Mutations in the human TGFBI gene encoding TGFBIp have been linked to protein deposits in the cornea leading to visual impairment. The protein consists of an N-terminal Cys-rich EMI domain and four consecutive fasciclin 1 (FAS1) domains. We have compared the stabilities of wild-type (WT) human TGFBIp and six mutants known to produce phenotypically distinct deposits in the cornea. Amino acid substitutions in the first FAS1 (FAS1-1) domain (R124H, R124L, and R124C) did not alter the stability. However, substitutions within the fourth FAS1 (FAS1-4) domain (A546T, R555Q, and R555W) affected the overall stability of intact TGFBIp revealing the following stability ranking R555W>WT>R555Q>A546T. Significantly, the stability ranking of the isolated FAS1-4 domains mirrored the behavior of the intact protein. In addition, it was linked to the aggregation propensity as the least stable mutant (A546T) forms amyloid fibrils while the more stable variants generate non-amyloid amorphous deposits in vivo. Significantly, the data suggested that both an increase and a decrease in the stability of FAS1-4 may unleash a disease mechanism. In contrast, amino acid substitutions in FAS1-1 did not affect the stability of the intact TGFBIp suggesting that molecular the mechanism of disease differs depending on the FAS1 domain carrying the mutation.

Cells are under constant onslaught from several intrinsic and extrinsic stressors, which lead to the occurrence and accumulation of molecular damage, functional impairment, aging, and eventual death. Protein misfolding is both a cause and a consequence of increased cellular stress. An age-related failure of the complex systems for handling protein misfolding results in the accumulation of misfolded and aggregated proteins, and consequent conformational diseases. However, some misfolded proteins have been found to be both toxic and, in some cases, protective, highlighting the various complex, dynamic, and interdependent mechanisms at play. Molecular mechanisms are being elucidated for the occurrence of protein misfolding and for its prevention by chaperones and various pathways of degradation. Insights from the knowledge about proteodynamics are likely to impact future interventional strategies to counter stress and to promote healthy aging by preventing and/or treatment of protein conformational diseases.

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In higher education (HE), science and technology (STEM) institutions were early adopters of entrepreneurship education; recognizing that STEM majors in particular have a disproportional potential to form high-growth ventures in high-tech industries with high-value prospects. Yet, only limited empirical work has been carried out to shed light on how these programs are developed and how and why they are designed and organized the way that they are. What we do know typically comes to us from single-case reports on isolated programs. This study aims to provide deeper insights through an innovative and comprehensive research design that provides a way to compare and contrast case studies of five programs, developed by different educators, in different Nordic nations, and at different HE STEM institutions. The study mainly aims to explore how these cross-case and cross-national studies can guide future entrepreneurship education program development. However, considering the deliberate selection of comparable cases, this study finds a striking diversity in effective and successful programs, and uncovers strong interdependencies between program design and inception and the program developers. As such, in addition to providing guidance for program developers, the study identifies implications for other stakeholders; including students, university management, and entrepreneurship education research.

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