Amyloid fibers are aggregated, yet highly ordered, β-sheet-rich assemblies of misfolded proteins. Order is established in such systems following profiles indicative of nucleation-dependent assembly. Nucleation dependence suggests that specific interactions, such as long-range contacts and/or strand registration, are critical to establishing initial fiber structure. Here, we show that amino acids at selected positions participate in key interactions that modulate the pathway of amyloid fiber formation by the hormone, islet amyloid polypeptide (IAPP). Specifically, we investigated the role of amide side-chain interactions in the process of IAPP assembly. We mutated five of the asparagine side chains in IAPP and assessed their effects on the kinetics of assembly. We find that the asparagine amide side chains strongly dictate the ability of IAPP to form fibers. In particular, the elimination of two specific asparagines results in near and total loss of amyloid, respectively. Interestingly, the two asparagines are located in a recently identified domain with α-helical bias. These sensitivities are unusual for IAPP, as IAPP is generally tolerant to mutation. Here, we demonstrate this mutational tolerance by assessing 10 alterations at five distinct sites. In all cases, the constructs form fibers on timescales perturbed by less than a factor of two compared with wild-type protein. These findings indicate the presence of key specific interactions that are the determinants of IAPP amyloid formation.

Prestin is the motor protein within the lateral membrane of outer hair cells (OHCs), and it is required for mammalian cochlear amplification. Expression of prestin precedes the onset of hearing in mice, and it has been suggested that prestin undergoes a functional maturation within the membrane coincident with the onset of hearing. We have developed a tetracycline-inducible prestin-expressing cell line that we have used to model prestin's functional maturation. We used prestin's voltage-dependent nonlinear charge movement (or nonlinear capacitance) as a test of function and correlated it to biochemical measures of prestin expressed on the cell surface. An initial stage of slow growth in charge density is accompanied by a rapid increase in our estimate of charge carried by an individual motor. A rapid growth in charge density follows and strongly correlates with an increasing ratio between an apparently larger and smaller monomer, suggesting that the latter exerts a dominant-negative effect on function. Finally, there is a gradual depolarizing shift in the voltage of peak capacitance, similar to that observed in developing OHCs. This inducible system offers many opportunities for detailed studies of prestin.

The Science Education Program for Public Understanding System (SEPUP) at the Lawrence Hall of Science at the University of California, Berkeley, recently redesigned its high school biology program, Science and Global Issues, which is centered around sustainability-related socioscientific issues. The goal of this work was to fill a gap in standards-based, sustainability-themed high school biology curricula. Curriculum developers began the redesign process by asking the question: What does it look like for students to think about sustainability/sustainable development in the context of operationalized goals for sustainability (such as the UN Sustainable Development Goals) while also allowing them to be successful in meeting rigorous science standards (in this case, the US Next Generation Science Standards)? The process used by the developers is described, from conceptualizing the program and units to enacting the program in student-facing materials. The framework for presenting sustainability to students is described, as are the specific contexts that allow students to develop a deep understanding of scientific concepts while addressing current and important socioscientific issues. A selection of feedback from teachers and students gathered during the field test of the curriculum is shared, as is feedback from teachers who used the published program. The developers concluded that sustainability provides a powerful framework for allowing students to learn biological concepts and apply them to real-world issues.

The Likert item response format for items is almost ubiquitous in the social sciences and has particular virtues regarding the relative simplicity of item-generation and the efficiency for coding responses. However, in this article, we critique this very common item format, focusing on its affordance for interpretation in terms of internal structure validity evidence. We suggest an alternative, the Guttman response format, which we see as providing a better approach for gathering and interpreting internal structure validity evidence. Using a specific survey-based example, we illustrate how items in this alternative format can be developed, exemplify how such items operate, and explore some comparisons between the results from using the two formats. In conclusion, we recommend usage of the Guttman response format for improving the interpretability of the resulting outcomes. Finally, we also note how this approach may be used in tandem with items that use the Likert response format to help balance efficiency with interpretability. Translational Abstract The Likert item response format for items, which features a stem statement, and a series of simple alternatives for the respondent (usually Strongly Agree to Strongly Disagree) is almost ubiquitous in the social sciences and has particular virtues regarding the relative simplicity of item-generation and the efficiency for coding responses. However, in this article, we critique this very common item format, focusing on its affordance for interpretation in terms of internal structure validity evidence, that is, whether there is evidence in the response data that supports the underlying structure of the latent variable being measured. We suggest an alternative, the Guttman response format, which we see as providing a better approach for gathering and interpreting this internal structure validity evidence. Using a specific survey-based example, we illustrate how items in this alternative format can be developed, exemplify how such items operate, and explore some comparisons between the results from using the two formats. In conclusion, we recommend usage of the Guttman response format for improving the interpretability of the resulting outcomes. Finally, we also note how this approach may be used in tandem with items that use the Likert response format to help balance efficiency with interpretability.

While the impact of authentic research experiences in STEM on student engagement and interest in science has been documented, less is known about the role of peer communities in fostering this interest and engagement. This research explores the idea that a strong peer community can catalyze deep learning and engagement in scientific research among high school students. The program engaged 20 high school students in a year-long community-based participatory research project in public health each year. The study used a mixed methods approach, combining data from focus group discussions, observations, and surveys to describe the program’s impact on participants. Analysis across three years reveals that (a) the program was associated with a statistically significant shift in students’ identity as researchers, with a medium growth effect size (Cohen's d) for the second and third years, which moderated by the end of the program, and (b) the peer community played a central role in the participants’ engagement in the program, on their identity as researchers, and strengthened their interest in STEM. These findings convey the importance of designing STEM experiences that build strong peer communities around science practices and how such communities can have profound impacts on students’ identities in STEM.