As many as 10% of humans suffer chronic sleep disturbances, yet the genetic mechanisms that regulate sleep remain essentially unknown. It is therefore crucial to develop simple and cost-effective vertebrate models to study the genetic regulation of sleep. The best characterized mammalian sleep/wake regulator is hypocretin/orexin (Hcrt), whose loss results in the sleep disorder narcolepsy and that has also been implicated in feeding behavior, energy homeostasis, thermoregulation, reward seeking, addiction, and maternal behavior. Here we report that the expression pattern and axonal projections of embryonic and larval zebrafish Hcrt neurons are strikingly similar to those in mammals. We show that zebrafish larvae exhibit robust locomotive sleep/wake behaviors as early as the fifth day of development and that Hcrt overexpression promotes and consolidates wakefulness and inhibits rest. Similar to humans with insomnia, Hcrtoverexpressing larvae are hyperaroused and have dramatically reduced abilities to initiate and maintain rest at night. Remarkably, Hcrt function is modulated by but does not require normal circadian oscillations in locomotor activity. Our zebrafish model of Hcrt overexpression indicates that the ancestral function of Hcrt is to promote locomotion and inhibit rest and will facilitate the discovery of neural circuits, genes, and drugs that regulate Hcrt function and sleep.

␣7 nAChRs are expressed widely throughout the brain, where they are important for synaptic signaling, gene transcription, and plastic changes that regulate sensory processing, cognition, and neural responses to chronic nicotine exposure. However, the mechanisms by which ␣7 nAChRs are regulated are poorly understood. Here we show that trafficking of ␣7-subunits is controlled by endogenous membrane-associated prototoxins in the Ly6 family. In particular, we find that Ly6h reduces cell-surface expression and calcium signaling by ␣7 nAChRs. We detect Ly6h in several rat brain regions, including the hippocampus, where we find it is both necessary and sufficient to limit the magnitude of ␣7-mediated currents. Consistent with such a regulatory function, knockdown of Ly6h in rat hippocampal pyramidal neurons enhances nicotine-induced potentiation of glutamatergic mEPSC amplitude, which is known to be mediated by ␣7 signaling. Collectively our data suggest a novel cellular role for Ly6 proteins in regulating nAChRs, which may be relevant to plastic changes in the nervous system including rewiring of glutamatergic circuitry during nicotine addiction.

Relating macromolecular “structure to function” is considered a foundational skill in biochemistry and molecular biology course curriculums. The molecular visualization skills necessary to interpret information in 3D models of biological macromolecules, however, are often lacking. Moreover, current technologies aimed at spanning this skills gap often require varying degrees of prior knowledge, training, and/or hardware requirements that can make implementation difficult. To address this we have developed a simple classroom activity using augmented reality technology that allows students to quickly and easily interact with high‐resolution images of a 3D macromolecule. The activity was implemented in a junior/senior level biochemistry course as part of a class discussion on the structure and function of the potassium channel. The 3D images were integrated as an iPad application in which a 3D virtual image of the molecule would appear superimposed on the real world on the iPad screen when the iPad camera was directed towards a printed QR code. Students were able to rotate, translate, and zoom in on the molecule by physically moving either the iPad or the QR code sheet. The activity was also accompanied with worksheet questions aimed at developing an interpretation of the 3D structure. Student attitudes were assessed using a pre/post survey analysis. Results indicate increases in student confidence towards visualizing the 3D structures of biological macromolecules, as well as an increase in positive student perceptions of the helpfulness of looking at 3D structures for learning protein biochemistry. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A recent push toward addressing antiracism in science reveals a need to integrate discussions of racism, social justice, and equity into undergraduate STEM classes. Toward this end, in Fall 2020, a theme of "Racism is a Public Health Emergency" was incorporated as an overlay for an existing undergraduate biochemistry curriculum. This theme was used throughout the entire semester and involved discussions of racism, social justice, and equity that were directly integrated with the science content of the course. Students enrolled in the class were surveyed at the end of the semester regarding their perceptions of integrating discussions of racism, social justice, and/or equity into chemistry courses. Students indicated that the inclusion of the overlay increased the relevance of the course material, indicated a high level of understanding of the impact of bias and race on the field of biochemistry, and expressed overwhelmingly positive views regarding future inclusion of similar themes of equity and antiracism in chemistry courses. Additionally, student scores and answers on common final exam questions were compared to previous semesters, revealing that the inclusion of this overlay did not negatively impact coverage of biochemistry content.

No abstract