Neue Epidemiologie der akuten gastrointestinalen Blutung

Zusammenfassung: Die allgemeinen medizinischen, noch mehr aber die gastroenterologischen Fortschritte der letzten 25Jahre würden erwarten lassen, dass gastrointestinale Blutungen seltener und deren Letalität heute geringer sind. Die publizierten epidemiologischen Daten können dies insgesamt nicht oder nicht im erhofften Ausmaß bestätigen. Die Datenqualität vieler Studien ist aber unbefriedigend. So scheint es beispielsweise, dass fragwürdige Blutungsquellen wie Erosionen im oberen Gastrointestinaltrakt und Kolondivertikel oft wenig kritisch als definitive Ursache der Blutung bezeichnet werden. Klare Hinweise auf Veränderungen finden sich jedoch in Untergruppen. Nach dem Rückgang von H.pylori in der jüngeren Bevölkerung sind bei der Ulkusblutung heute vermehrt ältere Personen mit zusätzlichen Risikofaktoren wie schwerwiegenden Begleiterkrankungen sowie Einnahme von NSAR, Low-dose-Aspirin und Antikoagulantien betroffen. Nicht unerwartet findet sich in dieser Gruppe generell keine Veränderung oder sogar eine Verschlechterung der Prognose bei akuter Blutun

Z-11-TETRADECENYL ACETATE: SEX ATTRACTANT OF AGAPETA ZOEGANA (LEPIDOPTERA: TORTRICIDAE), A POTENTIAL SPECIES FOR THE BIOLOGICAL CONTROL OF KNAPWEED

In Canada, 78 of the most important weed species are introductions from Eurasia (Frankton and Mulligan 1970). Classical biological control aims to reduce the density of alien weeds below the economic threshold through introduction of specific herbivores from the native distribution area (Peschken 1979). During extended field surveys in central and southeastern Europe, the Commonwealth Institute of Biological Control established the root-mining tortricid Agapeta zoegana Haw. as a promising control agent for Centaurea diffusa Lam. and C. maculosa Lam., 2 important ranch weeds in southwestern Canada (Harris and Myers 1984) and the northwestern United States (Maddox 1982). Due to the limited host range and suitable climatic conditions this moth was chosen for introduction into North America (Müller et al. 1982; Müller 1984). We wish to report an attractant that may be used to monitor the establishment of this beneficial species in its new habita

The Measurement Bench for the LHC Spool Corrector Magnets in Industry

The LHC accelerator will be equipped with more than 3500 superconducting spool corrector magnets. CERN has awarded the contract for the series production and testing of these corrector magnets to industry. Magnetic field measurements are done at the factory. Dedicated magnetic measurement benches have been built to test these corrector magnets in the resistive state at room temperature. The benches allow to measure the strength of the main field, normal and skew harmonics, the magnetic axis position and orientation of the main field with respect to the mechanical reference points of the magnet. This paper presents the objectives, a description and the performances obtained with the benches during first measurements at industry

Evaluating the Classical Versus an Emerging Conceptual Model of Peatland Methane Dynamics

We appreciate discussions with M. Firestone and S. Blazewicz. We received assistance in the field and lab from K. Smetak, H. Dang, and A. McDowell. This research was funded by grants to W.L.S. from the U.S. National Science Foundation (ATM-0842385 and DEB-0543558) and the California Department of Fish and Wildlife (CDFW) and California Department of Water Resources (DWR) contract 4600011240. The data used are listed in the references, tables, supporting information, and the Illinois Digital Environment for Access to Learning and Scholarship (IDEALS) repository at https://www.ideals.illinois.edu/.Peer reviewedPublisher PD

Insight in Genome-Wide Association of Metabolite Quantitative Traits by Exome Sequence Analyses

Metabolite quantitative traits carry great promise for epidemiological studies, and their genetic background has been addressed using Genome-Wide Association Studies (GWAS). Thus far, the role of less common variants has not been exhaustively studied. Here, we set out a GWAS for metabolite quantitative traits in serum, followed by exome sequence analysis to zoom in on putative causal variants in the associated genes. 1H Nuclear Magnetic Resonance (1H-NMR) spectroscopy experiments yielded successful quantification of 42 unique metabolites in 2,482 individuals from The Erasmus Rucphen Family (ERF) study. Heritability of metabolites were estimated by SOLAR. GWAS was performed by linear mixed models, using HapMap imputations. Based on physical vicinity and pathway analyses, candidate genes were screened for coding region variation using exome sequence data. Heritability estimates for metabolites ranged between 10% and 52%. GWAS replicated three known loci in the metabolome wide significance: CPS1 with glycine (P-value  = 1.27×10−32), PRODH with proline (P-value  = 1.11×10−19), SLC16A9 with carnitine level (P-value  = 4.81×10−14) and uncovered a novel association between DMGDH and dimethyl-glycine (P-value  = 1.65×10−19) level. In addition, we found three novel, suggestively significant loci: TNP1 with pyruvate (P-value  = 1.26×10−8), KCNJ16 with 3-hydroxybutyrate (P-value  = 1.65×10−8) and 2p12 locus with valine (P-value  = 3.49×10−8). Exome sequence analysis identified potentially causal coding and regulatory variants located in the genes CPS1, KCNJ2 and PRODH, and revealed allelic heterogeneity for CPS1 and PRODH. Combined GWAS and exome analyses of metabolites detected by high-resolution 1H-NMR is a robust approach to uncover metabolite quantitative trait loci (mQTL), and the likely causative variants in these loci. It is anticipated that insight in the genetics of intermediate phenotypes will provide additional insight into the genetics of complex traits

Genomewide identification of \u3ci\u3ePseudomonas syringae\u3c/i\u3e pv.\u3ci\u3etomato\u3c/i\u3e DC3000 promoters controlled by the HrpL alternative sigma factor

The ability of Pseudomonas syringae pv. tomato DC3000 to parasitize tomato and Arabidopsis thaliana depends on genes activated by the HrpL alternative sigma factor. To support various functional genomic analyses of DC3000, and specifically, to identify genes involved in pathogenesis, we developed a draft sequence of DC3000 and used an iterative process involving computational and gene expression techniques to identify virulence-implicated genes downstream of HrpLresponsive promoters. Hypersensitive response and pathogenicity (Hrp) promoters are known to control genes encoding the Hrp (type III protein secretion) machinery and a few type III effector proteins in DC3000. This process involved (i) identification of 9 new virulenceimplicated genes in the Hrp regulon by miniTn5gus mutagenesis, (ii) development of a hidden Markov model (HMM) trained with known and transposon-identified Hrp promoter sequences, (iii) HMM identification of promoters upstream of 12 additional virulence-implicated genes, and (iv) microarray and RNA blot analyses of the HrpLdependent expression of a representative subset of these DC3000 genes. We found that the Hrp regulon encodes candidates for 4 additional type III secretion machinery accessory factors, homologs of the effector proteins HopPsyA, AvrPpiB1 (2 copies), AvrPpiC2, AvrPphD (2 copies), AvrPphE, AvrPphF, and AvrXv3, and genes associated with the production or metabolism of virulence factors unrelated to the Hrp type III secretion system, including syringomycin synthetase (SyrE), N-(indole-3-acetyl)-L-lysine synthetase (IaaL), and a subsidiary regulon controlling coronatine production. Additional candidate effector genes, hopPtoA2, hopPtoB2, and an avrRps4 homolog, were preceded by Hrp promoter-like sequences, but these had HMM expectation values of relatively low significance and were not detectably activated by HrpL

Nitroimidazole Action in Entamoeba histolytica: A Central Role for Thioredoxin Reductase

Metronidazole, a 5-nitroimidazole drug, has been the gold standard for several decades in the treatment of infections with microaerophilic protist parasites, including Entamoeba histolytica. For activation, the drug must be chemically reduced, but little is known about the targets of the active metabolites. Applying two-dimensional gel electrophoresis and mass spectrometry, we searched for protein targets in E. histolytica. Of all proteins visualized, only five were found to form adducts with metronidazole metabolites: thioredoxin, thioredoxin reductase, superoxide dismutase, purine nucleoside phosphorylase, and a previously unknown protein. Recombinant thioredoxin reductase carrying the modification displayed reduced enzymatic activity. In treated cells, essential non-protein thiols such as free cysteine were also affected by covalent adduct formation, their levels being drastically reduced. Accordingly, addition of cysteine allowed E. histolytica to survive in the presence of otherwise lethal metronidazole concentrations and reduced protein adduct formation. Finally, we discovered that thioredoxin reductase reduces metronidazole and other nitro compounds, suggesting a new model of metronidazole activation in E. histolytica with a central role for thioredoxin reductase. By reducing metronidazole, the enzyme renders itself and associated thiol-containing proteins vulnerable to adduct formation. Because thioredoxin reductase is a ubiquitous enzyme, similar processes could occur in other eukaryotic or prokaryotic organisms

Metabolomics Profile in Depression:A Pooled Analysis of 230 Metabolic Markers in 5283 Cases With Depression and 10,145 Controls

Background: Depression has been associated with metabolic alterations, which adversely impact cardiometabolic health. Here, a comprehensive set of metabolic markers, predominantly lipids, was compared between depressed and nondepressed persons. Methods: Nine Dutch cohorts were included, comprising 10,145 control subjects and 5283 persons with depression, established with diagnostic interviews or questionnaires. A proton nuclear magnetic resonance metabolomics platform provided 230 metabolite measures: 51 lipids, fatty acids, and low-molecular-weight metabolites; 98 lipid composition and particle concentration measures of lipoprotein subclasses; and 81 lipid and fatty acids ratios. For each metabolite measure, logistic regression analyses adjusted for gender, age, smoking, fasting status, and lipid-modifying medication were performed within cohort, followed by random-effects meta-analyses. Results: Of the 51 lipids, fatty acids, and low-molecular-weight metabolites, 21 were significantly related to depression (false discovery rate q <.05). Higher levels of apolipoprotein B, very-low-density lipoprotein cholesterol, triglycerides, diglycerides, total and monounsaturated fatty acids, fatty acid chain length, glycoprotein acetyls, tyrosine, and isoleucine and lower levels of high-density lipoprotein cholesterol, acetate, and apolipoprotein A1 were associated with increased odds of depression. Analyses of lipid composition indicators confirmed a shift toward less high-density lipoprotein and more very-low-density lipoprotein and triglyceride particles in depression. Associations appeared generally consistent across gender, age, and body mass index strata and across cohorts with depressive diagnoses versus symptoms. Conclusions: This large-scale meta-analysis indicates a clear distinctive profile of circulating lipid metabolites associated with depression, potentially opening new prevention or treatment avenues for depression and its associated cardiometabolic comorbidity