Heterologous prion-forming proteins interact to cross-seed aggregation in Saccharomyces cerevisiae

AbstractThe early stages of protein misfolding remain incompletely understood, as most mammalian proteinopathies are only detected after irreversible protein aggregates have formed. Cross-seeding, where one aggregated protein templates the misfolding of a heterologous protein, is one mechanism proposed to stimulate protein aggregation and facilitate disease pathogenesis. Here, we demonstrate the existence of cross-seeding as a crucial step in the formation of the yeast prion [PSI+], formed by the translation termination factor Sup35. We provide evidence for the genetic and physical interaction of the prion protein Rnq1 with Sup35 as a predominant mechanism leading to self-propagating Sup35 aggregation. We identify interacting sites within Rnq1 and Sup35 and determine the effects of breaking and restoring a crucial interaction. Altogether, our results demonstrate that single-residue disruption can drastically reduce the effects of cross-seeding, a finding that has important implications for human protein misfolding disorders.</jats:p

Subjectivity and Mutuality: Feminist Theology in Film

One of the central concepts in feminist film criticism is that of gaze, also called male gaze: the objectifying lens, both literal and metaphorical, that an assumed default male viewer has through media that depicts women from a masculine point of view. This gaze is constructed as necessarily objectifying; when scholars posit a female gaze, it is sometimes also cast as objectifying, simply swapping the genders of the seer and the seen. I argue that gaze can also be subjectifying through the process of relation between people who hold each other in equal regard and do not assert power one over the other. In both seeing and being seen, there is power to restore agency to the objectified through reciprocal relation. I explore this idea in the context of film, not only as a vehicle of illustration, but also as an interaction between artist and audience, and assert that gaze has equal power to harm or heal, and to reduce or restore agency

The Importance of Formative Assessment in Science and Engineering Ethics Education: Some Evidence and Practical Advice

Recent research in ethics education shows a potentially problematic variation in content, curricular materials, and instruction. While ethics instruction is now widespread, studies have identified significant variation in both the goals and methods of ethics education, leaving researchers to conclude that many approaches may be inappropriately paired with goals that are unachievable. This paper speaks to these concerns by demonstrating the importance of aligning classroom-based assessments to clear ethical learning objectives in order to help students and instructors track their progress toward meeting those objectives. Two studies at two different universities demonstrate the usefulness of classroom-based, formative assessments for improving the quality of students’ case responses in computational modeling and research ethics

Costs and Revenues Associated With Overweight Trucks in Indiana

This study established the unit costs of pavement and bridge damage due to overweight vehicles, and discussed issues concerning overweight vehicle e enforcement in Indiana. The study identified gaps in the existing practice and research, and established a practical framework that includes the development of asset families; establishment of realistic types and timings of reconstruction, rehabilitation, and maintenance, traffic volumes and growth projections; and damage cost estimation for each asset family and age group. The sensitivity of asset damage cost with respect to key policy and analysis variables was explored. Finally, the study examined the cost and operational issues associated with the enforcement of overweight truck policies. For pavement assets, the damage cost estimates were found to range from $0.006 per ESAL-mile on Interstates to$0.218 per ESAL-mile on non-national highways. The results also suggested that the pavement damage cost estimates are highly sensitive to the pavement life-cycle length, interest rate, rest period, and the costs and service lives of rehabilitation treatments. For bridges, an incremental-design methodology was used to assign damage cost to vehicle classes based on axle configurations and vehicle-miles of travel. Each FHWA vehicle weight group was classified into an equivalent AASHTO loading using the modified equivalent vehicle model which is based on gross vehicle weight, axle loading and axle spacing. Adopting a permit structure on the basis of gross vehicle weight only, will result in some vehicles underpaying by as much as 92% of their actual contribution to bridge damage. Finally, the study examined the cost and operational issues associated with the enforcement of overweight truck policies and made recommendations regarding equipment types and locations, staffing, and staff schedules, in order to promote cost-effective practices in weight enforcement