Praxisbericht aus dem mediendidaktischen Projekt FEEDBACK in der Lehre

„Was ist gute Lehre?“ Dieser Frage wollen wir auf den Grund gehen. Erneut haben wir zur Auseinandersetzung damit ein Vorhaben auf den Weg gebracht, das insbesondere auch nach dem Beitrag die digitalen Medien zur Entwicklung didaktischer Qualität fragt und die Rahmenbedingungen, unter denen sich ihr Potenzial für die Hochschullehre erschließen lässt, zu beschreiben versucht. Mit dem Projekt „FEEDBACK in der Lehre“ fokussieren wir einen wesentlichen Aspekt unseres Lehr-Lern-Handelns und machen ihn explizit zum Gegenstand der Reflexion von Unterrichtsmethoden und Mediengebrauch. Ein weiteres Mal versuchen wir Antworten auf diese Frage aus der Praxis unserer Lehre an der Hochschule Bremen zu erzeugen – nicht zuletzt als Konsequenz aus dem vorhergehenden Projekt „WELLDONE“, in dessen Evaluation einer angemessenen und konstruktiven Kommunikation über Lernerwartungen und Lernergebnissen für den Studienerfolg von der Mehrheit der Teilvorhaben eine besondere Bedeutung beigemessen wurde. Wie gute Lehre gestaltet werden kann oder als solche erfahren wird erleben wir alltäglich im Studienbetrieb – auch ohne besondere Vorhaben. Sie äußern sich in den kleinen und großen Beispielen positiver Rückmeldungen, nach einer als gelungen empfundenen Diskussion im Seminar, in der Freude eines Studierenden-Teams über einen erfolgreichen Laborversuch, in der von einer Kollegin ausgesprochenen Ermutigung, den Einsatz eines neuen Mediums weiterhin zu verfolgen, auch wenn es beim ersten Mal noch nicht optimal geklappt hat. Die in der Alltagspraxis vorgefundenen Antworten sind so unterschiedlich und mannigfaltig wie das Spektrum der Studienangebote an unserer Hochschule. Sie sind einem ständigen Wandel unterworfen, einerseits bedingt durch neue Ziele und Rahmenbedingungen, andererseits auch immer wieder gründend in der didaktischen Kreativität von Lehrenden, die mit der Freiheit der Lehre auch methodische Spielräume verbinden und sie zur Bereicherung ihres Lehrangebots nutzen. All das ist es wert, anderen zugänglich gemacht und – gern auch kontrovers – diskutiert zu werden. Dafür brauchen wir den besonderen Rahmen, den wir mittels unserer Vorhaben herstellen wollen: Eine Umgebung, in der wir aus Beispielen lernen können, in der wir im kollegialen Gespräch erfragen können, wie sich theoretisch fundierte und didaktisch sorgfältig ausgewählte Methoden und Medien in der konkreten Unterrichtspraxis bewährt haben, in der wir uns die Zeit nehmen können, anderen Lehrenden zuzuhören, auch unsere Neugier zu stillen oder den kritischen Blick auf unsere eigene Routine zu schärfen.8

The Myxobacterial Antibiotic Myxovalargin: Biosynthesis, Structural Revision, Total Synthesis, and Molecular Characterization of Ribosomal Inhibition

Resistance of bacterial pathogens against antibiotics is declared by WHO as a major global health threat. As novel antibacterial agents are urgently needed, we re-assessed the broad-spectrum myxobacterial antibiotic myxovalargin and found it to be extremely potent against Mycobacterium tuberculosis. To ensure compound supply for further development, we studied myxovalargin biosynthesis in detail enabling production via fermentation of a native producer. Feeding experiments as well as functional genomics analysis suggested a structural revision, which was eventually corroborated by the development of a concise total synthesis. The ribosome was identified as the molecular target based on resistant mutant sequencing, and a cryo-EM structure revealed that myxovalargin binds within and completely occludes the exit tunnel, consistent with a mode of action to arrest translation during a late stage of translation initiation. These studies open avenues for structure-based scaffold improvement toward development as an antibacterial agent

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Association of the PHACTR1/EDN1 genetic locus with spontaneous coronary artery dissection

Background: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene. Objectives: This study sought to test the association between the rs9349379 genotype and SCAD. Methods: Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD. Results: The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence. Conclusions: The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression