Developing a problem-based learning (PBL) curriculum for professionalism and scientific integrity training for biomedical graduate students.

A multidisciplinary faculty committee designed a curriculum to shape biomedical graduate students into researchers with a high commitment to professionalism and social responsibility and to provide students with tools to navigate complex, rapidly evolving academic and societal environments with a strong ethical commitment. The curriculum used problem-based learning (PBL), because it is active and learner-centred and focuses on skill and process development. Two courses were developed: Scientific Professionalism: Scientific Integrity addressed discipline-specific and broad professional norms and obligations for the ethical practice of science and responsible conduct of research (RCR). Scientific Professionalism: Bioethics and Social Responsibility focused on current ethical and bioethical issues within the scientific profession, and implications of research for society. Each small-group session examined case scenarios that included: (1) learning objectives for professional norms and obligations; (2) key ethical issues and philosophies within each topic area; (3) one or more of the RCR instructional areas; and (4) at least one type of moral reflection. Cases emphasised professional standards, obligations and underlying philosophies for the ethical practice of science, competing interests of stakeholders and oversight of science (internal and external). To our knowledge, this is the first use of a longitudinal, multi-semester PBL course to teach scientific integrity and professionalism. Both faculty and students endorsed the active learning approach for these topics, in contrast to a compliance-based approach that emphasises learning rules and regulations.

Smooth muscle alpha-actin gene requires two E-boxes for proper expression in vivo and is a target of class I basic helix-loop-helix proteins.

Changes in the differentiated state of smooth muscle cells (SMCs) play a key role in vascular diseases, yet the mechanisms controlling SMC differentiation are still largely undefined. We addressed the role of basic helix-loop-helix (bHLH) proteins in SMC differentiation by first determining the role of two E-box (CAnnTG) motifs, binding sites for bHLH proteins, in the transcriptional regulation of the SMC differentiation marker gene, smooth muscle alpha-actin (SM alpha-actin), in vivo. Mutation of one or both E-boxes significantly reduced the expression of a -2560- to 2784-bp SM alpha-actin promoter/LacZ reporter gene in vivo in transgenic mice. We then determined the potential role of class I bHLH proteins, E12, E47, HEB, and E2-2, in SM alpha-actin regulation. In cotransfection experiments, E12, HEB, and E2-2 activated the SM alpha-actin promoter. Activation by HEB and E2-2 was synergistic with serum response factor. Additionally, the dominant-negative/inhibitory HLH proteins, Id2, Id3, and Twist, inhibited both the E12 and serum response factor-induced activations of the SM alpha-actin promoter. Finally, we demonstrated that E2A proteins (E12/E47) specifically bound the E-box-containing region of the SM alpha-actin promoter in vivo in the context of intact chromatin in SMCs. Taken together, these results provide the first evidence of E-box-dependent regulation of a SMC differentiation marker gene in vivo in transgenic mice. Moreover, they demonstrate a potential role for class I bHLH factors and their inhibitors, Id and Twist, in SM alpha-actin regulation and suggest that these factors may play an important role in control of SMC differentiation and phenotypic modulation.