Activity

Among various CT findings, it exhibits good diagnostic accuracy with 61% sensitivity and 88.8% specificity. © 2020 Published by Scientific Scholar on behalf of Journal of Clinical Imaging Science.Ergothioneine is a thiohistidine derivative with potential benefits on many aging-related diseases. The central step of aerobic ergothioneine biosynthesis is the oxidative C-S bond formation reaction catalyzed by mononuclear nonheme iron sulfoxide synthases (EgtB and Egt1). Thus far, only the Mycobacterium thermoresistibile EgtB (EgtB Mth ) crystal structure is available, while the structural information for the more industrially attractive Egt1 enzyme is not. Herein, we reported the crystal structure of the ergothioneine sulfoxide synthase (EgtB Cth ) from Candidatus Chloracidobacterium thermophilum. EgtB Cth has both EgtB- and Egt1-type of activities. Guided by the structural information, we conducted Rosetta Enzyme Design calculations, and we biochemically demonstrated that EgtB Cth can be engineered more toward Egt1-type of activity. This study provides information regarding the factors governing the substrate selectivity in Egt1- and EgtB-catalysis and lays the groundwork for future sulfoxide synthase engineering toward the development of an effective ergothioneine process through a synthetic biology approach.Engineered myoglobins and other hemoproteins have recently emerged as promising catalysts for asymmetric olefin cyclopropanation reactions via carbene transfer chemistry. Despite this progress, the transformation of electron-poor alkenes has proven very challenging using these systems. Here, we describe the design of a myoglobin-based carbene transferase incorporating a non-native iron-porphyrin cofactor and axial ligand, as an efficient catalyst for the asymmetric cyclopropanation of electron-deficient alkenes. Using this metalloenzyme, a broad range of both electron-rich and electron-deficient alkenes are cyclopropanated with high efficiency and high diastereo- and enantioselectivity (up to >99% de and ee). Mechanistic studies revealed that the expanded reaction scope of this carbene transferase is dependent upon the acquisition of metallocarbene radical reactivity as a result of the reconfigured coordination environment around the metal center. The radical-based reactivity of this system diverges from the electrophilic reactivity of myoglobin and most of known organometallic carbene transfer catalysts. This work showcases the value of cofactor redesign toward tuning and expanding the reactivity of metalloproteins in abiological reactions and it provides a biocatalytic solution to the asymmetric cyclopropanation of electrodeficient alkenes. The metallocarbene radical reactivity exhibited by this biocatalyst is anticipated to prove useful in the context of a variety of other synthetic transformations.We report the development of an iron-based biocatalytic strategy for the asymmetric synthesis of fused cyclopropane-γ-lactams, which are key structural motifs found in synthetic drugs and bioactive natural products. Using a combination of mutational landscape and iterative site-saturation mutagenesis, sperm whale myoglobin was evolved into a biocatalyst capable of promoting the cyclization of a diverse range of allyl diazoacetamide substrates into the corresponding bicyclic lactams in high yields and with high enantioselectivity (up to 99% ee). These biocatalytic transformations can be performed in whole cells and could be leveraged to enable the efficient (chemo)enzymatic construction of chiral cyclopropane-γ-lactams as well as β-cyclopropyl amines and cyclopropane-fused pyrrolidines, as valuable building blocks and synthons for medicinal chemistry and natural product synthesis.Background Hangman’s fractures (HF) are defined by bilateral fractures of pars interarticularis of the axis. Most can be treated with a collar. However, the treatment strategies for atypical HF (AHF) involve the pedicles, are unstable, and require fusion. Here, we present three cases of AHF that failed anterior arthrodesis warranting repeat anterior (one case), and posterior fusions (three cases). Case Description One female and two males, ranging from 48 to 69 years of age, presented with AHF. All three were originally treated with C2-3 anterior cervical discectomy/fusion, and all three failed (e.g., resulted in pseudarthrosis/ anterolisthesis/instability). The first patient required a secondary C3 corpectomy/C2-4 arthrodesis, with C1-C4 posterior instrumentation. The latter two patients required secondary C1-C3 posterior fusions. For all three patients, 3-12 months follow-up X-rays confirmed the excellent alignment of the instrumentation and bony fusion. Conclusion Anterior arthrodesis can be utilized to treat AHF, but often fail when addressing AHF. All AHF warranted secondary posterior fusions (e.g., C1-C3 two cases; and C1-C4 one case) and a subset may additionally require more extensive anterior fusions (e.g., C2-C4 with corpectomy of C3). Copyright © 2020 Surgical Neurology International.Background Spinal osteochondromas are rare, benign tumors arising from the cartilaginous elements of the spine that may appear as solitary lesions versus multiple lesions in patients with hereditary multiple exostoses. Here, we present a 15-year-old female with a solitary C3-C4 osteochondroma who presented with a progressive quadriparesis and hand contracture successfully managed with a laminectomy/posterior spinal fusion. Case Description A 15-year-old female presented with a 3-month history of progressive quadriparesis and hand contracture secondary to a magnetic resonance (MR) documented C3-C4 cervical spine osteochondroma. this website The MR imaging revealed a solitary osseous extramedullary outgrowth arising from the left laminar cortex of the C-3 vertebral body extending to C-4. Due to the marked resultant canal stenosis, the patient underwent a cervical laminectomy of C3- C4 with posterior spinal fusion. Gross total resection was achieved, and the pathology confirmed an osteochondroma. The patient’s myelopathy resolved, and 2 years later, she demonstrated no residual deficits or tumor recurrence. Conclusion Here, we report the successful management of a 15-year-old female with a C3-C4 osteochondroma and progressive quadriparesis through cervical laminectomy/fusion. Copyright © 2020 Surgical Neurology International.