Systematic Characterisation of Cellular Localisation and Expression Profiles of Proteins Containing MHC Ligands

Presentation of peptides on Major Histocompatibility Complex (MHC) molecules is the cornerstone in immune system activation and increased knowledge of the characteristics of MHC ligands and their source proteins is highly desirable.In the present large-scale study, we used a large data set of proteins containing experimentally identified MHC class I or II ligands and examined the proteins according to their expression profiles at the mRNA level and their Gene Ontology (GO) classification within the cellular component ontology. Proteins encoded by highly abundant mRNA were found to be much more likely to be the source of MHC ligands. Of the 2.5% most abundant mRNAs as much as 41% of the proteins encoded by these mRNAs contained MHC class I ligands. For proteins containing MHC class II ligands, the corresponding percentage was 11%. Furthermore, we found that most proteins containing MHC class I ligands were localised to the intracellular parts of the cell including the cytoplasm and nucleus. MHC class II ligand donors were, on the other hand, mostly membrane proteins.The results contribute to the ongoing debate concerning the nature of MHC ligand-containing proteins and can be used to extend the existing methods for MHC ligand predictions by including the source protein's localisation and expression profile. Improving the current methods is important in the growing quest for epitopes that can be used for vaccine or diagnostic purposes, especially when it comes to large DNA viruses and cancer

Quantitative estimates of velocity sensitivity to surface melt variations at a large Greenland outlet glacier

This is the publisher's version, also available electronically from "http://www.ingentaconnect.com".The flow speed of Greenland outlet glaciers is governed by several factors, the relative importance of which is poorly understood. The delivery of surface-generated meltwater to the bed of alpine glaciers has been shown to influence glacier flow speed when the volume of water is sufficient to increase basal fluid pressure and hence basal lubrication. While this effect has also been demonstrated on the Greenland ice-sheet margin, little is known about the influence of surface melting on the large, marine-terminating outlet glaciers that drain the ice sheet. We use a validated model of meltwater input and GPS-derived surface velocities to quantify the sensitivity of glacier flow speed to changes in surface melt at Helheim Glacier during two summer seasons (2007–08). Our observations span ∼55 days near the middle of each melt season. We find that relative changes in glacier speed due to meltwater input are small, with variations of ∼45% in melt producing changes in velocity of ∼2–4%. These velocity variations are, however, of similar absolute magnitude to those observed at smaller glaciers and on the ice-sheet margin. We find that the glacier's sensitivity to variations in meltwater input decreases approximately exponentially with distance from the calving front. Sensitivity to melt varies with time, but generally increases as the melt season progresses. We interpret the time-varying sensitivity of glacier flow to meltwater input as resulting from changes in subglacial hydraulic routing caused by the changing volume of meltwater input

Metabolic effects of a 24-week energy-restricted intervention combined with low or high dairy intake in overweight women:An NMR-based metabolomics investigation

We investigated the effect of a 24-week energy-restricted intervention with low or high dairy intake (LD or HD) on the metabolic profiles of urine, blood and feces in overweight/obese women by NMR spectroscopy combined with ANOVA-simultaneous component analysis (ASCA). A significant effect of dairy intake was found on the urine metabolome. HD intake increased urinary citrate, creatinine and urea excretion, and decreased urinary excretion of trimethylamine-N-oxide (TMAO) and hippurate relative to the LD intake, suggesting that HD intake was associated with alterations in protein catabolism, energy metabolism and gut microbial activity. In addition, a significant time effect on the blood metabolome was attributed to a decrease in blood lipid and lipoprotein levels due to the energy restriction. For the fecal metabolome, a trend for a diet effect was found and a series of metabolites, such as acetate, butyrate, propionate, malonate, cholesterol and glycerol tended to be affected. Overall, even though these effects were not accompanied by a higher weight loss, the present metabolomics data reveal that a high dairy intake is associated with endogenous metabolic effects and effects on gut microbial activity that potentially impact body weight regulation and health. Moreover, ASCA has a great potential for exploring the effect of intervention factors and identifying altered metabolites in a multi-factorial metabolomic study