A large-scale peer teaching programme - acceptance and benefit.

INTRODUCTION: The involvement of students in the embodiment of university teaching through peer-assisted learning formats is commonly applied. Publications on this topic exclusively focus on strictly defined situations within the curriculum and selected target groups. This study, in contrast, presents and evaluates a large-scale structured and quality-assured peer teaching programme, which offers diverse and targeted courses throughout the preclinical part of the medical curriculum. METHODS: The large-scale peer teaching programme consists of subject specific and interdisciplinary tutorials that address all scientific, physiological and anatomic subjects of the preclinical curriculum as well as tutorials with contents exceeding the formal curriculum. In the study year 2013/14 a total of 1,420 lessons were offered as part of the programme. Paper-based evaluations were conducted over the full range of courses. Acceptance and benefit of this peer teaching programme were evaluated in a retrospective study covering the period 2012 to 2014. Usage of tutorials by students who commenced their studies in 2012/13 (n=959) was analysed from 2012 till 2014. Based on the results of 13 first assessments in the preclinical subjects anatomy, biochemistry and physiology, the students were assigned to one of five groups. These groups were compared according to participation in the tutorials. To investigate the benefit of tutorials of the peer teaching programme, the results of biochemistry re-assessments of participants and non-participants of tutorials in the years 2012 till 2014 (n=188, 172 and 204, respectively) were compared using Kolmogorov-Smirnov- and Chi-square tests as well as the effect size Cohen's d. RESULTS: Almost 70 % of the students attended the voluntary additional programme during their preclinical studies. The students participating in the tutorials had achieved different levels of proficiency in first assessments. The acceptance of different kinds of tutorials appears to correlate with their performance in first assessments. 94% of the students participating in tutorials offered in the study year 2013/14 rated the tutorials as "excellent" or "good". An objective benefit has been shown by a significant increase in re-assessment scores with an effect size between the medium and large magnitudes for participants of tutorials compared to non-participants in the years 2012, 2013 and 2014. In addition, significantly higher pass rates of re-assessments could be observed. CONCLUSION: Acceptance, utilisation and benefit of the assessed peer teaching programme are high. Beyond the support of students, a contribution to the individualisation of studies and teaching is made. Further studies are necessary to investigate possible influences of large-scale peer teaching programmes, for example on the reduction of study length and drop-off rates, as well as additional effects on academic achievements.

Hey bHLH Proteins Interact with a FBXO45 Containing SCF Ubiquitin Ligase Complex and Induce Its Translocation into the Nucleus.

The Hey protein family, comprising Hey1, Hey2 and HeyL in mammals, conveys Notch signals in many cell types. The helix-loop-helix (HLH) domain as well as the Orange domain, mediate homo- and heterodimerization of these transcription factors. Although distinct interaction partners have been identified so far, their physiological relevance for Hey functions is still largely unclear. Using a tandem affinity purification approach and mass spectrometry analysis we identified members of an ubiquitin E3-ligase complex consisting of FBXO45, PAM and SKP1 as novel Hey1 associated proteins. There is a direct interaction between Hey1 and FBXO45, whereas FBXO45 is needed to mediate indirect Hey1 binding to SKP1. Expression of Hey1 induces translocation of FBXO45 and PAM into the nucleus. Hey1 is a short-lived protein that is degraded by the proteasome, but there is no evidence for FBXO45-dependent ubiquitination of Hey1. On the contrary, Hey1 mediated nuclear translocation of FBXO45 and its associated ubiquitin ligase complex may extend its spectrum to additional nuclear targets triggering their ubiquitination. This suggests a novel mechanism of action for Hey bHLH factors.

ETO, but not leukemogenic fusion protein AML1/ETO, augments RBP-Jkappa/SHARP-mediated repression of notch target genes.

Notch is a transmembrane receptor that determines cell fates and pattern formation in all animal species. After specific ligand binding, the intracellular part of Notch is cleaved off and translocates to the nucleus, where it targets the DNA binding protein RBP-Jkappa. In the absence of Notch, RBP-Jkappa represses Notch target genes by recruiting a corepressor complex. We and others have previously identified SHARP as one component of this complex. Here, we show that the corepressor ETO as well as the leukemogenic fusion protein AML1/ETO directly interacts with SHARP, that ETO is part of the endogenous RBP-Jkappa-containing corepressor complex, and that ETO is found at Notch target gene promoters. In functional assays, corepressor ETO, but not AML1/ETO, augments SHARP-mediated repression in an histone deacetylase-dependent manner. Furthermore, either the knockdown of ETO or the overexpression of AML1/ETO activates Notch target genes. Therefore, we propose that AML1/ETO can disturb the normal, repressive function of ETO at Notch target genes. This activating (or derepressing) effect of AML1/ETO may contribute to its oncogenic potential in myeloid leukemia.