Essential requirement of cytosolic phospholipase A2 for activation of the phagocyte NADPH oxidase

Arachidonic acid (AA) can trigger activation of the phagocyte NADPH oxidase in a cell-free assay. However, a role for AA in activation of the oxidase in intact cells has not been established, nor has the AA generating enzyme critical to this process been identified. The human myeloid cell line PLB-985 was transfected to express p85 cytosolic phospholipase A2 (cPLA2) antisense mRNA and stable clones were selected that lack detectable cPLA2. cPLA2-deficient PLB-985 cells differentiate similarly to control PLB-985 cells in response to retinoic acid or 1,25-dihydroxyvitamin D3, indicating that cPLA2 is not involved in the differentiation process. Neither cPLA2 nor stimulated [3H]AA release were detectable in differentiated cPLA2-deficient PLB-985 cells, demonstrating that cPLA2 is the major type of PLA2 activated in phagocytic-like cells. Despite the normal synthesis of NADPH oxidase subunits during differentiation of cPLA2-deficient PLB-985 cells, these cells fail to activate NADPH oxidase in response to a variety of soluble and particulate stimuli, but the addition of exogenous AA fully restores oxidase activity. This establishes an essential requirement of cPLA2-generated AA for activation of phagocyte NADPH oxidase.     

Attentional Biases for Negative Interpersonal Stimuli in Clinical Depression.

An information-processing paradigm was used to examine attentional biases in clinically depressed participants, participants with generalized anxiety disorder (GAD), and nonpsychiatric control participants for faces expressing sadness, anger, and happiness. Faces were presented for 1,000 ms, at which point depressed participants had directed their attention selectively to depression-relevant (i.e., sad) faces. This attentional bias was specific to the emotion of sadness; the depressed participants did not exhibit attentional biases to the angry or happy faces. This bias was also specific to depression; at 1,000 ms, participants with GAD were not attending selectively to sad, happy, or anxiety-relevant (i.e., angry) faces. Implications of these findings for both the cognitive and the interpersonal functioning of depressed individuals are discussed and directions for future research are advanced. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of trichloroethylene on the exploratory and locomotor activity of rats exposed during development

Trichloroethylene (TCE) is a common contaminant of underground water supplies. To examine the effect of TCE on the developing central nervous system, rats were exposed to TCE throughout gestation until 21 days postpartum via their dams' drinking water. TCE concentrations of 312 mg/l, 625 mg/l and 1250 mg/l were tested. Exploratory behavior was higher in 60- and 90-day old male rats which were exposed to any level of TCE. The effect of TCE-exposure on locomotor activity (running wheel) was also examined in 60-day old males (625 and 1250 ppm exposure groups). Locomotor activity was significantly higher in rats exposed to 1250 ppm TCE. These data suggest that TCE has long-term effects on behaviour.     

Spiking and Bursting in Josephson Junction

This brief reports spiking and bursting in numerical simulations of the resistive-capacitive-inductive shunted Josephson junction model. Regular spiking, intrinsic bursting, and fast spiking, which are usually seen in the mammalian neocortex, are observed in the junction dynamics under external dc bias. The junction voltage is amplitude and frequency modulated when forced by weaker sinusoidal forcing of frequency much lower than the junction resonant frequency. For stronger forcing, bursting is observed. The autonomous junction also shows bursting in the high inductive regime. Bifurcation scenarios of bursting are discussed for both autonomous and nonautonomous cases     

N‐Arylsulfonyl Indolines as Retinoic Acid Receptor‐Related Orphan Receptor γ (RORγ) Agonists

The nuclear retinoic acid receptor‐related orphan receptor γ (RORγ; NR1F3) is a key regulator of inflammatory gene programs involved in T helper 17 (T_H17) cell proliferation. As such, synthetic small‐molecule repressors (inverse agonists) targeting RORγ have been extensively studied for their potential as therapeutic agents for various autoimmune diseases. Alternatively, enhancing T_H17 cell proliferation through activation (agonism) of RORγ may boost an immune response, thereby offering a potentially new approach in cancer immunotherapy. Herein we describe the development of N‐arylsulfonyl indolines as RORγ agonists. Structure–activity studies reveal a critical linker region in these molecules as the major determinant for agonism. Hydrogen/deuterium exchange coupled to mass spectrometry (HDX‐MS) analysis of RORγ–ligand complexes help rationalize the observed results.     

Modeling the evolution and rupture of stretching pendular liquid bridges

A simplified mathematical model and numerical simulations of the governing Navier–Stokes equations are used to predict the shape evolution, rupture distance, and liquid distribution of stretching pendular liquid bridges between two equal-sized spherical solid particles. In the simplified model, the bridge shape is approximated with a parabola, and it is assumed that the surface tension effects dominate the viscous, inertial, and gravitational effects. For the numerical simulations, a commercial Computational Fluid Dynamics (CFD) software package – FLUENT – is used. The rupture distance predictions obtained with both models are compared with experimental data and a reasonable agreement is found. The results of the numerical investigations show that for simulations with negligible viscous, inertial, and gravitational effects, the rupture distance approaches an asymptotic value, which is close to the value predicted by the simplified model. The bridge profiles predicted using the simplified model and the numerical simulation are compared. It is found that a second-order polynomial appropriately represents the stable bridge shape for particles with identical contact angles; however, for liquid bridges between particles with different contact angles, the numerical simulations of the governing Navier–Stokes equations should be used.     

Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease characterized by unexplained physical fatigue, cognitive and sensory dysfunction, sleeping disturbances, orthostatic intolerance, and gastrointestinal problems. People with ME/CFS often report a prodrome consistent with infections. Using regression, Bayesian and enrichment analyses, we conducted targeted and untargeted metabolomic analysis of plasma from 106 ME/CFS cases and 91 frequency-matched healthy controls. Subjects in the ME/CFS group had significantly decreased levels of plasmalogens and phospholipid ethers (p < 0.001), phosphatidylcholines (p < 0.001) and sphingomyelins (p < 0.001), and elevated levels of dicarboxylic acids (p = 0.013). Using machine learning algorithms, we were able to differentiate ME/CFS or subgroups of ME/CFS from controls with area under the receiver operating characteristic curve (AUC) values up to 0.873. Our findings provide the first metabolomic evidence of peroxisomal dysfunction, and are consistent with dysregulation of lipid remodeling and the tricarboxylic acid cycle. These findings, if validated in other cohorts, could provide new insights into the pathogenesis of ME/CFS and highlight the potential use of the plasma metabolome as a source of biomarkers for the disease.     

Evaluation of alkane sulfonic acid catalysts and derivatives for curing activity in a melamine/acrylic polyol coating formulation using fourier transform infrared spectroscopy

FTIR measurements may be able to replace more laborious physical property determinations and thus serve as an efficient screening methodology in catalysis driven processes. This possibility was considered in evaluating alkane sulfonic acids catalyst performance to promote the cure of a melamine resin with acrylic polyols. The example chosen here is an evaluation of alkane sulfonic acid derivatives to measure catalytic efficiency of the cure reaction between hexamethoxymethylmelamine (HMMM) and an acrylicpolyol. The IR measurements provided information on the extent of reaction, via monitoring the disappearance of the OH stretching mode at 3472 cm⁻¹ associated with the acrylic polyol. This method may also be used to provide detailed information on reaction kinetics and insight into the cure mechanism. As the reaction proceeds, the coating’s properties change and IR measurements can serve as a probe for these changes. 900 First Ave., King of Prussia, PA 19406.     

Alkaline hydrothermal kinetics in titanate nanostructure formation

In this study, the mechanism of precursor dissolution and the influence of kinetics of dissolution on titanate nanotube formation were investigated. This comparative study explored the dissolution kinetics for the case of commercial titania powders, one composed of predominantly anatase (>95%) and the other rutile phase (>93%). These nanoparticle precursors were hydrothermally reacted in 9 mol L⁻¹ NaOH at 160 °C over a range of reaction times of between 2 and 32 h. The high surface area nanotube-form product was confirmed using X-ray diffraction, FT-Raman spectroscopy, and transmission electron microscopy. The concentration of nanotubes produced from the different precursors was established using Rietveld analysis with internal and external corundum standardization to calibrate the absolute concentrations of the samples. Interpretation of the dissolution process of the precursor materials indicated that the dissolution of anatase proceeds via a zero-order kinetic process, whereas rutile dissolution is through a second-order process. The TiO₂ nanostructure formation process and mechanism of TiO₂ precursor dissolution was confirmed by non-invasive dynamic light scattering measurements. Significant observations are that nanotube formation occurred over a broad range of hydrothermal treatment conditions and was strongly influenced by the order of precursor dissolution.     

Discrimination in the 21st century: Are science and the law aligned?

Although scholars agree that traditional forms of discrimination have generally been supplanted by subtler interpersonal manifestations of discrimination, it is yet unknown whether targets of these behaviors or the American judicial branch recognize such negative behaviors as violations of extant law. Extending research and theory, we propose that denigrating messages toward women and ethnic minorities (i.e., microaggressions) emerge in workplace interactions and are sometimes interpreted as discrimination. Specifically, this research explores the presence, severity, and frequency of microaggressions that appear in a random sample of race and gender discrimination cases in federal court dockets since the year 2000. The results suggest that microinsults, microinvalidations, and microassaults are reported in a variety of discrimination claims. However, only overt and intentional forms of microaggressions (microassaults) increased the likelihood that decisions favored plaintiffs. Thus, there may be a disconnect between forms of discrimination perceived by claimants and how those forms are evaluated by the legal system that protects victims of discrimination. This potential misalignment of science and practice is discussed, as are directions for future research. (PsycINFO Database Record (c) 2011 APA, all rights reserved)