The structure of human EXD2 reveals a chimeric 3' to 5' exonuclease domain that discriminates substrates via metal coordination.

EXD2 (3'-5' exonuclease domain-containing protein 2) is an essential protein with a conserved DEDDy superfamily 3'-5' exonuclease domain. Recent research suggests that EXD2 has two potential functions: as a component of the DNA double-strand break repair machinery and as a ribonuclease for the regulation of mitochondrial translation. Herein, electron microscope imaging analysis and proximity labeling revealed that EXD2 is anchored to the mitochondrial outer membrane through a conserved N-terminal transmembrane domain, while the C-terminal region is cytosolic. Crystal structures of the exonuclease domain in complex with Mn2+/Mg2+ revealed a domain-swapped dimer in which the central α5-α7 helices are mutually crossed over, resulting in chimeric active sites. Additionally, the C-terminal segments absent in other DnaQ family exonucleases enclose the central chimeric active sites. Combined structural and biochemical analyses demonstrated that the unusual dimeric organization stabilizes the active site, facilitates discrimination between DNA and RNA substrates based on divalent cation coordination and generates a positively charged groove that binds substrates.Cell Logistics Research Center [2016R1A5A1007318]; Basic Research Program, National Research Foundation of Korea [NRF-2019R1A2C3008463]; Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea [HI18C1395]; Institute for Basic Science [IBS-R022-D1]. Funding for open access charge: Cell Logistics Research Center, National Research Foundation of Korea [2016R1A5A1007318]

Comparison of clinical methods for detecting carbapenem-resistant Enterobacteriaceae

We evaluated detection of carbapenem-resistant Enterobacteriaceae (CRE) by routine minimal inhibitory concentration (MIC) testing, polymerase chain reaction (PCR) using Xpert® Carba-R assay, hydrolysis of ertapenem and imipenem detected by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS), and hydrolysis by colorimetry using the EPI-CRE assay.Ninety-six Enterobacteriaceae isolates possessing carbapenemase genes and 29 carbapenem-susceptible Enterobacteriaceae were available for testing. The sensitivity and specificity of each assay was determined. For sensitivity, discrepant results from each assay compared to reference genotype were arbitrated with MIC and/ or PCR testing to assess loss of plasmid-mediated resistance. Xpert Carba-R was evaluated for resistance genes in their FDA claim (i.e., the genes encoding KPC; NDM; VIM; IMP; and OXA-48).The sensitivity for the assays was: MIC (N=96), 96.8%, (discrepant analysis to 98.9% [2 cured plasmids]); Xpert Carba-R (N=85), 97.6% (discrepant analysis to 100% % [2 cured plasmids]); EPI-CRE (N=96), 91.7% (discrepant analysis to 91.7%); MALDI-TOF MS (N=96) ertapenem hydrolysis using Compass software for interpretation (2 h incubation), 92.7% (discrepant analysis to 94.7% % [2 cured plasmids]); MALDI-TOF MS (N=96) imipenem hydrolysis (1 h incubation), 97.9% (discrepant analysis to 98.9% % [1 cured plasmid]). The specificity for each assay was: MIC (N=29), 100%; EPI-CRE (N=29), 96.6%; MALDI-TOF MS ertapenem hydrolysis (N=29), 100%; MALDI-TOF MS imipenem hydrolysis (N=29), 96.6%. All isolates tested to ensure specificity demonstrated susceptible MIC results for carbapenems and did not qualify for testing with Xpert Carba-R.No single assay detected all of the known genetic markers of carbapenem hydrolysis. Keywords: Carbapenemase, Enterobacteriaceae, Pilots Pointe EPI-CRE, Bruker MALDI-TOF MS, Cepheid Xpert Carba-

Comparison of clinical methods for detecting carbapenem-resistant Enterobacteriaceae

We evaluated detection of carbapenem-resistant Enterobacteriaceae (CRE) by routine minimal inhibitory concentration (MIC) testing, polymerase chain reaction (PCR) using Xpert® Carba-R assay, hydrolysis of ertapenem and imipenem detected by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS), and hydrolysis by colorimetry using the EPI-CRE assay.Ninety-six Enterobacteriaceae isolates possessing carbapenemase genes and 29 carbapenem-susceptible Enterobacteriaceae were available for testing. The sensitivity and specificity of each assay was determined. For sensitivity, discrepant results from each assay compared to reference genotype were arbitrated with MIC and/ or PCR testing to assess loss of plasmid-mediated resistance. Xpert Carba-R was evaluated for resistance genes in their FDA claim (i.e., the genes encoding KPC; NDM; VIM; IMP; and OXA-48).The sensitivity for the assays was: MIC (N=96), 96.8%, (discrepant analysis to 98.9% [2 cured plasmids]); Xpert Carba-R (N=85), 97.6% (discrepant analysis to 100% % [2 cured plasmids]); EPI-CRE (N=96), 91.7% (discrepant analysis to 91.7%); MALDI-TOF MS (N=96) ertapenem hydrolysis using Compass software for interpretation (2 h incubation), 92.7% (discrepant analysis to 94.7% % [2 cured plasmids]); MALDI-TOF MS (N=96) imipenem hydrolysis (1 h incubation), 97.9% (discrepant analysis to 98.9% % [1 cured plasmid]). The specificity for each assay was: MIC (N=29), 100%; EPI-CRE (N=29), 96.6%; MALDI-TOF MS ertapenem hydrolysis (N=29), 100%; MALDI-TOF MS imipenem hydrolysis (N=29), 96.6%. All isolates tested to ensure specificity demonstrated susceptible MIC results for carbapenems and did not qualify for testing with Xpert Carba-R.No single assay detected all of the known genetic markers of carbapenem hydrolysis. Keywords: Carbapenemase, Enterobacteriaceae, Pilots Pointe EPI-CRE, Bruker MALDI-TOF MS, Cepheid Xpert Carba-

Identifying Technology Opportunities for Electric Motors of Railway Vehicles with Patent Analysis

An electric motor is a device that changes electrical energy into mechanical energy for railway vehicles. When developing the electric motor, it used to be developed simply for structures or control methods of the motor itself without considering convergence with other devices or technologies. However, as the railway vehicles become more advanced, technology development through convergence with other devices or technologies is spreading. Therefore, based on patent data related to the electric motors applied to the railway vehicles, this research aims to carry out technical forecasting for establishing research and development (R and D) direction for new technologies by predicting vacant technologies from the point of view of technology convergence. In other words, we studied how to find the vacant technologies in a field of convergence technology for the electric motor of the railway vehicles by analyzing the patent data. More specifically, we search the patents data associated with the electric motor of the railway vehicle that contain multiple IPC codes, and use multiple IPC codes to determine the field of convergence technology. In addition, we extract keywords from the patents data related to each of the determined convergence technologies and define the vacant technologies by interpreting the field of convergence technology and the extracted keywords

Characterization of virus-specific immune response during varicella zoster virus encephalitis in a young adult

An immunocompetent adult received corticosteroids for chest pain, which later was clinically found to be herpes zoster (HZ). She developed severe disease and rapid viral dissemination that elicited an exceptionally strong varicella zoster virus-specific B-cell and CD8 T-cell response. Clinicians should consider atypical HZ presentation prior to corticosteroid administration

Pediatric Dental Clinic-Associated Outbreak of Mycobacterium abscessus Infection.

BACKGROUND: Mycobacterium abscessus is an uncommon cause of invasive odontogenic infection. METHODS: M abscessus-associated odontogenic infections occurred in a group of children after they each underwent a pulpotomy. A probable case-child was defined as a child with facial or neck swelling and biopsy-confirmed granulomatous inflammation after a pulpotomy between October 1, 2013, and September 30, 2015. M abscessus was isolated by culture in confirmed case-children. Clinical presentation, management, and outcomes were determined by medical record abstraction. RESULTS: Among 24 children, 14 (58%) were confirmed case-children. Their median age was 7.3 years (interquartile range, 5.8-8.2 years), and the median time from pulpotomy to symptom onset was 74 days (range, 14-262 days). Clinical diagnoses included cervical lymphadenitis (24 [100%] of 24), mandibular or maxillary osteomyelitis (11 [48%] of 23), and pulmonary nodules (7 [37%] of 19). Each child had ≥1 hospitalization and a median of 2 surgeries (range, 1-6). Of the 24 children, 12 (50%) had surgery alone and 11 (46%) received intravenous (IV) antibiotics. Nineteen of the 24 (79%) children experienced complications, including vascular access malfunction (7 [64%] of 11), high-frequency hearing loss (5 [56%] of 9), permanent tooth loss (11 [48%] of 23), facial nerve palsy (7 [29%] of 24), urticarial rash (3 [25%] of 12), elevated liver enzyme levels (1 [20%] of 5), acute kidney injury (2 [18%] of 11), incision dehiscence/fibrosis (3 [13%] of 24), and neutropenia (1 [9%] of 11). CONCLUSIONS: M abscessus infection was associated with significant medical morbidity and treatment complications. Unique manifestations included extranodal mandibular or maxillary osteomyelitis and pulmonary nodules. Challenges in the identification of case-children resulted from an extended incubation period and various clinical manifestations. Clinicians should consider the association between M abscessus infection and pulpotomy in children who present with subacute cervical lymphadenitis. The use of treated/sterile water during pulpotomy might prevent further outbreaks