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

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

The structure of the tetrasialoganglioside from human brain

Autosomal dominant retinal vasculopathy with cerebral leukodystrophy is a microvascular endotheliopathy with middle- age onset. In nine families, we identified heterozygous C- terminal frameshift mutations in TREX1, which encodes a 3'-5' exonuclease. These truncated proteins retain exonuclease activity but lose normal perinuclear localization. These data have implications for the maintenance of vascular integrity in the degenerative cerebral microangiopathies leading to stroke and dementias

Gene co-expression analysis identifies brain regions and cell types involved in migraine pathophysiology

Migraine is a common disabling neurovascular brain disorder typically characterised by attacks of severe headache and associated with autonomic and neurological symptoms. Migraine is caused by an interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified over a dozen genetic loci associated with migraine. Here, we integrated migraine GWAS data with high-resolution spatial gene expression data of normal adult brains from the Allen Human Brain Atlas to identify specific brain regions and molecular pathways that are possibly involved in migraine pathophysiology. To this end, we used two complementary methods. In GWAS data from 23,285 migraine cases and 95,425 controls, we first studied modules of co-expressed genes that were calculated based on human brain expression data for enrichment of genes that showed association with migraine. Enrichment of a migraine GWAS signal was found for five modules that suggest involvement in migraine pathophysiology of: (i) neurotransmission, protein catabolism and mitochondria in the cortex; (ii) transcription regulation in the cortex and cerebellum; and (iii) oligodendrocytes and mitochondria in subcortical areas. Second, we used the high-confidence genes from the migraine GWAS as a basis to construct local migraine-related co-expression gene networks. Signatures of all brain regions and pathways that were prominent in the first method also surfaced in the second method, thus providing support that these brain regions and pathways are indeed involved in migraine pathophysiology

AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders.

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission

Changes in Migraine Symptoms after Ischemic Stroke:A Cohort Study

Introduction: Migraine symptoms are postulated to improve post-stroke. We aimed to determine post-stroke changes in patients with active migraine pre-stroke and explored the relation with stroke location and stroke-preventive medication use. Methods: Patients with active migraine who had an ischemic stroke were retrieved from three research-cohorts between 2014 and 2021. By an interview, we retrospectively investigated first-year post-stroke changes for those ischemic stroke patients that suffered from migraine pre-stroke. Associations between change in migraine frequency/intensity/aura (decrease, no change, increase), stroke location (posterior location vs. other), and use of secondary stroke preventive medication were assessed by ordinal regression with adjustment for con-founders. Results: We included 78 patients (mean age 48 years, 86% women, 47% with aura). Change in migraine symptomatology was reported by 63 (81%) patients; 51 (81%) noticed a decrease in attack frequency (27 no attacks) and 12 (19%) an increase. Pain intensity change was reported by 18 (35%) patients (50% increase, 50% decrease). Aura symptomatology improved in 4 (11%). Reduced attack frequency was not related to posterior stroke (OR = 1.5, 95% CI: 0.6–3.9), or preventive medication (antiplatelets OR = 1.0, 95% CI: 0.2–3.7; coumarin OR = 2.7, 95% CI: 0.4–20.6). Conclusions: Most patients with active pre-stroke migraine experience improvement of their symptoms in the first year after ischemic stroke. This change does not seem to be related to secondary stroke preventive medication or posterior stroke location.</p

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

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