Myelin Proteomics: Molecular Anatomy of an Insulating Sheath

Fast-transmitting vertebrate axons are electrically insulated with multiple layers of nonconductive plasma membrane of glial cell origin, termed myelin. The myelin membrane is dominated by lipids, and its protein composition has historically been viewed to be of very low complexity. In this review, we discuss an updated reference compendium of 342 proteins associated with central nervous system myelin that represents a valuable resource for analyzing myelin biogenesis and white matter homeostasis. Cataloging the myelin proteome has been made possible by technical advances in the separation and mass spectrometric detection of proteins, also referred to as proteomics. This led to the identification of a large number of novel myelin-associated proteins, many of which represent low abundant components involved in catalytic activities, the cytoskeleton, vesicular trafficking, or cell adhesion. By mass spectrometry-based quantification, proteolipid protein and myelin basic protein constitute 17% and 8% of total myelin protein, respectively, suggesting that their abundance was previously overestimated. As the biochemical profile of myelin-associated proteins is highly reproducible, differential proteome analyses can be applied to material isolated from patients or animal models of myelin-related diseases such as multiple sclerosis and leukodystrophies

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Narcissism: a factor behind the selective sharing of news online

The current study examined the extent to which narcissism influences the social network users’ intention to share positive and negative life events with (close or unknown) online contacts. Using an online survey, small vignettes and a cross-sectional convenience sample of 119 participants, the results showed that narcissism positively predicted sharing intention of positive and negative life events with strangers. However, individuals rating higher in narcissism were less likely to share negative news with family. The research findings suggest that personality traits such as narcissism, the type of contacts online, and the nature of the news may shape what information is shared by online users. The type of news presented may therefore be a function of who is posting the content, their personality, and the kind of social network contacts they have online

A Neuron-Glial Perspective for Computational Neuroscience

International audienceThere is growing excitement around glial cells, as compelling evidence point to new, previously unimaginable roles for these cells in information processing of the brain, with the potential to affect behavior and higher cognitive functions. Among their many possible functions, glial cells could be involved in practically every aspect of the brain physiology in health and disease. As a result, many investigators in the field welcome the notion of a Neuron-Glial paradigm of brain function, as opposed to Ramon y Cayal's more classical neuronal doctrine which identifies neurons as the prominent, if not the only, cells capable of a signaling role in the brain. The demonstration of a brain-wide Neuron-Glial paradigm however remains elusive and so does the notion of what neuron-glial interactions could be functionally relevant for the brain computational tasks. In this perspective, we present a selection of arguments inspired by available experimental and modeling studies with the aim to provide a biophysical and conceptual platform to computational neuroscience no longer as a mere prerogative of neuronal signaling but rather as the outcome of a complex interaction between neurons and glial cells

Direct activation of glucose transport in primary human myotubes after activation of peroxisome proliferator-activated receptor delta

Activators of peroxisome proliferator-activated receptor (PPAR)γ have been studied intensively for their insulin-sensitizing properties and antidiabetic effects. Recently, a specific PPARδ activator (GW501516) was reported to attenuate plasma glucose and insulin levels when administered to genetically obese ob/ob mice. This study was performed to determine whether specific activation of PPARδ has direct effects on insulin action in skeletal muscle. Specific activation of PPARδ using two pharmacological agonists (GW501516 and GW0742) increased glucose uptake independently of insulin in differentiated C2C12 myotubes. In cultured primary human skeletal myotubes, GW501516 increased glucose uptake independently of insulin and enhanced subsequent insulin stimulation. PPARδ agonists increased the respective phosphorylation and expression of AMP-activated protein kinase 1.9 fold (P < 0.05) and 1.8 fold (P < 0.05), of extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (MAPK) 2.2-fold (P < 0.05) and 1.7-fold (P < 0.05), and of p38 MAPK 1.2-fold (P < 0.05) and 1.4-fold (P < 0.05). Basal and insulin-stimulated protein kinase B/Akt was unaltered in cells pre-exposed to PPARδ agonists. Preincubation of myotubes with the p38 MAPK inhibitor SB203580 reduced insulin- and PPARδ-mediated increase in glucose uptake, whereas the mitogen-activated protein kinase kinase inhibitor PD98059 was without effect. PPARδ agonists reduced mRNA expression of PPARδ, sterol regulatory element binding protein (SREBP)-1a, and SREBP-1c (P < 0.05). In contrast, mRNA expression of PPARγ, PPARγ coactivator 1, GLUT1, and GLUT4 was unaltered. Our results provide evidence to suggest that PPARδ agonists increase glucose metabolism and promote gene regulatory responses in cultured human skeletal muscle. Moreover, we provide biological validation of PPARδ as a potential target for antidiabetic therapy

Load-bearing capacity of CAD/CAM milled polymeric three-unit fixed dental prostheses: Effect of aging regimens

OBJECTIVE: This study tested the fracture load of milled and conventionally fabricated polymeric and glass-ceramic three-unit fixed dental prostheses (FDPs) after aging. MATERIALS AND METHODS: FDPs were fabricated (N = 1,050) from four computer-aided design and computer-aided manufacturing (CAD/CAM) resins: (1) AT (artBlock Temp); (2) TC (Telio CAD); (3) ZP (ZENO PMMA); (4) CT (CAD-Temp); two conventionally fabricated resins, (5) IES (integral esthetic press), (6) CMK (CronMix K), and a glass-ceramic (control) (7) PG (IMAGINE PressX). Specimens of each group were tested immediately after fabrication (n = 15 per material). Seventy-five FDPs per material type were stored in artificial saliva (37°C) and 15 of them were randomly selected after aging (1, 7, 28, 90, and 180 days) for fracture load measurement. The remaining specimens (n = 60 per material) were subjected to chewing simulation (×120.000-1.200.000, 49 N, 5°C/50°C). The data were analyzed using two-way and one-way ANOVA followed by Scheffé test. RESULTS: The interactions between FDP materials and aging time in both storage media showed a significant impact on the results (p < 0.001). Among saliva storage groups, TC and ZP showed the highest, and PG the lowest fracture load (p < 0.05). AT and CT were not affected from chewing simulation. TC, ZP, and AT presented the highest in ascending order (p < 0.05), PG and CMK showed the lowest fracture load after chewing simulation (p < 0.001). CONCLUSIONS: Aging did not influence the fracture load of FDPs made of CAD/CAM resins. FDPs made of glass-ceramic showed significantly lower fracture load than those of all resin FDPs. Clinical relevance: Considering fracture load measurements, CAD/CAM resins tested could be alternative materials to glass-ceramic for FDP construction

Abiotic stress effects on the antioxidative response profile of Albizia julibrissin Durazz. (Fabaceae)

Abiotic stresses (e.g., heavy metals, drought, cold, or combinations) induce oxidative stress with overproduction of reactive oxygen species (ROS). We have investigated the antioxidative responses of Albizia julibrissin Durazz. (silk tree, Fabaceae). Four-month-old plants grown in sand cultures were subjected to various single or sequential treatments involving exposure to cadmium (50-250 mu mol L-1 Cd), lead (1000-5000 mu mol L-1 Pb), chilling at 4 degrees C (CH), or drought (DR), for a period of 7-45 days. Leaf extracts were assayed for glutathione peroxidase (GPX), glutathione-disulfide reductase (GR), catalase (CAT), soluble proline (Pro), ascorbate peroxidase (APX), and guaiacol peroxidase (GUAPX). Cd and Pb accumulation in the leaves was also measured. CAT activity decreased strongly with increasing Pb exposure and after CH. It was also found to be reduced after Cd and DR treatments. GR activity increased highly in nearly all treatments, most strongly at high Cd or Pb, after DR ? CH, and after CH followed by Cd. GUAPX and GPX showed similar trends of increase. APX activity dropped after CH, but increased after low Cd treatment and in CH ? DR sequential stresses. Massive accumulation of soluble Pro occurred after 14-21 days in highly Cd-or Pb-stressed plants. CH or DR acclimation led to some alterations of antioxidative responses, particularly for CAT, GR, and APX. Our data indicate that GSH, GSH-linked redox systems, peroxidases, and Pro are possibly the more important antioxidants under severe stress