Detection and sequence analysis of a nickel-induced mutation in a retroviral model system

We have developed a novel way to assess the mutagenicity of environmentally important metal carcinogens, such as nickel, by creating a positive selection system based upon the conditional expression of a retroviral transforming gene. The target gene is the v-mos gene in MuSVts110, a murine retrovirus possessing a growth temperature dependent defect in expression of the transforming gene due to viral RNA splicing. In normal rat kidney cells infected with MuSVts110 (6m2 cells), splicing of the MuSVts110 RNA to form the mRNA from which the transforming protein, p85$\sp{\rm gag-mos}$, is translated is growth-temperature dependent, occurring at 33 C and below but not at 39 C and above. This splicing "defect" is mediated by cis-acting viral sequences. Nickel chloride treatment of 6m2 cells followed by growth at 39 C, allowed the selection of "revertant" cells which constitutively express p85$\sp{\rm gag-mos}$ due to stable changes in the viral RNA splicing phenotype, suggesting that nickel, a carcinogen whose mutagenicity has not been well established, could induce mutations in mammalian genes. We also show by direct sequencing of PCR-amplified integrated MuSVts110 DNA from a 6m2 nickel-revertant cell line that the nickel-induced mutation affecting the splicing phenotype is a cis-acting 70-base duplication of a region of the viral DNA surrounding the 3$\sp\prime$ splice site. These findings provide the first example of the molecular basis for a nickel-induced DNA lesion and establish the mutagenicity of this potent carcinogen. ^

Der Stadt zur Zierde, dem Publico zur Freude: Theater in Bern im 18. und 19. Jh.

Die Stadt Bern bildete im 18. Jahrhundert den grössten Stadtstaat nördlich der Alpen. Sie wurde von vielen ausländischen Reisenden als eine der schönsten Städte der Eidgenossenschaft gepriesen und trotz ihrer aristokratischen Regierungsform als vorbildliches Staatswesen dargestellt. Nach dem Untergang des Ancien Régime 1798 und den folgenden gesellschaftlichen und politischen Umwälzungen wurde Bern 1848 zur Bundesstadt der Schweiz erkoren. Als reformiertes, urbanes Zentrum, an der Schnittstelle von deutschen und französischen Einflüssen gelegen, kannte Bern eine überraschend vielgestaltige Theaterkultur, die für die Zeitspanne des 18. und 19. Jahrhunderts noch nie systematisch untersucht worden ist. Das vorliegende Werk leistet einen Beitrag, um diese Forschungslücke in der Schweizer Theaterhistoriographie zu schliessen. Kulturelle Ausdrucksformen des Menschen im Allgemeinen und Theaterpraktiken im Besonderen stehen in enger Wechselwirkung mit den sozialen, politischen und geistesgeschichtlichen Gegebenheiten einer Zeit. Erscheinungsformen theatralen Handelns im Kontext der konkreten gesellschaftshistorischen Bedingungen bilden denn auch den Untersuchungsgegenstand dieser quellennahen Studie. Vier Schwerpunktkapitel behandeln je eine Theaterform, die den Untersuchungszeitraum in besonderem Masse prägten: Reisende Theatergesellschaften, Liebhabertheater, Schauereignisse des Äusseren Stands sowie historische Festzüge und Festspiele. In der Schweiz, die keine Königshöfe oder Fürstenresidenzen kannte, gehörten die reisenden Theatergesellschaften zu den wichtigsten Akteuren im Berufstheaterwesen. Der komplizierte obrigkeitliche Verwaltungsapparat, dem sich die fremden Theatertruppen stellen mussten, das Zusammenleben in der städtischen Gemeinschaft und die bunte Palette des theatralen Unterhaltungsangebots werden in einem ersten Teil anhand exemplarischer Beispiele vorgestellt. Während das professionelle Theaterschaffen im Berichtszeitraum weitgehend von ausländischen Kräften getragen wurde, pflegte die einheimische Bevölkerung mehrheitlich die dilettierende Kunstausübung. Im Unterschied zum gewerbsmässig betriebenen Theater genoss das Liebhabertheater ein weit höheres Sozialprestige. Die vielfältigen Ausformungen der bernischen Laientheaterkultur sind Gegenstand des zweiten Kapitels, wobei der Bogen gespannt wird von der Salongeselligkeit des 18. Jahrhunderts bis zum Vereinstheaterwesen des 19. Jahrhunderts. Eine interessante Facette des sozialen Rollenspiels wird in den Aktionen des Äusseren Standes nachgewiesen, einer Vereinigung junger Patriziersöhne, die sich mit fiktiven Regierungssitzungen, Gerichtsverhandlungen und farbenprächtigen Umzügen, auf ihre künftige Magistratsrolle vorbereiteten. Die Institution des Äusseren Stands und die von ihr organisierten Schauereignisse stehen ziemlich exzeptionell in der schweizerischen, ja sogar in der europäischen Theaterlandschaft da. Für das Nationalbewusstsein und das Selbstverständnis des 1848 gegründeten Schweizer Bundesstaats waren die historischen Festzüge und Festspiele von besonderer Bedeutung. Die Stadt Bern setzte mit ihrer monumental aufgezogenen Gründungsfeier im Jahre 1891 Massstäbe. Die Wirkungsästhetik der Festspielinszenierung beruhte im Wesentlichen auf einer präzisen Choreographie der Masse und der eigens zu diesem Anlass komponierten Musik. Die Rezeptionsbelege zeugen durchweg von einer gefühlsmässigen Überwältigung des Publikums. Die nicht nur für Bern typische Festspieleuphorie des ausgehenden 19. Jahrhunderts war eine Antwort auf die von vielen Zeitgenossen als brüchig empfundene Lebenswirklichkeit. Die Autorin liefert mit ihrer Studie zum Theater in Bern eine facettenreiche Darstellung der einzelnen Theaterformen, benennt Akteure, Zuschauer und Interessenvertreter, beschreibt die Spielstätten und die Aufführungspraxis, situiert die szenischen Vorgänge im historischen Kontext und fragt nach den Funktionen, die sie erfüllten. Auf diese Weise entfaltet sich ein einzigartiges kulturgeschichtliches Panorama einer reformierten Stadt der Eidgenossenschaft im Übergang vom 18. ins 19. Jahrhundert. Es gelingt der Autorin, ein anschauliches Bild der vielfältigen Theaterlandschaft der Stadt Bern von 1700-1900 zu zeichnen und vor dem Hintergrund der gesellschaftspolitischen Bedingungen die Kontinuitäten, Brüche und Besonderheiten im bernischen Theatralitätsgefüge sichtbar zu machen. Die vorliegende Arbeit entstand im Rahmen des Forschungsprojekts »Berner Theatergeschichte« des Instituts für Theaterwissenschaft Bern und der Schweizerischen Theatersammlung. Die Historikerin und Theaterwissenschaftlerin Susanna Tschui promovierte mit dieser Arbeit an der Universität Bern. Sie ist als wissenschaftliche Mitarbeiterin im Archiv- und Museumswesen tätig.

Subgingival Aggregatibacter actinomycetemcomitans associates with the risk of coronary artery disease

AIM We investigated the association between angiographically verified coronary artery disease (CAD) and subgingival Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola. MATERIALS AND METHODS The cross-sectional study population (n = 445) comprised 171 (38.4%) patients with Stable CAD, 158 (35.5%) with acute coronary syndrome (ACS) and 116 (26.1%) with no significant CAD (No CAD). All patients participated in clinical and radiological oral health examinations. Pooled subgingival bacterial samples were analysed by checkerboard DNA-DNA hybridization assays. RESULTS In all study groups, the presence of P. gingivalis, T. forsythia and T. denticola indicated a significant (p ≤ 0.001) linear association with the extent of alveolar bone loss (ABL), but A. actinomycetemcomitans did not (p = 0.074). With a threshold level of bacterial cells 1 × 10(5) A. actinomycetemcomitans was significantly more prevalent in the Stable CAD group (42.1%) compared to the No CAD group (30.2%) (p = 0.040). In a multi-adjusted logistic regression analysis using this threshold, A. actinomycetemcomitans positivity associated with Stable CAD (OR 1.83, 95% CI 1.00-3.35, p = 0.049), but its level or levels of other bacteria did not. CONCLUSIONS The presence of subgingival A. actinomycetemcomitans associates with an almost twofold risk of Stable CAD independently of alveolar bone loss.

Effect of ticagrelor on the outcomes of patients with prior coronary artery bypass graft surgery: insights from the PLATelet inhibition and patient outcomes (PLATO) trial

BACKGROUND Patients with prior coronary artery bypass graft surgery (CABG) who present with an acute coronary syndrome have a high risk for recurrent events. Whether intensive antiplatelet therapy with ticagrelor might be beneficial compared with clopidogrel is unknown. In this substudy of the PLATO trial, we studied the effects of randomized treatment dependent on history of CABG. METHODS Patients participating in PLATO were classified according to whether they had undergone prior CABG. The trial's primary and secondary end points were compared using Cox proportional hazards regression. RESULTS Of the 18,613 study patients, 1,133 (6.1%) had prior CABG. Prior-CABG patients had more high-risk characteristics at study entry and a 2-fold increase in clinical events during follow-up, but less major bleeding. The primary end point (composite of cardiovascular death, myocardial infarction, and stroke) was reduced to a similar extent by ticagrelor among patients with (19.6% vs 21.4%; adjusted hazard ratio [HR], 0.91 [0.67, 1.24]) and without (9.2% vs 11.0%; adjusted HR, 0.86 [0.77, 0.96]; P(interaction) = .73) prior CABG. Major bleeding was similar with ticagrelor versus clopidogrel among patients with (8.1% vs 8.7%; adjusted HR, 0.89 [0.55, 1.47]) and without (11.8% vs 11.4%; HR, 1.08 [0.98, 1.20]; P(interaction) = .46) prior CABG. CONCLUSIONS Prior-CABG patients presenting with acute coronary syndrome are a high-risk cohort for death and recurrent cardiovascular events but have a lower risk for major bleeding. Similar to the results in no-prior-CABG patients, ticagrelor was associated with a reduction in ischemic events without an increase in major bleeding.

Effects of overt self-­talk on team partners’ other-efficacy and performance in a golf putting task

Introduction According to Lent and Lopez’ (2002) tripartite view of efficacy beliefs, members of a team form beliefs about the efficacy of their team partners. This other-efficacy belief can influence individual performance as shown by Dunlop, Beatty, and Beauchamp (2011) in their experimental study using manipulated performance feedback to alter other-efficacy beliefs. Participants holding favorable other-efficacy beliefs outperformed those with lower other--‐efficacy beliefs. Antecedents of such other-efficacy beliefs are amongst others perceptions regarding motivation and psychological factors of the partner (Jackson, Knapp, & Beauchamp, 2008). Overt self-talk could be interpreted as the manifestation of such motivational or psychological factors. In line with this assumption, in an experimental study using dubbed videos of the same segment of a tennis match, Van Raalte, Brewer, Cornelius, and Petitpas (2006) found that players were perceived more favorably (e.g., more concentrated, and of higher ability levels) when shown with dubbed positive self-talk as compared to dubbed negative or no dubbed self--‐talk. Objectives The aim of the study was to examine the possible effects of a confederate’s overt self-talk on participants’ other-efficacy beliefs and performance in a team setting. Method In a laboratory experiment (between-subjects, pre-post-test design, matched by pretest performance) 89 undergraduate students (female = 35, M = 20.81 years, SD = 2.34) participated in a golf putting task together with a confederate (same gender groups). Depending on the experimental condition (positive, negative, or no self-talk), the confederate commented his or her putts according to a self-talk script. Bogus performance feedback assured that the performance of the confederate was held constant. Performance was measured as the distance to the center of the target, other-efficacy by a questionnaire. Results The data collection has just finished and the results of repeated measures analyses of variance will be presented and discussed at the congress. We expect to find higher other-efficacy beliefs and better individual performance in the positive self-talk condition. References Dunlop, W.L., Beatty, D.J., & Beauchamp, M.R. (2011). Examining the influence of other-efficacy and self-efficacy on personal performance. Journal of Sport & Exercise Psychology, 33, 586-593. Jackson, B., Knapp, P., & Beauchamp, M.R. (2008). Origins and consequences of tripartite efficacy beliefs within elite athlete dyads. Journal of Sport and Exercise Psychology, 30, 512-540. Lent, R.W., & Lopez, F.G. (2002). Cognitive ties that bind: A tripartite view of efficacy beliefs in growth--‐promoting relationships. Journal of Social and Clinical Psychology, 21, 256-286. Van Raalte, J.L., Brewer, B.W, Cornelius, A.E., & Petitpas, A.J. (2006). Self-presentational effects of self-talk on perceptions of tennis players. Hellenic Journal of Psychology, 3, 134-149.

Local and general anaesthesia do not influence outcome of transfemoral aortic valve implantation.

BACKGROUND There is great variability for the type of anaesthesia used during TAVI, with no clear consensus coming from comparative studies or guidelines. We sought to detect regional differences in the anaesthetic management of patients undergoing transcatheter aortic valve implantation (TAVI) in Europe and to evaluate the relationship between type of anaesthesia and in-hospital and 1year outcome. METHODS Between January 2011 and May 2012 the Sentinel European TAVI Pilot Registry enrolled 2807 patients treated via a transfemoral approach using either local (LA-group, 1095 patients, 39%) or general anaesthesia (GA-group, 1712 patients, 61%). RESULTS A wide variation in LA use was evident amongst the 10 participating countries. The use of LA has increased over time (from a mean of 37.5% of procedures in the first year, to 57% in last 6months, p<0.01). MI, major stroke as well as in-hospital death rate (7.0% LA vs 5.3% GA, p=0.053) had a similar incidence between groups, confirmed in multivariate regression analysis after adjusting for confounders. Dividing our population in tertiles according to the Log-EuroSCORE we found similar mortality under LA, whilst mortality was higher in the highest risk tertile under GA. Survival at 1year, compared by Kaplan-Meier analysis, was similar between groups (log-rank: p=0.1505). CONCLUSIONS Selection of anaesthesia appears to be more influenced by national practice and operator preference than patient characteristics. In the absence of an observed difference in outcomes for either approach, there is no compelling argument to suggest that operators and centres should change their anaesthetic practice.

Inhibition of matrix metalloproteinases attenuates brain damage in experimental meningococcal meningitis.

BackgroundApproximately 7% of survivors from meningococcal meningitis (MM) suffer from neurological sequelae due to brain damage in the course of meningitis. The present study focuses on the role of matrix metalloproteinases (MMPs) in a novel mouse model of MM-induced brain damage.MethodsThe model is based on intracisternal infection of BALB/c mice with a serogroup C Neisseria meningitidis strain. Mice were infected with meningococci and randomised for treatment with the MMP inhibitor batimastat (BB-94) or vehicle. Animal survival, brain injury and host-response biomarkers were assessed 48 h after meningococcal challenge.ResultsMice that received BB-94 presented significantly diminished MMP-9 levels (p¿<¿0.01), intracerebral bleeding (p¿<¿0.01), and blood-brain barrier (BBB) breakdown (p¿<¿0.05) in comparison with untreated animals. In mice suffering from MM, the amount of MMP-9 measured by zymography significantly correlated with both intracerebral haemorrhage (p¿<¿0.01) and BBB disruption (p¿<¿0.05).ConclusionsMMPs significantly contribute to brain damage associated with experimental MM. Inhibition of MMPs reduces intracranial complications in mice suffering from MM, representing a potential adjuvant strategy in MM post-infection sequelae.

Percutaneous mitral valve edge-to-edge repair: in-hospital results and 1-year follow-up of 628 patients of the 2011-2012 Pilot European Sentinel Registry.

BACKGROUND The use of transcatheter mitral valve repair (TMVR) has gained widespread acceptance in Europe, but data on immediate success, safety, and long-term echocardiographic follow-up in real-world patients are still limited. OBJECTIVES The aim of this multinational registry is to present a real-world overview of TMVR use in Europe. METHODS The Transcatheter Valve Treatment Sentinel Pilot Registry is a prospective, independent, consecutive collection of individual patient data. RESULTS A total of 628 patients (mean age 74.2 ± 9.7 years, 63.1% men) underwent TMVR between January 2011 and December 2012 in 25 centers in 8 European countries. The prevalent pathogenesis was functional mitral regurgitation (FMR) (n = 452 [72.0%]). The majority of patients (85.5%) were highly symptomatic (New York Heart Association functional class III or higher), with a high logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) (20.4 ± 16.7%). Acute procedural success was high (95.4%) and similar in FMR and degenerative mitral regurgitation (p = 0.662). One clip was implanted in 61.4% of patients. In-hospital mortality was low (2.9%), without significant differences between groups. The estimated 1-year mortality was 15.3%, which was similar for FMR and degenerative mitral regurgitation. The estimated 1-year rate of rehospitalization because of heart failure was 22.8%, significantly higher in the FMR group (25.8% vs. 12.0%, p[log-rank] = 0.009). Paired echocardiographic data from the 1-year follow-up, available for 368 consecutive patients in 15 centers, showed a persistent reduction in the degree of mitral regurgitation at 1 year (6.0% of patients with severe mitral regurgitation). CONCLUSIONS This independent, contemporary registry shows that TMVR is associated with high immediate success, low complication rates, and sustained 1-year reduction of the severity of mitral regurgitation and improvement of clinical symptoms.

Extent of coronary artery disease and outcomes after ticagrelor administration in patients with an acute coronary syndrome: Insights from the PLATelet inhibition and patient Outcomes (PLATO) trial.

BACKGROUND Extensive coronary artery disease (CAD) is associated with higher risk. In this substudy of the PLATO trial, we examined the effects of randomized treatment on outcome events and safety in relation to the extent of CAD. METHODS Patients were classified according to presence of extensive CAD (defined as 3-vessel disease, left main disease, or prior coronary artery bypass graft surgery). The trial's primary and secondary end points were compared using Cox proportional hazards regression. RESULTS Among 15,388 study patients for whom the extent of CAD was known, 4,646 (30%) had extensive CAD. Patients with extensive CAD had more high-risk characteristics and experienced more clinical events during follow-up. They were less likely to undergo percutaneous coronary intervention (58% vs 79%, P < .001) but more likely to undergo coronary artery bypass graft surgery (16% vs 2%, P < .001). Ticagrelor, compared with clopidogrel, reduced the composite of cardiovascular death, myocardial infarction, and stroke in patients with extensive CAD (14.9% vs 17.6%, hazard ratio [HR] 0.85 [0.73-0.98]) similar to its reduction in those without extensive CAD (6.8% vs 8.0%, HR 0.85 [0.74-0.98], Pinteraction = .99). Major bleeding was similar with ticagrelor vs clopidogrel among patients with (25.7% vs 25.5%, HR 1.02 [0.90-1.15]) and without (7.3% vs 6.4%, HR 1.14 [0.98-1.33], Pinteraction = .24) extensive CAD. CONCLUSIONS Patients with extensive CAD have higher rates of recurrent cardiovascular events and bleeding. Ticagrelor reduced ischemic events to a similar extent both in patients with and without extensive CAD, with bleeding rates similar to clopidogrel.

Indigenous enteric eosinophils control DCs to initiate a primary Th2 immune response in vivo.

Eosinophils natively inhabit the small intestine, but a functional role for them there has remained elusive. Here, we show that eosinophil-deficient mice were protected from induction of Th2-mediated peanut food allergy and anaphylaxis, and Th2 priming was restored by reconstitution with il4(+/+) or il4(-/-) eosinophils. Eosinophils controlled CD103(+) dendritic cell (DC) activation and migration from the intestine to draining lymph nodes, events necessary for Th2 priming. Eosinophil activation in vitro and in vivo led to degranulation of eosinophil peroxidase, a granule protein whose enzymatic activity promoted DC activation in mice and humans in vitro, and intestinal and extraintestinal mouse DC activation and mobilization to lymph nodes in vivo. Further, eosinophil peroxidase enhanced responses to ovalbumin seen after immunization. Thus, eosinophils can be critical contributors to the intestinal immune system, and granule-mediated shaping of DC responses can promote both intestinal and extraintestinal adaptive immunity.

Na 1 Nachlass Max Horkheimer, 75 - Korrespondenzen u.a. mit Armin Hodler (p. II 9, 1-88b)

37 Briefe und Beilage zwischen Armin Hodler und Max Horkheimer, 1935-1948; 14 Briefe und Beilage zwischen Hans Honegger und Max Horkheimer, 1941-1946; 1 Brief und Beilage von Max Horkheimer an Paul Honigsheim, 1943; 9 Briefe zwischen Hans Horkheimer und Max Horkheimer, 1945-1948 sowie 1 Reisebericht, Peru, 1939; 2 Briefe zwischen Susanna Huber-Weisser und Max Horkheimer, 1949; 5 Briefe zwischen Helen MacGill-Hughes vom The American Journal of Sociology und Max Horkheimer, 1949; 1 Briefabschrift von Max Horkheimer an Edmund Husserl, 28.10.1931; 1 Brief von Elizabeth Husserl-Rosenberg, 06.01.1948;