To scaffold the development of problem-solving skills in chemistry, chemistry educators are exploring a variety of instructional techniques. In this study, we have designed, implemented, and evaluated a problem-solving workflow – “Goldilocks Help”. This workflow builds on work done in the field of problem solving in chemistry and provides specific scaffolding for students who experience procedural difficulties during problem solving, such as dead ends (not being able to troubleshoot) and false starts (not knowing how to initiate the problem-solving process). The Goldilocks Help workflow has been designed to scaffold a systematic problem-solving process with a designation of explicit phases of problem solving, to introduce students to the types of questions/prompts that should guide them through the process, to encourage explicit reasoning necessary for successful conceptual problem solving, and to promote the development of metacognitive self-regulation skills. The tool has been implemented and evaluated over a two-year period and modified based on student and instructor feedback. The evaluation demonstrated a shift in students’ beliefs in their capacities to use the strategies required to achieve successful problem solving and showed their capacity to employ such strategies.

l-DOPA treatment for Parkinson’s disease frequently leads to dyskinesias, the pathophysiology of which is poorly understood. We used MALDI-MSI to map the distribution of l-DOPA and monoaminergic pathways in brains of dyskinetic and nondyskinetic primates. We report elevated levels of l-DOPA, and its metabolite 3-O-methyldopa, in all measured brain regions of dyskinetic animals and increases in dopamine and metabolites in all regions analyzed except the striatum. In dyskinesia, dopamine levels correlated well with l-DOPA levels in extrastriatal regions, such as hippocampus, amygdala, bed nucleus of the stria terminalis, and cortical areas, but not in the striatum. Our results demonstrate that l-DOPA–induced dyskinesia is linked to a dysregulation of l-DOPA metabolism throughout the brain. The inability of extrastriatal brain areas to regulate the formation of dopamine during l-DOPA treatment introduces the potential of dopamine or even l-DOPA itself to modulate neuronal signaling widely across the brain, resulting in unwanted side effects.

Fluorescently labeled ligands are useful pharmacological research tools for studying receptor localization, trafficking, and signaling processes via fluorescence imaging. They are also employed in fluorescent binding assays. This study is centered on the design, synthesis, and pharmacological evaluation of fluorescent probes for the opioid receptors, for which relatively few non-peptidic fluorescent probes currently exist. The known μ-opioid receptor (MOR) partial agonist, buprenorphine, was structurally elaborated to include an amidoalkylamine linker moiety that was coupled with a range of fluorophores to afford new fluorescent probes. All compounds proved to be selective MOR antagonists. Confocal fluorescence microscopy studies revealed that the probe incorporating a sulfonated cyanine-5 fluorophore was the most appropriate for imaging studies. This ligand was subsequently employed in an automated fluorescence-based competition binding assay, allowing the pKi values of several well-known opioid ligands to be determined. Thus, this new probe will prove useful in future studies of MOR receptor pharmacology.