lengths of up to 15 µm, which persist for over 5 min after the field is switched off again. <b>6⁺</b> is thus the first amphiphile to exhibit a shape-hysteresis effect. The self-assembly/disassembly processes and their dynamics were studied live and in situ by optical birefringence measurements coupled to light scattering. <br>

Ferro-Self-Assembly: Magnetic and Electrochemical Adaptation of a Multiresponsive Zwitterionic Metalloamphiphile Showing a Shape-Hysteresis Effect

We report on a novel multi-stimuli-responsive amphiphile, 1-(<i>Z</i>)-heptenyl-1’-dimethylammonium-methyl-(3-sulfopropyl)ferrocene<b> </b>(<b>6</b>), whose self-assembly properties can be altered by three different stimuli, namely: (i) the addition of external salts which serve to unfold the sultone headgroup, thus triggering self-assembly of <b>6</b> into vesicles; (ii) oxidation to <b>6⁺</b>, which changes the lipophilic ferrocene to a hydrophilic ferrocenium entity, thereby broadening the size-distribution of the aggregates; and (iii) exposition of <b>6⁺ </b>to an external magnetic field of 0.8 T. Under thease conditions and at sufficient concentration, <b>6</b>^<b>+</b>forms large, tubular aggregates with lengths of up to 15 µm, which persist for over 5 min after the field is switched off again. <b>6⁺</b> is thus the first amphiphile to exhibit a shape-hysteresis effect. The self-assembly/disassembly processes and their dynamics were studied live and in situ by optical birefringence measurements coupled to light scattering. <br>

Stormorken Syndrome: A Rare Cause of Myopathy With Tubular Aggregates and Dystrophic Features

Stormorken syndrome is a rare genetic disorder (MIM 185070) first reported in 1983 with thrombocytopenia, muscle weakness, asplenia, and miosis caused by a mutation of the stromal interaction molecule 1 ( STIM1) gene.1 The muscle weakness is caused by a myopathy with tubular aggregate formation. We report a family in which both child and mother presented with proximal muscle weakness and thrombocytopenia. Histologic, histochemical, and electron microscopy studies were performed on the muscle specimen. It documented accumulation of tubular aggregates and chronic myopathic changes with dystrophic features. Genetic testing revealed that both mother and son carried a missense mutation of c.326A>G in exon 3 of the STIM1 gene, which is novel for Stormorken syndrome. We suggest that patients with unexplained chronic idiopathic thrombocytopenia and proximal weakness have genetic testing for Stormorken syndrome.

Sheet-like and tubular aggregates of protein nanofibril–phosphate hybrids

Nanofibrils assembled by bovine serum albumin aligned into microtubes and nanosheets upon heating and cooling its solution in phosphate buffer.