Development of an Online SARS-CoV-2/COVID-19 Elective Course for Fourth-Year Medical Students.

As a result of the COVID-19 pandemic, the Paul L. Foster School of Medicine incorporated supplementary online learning for 4th year medical students who were unable to participate in clinical activities due to clinical site restrictions to reduce SARS-CoV-2 transmission. An online elective was developed aimed to increase student knowledge of COVID-19: "COVID-19: Utilizing basic sciences to implement what you need to know as a physician." This course required students to further their understanding of SARS-CoV-2 and COVID-19 through directed self-study to identify and summarize the latest scientific literature followed by presenting an online seminar to peers and faculty.

Analysis of Pre-clerkship Medical Students' Perceptions and Performance During the COVID-19 Pandemic.

Purpose: Virtual instruction became the primary educational delivery method for pre-clerkship medical students during the COVID-19 pandemic. The aims of this study were to evaluate the effectiveness of a virtual and blended pre-clerkship curriculum and to assess its impact on students. Methods: We surveyed 223 1st- and 2nd-year medical students (MS1s and MS2s) enrolled at the Paul L Foster School of Medicine. We analyzed student satisfaction with their courses, along with summative exam scores, compared to previous academic years. Results: The survey was completed by 125 of 223 students (56%). Most students changed their study methods (78%), experienced technical issues (85%), and had difficulty communicating with faculty (62%). MS1s were significantly more likely than MS2s to report difficulty in adjusting to virtual instruction (p = 0.037) and a negative impact on their learning skills (p = 0.005) and academic performance (p = 0.003). Students reported the virtual environment negatively affected their social skills (77%), connectedness to peers (89%), and professional development (62%). MS1s were more likely than MS2s to perceive a negative effect on their sense of wellness (p = 0.002). The overall satisfaction with the courses was similar to previous academic years. Student performance in the summative examination of the first virtually delivered unit was lower (p = 0.007) than the previous year's cohorts. Conclusion: The difference in MS1s and MS2s perceptions of virtual and blended instruction highlights the importance of face-to-face learning during the first year. Benefits and drawbacks were identified which may help inform educators when designing future learning models. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-022-01723-6.

Personalized Medicine in Undergraduate Medical Education: a Spiral Learning Model.

Educational strategies to introduce medical students to scientific advances are needed as evidence continues to evolve regarding their clinical application in personalized medicine. Our overall project goal is to design an evidence-based, clinically relevant, personalized medicine curriculum spanning the 4 years of undergraduate medical education.

Translational regulation of the JunD messenger RNA.

JunD, a member of the Jun family of nuclear transcription proteins, dimerizes with Fos family members or other Jun proteins (c-Jun or JunB) to form the activator protein 1 (AP-1) transcription factor. The junD gene contains no introns and generates a single mRNA. Here we show that two predominant JunD isoforms are generated by alternative initiation of translation, a 39-kDa full-length JunD protein (JunD-FL) by initiation at the first AUG codon downstream of the mRNA 5' cap and a shorter, 34-kDa JunD protein (DeltaJunD) by initiation at a second in-frame AUG codon. The JunD mRNA contains a long, G/C-rich 5'-untranslated region that is predicted to be highly structured and is important for regulating the ratio of JunD-FL and DeltaJunD protein expression. A third functional out-of-frame AUG directs translation from a short open reading frame positioned between the JunD-FL and DeltaJunD start sites. In addition, three non-AUG codons also support translation, an ACG codon (in-frame with JunD) and a CUG are positioned in the 5'-untranslated region, and a CUG codon (also in-frame with JunD) is located downstream of the short open reading frame. Mutation of these start sites individually had no affect on DeltaJunD protein levels, but mutation of multiple upstream start sites led to an increase in DeltaJunD protein levels, indicating that these codons can function cumulatively to suppress DeltaJunD translation. Finally, we show that the JunD mRNA does not possess an internal ribosome entry site and is translated in a cap-dependent manner.

Regulation of two JunD isoforms by Jun N-terminal kinases.

The JunD transcription factor is one member of the Jun family of proteins that also includes c-Jun and JunB. Although c-Jun can function to promote cell proliferation and can cooperate with other oncogenes to transform cells, JunD slows proliferation of fibroblasts and antagonizes transformation by activated ras. Two isoforms of JunD, a full-length isoform containing 341 amino acids (JunD-FL) and a truncated isoform lacking 48 amino acids at the N terminus (Delta JunD), are generated through utilization of two translation start sites within a single mRNA. Here we show that both isoforms of JunD are phosphorylated by Jun N-terminal kinases (JNKs) at three identical residues and that both contain a docking domain that specifically binds JNKs. The JunD-FL isoform binds to and is phosphorylated by JNK more efficiently than Delta JunD in vitro; correspondingly, JunD-FL is a more potent transcriptional activator than Delta JunD. Although increased JNK signaling can activate both JunD isoforms, mutating either the JNK docking domain or the target JNK phosphorylation sites blocks this activation. These results identify two distinct isoforms of JunD with differential responses to JNK signaling pathways.

Transcriptional activity of CCAAT/enhancer-binding proteins is controlled by a conserved inhibitory domain that is a target for sumoylation.

CCAAT/enhancer-binding proteins (C/EBPs) are basic region/leucine zipper transcription factors that function as regulators of cell growth and differentiation in numerous cell types. We previously localized transcriptional activation and inhibitory regions in one family member, C/EBP epsilon. Here we describe the further characterization of a C/EBP epsilon inhibitory domain termed regulatory domain I. We show that functionally related domains are present in C/EBP alpha, C/EBP beta, and C/EBP delta. These domains contain an evolutionarily conserved five-amino acid motif (the regulatory domain motif (RDM)) that conforms to the consensus sequence (I/V/L)KXEP. Mutagenesis studies revealed that the residues at positions 1, 2, and 4 of the RDM are critical for inhibitory domain function. Data base searches identified RDM-like sequences in a number of nuclear proteins. We found that small regions from c-Jun, JunB, and JunD containing this sequence also function as transcriptional inhibitory domains. Importantly, the RDM is similar to the recognition sequence for attachment of the ubiquitin-like protein, small ubiquitin-like modifier-1 (SUMO-1), and the conserved lysine residue of each C/EBP RDM served as an attachment site for SUMO-1. SUMO-1 attachment decreased the inhibitory effect of the C/EBP epsilon regulatory domain, suggesting that sumoylation may play an important role in modulating C/EBP epsilon activity as well as that of the other C/EBP family members.