The Actinobacillus pleuropneumoniae HMW1C-Like Glycosyltransferase Mediates N-Linked Glycosylation of the Haemophilus influenzae HMW1 Adhesin

The Haemophilus influenzae HMW1 adhesin is an important virulence exoprotein that is secreted via the two-partner secretion pathway and is glycosylated at multiple asparagine residues in consensus N-linked sequons. Unlike the heavily branched glycans found in eukaryotic N-linked glycoproteins, the modifying glycan structures in HMW1 are mono-hexoses or di-hexoses. Recent work demonstrated that the H. influenzae HMW1C protein is the glycosyltransferase responsible for transferring glucose and galactose to the acceptor sites of HMW1. An Actinobacillus pleuropneumoniae protein designated ApHMW1C shares high-level homology with HMW1C and has been assigned to the GT41 family, which otherwise contains only O-glycosyltransferases. In this study, we demonstrated that ApHMW1C has N-glycosyltransferase activity and is able to transfer glucose and galactose to known asparagine sites in HMW1. In addition, we found that ApHMW1C is able to complement a deficiency of HMW1C and mediate HMW1 glycosylation and adhesive activity in whole bacteria. Initial structure-function studies suggested that ApHMW1C consists of two domains, including a 15-kDa N-terminal domain and a 55-kDa C-terminal domain harboring glycosyltransferase activity. These findings suggest a new subfamily of HMW1C-like glycosyltransferases distinct from other GT41 family O-glycosyltransferases

Kikuchi's Disease in Children: Clinical Manifestations and Imaging Features

Previously published studies on Kikuchi disease (KD) have frequently addressed the computed tomography (CT) findings in the adult population, however, only a few studies have been reported for the pediatric age group. The purpose of this study is to analyze the clinical characteristics and imaging features of KD in children. Fifteen children (2-14 yr) who had a neck CT and pathology diagnosis of KD were included in this study. Clinical features, including the duration of lymphadenopathy and fever, prognosis, and laboratory values, were evaluated. We analyzed the sites, size, and lymph node pattern as seen on their CT scans. The median duration of fever was 10 days. Fourteen patients experienced improvement in their condition, although four of these patients experienced recurrent episodes of KD. All patients had affected cervical nodes at level V. Perinodal infiltrates were observed in the affected cervical nodes in 14 cases (93%), and non-enhancing necrosis was also noted within the affected cervical nodes in 10 cases (63%). In conclusion, the combination of imaging findings in conjunction with clinical findings of KD may help to determine whether or not to perform pathology analysis and follow-up studies

Quantitative Analysis and Biological Efficacies regarding the Neuroprotective and Antineuroinflammatory Actions of the Herbal Formula Jodeungsan in HT22 Hippocampal Cells and BV-2 Microglia

Jodeungsan (JDS) is a traditional herbal formula that comprises seven medicinal herbs and is broadly utilized to treat hypertension, dementia, and headache. However, the effects of JDS and its herbal components on neurodegenerative diseases have not been reported. We examined the inhibitory effects of JDS and its seven components on neuronal cell death and inflammation using HT22 hippocampal cells and BV-2 microglia, respectively. Among its seven herbal components, Uncaria sinensis (US), Chrysanthemum morifolium (CM), Zingiber officinale (ZO), Pinellia ternata (PT), Citrus unshiu (CU), and Poria cocos (PC) exhibited significant neuroprotective effects in HT22 cells. In BV-2 cells, JDS significantly suppressed the production of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), indicating the antineuroinflammatory activity of JDS. In addition, the herbal extracts from ZO, Panax ginseng (PG), PT, CU, and PC exhibited inhibitory effects on the inflammatory response in microglia. These data imply that the JDS effect on neurodegeneration occurs via coordination among its seven components. To establish a quality control for JDS, a simultaneous analysis using five standard compounds identified hesperidin (37.892±1.228 mg/g) as the most abundant phytochemical of JDS. Further investigation of the combinatorial activities of two or more standard compounds will be necessary to verify their antineurodegenerative regulatory mechanisms

Effects of Korean Red Ginseng on Cognitive and Motor Function: A Double-blind, Randomized, Placebo-controlled Trial

Ginseng has a long history of use for health enhancement, and there is some evidence from animal studies that it has a beneficial effect on cognitive performance. The purpose of this study was to investigate the effect of Korean red ginseng on cognitive performance in humans. A total of 15 healthy young males with no psychiatric or cognitive problems were selected based on an interview with a board-certified psychiatrist. The subjects were randomly assigned to receive a daily dose of 4,500 mg red ginseng or placebo for a 2-week trial. There were 8 subjects in the red ginseng group and 7 subjects in the placebo group. All of the subjects were analyzed with the Vienna test system and a P300 event-related potential (ERP) test. There were no significant differences in the Vienna test system scores between the red ginseng group and the placebo group. In the event-related potential test, the C3 latency of the red ginseng group tended to decrease during the study period (p=0.005). After 2 wk, significant decreases were observed in the P300 latencies at Cz (p=0.008), C3 (p=0.005), C4 (p=0.002), and C mean (p=0.003) in the red ginseng group. Our results suggest that the decreased latency in ERP is associated with improved cognitive function. Further studies with a higher dosage of ginseng, a larger sample size, and a longer follow-up period are necessary to confirm the clinical efficacy of Korean red ginseng.OAIID:oai:osos.snu.ac.kr:snu2012-01/102/2014017262/7SEQ:7PERF_CD:SNU2012-01EVAL_ITEM_CD:102USER_ID:2014017262ADJUST_YN:YEMP_ID:A079623DEPT_CD:801CITE_RATE:0DEPT_NM:의학과SCOPUS_YN:NCONFIRM:

The dynamic transcriptional and translational landscape of the model antibiotic producer Streptomyces coelicolor A3(2)

Individual Streptomyces species have the genetic potential to produce a diverse array of natural products of commercial, medical and veterinary interest. However, these products are often not detectable under laboratory culture conditions. To harness their full biosynthetic potential, it is important to develop a detailed understanding of the regulatory networks that orchestrate their metabolism. Here we integrate nucleotide resolution genome-scale measurements of the transcriptome and translatome of Streptomyces coelicolor, the model antibiotic-producing actinomycete. Our systematic study determines 3,570 transcription start sites and identifies 230 small RNAs and a considerable proportion (∼21%) of leaderless mRNAs; this enables deduction of genome-wide promoter architecture. Ribosome profiling reveals that the translation efficiency of secondary metabolic genes is negatively correlated with transcription and that several key antibiotic regulatory genes are translationally induced at transition growth phase. These findings might facilitate the design of new approaches to antibiotic discovery and development

GSK3B induces autophagy by phosphorylating ULK1

Unc-51-like autophagy activating kinase 1 (ULK1), a mammalian homolog of the yeast kinase Atg1, has an essential role in autophagy induction. In nutrient and growth factor signaling, ULK1 activity is regulated by various posttranslational modifications, including phosphorylation, acetylation, and ubiquitination. We previously identified glycogen synthase kinase 3 beta (GSK3B) as an upstream regulator of insulin withdrawal-induced autophagy in adult hippocampal neural stem cells. Here, we report that following insulin withdrawal, GSK3B directly interacted with and activated ULK1 via phosphorylation of S405 and S415 within the GABARAP-interacting region. Phosphorylation of these residues facilitated the interaction of ULK1 with MAP1LC3B and GABARAPL1, while phosphorylation-defective mutants of ULK1 failed to do so and could not induce autophagy flux. Furthermore, high phosphorylation levels of ULK1 at S405 and S415 were observed in human pancreatic cancer cell lines, all of which are known to exhibit high levels of autophagy. Our results reveal the importance of GSK3B-mediated phosphorylation for ULK1 regulation and autophagy induction and potentially for tumorigenesis. © 2021, The Author(s).1