Alternative final steps in berberine biosynthesis in Coptis japonica cell cultures

In Coptis japonica cell cultures an alternative pathway has been discovered which leads from (S)-tetrahydrocolumbamine via (S)-canadine to berberine. The two enzymes involved have been partially purified. (S)-Tetrahydrocolumbamine is stereospecifically transformed into (S)-canadine under formation of the methylenedioxy bridge in ring A. This new enzyme was named (S)-canadine synthase. (S)-Canadine in turn is stereospecifically dehydrogenated to berberine by an oxidase, (S)-canadine oxidase (COX), which was partially purified (25-fold). This enzyme has many physical properties in common with the already known (S)-tetrahydroprotoberberine oxidase from Berberis but grossly differs from the latter enzyme in its cofactor requirement (Fe) and its substrate specificity. Neither (S)-norreticuline nor (S)-scoulerine serves as substrate for the Coptis enzyme, while both substrates are readily oxidized by the Berberis enzyme. The four terminal enzymes catalyzing the pathway from (S)-reticuline to berberine are housed in Berberis as well as in Coptis in smooth vesicles with a density of =1.14 g/ml. These vesicles have been enriched and characterized by electron microscopy

Konflikte in der Hochschullehre. Die Moderationsmethode als Möglichkeit der Bearbeitung

Konflikte sind so alt wie die Menschheit selbst und beeinflussen das Zusammenleben auf allen Ebenen, sie sind eine grundsätzliche Möglichkeit der Form des Sozialen. Somit machen sie natürlich auch vor der Hochschullehre nicht Halt. Der vorliegende Beitrag ermutigt Hochschullehrende dazu, sich mit der Konfliktthematik auseinanderzusetzen und sich Konflikten zu stellen. Hochschullehrende haben die asymmetrisch vergebene Chance, Lehre zu gestalten. Diese Chance sollten sie nutzen. Denn verortet man Lehre in einem Dreieck von Lehrenden, Lernenden und wissenschaftlichem Wissen, kommt es nicht allein auf die reine Wissensvermittlung oder auf die Person des Lehrenden an, sondern dann wird auch die Situationsgestaltung zentral. Als besonders typisch für die Hochschullehre können mikro-soziale Konflikte mit geringem und mittlerem Eskalationsgrad gelten. Diese werden im vorliegenden Beitrag fokussiert und für deren Bearbeitung wird die Moderationsmethode als Interventionsmöglichkeit vorgestellt

Cytogenetic Characterization of the TM4 Mouse Sertoli Cell Line. II. Chromosome Microdissection, FISH, Scanning Electron Microscopy, and Confocal Laser Scanning Microscopy

The chromosomes and interphase cell nuclei of the permanent mouse Sertoli cell line TM4 were examined by chromosome microdissection, FISH, scanning electron microscopy, and confocal laser scanning microscopy. The already known marker chromosomes m1-m5 were confirmed, and 2 new large marker chromosomes m6 and m7 were characterized. The minute heterochromatic marker chromosomes m4 and m5 were microdissected and their DNA amplified by DOP-PCR. FISH of this DNA probe on TM4 metaphase chromosomes demonstrated that the m4 and m5 marker chromosomes have derived from the centromeric regions of normal telocentric mouse chromosomes. Ectopic pairing of the m4 and m5 marker chromosomes with the centromeric region of any of the other chromosomes (centromeric associations) was apparent in ∼60% of the metaphases. Scanning electron microscopy revealed DNA-protein bridges connecting the centromeric regions of normal chromosomes and the associated m4 and m5 marker chromosomes. Interphase cell nuclei of TM4 Sertoli cells did not exhibit the characteristic morphology of Sertoli cells in the testes of adult mice as shown by fluorescence microscopy and confocal laser scanning microscopy

Creación de espacios de aprendizaje y enseñanza para la investigación transformadora y transdisciplinar : el Laboratorio de Innovación Transformadora

Para lograr una transición hacia el desarrollo sostenible son fundamentales la ciencia y la educación, especialmente la educación superior. Se necesitan formatos educativos para capacitar a los estudiantes en la realización de investigaciones transformadoras. Con base en la investigación transdisciplinaria y transformadora en laboratorios del mundo real y estudios del futuro, desarrollamos un módulo de aprendizaje y enseñanza integral: el Laboratorio de Innovación Transformadora (lit). El laboratorio desarrolla cinco competencias clave y tres tipos de conocimiento necesarios para impulsar innovaciones en sostenibilidad socialmente robustas. En este artículo se presentan las principales características de este formato vivencial y reflexivo, además de un manual para facilitar el laboratorio. También se comparten y discuten los aprendizajes centrales de la implementación de este formato en programas de estudio existentes a partir de dos pruebas realizadas en dos universidades alemanas

Transformatives Lernen durch Engagement : soziale Innovationen als Impulsgeber für Umweltbildung und Bildung für nachhaltige Entwicklung ; Abschlussbericht

Zentraler Ausgangspunkt des Vorhabens war die Frage nach der Rolle und Bedeutung von transformativem Lernen im Kontext sozial-ökologischer Transformationen und wie dieses im Rahmen schulischer und außerschulischer Umweltbildung und BNE ermöglicht und von der Umweltpolitik gestärkt und adressiert werden kann. Dazu entwickelte das Projekt in Kooperation zwischen Schulen und zivilgesellschaftlichen Nachhaltigkeitsinitiativen Lernwerkstätten im Modus des Service Learning und erprobte mittels Reallaborforschung, wie gesellschaftliches Engagement von Jugendlichen an Orten sozialer Innovationen mit fachlichem Lernen im Unterricht verknüpft werden kann. Der Schlussbericht präsentiert die zentralen theoretischen und empirischen Erkenntnisse des Projekts und liefert zudem eine umfassende Literaturanalyse zu bestehenden konzeptionellen Lerntheorien und Ansätzen um transformatives Lernen, BNE und Service Learning. Die Empfehlungen zur Förderung von Lernen im Kontext sozial-ökologischer Transformationsprozesse richten sich an Entscheidungsträger*innen in Umwelt- und Bildungspolitik und zeigen, dass hierfür das Lernen durch Engagement an Orten sozialer Innovationen als auch das Lernen in Kooperationen besonderes Potential haben

Empagliflozin reduces the risk of a broad spectrum of heart failure outcomes regardless of heart failure status at baseline

No abstract available

Heart failure outcomes according to heart rate and effects of empagliflozin in patients of the EMPEROR-Preserved trial

Aims Empagliflozin reduces cardiovascular death (CVD) or heart failure hospitalization (HHF) in patients with heart failure and preserved ejection fraction (HFpEF). Treatment effects and safety in relation to resting heart rate (RHR) have not been studied. Methods and results The interplay of RHR and empagliflozin effects in EMPEROR-Preserved was evaluated. We grouped patients (n = 5988) according to their baseline RHR (75 bpm [n = 1736]) and explored the influence of RHR on CVD or HHF (primary outcome) and its components in sinus rhythm or atrial fibrillation/flutter (AF) and adverse events. We studied the efficacy of empagliflozin across the RHR spectrum. Compared to placebo, empagliflozin did not change heart rate over time. The primary outcome (p for trend = 0.0004) and its components CVD (p trend = 0.0002), first HHF (p for trend = 0.0099) and all-cause death (p <  0.0001) increased with RHR only in sinus rhythm but not AF. The risk increase with RHR was similar in patients with heart failure and mildly reduced ejection fraction (left ventricular ejection fraction [LVEF] 40–49%) and HFpEF (LVEF ≥50%). Baseline RHR had no influence on the effect of empagliflozin on the primary outcomes (p for trend = 0.20), first HHF (p for trend = 0.49). There were no clinically relevant differences in adverse events between empagliflozin and placebo across the RHR groups. Conclusion Resting heart rate associates with outcomes only in sinus rhythm but not in AF. Empagliflozin reduced outcomes over the entire RHR spectrum without increase of adverse events

Liver tests, cardiovascular outcomes and effects of empagliflozin in patients with heart failure and preserved ejection fraction: The EMPEROR-Preserved trial

Aim The prognostic implication of elevated liver tests in heart failure with preserved ejection fraction (HFpEF) is uncertain. This analysis investigates the association of liver markers with hospitalization for heart failure (HHF) and cardiovascular death (CVD), and the treatment effect of empagliflozin across the range of liver marker levels. Methods and results The double-blind, placebo-controlled EMPEROR-Preserved (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure with Preserved Ejection Fraction) enrolled 5988 patients with HFpEF (ejection fraction >40%). Patients in New York Heart Association class II–IV and elevated N-terminal pro-B-type natriuretic peptide were randomized to receive empagliflozin 10 mg daily or placebo in addition to usual therapy. Patients with significant liver disease were excluded. The primary endpoint was time to first adjudicated HHF or CVD. We explored the association of liver function abnormalities with heart failure outcomes in patients on placebo, the effects of empagliflozin on liver tests and the treatment effects of empagliflozin on heart failure outcomes across categories of liver laboratory values. High alkaline phosphatase (p trend < 0.0001), low albumin (p trend < 0.0001) and high bilirubin (p = 0.02) were associated with poorer outcomes for HHF or CVD, while high aspartate aminotransferase was not, and high alanine aminotransferase was associated with better outcomes. Empagliflozin had no significant effects on liver tests compared to placebo except for albumin which was significantly increased. The treatment effect of empagliflozin on outcomes was not modified by liver tests. Conclusion Abnormalities of liver function tests are associated differently with heart failure outcomes. Salutary effects of empagliflozin on liver tests were not observed although albumin increased. The treatment benefits of empagliflozin were not affected by baseline values of liver parameters

Early benefits of empagliflozin in patients with or without heart failure: findings from EMPA-REG OUTCOME

Aims: The EMPA‐REG OUTCOME trial demonstrated reductions in cardiovascular (CV) death and heart failure (HF) outcomes with empagliflozin, a sodium–glucose co‐transporter 2 inhibitor, in patients with type 2 diabetes and established CV disease over a study period of 3 years. We aimed to investigate the early benefit–risk profile of empagliflozin in patients enrolled in the EMPA‐REG OUTCOME trial according to HF status at baseline. Methods and results: The effects of treatments on glycated haemoglobin, systolic blood pressure and body weight, and on the HF endpoints of hospitalization for HF (HHF), HHF or CV death, and HHF or all‐cause mortality were evaluated at 12 weeks, 6 months, and 1 year after randomization. Occurrence of adverse events (AEs) during these time points was also evaluated. Compared with placebo, empagliflozin lowered glycated haemoglobin, systolic blood pressure, and body weight and rates of all the HF endpoints, as early as at 12 weeks, regardless of HF status at baseline. Favourable clinical and metabolic effects were maintained over time. AEs were generally higher in those with HF than without HF; however, compared with placebo, empagliflozin did not increase risk of developing AEs over the first year of treatment. Conclusions: In the EMPA‐REG OUTCOME trial, the use of empagliflozin led to early and beneficial effects on clinical, metabolic, and HF outcomes in patients with type 2 diabetes with or without HF at baseline, which were already apparent within 12 weeks from initiation of treatment. Over the first year of treatment, no safety concern was detected with the use of empagliflozin