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Notes: Abstract: Growing evidence supports the notion of a functional relationship between the presence of the β-amyloid (Aβ) peptide and the production of inflammatory mediators in and around neuritic plaques of Alzheimer's disease. Tissue remodeling enzymes that are critical in peripheral inflammatory responses are the matrix metalloproteinases (MMPs), enzymes produced by neurons and glia. Thus, it was of interest to determine whether Aβ may alter the expression of MMPs in glial and neuronal cultures. It was demonstrated that Aβ (1–40) is a potent stimulator of MMP-9 and MMP-2 activity in addition to inducing the expression of a lower molecular weight, unidentified gelatinase activity in mixed hippocampal and astrocyte cultures. Shorter fragments of Aβ were less effective in stimulating the production of these enzymes. The lower molecular weight activity was observed only in response to Aβ, and not after treatment with various cytokines. In addition, both cultures express MMP-3 (stromelysin-1) in response to Aβ peptides. These results suggest that MMPs may play a role in the development or progression of neuritic plaques, i.e., abnormal neurite outgrowth.

Notes: Abstract: Under a tightly regulated expression mechanism, matrix metalloproteinases degrade extracellular matrix proteins and are though to play a role in injury repair and tumor metastasis in peripheral tissues. Little is known about the function of matrix metalloproteinases or agents that regulate their production in adult brain; however, it has been shown that the activity of a calcium-dependent metalloproteinase is elevated in Alzheimer's hippocampus. The goals of this study were to determine whether cultured rat astrocytes produce matrix metalloproteinases and to identify agents that regulate protease activity. Enriched astrocyte cultures were prepared from brains of 1-day-old rat pups, and experiments were performed 13 days later. Gelatinase activity in astrocyte conditioned medium was determined using zymography with gelatin copolymerized with acrylamide in the gel. Under basal conditions after a 24-h incubation, rat astrocytes produce gelatinases of 58 and 66 kDa. On stimulation of astrocytes with lipopolysaccharide, interleukin-1α or -β, or tumor necrosis factor-α for 24 h, a dose-dependent increase in the activity of the 58- and 66-kDa gelatinases and the induction of a 94-kDa gelatinase occurred. All three astrocyte-derived proteases showed maximal activity in the presence of millimolar levels of Ca2+, their activity was inhibited in the presence of 1,10-phenanthroline, and their proenzymes were cleaved and activated after incubation with p-aminophenylmercuric acetate. Using immunoblotting, immunopositive bands at the respective molecular sizes indicated that the 58-kDa gelatinase was gelatinase A (matrix metalloproteinase 2) and the 94-kDa activity was gelatinase B (matrix metalloproteinase 9). Induction of the 94-kDa gelatinase by lipopolysaccharide was not influenced when interleukin-1 receptor antagonist was included during the 24-h incubation period; however, the antagonist completely blocked interleukin-1β-induced 94-kDa activity and diminished the activity of the 58- and 66-kDa gelatinases. Dexamethasone inhibited both lipopolysaccharide and interleukin-1β stimulation of the 94-kDa gelatinase. These results indicate that cytokines regulate matrix metalloproteinase expression in cultured rat astrocytes. Because astrocytes become “activated” (are hypertrophic and express increased levels of glial fibrillary acidic protein) in the presence of several inflammatory cytokines, it is possible that these astrocyte-derived enzymes contribute to the activation process and may participate in tissue remodeling after brain injury.

Notes: Molecular dynamics (MD) simulations have been used to determine the two dimensional free energy surface of the alanine dipeptide in solution. The intramolecular dipeptide interactions were described by the CHARMM22 force field. Three models of solvation were considered; (i) a simple scaling of electrostatic interactions, (ii) solvation energies determined by finite difference Poisson–Boltzmann calculations, and (iii) inclusion of explicit TIP3P solvent molecules. All three solvation models produced qualitatively similar effects, but differed significantly in their quantitative values. In particular, the continuum based models predicted the β (extended) conformation to be most stable, whereas the explicit solvent model favored the αR (folded) conformation. Comparison with experimental data for the H–N–Cα-Hα coupling constant, helix–coil transition thermodynamics, and polypeptide infinite chain length characteristic ratios was performed. The explicit solvent surface produced the strongest agreement with experiment, although there is no unambiguous data to support any of the solvent models. © 1999 American Institute of Physics.

Notes: Expressions are derived within the relativistic regular approximation (ZORA) for the evaluation of the magnetic hyperfine interactions in paramagnetic molecules. For hydrogen-like atoms exact first order relations between the ZORA and Dirac formalism are given for the calculation of g- and A-tensors. Density functional calculations are performed on the neutral atoms Cu, Ag and Au, on some small test molecules NO2, HCO, and TiF3, and on some paramagnetic clusters consisting of 5 or 7 atoms of the group IB metals: Cu7, Cu2Ag5, CuAg6, Ag5, Ag7, and Au7. It is shown that the calculated ESR parameters of the heptamers are in good agreement with results of experiments, which originally were assigned to pentamers. © 1998 American Institute of Physics.

Notes: We demonstrate a novel method for the growth of abrupt InGaAs(P)/In(GaAs)P heterojunctions by gas source molecular beam epitaxy. We find that exposure of freshly grown InP to an As flux during growth interruption between layers of different compositions results in the substitution of surface P atoms and As atoms, thereby generating a strained transition layer at each interface. By assuring a group-III stabilized surface during interruption required to grow InGaAs(P)/In(GaAs)P heterointerfaces, As/P substitution can be avoided, thereby resulting in improved interface quality. Heterointerface abruptness was examined by double-crystal x-ray diffraction and low temperature photoluminescence. The results show that the interfaces grown with the modified switching sequence are considerably more abrupt than those obtained using conventional sequences where As/P interdiffusion extends over several monolayers. © 1995 American Institute of Physics.

Notes: We apply tensor methods to formulate theories of electron correlation in nonorthogonal basis sets. The resulting equations are manifestly invariant to nonorthogonal basis transformations, between functions spanning either the occupied or virtual subspaces of the one-particle Hilbert space. The tensor approach is readily employed in either first or second quantization. As examples, second-order Møller–Plesset perturbation theory, and coupled cluster theory with single and double substitutions, including noniterative triples, are recast using the tensor formalism. This gives equations which are invariant to larger classes of transformations than existing expressions. Procedures for truncating these equations are discussed. © 1998 American Institute of Physics.

Notes: A method has been developed for the calculation of the g-tensor of Kramers doublet open shell molecules, which uses the spinor of the unpaired electron of the paramagnetic molecule, obtained from a density functional calculation. Spin–orbit coupling is taken into account variationally using the zeroth-order regular approximation (ZORA) to the Dirac equation. The problem of gauge dependence is solved by using gauge including atomic orbitals (GIAO's). The method gives fair agreement with experimental values for the g values of some small test molecules NO2, HCO, and TiF3. © 1997 American Institute of Physics.

Notes: Reported here is a theoretical calculation of the spectrum of the argon–methane complex based upon a previously reported ab initio potential energy surface [T. G. A. Heijmen et al., J. Chem. Phys. 107, 902 (1997)]. The irregular rotational structure observed in the spectrum is traced to a combination of the fact that the excited vibrational state of the methane has vibrational angular momentum and the methane rotates nearly freely within the complex. The theoretical spectrum is compared qualitatively with the experimental results obtained using the optothermal method, a more complete discussion of which is given in a companion paper, hereafter referred to as paper II. © 1999 American Institute of Physics.