Pressure overload induces ISG15 to facilitate adverse ventricular remodeling and promote heart failure.

Inflammation promotes adverse ventricular remodeling, a common antecedent of heart failure. Here, we set out to determine how inflammatory cells affect cardiomyocytes in the remodeling heart. Pathogenic cardiac macrophages induced an IFN response in cardiomyocytes, characterized by upregulation of the ubiquitin-like protein IFN-stimulated gene 15 (ISG15), which posttranslationally modifies its targets through a process termed ISGylation. Cardiac ISG15 is controlled by type I IFN signaling, and ISG15 or ISGylation is upregulated in mice with transverse aortic constriction or infused with angiotensin II; rats with uninephrectomy and DOCA-salt, or pulmonary artery banding; cardiomyocytes exposed to IFNs or CD4+ T cell-conditioned medium; and ventricular tissue of humans with nonischemic cardiomyopathy. By nanoscale liquid chromatography-tandem mass spectrometry, we identified the myofibrillar protein filamin-C as an ISGylation target. ISG15 deficiency preserved cardiac function in mice with transverse aortic constriction and led to improved recovery of mouse hearts ex vivo. Metabolomics revealed that ISG15 regulates cardiac amino acid metabolism, whereas ISG15 deficiency prevented misfolded filamin-C accumulation and induced cardiomyocyte autophagy. In sum, ISG15 upregulation is a feature of pathological ventricular remodeling, and protein ISGylation is an inflammation-induced posttranslational modification that may contribute to heart failure development by altering cardiomyocyte protein turnover.

Covidaze Juggle: Undergraduate Teaching Assistants (TAs) with a Large Online Freshmen Course

As undergraduate students in a Health Sciences Program we were selected as teaching assistants (TAs) in a freshman introductory Cellular and Molecular Biology course that we had all taken in a standard format. The course was tightly focused on cell communication (Adv Physiol Educ 36: 13?19, 2012, Biochem Mol Biol Educ. 2013 May-Jun;41(3):145-55). The new version was offered synchronously on-line to 273 students who were in different time zones (within Canada and abroad, Africa, Asia). Didactic sessions (both flipped/non-flipped) were followed by TA sessions (60-90 mins.) designed to help students consolidate content and prepare them for active assessments used (The FASEB Journal, 31: 575.2-575.2.). Each tutorial Group had on the average, twenty students. For the tutorials, we met them in virtual break-out rooms where we had considerable flexibility to organize our sessions. Larger groups were reconvened to meet the instructors either on the same day or on a separate session. These sessions served to further consolidate their learning. In addition, we had the options of organizing office hours on our own to deal with our students. We were taking several of our own on-line courses in parallel. These dual obligations as teachers in one course and learners for several others posed many challenges. As teachers, we had to foster engagement, promote interactions, gauge comprehension, maintain enthusiasm, identify individual learning needs despite lack of verbal, non-verbal cues as many students remained both silent and invisible and also deal with technical glitches. To prepare for our own courses we faced similar technical issues, maintained enthusiasm, battled online fatigue, engaged with our Professors and TAs, dealt with conflicting schedules, found resources, remained flexible, and stayed focused as the lack of a distinct campus environment blurred boundaries between home and academia. We adapted rapidly to cope with these concurrent contrary demands.