TNNI3K delays atrioventricular conduction and reduces connexin-45 gap junctional coupling

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Dutch Research Council (NWO Talent Scheme) Introduction Cardiac conduction delay is the main substrate for triggering arrhythmias. Hence, prolongation of the PR interval on the electrocardiogram (ECG) is a strong predictor of atrial fibrillation, the most common cardiac arrhythmia. In previous research, cardiac troponin I-interacting kinase (TNNI3K) has been identified as a regulator of the PR interval. Various inbred mouse strains showed a correlation between Tnni3k expression levels and PR interval durations. Additionally, transgenic mice overexpressing hTNNI3K presented an extreme PR interval prolongation. Objective This study aims to unravel the mechanism underlying TNNI3K-driven PR interval prolongation. Methods ECG parameters were recorded in mice expressing physiological levels of Tnni3k (congenic), overexpressing hTNNI3K (TNNI3Ktg), or overexpressing kinase-dead hTNNI3K (TNNI3K-KDtg) and were compared to low-Tnni3k expressing DBA/2J control mice. Atrioventricular (AV) conduction was measured in Langendorff-perfused isolated hearts by electrical mapping. Cellular electrophysiology and conductance were measured using the (dual) patch-clamp technique. AV nodal collagen levels were identified by Pico Sirius Red staining. Candidate interactors were identified by immunoprecipitation of transfected HEK293A cell lysates. In stable HeLa-Connexin 45 (Cx45) cell lines expressing TNNI3K, Cx45 protein expression and phosphorylation levels were investigated by Western blot. Localisation of Cx45 was characterised by immunofluorescence. Results At six weeks of age, congenic and TNNI3Ktg mice show a 17% and 35% prolonged PR interval duration, respectively. Nonetheless, the PR interval of TNNI3K-KDtg mice did not change. Electrical mapping experiments on TNNI3Ktg mouse hearts show a corresponding AV conduction delay, which was neither driven by changes in cellular atrial cardiomyocyte electrophysiology nor driven by AV-nodal fibrosis. We next identified Cx45, a highly expressed connexin in the AV node, as a potential TNNI3K interactor. HeLa-Cx45 cells expressing TNNI3K demonstrated a reduced Cx45 conductance compared to controls without changes in kinetics. Moreover, we observed relatively decreased Cx45 phosphorylation and increased Cx45 intracellular accumulation. Conclusion We here present TNNI3K as a kinase-driven modulator of PR interval prolongation and AV conduction delay, which is independent of atrial electrophysiology and AV nodal fibrosis. We further identified Cx45 as a novel interactor of TNNI3K. The presence of TNNI3K reduces Cx45 gap junctional conductance and promotes intracellular Cx45 protein accumulation, which could explain the PR interval prolongation in vivo. Altogether, this study implies a crucial role for TNNI3K in AV nodal conduction. </jats:sec

Practice-Based Learning and Professional Education

This chapter discusses some ways in which practice-based learning experiences can be used in sustainable ways within professional education. It proposes that learning through engagement in authentic practice-based experiences is increasingly seen as an essential component of initial occupational preparatory programs offered through universities. Yet, how those experiences are organised and enacted, and integrated with the other experiences that comprise students' curriculum will be central to the quality of the learning outcomes they secure. In particular, it is proposed that a scholarly teaching practice needs to be developed by those who organise and enact these experiences (i.e. university teachers) that effectively engages, supports and integrates the contributions arising from student engagement in practice settings. It is proposed that existing concepts and practices within educational science may not always be helpful in guiding the effective utilisation of these experiences in educational programs, because its base is limited and new challenges are emerging. Hence, academics need to develop their understandings and these practices, and thereby inform both their practice and that science. This case is made through considering the nature and contributions of learning through practice, how that relates to the provision of professional education and ways in which the utilisation of these experiences can be sustainable and effective. In doing so, it draws upon the findings of a recent national teaching fellowship program involving 20 projects across a range of disciplines within six Australian universities that comprised university teachers engaging in projects that addressed practice-based concerns.Arts, Education & Law Group, School of Education and Professional StudiesNo Full Tex

Emerging Perspectives and the Challenges for Workplace Learning

The provision of learning experiences in work settings is becoming commonly discussed, included in educational programs at all levels, and seen as means of addressing individuals' need for learning across all stages of their working lives. Indeed, they are now being directed to an increasingly broad set of personal, workplace, community and national purposes. These purposes include developing skilful occupational capacities, those required for specific workplace performance, responding effectively to ongoing transformations in occupational practice and the changing performance requirements in workplaces. Yet, there is much still needed to be understood about these learning settings and improving their learning experiences. The scope of these concerns includes the provision of experiences to sustain workers' employability across the different stages in their working lives, and for securing, sustaining and extending their learning in ways that is essential for finding employment, remaining employed and then securing advancement across working lives. Here, concerns about the constant change and lengthening working lives come together as a dual set of problems that need addressing through workplace-based learning experiences. Then, there are emerging understandings about the learning process, what it comprises and how it is shaped and what this means for learning in socially authentic settings when individuals are engaged in goal-directed work activities. Given the significance of these purposes and the importance of these concerns, it is necessary that understandings about the processes of learning and means by which that learning is realised needs to be well informed and buoyed by current developments and emerging understandings. Consequently, it is helpful at this time to set out some of the emerging perspectives and note how they might redress some of the challenges for securing effective workplace learning.Arts, Education & Law Group, School of Education and Professional StudiesNo Full Tex

Students’ perceptions of STEM learning after participating in a summer informal learning experience

Abstract Background Informal learning environments increase students’ interest in STEM (e.g., Mohr‐Schroeder et al. School Sci Math 114: 291–301, 2014) and increase the chances a student will pursue a STEM career (Kitchen et al. Sci Educ 102: 529–547, 2018). The purpose of this study was to examine the impact of an informal STEM summer learning experience on student participants, to gain in-depth perspectives about how they felt this experience prepared them for their in-school mathematics and science classes as well as how it influenced their perception of STEM learning. Students’ attitudes and perceptions toward STEM are affected by their motivation, experience, and self-efficacy (Brown et al. J STEM Educ Innov Res 17: 27, 2016). The academic and social experiences students’ have are also important. Traditionally, formal learning is taught in a solitary form (Martin Science Education 88: S71–S82, 2004), while, informal learning is brimming with chances to connect and intermingle with peers (Denson et al. J STEM Educ: Innovations and Research 16: 11, 2015). Results We used a naturalistic inquiry, phenomenological approach to examine students’ perceptions of STEM while participating in a summer informal learning experience. Data came from students at the summer informal STEM learning experiences at three diverse institutions across the USA. Data were collected from reflection forms and interviews which were designed to explore students’ “lived experiences” (Van Manen 1990, p. 9) and how those experiences influenced their STEM learning. As we used a situative lens to examine the research question of how participation in an informal learning environment influences students’ perceptions of STEM learning, three prominent themes emerged from the data. The informal learning environment (a) provided context and purpose to formal learning, (b) provided students opportunity and access, and (c) extended STEM content learning and student engagement. Conclusions By using authentic STEM workplaces, the STEM summer learning experience fostered a learning environment that extended and deepened STEM content learning while providing opportunity and access to content, settings, and materials that most middle level students otherwise would not have access to. Students also acknowledged the access they received to hands-on activities in authentic STEM settings and the opportunities they received to interact with STEM professionals were important components of the summer informal learning experience