Gliotoxicity, reverse transcriptase activity and retroviral RNA in monocyte/macrophage culture supernatants from patients with multiple sclerosis

Utilizing cultured lenses from normal and homozygous glutathione peroxidase (GSHPx-1) knockout mice and inhibitors for GSSG Reductase (GSSG Red), 1,3-bis(2-chlorethyl)-1-nitrosourea (BCNU) and catalase (Cat), 3-aminotriazole (3-AT), the ability to degrade H2O2 was examined at two H2O2 concentrations, 300 microM and 80 microM. It was found that GSHPx-1 contributed about 15% to the H2O2 degradation. The Cat contribution was concentration dependent being about 30% at 300 microM H2O2 and approximately 8% to 15% at 80 microM H2O2. GSH loss measured as nonprotein thiol (NP-SH) was shown to be linked to most of the remaining H2O2 degradation accounting for about 54% to 72% of the H2O2 degradation at 300 microM and 80 microM, respectively. However, based on evaluation of the ability of GSH to nonenzymatically degrade H2O2, it can only account for about 36% at 300 microM and 19% at 80 microM H2O2 of the observed lens H2O2 degradation. It is, therefore, concluded that lens GSH must be involved in other reactions either directly or indirectly related to H2O2 degradation.     

Autonomy and gender: Some questions for therapists.

Discusses the nature of autonomy and explores how autonomy as a therapeutic goal relates to clinical practice and the conduct of psychotherapy. Autonomy has been defined as the power to determine one's own best interests, and it has been criticized for promoting selfishness and reflecting upper-class values and gender bias. It is suggested that issues of autonomy are involved in the process of psychotherapy as well as its aim. In therapy, there is a dynamic tension between the principle of autonomy, the right of clients to determine their own interests, and the principle of beneficence, the therapist's obligation to protect the client's welfare. Whether autonomy is an appropriate ideal in psychotherapy for women or for men is considered. Feminist theorists have criticized aspects of masculine autonomy, contrasting it with feminine relatedness; however, the idealization of relatedness is questioned. It is concluded that the present conceptualizations of autonomy do not fully encompass the complexity of human interaction. It is argued that (a) autonomy and relatedness are not essential aspects of male and female nature but depend on power and status and (b) without social change, autonomy may not be a realistic goal of therapy for women. (46 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Class sigma glutathione transferase unfolds via a dimeric and a monomeric intermediate: impact of subunit interface on conformational stability in the superfamily

Solvent-induced equilibrium unfolding of a homodimeric class sigma glutathione transferase (GSTS1-1, EC 2.5.1.18) was characterized by tryptophan fluorescence, anisotropy, enzyme activity, 8-anilino-1-naphthalenesulfonate (ANS) binding, and circular dichroism. Urea induces a triphasic unfolding transition with evidence for two well-populated thermodynamically stable intermediate states of GSTS1-1. The first unfolding transition is protein concentration independent and involves a change in the subunit tertiary structure yielding a partially active dimeric intermediate (i.e., N2 left and right arrow I2). This is followed by a protein concentration dependent step in which I2 dissociates into compact inactive monomers (M) displaying enhanced hydrophobicity. The third unfolding transition, which is protein concentration independent, involves the complete unfolding of the monomeric state. Increasing NaCl concentrations destabilize N2 and appear to shift the equilibrium toward I2 whereas the stability of the monomeric intermediate M is enhanced. The binding of substrate or product analogue (i.e., glutathione or S-hexylglutathione) to the protein's active site stabilizes the native dimeric state (N2), causing the first two unfolding transitions to shift toward higher urea concentrations. The stability of M was not affected. The data implicate a region at/near the active site in domain I (most likely alpha-helix 2) as being highly unstable/flexible which undergoes local unfolding, resulting initially in I2 formation followed by a disruption in quaternary structure to a monomeric intermediate. The unfolding/refolding pathway is compared with those observed for other cytosolic GSTs and discussed in light of the different structural features at the subunit interfaces, as well as the evolutionary selection of this GST as a lens crystallin.     

Electrical conductivity,self-diffusion,and volume expansion of alkali halides at the melting point

In an earlier paper, Heisenberg's uncertainty principle was invoked at the melting point T _m of crystalline solids to provide fundamental justification for Lindemann's melting law and to compute diffusion coefficients of several alkali halides. The uncertainty principle defines breakdown of Debye zone boundary (ZB) phonons as valid collective excitations when phonon energies and line widths due to anharmonicity become comparable at T _m. Upon breakdown, random, high-frequency single-particle motion or partial decoupling of crystal ions sets in. Lifetimes of these single-particle ZB motions are determined from the minimum-uncertainty product inequality by assuming that it becomes an equality at T _m for ZB phonons. The present paper addresses improved formulation of that work and extended application to ionic electrical conductivities of 18 molten alkali halides at T _m. It is shown that use of the Debye model produces an approximate lower bound to the mean free time, not the unconstrained direct estimate previouslu implied. This feature is generally reflected in results for ionic conductivities and alkali halide diffusion coefficients for which comparison experimental data were found. However, in spite of this lower-bound formulation and the simple nature of the computation, the results compare favorably with experiment. A model of random single-particle harmonic motion superimposed on the lower-frequency collective motion is proposed to account for volume expansion accompanying the partial decoupling for hard-sphere ions. Experimental comparisons for 15 alkali halides show the decoupling volume change to account largely for the total volume change of melting (in the hard-sphere approximation), yielding a closer agreement with experiment than recent calculations aimed explicitly at the total volume change.Paper presented at the Tenth Symposium on Thermophysical Properties, June 20–23, 1988, Gaithersburg, Maryland, U.S.A.     

Curing characteristics of a composite matrix

The account describes investigations into the variations of specific volume and viscosity of a typical high-performance epoxy resin during various time-temperature cycles. The work was undertaken primarily to provide additional background information relating to the nature and causes of fibre kinking which has been observed in laminates comprising epoxy-carbon composite. The investigation has quantified certain characteristics of the resin which are presumed to be major contributory factors in the occurrence of fibre kinking. It is concluded that a simple solution to the general problem cannot be identified, although some possibilities are discussed for individual cases.     

Micron-Scale Soft Actuators Fabricated from Multi-Shell Polystyrene Particle-Gold Nanoparticle Nanohybrids

Actuators made of soft matter are needed for a variety of fields ranging from biomedical devices to soft robotics to microelectromechanical systems. While there are a variety of excellent methods of soft actuation known, the field is still an area of intense research activity as new niches and needs emerge with new technology development. Here, a soft actuation system is described, based on a core-multi-shell particle, which moves via photothermal expansion. The system consists of a novel polystyrene-based thermally expandable microsphere, with a secondary shell of a silicate-silane graft copolymer, to which gold nanoparticles are covalently linked. The gold nanoparticles act as photothermal nano-transducers, converting light energy into the thermal energy necessary for microsphere expansion, which in turn results in material movement. Actuation is shown in isolated particles in thermal and photothermal regimes using metal ceramic heaters or 520 nm laser illumination, respectively. Macroscale actuation is demonstrated by making a composite material of particles suspended in the transparent elastomer polydimethylsiloxane. The sample demonstrates an inchworm-like movement by starting from an arched geometry. Overall, this work describes a new particle-based actuation method for soft materials, and demonstrates its utility in driving the movement of a composite elastomer.     

Characterization of Apo-Form Selective Inhibition of Indoleamine 2,3-Dioxygenase**

Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that catalyzes the rate-limiting step in the kynurenine pathway of tryptophan (TRP) metabolism. As it is an inflammation-induced immunoregulatory enzyme, pharmacological inhibition of IDO1 activity is currently being pursued as a potential therapeutic tool for the treatment of cancer and other disease states. As such, a detailed understanding of the mechanism of action of IDO1 inhibitors with various mechanisms of inhibition is of great interest. Comparison of an apo-form-binding IDO1 inhibitor (GSK5628) to the heme-coordinating compound, epacadostat (Incyte), allows us to explore the details of the apo-binding inhibition of IDO1. Herein, we demonstrate that GSK5628 inhibits IDO1 by competing with heme for binding to a heme-free conformation of the enzyme (apo-IDO1), whereas epacadostat coordinates its binding with the iron atom of the IDO1 heme cofactor. Comparison of these two compounds in cellular systems reveals a long-lasting inhibitory effect of GSK5628, previously undescribed for other known IDO1 inhibitors. Detailed characterization of this apo-binding mechanism for IDO1 inhibition might help design superior inhibitors or could confer a unique competitive advantage over other IDO1 inhibitors vis-à-vis specificity and pharmacokinetic parameters.     

NMR and sedimentation studies of a polymeric steric stabilizer for alumina

The sedimentation behavior of alumina powder has been studied in the presence of poly-vinylpyrrolidone (PVP) and poly(vinylpyrrolidone-co-vinyl acetate) (PVP/VA) in both thermodynamically “good” and “poor” solvents for the PVP homopolymer. PVP/VA provides higher sediment densities than does its PVP homopolymer counterpart. Solutionstate ¹³C-T₁ spin-lattice relaxation measurements were made on analogous mixtures both with and without alumina powder. The NMR results suggest that the PVP/VA copolymer is anchored to the alumina powder surface by means of VA moieties, whereas the PVP moieties extend into the continuous phase of the slurry medium. Thus, the higher settling densities that are observed in the presence of PVP/VA can be attributed to a steric stabilization mechanism. © 1993 John Wiley & Sons, Inc.