Aufbau und Eigenschaften von PVD-Hartstoffschichten in den Systemen Cr-Zr-O und Cr-Zr-O-N

Diese Arbeit beschreibt die Charakterisierung oxidischer PVD-Dünnschichten in den Systemen Cr-Zr-O und Cr-Zr-O-N, die mittels Hochleistungskathodenzerstäubens und unter Anwendung eines experimentellen materialkombinatorischen Ansatzes abgeschieden wurden. In Abhängigkeit der Zusammensetzung und der variierten Abscheideparameter treten hauptsächlich vier Phasen auf: eine Cr2O3-basierte Phase sowie drei ZrO2-basierte Phasen

Das Basler FePsy Projekt zur Früherkennung von Psychosen

Schizophrene Psychosen beginnen meist schleichend und atypisch, wodurch sie oft lange unerkannt und unbehandelt bleiben. Dies verschlechtert die Prognose deutlich. Im Rahmen des Basler FePsy Projektes (Früherkennung von Psychosen) wollen wir die Frühdiagnose und Einschätzung des Psychoserisikos verbessern. Eine Aufklärung der Betroffenen über ihr Risiko mit anschließender Begleitung, wenn nötig auch symptomatische Behandlung, sollten in diesem Falle unbedingt erfolgen. Vor allem muss mit dem Patienten/der Patientin in diesem Stadium eine vertrauensvolle Beziehung aufgebaut werden, um bei tatsächlichem Übergang in eine Psychose auch eine spezifische Behandlung einleiten zu können

Helical stability of the GnTV transmembrane domain impacts on SPPL3 dependent cleavage

Signal-Peptide Peptidase Like-3 (SPPL3) is an intramembrane cleaving aspartyl protease that causes secretion of extracellular domains from type-II transmembrane proteins. Numerous Golgi-localized glycosidases and glucosyltransferases have been identified as physiological SPPL3 substrates. By SPPL3 dependent processing, glycan-transferring enzymes are deactivated inside the cell, as their active site-containing domain is cleaved and secreted. Thus, SPPL3 impacts on glycan patterns of many cellular and secreted proteins and can regulate protein glycosylation. However, the characteristics that make a substrate a favourable candidate for SPPL3-dependent cleavage remain unknown. To gain insights into substrate requirements, we investigated the function of a GxxxG motif located in the transmembrane domain of N-acetylglucosaminyltransferase V (GnTV), a well-known SPPL3 substrate. SPPL3-dependent secretion of the substrate’s ectodomain was affected by mutations disrupting the GxxxG motif. Using deuterium/hydrogen exchange and NMR spectroscopy, we studied the effect of these mutations on the helix flexibility of the GnTV transmembrane domain and observed that increased flexibility facilitates SPPL3-dependent shedding and vice versa. This study provides first insights into the characteristics of SPPL3 substrates, combining molecular biology, biochemistry, and biophysical techniques and its results will provide the basis for better understanding the characteristics of SPPL3 substrates with implications for the substrates of other intramembrane proteases

Non-canonical shedding of TNFα by SPPL2a is determined by the conformational flexibility of its transmembrane helix

Ectodomain (EC) shedding defines the proteolytic removal of a membrane protein EC and acts as an important molecular switch in signaling and other cellular processes. Using tumor necrosis factor (TNF)α as a model substrate, we identify a non-canonical shedding activity of SPPL2a, an intramembrane cleaving aspartyl protease of the GxGD type. Proline insertions in the TNFα transmembrane (TM) helix strongly increased SPPL2a non-canonical shedding, while leucine mutations decreased this cleavage. Using biophysical and structural analysis, as well as molecular dynamic simulations, we identified a flexible region in the center of the TNFα wildtype TM domain, which plays an important role in the processing of TNFα by SPPL2a. This study combines molecular biology, biochemistry, and biophysics to provide insights into the dynamic architecture of a substrate\u27s TM helix and its impact on non-canonical shedding. Thus, these data will provide the basis to identify further physiological substrates of non-canonical shedding in the future

Hide and seek in the Bay of Biscaya functional investigation of marine megafauna and small pelagic fish interactions

Prey and predator distributions influence one another. Understanding the scale and the orientation of predator-prey spatial correlations is crucial in foraging ecology. Growing evidence suggests that predator-prey interactions are more constrained by functional characteristics of both the predator and the prey. Unfortunately, in marine pelagic systems, the scale and orientation of spatial correlations between predators and prey have been only little explored from a functional point of view. We tested the existence of fine-scale association between predators and fish functional groups. Visual predator sightings and acoustic fish records were collected synchronously during oceanographic surveys from 2004 to 2014. Prey biomass was integrated by nautical miles and split into four size classes (30 cm) and two depth layers (surface, deep). We computed the relative biomass by prey size and depth category from 0 to 12 nm around predator sightings to determine the predators' proximity to local prey biomass. Two cetaceans (common, bottlenose dolphins) and three seabirds (northern gannets, auks, northern fulmars) were studied. No association was found in fulmars, indicating they probably do not feed on considered fishes in the area. Gannets and auks were positively correlated with local prey biomass for sizes <20 cm at both depth layers. Significant negative relationships were found between common dolphins and prey size classes <20 cm at both depth layers, and between bottlenose dolphins and all size ranges at the deeper layer. Our results suggest that the fine-scale spatial overlap of predator and prey is influenced by their functional traits, and that prey exhibit predator avoidance behaviour in presence of swimming predators but not of flying ones

Gender differences in the psychopathology of emerging psychosis

Gender differences have often been found in psychopathological symptoms among chronic schizophrenia and first-episode psychosis (FEP) patients. However, many of these studies suffer from methodological problems and show inconsistent results. Furthermore, very few studies have investigated gender differences in individuals with an at-risk mental state (ARMS) for psychosis.; Psychopathological symptoms were assessed in 117 ARMS and 87 FEP patients by two observer-rated scales, namely, the expanded version of the Brief Psychiatric Rating Scale (BPRS) and the Scale for the Assessment of Negative Symptoms (SANS), and by one self-report scale, the Frankfurt Complaint Questionnaire (FCQ). Gender differences were investigated by applying Analyses of Variance using the BPRS, SANS and FCQ subscales as dependent variables, and group and sex as between-subject factors - in a second step by including age, antipsychotic, antidepressant and cannabis use as covariates.; There were no significant gender × patient group interactions, suggesting that gender effects did not differ between patient groups. Women had higher scores in positive psychotic symptoms (BPRS Psychosis/ Thought Disturbance) while men had higher scores in negative symptoms (BPRS negative symptoms, SANS total score, as well as subscales Affective Flattening, Avolition-Apathy and Asociality-Anhedonia). However, the differences did not withstand correction for multiple testing. The results did not change when corrected for potential confounders.; There do not seem to be any gender differences in psychopathology, neither in ARMS nor in FEP patients, as regards self-reported or observerrated symptoms, when corrected for multiple testing and potential confounders