Virus-Induced Type I Interferon Deteriorates Control of Systemic Pseudomonas Aeruginosa Infection

BACKGROUND: Type I interferon (IFN-I) predisposes to bacterial superinfections, an important problem during viral infection or treatment with interferon-alpha (IFN-alpha). IFN-I-induced neutropenia is one reason for the impaired bacterial control; however there is evidence that more frequent bacterial infections during IFN-alpha-treatment occur independently of neutropenia. METHODS: We analyzed in a mouse model, whether Pseudomonas aeruginosa control is influenced by co-infection with the lymphocytic choriomeningitis virus (LCMV). Bacterial titers, numbers of neutrophils and the gene-expression of liver-lysozyme-2 were determined during a 24 hours systemic infection with P. aeruginosa in wild-type and Ifnar(-/-) mice under the influence of LCMV or poly(I:C). RESULTS: Virus-induced IFN-I impaired the control of Pseudomonas aeruginosa. This was associated with neutropenia and loss of lysozyme-2-expression in the liver, which had captured P. aeruginosa. A lower release of IFN-I by poly(I:C)-injection also impaired the bacterial control in the liver and reduced the expression of liver-lysozyme-2. Low concentration of IFN-I after infection with a virulent strain of P. aeruginosa alone impaired the bacterial control and reduced lysozyme-2-expression in the liver as well. CONCLUSION: We found that during systemic infection with P. aeruginosa Kupffer cells quickly controlled the bacteria in cooperation with neutrophils. Upon LCMV-infection this cooperation was disturbed

Phonons and related properties of extended systems from density-functional perturbation theory

This article reviews the current status of lattice-dynamical calculations in crystals, using density-functional perturbation theory, with emphasis on the plane-wave pseudo-potential method. Several specialized topics are treated, including the implementation for metals, the calculation of the response to macroscopic electric fields and their relevance to long wave-length vibrations in polar materials, the response to strain deformations, and higher-order responses. The success of this methodology is demonstrated with a number of applications existing in the literature.Comment: 52 pages, 14 figures, submitted to Review of Modern Physic

Controlled Crystallization of the Amorphous Phase in Silicon Nitride Ceramics

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65986/1/j.1151-2916.1987.tb05676.x.pd

Cholesterol and oxysterol sulfates:Pathophysiological roles and analytical challenges

Cholesterol and oxysterol sulfates are important regulators of lipid metabolism, inflammation, cell apoptosis, and cell survival. Among the sulfate-based lipids, cholesterol sulfate (CS) is the most studied lipid both quantitatively and functionally. Despite the importance, very few studies have analysed and linked the actions of oxysterol sulfates to their physiological and pathophysiological roles. Overexpression of sulfotransferases confirmed the formation of a range of oxysterol sulfates and their antagonistic effects on liver X receptors (LXRs) prompting further investigations how are the changes to oxysterol/oxysterol sulfate homeostasis can contribute to LXR activity in the physiological milieu. Here, we aim to bring together for novel roles of oxysterol sulfates, the available techniques and the challenges associated with their analysis. Understanding the oxysterol/oxysterol sulfate levels and their pathophysiological mechanisms could lead to new therapeutic targets for metabolic diseases

Independent age estimates resolve the controversy of ancient human footprints at White Sands

Human footprints at White Sands National Park, New Mexico, USA, reportedly date to between ~23,000 and 21,000 years ago according to radiocarbon dating of seeds from the aquatic plant Ruppia cirrhosa. These ages remain controversial because of potential old carbon reservoir effects that could compromise their accuracy. We present new calibrated 14C ages of terrestrial pollen collected from the same stratigraphic horizons as those of the Ruppia seeds, along with optically stimulated luminescence ages of sediments from within the human footprint–bearing sequence, to evaluate the veracity of the seed ages. The results show that the chronologic framework originally established for the White Sands footprints is robust and reaffirm that humans were present in North America during the Last Glacial Maximum

An Introduction to Sphingolipid Metabolism and Analysis by New Technologies

Sphingolipids (SP) are a complex class of molecules found in essentially all eukaryotes and some prokaryotes and viruses where they influence membrane structure, intracellular signaling, and interactions with the extracellular environment. Because of the combinatorial nature of their biosynthesis, there are thousands of SP subspecies varying in the lipid backbones and complex phospho- and glycoheadgroups. Therefore, comprehensive or “sphingolipidomic” analyses (structure-specific, quantitative analyses of all SP, or at least all members of a critical subset) are needed to know which and how much of these subspecies are present in a system as a step toward understanding their functions. Mass spectrometry and related novel techniques are able to quantify a small fraction, but nonetheless a substantial number, of SP and are beginning to provide information about their localization. This review summarizes the basic metabolism of SP and state-of-art mass spectrometric techniques that are producing insights into SP structure, metabolism, functions, and some of the dysfunctions of relevance to neuromedicine

Increased numbers of oligodendrocyte lineage cells in the optic nerves of cerebroside sulfotransferase knockout mice

Sulfatide is a myelin glycolipid that functions in the formation of paranodal axo-glial junctions in vivo and in the regulation of oligodendrocyte differentiation in vitro. Cerebroside sulfotransferase (CST) catalyzes the production of two sulfated glycolipids, sulfatide and proligodendroblast antigen, in oligodendrocyte lineage cells. Recent studies have demonstrated significant increases in oligodendrocytes from the myelination stage through adulthood in brain and spinal cord under CST-deficient conditions. However, whether these result from excess migration or in situ proliferation during development is undetermined. In the present study, CST-deficient optic nerves were used to examine migration and proliferation of oligodendrocyte precursor cells (OPCs) under sulfated glycolipid-deficient conditions. In adults, more NG2-positive OPCs and fully differentiated cells were observed. In developing optic nerves, the number of cells at the leading edge of migration was similar in CST-deficient and wild-type mice. However, BrdU+ proliferating OPCs were more abundant in CST-deficient mice. These results suggest that sulfated glycolipids may be involved in proliferation of OPCs in vivo

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