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

Phase-Sensitive Impurity Effects in Vortex Core of Moderately Clean Chiral Superconductors

We study impurity effects in vortex core of two-dimensional moderately clean su perconductors within the quasiclassical theory. The impurity scattering rate \G amma(E) of the Andreev bound states in vortex core with +1 vorticity of p-wav e superconductors with {\mib d}=\hat{\mib z}(p_x+\iu p_y) is suppre ssed, compared to the normal state scattering rate $\Gamma_{\rm n}$ in the energ y region \Gamma_{\rm n}^3/E_\delta^2\ll E\ll E_\delta\equiv |\delta_0|\Delta_\i nfty with scattering phase shift $\delta_0$ $(|\delta_0|\ll 1)$ and the pair-po tential in bulk $\Delta_\infty$. Further we find that $\Gamma(E)/\Gamma_{\rm n}$ for p-wave superconductors with {\mib d}=\hat{\mib z}(p_x-\iu p_y) is at most {\cal O}(E/\Delta_\i nfty). These results are in marked contrast to the even-parity case (s,d-wave), where $\Gamma(E)/\Gamma_{\rm n}$ is known to be proportional to \ln(\Delta_\i nfty/E) . Parity- and chirality-dependences of impurity effects are attributed to the Andr eev reflections involved in the impurity-induced scattering between bound states . Implications for the flux flow conductivity is also discussed. Novel enhanceme nt of flux flow conductivity is expected to occur at $T\ll E_\delta$ for {\mib d}=\hat{\mib z}(p_x+\iu p_y) and at $T\ll \Delta_\infty$ for {\mib d}=\hat{\mib z}(p_x-\iu p_y).Comment: 9 pages, No figures, To appear in JPSJ Vol. 69, No. 10 (2000

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.

Numerical Study of Impurity Effects on Quasiparticles within S-wave and Chiral P-wave Vortices

The impurity problems within vortex cores of two-dimensional s-wave and chiral p-wave superconductors are studied numerically in the framework of the quasiclassical theory of superconductivity and self-consistent Born approximation under a trial form of the pair potential. The dispersion and impurity scattering rate (the inverse of the relaxation time) of the Andreev bound state localized in vortex cores are deduced from the angular-resoloved local density of states. The energy dependence of the impurity scattering rates depends on the pairing symmetry; particularly, in the chiral p-wave vortex core where chirality and vorticity have opposite sign and hence the total angular momentum is zero, the impurities are ineffective and the scattering rate is vanishingly small. Owing to the cancellation of angular momentum between chirality and vorticity, the chiral p-wave vortex core is similar to locally realized s-wave region and therefore non-magnetic impurity is harmless as a consequence of Anderson's theorem. The results of the present study confirm the previous results of analytical study (J. Phys. Soc. Jpn. {\bf 69} (2000) 3378) in the Born limit.Comment: 8pages, 9figures, submitted to J. Phys. Soc. Jp

Towards the design of an intensified coagulator

This study compares the hydrodynamics in three millimeter-scale continuous reactor geometries that can be easily used in laboratories and industries – a straight tube, a coiled tube and a Dean-Hex reactor – via numerical simulations and analyses the data in a way that is specifically relevant to coagulation processes, thereby offering insights for engineers to develop new coagulation reactors. A numerical approach based on Lagrangian particle tracking is presented to better understand the impact of the geometry and flow on properties that influence coagulation. The results show that the Dean-Hex meandering geometry provides narrower residence time and shear rate distributions, as well as higher mean average shear rates and Camp number distribution than the other geometries. This is attributed to the generation of transverse flows and radial mixing in the Dean-Hex reactor and suggests that a faster and more homogenous coagulation can be expected

Proteomic features of skeletal muscle adaptation to resistance exercise training as a function of age

YesResistance exercise training (RET) can counteract negative features of muscle ageing but older age associates with reduced adaptive capacity to RET. Altered muscle protein networks likely contribute to ageing RET adaptation; therefore, associated proteome-wide responses warrant exploration. We employed quantitative sarcoplasmic proteomics to compare age-related proteome and phosphoproteome responses to RET. Thigh muscle biopsies were collected from eight young (25 ± 1.1 years) and eight older (67.5 ± 2.6 years) adults before and after 20 weeks supervised RET. Muscle sarcoplasmic fractions were pooled for each condition and analysed using Isobaric Tags for Relative and Absolute Quantification (iTRAQ) labelling, tandem mass spectrometry and network-based hub protein identification. Older adults displayed impaired RET-induced adaptations in whole-body lean mass, body fat percentage and thigh lean mass (P > 0.05). iTRAQ identified 73 differentially expressed proteins with age and/or RET. Despite possible proteomic stochasticity, RET improved ageing profiles for mitochondrial function and glucose metabolism (top hub; PYK (pyruvate kinase)) but failed to correct altered ageing expression of cytoskeletal proteins (top hub; YWHAZ (14-3-3 protein zeta/delta)). These ageing RET proteomic profiles were generally unchanged or oppositely regulated post-RET in younger muscle. Similarly, RET corrected expression of 10 phosphoproteins altered in ageing, but these responses were again different vs. younger adults. Older muscle is characterised by RET-induced metabolic protein profiles that, whilst not present in younger muscle, improve untrained age-related proteomic deficits. Combined with impaired cytoskeletal adhesion responses, these results provide a proteomic framework for understanding and optimising ageing muscle RET adaptation.TE was supported by a postdoctoral fellowship from the Japan Society for the Promotion of Science and the Royal Society (JSPS/FF1/435). This work was supported by grants from the Medical Research Council (MR/T026014/1 and G0801271) and the Biotechnology and Biological Sciences Research Council (BB/X510697/1 and BB/C516779/1)

Spontaneous magnetization and Hall effect in superconductors with broken time-reversal symmetry

Broken time reversal symmetry (BTRS) in d wave superconductors is studied and is shown to yield current carrying surface states. The corresponding spontaneous magnetization is temperature independent near the critical temperature Tc for weak BTRS, in accord with recent data. For strong BTRS and thin films we expect a temperature dependent spontaneous magnetization with a paramagnetic anomaly near Tc. The Hall conductance is found to vanish at zero wavevector q and finite frequency w, however at finite q,w it has an unusual structure.Comment: 7 pages, 1 eps figure, Europhysics Letters (in press

Mass coupling and Q−1ofimpurity−limitednormalQ^{-1} of impurity-limited normal ^3$He in a torsion pendulum

We present results of the $Q^{-1}$ and period shift, $\Delta P$, for $^3$He confined in a 98% nominal open aerogel on a torsion pendulum. The aerogel is compressed uniaxially by 10% along a direction aligned to the torsion pendulum axis and was grown within a 400 $\mu$m tall pancake (after compression) similar to an Andronikashvili geometry. The result is a high $Q$ pendulum able to resolve $Q^{-1}$ and mass coupling of the impurity-limited $^3$He over the whole temperature range. After measuring the empty cell background, we filled the cell above the critical point and observe a temperature dependent period shift, $\Delta P$, between 100 mK and 3 mK that is 2.9$$ of the period shift (after filling) at 100 mK. The $Q^{-1}$ due to the $^3$He decreases by an order of magnitude between 100 mK and 3 mK at a pressure of $0.14\pm0.03$ bar. We compare the observable quantities to the corresponding calculated $Q^{-1}$ and period shift for bulk $^3$He.Comment: 8 pages, 3 figure

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

Edge Current due to Majorana Fermions in Superfluid 3^3He A- and B-Phases

We propose a method utilizing edge current to observe Majorana fermions in the surface Andreev bound state for the superfluid $^3$He A- and B-phases. The proposal is based on self-consistent analytic solutions of quasi-classical Green's function with an edge. The local density of states and edge mass current in the A-phase or edge spin current in the B-phase can be obtained from these solutions. The edge current carried by the Majorana fermions is partially cancelled by quasiparticles (QPs) in the continuum state outside the superfluid gap. QPs contributing to the edge current in the continuum state are distributed in energy even away from the superfluid gap. The effect of Majorana fermions emerges in the depletion of the edge current by temperature within a low-temperature range. The observations that the reduction in the mass current is changed by $T^2$-power in the A-phase and the reduction in the spin current is changed by $T^3$-power in the B-phase establish the existence of Majorana fermions. We also point out another possibility for observing Majorana fermions by controlling surface roughness.Comment: 13 pages, 4 figures, published versio