Correction: HIF-1α:CRAT:miR-144-3p axis dysregulation promotes osteoarthritis chondrocyte apoptosis and VLCFA accumulation.

[This corrects the article DOI: 10.18632/oncotarget.20615.].

HIF-1α:CRAT:miR-144-3p axis dysregulation promotes osteoarthritis chondrocyte apoptosis and VLCFA accumulation.

The functional role(s) of peroxisomes in osteoarthritis remains unclear. We demonstrated that peroxisomal dysfunction in osteoarthritis is responsible for very-long-chain fatty acid (VLCFA) accumulation. Through gene-profiling analyses, we identified CRAT as the gene responsible for this event. CRAT expression was suppressed in osteoarthritis chondrocytes, and its knockdown yielded pathological osteoarthritic characteristics, including VLCFA accumulation, apoptosis, autophagic inhibition, and mitochondrial dysfunction. Subsequent miRNA profiling revealed that peroxisomal dysfunction upregulates miR-144-3p, which overlapped with the osteoarthritis pathological characteristics observed upon CRAT knockdown. Moreover, knocking down HIF-1α in normal chondrocytes suppressed CRAT expression while stimulating miR-144-3p. Our data indicate that deregulation of a HIF-1a:CRAT:miR-144-3p axis impairs peroxisomal function during the pathogenesis of osteoarthritis.

Genome Sequence of Bacteriophage GG32, Which Can Infect both Salmonella enterica Serovar Typhimurium and Escherichia coli O157:H7.

We report here a new virulent Salmonella enterica serovar Typhimurium (S Typhimurium) bacteriophage, GG32, which was isolated from the Guem River in the Republic of Korea. The strain can infect both S Typhimurium and Escherichia coli (E. coli) O157:H7 and may be a good candidate for a bio-control agent.

Complete Genome Sequence of Bacteriophage MA12, Which Infects both Campylobacter jejuni and Salmonella enterica Serovar Enteritidis.

Here, we announce the complete genome sequence of Salmonella enterica serovar Enteritidis (S Enteritidis) bacteriophage MA12, a 41-Kb chromosome. The strain can infect both Campylobacter jejuni (C. jejuni) and S Enteritidis and can be used in phage therapy experiments with poultry and poultry meat.

Beneficial reward-to-risk action of glucosamine during pathogenesis of osteoarthritis.

OBJECTIVE: Glucosamine is widely used to improve the symptoms and to delay the structural progression of osteoarthritis. However, its efficacy in osteoarthritis has been controversial and its underlying mechanism of action remains unclear. The aim of this study was to investigate the effects of glucosamine and the underlying mechanisms in human chondrocytes. METHODS: Chondrocytes from normal human articular cartilage were treated with glucosamine (10-100 mM). Subsequently, cell death was analyzed by Annexin V staining and FACS and mitochondrial function was studied by measuring the mitopotential. Peroxisomal function was analyzed by BODIPY staining, and gene expression of PMP70 and acyl-CoA oxidase 1, by real-time PCR. Total lipids were analyzed by gas chromatography/mass spectrometry. Autophagy activation was determined by western blotting of beclin and light chain 3B. Autophagosome formation was analyzed by introduction of green fluorescent protein (GFP) LC3, and pexophagy was determined by introduction of mRFP-EGFP-SKL plasmids. RESULTS: Treatment of chondrocytes with glucosamine exerts exposure time-dependent dual effects on apoptosis/autophagy. Short time exposure of glucosamine to chondrocytes activated autophagy, pexophagy, and peroxidation. On the other hand, long time exposure of glucosamine had opposite effects, namely accumulation of very long chain fatty acids and peroxisomal dysfunction. CONCLUSION: We highlight the dual role of glucosamine in apoptosis/autophagy in human chondrocytes depending on exposure time. Although further research is required to fully understand the dual effects of glucosamine, dosage and duration of glucosamine treatment are clear contributing factors towards the line of beneficial reward-to-risk action.

Cluster of serogroup W-135 meningococcal disease in 3 military recruits.

We describe a group of 3 cases of invasive meningococcal disease that occurred in a military training camp in April 2011. All three patients were hospitalized. Ultimately, two patients recovered and one died. One patient had meningitis, one patient had septicemia and meningitis, and the other had no definite septicemia or meningitis. Neisseria meningitidis serogroup W-135 was detected in the serum and cerebrospinal fluid (CSF) of all patients by real-time polymerase chain reaction. In the one case of mortality, two strains were isolated from the patient's blood and CSF. Using multilocus sequence typing analysis, these strains were identified as a novel sequence type, ST-8912. Special attention is required for the meningococcal disease in military camp because the military personnels are in high risk of contact transmission.

Down-regulation of Phospholipase D Stimulates Death of Lung Cancer Cells Involving Up-regulation of the Long ncRNA ANRIL.

Dysregulation of phospholipase D (PLD) has been found in several types of human cancer, but the underlying regulatory mechanism remains poorly-understood. Herein we found PLD inhibition in human H460 lung cancer cells has anti-tumorigenic effects such as stimulation of apoptosis and autophagy. In the present study, in order to identify the responsible key regulator of these anti-tumorigenic effects of PLD inhibition, we analyzed the expression levels of 90 long non-coding RNAs (lncRNAs). Among them, the expression level of antisense noncoding RNA in the INK4 locus (ANRIL) was increased up to 13.6-fold by PLD inhibition in H460 human lung cancer cells. Moreover, knockdown of ANRIL using its specific small-interfering RNA significantly suppressed PLD inhibition-induced apoptosis. Collectively, our findings showed that ANRIL is an lncRNA responsible in anti-tumorigenesis caused by PLD inhibition and combined incorporation of ANRIL into PLD inhibition-induced anti-tumorigenic signaling network could be a new effective therapeutic approach for controlling lung cancer.

Epidemics of Norovirus GII.4 Variant in Outbreak Cases in Korea, 2004-2012.

Norovirus GII.4 is recognized as a worldwide cause of nonbacterial outbreaks. In particular, the GII.4 variant occurs every 2-3 years according to antigenic variation. The aim of our study was to identify GII.4 variants in outbreaks in Korea during 2004-2012. Partial VP1 sequence of norovirus GII.4-related outbreaks during 2004-2012 was analyzed. The partial VP1 sequence was detected with reverse transcription-polymerase chain reaction, seminested polymerase chain reaction, and nucleotide sequence of 312-314 base pairs for phylogenetic comparison. Nine variants emerged in outbreaks, with the Sydney variant showing predominance recently. This predominance may persist for at least 3 years, although new variants may appear in Korea.

Occurrence of Norovirus GII.4 Sydney Variant-related Outbreaks in Korea.

Human noroviruses are major causative agents of food and waterborne outbreaks of nonbacterial acute gastroenteritis. In this study, we report the epidemiological features of three outbreak cases of norovirus in Korea, and we describe the clinical symptoms and distribution of the causative genotypes. The incidence rates of the three outbreaks were 16.24% (326/2,007), 4.1% (27/656), and 16.8% (36/214), respectively. The patients in these three outbreaks were affected by acute gastroenteritis. These schools were provided unheated food from the same manufacturing company. Two genotypes (GII.3 and GII.4) of the norovirus were detected in these cases. Among them, major causative strains of GII.4 (Hu-jeju-47-2007KR-like) were identified in patients, food handlers, and groundwater from the manufacturing company of the unheated food. In the GII.4 (Hu-jeju-47-2007KR-like) strain of the norovirus, the nucleotide sequences were identical and identified as the GII.4 Sydney variant. Our data suggests that the combined epidemiological and laboratory results were closely related, and the causative pathogen was the GII.4 Sydney variant strain from contaminated groundwater.

Alpha1-Adrenoceptor Antagonists Improve Memory by Activating N-methyl-D-Aspartate-Induced Ion Currents in the Rat Hippocampus.

PURPOSE: Alpha1 (α1)-adrenoceptor antagonists are widely used to treat lower urinary tract symptoms. These drugs not only act on peripheral tissues, but also cross the blood-brain barrier and affect the central nervous system. Therefore, α1-adrenoceptor antagonists may enhance brain functions. In the present study, we investigated the effects of tamsulosin, an α1-adrenoceptor antagonist, on short-term memory, as well as spatial learning and memory, in rats. METHODS: The step-down avoidance test was used to evaluate short-term memory, and an eight-arm radial maze test was used to evaluate spatial learning and memory. TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling) staining was performed in order to evaluate the effect of tamsulosin on apoptosis in the hippocampal dentate gyrus. Patch clamp recordings were used to evaluate the effect of tamsulosin on ionotropic glutamate receptors, such as N-methyl-D-aspartate (NMDA), amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and kainate receptors, in hippocampal CA1 neurons. RESULTS: Tamsulosin treatment improved short-term memory, as well as spatial learning and memory, without altering apoptosis. The amplitudes of NMDA-induced ion currents were dose-dependently increased by tamsulosin. However, the amplitudes of AMPA- and kainate-induced ion currents were not affected by tamsulosin. CONCLUSIONS: Tamsulosin enhanced memory function by activating NMDA receptor-mediated ion currents in the hippocampus without initiating apoptosis. The present study suggests the possibility of using tamsulosin to enhance memory under normal conditions, in addition to its use in treating overactive bladder.

Complete nucleotide sequence of the IncI1 plasmid pSH4469 encoding CTX-M-15 extended-spectrum ß-lactamase in a clinical isolate of Shigella sonnei from an outbreak in the Republic of Korea.

An outbreak of extended-spectrum ß-lactamase (ESBL)-producing Shigella sonnei infections occurred in a school for disabled children in Gyeongbuk Province, Republic of Korea, in 2008. Five students were affected. Pulsed-field gel electrophoresis (PFGE) analysis revealed that all of the ESBL-producing S. sonnei isolates belonged to the same clone, and nucleotide sequence analysis of ESBL genes revealed that they harboured bla(CTX-M-15). This is the first identification of bla(CTX-M-15) in Shigella spp. in South Korea. In this study, a plasmid carrying the bla(CTX-M-15) gene, designated pSH4469, recovered from a S. sonnei isolate responsible for the outbreak was characterised. Replicon typing and plasmid multilocus sequence typing (pMLST) analysis of plasmids in the outbreak strain identified that the bla(CTX-M-15) gene was located on an IncI1 incompatibility group plasmid of sequence type 16 (ST16). The complete nucleotide sequence of pSH4469 revealed that this plasmid is 91109bp and harbours 119 putative genes, including another antibiotic resistance gene (bla(TEM-1b)) that is often associated with the ISEcp1-bla(CTX-M-15)-orf477delta transposable unit. The plasmid consists of a large backbone with considerable homology to the pEK204 plasmid isolated from Escherichia coli in the UK, except for insertion of an IS66 element found in pEK204. These data demonstrate that IncI1 plasmids are used as a successful platform for efficient horizontal gene transfer, thereby resulting in the dissemination of CTX-M-type ß-lactamases among Enterobacteriaceae.

Genetic diversity of Campylobacter jejuni isolates from Korea and travel-associated cases from east and southeast Asian countries.

Forty domestic and travel-associated Campylobacter jejuni isolates were analyzed by profiling 7 pathogenic genes (cdtB, cadF, Cj0131, ciaB, racR, wlaN, and virB11) along with multilocus sequence typing (MLST) and antimicrobial susceptibility testing. cdtB, cadF, and Cj0131 were present in all isolates, whereas virB11 was not detected in either domestic or travel-associated isolates. ciaB was present in all domestic isolates and 94% of travel-associated isolates. The respective detection rates of racR and wlaN in domestic and travel-associated isolates were 94% and 71% and 35.3% and 23%, respectively. MLST analyses of the 40 isolates generated 25 different sequence types (STs). ST-443 (12 isolates) and ST-21 (8 isolates) were dominant among the domestic isolates; however, STs varied among travel-associated isolates. Nalidixic acid, tetracycline, and ciprofloxacin resistance rates of the 40 isolates were 100% (40/40), 95% (38/40), and 88% (35/40), respectively. Domestic isolates exhibited 2-fold higher ciprofloxacin, telithromycin, and chloramphenicol resistance rates than travel-associated isolates. These results indicate a diverse genetic background for travel-associated C. jejuni and suggest that this pathogen may be an important emerging public health threat to travelers.

Possibility of CTX-M-14 Gene Transfer from Shigella sonnei to a Commensal Escherichia coli Strain of the Gastroenteritis Microbiome.

OBJECTIVES: To investigated whether the CTX-M-14 gene could be transferred from a clinical Shigella sonnei strain to commensal Escherichia coli strain in the gastroenteritis microbiome. METHODS: E. coli strains were isolated from 30 stool samples of S. sonnei infected students in a gastroenteritis outbreak in 2004 and were characterized by antibiotic resistance analysis, in vitro conjugation and in vivo transfer of CTX-M-14 gene and molecular assays. RESULTS: One strain of Escherichia coli that had high levels of resistance to cefotaxime was isolated from a patient infected with S. sonnei. Isoelectric focusing showed that the E. coli and S. sonnei strains produced a ß-lactamase with an isoelectric point of 8.1. Moreover, polymerase chain reaction analysis indicated that both strains possessed the same DNA sequences for CTX-M-14. The results of in vitro and in vivo conjugation showed that the efficiency of CTX-M-14 transfer from S. sonnei to E. coli was similar to CTX-M-14 transfer between E. coli strains. CONCLUSION: The data suggest that the acquisition of the extended-spectrum ß-lactamases gene by pathogenic bacteria in the human intestinal tract to commensal microbiome bacteria can cause serious infectious diseases.

Characterization of CTX-M-type extended-spectrum beta-lactamase-producing diarrheagenic Escherichia coli isolates in the Republic of Korea during 2008-2011.

To characterize the extended-spectrum beta-lactamases (ESBLs) in diarrheagenic Escherichia coli from Korea in 2008-2011, we screened seven enterotoxigenic E. coli (ETEC) and one enteroaggregative E. coli (EAEC) that produce ESBLs from a nationwide survey. All eight isolates produced CTX-M-type ESBLs, including CTX-M-12 (n = 4), CTX-M-14 (n = 2), and CTX-M-15 (n = 2). PCR-based replicon typing indicated that the blaCTX-M-12 genes of four ETEC isolates were carried on a conjugative IncF plasmid, whereas the blaCTX-M-14 of one EAEC was located on an IncK plasmid. This is the first report of the occurrence of blaCTX-M genes in clinical isolates of EAEC in Korea. The ESBL-producing isolates were shown to be different based on pulsed-field gel electrophoresis and multilocus sequence typing, whereas the four isolates with CTX-M-12 were clonally related. These observations raise an alarm for the spread of plasmid-mediated resistance to ESBL among diarrheagenic E. coli.

Comparative proteomic label-free analysis of Campylobacter jejuni NCTC 11168 cultured with porcine mucin.

Campylobacter jejuni is a major gastrointestinal pathogen in humans. Poultry is a primary reservoir for C. jejuni, and C. jejuni appears to be highly adapted to the gastrointestinal tracts of avian species. We determined the protein expression profiles of C. jejuni NCTC 11168 cultured in medium containing porcine mucin. Differentially expressed proteins in the presence and absence of porcine mucin were identified using the label-free method. We identified 52 proteins with expression that was either upregulated (32 proteins) or downregulated (20 proteins) by porcine mucin. These proteins are involved in diverse cellular functions, such as motility, cell wall synthesis, iron transport, energy production, and amino acid metabolism. In particular, the upregulated proteins were involved in chemotaxis (CheV and CetA), motility (FlaA), colonization and adherence (CadF, FrdA, CfrA, MapA, and HydA), and stress tolerance (TrxB and ClpB). These results suggest that C. jejuni changes its protein expression in response to porcine mucin and that this change in expression may contribute to host adaptation of C. jejuni NCTC 11168.

Macrolide resistance of Mycoplasma pneumoniae, South Korea, 2000-2011.

In Korea, Mycoplasma pneumoniae was detected in 255/2,089 respiratory specimens collected during 2000-2011; 80 isolates carried 23S rRNA gene mutations, and 69/123 culture-positive samples with the mutation were resistant to 5 macrolides. During 2000-2011, prevalence of the mutation increased substantially. These findings have critical implications for the treatment of children with mycoplasma pneumonia.

A foodborne outbreak of Staphylococcus aureus associated with fried chicken in Republic of Korea.

An outbreak of Staphylococcus aureus infections occurred in a university with an enrollment of 80 students in the city of Daejon, Republic of Korea. All nine S. aureus isolates from patients (n = 7), staff members (n = 1), and the fried chicken served as the lunch (n = 1) harbored the enterotoxin A gene and showed an identical antibioticresistant profile, PFGE banding pattern (STAS16.001), and sequence type, ST 6. These results suggested that the outbreak was associated with eating the fried chicken that had been handled by an infected staff member. This case report demonstrated a practical approach to identifying the source and transmission of an infection.

Carriage rates and serogroups of Neisseria meningitidis among freshmen in a University dormitory in Korea.

PURPOSE: Neisseria meningitidis is a leading cause of bacterial meningitis in young adults. University students, especially those living in dormitories, have been known to be at increased risk of meningococcal disease. We performed a longitudinal study to determine the carriage rates of N. meningitidis and the changes thereof. MATERIALS AND METHODS: We recruited Inha University freshmen who were, at that time, admitted to a student dormitory. A pharyngeal swab was taken from all participant who were also asked to complete a questionnaire. This was repeated four weeks later. RESULTS: A total of 136 students were enrolled at the first culture. After four weeks, 128 students were enrolled, including 106 re-participants. The overall carriage rates changed from 11.8% to 14.1%. In analysis of the 106 re-participants, "visiting to pubs" was associated with carriage of N. meningitis for both the first (p=0.047) and second cultures (p=0.026). Serogroup C was found to be the most frequent serogroup (5 isolates), while 3 isolates were found from serogroup B. The most prevalent PorA types were P1.22,14-6 (4 isolates) and P1.19,15 (3 isolates). The DNA sequences of PorA VR2 were changed in 2 students during prolonged carriage. CONCLUSION: The meningococcal carriage rate among first year university students who resided in a dormitory did not significantly increase over 4-week interval between cultures, which is markedly different from those reported in Western studies. Close social contact appeared to be related with carriage. Our data also revealed diversity in PorA types, suggesting the possibility of rapid mutation of the PorA gene during the 4-week interval.

Structural analysis and serological test of arginine periplasmic binding protein 2 from Chlamydophila pneumoniae.

The 'art' genes encode specific arginine uptake proteins, and are repressed by the repressible promoters of ArgR, affecting transcription of artJ. Cpb0502, the arginine-binding periplasmic protein 2 precursor from Chlamydophila pneumoniae TW-183 strains, is responsible for arginine transport. As C. pneumoniae is difficult to isolate and culture, there have been many studies of better ways to detect it. A microimmunofluorescence assay (MIF) is still considered to be the 'gold standard' for detecting C. pneumoniae. Although MIF has its own limitations, a number of immunogenic antigens have been shown to be C. pneumoniae specific by this test. Here, we report Cpb0502 as a specific immunogenic antigen against C. pneumoniae as it was detected only in human infection sera of C. pneumoniae but not in Legionella pneumophila and Mycoplasma pneumoniae infection sera, showing high specificity and sensitivity by MIF, western blot and ELISA analysis. And also the crystal structure of Cpb0502 was determined to be a dimer at 2.07Å, revealing a similar backbone structure to a histidine kinase receptor, HK29S. Therefore we may suggest that Cpb0502 is a candidate immunogenic antigen for better diagnosis of C. pneumoniae.