The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia : further evidence and meta-analysis

NO is a pleiotropic signaling molecule and has an important role in cognition and emotion. In the brain, NO is produced by neuronal nitric oxide synthase (NOS-I, encoded by NOS1) coupled to the NMDA receptor via PDZ. interactions; this protein-protein interaction is disrupted upon binding of NOS1 adapter protein (encoded by NOS1AP) to NOS-I. As both NOS1 and NOS1AP were associated with schizophrenia, we here investigated these genes in greater detail by genotyping new samples and conducting a meta-analysis of our own and published data. In doing so, we confirmed association of both genes with schizophrenia and found evidence for their interaction in increasing risk towards disease. Our strongest finding was the NOS1 promoter SNP rs41279104, yielding an odds ratio of 1.29 in the meta-analysis. As findings from heterologous cell systems have suggested that the risk allele decreases gene expression, we studied the effect of the variant on NOS1 expression in human post-mortem brain samples and found that the risk allele significantly decreases expression of NOS1 in the prefrontal cortex. Bioinformatic analyses suggest that this might be due the replacement of six transcription factor binding sites by two new binding sites as a consequence of proxy SNPs. Taken together, our data argue that genetic variance in NOS1 resulting in lower prefrontal brain expression of this gene contributes to schizophrenia liability, and that NOS1 interacts with NOS1AP in doing so. The NOS1-NOS1AP PDZ interface may thus well constitute a novel target for small molecules in at least some forms of schizophrenia. PostprintPeer reviewe

Modifying effect of dual antiplatelet therapy on incidence of stent thrombosis according to implanted drug-eluting stent type

Aim To investigate the putative modifying effect of dual antiplatelet therapy (DAPT) use on the incidence of stent thrombosis at 3 years in patients randomized to Endeavor zotarolimus-eluting stent (E-ZES) or Cypher sirolimus-eluting stent (C-SES). Methods and results Of 8709 patients in PROTECT, 4357 were randomized to E-ZES and 4352 to C-SES. Aspirin was to be given indefinitely, and clopidogrel/ticlopidine for ≥3 months or up to 12 months after implantation. Main outcome measures were definite or probable stent thrombosis at 3 years. Multivariable Cox regression analysis was applied, with stent type, DAPT, and their interaction as the main outcome determinants. Dual antiplatelet therapy adherence remained the same in the E-ZES and C-SES groups (79.6% at 1 year, 32.8% at 2 years, and 21.6% at 3 years). We observed a statistically significant (P = 0.0052) heterogeneity in treatment effect of stent type in relation to DAPT. In the absence of DAPT, stent thrombosis was lower with E-ZES vs. C-SES (adjusted hazard ratio 0.38, 95% confidence interval 0.19, 0.75; P = 0.0056). In the presence of DAPT, no difference was found (1.18; 0.79, 1.77; P = 0.43). Conclusion A strong interaction was observed between drug-eluting stent type and DAPT use, most likely prompted by the vascular healing response induced by the implanted DES system. These results suggest that the incidence of stent thrombosis in DES trials should not be evaluated independently of DAPT use, and the optimal duration of DAPT will likely depend upon stent type (Clinicaltrials.gov number NCT00476957

Iberian red deer: paraphyletic nature at mtDNA but nuclear markers support its genetic identity

Red deer populations in the Iberian glacial refugium were the main source for postglacial recolonization and subspecific radiation in north-western Europe. However, the phylogenetic history of Iberian red deer (Cervus elaphus hispanicus) and its relationships with northern European populations remain uncertain. Here, we study DNA sequences at the mitochondrial control region along with STR markers for over 680 specimens from all the main red deer populations in Spain and other west European areas. Our results from mitochondrial and genomic DNA show contrasting patterns, likely related to the nature of these types of DNA markers and their specific processes of change over time. The results, taken together, bring support to two distinct, cryptic maternal lineages for Iberian red deer that predated the last glacial maximum and that have maintained geographically well differentiated until present. Haplotype relationships show that only one of them contributed to the northern postglacial recolonization. However, allele frequencies of nuclear markers evidenced one main differentiation between Iberian and northern European subspecies although also supported the structure of both matrilines within Iberia. Thus, our findings reveal a paraphyletic nature for Iberian red deer but also its genetic identity and differentiation with respect to northern subspecies. Finally, we suggest that maintaining the singularity of Iberian red deer requires preventing not only restocking practices with red deer specimens belonging to other European populations but also translocations between both Iberian lineages.This work was partly supported by project CGL2010-17163/BOS from the Spanish MInistry of Science and by Extremadura and Andalusian Regional Goverments

Pestizide im Nebel. Vorkommen und atmosphaerischer Eintrag von Herbiziden und phytotoxischen Nitrophenolen an zwei emissionsfernen Waldstandorten in Bayern Abschlussbericht

This investigation had the aim to determine and evaluate the atmospheric incidence of herbicides and nitrophenols with a view to ecotoxicological risks. For this purpose, precipitation samples from the Wank mountain in the Fichtelgebirge were analysed for commonly used herbicides and traffic-related nitrophenols. Within the framework of forest decline research in the Wank, measurements were carried through mainly for phytotoxic nitrophenols along an altitudinal profile. Fog water samples from farming areas completed the range of samples. The air-hygienic aspects of the enrichment of herbicides in fog water are discussed. Atrazine and nitrophenols are used as examples to demonstrate the behaviour of such air pollutants from farming and traffic in the atmosphere. The characterization of these model substances in terms of physico-chemical and toxicological properties permits to objectively assess the environmental risks emanating from the atmospheric incidence of herbicides as compared to organic environmental chemicals from other sources. The conclusion is drawn that the incidence of herbicides in the atmosphere currently constitutes no environmental threat. (orig.)Gegenstand dieser Untersuchung war die Erfassung und Bewertung des atmosphaerischen Vorkommens von Pflanzenschutzmitteln und Nitrophenolen mit Blick auf oekotoxokologische Risiken. Zu diesem Zweck wurden Niederschlagsproben vom Wank aus dem Fichtelgebirge auf verbreitet eingesetzte Herbizide und auf verkehrsbuertige Nitrophenole hin untersucht. Im Rahmen der Waldschadensforschung am Wank konzentrierten wir uns auf Messungen der phytotoxischen Nitrophenole an einem Hoehenprofil. Nebelwasserproben aus landwirtschaftlich genutzten Raeumen ergaenzten die Probenpalette. Die lufthygienischen Aspekte der Anreicherung von Pflanzenschutzmitteln im Nebelwasser werden diskutiert. Am Beispiel des Atrazins und den Nitrophenolen wird das Verhalten dieser Luftverunreinigung aus landwirtschaftlichen und verkehrsbuertigen Quellen in der Atmosphaere aufgezeigt. Die Einordnung dieser Modellsubstanzen nach physikalisch-chemischen und toxokologischen Eigenschaften erlaubt eine objektive Einschaetzung der Umweltrisiken des atmosphaerischen Vorkommens von Pflanzenschutzmitteln im Vergleich zu organischen Umweltchemikalien aus anderen Quellen. Wir kommen zum Schluss, dass das Vorkommen von Pflanzenschutzmitteln in der Atmosphaere gegenwaertig kein Umweltrisiko beinhaltet. (orig.)SIGLEAvailable from TIB Hannover: F93B900 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBayerisches Staatsministerium fuer Ernaehrung, Landwirtschaft und Forsten, Muenchen (Germany)DEGerman

Neuartige gewellte Multikanalelemente aus Keramik für die Mikro- und Ultrafiltration

Es wurden neue, gewellte keramische Flachmembranen für die Mikro- und Ultrafiltration entwickelt. Über ein Foliengießverfahren und nachfolgende Laminierprozesse wird ein Flachträger mit selektiven Schichten überzogen und mit einem zweiten gewellten Flachträger verbunden. Diese Multikanalelement-Einheit kann als gesamtes in einem einzigen Brennprozess gebrannt werden, was zu erheblich niedrigeren Herstellkosten als bei herkömmlichen keramischen Membranen führt. Außerdem können damit um etwa 5-fach höhere Packungsdichten als mit herkömmlichen Multikanalelementen erzielt werden