Supraspinal inactivation of mitochondrial superoxide dismutase is a source of peroxynitrite in the development of morphine antinociceptive tolerance.

Effective treatment of chronic pain with morphine is limited by decreases in the drug’s analgesic action with chronic administration (antinociceptive tolerance). Because opioids are mainstays of pain management, restoring their efficacy has great clinical importance. We have recently reported that formation of peroxynitrite (ONOO(−), PN) in the dorsal horn of the spinal cord plays a critical role in the development of morphine antinociceptive tolerance and have further documented that nitration and enzymatic inactivation of mitochondrial superoxide dismutase (MnSOD) at that site provides a source for this nitroxidative species. We now report for the first time that antinociceptive tolerance is also associated with the inactivation of MnSOD at supraspinal sites. Inactivation of MnSOD led to nitroxidative stress as evidenced by increased levels of products of oxidative DNA damage and activation of the nuclear factor poly (ADP-ribose) polymerase in whole brain homogenates. Co-administration of morphine with potent Mn porphyrin-based peroxynitrite scavengers, (MnTE-2-PyP(5+) and MnTnHex-2-PyP(5+)) (1) restored the enzymatic activity of MnSOD, (2) attenuated PN derived nitroxidative stress, and (3) blocked the development of morphine induced antinociceptive tolerance. The more lipophilic analogue, MnTnHex-2-PyP(5+) was able to cross the blood brain barrier at higher levels than its lipophylic counterpart MnTE-2-PyP(5+) and was about 30 fold more efficacious. Collectively, these data suggest that peroxynitrite mediated enzymatic inactivation of supraspinal MnSOD provides a source of nitroxidative stress, which in turn contributes to central sensitization associated with the development of morphine antinociceptive tolerance. These results support our general contention that PN-targeted therapeutics may have potential as adjuncts to opiates in pain management

Can Posting be a Catalyst for Dating Violence? Social Media Behaviors and Physical Interactions

Although Social Media can fuel jealousy between romantic partners, by providing a convenient and socially acceptable means of monitoring one another’s online behavior, little has been written about the possible role of Social Media in Dating Violence. We examine if and how Social Media behaviors fuel victimization during physical interactions. In addition, we consider if and how one’s partner in a physical relationship attempts to manipulate his or her Social Media behaviors. We car- ried out parallel questionnaires using the Dating Violence Questionnaire (DVQ), using both the un- altered version of the instrument as well as one in which questions were adapted to the Social Me- dia setting (e.g., “Has your partner beaten you as a consequence of something you said or did on social media?”). Participants (n = 144), were equally selected from both genders, in a counterbal- anced experimental design. We assigned half of the participants (n =72) to the Control group, who were administered the unaltered instrument, and half to the Social Media group. Similar rates of Dating Violence were reported by both groups. Respondents in the Social Media group reported experiencing physical, sexual and psychological violence, because of something said or done on Social Media. We also found that physical interactions between the romantic partners affects and alters the Social Media behaviors; Social Media spaces were often monitored by one’s partner, and altered in response to the partner’s demands. Overall, those involved in stable relationships were less likely to have experienced victimization, with men reporting more victimization as compared to women. To conclude, up to 76% of respondents experienced some form of Dating Violence and up to 83% of respondents experienced some form of manipulation related to their Social Media use, demonstrating the significance of this phenomenon in the lives of today’s youth

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

Near threshold eta production in proton-proton collisions

The total cross section for the near threshold eta production in proton-proton collisions has been investigated with the assumption that the production mechanism is due to the emission of a meson x (pi, eta, sigma) from one of the nucleons followed by a x N --> eta N transition on the second one. The x N --> eta N amplitudes are generated from the unitary multi-channel multi-resonance model which has recently been constructed in analyzing the pi N scattering and pi N --> eta N reaction. The initial and final pp distortions are calculated from a coupled-channel pi-NN model which describes the NN scattering data up to about 2 GeV. With the x-NN vertex functions taken from the Bonn potential, the predicted total cross sections of threshold pp --> eta pp reaction are in good agreement with the data. In contrast to previous works, we find that the eta-exchange plays an important role. The effect of the two-pion exchange, simulated by sigma- exchange, is found to be significant but not as dominant as the vector meson-exchange introduced in previous works.Comment: 9 pages (latex: elsart.sty) + 3 figures (PostScript gzip+uuencode) Submitted to Phys.Lett.

Chiral unitary approach to S-wave meson baryon scattering in the strangeness S=0 sector

We study the S-wave interaction of mesons with baryons in the strangeness S=0 sector in a coupled channel unitary approach. The basic dynamics is drawn from the lowest order meson baryon chiral Lagrangians. Small modifications inspired by models with explicit vector meson exchange in the t-channel are also considered. In addition the pi pi N channel is included and shown to have an important repercussion in the results, particularly in the isospin 3/2 sector.Comment: 23 pages, LaTeX, 21 figure

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

When linearity prevails over hierarchy in syntax

Hierarchical structure has been cherished as a grammatical universal. We use experimental methods to show where linear order is also a relevant syntactic relation. An identical methodology and design were used across six research sites on South Slavic languages. Experimental results show that in certain configurations, grammatical production can in fact favor linear order over hierarchical structure. However, these findings are limited to coordinate structures and distinct from the kind of production errors found with comparable configurations such as “attraction” errors. The results demonstrate that agreement morphology may be computed in a series of steps, one of which is partly independent from syntactic hierarchy

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

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

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