Knock-In Mice Expressing a 15-Lipoxygenating Alox5 Mutant Respond Differently to Experimental Inflammation Than Reported Alox5−/− Mice

Arachidonic acid 5-lipoxygenase (ALOX5) is the key enzyme in the biosynthesis of pro-inflammatory leukotrienes. We recently created knock-in mice (Alox5-KI) which express an arachidonic acid 15-lipoxygenating Alox5 mutant instead of the 5-lipoxygenating wildtype enzyme. These mice were leukotriene deficient but exhibited an elevated linoleic acid oxygenase activity. Here we characterized the polyenoic fatty acid metabolism of these mice in more detail and tested the animals in three different experimental inflammation models. In experimental autoimmune encephalomyelitis (EAE), Alox5-KI mice displayed an earlier disease onset and a significantly higher cumulative incidence rate than wildtype controls but the clinical score kinetics were not significantly different. In dextran sodium sulfate-induced colitis (DSS) and in the chronic constriction nerve injury model (CCI), Alox5-KI mice performed like wildtype controls with similar genetic background. These results were somewhat surprising since in previous loss-of-function studies targeting leukotriene biosynthesis (Alox5(-/-) mice, inhibitor studies), more severe inflammatory symptoms were observed in the EAE model but the degree of inflammation in DSS colitis was attenuated. Taken together, our data indicate that these mutant Alox5-KI mice respond differently in two models of experimental inflammation than Alox5(-/-) animals tested previously in similar experimental setups

Grsf1-induced translation of the SNARE protein use1 is required for expansion of the erythroid compartment

Induction of cell proliferation requires a concomitant increase in the synthesis of glycosylated lipids and membrane proteins, which is dependent on ER-Golgi protein transport by CopII-coated vesicles. In this process, retrograde transport of ER resident proteins from the Golgi is crucial to maintain ER integrity, and allows for anterograde transport to continue. We previously showed that expression of the CopI specific SNARE protein Use1 (Unusual SNARE in the ER 1) is tightly regulated by eIF4E-dependent translation initiation of Use1 mRNA. Here we investigate the mechanism that controls Use1 mRNA translation. The 5'UTR of mouse Use1 contains a 156 nt alternatively spliced intron. The non-spliced form is the predominantly translated mRNA. The alternatively spliced sequence contains G-repeats that bind the RNA-binding protein G-rich sequence binding factor 1 (Grsf1) in RNA band shift assays. The presence of these G-repeats rendered translation of reporter constructs dependent on the Grsf1 concentration. Down regulation of either Grsf1 or Use1 abrogated expansion of erythroblasts. The 5'UTR of human Use1 lacks the splice donor site, but contains an additional upstream open reading frame in close proximity of the translation start site. Similar to mouse Use1, also the human 5'UTR contains G-repeats in front of the start codon. In conclusion, Grsf1 controls translation of the SNARE protein Use1, possibly by positioning the 40S ribosomal subunit and associated translation factors in front of the translation start site

From pole to pole : 33 years of physical oceanography onboard R/V Polarstern

Measuring temperature and salinity profiles in the world's oceans is crucial to understanding ocean dynamics and its influence on the heat budget, the water cycle, the marine environment and on our climate. Since 1983 the German research vessel and icebreaker Polarstern has been the platform of numerous CTD (conductivity, temperature, depth instrument) deployments in the Arctic and the Antarctic. We report on a unique data collection spanning 33 years of polar CTD data. In total 131 data sets (1 data set per cruise leg) containing data from 10 063 CTD casts are now freely available at doi: 10.1594/PANGAEA.860066. During this long period five CTD types with different characteristics and accuracies have been used. Therefore the instruments and processing procedures (sensor calibration, data validation, etc.) are described in detail. This compilation is special not only with regard to the quantity but also the quality of the data -the latter indicated for each data set using defined quality codes. The complete data collection includes a number of repeated sections for which the quality code can be used to investigate and evaluate long-term changes. Beginning with 2010, the salinity measurements presented here are of the highest quality possible in this field owing to the introduction of the OPTIMARE Precision Salinometer.Peer reviewe

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Imaging Sensory Effects of Occipital Nerve Stimulation: A New Computer-based Method in Neuromodulation

Background: Within the last years, occipital nerve stimulation (ONS) has proven to be an important method in the treatment of severe therapy-resistant neurological pain disorders. The correspondence between lead placement as well as possible stimulation parameters and the resulting stimulation effects remains unclear. Objective: The method aims to directly relate the neuromodulatory mechanisms with the clinical treatment results, to achieve insight in the mode of action of neuromodulation, to identify the most effective stimulation sets and to optimize individual treatment effects. Methods: We describe a new computer-based imaging method for mapping the spatial, cognitive and affective sensory effects of ONS. The procedure allows a quantitative and qualitative analysis of the relationship between lead positioning, the stimulation settings as well as the sensory and clinical stimulation effects. Conclusion: A regular mapping of stimulation and sensory parameters allows a coordinated monitoring. The stimulation results can be reviewed and compared with regards to clinical effectiveness. (C) 2015 Elsevier Inc. All rights reserved

Scientific background document in support of the development of a CCAMLR MPA in the Weddell Sea (Antarctica) – Version 2014

Germany intends to present the Scientific Committee the background document that provides the scientific basis for the evaluation of marine protected areas (MPAs) in the Weddell Sea. Please note, that the current state of the background document presents a comprehensive yet incomplete first version concerning chapters that have to be (further) developed or revised. The contents and structure of the document reflect also its main objectives, i.e. (i) to set out the general background and context of the establishment of MPAs, (ii) to describe the boundaries of the Weddell Sea MPA Planning Area, (iii) to inform on the data retrieval process, (iv) to provide - for the first time- a comprehensive, yet succinct, general description of the Weddell Sea ecosystem to reflect the state of the science, and additionally to present the results of the various preliminary scientific analyses that were carried out so far within the framework of the MPA Weddell Sea project, and finally (v) to describe future work beyond the development of the scientific basis for the evaluation of a Weddell Sea MPA