Detecting mpox infection in the early epidemic: an epidemiologic investigation of the third and fourth cases in Korea.

OBJECTIVES: As few mpox cases have been reported in Korea, we aimed to identify the characteristics of mpox infection by describing our epidemiologic investigation of a woman patient (index patient, the third case in Korea) and a physician who was infected by a needlestick injury (the fourth case). METHODS: We conducted contact tracing and exposure risk evaluation through interviews with these 2 patients and their physicians and contacts, as well as field investigations at each facility visited by the patients during their symptomatic periods. We then classified contacts into 3 levels according to their exposure risk and managed them to minimize further transmission by recommending quarantine and vaccination for post-exposure prophylaxis and monitoring their symptoms. RESULTS: The index patient had sexual contact with a man foreigner during a trip to Dubai, which was considered the probable route of transmission. In total, 27 healthcare-associated contacts across 7 healthcare facilities and 9 community contacts were identified. These contacts were classified into high (7 contacts), medium (9 contacts), and low (20 contacts) exposure risk groups. One high-risk contact was identified as a secondary patient: a physician who was injured while collecting specimens from the index patient. CONCLUSIONS: The index patient visited several medical facilities due to progressive symptoms prior to isolation. Although the 2022 mpox epidemic mainly affected young men, especially men who have sex with men, physicians should also consider mpox transmission in the general population for the timely detection of mpox-infected patients.

Re-transmissibility of mouse-adapted ME7 scrapie strain to ovine PrP transgenic mice.

Scrapie is a mammalian transmissible spongiform encephalopathy or prion disease that predominantly affects sheep and goats. Scrapie has been shown to overcome the species barrier via experimental infection of other rodents. To confirm the re-transmissibility of the mouse-adapted ME7 scrapie strain to ovine prion protein (PrP) transgenic mice, mice of an ovinized transgenic mouse line carrying the Suffolk sheep PrP gene that contained the A136 R154 Q171/ARQ allele were intracerebrally inoculated with brain homogenates obtained from terminally ill ME7-infected C57BL/6J mice. Herein, we report that the mouse-adapted ME7 scrapie strain was successfully re-transmitted to the transgenic mice expressing ovine PrP. In addition, we observed changes in the incubation period, glycoform profile, and pattern of scrapie PrP (PrPSc) deposition in the affected brains. PrPSc deposition in the hippocampal region of the brain of 2nd-passaged ovine PrP transgenic mice was accompanied by plaque formation. These results reveal that the mouse-adapted ME7 scrapie strain has the capacity to act as a template for the conversion of ovine normal monomeric precursors into a pathogenic form in ovine PrP transgenic mice. The change in glycoform pattern and the deposition of plaques in the hippocampal region of the brain of the 2nd-passaged PrP transgenic mice are most likely cellular PrP species dependent rather than being ME7 scrapie strain encoded.

AKT-independent Reelin signaling requires interactions of heterotrimeric Go and Src.

Reelin, a large secreted extracellular matrix glycoprotein, plays a key role in neuronal migration during cortical development and promotes neuronal maturation. The signaling pathway regulating neuronal maturation in the postnatal period are relatively less well understood. In this study, we demonstrated that a heterotrimeric G protein, Go, is a novel target of Reelin-induced signaling to promote neurite outgrowth. In primary hippocampal neurons of Reelin-deficient reeler mice, neurite outgrowth was significantly reduced and rescued upon addition of Reelin. Pertussis toxin (PTX) treatment or transfection with Gαo-siRNA suppressed Reelin-mediated neurite outgrowth in wild-type neurons. Additionally, Reelin treatment led to increased phosphorylation of AKT, GSK3ß, and JNK, which were all effectively blocked by the PI3K inhibitor, LY294002. By comparison, PTX specifically blocked JNK activation, but not AKT and GSK3ß. Immunoprecipitation assays disclosed that Reelin increases the active forms of both Src and Gαo and promotes their direct association. Notably, Dab1, a cytoplasmic adaptor molecule that mediates Reelin signaling, did not interact with Gαo. Neurite outgrowth by Reelin was induced via activating Src kinase, which directly stimulated Gαo, activity, leading to JNK activation. Based on the collective findings, we suggest that Reelin-dependent signaling mechanisms may be split into Src-AKT-dependent and Src-Go-dependent pathways. Our results additionally provide evidence that Reelin receptors cross-communicate with heterologous G protein-coupled receptors (GPCR) independently of the cognate ligands of GPCR.

Gene expression profiling using DNA microarray analysis of the cerebellum of mice treated with methylmercury.

To elucidate the molecular mechanism involved in methylmercury-induced cerebellar disorder, we performed DNA microarray analysis of the cerebellum of methylmercury-treated mice. The expression levels of 21 genes were elevated 2-fold or higher in response to methylmercury, including many genes encoding proteins involved in inflammatory reactions associated with chemokines. The expression levels of 11 genes were reduced by half or more in response to methylmercury.

Suppression of prostaglandin E2-induced MUC5AC overproduction by RGS4 in the airway.

The mechanism by which E-prostanoid (EP) receptor is critically involved in PGE(2)-induced mucin 5AC (MUC5AC) gene expression in the airway has been unclear. Furthermore, there have been little reports regarding the negative regulatory mechanism and/or proteins that affect PGE(2)-induced MUC5AC overproduction. In the present study, we found that PGE(2) induced MUC5AC gene expression in a dose-dependent manner (EC(50): 73.31 +/- 3.13 nM) and that the EP(2/4)-specific agonist, misoprostol, increased MUC5AC mRNA level, whereas the EP(1/3)-specific agonist, sulprostone, had no effect. Interestingly, the cAMP concentration (685.1 +/- 14.9 pM) of the EC(50) value of EP(4)-mediated cAMP production was much higher than that of EP(2) (462.33 +/- 23.79 pM), suggesting that EP(4) has higher sensitivity to PGE(2) compared with EP(2). Moreover, PGE(2)-induced Muc5ac overproduction was much increased in regulator of G protein signaling (Rgs) 4 knockout (KO) mice compared with wild-type mice at both transcriptional and translational levels, and it was dramatically suppressed in Rgs4 KO mice that had been infected with lentivirus expressing RGS4 (lenti::RGS4) compared with lentivirus expressing enhanced green fluorescent protein (lenti::eGFP). Finally, we demonstrate that PGE(2) can induce MUC5AC overproduction via the EP(4) receptor and that RGS4 may have suppressive effects in controlling MUC5AC overexpression in the airway. These findings may provide a molecular paradigm for the development of novel drugs for respiratory diseases.