The stability of R-spine defines RAF inhibitor resistance: A comprehensive analysis of oncogenic BRAF mutants with in-frame insertion of αC-β4 loop.

Although targeting BRAF mutants with RAF inhibitors has achieved promising outcomes in cancer therapy, drug resistance remains a remarkable challenge, and underlying molecular mechanisms are not fully understood. Here, we characterized a previously unknown group of oncogenic BRAF mutants with in-frame insertions (LLR or VLR) of αC-β4 loop. Using structure modeling and molecular dynamics simulation, we found that these insertions formed a large hydrophobic network that stabilizes R-spine and thus triggers the catalytic activity of BRAF.

Looking at remembering: Eye movements, pupil size, and autobiographical memory.

To examine the relationship between visual imagery and autobiographical memory, eye position and pupil size were recorded while participants first searched for memories and then reconstructed the retrieved memories (Experiment 1), or only searched for memories (Experiment 2). In Experiment 1, we observed that, although recollective experience was not associated with the number of fixations per minute, memories that took longer to retrieve were linked to increased pupil size. In Experiment 2, we observed that directly retrieved memories were recalled more quickly and were accompanied by smaller pupils than generatively retrieved memories.