Engineered liposomes sequester bacterial exotoxins and protect from severe invasive infections in mice

Gram-positive bacterial pathogens that secrete cytotoxic pore-forming toxins, such as Staphylococcus aureus and Streptococcus pneumoniae, cause a substantial burden of disease. Inspired by the principles that govern natural toxin-host interactions, we have engineered artificial liposomes that are tailored to effectively compete with host cells for toxin binding. Liposome-bound toxins are unable to lyse mammalian cells in vitro. We use these artificial liposomes as decoy targets to sequester bacterial toxins that are produced during active infection in vivo. Administration of artificial liposomes within 10 h after infection rescues mice from septicemia caused by S. aureus and S. pneumoniae, whereas untreated mice die within 24-33 h. Furthermore, liposomes protect mice against invasive pneumococcal pneumonia. Composed exclusively of naturally occurring lipids, tailored liposomes are not bactericidal and could be used therapeutically either alone or in conjunction with antibiotics to combat bacterial infections and to minimize toxin-induced tissue damage that occurs during bacterial clearance

Sefer ha- Kuzari

des Jehuda Halevi, nach dem hebräischen Texte des Jehuda Ibn-Tibbon hrsg., übers. und mit einem Commentar, so wie mit einer allgemeinen Einleitung versehen von David Cassel

Increased nuclear suppressor of cytokine signaling 1 in asthmatic bronchial epithelium suppresses rhinovirus induction of innate interferons.

BACKGROUND Rhinovirus infections are the dominant cause of asthma exacerbations, and deficient virus induction of IFN-α/β/λ in asthmatic patients is important in asthma exacerbation pathogenesis. Mechanisms causing this interferon deficiency in asthmatic patients are unknown. OBJECTIVE We sought to investigate the expression of suppressor of cytokine signaling (SOCS) 1 in tissues from asthmatic patients and its possible role in impaired virus-induced interferon induction in these patients. METHODS We assessed SOCS1 mRNA and protein levels in vitro, bronchial biopsy specimens, and mice. The role of SOCS1 was inferred by proof-of-concept studies using overexpression with reporter genes and SOCS1-deficient mice. A nuclear role of SOCS1 was shown by using bronchial biopsy staining, overexpression of mutant SOCS1 constructs, and confocal microscopy. SOCS1 levels were also correlated with asthma-related clinical outcomes. RESULTS We report induction of SOCS1 in bronchial epithelial cells (BECs) by asthma exacerbation-related cytokines and by rhinovirus infection in vitro. We found that SOCS1 was increased in vivo in bronchial epithelium and related to asthma severity. SOCS1 expression was also increased in primary BECs from asthmatic patients ex vivo and was related to interferon deficiency and increased viral replication. In primary human epithelium, mouse lung macrophages, and SOCS1-deficient mice, SOCS1 suppressed rhinovirus induction of interferons. Suppression of virus-induced interferon levels was dependent on SOCS1 nuclear translocation but independent of proteasomal degradation of transcription factors. Nuclear SOCS1 levels were also increased in BECs from asthmatic patients. CONCLUSION We describe a novel mechanism explaining interferon deficiency in asthmatic patients through a novel nuclear function of SOCS1 and identify SOCS1 as an important therapeutic target for asthma exacerbations.

No sports – no mental health? Analysis of longitudinal effects in SHP data.

Results from the Zurich study have shown lasting associations between sport practice and mental health. The effects are pronounced in people with pre-exising mental health problems. This analysis aims to replicate these results with the large Swiss Household Panel data set and to provide more differentiated results. The analysis covered the interviews 1999-2003 and included 3891 stayers, i.e., participants who were interviewed in all years. The outcome variables are depression / blues / anxiety, weakness / weariness, sleeping problems, energy / optimism. Confounding variables include sex, age, education level, citizenship. The analyses were carried out with mixed models (depression, optimism) and GEE models (weakness, sleep). About 60% of the SHP participants practise weekly or daily an individual or a team sport. A similar proportion enjoys a frequent physical activity (for half an hour minimum) which makes oneself slightly breathless. There are slight age-specific differences but also noteworthy regional differences. Practice of sport is clearly interrelated with self-reported depressive symptoms, optimism and weakness. This applies even though some relevant confounders – sex, educational level and citizenship – were introduced into the model. However, no relevant interaction effects with time could be shown. Moreover, direct interrelations commonly led to better fits than models with lagged variables, thus indicating that delayed effects of sport practice on the self-reported psychological complaints are less important. Model variants resulted for specific subgroups, for example, participants with a high vs. low initial activity level. Lack of sport practice is an interesting marker for serious psychological symptoms and mental disorders. The background of this association may differ in different subgroups, and should stimulate further investigations in this area.

Arbeitsweisen im Gegenwartstheater

"Arbeitsweisen im Gegenwartstheater", Band 1 der neuen theaterwissenschaftlichen Reihe, ist im April 2015 im Berliner Alexander Verlag erschienen. Die regelmäßig erscheinenden Ausgaben sind als Arbeitsbücher zu den "itw : im dialog"-Symposien des Instituts für Theaterwissenschaft der Universität Bern konzipiert. Die Beiträge des ersten Bandes reflektieren die komplexen und divergenten Erscheinungsformen zeitgenössischen Theaters und nähern sich aus unterschiedlichen Perspektiven der Frage nach den Zusammenhängen von Arbeitsweisen und Ästhetiken: z. B. Kollektivität und Reflexivität im Gegenwartstheater, Formen und Mobilität internationalisierten Theaters, Allianzen zwischen Freier Szene und Stadttheater sowie Autorenregie. Mit Beiträgen von Annemarie Matzke, Barbara Gronau, Sandra Umathum, Philipp Schulte, Karin Nissen-Rizvani und Gesprächen mit Alexandre Devriendt und Joeri Smet (Ontroerend Goed, Gent), Sebastian Brünger (Rimini Protokoll, Berlin), Tomas Schweigen (FADC/Theater Basel), Sabine Harbeke (Autorin/Regisseurin, Zürich).

A novel mutation in BCS1L associated with deafness, tubulopathy, growth retardation and microcephaly

We report a novel homozygous missense mutation in the ubiquinol-cytochrome c reductase synthesis-like (BCS1L) gene in two consanguineous Turkish families associated with deafness, Fanconi syndrome (tubulopathy), microcephaly, mental and growth retardation. All three patients presented with transitory metabolic acidosis in the neonatal period and development of persistent renal de Toni-Debré-Fanconi-type tubulopathy, with subsequent rachitis, short stature, microcephaly, sensorineural hearing impairment, mild mental retardation and liver dysfunction. The novel missense mutation c.142A>G (p.M48V) in BCS1L is located at a highly conserved region associated with sorting to the mitochondria. Biochemical analysis revealed an isolated complex III deficiency in skeletal muscle not detected in fibroblasts. Native polyacrylamide gel electrophoresis (PAGE) revealed normal super complex formation, but a shift in mobility of complex III most likely caused by the absence of the BCS1L-mediated insertion of Rieske Fe/S protein into complex III. These findings expand the phenotypic spectrum of BCS1L mutations, highlight the importance of biochemical analysis of different primary affected tissue and underline that neonatal lactic acidosis with multi-organ involvement may resolve after the newborn period with a relatively spared neurological outcome and survival into adulthood. CONCLUSION Mutation screening for BCS1L should be considered in the differential diagnosis of severe (proximal) tubulopathy in the newborn period. What is Known: • Mutations in BCS1L cause mitochondrial complex III deficiencies. • Phenotypic presentations of defective BCS1L range from Bjornstad to neonatal GRACILE syndrome. What is New: • Description of a novel homozygous mutation in BCS1L with transient neonatal acidosis and persistent de Toni-Debré-Fanconi-type tubulopathy. • The long survival of patients with phenotypic presentation of severe complex III deficiency is uncommon.

Implications of the sustainable development paradigm for Switzerland

The sustainable development paradigm raises issues of global, intra- and intergenerational social equity as well as respect for nature, and economic welfare. Switzerland is confronted by these issues within its own country, and has a moral responsibility vis-a-vis the rest of the world. Syndromes of global change are affecting many eco-regions, not only in developing and transition countries, but to a lesser extent also the affluent countries. Switzerland as a nation has an impact on syndromes through its far-reaching economic activities, which are non-sustainable. At the global level, more modest consumption patterns, a considerably slowed demographic change, a nonconsumptive but sustainable use of natural resources, and conflict transformation are the main prerequisites for improving sustainability. Switzerland's current contribution to sustainability is much less than what it could be, hence the need for additional action along general principles in,accordance with Swiss traditions and innovative potentials. A number of concrete actions could be taken immediately. These are: labelling the socially and ecologically sustainable production of goods and services, and their negotiation at WTO level; enhancing international cooperation and research; strengthening education and research for sustainability, and emphasizing energy and material flux efficiency at home and abroad.

The SOLUTIONS project: challenges and responses for present and future emerging pollutants in land and water resources management.

SOLUTIONS (2013 to 2018) is a European Union Seventh Framework Programme Project (EU-FP7). The project aims to deliver a conceptual framework to support the evidence-based development of environmental policies with regard to water quality. SOLUTIONS will develop the tools for the identification, prioritisation and assessment of those water contaminants that may pose a risk to ecosystems and human health. To this end, a new generation of chemical and effect-based monitoring tools is developed and integrated with a full set of exposure, effect and risk assessment models. SOLUTIONS attempts to address legacy, present and future contamination by integrating monitoring and modelling based approaches with scenarios on future developments in society, economy and technology and thus in contamination. The project follows a solutions-oriented approach by addressing major problems of water and chemicals management and by assessing abatement options. SOLUTIONS takes advantage of the access to the infrastructure necessary to investigate the large basins of the Danube and Rhine as well as relevant Mediterranean basins as case studies, and puts major efforts on stakeholder dialogue and support. Particularly, the EU Water Framework Directive (WFD) Common Implementation Strategy (CIS) working groups, International River Commissions, and water works associations are directly supported with consistent guidance for the early detection, identification, prioritisation, and abatement of chemicals in the water cycle. SOLUTIONS will give a specific emphasis on concepts and tools for the impact and risk assessment of complex mixtures of emerging pollutants, their metabolites and transformation products. Analytical and effect-based screening tools will be applied together with ecological assessment tools for the identification of toxicants and their impacts. The SOLUTIONS approach is expected to provide transparent and evidence-based candidates or River Basin Specific Pollutants in the case study basins and to assist future review of priority pollutants under the WFD as well as potential abatement options.

Variation in Current Management of Term and Late-Preterm Neonates at Risk for Early-Onset Sepsis "An International Survey and Review of Guidelines"

BACKGROUND Uncertainty about the presence of infection results in unnecessary and prolonged empiric antibiotic treatment of newborns at risk for early-onset sepsis (EOS). This study evaluates the impact of this uncertainty on the diversity in management. METHODS A web-based survey with questions addressing management of infection risk-adjusted scenarios was performed in Europe, North America, and Australia. Published national guidelines (n=5) were reviewed and compared to the results of the survey. RESULTS 439 Clinicians (68% were neonatologists) from 16 countries completed the survey. In the low-risk scenario, 29% would start antibiotic therapy and 26% would not, both groups without laboratory investigations; 45% would start if laboratory markers were abnormal. In the high-risk scenario, 99% would start antibiotic therapy. In the low-risk scenario, 89% would discontinue antibiotic therapy before 72 hours. In the high-risk scenario, 35% would discontinue therapy before 72 hours, 56% would continue therapy for five to seven days, and 9% for more than 7 days. Laboratory investigations were used in 31% of scenarios for the decision to start, and in 72% for the decision to discontinue antibiotic treatment. National guidelines differ considerably regarding the decision to start in low-risk and regarding the decision to continue therapy in higher risk situations. CONCLUSIONS There is a broad diversity of clinical practice in management of EOS and a lack of agreement between current guidelines. The results of the survey reflect the diversity of national guidelines. Prospective studies regarding management of neonates at risk of EOS with safety endpoints are needed.

Na 1 Nachlass Max Horkheimer, 105 - Korrespondenzen u.a. mit Bertold Scheller und Alfred Schmidt (p. III 12, 175-380)

Briefwechsel zwischen Bertold Scheller und Max Horkheimer, 1955; Briefwechsel zwischen dem Diplom-Volkswirt Albert Schiefer und Max Horkheimer, 1957; Briefwechsel zwischen dem Bayerischer Schulbuch-Verlag und Max Horkheimer, 1954; Briefwechsel mit Beilagen zwischen der Deutschen Schlafwagen- und Speisewagen-Gesellschaft und Max Horkheimer, 1954; 1 Brief von Ludwig Benedict Schlesinger an Max Horkheimer, 1958; 1 Brief von dem Professor Alfred Schmidt an Max Horkheimer, 1957 und 1 Gutachten von Max Horkheimer, 1958; 1 Brief von Hermann Schweppenhäuser an Max Horkheimer, 1957; Briefwechsel zwischen W. Schmidt-Richberg und Max Horkheimer, 1957-1958; Briefwechsel zwischen Alfred Schmidweber und Max Horkheimer, 1956; 1 Brief von Katja Schmitz? an Max Horkheimer, 1955; Briefwechsel zwischen der Studentin Elsmarie Schmitz und Max Horkheimer, 1958; Briefwechsel zwischen dem Professor Günter Schmölders und Max Horkheimer, 1957-1958; 1 Brief an Diplom-Volkswirt Helmut Schneider von Max Horkheimer, 1955; Briefwechsel zwischen Marianne Schneider und Max Horkheimer, 1955-1956; Briefwechsel zwischen Georg von Schnitzler und Max Horkheimer, 1954; 1 Todenanzeige von Louis Schnürpel, 1956; Briefwechsel zwischen Roman Schnur und Max Horkheimer, 1955-1958; 1 Brief mit Anlagen an Günter P. Schölzel von Max Horkheimer, 1958; Briefwechsel zwischen Hans W. Schoenberg und Max Horkheimer, 1955; 1 Anzeige von Arnold Schoenberg, 1955; Briefwechsel zwischen der Studentin Annemarie Schöne und Max Horkheimer, 1956; Briefwechsel zwischen dem Professor Hans Joachim Schoeps und Max Horkheimer, 1955-1956; 1 Brief an den Professor Rudolf Schottlaender von Max Horkheimer, 1955; 1 Anzeige von Joachim Schroeter, 1955; Briefwechsel zwischen Karl Schück und Max Horkheimer, 1954; Briefwechsel zwischen Julia von der Schulenburg und Max Horkheimer, 1957; Briefwechsel zwischen dem Bankdirektor Felix W. Schulthess und Max Horkheimer, 1955; 1 Brief an den Privatdozent Walter Schulz von Max Horkheimer, 1954; Briefwechsel mit Beilagen zwischen dem Bürgermeister Wolfgang Schwabe und Max Horkheimer, 1954; Breifwechsel mit Beilagen zwischen Hans Schwalbach und Max Horkheimer, 1954; Briefwechsel mit Beilagen zwischen Poldi Schwalbach und Max Horkheimer, 1954; 1 Brief von Louis Daniel Schwallbach an Max Horkheimer, 1955; Briefwechsel zwischen Dorothea de Schweinitz und Max Horkheimer, 1958; 1 Aktennotiz von Hans Zulliger, 1956; Briefwechsel zwischen William Schwitzer und Max Horkheimer, 1954; Briefwechsel zwischen Karl von Stackelberg und Max Horkheimer, 1954; 1 Brief von Clemens Köttelwesch und Max Horkheimer, 1957; 1 Brief von dem Oberlandesgerichtspräsidenten Bruno Heusinger an Max Horkheimer, 1954; Briefwechsel zwischen dem Oberstadtdirektor Erich Walter Lotz und Max Horkheimer, 1953-1954; Briefwechsel zwischen der Stadtverwaltung Iserlohn und Max Horkheimer, 1954; Briefwechsel mit Beilagen zwischen dem Diplom Ingenieur und Oberbaurat Julius Schwalm und Max Horkheimer, 1954; 1 Brief an den Professor Herbert Plügge von Max Horkheimer, 1957; Briefwechsel zwischen den Professor und Oberlandesgerichtspräsidenten Curt Staffund Max Horkheimer, 1956-1957; 1 Brief von dem Professor B. M. Stanfield an Max Horkheimer, 1957; 1 Vermählungsanzeige von den Professor Dietrich Starck, 1956 und 1 Brief an den Professor Dietrich Starck von Max Horkheimer, 1958; Briefwechsel zwischen den Professor Werner Stark und Max Horkheimer, 1958; Briefwechsel mit Beilagen zwischen Rolf Stätter und Max Horkheimer, 1954; 1 Brief von Karl Staufen an Max Horkheimer, 1952; 1 Brief von Direktor Adolf Stauss an Max Horkheimer, 1954; Briefwechsel zwischen dem Bankier Alwin Steffan und Max Horkheimer, 1954-1957; 2 Briefe an den Professor Wolfgang Stegmüller von Max Horkheimer, 1957; Briefwechsel zwischen dem Professor und MinisterErwin Stein und Max Horkheimer, 1956-1957; 1 Brief an Lotte Steinberger von Max Horkheimer, 1954; 1 Brief von Ernst Steindorf an Max Horkheimer, ohne Jahr; Briefwechsel zwischen Helmut von den Steinen und Max Horkheimer, 1955 und 1 Brief an Helmut von den Steinen von Theodor W. Adorno, 1955; Briefwechsel zwischen den Professor Hans Erich Stier, 1958; Briefwechsel zwischen Elsbeth Stocker und Max Horkheimer, 1955; Briefwechsel zwischen Eric W. Stoetzner und Max Horkheimer, 1957-1958; Briefwechsel zwischen Gertrud Straulino und Max Horkheimer, 1957-1958; Briefwechsel zwischen den Professor Siegfried Strugger und Max Horkheimer, 1955; Briefwechsel mit Beilagen zwischen Willy Strzelewicz und Max Horkheimer, 1955-1957; Briefwechsel mit Beilagen zwischen der Studentenschaft der Universität Köln und Max Horkheimer, 1953;

Auswahl kabbalistischer Mystik : zum Theil nach Handschriften zu Paris und Hamburg, nebst historischen Untersuchungen und Charakteristiken

hrsg. von Adolph Jellinek

NMR spectrum of lindgomycin from a Marine Fungus of the Lindgomycetaceae

An unusual polyketide with a new carbon skeleton, lindgomycin (1), and the recently described ascosetin (2) were extracted from mycelia and culture broth of different Lindgomycetaceae strains, which were isolated from a sponge of the Kiel Fjord in the Baltic Sea (Germany) and from the Antarctic. Their structures were established by spectroscopic means. In the new polyketide, two distinct domains, a bicyclic hydrocarbon and a tetramic acid, are connected by a bridging carbonyl. The tetramic acid substructure of compound 1 was proved to possess a unique 5-benzylpyrrolidine-2,4-dione unit. The combination of 5-benzylpyrrolidine-2,4-dione of compound 1 in its tetramic acid half and 3-methylbut-3-enoic acid pendant in its decalin half allow the assignment of a new carbon skeleton. The new compound 1 and ascosetin showed antibiotic activities with IC50 value of 5.1 (±0.2) µM and 3.2 (±0.4) µM, respectively, against methicillin-resistant Staphylococcus aureus.