Accumulating evidence suggests that the copper-binding amyloid precursor protein (APP) has an essential synaptic function. APP synaptogenic function depends on trans-directed dimerization of the extracellular E1 domain encompassing a growth factor-like domain (GFLD) and a copper-binding domain (CuBD). Here we report the 1.75 Å crystal structure of the GFLD in complex with a copper ion bound with high affinity to an extended hairpin loop at the dimerization interface. In coimmunoprecipitation assays copper binding promotes APP interaction, whereas mutations in the copper-binding sites of either the GFLD or CuBD result in a drastic reduction in APP cisorientated dimerization. We show that copper is essential and sufficient to induce trans-directed dimerization of purified APP. Furthermore, a mixed culture assay of primary neurons with HEK293 cells expressing different APP mutants revealed that APP potently promotes synaptogenesis depending on copper binding to the GFLD. Together, these findings demonstrate that copper binding to the GFLD of APP is required for APP cis-/trans-directed dimerization and APP synaptogenic function. Thus, neuronal activity or diseaseassociated changes in copper homeostasis likely go along with altered APP synaptic function.

First-semester general chemistry is a known “gatekeeper” course due to its high failure rate. These higher education courses are taken by students who for the most part are regularly admitted freshmen, yet many struggle to succeed. In this investigation researchers from six higher-education institutions of varied sizes with student bodies of different ethnic composition teamed up to investigate the Math-Up Skills Test (MUST) as a potential tool to identify at-risk students in first-semester general chemistry (Chem I). A large population (N = 1073) was given the MUST at the beginning of the semester. The MUST had good internal consistency with the sample (Cronbach's alpha = 0.856). The MUST offers a quick 15 minute assessment of basic mathematics ability without a calculator. Instructors may find it easier than other documented predictors, which may take more time or involve obtaining student records (e.g., Math SAT). Results from the MUST support prior findings that mathematics skills correlate with course grades in chemistry. Poor arithmetic automaticity may be an underlying factor in lower performance by many students. With statistical modeling, the MUST, along with other demographic variables, was able to identify students who would go on to make a 69.5% or better in Chem I with a high percent of accuracy. The MUST, in tandem with other demographic variables, should be considered a potential tool for early identification of students at-risk for failing the class.

No abstract

This report summarizes one of the invited papers to the ConfChem online conference on Mathematics in Undergraduate Chemistry Instruction, held from October 23 to November 27, 2017, and hosted by the ACS DivCHED Committee on Computers in Chemical Education (CCCE). Combining data collected by a team of nine instructors from six Texas institutions for an IRB-approved investigation, this research correlated the arithmetic skills of first-year general chemistry students (n = 2127) to final course grades. The validated, highly reliable (KR-21 = 0.821) instrument, named the Math-Up Skills Test (MUST), evaluated the following topics using 16 questions: multiplication, division, fractions, scientific notation, exponential notation, logarithms, square roots, and balancing chemical equations. The MUST was given twice to each student: first without the use of a calculator followed by a similar, modified version with the use of a calculator. Outcomes suggest that general chemistry students’ arithmetic skills are more correlated with course grades when calculators are not used than when calculators are used. Perhaps more emphasis should be placed on improving students’ mathematics automaticity.