The Next Generation Science Standards (NGSS) [Achieve, Inc. []] represent a broad consensus that teaching and learning expectations must change. Rather than memorizing and reciting information, students are now expected to engage in science practices to develop a deep understanding of core science ideas. While we want to share in the optimism about NGSS, the standards are not a silver bullet for transforming science classrooms. They are, instead, another reform document designed to suggest opportunities for students to actively engage in knowledge construction themselves—to be doers of science, rather than receivers of facts. A foundational contradiction underlies these efforts—while we want students to do science, we seem to mean that students should mimic practices others have selected as important to learn, and content others have selected as foundational. As a result, students are rarely positioned with epistemic agency: the power to shape the knowledge production and practices of a community [Stroupe [] Science Education 98:487–516]. We argue that unless the field tackles significant questions around precisely how students can be active agents in knowledge construction, we will likely continue to implement learning environments that position students as receivers of scientific facts and practices, even as classrooms adopt NGSS. In this conceptual analysis article, we unpack the construct of “epistemic agency” and its relationship to the NGSS, using a vignette to illustrate how students are typically positioned in researcher‐developed curricula. The vignette, which describes a seventh‐grade class exploring which of two lakes is more at risk for invasion by the spiny water flea, provides an exemplar of what we take to be a loose consensus about learning environments consistent with the NGSS. However, when we look beneath the surface of the consensus, the vignette reveals contradictions and unresolved issues around epistemic agency.

BackgroundPodocytes are highly specialized epithelial cells on the visceral side of the glomerulus. Their interdigitating primary and secondary foot processes contain an actin based contractile apparatus that can adjust to changes in the glomerular perfusion pressure. Thus, the dynamic regulation of actin bundles in the foot processes is critical for maintenance of a well functioning glomerular filtration barrier. Since the actin binding protein, cofilin-1, plays a significant role in the regulation of actin dynamics, we examined its role in podocytes to determine the impact of cofilin-1 dysfunction on glomerular filtration.Methods and FindingsWe evaluated zebrafish pronephros function by dextran clearance and structure by TEM in cofilin-1 morphant and mutant zebrafish and we found that cofilin-1 deficiency led to foot process effacement and proteinuria. In vitro studies in murine and human podocytes revealed that PMA stimulation induced activation of cofilin-1, whereas treatment with TGF-β resulted in cofilin-1 inactivation. Silencing of cofilin-1 led to an accumulation of F-actin fibers and significantly decreased podocyte migration ability. When we analyzed normal and diseased murine and human glomerular tissues to determine cofilin-1 localization and activity in podocytes, we found that in normal kidney tissues unphosphorylated, active cofilin-1 was distributed throughout the cell. However, in glomerular diseases that affect podocytes, cofilin-1 was inactivated by phosphorylation and observed in the nucleus.ConclusionsBased on these in vitro and in vivo studies we concluded cofilin-1 is an essential regulator for actin filament recycling that is required for the dynamic nature of podocyte foot processes. Therefore, we describe a novel pathomechanism of proteinuria development.

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Vascular smooth muscle cells (SMC) maintained in high glucose are more responsive to IGF-I than SMC maintained in normal glucose due to a difference in the Shc phosphorylation response. In this study we aimed to determine the mechanism by which glucose regulates the sensitivity of SMC to IGF-I. For Shc to be phosphorylated in response to IGF-I it must be recruited to tyrosine-phosphorylated sites on Src homology 2 domain-containing phosphatase (SHP) substrate-1 (SHPS-1). The association of integrin-associated protein (IAP) with SHPS-1 is required for SHPS-1 tyrosine phosphorylation. When SMC were grown in 5 mm glucose, the amount of intact IAP was reduced, compared with SMC grown in 25 mm glucose. This reduction was due to proteolytic cleavage of IAP. Proteolysis of IAP resulted in loss of its SHPS-1 binding site, which led to loss of SHPS-1 phosphorylation. Analysis of the conditioned medium showed that there was more protease activity in the medium from SMC cultured in 5 mm glucose as compared with 25 mm. Inhibition of matrix metalloprotease-2 synthesis using RNA interference or its activity using a specific protease inhibitor protected IAP from cleavage. This protection was associated with an increase in IAP-SHPS-1 association, increased recruitment and phosphorylation of Shc, and increased cell growth in response to IGF-I. Our results show that the enhanced response of SMC in 25 mm glucose to IGF-I is due to the protection of IAP from proteolytic degradation, thereby increasing its association with SHPS-1 and allowing the formation of the SHPS-1-Shc signaling complex.

In this paper, we present a design solution that involves the bringing together of Project-based Learning (PBL) with the theory of usable knowledge (Pellegrino & Hilton, Developing transferable knowledge and skills in the 21st century, 2012). Usable knowledge is the ability to use ideas to solve problems and explain phenomena, an approach to science learning put forth by the Framework for K-12 Science Education (National Research Council (NRC), A framework for K-12 science education: Practices, crosscutting concepts, and core ideas, 2012) to optimize science learning environments. We offer a process for designing a curricular system that enhances how students learn science as a progression toward sophisticated practice of usable knowledge by focusing on coherence, depth, and motivation. We saw the potential of these distinct approaches for informing one another, and we extrapolate on 4 years of research that involves the process of iterating on our curricular design to best integrate the two approaches to support student learning.