The uncoating of EV71 in mature late endosomes requires CD-M6PR

Enterovirus 71 (EV71) is one of the causative agents of hand-foot-and-mouth disease, which in some circumstances could lead to severe neurological diseases. Despite of its importance for human health, little is known about the early stages of EV71 infection. EV71 starts uncoating with its receptor, human scavenger receptor B2 (hSCARB2), at low pH. We show that EV71 was not targeted to lysosomes in human rhabdomyosarcoma cells overexpressing hSCARB2 and that the autophagic pathway is not essential for EV71 productive uncoating. Instead, EV71 was efficiently uncoated 30 minutes after infection in late endosomes (LEs) containing hSCARB2, mannose-6-phosphate receptor (M6PR), RAB9, bis(monoacylglycero)phosphate and lysosomal associated membrane protein 2 (LAMP2). Furthering the notion that mature LEs are crucial for EV71 uncoating, cation-dependent (CD)-M6PR knockdown impairs EV71 infection. Since hSCARB2 interacts with cation-independent (CI)-M6PR through M6P-binding sites and CD-M6PR also harbor a M6P-binding site, CD-M6PR is likely to play important roles in EV71 uncoating in LEs

Overexpression of AtCpNifS enhances selenium tolerance and accumulation in Arabidopsis

Selenium (Se) is an essential element for many organisms but is toxic at higher levels. CpNifS is a chloroplastic NifS-like protein in Arabidopsis (Arabidopsis thaliana) that can catalyze the conversion of cysteine into alanine and elemental sulfur (S 0 ) and of selenocysteine into alanine and elemental Se (Se 0 ). We overexpressed CpNifS to investigate the effects on Se metabolism in plants. CpNifS overexpression significantly enhanced selenate tolerance (1.9-fold) and Se accumulation (2.2-fold). CpNifS overexpressors showed significantly reduced Se incorporation into protein, which may explain their higher Se tolerance. Also, sulfur accumulation was enhanced by approximately 30% in CpNifS overexpressors, both on media with and without selenate. Root transcriptome changes in response to selenate mimicked the effects observed under sulfur starvation. There were only a few transcriptome differences between CpNifS-overexpressing plants and wild type, besides the 25-to 40-fold increase in CpNifS levels. Judged from x-ray analysis of near edge spectrum, both CpNifS overexpressors and wild type accumulated mostly selenate (Se VI ). In conclusion, overexpression of this plant NifS-like protein had a pronounced effect on plant Se metabolism. The observed enhanced Se accumulation and tolerance of CpNifS overexpressors show promise for use in phytoremediation

2019年度 八戸工業大学公開講座

Last updated: 6/15/201

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

The Efficacy of Device Designs (Mono-block or Bi-block) in Oral Appliance Therapy for Obstructive Sleep Apnea Patients: A Systematic Review and Meta-Analysis

Oral appliance (OAm) therapy has demonstrated efficacy in treating obstructive sleep apnea (OSA). The aim of this systematic review was to clarify the efficacy of device designs (Mono-block or Bi-block) in OAm therapy for OSA patients. We performed a meta-analysis using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. Two studies (Mono-block OAm versus Bi-block OAm) remained eligible after applying the exclusion criteria. When comparing Mono-block OAm and Bi-block OAm, Mono-block OAm significantly reduced the apnea–hypopnea index (2.92; 95% confidence interval (95%CI), 1.26 to 4.58; p = 0.0006), and patient preference for Mono-block OAm was significantly higher (2.06; 95%CI, 1.44 to 2.06; p < 0.0001). Lowest SpO2, arousal index, non-REM stage 3, sleep efficiency, Epworth Sleepiness Scale (ESS), Snoring Scale, and side effects were not significantly different between the two groups (lowest SpO2: −11.18; 95%CI, −26.90 to 4.54; p = 0.16, arousal index: 4.40; 95%CI, −6.00 to 14.80; p = 0.41, non-REM stage 3: −2.00; 95%CI, −6.00 to 14.80; p = 0.41, sleep efficiency: −1.42, 95%CI, −4.71 to 1.86; p = 0.40, ESS: 0.12; 95%CI, −1.55 to 1.79; p = 0.89, Snoring Scale: 0.55; 95%CI, −0.73 to 1.83, p = 0.55, side effects: 1.00, 95%CI, 0.62 to 1.61, p = 1.00). In this systematic review, the use of Mono-block OAm was more effective than Bi-block OAm for OSA patients