Has The World Changed? My Neighbor Might Know Effects of Social Context on Routine Deviation

In two experiments we studied the effects of behavioral models on routine deviation decisions in observers. Participants repeatedly chose among four card-deck lotteries together with a human model (confederate, Exp. 1) or a non-human model (computer, Exp. 2) that made correct decisions in the majority of the trials. In a learning phase, participants acquired a choice routine (preferring one deck over others). In a subsequent test phase, participants had to adapt to changes in the payoff structure that required them to deviate from their routine. We found a strong tendency to maintain the routine despite negative feedback (routine effect). In a social situation (Exp.1), models decrease routine effects more intensely than in non social situations (Exp.2). The process of adaptation follows a belief updating process. Results indicate that the model effect is not due to an increase of the sample of relevant information nor to application of a simply copy heuristic. Rather, deviation models may provide a cue for change that fosters reevaluation of the situation in the observer.Experienced-based decision making, routine, habit, adaptation, social influence, Bayesian updating, novelty

Fine discrimination of volatile compounds by graphene-immobilized odorant-binding proteins

Abstract We describe the fabrication and performance of a biosensor for odorants, using wildtype and engineered mutants of the Italian honeybee (Apis mellifera ligustica) odorant binding protein 14 (OBP14), immobilized onto a reduced graphene oxide field-effect transistor (rGO-FET). The binding properties of the protein when immobilized on the biosensor are similar to those measured in solution, thus providing a method for measuring affinities to small molecules as an alternative to the current fluorescence assay. Out of the 14 chemicals tested, the best ligands for wildtype OBP14 were eugenol, homovanillic acid and related compounds sharing a phenol-methoxy backbone. Other chemicals, including methyl eugenol, showed affinities to OBP14 100–1000 times lower. We have also tested two mutants of OBP14. The first, bearing a HisTag at its N-terminus for better orientation on the sensor surface, showed only minor differences in its binding properties for chemicals when compared to the wildtype. The second contained an additional disulfide bond between helices α3 and α6, thus reducing the dynamics of OBP14 and leading to a higher affinity for eugenol. These data also demonstrate that it is feasible to produce biosensors with desired ligand specificities by introducing selected mutations into the structure of OBPs or other active proteins

Investigating the communicative function of breathing and non-breathing "silent" pauses

Cwiek A, Neueder S, Wagner P. Investigating the communicative function of breathing and non-breathing "silent" pauses. In: Draxler C, Kleber F, eds. Tagungsband der 12. Tagung Phonetik und Phonologie im deutschsprachigen Raum. München, Deutschland: Ludwig-Maximilians-Universität München; 2016: 27-29

Deriving a strategy for synthesizing lengthening disfluencies based on spontaneous conversational speech data

Betz S, Wagner P, Voße J. Deriving a strategy for synthesizing lengthening disfluencies based on spontaneous conversational speech data. In: Draxler C, Kleber F, eds. Tagungsband der 12. Tagung Phonetik und Phonologie im deutschsprachigen Raum. München: LMU; 2016: 19-22

Fibroblast activation protein is expressed by rheumatoid myofibroblast-like synoviocytes

Fibroblast activation protein (FAP), as described so far, is a type II cell surface serine protease expressed by fibroblastic cells in areas of active tissue remodelling such as tumour stroma or healing wounds. We investigated the expression of FAP by fibroblast-like synoviocytes (FLSs) and compared the synovial expression pattern in rheumatoid arthritis (RA) and osteoarthritis (OA) patients. Synovial tissue from diseased joints of 20 patients, 10 patients with refractory RA and 10 patients with end-stage OA, was collected during routine surgery. As a result, FLSs from intensively inflamed synovial tissues of refractory RA expressed FAP at high density. Moreover, FAP expression was co-localised with matrix metalloproteinases (MMP-1 and MMP-13) and CD44 splice variants v3 and v7/8 known to play a major role in the concert of extracellular matrix degradation. The pattern of signals appeared to constitute a characteristic feature of FLSs involved in rheumatoid arthritic joint-destructive processes. These FAP-expressing FLSs with a phenotype of smooth muscle actin-positive myofibroblasts were located in the lining layer of the synovium and differ distinctly from Thy-1-expressing and non-proliferating fibroblasts of the articular matrix. The intensity of FAP-specific staining in synovial tissue from patients with RA was found to be different when compared with end-stage OA. Because expression of FAP by RA FLSs has not been described before, the findings of this study highlight a novel element in cartilage and bone destruction of arthritic joints. Moreover, the specific expression pattern qualifies FAP as a therapeutic target for inhibiting the destructive potential of fibroblast-like synovial cells

Infektionsmedizinische und chirurgische Herausforderungen durch Carbapenem-resistente bakterielle Erreger bei der Versorgung Kriegsverletzter aus der Ukraine

Aufgrund von Hygienedefiziten und dem sehr breiten, kalkulierten Antibiotikaeinsatz bei zeit¬gleich offener Wundbehandlung in ukrainischen Militärkrankenhäusern ist das Risiko für schwerwiegende Wundinfektionen mit multiresis¬tenten Erregern (MRE) bei Übernahme ziviler Kriegsopfer hoch. Insofern kommt der Surveillance mit risikoadaptiertem Screening auf MRE, welches am Universitätsklinikum Leipzig seit 2012 durchgeführt wird, eine große Bedeutung zu. Es werden die Komplexität der Versorgung Kriegsverletzter aus der Ukraine sowie die damit einhergehenden Infektions- und Resistenzprobleme dargestellt und auf die Notwendigkeit eines interdisziplinären und -professionellen Managements hingewiesen.Peer Reviewe

Genome-Wide Association Analysis for Severity of Coronary Artery Disease Using the Gensini Scoring System

Coronary artery disease (CAD) has a complex etiology involving numerous environmental and genetic factors of disease risk. To date, the genetic 9p21 locus represents the most robust genetic finding for prevalent and incident CAD. However, limited information is available on the genetic background of the severity and distribution of CAD. CAD manifests itself as stable CAD or acute coronary syndrome. The Gensini score quantifies the extent CAD but requires coronary angiography. Here, we aimed to identify novel genetic variants associated with Gensini score severity and distribution of CAD. A two-stage approach including a discovery and a replication stage was used to assess genetic variants. In the discovery phase, a meta-analysis of genome-wide association data of 4,930 CAD-subjects assessed by the Gensini score was performed. Selected single nucleotide polymorphisms (SNPs) were replicated in 2,283 CAD-subjects by de novo genotyping. We identified genetic loci located on chromosome 2 and 9 to be associated with Gensini score severity and distribution of CAD in the discovery stage. Although the loci on chromosome 2 could not be replicated in the second stage, the known CAD-locus on chromosome 9p21, represented by rs133349, was identified and, thus, was confirmed as risk locus for CAD severity

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. Findings: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14–1·83) and the presence of either LPA SNP (1·88, 1·40–2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81–1·11 and either LPA SNP 1·10, 0·92–1·31) or cardiovascular mortality (0·99, 0·81–1·2 and 1·13, 0·90–1·40, respectively) or in the validation studies. Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. Funding: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny

RP1 is a phosphorylation target of CK2 and is involved in cell adhesion

RP1 (synonym: MAPRE2, EB2) is a member of the microtubule binding EB1 protein family, which interacts with APC, a key regulatory molecule in the Wnt signalling pathway. While the other EB1 proteins are well characterized the cellular function and regulation of RP1 remain speculative to date. However, recently RP1 has been implicated in pancreatic cancerogenesis. CK2 is a pleiotropic kinase involved in adhesion, proliferation and anti-apoptosis. Overexpression of protein kinase CK2 is a hallmark of many cancers and supports the malignant phenotype of tumor cells. In this study we investigate the interaction of protein kinase CK2 with RP1 and demonstrate that CK2 phosphorylates RP1 at Ser(236) in vitro. Stable RP1 expression in cell lines leads to a significant cleavage and down-regulation of N-cadherin and impaired adhesion. Cells expressing a Phospho-mimicking point mutant RP1-ASP(236) show a marked decrease of adhesion to endothelial cells under shear stress. Inversely, we found that the cells under shear stress downregulate endogenous RP1, most likely to improve cellular adhesion. Accordingly, when RP1 expression is suppressed by shRNA, cells lacking RP1 display significantly increased cell adherence to surfaces. In summary, RP1 phosphorylation at Ser(236) by CK2 seems to play a significant role in cell adhesion and might initiate new insights in the CK2 and EB1 family protein association

Serum amyloid A: high-density lipoproteins interaction and cardiovascular risk

Aims High-density lipoproteins (HDLs) are considered as anti-atherogenic. Recent experimental findings suggest that their biological properties can be modified in certain clinical conditions by accumulation of serum amyloid A (SAA). The effect of SAA on the association between HDL-cholesterol (HDL-C) and cardiovascular outcome remains unknown. Methods and results We examined the association of SAA and HDL-C with mortality in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, which included 3310 patients undergoing coronary angiography. To validate our findings, we analysed 1255 participants of the German Diabetes and Dialysis study (4D) and 4027 participants of the Cooperative Health Research in the Region of Augsburg (KORA) S4 study. In LURIC, SAA concentrations predicted all-cause and cardiovascular mortality. In patients with low SAA, higher HDL-C was associated with lower all-cause and cardiovascular mortality. In contrast, in patients with high SAA, higher HDL-C was associated with increased all-cause and cardiovascular mortality, indicating that SAA indeed modifies the beneficial properties of HDL. We complemented these clinical observations by in vitro experiments, in which SAA impaired vascular functions of HDL. We further derived a formula for the simple calculation of the amount of biologically ‘effective' HDL-C based on measured HDL-C and SAA from the LURIC study. In 4D and KORA S4 studies, we found that measured HDL-C was not associated with clinical outcomes, whereas calculated ‘effective' HDL-C significantly predicted better outcome. Conclusion The acute-phase protein SAA modifies the biological effects of HDL-C in several clinical conditions. The concomitant measurement of SAA is a simple, useful, and clinically applicable surrogate for the vascular functionality of HD