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.

Cholesteric liquid crystals with a helical pitch gradient: spatial distribution of the concentration of chiral groups by Raman mapping in relation with the optical response and the microstructure.

Cholesteric liquid crystals (CLC) selectively reflect light when the helical pitch is of the order of the wavelength of the incident beam propagating along the helix axis. The wavelength bandwidth, related to the optical anisotropy, is typically limited to a few tens of nanometers in the visible part of the spectrum, which is insufficient for applications such as white-or-black polarizer-free reflective displays and smart windows for the control of the solar light and heat. A way to make cholesteric films reflecting in a broad wavelength band consists in associating various cholesteric pitches in the same film. In this work, it is shown how a study by confocal micro Raman spectrometry mapping makes it possible to have access to information accounting for the local organization of CLCs in the case of graded pitch materials. These investigations will be correlated to the optical response and the transverse microstructure of the CLC material as investigated by transmission electron microscopy. An accurate analysis of the vibrational behavior evolution of the C==O can be correlated to the evolution of the populations of the chiral and achiral groups in the case of the interdiffusion of two CLC substances with various stoechiometries. Besides an easy measurement of the Raman spectrum gives the opportunity to quantify the relative ratio of the mesogenic species and thus to go up by a simple way to the pitch of the helical structure.

Polymer-stabilized cholesteric liquid crystals as switchable photonic broad bandgaps.

A cholesteric liquid crystal can be considered as a one-dimensional photonic crystal with a refractive index that is regularly modulated along the helix axis because of the particular arrangement of the molecules. The result is that the propagation of light is suppressed for a particular range of wavelengths (bandgap). A polymer-stabilized cholesteric liquid crystal (PSCLC), which is obtained by in situ photopolymerization of reactive liquid-crystal molecules in the presence of non-reactive liquid-crystal molecules in an oriented Bragg planar texture, is elaborated by combining the UV-curing with a thermally induced pitch variation. As a consequence, it is shown here that memory effects are introduced into the characteristics of the reflection band of the material at room temperature. In the visible spectrum, the reflection bandwidth can be tuned in agreement with the thermal ramp and broadened. In addition, the bandgap filters can be switched between broadband reflective, scattering and transparent states by subjecting them to an electric field. Related application fields of these functional materials are switchable smart windows for the control of the solar-light spectrum and white-or-black polarizer-free reflective displays.

Administration of Zn-Co-Mn basic salt to chickens with ascaridiosis. I. A mathematical model for Ascaridia galli populations and host growth with and without treatment.

A newly synthesized basic mixed salt (Zn(x)Co(y)Mn(1-x-y)) x (OH)6SO4 x 2H2O) was administered to chickens with ascaridiosis. Improvement in survival, gain in body weight (of 19.03%) and restoration of microelement content were observed in the treated chickens. An increase in the gain in body weight of 7.62% in uninfected treated chickens was also observed. The establishment of Ascaridia galli populations in chickens, and chicken growth in control and infected hosts, untreated and treated, were modelled mathematically. Some kinetic parameters (the rate of reduction of the nematode population nu and the relative rate mu of gain in body weight of the host) were determined. The values of nu =0.027 day(-1) and nu* =0.032 day(-1) were calculated for the reduction rates in infected, untreated chickens and in infected, treated chickens, respectively. The worm burden in infected, treated chickens was 20.4% lower than in infected, untreated chickens.

Administration of Zn-Co-Mn basic salt to chickens with ascaridiosis. II. Sex ratio and microelement levels in Ascaridia galli and in treated and untreated chickens.

Hisex chickens were infected with 1,450 embryonated Ascaridia galli eggs and treated with a new synthesized basic mixed salt (Zn(x)Co(y)Mn(1-x-y)) x (OH)6SO4 x 2H2O). The worm burden was determined and sex ratios for A. galli of M:F = 1.4 and M:F = 2 in untreated and treated chickens, respectively, were found. A decrease in the mean establishment rate of A. galli in treated chickens was observed. The levels of zinc, cobalt and manganese were determined in liver and muscle of the host and in male and female A. galli. The survival of the chickens and gain in body weight were improved, and the restoration of microelement content was observed by treatment with the salt. A positive effect of the basic Zn-Co-Mn salt was also observed in the nematode microelement levels. Significant differences were found between the levels of zinc, cobalt and manganese in male and female A. galli.

Effects of glycine-metal compounds on Ascaridia galli-infected chickens expressed by a kinetic model.

The biogenic elements zinc, manganese and cobalt are essential for metabolic processes in animals. Compounds of nGly.Me2+A. mH2O (Me2+=Zn2+, Mn2+, Co2+; A=Cl(-), SO4(2-), n=1, 2; m=2, 5), as supplements in the diet, were used separately on different experimental groups of male Hisex chickens to correct the mineral deficiency caused by Ascaridia galli infections. An amelioration of body weight gain, reduction of mortality and restoration of trace element levels were estimated in infected chickens. A mathematical model has been proposed for A. galli population kinetics in chickens, taking into account the stimulating effect of these elements on the nematodes. The model parameters are considered as phenomenological constants of the host-parasite system. An agreement with experimental data is observed using, for the parameters psi, alpha, micro and micros, values equal to those calculated in previously investigated A. galli-chicken systems. For parameter nu (immunological constant) the same value was obtained as in a previous experiment with high infection. This model is likely to be suitable for a range of host-nematode systems, including varying degrees of infection and treatment with different trace elements.

The effect of cobalt compounds on uninfected and Ascaridia galli-infected chickens: a kinetic model for Ascaridia galli populations and chicken growth.

The effect of dietary cobalt from three different sources on uninfected and Ascaridia galli-infected Hisex chickens, has been studied. The chicken diet was supplemented with 0.06 Co2+ kg-1 food either in the form of two glycine-cobalt compounds or mixed zinc-cobalt basic salt. An excess of dietary cobalt in small doses increases the gain of body weight and decreases host mortality. A greater bioefficiency of cobalt was established in infected chickens. A mathematical model has been used to provide a quantitative interpretation of the observed results. The model solutions of the kinetics of worm numbers and body weight are in a good agreement with experimental data. The model is valid for different degrees of A. galli infections and for treatment with different trace elements. The value of the kinetic parameter, regarded as a phenomenological constant of the host immune response, depends on the degree of infection.

Glassy cholesteric structure: thickness variation induced by electron radiation in transmission electron microscopy investigated by atomic force microscopy.

During the observation of glassy cholesteric liquid crystals in transmission electron microscopy (TEM), a new contrast is created or enhanced by electron radiation which has a direct relationship with the periodic microstructure of the specimen. In this paper, we investigate the variations of the sample thickness and mass density as possible causes of this irradiation contrast. By means of observations in atomic force microscopy (AFM) coupled to TEM, we compared the surface corrugations of non-irradiated and irradiated specimens. It is shown that the final contrast is the result of several processes. including fracture during ultramicrotomy and mass loss during irradiation. Mass loss acts as an etching, and hence results in a decrease of the sample thickness. The etching depends on the initial molecular orientation, thus evidencing the latent structure. An electron channelling mechanism is suggested to explain this behaviour.

Mechanical properties of model membranes studied from shape transformations of giant vesicles.

Membrane deformations occur frequently in cell functioning. From the physical point of view, the understanding of such shape changes requires the introduction of mechanical parameters like bending elasticity. In this article it is shown how this physical property can be obtained from the analysis of small or large shape transformations from giant vesicles. Then it is demonstrated that the bending modulus is strongly dependent on the membrane composition and environmental conditions. This is the case for one-component bilayers (dilauroylphosphatidylcholine (DLPC), dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidylcholine and stearoyloleoyl-phosphatidylcholine (SOPC) and for two-component lipid mixtures (DMPC/cholesterol, DLPC/dilauroylphosphatidic acid). Further it is shown that the bending elasticity of natural lipid extracts (egg phosphatidylcholine, digalactosyl diglyceride and red blood cell lipid extracts) is generally smaller than that of comparable synthetic model membranes. The role of transmembrane proteins is examined by measuring the bending elasticity of SOPC/gramicidin mixtures. Finally, larger scale shape transformations of giant vesicles under an alternative electric field are discussed.

Bending elasticities of model membranes: influences of temperature and sterol content.

Giant liposomes obtained by electroformation and observed by phase-contrast video microscopy show spontaneous deformations originating from Brownian motion that are characterized, in the case of quasispherical vesicles, by two parameters only, the membrane tension sigma and the bending elasticity k(c). For liposomes containing dimyristoyl phosphatidylcholine (DMPC) or a 10 mol% cholesterol/DMPC mixture, the mechanical property of the membrane, k(c), is shown to be temperature dependent on approaching the main (thermotropic) phase transition temperature T(m). In the case of DMPC/cholesterol bilayers, we also obtained evidence for a relation between the bending elasticity and the corresponding temperature/cholesterol molecular ratio phase diagram. Comparison of DMPC/cholesterol with DMPC/cholesterol sulfate bilayers at 30 degrees C containing 30% sterol ratio shows that k(c) is independent of the surface charge density of the bilayer. Finally, bending elasticities of red blood cell (RBC) total lipid extracts lead to a very low k(c) at 37 degrees C if we refer to DMPC/cholesterol bilayers. At 25 degrees C, the very low bending elasticity of a cholesterol-free RBC lipid extract seems to be related to a phase coexistence, as it can be observed by solid-state (31)P-NMR. At the same temperature, the cholesterol-containing RBC lipid extract membrane shows an increase in the bending constant comparable to the one observed for a high cholesterol ratio in DMPC membranes.