Mitochondrial ROS cause motor deficits induced by synaptic inactivity:implications for synapse pruning

Developmental synapse pruning refines burgeoning connectomes. The basic mechanisms of mitochondrial reactive oxygen species (ROS) production suggest they select inactive synapses for pruning: whether they do so is unknown. To begin to unravel whether mitochondrial ROS regulate pruning, we made the local consequences of neuromuscular junction (NMJ) pruning detectable as motor deficits by using disparate exogenous and endogenous models to induce synaptic inactivity en masse in developing Xenopus laevis tadpoles. We resolved whether: (1) synaptic inactivity increases mitochondrial ROS; and (2) antioxidants rescue synaptic inactivity induced motor deficits. Regardless of whether it was achieved with muscle (α-bugarotoxin), nerve (α-latrotoxin) targeted neurotoxins or an endogenous pruning cue (SPARC), synaptic inactivity increased mitochondrial ROS in vivo. The manganese porphyrins MnTE-2-PyP5+ and/or MnTnBuOE-2-PyP5+ blocked mitochondrial ROS to significantly reduce neurotoxin and endogenous pruning cue induced motor deficits. Selectively inducing mitochondrial ROS—using mitochondria-targeted Paraquat (MitoPQ)—recapitulated synaptic inactivity induced motor deficits; which were significantly reduced by blocking mitochondrial ROS with MnTnBuOE-2-PyP5+. We unveil mitochondrial ROS as synaptic activity sentinels that regulate the phenotypical consequences of forced synaptic inactivity at the NMJ. Our novel results are relevant to pruning because synaptic inactivity is one of its defining features

The importance of the nucleon-nucleon correlations for the eta alpha S-wave scattering length, and the pi-eta mixing angle in the low-energy eta alpha scattering length model

Using the new set of dd --> eta alpha near threshold experimental data, the estimate of the importance of the nucleon-nucleon correlations for the eta alpha S-wave scattering length in the multiple scattering theory is obtained using the low-energy scattering length model. The contribution turns out to be much bigger then previously believed. The pi-eta mixing angle is extracted using the experimental data on the dd --> eta alpha and dd --> pi alpha processes. The model is dominated by the subthreshold extrapolation recipe for the eta alpha scattering amplitudes. When the recipe is chosen the model is completely insensitive to the eta alpha parameters for the subthreshold value of the eta cm momentum of p_{eta}^2 = -(0.46)^2 fm^{-2}. Provided that the subthreshold extrapolation recipe is correct, a good estimate of the pi-eta mixing angle is obtained, if the experimental cross sections for the dd --> pi alpha reaction at the corresponding deuteron input energy are taken from the literature.Comment: 8 pages, 2 figure

The nucleon-nucleon interaction

We review the major progress of the past decade concerning our understanding of the nucleon-nucleon interaction. The focus is on the low-energy region (below pion production threshold), but a brief outlook towards higher energies is also given. The items discussed include charge-dependence, the precise value of the $\pi NN$ coupling constant, phase shift analysis and high-precision NN data and potentials. We also address the issue of a proper theory of nuclear forces. Finally, we summarize the essential open questions that future research should be devoted to.Comment: 42 pages, 12 figures, iopart.cls style; Topical Review prepared for J. Phys. G: Nucl. Part. Phy

Level crossing of particle-hole and mesonic modes in eta mesic nuclei

We study eta meson properties in the infinite nuclear matter and in atomic nuclei with an emphasis on effects of the eta coupling to N*(1535)--nucleon-hole modes. The N*(1535) resonance, which dominates the low-energy eta-nucleon scattering, can be seen as a chiral partner of the nucleon. The change of the chiral mass gap between the N* and the nucleon in a nuclear medium has an impact on the properties of the eta-nucleus system. If the N*-nucleon mass gap decreases with a density increase (chiral symmetry restoration) the calculations show the existence of the resonance state at the energy about 60 MeV and two bound eta-nucleus states with the binding energies about -80 MeV. These states can have strong effect on predicted cross sections of the ^12C (gamma,p) ^11B reaction with eta-meson production.Comment: 22 pages, 12 figure

Redox Proteomic Identification of HNE-Bound Mitochondrial Proteins in Cardiac Tissues Reveals a Systemic Effect on Energy Metabolism After Doxorubicin Treatment

Doxorubicin (DOX), one of the most effective anticancer drugs, is known to generate progressive cardiac damage, which is due, in part, to DOX-induced reactive oxygen species (ROS). The elevated ROS often induce oxidative protein modifications that result in alteration of protein functions. This study demonstrates that the level of proteins adducted by 4-hydroxy-2-nonenal (HNE), a lipid peroxidation product, is significantly increased in mouse heart mitochondria after DOX treatment. A redox proteomics method involving two-dimensional electrophoresis followed by mass spectrometry and investigation of protein databases identified several HNE-modified mitochondrial proteins, which were verified by HNE-specific immunoprecipitation in cardiac mitochondria from the DOX-treated mice. The majority of the identified proteins are related to mitochondrial energy metabolism. These include proteins in the citric acid cycle and electron transport chain. The enzymatic activities of the HNE-adducted proteins were significantly reduced in DOX-treated mice. Consistent with the decline in the function of the HNE-adducted proteins, the respiratory function of cardiac mitochondria as determined by oxygen consumption rate was also significantly reduced after DOX treatment. Treatment with Mn(III) meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin, an SOD mimic, averted the doxorubicin-induced mitochondrial dysfunctions as well as the HNE–protein adductions. Together, the results demonstrate that free radical-mediated alteration of energy metabolism is an important mechanism mediating DOX-induced cardiac injury, suggesting that metabolic intervention may represent a novel approach to preventing cardiac injury after chemotherapy

Exotic Anti-Decuplet of Baryons: Prediction from Chiral Solitons

We predict an exotic Z^+ baryon (having spin 1/2, isospin 0 and strangeness +1) with a relatively low mass of about 1530 MeV and total width of less than 15 MeV. It seems that this region of masses has avoided thorough searches in the past.Comment: Revised version, to appear in Z. fuer Phys. A. The importance of 1/Nc corrections to antidecuplet widths is demonstrated. 21 pages, 1 LaTeX figur

Electromagnetic Meson Production in the Nucleon Resonance Region

Recent experimental and theoretical advances in investigating electromagnetic meson production reactions in the nucleon resonance region are reviewed.Comment: 75 pages, 42 figure

Intermediate mass excess of dilepton production in heavy ion collisions at BEVALAC energies

Dielectron mass spectra are examined for various nuclear reactions recently measured by the DLS collaboration. A detailed description is given of all dilepton channels included in the transport model UrQMD 1.0, i.e. Dalitz decays of $\pi^0,\eta,\omega,\eta'$ mesons and of the $\Delta(1232)$ resonance, direct decays of vector mesons and $pn$ bremsstrahlung. The microscopic calculations reproduce data for light systems fairly well, but tend to underestimate the data in $pp$ at high energies and in $pd$ at low energies. These conventional sources, however, cannot explain the recently reported enhancement for nucleus-nucleus collisions in the mass region 0.15 GeV<$M_{ee}$<0.6 GeV. Chiral scaling and $\omega$ meson broadening in the medium are investigated as a source of this mass excess. They also cannot explain the recent DLS data.Comment: 26 pages, 9 figures, references update