Molecular organization of the cholesteryl ester droplets in the fatty streaks of human aorta

X-ray diffraction patterns from human arterial specimens containing atherosclerotic fatty streak lesions exhibited a single sharp reflection, corresponding to a structural spacing of about 35 A. Specimens without lesions did not. When specimens with fatty streaks were heated, an order-to-disorder phase transition was revealed by the disappearance of the sharp reflection. The transition was thermally reversible and its temperature varied from aorta to aorta over a range from 28 degrees to 42 degrees C. Since cholesteryl ester droplets are a major component of fatty streaks, comparison studies were made of the diffraction behavior from pure cholesteryl esters. We found that the diffraction patterns of the fatty streak material could be accounted for by the organization of the cholesteryl esters into a liquid-crystalline smectic phase that melts from the smectic to a less ordered phase upon heating. When combined with the conclusions of others from polarized light microscopy, our study shows that a droplet in the smectic phase has well-defined concentric layers of lipid molecules. In each layer, the long axes of the molecules have a net radial orientation with respect to the droplet, but the side-to-side organization is disordered. We suggest that the accessibility of portions of the lipids for specific binding to enzymes or transport proteins may be restricted when they are in the smectic state, and that exchange of lipids with surrounding membranes or other potential binding sites may likewise be inhibited. The restriction in the smectic phase should be greater than in the less ordered phases that exist at higher temperatures.     

A G protein gamma subunit-like domain shared between RGS11 and other RGS proteins specifies binding to Gbeta5 subunits

Regulators of G protein signaling (RGS) proteins act as GTPase-activating proteins (GAPs) toward the alpha subunits of heterotrimeric, signal-transducing G proteins. RGS11 contains a G protein gamma subunit-like (GGL) domain between its Dishevelled/Egl-10/Pleckstrin and RGS domains. GGL domains are also found in RGS6, RGS7, RGS9, and the Caenorhabditis elegans protein EGL-10. Coexpression of RGS11 with different Gbeta subunits reveals specific interaction between RGS11 and Gbeta5. The expression of mRNA for RGS11 and Gbeta5 in human tissues overlaps. The Gbeta5/RGS11 heterodimer acts as a GAP on Galphao, apparently selectively. RGS proteins that contain GGL domains appear to act as GAPs for Galpha proteins and form complexes with specific Gbeta subunits, adding to the combinatorial complexity of G protein-mediated signaling pathways.     

Structure and stability of an immunoglobulin superfamily domain from twitchin, a muscle protein of the nematode Caenorhabditis elegans

The NMR solution structure of an immunoglobulin superfamily module of twitchin (Ig 18') has been determined and the kinetic and equilibrium folding behaviour characterised. Thirty molecular coordinates were calculated using a hybrid distance geometry-simulated annealing protocol based on 1207 distance and 48 dihedral restraints. The atomic rms distributions about the mean coordinate for the ensemble of structures is 0.55( +/- 0.09) A for backbone atoms and 1.10( +/- 0.08) A for all heavy atoms. The protein has a topology very similar to that of telokin and the titin Ig domains and thus it falls into the I set of the immunoglobulin superfamily. The close agreement between the predicted and observed structures of Ig 18' demonstrates clearly that the I set profile can be applied in the structure prediction of immunoglobulin-like domains of diverse modular proteins. Folding studies reveal that the protein has relatively low thermodynamic stability, deltaG(H2O)U-F = 4.0 kcal mol(-1) at physiological pH. Unfolding studies suggest that the protein has considerable kinetic stability, the half life of the unfolding is greater than 40 minutes in the absence of denaturant.     

The predictors of quality care

Patients' perceptions of quality are important to the performance ratings, financial viability, and operational options afforded to purchasers of health care. Through TRICARE, the Department of Defense provides care for the more than 1.5 million active duty service members charged with the defense of the nation. As patients, these service members are typically incapable of assessing the technical quality of the care they receive. This study examines the attributes of health care delivery that define military patients' perceptions of quality and discusses the implications of these assessments.     

Effect of dietary zinc levels on health and productivity of gilts and sows through two parities

The influence of 0, 50, 500 or 5,000 ppm supplemental Zn on productive characteristics, weight change, and serum and organ mineral concentrations of 60 crossbred and purebred Yorkshire gilts was evaluated. Gilts were fed their respective treatment from 30 kg body weight until the completion of two parities. Sows fed 5,000 ppm supplemental Zn weighed significantly less than sows from the other treatments when killed. Serum alkaline phosphatase activity was higher for the sows fed the highest level of Zn in all replications at 10 and 14 mo of age than for sows from the other treatments. Sows fed 0, 50 or 500 ppm had lower serum Zn and higher serum Cu concentrations than sows fed 5,000 ppm Zn at 10 and 14 mo of age. The number of pigs farrowed (total and live) and birth weight were not affected by dam's dietary treatment. However, sows receiving no additional Zn had a higher number of abnormal pigs/litter than sows on the other treatments. Sows fed 5,000 ppm additional Zn weaned fewer pigs that weighed less at weaning than sows on the other treatments. The concentration of Zn in the sow's liver increased significantly and liver Cu decreased as dietary level of Zn increased. Sows receiving 5,000 ppm Zn had lower hepatic Fe stores compared with sows receiving 500 ppm Zn. Elevated renal Cu and Zn concentrations were found in sows fed the highest level of Zn supplementation. The Zn concentration was higher and the Cu concentration lower in the aorta of sows fed 5,000 ppm Zn compared with sows fed 0 or 50 ppm additional Zn. Incidence of osteochondrosis was higher in sows supplemented with 5,000 ppm Zn than for sows from the other treatments.     

Proinflammatory macrophage-activating properties of the novel phospholipid diacylglycerol pyrophosphate

We have found that the novel phospholipid diacylglycerol pyrophosphate (DGPP), identified in bacteria, yeast, and plants, but not in mammalian cells, is able to potently activate macrophages for enhanced secretion of arachidonate metabolites, a key event in the immunoinflammatory response of leukocytes. Macrophage responses to DGPP are specific and are not mediated by its conversion into other putative lipid mediators such as phosphatidic acid, lysophosphatidic acid, or diacylglycerol. The responses to DGPP are compatible with a receptor-recognition event because they are blocked by suramin. Intracellular signaling initiated by DGPP includes phosphorylation and activation of the Group IV cytosolic phospholipase A2 and of the extracellular-signal regulated p42 mitogen-activated protein kinase (MAPK) and p44 MAPK, and membrane translocation of the protein kinase C isoenzymes alpha, epsilon, delta. These results establish DGPP as a novel macrophage-activating factor and suggest a potential role for this compound in triggering homeostatic cellular responses.