Mitochondrial dysfunction causes Ca2+ overload and ECM degradation-mediated muscle damage in C. elegans

This is the final version. Available on open access from the Federation of American Society of Experimental Biology via the DOI in this recordMitochondrial dysfunction impairs muscle health and causes subsequent muscle wasting. This study explores the role of mitochondrial dysfunction as an intramuscular signal for the extracellular matrix (ECM)-based proteolysis and, consequentially, muscle cell dystrophy. We found that inhibition of the mitochondrial electron transport chain causes paralysis as well as muscle structural damage in the nematode Caenorhabditis elegans. This was associated with a significant decline in collagen content. Both paralysis and muscle damage could be rescued with collagen IV overexpression, matrix metalloproteinase (MMP), and Furin inhibitors in Antimycin A-treated animal as well as in the C. elegans Duchenne muscular dystrophy model. Additionally, muscle cytosolic calcium increased in the Antimycin A-treated worms, and its down-regulation rescued the muscle damage, suggesting that calcium overload acts as one of the early triggers and activates Furin and MMPs for collagen degradation. In conclusion, we have established ECM degradation as an important pathway of muscle damage.-Sudevan, S., Takiura, M., Kubota, Y., Higashitani, N., Cooke, M., Ellwood, R. A., Etheridge, T., Szewczyk, N. J., Higashitani, A. Mitochondrial dysfunction causes Ca2+ overload and ECM degradation-mediated muscle damage in C. elegans.Ministry of Education, Culture, Sports, Science, and Technology (MEXT)Cross-Ministerial Strategic Innovation Promotion ProgramAdvanced Research and Development Programs for Medical Innovation (AMED-CRESTBiotechnology and Biological Sciences Research Council (BBSRC)UK Space AgencyScience and Technology Facilities Council (STFC)Otsuka Toshimi FoundationTohoku UniversityJapan Student Services Organizatio

Rough Surface Effect on Meissner Diamagnetism in Normal-layer of N-S Proximity-Contact System

Rough surface effect on the Meissner diamagnetic current in the normal layer of proximity contact N-S bi-layer is investigated in the clean limit. The diamagnetic current and the screening length are calculated by use of quasi-classical Green's function. We show that the surface roughness has a sizable effect, even when a normal layer width is large compared with the coherence length $\xi =v_{\rm F}/\pi T_{\rm c}$. The effect is as large as that of the impurity scattering and also as that of the finite reflection at the N-S interface.Comment: 12 pages, 3 figures. To be published in J. Phys. Soc. Jpn. Vol.71-

Magnetic breakdown in a normal-metal - superconductor proximity sandwich

We study the magnetic response of a clean normal-metal slab of finite thickness in proximity with a bulk superconductor. We determine its free energy and identify two (meta-)stable states, a diamagnetic one where the applied field is effectively screened, and a second state, where the field penetrates the normal-metal layer. We present a complete characterization of the first order transition between the two states which occurs at the breakdown field, including its spinodals, the jump in the magnetization, and the latent heat. The bistable regime terminates at a critical temperature above which the sharp transition is replaced by a continuous cross-over. We compare the theory with experiments on normal-superconducting cylinders.Comment: 7 pages Revtex, 3 Postscript figures, needs psfig.te

Electromagnetic Response of a kx±ikyk_x\pm ik_y Superconductor: Effect of Order Parameter Collective Modes

Effects of order parameter collective modes on electromagnetic response are studied for a clean spin-triplet superconductor with $k_x\pm ik_y$ orbital symmetry, which has been proposed as a candidate pairing symmetry for Sr$_2$RuO$_4$. It is shown that the $k_x \pm ik_y$ superconductor has characteristic massive collective modes analogous to the clapping mode in the A-phase of superfluid $^3$He. We discuss the contribution from the collective modes to ultrasound attenuation and electromagnetic absorption. We show that in the electromagnetic absorption spectrum the clapping mode gives rise to a resonance peak well below the pair breaking frequency, while the ultrasound attenuation is hardly influenced by the collective excitations.Comment: 4 pages RevTex, 1 eps figur

Quasiparticle States near the Surface and the Domain Wall in a p_x\pm i p_y-Wave Superconductor

The electronic states near a surface or a domain wall in the p-wave superconductor are studied for the order parameter of the form p_x\pm i p_y-wave, which is a unitary odd-parity state with broken time-reversal symmetry. This state has been recently suggested as the superconducting state of Sr_2 Ru O_4. The spatial variation of the order parameter and vector potential is determined self-consistently within the quasi-classical approximation. The local density of states at the surface is constant and does not show any peak-like or gap-like structure within the superconducting energy gap, in contrast to the case of the d-wave superconductors. The influence of an external magnetic field is mainly observable in the energy range above the bulk gap. On the other hand, there is a small energy gap in the local density of states at the domain wall between domains of the two degenerate p_x+i p_y-wave and p_x-i p_y-wave states.Comment: 26 pages, 9 figures, to be published in J. Phys. Soc. Jpn. Vol. 68 (1999) No. 3, erratum: to appear in J. Phys. Soc. Jpn. Vol. 68 (1999) No.