Integrative STEM education for undergraduate neuroscience: Design and implementation.

As an integrative discipline, neuroscience can serve as a vehicle for the development of integrative thinking skills and broad-based scientific proficiency in undergraduate students. Undergraduate neuroscience curricula incorporate fundamental concepts from multiple disciplines. Deepening the explicit exploration of these connections in a neuroscience core curriculum has the potential to support more meaningful and successful undergraduate STEM learning for neuroscience students. Curriculum and faculty development activities related to an integrative core curriculum can provide opportunities for faculty across disciplines and departments to advance common goals of inclusive excellence in STEM. These efforts facilitate analysis of the institutional STEM curriculum from the student perspective, and assist in creating an internal locus of accountability for diversity, equity, and inclusion within the institution. Faculty at the College of the Holy Cross have undertaken the collaborative design and implementation of an integrative core curriculum for neuroscience that embraces principles of inclusive pedagogy, emphasizes the connections between neuroscience and other disciplines, and guides students to develop broad proficiency in fundamental STEM concepts and skills.

An Integrative Approach to STEM Concepts in an Introductory Neuroscience Course: Gains in Interdisciplinary Awareness.

Neuroscience is an integrative discipline for which students must achieve broad-based proficiency in many of the sciences. We are motivated by the premise that student pursuit of proficiency in science, technology, engineering, and mathematics (STEM) can be supported by awareness of the application of knowledge and tools from the various disciplines for solving complex problems. We refer to this awareness as "interdisciplinary awareness." Faculty from biology, chemistry, mathematics/computer science, physics, and psychology departments contributed to a novel integrative introductory neuroscience course with no pre-requisites. STEM concepts were taught in "flipped" class modules throughout the semester: Students viewed brief videos and completed accompanying homework assignments independently. In subsequent class meetings, students applied the STEM concepts to understand nervous system structure and function through engaged learning activities. The integrative introduction to neuroscience course was compared to two other courses to test the hypothesis that it would lead to greater gains in interdisciplinary awareness than courses that overlap in content but were not designed for this specific goal. Data on interdisciplinary awareness were collected using previously published tools at the beginning and end of each course, enabling within-subject analyses. Students in the integrative course significantly increased their identification of scientific terms as relevant to neuroscience in a term-discipline relevance survey and increased their use of terms related to levels of analysis (e.g., molecular, cellular, systems) in response to an open-ended prompt. These gains were seen over time within the integrative introduction to neuroscience course as well as relative to the other two courses.

Insect ryanodine receptor: distinct but coupled insecticide binding sites for [N-C(3)H(3)]chlorantraniliprole, flubendiamide, and [(3)H]ryanodine.

Radiolabeled anthranilic diamide insecticide [N-C(3)H(3)]chlorantraniliprole was synthesized at high specific activity. It was compared with phthalic diamide insecticide flubendiamide and [(3)H]ryanodine in radioligand binding studies with house fly muscle membranes to provide the first direct evidence with a native insect ryanodine receptor that the major anthranilic and phthalic diamide insecticides bind at different allosterically coupled sites, i.e., there are three distinct Ca(2+)-release channel targets for insecticide action.

Design, synthesis, and biological evaluation of estrone-derived hedgehog signaling inhibitors.

The design, synthesis and biological evaluation of new analogs of the naturally occurring compound cyclopamine, a Hedgehog signaling inhibitor, are described. Stucture-activity relationship studies lead to an evolving model for the pharmacophore of this medically promising compound class of anti-cancer chemotherapeutic agents.

Studies directed toward the elucidation of the pharmacophore of steroid-based Sonic Hedgehog signaling inhibitors.

Previous work from our laboratory has established that the readily available steroid-based analog 2 of cyclopamine 1 is, like 1, a highly potent inhibitor of Hedgehog signaling. The first structure-activity relationship studies on 2, i.e., the synthesis and biological evaluation of both the C-17 epi analog 4 and the C-3 deoxy analog 11, both of which are more potent than cyclopamine 1, are described. The implications of these results for the emerging pharmacophore of these Sonic Hedgehog signaling inhibitors are discussed.

Asymmetric total synthesis of rollicosin.

[structure: see text] The first total synthesis of rollicosin, a member of a rare subgroup of Annonaceous acetogenins containing two terminal gamma-lactones, is reported. The approach features a highly regio- and stereoselective tandem ring-closing/cross-metathesis reaction for construction of the east-wing lactone and incorporation of the alkyl spacer. Establishment of the C4 stereocenter and addition of the west-wing lactone were achieved by Sharpless asymmetric dihydroxylation and enolate alkylation.

Concise total synthesis of (-)-muricatacin by tandem ring-closing/cross metathesis.

A strategy for the synthesis of chiral 5-(1-hydroxyalk-2-enyl)-5H-furan-2-ones and its application to the total synthesis of (-)-muricatacin, in four steps and 37% overall yield from (R,R)-hexa-1,5-diene-3,4-diol, are described. The key synthetic step in this approach is a highly regioselective and stereoselective tandem ring-closing/cross metathesis reaction in which both lactone formation and alkyl chain extension are accomplished in an efficient one-pot process.