Attenuation of doxorubicin-induced cardiac injury by mitochondrial glutaredoxin 2

AbstractWhile the cardiotoxicity of doxorubicin (DOX) is known to be partly mediated through the generation of reactive oxygen species (ROS), the biochemical mechanisms by which ROS damage cardiomyocytes remain to be determined. This study investigates whether S-glutathionylation of mitochondrial proteins plays a role in DOX-induced myocardial injury using a line of transgenic mice expressing the human mitochondrial glutaredoxin 2 (Glrx2), a thiotransferase catalyzing the reduction as well as formation of protein–glutathione mixed disulfides, in cardiomyocytes. The total glutaredoxin (Glrx) activity was increased by 76% and 53 fold in homogenates of whole heart and isolated heart mitochondria of Glrx2 transgenic mice, respectively, compared to those of nontransgenic mice. The expression of other antioxidant enzymes, with the exception of glutaredoxin 1, was unaltered. Overexpression of Glrx2 completely prevents DOX-induced decreases in NAD- and FAD-linked state 3 respiration and respiratory control ratio (RCR) in heart mitochondria at days 1 and 5 of treatment. The extent of DOX-induced decline in left ventricular function and release of creatine kinase into circulation at day 5 of treatment was also greatly attenuated in Glrx2 transgenic mice. Further studies revealed that heart mitochondria overexpressing Glrx2 released less cytochrome c than did controls in response to treatment with tBid or a peptide encompassing the BH3 domain of Bid. Development of tolerance to DOX toxicity in transgenic mice is also associated with an increase in protein S-glutathionylation in heart mitochondria. Taken together, these results imply that S-glutathionylation of heart mitochondrial proteins plays a role in preventing DOX-induced cardiac injury

Attenuation of Doxorubicin-Induced Cardiac Injury by Mitochondrial Glutaredoxin 2

While the cardiotoxicity of doxorubicin (DOX) is known to be partly mediated through the generation of reactive oxygen species (ROS), the biochemical mechanisms by which ROS damage cardiomyocytes remain to be determined. This study investigates whether S-glutathionylation of mitochondrial proteins plays a role in DOX-induced myocardial injury using a line of transgenic mice expressing the human mitochondrial glutaredoxin 2 (Glrx2), a thiotransferase catalyzing the reduction as well as formation of protein–glutathione mixed disulfides, in cardiomyocytes. The total glutaredoxin (Glrx) activity was increased by 76% and 53 fold in homogenates of whole heart and isolated heart mitochondria of Glrx2 transgenic mice, respectively, compared to those of nontransgenic mice. The expression of other antioxidant enzymes, with the exception of glutaredoxin 1, was unaltered. Overexpression of Glrx2 completely prevents DOX-induced decreases in NAD- and FAD-linked state 3 respiration and respiratory control ratio (RCR) in heart mitochondria at days 1 and 5 of treatment. The extent of DOX-induced decline in left ventricular function and release of creatine kinase into circulation at day 5 of treatment was also greatly attenuated in Glrx2 transgenic mice. Further studies revealed that heart mitochondria overexpressing Glrx2 released less cytochrome c than did controls in response to treatment with tBid or a peptide encompassing the BH3 domain of Bid. Development of tolerance to DOX toxicity in transgenic mice is also associated with an increase in protein S-glutathionylation in heart mitochondria. Taken together, these results imply that S-glutathionylation of heart mitochondrial proteins plays a role in preventing DOX-induced cardiac injury

Effects of vertical distribution of soil inorganic nitrogen on root growth and subsequent nitrogen uptake by field vegetable crops

Information is needed about root growth and N uptake of crops under different soil conditions to increase nitrogen use efficiency in horticultural production. The purpose of this study was to investigate if differences in vertical distribution of soil nitrogen (Ninorg) affected root growth and N uptake of a variety of horticultural crops. Two field experiments were performed each over 2 years with shallow or deep placement of soil Ninorg obtained by management of cover crops. Vegetable crops of leek, potato, Chinese cabbage, beetroot, summer squash and white cabbage reached root depths of 0.5, 0.7, 1.3, 1.9, 1.9 and more than 2.4 m, respectively, at harvest, and showed rates of root depth penetration from 0.2 to 1.5 mm day)1 C)1. Shallow placement of soil Ninorg resulted in greater N uptake in the shallow-rooted leek and potato. Deep placement of soil Ninorg resulted in greater rates of root depth penetration in the deep-rooted Chinese cabbage, summer squash and white cabbage, which increased their depth by 0.2–0.4 m. The root frequency was decreased in shallow soil layers (white cabbage) and increased in deep soil layers (Chinese cabbage, summer squash and white cabbage). The influence of vertical distribution of soil Ninorg on root distribution and capacity for depletion of soil Ninorg was much less than the effect of inherent differences between species. Thus, knowledge about differences in root growth between species should be used when designing crop rotations with high N use efficiency

The influence of direct DD-meson production to the determination on the nucleon strangeness asymmetry via dimuon events in neutrino experiments

Experimentally, the production of oppositely charged dimuon events by neutrino and anti-neutrino deep inelastic scattering (DIS) is used to determine the strangeness asymmetry inside a nucleon. Here we point out that the direct production of $D$-meson in DIS may make substantial influence to the measurement of nucleon strange distributions. The direct $D$-meson production is via the heavy quark recombination (HQR) and via the light quark fragmentation from perturbative QCD (LQF-P). To see the influence precisely, we compute the direct $D$-meson productions via HQR and LQF-P quantitatively and estimate their corrections to the analysis of the strangeness asymmetry. The results show that HQR has stronger effect than LQF-P does, and the former may influence the experimental determination of the nucleon strangeness asymmetry.Comment: 9 latex pages, 7 figure

Transient elastohydrodynamic lubrication analysis of a novel metal-on-metal hip prosthesis with a non-spherical femoral bearing surface

Effective lubrication performance of metal-on-metal hip implants only requires optimum conformity within the main loaded area, while it is advantageous to increase the clearance in the equatorial region. Such a varying clearance can be achieved by using non-spherical bearing surfaces for either acetabular or femoral components. An elastohydrodynamic lubrication model of a novel metal-on-metal hip prosthesis using a non-spherical femoral bearing surface against a spherical cup was solved under loading and motion conditions specified by ISO standard. A full numerical methodology of considering the geometric variation in the rotating non-spherical head in elastohydrodynamic lubrication solution was presented, which is applicable to all non-spherical head designs. The lubrication performance of a hip prosthesis using a specific non-spherical femoral head, Alpharabola, was analysed and compared with those of spherical bearing surfaces and a non-spherical Alpharabola cup investigated in previous studies. The sensitivity of the lubrication performance to the anteversion angle of the Alpharabola head was also investigated. Results showed that the non-spherical head introduced a large squeeze-film action and also led to a large variation in clearance within the loaded area. With the same equatorial clearance, the lubrication performance of the metal-on-metal hip prosthesis using an Alpharabola head was better than that of the conventional spherical bearings but worse than that of the metal-on-metal hip prosthesis using an Alpharabola cup. The reduction in the lubrication performance caused by the initial anteversion angle of the non-spherical head was small, compared with the improvement resulted from the non-spherical geometry

Observation of Two New N* Peaks in J/psi -> ppi−nˉp pi^- \bar n and pˉπ+n\bar p\pi^+n Decays

The $\pi N$ system in decays of $J/\psi\to\bar NN\pi$ is limited to be isospin 1/2 by isospin conservation. This provides a big advantage in studying $N^*\to \pi N$ compared with $\pi N$ and $\gamma N$ experiments which mix isospin 1/2 and 3/2 for the $\pi N$ system. Using 58 million $J/\psi$ decays collected with the Beijing Electron Positron Collider, more than 100 thousand $J/\psi \to p \pi^- \bar n + c.c.$ events are obtained. Besides two well known $N^*$ peaks at 1500 MeV and 1670 MeV, there are two new, clear $N^*$ peaks in the $p\pi$ invariant mass spectrum around 1360 MeV and 2030 MeV. They are the first direct observation of the $N^*(1440)$ peak and a long-sought "missing" $N^*$ peak above 2 GeV in the $\pi N$ invariant mass spectrum. A simple Breit-Wigner fit gives the mass and width for the $N^*(1440)$ peak as $1358\pm 6 \pm 16$ MeV and $179\pm 26\pm 50$ MeV, and for the new $N^*$ peak above 2 GeV as $2068\pm 3^{+15}_{-40}$ MeV and $165\pm 14\pm 40$ MeV, respectively

Treatment of backscattering in a gas of interacting fermions confined to a one-dimensional harmonic atom trap

An asymptotically exact many body theory for spin polarized interacting fermions in a one-dimensional harmonic atom trap is developed using the bosonization method and including backward scattering. In contrast to the Luttinger model, backscattering in the trap generates one-particle potentials which must be diagonalized simultaneously with the two-body interactions. Inclusion of backscattering becomes necessary because backscattering is the dominant interaction process between confined identical one-dimensional fermions. The bosonization method is applied to the calculation of one-particle matrix elements at zero temperature. A detailed discussion of the validity of the results from bosonization is given, including a comparison with direct numerical diagonalization in fermionic Hilbert space. A model for the interaction coefficients is developed along the lines of the Luttinger model with only one coupling constant $K$. With these results, particle densities, the Wigner function, and the central pair correlation function are calculated and displayed for large fermion numbers. It is shown how interactions modify these quantities. The anomalous dimension of the pair correlation function in the center of the trap is also discussed and found to be in accord with the Luttinger model.Comment: 19 pages, 5 figures, journal-ref adde

Loop effects and non-decoupling property of SUSY QCD in gb→tH−g b\to tH^{-}

One-loop SUSY QCD radiative correction to $gb \to tH^{-}$ cross section is calculated in the Minimal Supersymmetric Standard Model. We found that SUSY QCD is non-decoupling if the gluino mass and the parameter $\mu$, $A_t$ or $A_b$ are at the same order and get large. The non-decoupling contribution can be enhanced by large $\tan\beta$ and therefore large corrections to the hadronic production rates at the Tevatron and LHC are expected in the large $\tan\beta$ limit. The fundamental reason for such non-decoupling behavior is found to be some couplings in the loops being proportional to SUSY mass parameters.Comment: 15 pages, 5 PS figures. A proof of non-decouplings of SUSY-QCD, Comments on corresponding QCD correction and references adde

Higgs-boson production associated with a bottom quark at hadron colliders with SUSY-QCD corrections

The Higgs boson production p p (p\bar p) -> b h +X via b g -> b h at the LHC, which may be an important channel for testing the bottom quark Yukawa coupling, is subject to large supersymmetric quantum corrections. In this work the one-loop SUSY-QCD corrections to this process are evaluated and are found to be quite sizable in some parameter space. We also study the behavior of the corrections in the limit of heavy SUSY masses and find the remnant effects of SUSY-QCD. These remnant effects, which are left over in the Higgs sector by the heavy sparticles, are found to be so sizable (for a light CP-odd Higgs and large \tan\beta) that they might be observable in the future LHC experiment. The exploration of such remnant effects is important for probing SUSY, especially in case that the sparticles are too heavy (above TeV) to be directly discovered at the LHC.Comment: Results for the Tevatron adde