RESUMEN
Research-oriented universities are known for prolific research activity that is often supported by students in faculty-guided research. To maintain ethical standards, universities require on-going training of both faculty and students to ensure Responsible Conduct of Research (RCR). However, previous research has indicated RCR-based training is insufficient to address the ethical dilemmas that are prevalent within academic settings: navigating issues of authorship, modeling relationships between faculty and students, minimization of risk, and adequate informed consent. U.S. universities must explore ways to identify and improve RCR concerns for current (faculty) and future researchers (students). This article reports the findings of a self-study (N = 50) of research stakeholders (students and faculty) at a top tier research institution. First, we report on their perceived importance of applying RCR principles. Second, we explore relationships between stakeholder backgrounds (e.g., prior training, field, and position) and how they ranked the degree of ethical concerns in fictitious vignettes that presented different unethical issues university students could encounter when conducting research. Vignette rankings suggested concerns of inappropriate relationships, predatory authorship and IRB violations which were judged as most unethical, which was dissimilar to what sampled researchers reported in practice as the most important RCR elements to understand and adhere to for successful research. Regression models indicated there was no significant relationship between individuals' vignette ethics scores and backgrounds, affirming previous literature suggesting that training can be ineffectual in shifting researcher judgments of ethical dilemmas. Recommendations for training are discussed.
RESUMEN
Recent studies implicate the muscle-specific ubiquitin ligase muscle RING finger-1 (MuRF1) in inhibiting pathological cardiomyocyte growth in vivo by inhibiting the transcription factor SRF. These studies led us to hypothesize that MuRF1 similarly inhibits insulin-like growth factor-I (IGF-I)-mediated physiological cardiomyocyte growth. We identified two lines of evidence to support this hypothesis: IGF-I stimulation of cardiac-derived cells with MuRF1 knockdown 1) exhibited an exaggerated hypertrophy and, 2) conversely, increased MuRF1 expression-abolished IGF-I-dependent cardiomyocyte growth. Enhanced hypertrophy with MuRF1 knockdown was accompanied by increases in Akt-regulated gene expression. Unexpectedly, MuRF1 inhibition of this gene expression profile was not a result of differences in p-Akt. Instead, we found that MuRF1 inhibits total protein levels of Akt, GSK-3ß (downstream of Akt), and mTOR while limiting c-Jun protein expression, a mechanism recently shown to govern Akt, GSK-3ß, and mTOR activities and expression. These findings establish that MuRF1 inhibits IGF-I signaling by restricting c-Jun activity, a novel mechanism recently identified in the context of ischemia-reperfusion injury. Since IGF-I regulates exercise-mediated physiological cardiac growth, we challenged MuRF1(-/-) and MuRF1-Tg+ mice and their wild-type sibling controls to 5 wk of voluntary wheel running. MuRF1(-/-) cardiac growth was increased significantly over wild-type control; conversely, the enhanced exercise-induced cardiac growth was lost in MuRF1-Tg+ animals. These studies demonstrate that MuRF1-dependent attenuation of IGF-I signaling via c-Jun is applicable in vivo and establish that further understanding of this novel mechanism may be crucial in the development of therapies targeting IGF-I signaling.