191 research outputs found
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 . 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-
Mitochondrial dysfunction causes Ca2+ overload and ECM degradation–mediated muscle damage in C. elegans
Mitochondrial 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
Spin susceptibility of the superfluid He-B in aerogel
The temperature dependence of paramagnetic susceptibility of the superfluid
^{3}He-B in aerogel is found. Calculations have been performed for an arbitrary
phase shift of s-wave scattering in the framework of BCS weak coupling theory
and the simplest model of aerogel as an aggregate of homogeneously distributed
ordinary impurities. Both limiting cases of the Born and unitary scattering can
be easily obtained from the general result. The existence of gapless
superfluidity starting at the critical impurity concentration depending on the
value of the scattering phase has been demonstrated. While larger than in the
bulk liquid the calculated susceptibility of the B-phase in aerogel proves to
be conspicuously smaller than that determined experimentally in the high
pressure region.Comment: 10 pages, 4 figures, REVTe
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.
Quasiclassical theory of superconductivity: a multiple interface geometry
The purpose of the paper is to suggest a new method which allows one to study
multiple coherent reflection/transmissions by partially transparent interfaces
(e.g. in multi-layer mesoscopic structures or grain boundaries in high-Tc's) in
the framework of the quasiclassical theory of superconductivity. It is argued
that typically the trajectory of the particle is a simply connected tree (no
loops) with knots, i.e. the points where interface scattering events occur and
ballistic pieces of the trajectory are mixed. A linear boundary condition for
the 2-component trajectory "wave function" which factorizes matrix (retarded)
Green's function, is formulated for an arbitrary interface, specular or
diffusive. To show the usage of the method, the current response to the vector
potential (the total superfluid density rho_s) of a SS' sandwich with the
different signs of the order parameter in S and S', is calculated. In this
model, a few percent of reflection by the SS' interface transforms the
paramagnetic response (rho_s < 0) created by the zero-energy Andreev bound
states near an ideal interface (see Fauchere et al. PRL, 82, 3336 (1999),
cond-mat/9901112), into the usual diamagnetic one (rho_s >0).Comment: Extended abstract submitted to "Electron Transport in Mesoscopic
Systems", Satellite conference to LT22, Goteborg, 12-15 August, 1999. 2 pages
Minor changes + the text height problem fixe
The Effectiveness of RNAi in Caenorhabditis elegans Is Maintained during Spaceflight
PublishedJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tThis is the final version of the article. Available from Public Library of Science via the DOI in this record.BACKGROUND: Overcoming spaceflight-induced (patho)physiologic adaptations is a major challenge preventing long-term deep space exploration. RNA interference (RNAi) has emerged as a promising therapeutic for combating diseases on Earth; however the efficacy of RNAi in space is currently unknown. METHODS: Caenorhabditis elegans were prepared in liquid media on Earth using standard techniques and treated acutely with RNAi or a vector control upon arrival in Low Earth Orbit. After culturing during 4 and 8 d spaceflight, experiments were stopped by freezing at -80°C until analysis by mRNA and microRNA array chips, microscopy and Western blot on return to Earth. Ground controls (GC) on Earth were simultaneously grown under identical conditions. RESULTS: After 8 d spaceflight, mRNA expression levels of components of the RNAi machinery were not different from that in GC (e.g., Dicer, Argonaute, Piwi; P>0.05). The expression of 228 microRNAs, of the 232 analysed, were also unaffected during 4 and 8 d spaceflight (P>0.05). In spaceflight, RNAi against green fluorescent protein (gfp) reduced chromosomal gfp expression in gonad tissue, which was not different from GC. RNAi against rbx-1 also induced abnormal chromosome segregation in the gonad during spaceflight as on Earth. Finally, culture in RNAi against lysosomal cathepsins prevented degradation of the muscle-specific α-actin protein in both spaceflight and GC conditions. CONCLUSIONS: Treatment with RNAi works as effectively in the space environment as on Earth within multiple tissues, suggesting RNAi may provide an effective tool for combating spaceflight-induced pathologies aboard future long-duration space missions. Furthermore, this is the first demonstration that RNAi can be utilised to block muscle protein degradation, both on Earth and in space.This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, the Japan Society for the Promotion of Science, and “Ground-Based Research Announcement for Space Utilization” promoted by the Japan Space Forum. TE was supported by the Medical Research Council UK (G0801271). NJS was supported by the National Institutes of Health (NIH NIAMS ARO54342). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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