Paradoxical roles of antioxidant enzymes:Basic mechanisms and health implications

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated from aerobic metabolism, as a result of accidental electron leakage as well as regulated enzymatic processes. Because ROS/RNS can induce oxidative injury and act in redox signaling, enzymes metabolizing them will inherently promote either health or disease, depending on the physiological context. It is thus misleading to consider conventionally called antioxidant enzymes to be largely, if not exclusively, health protective. Because such a notion is nonetheless common, we herein attempt to rationalize why this simplistic view should be avoided. First we give an updated summary of physiological phenotypes triggered in mouse models of overexpression or knockout of major antioxidant enzymes. Subsequently, we focus on a series of striking cases that demonstrate “paradoxical” outcomes, i.e., increased fitness upon deletion of antioxidant enzymes or disease triggered by their overexpression. We elaborate mechanisms by which these phenotypes are mediated via chemical, biological, and metabolic interactions of the antioxidant enzymes with their substrates, downstream events, and cellular context. Furthermore, we propose that novel treatments of antioxidant enzyme-related human diseases may be enabled by deliberate targeting of dual roles of the pertaining enzymes. We also discuss the potential of “antioxidant” nutrients and phytochemicals, via regulating the expression or function of antioxidant enzymes, in preventing, treating, or aggravating chronic diseases. We conclude that “paradoxical” roles of antioxidant enzymes in physiology, health, and disease derive from sophisticated molecular mechanisms of redox biology and metabolic homeostasis. Simply viewing antioxidant enzymes as always being beneficial is not only conceptually misleading but also clinically hazardous if such notions underpin medical treatment protocols based on modulation of redox pathways

De Broglie Wavelength of a Nonlocal Four-Photon

Superposition is one of the most distinct features of quantum theory and has been demonstrated in numerous realizations of Young's classical double-slit interference experiment and its analogues. However, quantum entanglement - a significant coherent superposition in multiparticle systems - yields phenomena that are much richer and more interesting than anything that can be seen in a one-particle system. Among them, one important type of multi-particle experiments uses path-entangled number-states, which exhibit pure higher-order interference and allow novel applications in metrology and imaging such as quantum interferometry and spectroscopy with phase sensitivity at the Heisenberg limit or quantum lithography beyond the classical diffraction limit. Up to now, in optical implementations of such schemes lower-order interference effects would always decrease the overall performance at higher particle numbers. They have thus been limited to two photons. We overcome this limitation and demonstrate a linear-optics-based four-photon interferometer. Observation of a four-particle mode-entangled state is confirmed by interference fringes with a periodicity of one quarter of the single-photon wavelength. This scheme can readily be extended to arbitrary photon numbers and thus represents an important step towards realizable applications with entanglement-enhanced performance.Comment: 19 pages, 4 figures, submitted on November 18, 200

Biology and Life History of Balcha indica, an Ectoparasitoid Attacking the Emerald Ash Borer, Agrilus planipennis, in North America

Balcha indica Mani and Kaul (Hymenoptera: Eupelmidae) is a solitary ectoparasitoid attacking larvae, prepupae, and pupae of the emerald ash borer, Agrilus planipennis Fairmaire (Hymenoptera: Eupelmidae). Its fecundity, oviposition rate, longevity, and development time were determined in the laboratory under standard rearing conditions (25 ± 2° C, 65 ± 10% relative humidity, and 14:10 L:D). Adults lived a mean of 59 days with a maximum of 117 days. Lifetime adult fecundity averaged 36 eggs with a maximum 94 eggs per female. The egg stage lasted for a maximum of four days with ∼ 50% eggs hatched within two days. The development time of the first instars lasted for a maximum of nine days; 50% of the first instars completed their development (i.e., molted to the next instar) within five days. Instars of the intermediate and final stage larvae (after molting of the first instars occurred) could not be distinguished until they reached the pupal stage, and 50% of those larvae pupated ∼ 62 days after adult oviposition. Under the standard rearing conditions, 50% of B. indica took ∼ 83 days to complete the life cycle (from egg to adult emergence) ranging from 47 to 129 days. These results suggest that B. indica may not have more than two generations in the mid-Atlantic and Midwest regions of United States, where normal growing seasons—with average temperature above 25° C—are normally less than six months (May–October). Because of the long life span and oviposition period of adults, however, B. indica is likely to have overlapping generations

STK295900, a Dual Inhibitor of Topoisomerase 1 and 2, Induces G<inf>2</inf> Arrest in the Absence of DNA Damage

STK295900, a small synthetic molecule belonging to a class of symmetric bibenzimidazoles, exhibits antiproliferative activity against various human cancer cell lines from different origins. Examining the effect of STK295900 in HeLa cells indicates that it induces G2 phase arrest without invoking DNA damage. Further analysis shows that STK295900 inhibits DNA relaxation that is mediated by topoisomerase 1 (Top 1) and topoisomerase 2 (Top 2) in vitro. In addition, STK295900 also exhibits protective effect against DNA damage induced by camptothecin. However, STK295900 does not affect etoposide-induced DNA damage. Moreover, STK295900 preferentially exerts cytotoxic effect on cancer cell lines while camptothecin, etoposide, and Hoechst 33342 affected both cancer and normal cells. Therefore, STK295900 has a potential to be developed as an anticancer chemotherapeutic agent. © 2013 Kim et al

SPH study of the evolution of water–water interfaces in dam break flows

The mixing process of upstream and downstream waters in the dam break flow could generate significant ecological impact on the downstream reaches and influence the environmental damages caused by the dam break flood. This is not easily investigated with the analytical and numerical models based on the grid method due to the large deformation of free surface and the water-water interface. In this paper, a weakly compressible Smoothed Particle Hydrodynamics (WCSPH) solver is used to study the advection and mixing process of the water bodies in two-dimensional dam-break flows over a wet bed. The numerical results of the mixing dynamics immediately after the release of the dam water are found to agree satisfactorily with the published experimental and numerical results. Then further investigations are carried out to study the interface development at the later stage of dambreak flows in a long channel. The analyses concentrate on the evolution of the interface at different ratios between the upstream and downstream water depths. The potential capabilities of the mesh-free SPH modelling approach for predicting the detailed development of the water-water interfaces are fully demonstrated.The first author acknowledges the Jafar Studentship during her PhD study at the University of Cambridge. The other authors acknowledge the support of the Major State Basic Research Development Program (973) of China (No. 2013CB036402), Open Fund of the State Key Laboratory of Hydraulics and Mountain River Engineering, Sichuan University (SKHL1404; SKHL1409), Start-up Grant for the Young Teachers of Sichuan University (2014SCU11056) and National Science and Technology Support Plan (2012BAB0513B0).This is the accepted manuscript. The final version is available at http://link.springer.com/article/10.1007%2Fs11069-015-1726-6

Experimental and theoretical investigation of ligand effects on the synthesis of ZnO nanoparticles

ZnO nanoparticles with highly controllable particle sizes(less than 10 nm) were synthesized using organic capping ligands in Zn(Ac)2 ethanolic solution. The molecular structure of the ligands was found to have significant influence on the particle size. The multi-functional molecule tris(hydroxymethyl)-aminomethane (THMA) favoured smaller particle distributions compared with ligands possessing long hydrocarbon chains that are more frequently employed. The adsorption of capping ligands on ZnnOn crystal nuclei (where n = 4 or 18 molecular clusters of(0001) ZnO surfaces) was modelled by ab initio methods at the density functional theory (DFT) level. For the molecules examined, chemisorption proceeded via the formation of Zn...O, Zn...N, or Zn...S chemical bonds between the ligands and active Zn2+ sites on ZnO surfaces. The DFT results indicated that THMA binds more strongly to the ZnO surface than other ligands, suggesting that this molecule is very effective at stabilizing ZnO nanoparticle surfaces. This study, therefore, provides new insight into the correlation between the molecular structure of capping ligands and the morphology of metal oxide nanostructures formed in their presence

Observation of the Ωc0\Omega_{c}^{0} Charmed Baryon at CLEO

The CLEO experiment at the CESR collider has used 13.7 fb$^{-1}$ of data to search for the production of the $\Omega_c^0$ (css-ground state) in $e^{+}e^{-}$ collisions at $\sqrt{s} \simeq 10.6$ {\rm GeV}. The modes used to study the $\Omega_c^0$ are $\Omega^- \pi^+$, $\Omega^- \pi^+ \pi^0$, $\Xi^- K^- pi^+ \pi^+$, $\Xi^0 K^- pi^+$, and $\Omega^- \pi^+ \pi^- \pi^+$. We observe a signal of 40.4$\pm$9.0(stat) events at a mass of 2694.6$\pm$2.6(stat)$\pm$1.9(syst) {\rm MeV/$c^2$}, for all modes combined.Comment: 10 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN

Simultaneous localization of MLL, AF4 and ENL genes in interphase nuclei by 3D-FISH: MLL translocation revisited

BACKGROUND: Haematological cancer is characterised by chromosomal translocation (e.g. MLL translocation in acute leukaemia) and two models have been proposed to explain the origins of recurrent reciprocal translocation. The first, established from pairs of translocated genes (such as BCR and ABL), considers the spatial proximity of loci in interphase nuclei (static "contact first" model). The second model is based on the dynamics of double strand break ends during repair processes (dynamic "breakage first" model). Since the MLL gene involved in 11q23 translocation has more than 40 partners, the study of the relative positions of the MLL gene with both the most frequent partner gene (AF4) and a less frequent partner gene (ENL), should elucidate the MLL translocation mechanism. METHODS: Using triple labeling 3D FISH experiments, we have determined the relative positions of MLL, AF4 and ENL genes, in two lymphoblastic and two myeloid human cell lines. RESULTS: In all cell lines, the ENL gene is significantly closer to the MLL gene than the AF4 gene (with P value < 0.0001). According to the static "contact first" model of the translocation mechanism, a minimal distance between loci would indicate a greater probability of the occurrence of t(11;19)(q23;p13.3) compared to t(4;11)(q21;q23). However this is in contradiction to the epidemiology of 11q23 translocation. CONCLUSION: The simultaneous multi-probe hybridization in 3D-FISH is a new approach in addressing the correlation between spatial proximity and occurrence of translocation. Our observations are not consistent with the static "contact first" model of translocation. The recently proposed dynamic "breakage first" model offers an attractive alternative explanation

Observation of B→ϕKB\to \phi K and B→ϕK∗B\to \phi K^{*}

We have studied two-body charmless hadronic decays of $B$ mesons into the final states phi K and phi K^*. Using 9.7 million $B\bar{B}$ pairs collected with the CLEO II detector, we observe the decays B- -> phi K- and B0 -> phi K*0 with the following branching fractions: BR(B- -> phi K-)=(5.5 +2.1-1.8 +- 0.6) x 10^{-6} and BR(B0 -> phi K*0)=(11.5 +4.5-3.7 +1.8-1.7) x 10^{-6}. We also see evidence for the decays B0 -> phi K0 and B- -> phi K*-. However, since the statistical significance is not overwhelming for these modes we determine upper limits of <12.3 x 10^{-6} and <22.5 x 10^{-6} (90% C.L.) respectively.Comment: 9 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN

Evidence of New States Decaying into Ξc′π\Xi^{\prime}_{c}\pi

Using 13.7 $fb^{-1}$ of data recorded by the CLEO detector at CESR, we report evidence for two new charmed baryons: one decaying into $\Xi_c^{0 \prime}\pi^+$ with the subsequent decay $\Xi_c^{0 \prime} \to \Xi_c^0 \gamma$, and its isospin partner decaying into $\Xi_c^{+ \prime} \pi^-$ followed by $\Xi_c^{+\prime} \to \Xi_c^+\gamma$. We measure the following mass differences for the two states: $M(\Xi_c^0 \gamma \pi^+)-M(\Xi_c^0)$=318.2+-1.3+-2.9 MeV, and $M(\Xi_c^+ \gamma \pi^-)-M(\Xi_c^+)$=324.0+-1.3+-3.0 MeV. We interpret these new states as the $J^P = 1/2^- \Xi_{c1}$ particles, the charmed-strange analogs of the $\Lambda_{c1}^+(2593)$.Comment: 10 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN