Identification of a Serum-Induced Transcriptional Signature Associated With Type 1 Diabetes in the BioBreeding Rat

OBJECTIVE - Inflammatory mediators associated with type 1 diabetes are dilute and difficult to measure in the periphery, necessitating development of more sensitive and informative biomarkers for studying diabetogenic mechanisms, assessing preonset risk, and monitoring therapeutic interventions. RESEARCH DESIGN AND METHODS - We previously utilized a novel bioassay in which human type 1 diabetes sera were used to induce a disease-specific transcriptional signature in unrelated, healthy peripheral blood mononuclear cells (PBMCs). Here, we apply this strategy to investigate the inflammatory state associated with type 1 diabetes in biobreeding (BB) rats. RESULTS - Consistent with their common susceptibility, sera of both spontaneously diabetic BB DRlyp/lyp and diabetes inducible BB DR+/+ rats induced transcription of cytokines, immune receptors, and signaling molecules in PBMCs of healthy donor rats compared with control sera. Like the human type 1 diabetes signature, the DRlyp/lyp signature, which is associated with progression to diabetes, was differentiated from that of the DR+/+ by induction of many interleukin (IL)-1-regulated genes. Supplementing cultures with an IL-1 receptor antagonist (IL-1Ra) modulated the DRlyp/lyp signature (P < 10-6), while administration of IL-1Ra to DRlyp/lyp rats delayed onset (P = 0.007), and sera of treated animals did not induce the characteristic signature. Consistent with the presence of immunoregulatory cells in DR+/+ rats was induction of a signature possessing negative regulators of transcription and inflammation. CONCLUSIONS - Paralleling our human studies, serum signatures in BB rats reflect processes associated with progression to type 1 diabetes. Furthermore, these studies support the potential utility of this approach to detect changes in the inflammatory state during therapeutic intervention

Integrating Teaching and Research in Undergraduate Biology Laboratory Education

A course recently designed and implemented at Stanford University applies practical suggestions for creating research-based undergraduate courses that benefit both teaching and research

Academic misconduct, misrepresentation and gaming: a reassessment

The motivation for this Special Issue is increasing concern not only with academic misconduct but also with less easily defined forms of misrepresentation and gaming. In an era of intense emphasis on measuring academic performance, there has been a proliferation of scandals, questionable behaviors and devious stratagems involving not just individuals but also organizations, including universities, editors and reviewers, journal publishers, and conference organizers. This introduction first reviews the literature on the prevalence of academic misconduct, misrepresentation and gaming (MMG). The core of the article is organized around a life-cycle model of the production and dissemination of research results. We synthesize the findings in the MMG literature at the level of the investigator or research team, emphasizing that misbehavior extends well beyond fabrication and falsification to include behaviors designed to exaggerate or to mislead readers as to the significance of research findings. MMG is next explored in the post-research review, publication, and post-publication realms. Moving from the individual researcher to the organizational level, we examine how MMG can be engaged in by either journals or organizations employing or funding the researchers. The changing institutional environment including the growth of research assessment exercises, increased quantitative output measurement and greater pressure to publish may all encourage MMG. In the final section, we summarize the main conclusions and offer suggestions both on how we might best address the problems and on topics for future research