線虫のミトコンドリア障害に伴う筋萎縮の主要因となる細胞外マトリックスの分解

要約のみTohoku University東谷篤志課

Multipartite entanglement and quantum error identification in DD-dimensional cluster states

An entangled state is said to be $m$-uniform if the reduced density matrix of any $m$ qubits is maximally mixed. This formal definition is known to be intimately linked to pure quantum error correction codes (QECCs), which allow not only to correct errors, but also to identify their precise nature and location. Here, we show how to create $m$-uniform states using local gates or interactions and elucidate several QECC applications. We first point out that $D$-dimensional cluster states, i.e. the ground states of frustration-free local cluster Hamiltonians, are $m$-uniform with $m=2D$. We discuss finite size limitations of $m$-uniformity and how to achieve larger $m$ values using quasi-$D$ dimensional cluster states. We demonstrate experimentally on a superconducting quantum computer that the 1D cluster state allows to detect and identify 1-qubit errors, distinguishing, $X$, $Y$ and $Z$ errors. Finally, we show that $m$-uniformity allows to formulate pure QECCs with a finite logical space

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

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

Sulfur amino acid supplementation displays therapeutic potential in a C. elegans model of Duchenne muscular dystrophy

Mutations in the dystrophin gene cause Duchenne muscular dystrophy (DMD), a common muscle disease that manifests with muscle weakness, wasting, and degeneration. An emerging theme in DMD pathophysiology is an intramuscular deficit in the gasotransmitter hydrogen sulfide (H2S). Here we show that the C. elegans DMD model displays reduced levels of H2S and expression of genes required for sulfur metabolism. These reductions can be offset by increasing bioavailability of sulfur containing amino acids (L-methionine, L-homocysteine, L-cysteine, L-glutathione, and L-taurine), augmenting healthspan primarily via improved calcium regulation, mitochondrial structure and delayed muscle cell death. Additionally, we show distinct differences in preservation mechanisms between sulfur amino acid vs H2S administration, despite similarities in required health-preserving pathways. Our results suggest that the H2S deficit in DMD is likely caused by altered sulfur metabolism and that modulation of this pathway may improve DMD muscle health via multiple evolutionarily conserved mechanisms