Apolipoprotein E controls cerebrovascular integrity via cyclophilin A

Human apolipoprotein E has three isoforms: APOE2, APOE3 and APOE4. APOE4 is a major genetic risk factor for Alzheimer's disease and is associated with Down's syndrome dementia and poor neurological outcome after traumatic brain injury and haemorrhage. Neurovascular dysfunction is present in normal APOE4 carriers and individuals with APOE4-associated disorders. In mice, lack of Apoe leads to blood-brain barrier (BBB) breakdown, whereas APOE4 increases BBB susceptibility to injury. How APOE genotype affects brain microcirculation remains elusive. Using different APOE transgenic mice, including mice with ablation and/or inhibition of cyclophilin A (CypA), here we show that expression of APOE4 and lack of murine Apoe, but not APOE2 and APOE3, leads to BBB breakdown by activating a proinflammatory CypA-nuclear factor-κB-matrix-metalloproteinase-9 pathway in pericytes. This, in turn, leads to neuronal uptake of multiple blood-derived neurotoxic proteins, and microvascular and cerebral blood flow reductions. We show that the vascular defects in Apoe-deficient and APOE4-expressing mice precede neuronal dysfunction and can initiate neurodegenerative changes. Astrocyte-secreted APOE3, but not APOE4, suppressed the CypA-nuclear factor-κB-matrix-metalloproteinase-9 pathway in pericytes through a lipoprotein receptor. Our data suggest that CypA is a key target for treating APOE4-mediated neurovascular injury and the resulting neuronal dysfunction and degeneration.     

Accumulation of a heat shock-like protein during differentiation of human erythroid cell line K562

The human erythroid cell line K562 provides a model system for studying erythroid differentiation and eukaryotic gene regulation. These cells express glycophorin A, spectrin and i antigen. They accumulate embryonic and fetal haemoglobins on induction of erythroid differentiation with haemin, sodium butyrate or hydroxyurea. In the present study, the protein composition of K562 cells during haemin-mediated induction of erythroid maturation was analysed by two-dimensional gel electrophoresis. Under conditions in which haemin did not effect cell viability and proliferation, a protein of approximately 70,000 molecular weight (MW) accumulated in the differentiated K562 cells. The accumulation appears to be due to an increase in the rate of RNA synthesis for this protein. The protein is related in sequence to a 70,000-MW heat shock protein. An antigenically related protein was also demonstrated in human bone marrow and accumulates at particular stages of human erythroid maturation.     

Synthesis of the 3D porous carbon-manganese oxide (3D-C@MnO) nanocomposite and its supercapacitor behavior study

A 3D porous carbon-manganese oxide ([email protected]) nanocomposite is successfully synthesized via a thermal plasma deposition method. The chemical bonds and compositions, phase structures, surface morphologies, etc. of as-obtained [email protected] nanocomposite were characterized by the various equipment, such as X-ray diffractometer, X-ray photoelectron spectroscopy, and electron microscopes. The electrochemical performances of the [email protected] nanocomposite electrode showed a specific capacitance of 780 F g^?1 at a current density of 2 A g^?1 and a capacitance retention rate of 99% after 5000 charge-discharge cycles at a high current density of 10 A g^?1. These excellent capacitive performances may be attributed to the encapsulation of MnO nanoparticles by porous carbon sheets in the [email protected] MnO nanocomposite structure. It is believed that the carbon-encapsulated MnO nanoparticles can be protected from a volume deformation during the charge adsorption/desorption cycle and can be electrically improved by the encapsulated carbon sheets, resulting in better overall capacitive performance. In addition, this study also demonstrates the practical applicability by assembling a supercapacitor using the as-obtained [email protected] nanocomposite to glow a light emitting diode.     

Free energy perturbation calculations on binding and catalysis after mutating Asn 155 in subtilisin

Site-directed mutagenesis is a very powerful approach to altering the biological functions of proteins, the structural stability of proteins and the interactions of proteins with other molecules. Several experimental studies in recent years have been directed at estimating the changes in catalytic properties, (rates of binding and catalysis) in site-directed mutants of enzymes compared to the native enzymes. Simulation approaches to the study of complex molecules have also become more powerful, in no small measure owing to the increase in computer power. These simulations have often allowed results of experiments to be rationalized and understood mechanistically. A new approach called the free-energy pertubation method, which uses statistical mechanics and molecular dynamics can often be used for quantitative calculation of free energy differences. We have applied such a technique to calculate the differential free energy of binding and free energy of activation for catalysis of a tripeptide substrate by native subtilisin and a subtilisin mutant (Asn 155----Ala 155). Our studies lead to a calculated difference in free energy of binding which is relatively small, but a calculated change in free energy of catalysis which is substantial. These energies are very close to those determined experimentally (J. A. Wells and D. A. Estell, personal communication), which were not known to us until the simulations were completed. This demonstrates the predictive power and utility of theoretical simulation methods in studies of the effects of site-specific mutagenesis on both enzyme binding and catalysis.     

Effect of electroslag remelting and homogenization on hydrogen flaking in AMS-4340 ultra-high-strength steels

Hydrogen flakes and elemental segregation are the main causes of steel rejection. To eliminate hydrogen flaking, the present study focuses on the manufacture of AMS-4340 ultra-high-strength steel through an alternate route. AMS-4340 was prepared using three different processing routes. The primary processing route consisted of melting in an electric arc furnace, refining in a ladle refining furnace, and vacuum degassing. After primary processing, the heat processes(D1, D2, and D3) were cast into cylindrical electrodes. For secondary processing, electroslag remelting(ESR) was carried out on the primary heats to obtain four secondary heats: E1, E2, E3, and E4. Homogenization of ingots E1, E2, E3, and E4 was carried out at 1220°C for 14, 12, 12, and 30 h, respectively, followed by an antiflaking treatment at 680°C and air cooling. In addition, the semi-finished ESR ingot E4 was again homogenized at 1220°C for 6–8 h and a second antiflaking treatment was performed at 680°C for 130 h followed by air cooling. The chemical segregation of each heat was monitored through a spectroscopy technique. The least segregation was observed for heat E4. Macrostructure examination revealed the presence of hydrogen flakes in heats E1, E2, and E3, whereas no hydrogen flakes were observed in heat E4. Ultrasonic testing revealed no internal defects in heat E4, whereas internal defects were observed in the other heats. A grain size investigation revealed a finer grain size for E4 compared with those for the other heats. Steel produced in heat E4 also exhibited superior mechanical properties. Therefore, the processing route used for heat E4 can be used to manufacture an AMS-4340 ultra-high-strength steel with superior properties compared with those of AMS-4340 prepared by the other investigated routes.     

Dielectric relaxation and conduction mechanism in Aurivillius ceramic Bi5Ti3FeO15

For this study, we synthesized Aurivillius Bi5Ti3FeO15 ceramic using the generic solid-state reaction route and then performed room-temperature X-ray diffraction to confirm that the compound had a single phase with no impurities. The surface morphology of the prepared sample was observed to contain microstructural grains approximately 0.2–2 μm in size. The dielectric properties of the sample were determ-ined as a function of frequency in a range of approximately 100 Hz to 1 MHz at various temperatures (303 K ≤ T ≤ 773 K). Nyquist plots of the impedance data were found to exhibit a semi-circular arc in the high-temperature region, which is explained by the equivalent electrical circuit (R1C1)(R2QC2), where R1 and R2 represent the resistances associated with the grains and grain boundaries, respectively, C1 and C2 are the re-spective capacitances, and Q is the constant phase element (CPE), which accounts for non-Debye type of behavior. Our results indicate that both the resistance and capacitance of the grain boundaries are more prominent than those of the grains. The alternating current (ac) conductiv-ity data were analyzed based on the Jonscher universal power law, which indicated that the conduction process is dominated by the hopping mechanism. The calculated activation energies of the relaxation and conduction processes were very similar (0.32 to 0.53 eV), from which we conclude that the same type of charge carriers are involved in both processes.     

Effect of Co substitution on the structural,dielectric and optical properties of KBiFe2O5

Cobalt (Co)-modified brownmillerite KBiFe2O5 (KBFO; [KBiFe2(1?x)Co2xO5 (x = 0, 0.05)]) polycrystalline is synthesized following the solid-state reaction route. Rietveld refinement of X-ray diffraction data confirmed the phase purity of KBFO and KBiFe1.9Co0.1O5 (KBFCO). The optical bandgap energy (Eg) of KBFO decreased from 1.59 to 1.51 eV because of Co substitution. The decrease in bandgap can be attributed to the tilting of the Fe–O tetrahedral structure of KBFCO. The observed room-temperature Raman peaks of KBFCO shifted by 3 cm?1 toward a lower wavenumber than that of KBFO. The shift in Raman active modes can be attributed to the change in the bond angles and bond lengths of the Fe–O tetrahedral structure and modification in response to oxygen deficiency in KBFO because of Co doping. Compared with that of KBFO, the frequency-dependent dielectric constant and dielectric loss of KBFCO decrease at room temperature, which is a con-sequence of the reduction in oxygen migration and modification in response to vibrational modes present in the sample.     

Evidence for a spin-aligned neutron-proton paired phase from the level structure of (92)Pd

Shell structure and magic numbers in atomic nuclei were generally explained by pioneering work that introduced a strong spin-orbit interaction to the nuclear shell model potential. However, knowledge of nuclear forces and the mechanisms governing the structure of nuclei, in particular far from stability, is still incomplete. In nuclei with equal neutron and proton numbers (N = Z), enhanced correlations arise between neutrons and protons (two distinct types of fermions) that occupy orbitals with the same quantum numbers. Such correlations have been predicted to favour an unusual type of nuclear superfluidity, termed isoscalar neutron-proton pairing, in addition to normal isovector pairing. Despite many experimental efforts, these predictions have not been confirmed. Here we report the experimental observation of excited states in the N = Z = 46 nucleus (92)Pd. Gamma rays emitted following the (58)Ni((36)Ar,2n)(92)Pd fusion-evaporation reaction were identified using a combination of state-of-the-art high-resolution γ-ray, charged-particle and neutron detector systems. Our results reveal evidence for a spin-aligned, isoscalar neutron-proton coupling scheme, different from the previous prediction. We suggest that this coupling scheme replaces normal superfluidity (characterized by seniority coupling) in the ground and low-lying excited states of the heaviest N = Z nuclei. Such strong, isoscalar neutron-proton correlations would have a considerable impact on the nuclear level structure and possibly influence the dynamics of rapid proton capture in stellar nucleosynthesis.     

Applications of Transition Metals in Organic Synthesis and Polymerization

1 Results Classic oxidants require rigorous control of the experimental conditions added with the problem of lack of selectivity. Catalysis by transition metals with environmentally safe oxidants provides synthetic routes to minimize pollution by giving environmental benign by-products. Fe (Ⅵ) is a powerful and a selective oxidant with Fe(Ⅲ) as a by-product, while hydrogen peroxide is clean with water as the only by-product. Separation of sodium or potassium ferrates requires tedious processes. Associat...     

Using an Action Research Framework to Explore Assessment: A South African Case Study

This article is a reflection of my first experience with action research in trying to devise a system of assessment that would benefit both first and second language speakers of English in an assessment system that is plagued by its separatist past. In this paper, I discuss an action research study on oral assessment implemented at two tertiary institutions in South Africa. The actual details of each phase of the assessments are not reported on, but the methods used to facilitate the processes are. The findings and adaptations after each phase of the assessments are discussed to show the effectiveness of using an action research methodology.