7We have developed new open-source software called cisTEM (computational imaging system 8 for transmission electron microscopy) for the processing of data for high-resolution electron 9 cryo-microscopy and single-particle averaging. cisTEM features a graphical user interface that is 10 used to submit jobs, monitor their progress, and display results. It implements a full processing 11 pipeline including movie processing, image defocus determination, automatic particle picking, 12 2D classification, ab-initio 3D map generation from random parameters, 3D classification, and 13high-resolution refinement and reconstruction. Some of these steps implement newly-developed 14 algorithms; others were adapted from previously published algorithms. The software is 15 optimized to enable processing of typical datasets (2000 micrographs, 200k -300k particles) on 16 a high-end, CPU-based workstation in half a day or less, comparable to GPU-accelerated 17 processing. Jobs can also be scheduled on large computer clusters using flexible run profiles that 18 can be adapted for most computing environments.

Biological membrane of many cell types contains large-pore channels that permeate a wide variety of ions and metabolites. Examples include connexin, innexin, and pannexin, which form gap junctions and/or bona fide cell surface channels. The most recently identified large-pore channels are the calcium homeostasis modulators (CALHMs), which permeate ions and ATP in a voltage-dependent manner to control neuronal excitability, taste signaling, and pathologies of depression and Alzheimer’s disease. Despite such critical biological roles, the structures and patterns of oligomeric assembly remain unclear. Here, we reveal the structures of two CALHMs, chicken CALHM1 and human CALHM2, by single particle cryo-electron microscopy, which show novel assembly of the four transmembrane helices into channels of 8-mers and 11-mers, respectively. Furthermore, molecular dynamics simulations suggest that lipids can favorably assemble into a bilayer within the larger CALHM2 pore, but not within CALHM1, demonstrating the potential correlation between pore-size, lipid accommodation, and channel activity.

Middle school students with learning disabilities in math (MLD) used two versions of Enhanced Anchored Instruction (EAI). In one condition, students learned how to compute with fractions on an as-needed basis while they worked to solve the EAI problems. In the other condition, teachers used a computer-based instructional module in place of one of the EAI problems to deliver formal fraction instruction. The results indicated that students in both instructional formats improved their fraction computational skills and that formal instruction provided an added benefit. Both instructional conditions improved students' problem-solving skills by about the same amount. The findings suggest that combining formal fraction instruction with EAI is a viable way to improve the problem-solving and computational skills of students with MLD.

No abstract