Micro-electron diffraction structure of the aggregation-driving N terminus of Drosophila neuronal protein Orb2A reveals amyloid-like ß-sheets.

Amyloid protein aggregation is commonly associated with progressive neurodegenerative diseases, however not all amyloid fibrils are pathogenic. The neuronal cytoplasmic polyadenylation element binding protein is a regulator of synaptic mRNA translation and has been shown to form functional amyloid aggregates that stabilize long-term memory. In adult Drosophila neurons, the cytoplasmic polyadenylation element binding homolog Orb2 is expressed as 2 isoforms, of which the Orb2B isoform is far more abundant, but the rarer Orb2A isoform is required to initiate Orb2 aggregation. The N terminus is a distinctive feature of the Orb2A isoform and is critical for its aggregation. Intriguingly, replacement of phenylalanine in the fifth position of Orb2A with tyrosine (F5Y) in Drosophila impairs stabilization of long-term memory. The structure of endogenous Orb2B fibers was recently determined by cryo-EM, but the structure adopted by fibrillar Orb2A is less certain. Here we use micro-electron diffraction to determine the structure of the first 9 N-terminal residues of Orb2A, at a resolution of 1.05 Å. We find that this segment (which we term M9I) forms an amyloid-like array of parallel in-register ß-sheets, which interact through side chain interdigitation of aromatic and hydrophobic residues. Our structure provides an explanation for the decreased aggregation observed for the F5Y mutant and offers a hypothesis for how the addition of a single atom (the tyrosyl oxygen) affects long-term memory. We also propose a structural model of Orb2A that integrates our structure of the M9I segment with the published Orb2B cryo-EM structure.

Don't Hang Around, It Could Be Incidental: A Case Report of Hangman's Fracture and Review of the Literature.

Neck injury fractures are commonly associated with high-impact trauma, such as motor vehicle accidents or falls from heights. However, this case underscores that it is possible to sustain such a fracture even from minor falls. As of now, there are no such reported cases. This case report highlights the importance of a thorough medical history when assessing patients with neck pain following falls. A 59-year-old male experienced a fainting episode after suffering from vomiting and diarrhea, resulting in him hitting his head. The patient attributed his neck pain to a sudden twisting of his neck. The pain originated from the base of his skull, primarily on the left side, extending to the scalp and the left shoulder. After enduring four days of intense pain that limited his ability to rotate his neck and bend to tie his shoes, he sought medical attention and underwent a neck CT scan, which led to the diagnosis of a "hangman's fracture." This injury was diagnosed in a clinical setting. Healthcare providers should inquire about the circumstances of the fall, the patient's position, associated symptoms, and any relevant pre-existing conditions. This approach ensures an accurate diagnosis and timely treatment. Comprehensive history-taking is essential for identifying high-risk situations and preventing complications that may arise from overlooked minor falls, ultimately enhancing patient safety, especially in cases of neck and spine injuries.