Kumsun Cho

Imaging the Upper Crust of the Korean Peninsula by Surface-Wave Tomography

Cross correlation of seismic-background motions (Campillo and Paul, 2003; Shapiro et al. , 2005) is applied to observations from the Korean Meteorological Administration seismic network to estimate the short-period Rayleigh and Love wave dispersion characteristics of the region. Standard processing procedures are applied to the cross correlation, except that signal whitening is used in place of one-bit sampling to equalize power in signals from different times. Multiple-filter analysis is used to extract the group velocities from the estimated Green’s functions, which are then used to image the spatially varying dispersion at periods between 0.5 and 20 sec. The tomographic inversion technique used inverts all periods simultaneously to provide a smooth dispersion curve as a function of period in addition to the usual smooth spatial image for a given period. The Gyeongsang Basin in the southeastern part of the peninsula is clearly resolved with lower group velocities.

Imaging the Three-Dimensional Crust of the Korean Peninsula by Joint Inversion of Surface-Wave Dispersion and Teleseismic Receiver Functions

Abstract A detailed study of the 3D variation of shear-wave velocities in thesouthern part of the Korean Peninsula is made by combining high-frequency surface-wave tomography results of Cho et al. (2006b) with teleseismic P -wave receiverfunctions at 80 locations on the peninsula. Receiver functions were derived fromhigh-gain acceleration, short-period, and broadband digital data streams of the KoreaMeteorological Administration ( KMA ) and Korean Institute for Geosciences andMineral Resources ( KIGAM ) networks. Vertical cross sections trace the lateral vari-ation in the depth to the Moho, the variation of low velocities near the surface, andthe variable thickness of the transition from surface velocities to midcrustal veloci-ties. The derived crustal structure provides new insights on the evolution of theKorean crust.Introduction Geophysics, and seismology, in particular, provides in-direct means for assessing the larger- to local-scale, present-day architecture of continental masses through remote sens-ing (Bostock, 1999). Although field geology has providedvast information on the upper crust, mapping variations instructure in depth through geophysical investigation is aprincipal step in unraveling and understanding the evolutionof the continental lithosphere. In an area whose genetic pro-cess is relatively unknown, such as the Korean Peninsula, itis important to add geophysical constraints to reveal the con-tinental evolution.The Korean Peninsula (Fig. 1), situated at the easternmargin of the Eurasian continent, is a tectonic assemblageof two Phanerozoic mobile belts, the Imjingang belt and theOkcheon (fold) belt; three Precambrian basement terrains,Nangrim, Gyeonggi, and Yeongnam Massifs from north tosouth; and one volcanoclastic basin, that is, Gyeongsang ba-sin (Reedmann and Um, 1975; Cluzel

Hypoxia-inducible Factor 1 Mediates Nasal Polypogenesis by Inducing Epithelial-to-Mesenchymal Transition

RATIONALE Nasal polyposis implies a refractory clinical course in case of chronic rhinosinusitis (CRS). Although hypoxia is believed to be associated with nasal polyposis, little is known about the mechanism underlying polypogenesis. OBJECTIVES To determine if hypoxia drives nasal polyposis by epithelial-to-mesenchymal transition (EMT). METHODS Immunoblotting, immunofluorescence, flow cytometry, and real-time polymerase chain reaction were performed to evaluate EMT and hypoxic markers in human nasal epithelial cells (hNECs) and in sinonasal tissues from patients with CRS with or without polyps. In addition, the effects of hypoxia-inducible factor (HIF)-1α inhibitors on nasal polypogenesis were investigated in a murine model. MEASUREMENTS AND MAIN RESULTS E-cadherin and α-smooth muscle actin (α-SMA) were down-regulated and up-regulated, respectively, in patients with polyps as compared with patients without polyps. Under hypoxia, hNECs transformed to a mesenchymal shape, and demonstrated representative changes in EMT markers; that is, mesenchymal markers (α-SMA, vimentin, and twist) increased but epithelial markers (E-cadherin and β-catenin) decreased. Mechanistically, E-cadherin level was recovered in hypoxia by silencing HIF-1α and decreased in normoxia by expressing HIF-1α. Furthermore, hypoxia was found to down-regulate PP2Ac phosphatase and up-regulate pSmad3, which led to α-SMA induction. In CRS sinonasal specimens, HIF-1α expression was found to correlate with E-cadherin loss and α-SMA expression. Finally, HIF-1α inhibitors suppressed nasal polypogenesis in a murine model. CONCLUSIONS hNECs undergo EMT during hypoxia and this process is critically mediated by HIF-1α and pSmad3. This study shows that hypoxia-induced EMT is likely to contribute to nasal polyposis in CRS, and suggests that HIF-1α be viewed as a therapeutic target for nasal polyposis.

Antihyperglycemic mechanism of metformin occurs via the AMPK/LXRα/POMC pathway

Metformin is a first-line drug for treating type 2 diabetes. Although metformin is known to phosphorylate AMP-activated protein kinase (AMPK), it is unclear how the glucose-lowering effect of metformin is related to AMPK activation. The aim of this study was to identify the urinary endogenous metabolites affected by metformin and to identify the novel underlying molecular mechanisms related to its anti-diabetic effect. Fourteen healthy male subjects were orally administered metformin (1000 mg) once. First morning urine samples were taken before and after administration to obtain metabolomic data. We then further investigated the anti-diabetic mechanism of metformin in vitro and in vivo. The fluctuation of the metabolite cortisol indicated that the neuroendocrine system was involved in the anti-diabetic effect of metformin. Actually we found that metformin induced AMPK/liver X receptor α (LXRα) phosphorylation, followed by pro-opiomelanocortin (POMC) suppression in rat pituitary cells. We confirmed this result by administering metformin in an animal study. Given that cortisol stimulates gluconeogenesis, we propose the anti-hyperglycemic effect of metformin is attributed to reduced POMC/adrenocorticotropic hormone (ACTH)/cortisol levels following AMPK/LXRα phosphorylation in the pituitaries.

Mad1 mediates hypoxia-induced doxorubicin resistance in colon cancer cells by inhibiting mitochondrial function.

Cancer cells acquire resistance to chemotherapy under hypoxia, which is mainly driven by the transcription factor HIF (hypoxia-inducible factor). Yet, it is uncertain which molecules mediate such resistance. While profiling gene expression in colon cancer cells, we found that Mad1 (MAX dimerization protein 1) is substantially induced during hypoxia. The hypoxic induction of Mad1 was confirmed by RT-PCR and Western blotting. The Mad1 expression was attenuated by HIF-1α small interfering (si) RNAs, but less so by HIF-2α siRNAs. Moreover, luciferase reporter and chromatin immunoprecipitation analyses revealed that HIF-1 transactivates the MAD1 gene by directly targeting a putative hypoxia-response element in the MAD1 promoter. We next investigated if Mad1 is responsible for the hypoxia-induced drug resistance. We treated colon cancer cells with doxorubicin and found that the cells under hypoxia survived more than those under normoxia. The doxorubicin resistance was not induced in Mad1-knocked-down cells even under hypoxia. Mad1 knockdown reactivated the caspase-9/caspase-3/PARP apoptotic pathway under hypoxia. Moreover, doxorubicin-induced production of reactive oxygen species was significantly reduced under hypoxia, which was reversed by Mad1 knockdown. During hypoxia, mitochondria became bigger in size and less active in respiration, both of which were attenuated by Mad1 knockdown. These data indicate that hypoxia-induced Mad1 lowers doxorubicin-stimulated generation of reactive oxygen species through mitochondrial inhibition and subsequently contributes to tumor resistance to doxorubicin. Therefore, Mad1 could be a potential target for sensitizing cancer cells to redox-cycling drugs such as doxorubicin.

Metabolomic analysis identifies potential diagnostic biomarkers for aspirin‐exacerbated respiratory disease

To date, there has been no reliable in vitro test to diagnose aspirin‐exacerbated respiratory disease (AERD).

A study on the prognostic value of clinical and surgical features of dermatofibrosarcoma protuberans in Korean patients

Background  Dermatofibrosarcoma protuberans (DFSP) is a rare spindle cell tumour with locally aggressive characteristics. Only few studies on the epidemiology of DFSP in Asians have been reported.

Combined untargeted and targeted metabolomic profiling reveals urinary biomarkers for discriminating obese from normal-weight adolescents.

Childhood and adolescent obesity may lead to obesity and related complications in adulthood. Biomarkers of obesity can be useful for screening for obesity complications and promoting early intervention during school age. Thus, the metabolomic differences in obese children and adolescents should be investigated for identification of potential biomarkers.

Exploration of the Sphingolipid Metabolite, Sphingosine-1-phosphate and Sphingosine, as Novel Biomarkers for Aspirin-exacerbated Respiratory Disease

Sphingolipid (SL) metabolites have been suggested to be important inflammatory mediators in airway inflammation and asthma. However, little is known about SL metabolites in aspirin-exacerbated respiratory disease (AERD). We aimed to explore the potential AERD biomarkers by conducting lipidomics targeting SL metabolites. The levels of SL metabolites in serum and urine samples from 45 AERD patients and 45 aspirin-tolerant asthma (ATA) patients were quantified through mass spectrometry. During the lysine-aspirin bronchoprovocation test (ASA-BPT), the levels of serum sphingomyelin (SM) were significantly decreased in AERD (P < 0.05) but not in ATA. The serum SM levels were positively correlated with airway responsiveness to methacholine. At the basal status before the ASA-BPT, the levels of serum sphingosine-1-phosphate (S1P) and urine sphingosine were significantly higher in the AERD patients compared with that of ATA patients (P < 0.001) and were positively correlated with a greater decrease in FEV1 (%) values following the ASA-BPT test (P < 0.001 for each), and with serum periostin level (P < 0.05 for each). This study is the first to evaluate serum S1P and urine sphingosine as potential biomarkers of AERD as well as to examine the metabolic disturbance of SL in AERD patients.

Application of IFN‐γ releasing assay for the diagnosis of erythema induratum of Bazin

Background  Erythema induratum of Bazin (EIB) is regarded to be a hypersensitive reaction to the concomitant tuberculosis. Recently, interferon‐γ releasing assay (IGRA) has been focused as a promising tool in the diagnosis of latent tuberculosis. However, there has been no large scale study to investigate the usefulness of IGRA in the diagnosis of EIB.