The mechanisms by which molecular chaperones assist quality control of cytosolic proteins are poorly understood. Analysis of the chaperone requirements for degradation of misfolded variants of a cytosolic protein, the VHL tumor suppressor, reveals that distinct chaperone pathways mediate its folding and quality control. While both folding and degradation of VHL require Hsp70, the chaperonin TRiC is essential for folding but is dispensable for degradation. Conversely, the chaperone Hsp90 neither participates in VHL folding nor is required to maintain misfolded VHL solubility but is essential for its degradation. The cochaperone HOP/Sti1p also participates in VHL quality control and may direct the triage decision by bridging the Hsp70-Hsp90 interaction. Our finding that a distinct chaperone complex is uniquely required for quality control provides evidence for active and specific chaperone participation in triage decisions and suggests that a hierarchy of chaperone interactions can control the alternate fates of a cytosolic protein.

Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are the most common hereditary cardiac conditions. Both are frequent causes of sudden death and are often associated with an adverse disease course. Alpha‐cardiac actin is one of the disease genes where different missense mutations have been found to cause either HCM or DCM. We have tested the hypothesis that the protein‐folding pathway plays a role in disease development for two actin variants associated with DCM and six associated with HCM. Based on a cell‐free coupled translation assay the actin variants could be graded by their tendency to associate with the chaperonin TCP‐1 ring complex/chaperonin containing TCP‐1 (TRiC/CCT) as well as their propensity to acquire their native conformation. Some variant proteins are completely stalled in a complex with TRiC and fail to fold into mature globular actin and some appear to fold as efficiently as the wild‐type protein. A fraction of the translated polypeptide became ubiquitinated and detergent insoluble. Variant actin proteins overexpressed in mammalian cell lines fail to incorporate into actin filaments in a manner correlating with the degree of misfolding observed in the cell‐free assay; ranging from incorporation comparable to wild‐type actin to little or no incorporation. We propose that effects of mutations on folding and fiber assembly may play a role in the molecular disease mechanism.

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The purpose of this study was to explore student perceptions of peer-evaluation experiences in an online RN-to-BSN nursing research course. A total of 140 students completed the online survey. A majority of students reported their peer-evaluation experience was helpful for learning (69%), and 81.8% of students indicated their writing skills improved. Findings of the study support the use of peer evaluation in online nursing courses.

Background: Discussion boards are frequently used as learning strategies in online nursing courses. Student perceptions of this strategy have not been fully explored. This study aimed to determine student perspectives and preferences of discussion boards as learning strategies in online accelerated nursing courses. Method: This mixed-method pilot study described RN-to-Bachelor of Science in Nursing (RN-to-BSN) ( n = 27) and Master of Science in Nursing: Nurse Educator (MSN-NE) ( n = 37) student perceptions and preferences for discussion boards as learning strategies. Results: Students had an overall positive perception about using discussion boards as learning strategies. RN-to-BSN students preferred a discussion summary over faculty participation. MSN-NE students preferred faculty participation but also found a summary to be helpful. Conclusion: A well-designed discussion can enhance student engagement and contribute to successful online learning experiences. Faculty should use a combination of real-time feedback through active participation and provide a discussion summary. Deciding how faculty should engage may depend on the complexity of course content being explored. [ J Nurs Educ . 2021;60(7):419–421.]