Magnetic Resonance Imaging for Spine Emergencies.

This article is devoted to the MR imaging evaluation of spine emergencies, defined as spinal pathologic conditions that pose an immediate risk of significant morbidity or mortality to the patient if not diagnosed and treated in a timely manner. MR imaging plays a central role in the timely diagnosis of spine emergencies. A summary of MR imaging indications and MR imaging protocols tailored for a variety of spinal emergencies will be presented followed by a review of key imaging findings for the most-encountered emergent spine pathologic conditions. Pathologic conditions will be broadly grouped into traumatic and atraumatic pathologic conditions. For traumatic injuries, a practical and algorithmic diagnostic approach based on the AO Spine injury classification system will be presented focused on subaxial spine trauma. Atraumatic spinal emergencies will be dichotomized into compressive and noncompressive subtypes. The location of external compressive disease with respect to the thecal sac is fundamental to establishing a differential diagnosis for compressive emergencies, whereas specific patterns of spinal cord involvement on MR imaging will guide the discussion of inflammatory and noninflammatory causes of noncompressive myelopathy.

Oxidative cyclizations in orthosomycin biosynthesis expand the known chemistry of an oxygenase superfamily.

Orthosomycins are oligosaccharide antibiotics that include avilamycin, everninomicin, and hygromycin B and are hallmarked by a rigidifying interglycosidic spirocyclic ortho-δ-lactone (orthoester) linkage between at least one pair of carbohydrates. A subset of orthosomycins additionally contain a carbohydrate capped by a methylenedioxy bridge. The orthoester linkage is necessary for antibiotic activity but rarely observed in natural products. Orthoester linkage and methylenedioxy bridge biosynthesis require similar oxidative cyclizations adjacent to a sugar ring. We have identified a conserved group of nonheme iron, α-ketoglutarate-dependent oxygenases likely responsible for this chemistry. High-resolution crystal structures of the EvdO1 and EvdO2 oxygenases of everninomicin biosynthesis, the AviO1 oxygenase of avilamycin biosynthesis, and HygX of hygromycin B biosynthesis show how these enzymes accommodate large substrates, a challenge that requires a variation in metal coordination in HygX. Excitingly, the ternary complex of HygX with cosubstrate α-ketoglutarate and putative product hygromycin B identified an orientation of one glycosidic linkage of hygromycin B consistent with metal-catalyzed hydrogen atom abstraction from substrate. These structural results are complemented by gene disruption of the oxygenases evdO1 and evdMO1 from the everninomicin biosynthetic cluster, which demonstrate that functional oxygenase activity is critical for antibiotic production. Our data therefore support a role for these enzymes in the production of key features of the orthosomycin antibiotics.