Protein oxidative damage in a transgenic mouse model of familial amyotrophic lateral sclerosis

The Gly93-->Ala mutation in the Cu,Zn superoxide dismutase (Cu,Zn-SOD) gene (SOD1) found in some familial amyotrophic lateral sclerosis (FALS) patients has been shown to result in an aberrant increase in hydroxyl radical production by the mutant enzyme that may cause oxidative injury to spinal motor neurons. In the present study, we analyzed the extent of oxidative injury to lumbar and cervical spinal cord proteins in transgenic FALS mice that overexpress the SOD1 mutation [TgN(SOD1-G93A)G1H] in comparison with nontransgenic mice. Total protein oxidation was examined by spectrophotometric measurement of tissue protein carbonyl content by the dinitrophenylhydrazine (DNPH) assay. Four ages were investigated: 30 (pre-motor neuron pathology and clinical disease), 60 (after initiation of pathology, but pre-disease), 100 (approximately 50% loss of motor neurons and function), and 120 (near complete hindlimb paralysis) days. Protein carbonyl content in 30-day-old TgN(SOD1-G93A)G1H mice was twice as high as the level found in age-matched nontransgenic mice. However, at 60 and 100 days of age, the levels were the same. Then, between 100 and 120 days of age, the levels in the TgN(SOD1-G93A)G1H mice increased dramatically (557%) compared with either the nontransgenic mice or transgenic animals that overexpress the wild-type human Cu,Zn-SOD [TgN(SOD1)N29]. The 100-120-day increase in spinal cord protein carbonyl levels was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoretic separation and western blot immunoassay, which enabled the identification of heavily oxidized individual proteins using a monoclonal antibody against DNPH-derivatized proteins. One of the more heavily oxidized protein bands (14 kDa) was identified by immunoprecipitation as largely Cu,Zn-SOD. Western blot comparison of the extent of Cu,Zn-SOD protein carbonylation revealed that the level in spinal cord samples from 120-day-old TgN(SOD1-G93A)G1H mice was significantly higher than that found in age-matched nontransgenic or TgN(SOD1)N29 mice. These results suggest that the increased hydroxyl radical production associated with the G93A SOD1 mutation and/or lipid peroxidation-derived radical species (peroxyl or alkoxyl) causes extensive protein oxidative injury and that the Cu,Zn-SOD itself is a key target, which may compromise its antioxidant function.     

数字化的另一面

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Corrosion behavior of porous magnesium coated by plasma electrolytic oxidation in simulated body fluid

Porous magnesium has a great potential to be used as degradable bone scaffolds. In this study, porous magnesium with 35% percolating porosity has been successfully fabricated through powder metallurgy route utilizing space holders. The intrinsic mechanical properties of the porous magnesium were measured by nanoindentation testing and analyzed with the Oliver–Pharr method. Afterward, a ceramic coating on the surface of the porous magnesium was performed by plasma electrolytic oxidation (PEO) treatment in a silicate‐based solution. The morphology and composition results of the PEO coatings indicated that it is possible to apply a homogenous and adhesive ceramic coating layer on all free surface of the porous magnesium through PEO method. The protective performance of the PEO coatings was evaluated using by potentiodynamic polarization and electrochemical impedance spectroscopy tests in simulated body fluid. The results revealed the PEO coating significantly improves biocorrosion resistance of the porous magnesium. Therefore, it can be used as an effective method to control the degradation rate of porous magnesium implants in the human body.     

Deformation of α-zirconium in the vicinity of 0.5 tinm

The creep behavior of specimens of α-Zr, machined from the three principal directions of a rolled slab or from swaged rod, has been studied in the temperature range 870 to 975 K, for stresses in the range 5 to 20 MPa. For a given stress and temperature, the creep rate depends on texture, being higher for specimens having their axes parallel to the longitudinal (rolling) direction than for specimens cut from either the transverse or short transverse directions. The activation energy for creep,Q _C, decreases with increasing stress, and becomes approximately equal toQ _D, the activation energy for self-diffusion, only for stresses in excess of about 20 MPa. The stress exponentn increases from 3 at low stresses to about 9 at high stresses, for the range of stresses and strain rates investigated. The results are incompatible with a simple, power-law representation of the steady-state creep rate in whichn is constant, andQ _C =Q _D, independent of stress. It is demonstrated that the data are consistent with models in which the glide process contributes to the stress and temperature dependencies of steady-state creep.     

Effect of inclusions and holes on the stiffness and strength of honeycombs

A finite element study has been performed on the effects of holes and rigid inclusions on the elastic modulus and yield strength of regular honeycombs under biaxial loading. The focus is on honeycombs that have already been weakened by a small degree of geometrical imperfection, such as a random distribution of fractured cell walls, as these imperfect honeycombs resemble commercially available metallic foams. Hashin–Shtrikman lower and upper bounds and self-consistent estimates of elastic moduli are derived to provide reference solutions to the finite element calculations. It is found that the strength of an imperfect honeycomb is relatively insensitive to the presence of holes and inclusions, consistent with recent experimental observations on commercial aluminium alloy foams.     

The failure of composite tubes due to combined compression and torsion

The strength of unidirectional carbon-fibre epoxy laminates has been measured for combined compression and shear loading. Failure was by plastic microbuckling. The axial compressive strength decreased linearly to zero as the shear stress parallel to the fibres was increased from zero to the shear strength. These experimental results support the predictions of Budiansky and Fleck and suggest an average fibre misalignment angle of 2°–3°.     

Methodology for the simultaneous optimization of location and parameters of friction dampers in the frequency domain

It is well known that the use of passive energy dissipation devices such as friction dampers reduces the dynamic response of structures subjected to earthquakes. However, the parameters of each damper as well as the best position of these devices in the structure remain difficult to determine. Although articles on optimum design of tuned mass dampers and viscous dampers have been published, there is a lack of studies on the optimization of friction dampers. In previous contributions, the authors proposed a method for optimum design of this kind of damper. The proposed method is very useful; however, the computational time required is high. Thus, in this article, a new methodology for the simultaneous optimization of placement and forces of friction dampers is proposed. As this new method is developed in the frequency domain, the computational time is considerably reduced. For this purpose, the search group algorithm, recently developed by the authors, is employed, which is able to deal with optimization problems involving mixed discrete and continuous variables. For illustrative purposes, a six-storey shear building is analysed. Forces and positions of friction dampers are the design variables, while the objective function is to minimize the root mean square displacement at the top of the building. The results showed the excellent performance of the proposed method, reducing the root mean square displacement by more than 82%, with only three friction dampers and in a relatively short computational time.     

Epidermal growth factor (EGF) increases the renal amino acid transport capacity in amino acid loaded rats

In anaesthetized adult female rats, the influence of epidermal growth factor (EGF) on renal amino acid handling was investigated in glutamine, arginine (both 50 mg/100 g b.wt. per hour), or alanine (90 mg/100 g b.wt. per hour) loaded animals. Continuous infusions of the three amino acids were followed by an increase in the fractional excretion (FE) of the administered amino acids as well as of the other endogenous amino acids. Under load conditions (alanine, arginine or glutamine), EGF pretreatment (8 micrograms/100 g b.wt. subcutaneously for 8 days, twice daily 8 a.m. and 4 p.m.) was followed by a stimulation of renal amino acid reabsorption. The increase in the fractional excretion of the administered amino acids was significantly lower than in non-EGF-treated rats. These changes in amino acid transport were connected with a significant reduction of GFR after EGF pretreatment (0.96 +/- 0.10 vs. 0.62 +/- 0.07 ml/min x 100 g b.wt.) and a distinct increase in sodium excretion (2.98 +/- 0.55 vs. 4.97 +/- 0.71 muval/100 g b.wt. x 20 min). After loading with p-aminohippurate (PAH; 200 mg/100 g b.wt.), PAH excretion in EGF rats was increased by about 20%, whereas urinary protein excretion was lower in EGF pretreated rats (control: 0.45 +/- 0.04 vs. EGF: 0.18 +/- 0.03 mg/100 g b.wt. x 20 min). The PAH load reduced amino acid reabsorption as a sign of overloading of renal tubular transport capacity, but in EGF pretreated animals the amino acid excretion was only slightly increased under these conditions. Furthermore, EGF pretreatment depressed normal kidney weight gain significantly (874 +/- 18 vs. 775 +/- 32 mg/100 g b.wt.). EGF can improve the renal tubular transport capacity, but, compared to well-known stimulators of renal transport like dexamethasone or triiodothyronine, its effect is only of a moderate degree.