[Show abstract][Hide abstract] ABSTRACT: Helicobacter pylori infection causes a variety of gastrointestinal diseases, including peptic ulcers and gastric cancer. Its colonization of the gastric mucosa of the human stomach is a prerequisite for survival in the stomach. Colonization depends on its motility, which is facilitated by the helical shape of the bacterium. In H. pylori, cross-linking relaxation or trimming of peptidoglycan muropeptides affects the helical cell shape. Csd4 has been identified as one of the cell shape-determining peptidoglycan hydrolases in H. pylori. It is a Zn(2+)-dependent D,L-carboxypeptidase that cleaves the bond between the γ-D-Glu and the mDAP of the non-cross-linked muramyltripeptide (muramyl-L-Ala-γ-D-Glu-mDAP) of the peptidoglycan to produce the muramyldipeptide (muramyl-L-Ala-γ-D-Glu) and mDAP. Here, the crystal structure of H. pylori Csd4 (HP1075 in strain 26695) is reported in three different states: the ligand-unbound form, the substrate-bound form and the product-bound form. H. pylori Csd4 consists of three domains: an N-terminal D,L-carboxypeptidase domain with a typical carboxypeptidase fold, a central β-barrel domain with a novel fold and a C-terminal immunoglobulin-like domain. The D,L-carboxypeptidase domain recognizes the substrate by interacting primarily with the terminal mDAP moiety of the muramyltripeptide. It undergoes a significant structural change upon binding either mDAP or the mDAP-containing muramyltripeptide. It it also shown that Csd5, another cell-shape determinant in H. pylori, is capable of interacting not only with H. pylori Csd4 but also with the dipeptide product of the reaction catalyzed by Csd4.
[Show abstract][Hide abstract] ABSTRACT: The general consensus is that immune cells are exposed to physiological hypoxia in vivo (PhyO2, 2-5% PO2). However, functional studies of B cells in hypoxic conditions are sparse. Recently, we reported the expression in mouse B cells of TASK-2, a member of pH-sensitive two-pore domain K(+) channels with background activity. In this study, we investigated the response of K(+) channels to sustained PhyO2 (sustained hypoxia [SH], 3% PO2 for 24 h) in WEHI-231 mouse B cells. SH induced voltage-independent background K(+) conductance (SH-Kbg) and hyperpolarized the membrane potential. The pH sensitivity and the single-channel conductance of SH-Kbg were consistent with those of TASK-2. Immunoblotting assay results showed that SH significantly increased plasma membrane expressions of TASK-2. Conversely, SH failed to induce any current following small interfering (si)TASK-2 transfection. Similar hypoxic upregulation of TASK-2 was also observed in splenic primary B cells. Mechanistically, upregulation of TASK-2 by SH was prevented by si hypoxia-inducible factor-1α (HIF-1α) transfection or by YC-1, a pharmacological HIF-1α inhibitor. In addition, TASK-2 current was increased in WEHI-231 cells overexpressed with O2-resistant HIF-1α. Importantly, [Ca(2+)]c increment in response to BCR stimulation was significantly higher in SH-exposed B cells, which was abolished by high K(+)-induced depolarization or by siTASK-2 transfection. The data demonstrate that TASK-2 is upregulated under hypoxia via HIF-1α-dependent manner in B cells. This is functionally important in maintaining the negative membrane potential and providing electrical driving force to control Ca(2+) influx.
Journal of immunology (Baltimore, Md. : 1950). 10/2014;
[Show abstract][Hide abstract] ABSTRACT: An unresolved issue in genotoxic stress response is identification of induced regulatory proteins and how these activate tumor suppressor p53 to determine appropriate cell responses. Transcription factor KAISO was previously described to repress transcription following binding to methylated DNA. In this study, we show that KAISO is induced by DNA damage in p53-expressing cells and then interacts with the p53-p300 complex to increase acetylation of p53 K320 and K382 residues, although decreasing K381 acetylation. Moreover, the p53 with this particular acetylation pattern shows increased DNA binding and potently induces cell cycle arrest and apoptosis by activating transcription of CDKN1A (cyclin-dependent kinase inhibitor 1) and various apoptotic genes. Analogously, in Kaiso KO mouse embryonic fibroblast cells, p53-to-promoter binding and up-regulation of p21 and apoptosis gene expression is significantly compromised. KAISO may therefore be a critical regulator of p53-mediated cell cycle arrest and apoptosis in response to various genotoxic stresses in mammalian cells.
Proceedings of the National Academy of Sciences of the United States of America. 10/2014;
[Show abstract][Hide abstract] ABSTRACT: PM2.5 carbonaceous particles were measured at Gosan, South Korea during 29 March-11 April 2002 which includes a pollution period (30 March-01 April) when the highest concentrations of major anthropogenic species (nss-SO4 (2-), NO3 (-), and NH4 (+)) were observed and a strong Asian dust (AD) period (08-10 April) when the highest concentrations of mainly dust-originated trace elements (Al, Ca, Mg, and Fe) were seen. The concentrations of elemental carbon (EC) measured in the pollution period were higher than those measured in the strong AD period, whereas an inverse variation in the concentrations of organic carbon (OC) was observed. Based on the OC/EC ratios, the possible source that mainly contributed to the highly elevated OC concentrations measured in the strong AD period was biomass burning. The influence of the long-range transport of smoke plumes emitted from regional biomass burning sources was evaluated by using MODIS (Moderate Resolution Imaging Spectroradiometer) satellite data for fire locations and the potential source contribution function analysis. The most potential source regions of biomass burning were the Primorsky and Amur regions in Far Eastern Russia and southeastern and southwestern Siberia, Russia. Further discussion on the source characteristics suggested that the high OC concentrations measured in the strong AD period were significantly affected by the smoldering phase of biomass burning. In addition to biomass burning, secondary OC (SOC) formed during atmospheric long-range transport should be also considered as an important source of OC concentration measured at Gosan. Although this study dealt with the episodic case of the concurrent increase of dust and biomass burning particles, understanding the characteristics of heterogeneous mixing aerosol is essential in assessing the radiative forcing of aerosol.
Environmental science and pollution research international. 09/2014;
[Show abstract][Hide abstract] ABSTRACT: Ciglitazone is a peroxisome proliferator-activated receptor γ (PPARγ) agonist and improves insulin sensitivity. Apart from antidiabetic activity, ciglitazone elicits inhibitory effects on cancer cell growth. Recent studies indicate glucose metabolism plays a key role in malignant diseases. Significant increase in glucose consumption is found in malignant conditions. The role of ciglitazone in cancer cell death in relation to glucose metabolism is unclear. Thus we designed this study to determine the effect of ciglitazone on glucose metabolism. First, we found ciglitazone inhibited glucose uptake in ovarian cancer cells but didn't affect hexokinase activity. Ciglitazone decreased expression levels of glucose transporter-1 (GLUT-1). We also found that ciglitazone and siGLUT-1 treatments induced cell death in ovarian cancer cells. We identified that ciglitazone decreased expressions of specific protein 1 (Sp-1) and β-catenin while increased phosphorylation levels of AMP-activated protein kinase. In vivo study using NOD-scid IL2Rgamma(null) mice confirmed that ciglitazone significantly decreased ovarian cancer mass transplanted onto the back of the mice. Finally, we determined GLUT-1 expressions in patients with serous type ovarian cancer and found that GLUT-1 expression was markedly increased in cancer patients and expression level was proportional to the degree of cancer stages. These results suggest ciglitazone induces apoptosis in ovarian cancer cells by the inhibition of GLUT-1 and provides a possible therapeutic effect of ciglitazone as an adjuvant drug in the treatment of ovarian cancer.
[Show abstract][Hide abstract] ABSTRACT: MEMS gyroscopes have favorable characteristics, including small size, high throughput, and low cost. The performance of MEMS gyroscopes depends on the displacement sensitivity of the capacitors. In this paper, we describe the fabrication of 300-?m-thick gyroscopes that can provide high displacement sensitivity and are robust to fabrication tolerances, i.e. deep reactive ion etch (DRIE) rate uniformity. When thick structures are perforated using DRIE to achieve high-aspect-ratio features, footing is commonly observed. However, we describe a fabrication method that circumvents problems associated with footing and side-wall etching, so that the gyroscopes can have uniform dimensions and small variations across the wafer. Using a post-fabrication translation approach, the position of capacitors is modified following DRIE, and the gap in the gyroscopes can be reduced to 3??m, which leads to an aspect ratio of 100. Using this method, we fabricated MEMS gyroscopes that can overcome the DRIE aspect ratio limit and have capacitors with higher sensitivities than those of other gyroscopes, which typically employ substrates that are less than 100??m thick. The gyroscope had a resonant frequency of 9.91?kHz, a quality factor of 2500 and a sensitivity of 23?mV/[deg/s].
Journal of Micromechanics and Microengineering 06/2014; 24(7):075013. · 1.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study is to investigate that effect of action observation training (AOT) on knee joint function and balance in total knee replacement (TKR) patients. The subjects consisted of eighteen post-TKR patients. All participants underwent conventional physical therapy. In addition, patients in the AOT group (n= 9) were asked to observe video clips showing daily actions and to imitate them afterward. Patients in the control group (n= 9) were asked to execute the same actions as patients in the AOT group. Outcome measures Western Ontario and Mc-Master Universities Osteoarthritis Index (WOMAC) included pain, stiffness, function and Timed Up and Go (TUG) test. After intervention, patients in the AOT group score better than patients in the control group. After TUG test, patients in the AOT group and control group were no significant difference between two groups. In addition to conventional physical therapy, AOT is effective in the rehabilitation of post-TKR patients. Action observation training is considered conducive to improving knee functions and ameliorating pain and stiffness, of patients who underwent TKR.
Journal of exercise rehabilitation. 06/2014; 10(3):168-71.
[Show abstract][Hide abstract] ABSTRACT: Document-level relevance judgments are a major component in the calculation of effectiveness metrics. Collecting high-quality judgments is therefore a critical step in information retrieval evaluation. However, the nature of and the assumptions underlying relevance judgment collection have not received much attention. In particular, relevance judgments are typically collected for each document in isolation, although users read each document in the context of other documents. In this work, we aim to investigate the nature of relevance judgment collection. We collect relevance labels in both isolated and conditional setting, and ask for judgments in various dimensions of relevance as well as overall relevance. Then we compare the relevance metrics based on various types of judgments with other metrics of quality such as user preference. Our analyses illuminate how these settings for judgment collection affect the quality and the characteristics of the judgments. We also find that the metrics based on conditional judgments show higher correlation with user preference than isolated judgments.
Proceedings of the 23rd international conference on World wide web; 04/2014
[Show abstract][Hide abstract] ABSTRACT: Background/Aim: Clinical trials have shown efficacy of the anti-HER2 monoclonal antibody trastuzumab in metastatic breast cancer patients. The aim of the present study was to elucidate the mechanisms by which up-regulation of fatty acid synthase (FAS) expression confers resistance to trastuzumab in HER2-positive breast cancers.
The expression of FAS as well as the cytotoxic effects of combinatorial treatment of trastuzumab and juglone was investigated by immunoblotting, BrdU incorporation, TUNEL assay, and soft agar assay.
Pin1 enhanced EGF-induced SREBP1c promoter activity, resulting in the induction of FAS expression in BT474 cells. In contrast, juglone, a potent Pin1 inhibitor, significantly enhanced trastuzumab-induced FAS down-regulation and cell death in BT474 cells. Furthermore, trastuzumab, when used in combination with gene silencing or chemical inhibition of Pin1, increased cleaved poly(ADP-ribose) polymerase and DNA fragmentation to increase trastuzumab sensitivity.
Pin1-mediated FAS overexpression is a major regulator of trastuzumab-resistant breast cancer growth and survival.
Anticancer research 03/2014; 34(3):1409-16. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Interleukin-22 (IL-22), one of the cytokines secreted by T helper 17 (Th17) cells, binds to a class II cytokine receptor containing an IL-22 receptor 1 (IL-22R1) and IL-10R2 and influences a variety of immune reactions. IL-22 has also been shown to modulate cell cycle and proliferation mediators such as extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but little is known about the underlying molecular mechanisms of IL-22 in tumorigenesis. In this paper, we propose that IL-22 has a crucial role to play in controlling epithelial cell proliferation and tumorigenesis in the breast. IL-22 increased MAP3K8 phosphorylation through IL-22R1, followed by the induction of MEK-ERK, JNK-c-Jun, and STAT3 signaling pathways. Furthermore, IL-22-IL-22R1 signaling pathway activated activator protein-1 (AP-1) and HER2 promoter activity. In addition, Pin1 was identified as a key positive regulator for the phosphorylation-dependent MEK, c-Jun, and STAT3 activity induced by IL-22. Pin1(-/-) mouse embryonic fibroblasts (MEF) exhibited significantly a decrease in IL-22-induced MEK1/2, c-Jun, and STAT3 phosphorylation compared to Pin1(+/+) MEF. In addition, a knockdown of Pin1 prevented phosphorylation induced by IL-22. The in vivo chorioallantoic membrane (CAM) assay also showed that IL-22 increased tumor formation of JB6 Cl41 cells. Moreover, the knockdown of MAP3K8 and Pin1 attenuated tumorigenicity of MCF7 cells. Consistent with these observations, IL-22 levels positively correlate with MAP3K8 and Pin1 expression in human breast cancer. Overall, our findings point to a critical role for the IL-22-induced MAP3K8 signaling pathway in promoting cancer-associated inflammation in the tumor microenvironment.
[Show abstract][Hide abstract] ABSTRACT: Recent development of ubiquitous technology prompted its application for the blinds. In this work, we developed an RFID goggle equipped with a voice guide for the blinds who have difficulties in obtaining medication informations. When a blind, wearing our RFID goggle, tags the RFID tag attached to a drug, the RFID goggle announces the already saved medication information. We used STM32 as MCU and MFRC523 for RFID chipset in the reader. Our miniaturized hardware supported ISO 14443A protocol, and the standardized conformance test was performed. When the blinds wear our RFID goggle, they can conveniently access to the medication informations, and thus the drug misuse cases may decrease.
Journal of Sensor Science and Technology. 01/2014; 23(2).
[Show abstract][Hide abstract] ABSTRACT: Purpose
To investigate the clinical utility of targeted next-generation sequencing (NGS) for predicting the responsiveness to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy, we compared the efficacy with conventional sequencing in never-smokers with lung adenocarcinoma (NSLAs).
Patients and Methods
We obtained DNA from 48 NSLAs who received gefitinib or erlotinib for their recurrent disease after surgery. Sanger sequencing and peptide nucleic acid clamp polymerase chain reaction (PCR) were used to analyze EGFR, KRAS, BRAF, and PIK3CA mutations. We analyzed ALK, RET, and ROS1 rearrangements by fluorescent in situ hybridization or reverse transcriptase-PCR and quantitative real-time PCR. After molecular screening, Ion Torrent NGS was performed in 31 cases harboring only EGFR exon 19 deletions (19DEL), an L858R mutation, or none of the above mutations.
The 31 samples were divided into four groups: 1) responders to EGFR-TKIs with only 19DEL or L858R (n = 15); 2) primary resistance to EGFR-TKI with only 19DEL or L858R (n = 4); 3) primary resistance to EGFR-TKI without any mutations (n = 8); 4) responders to EGFR-TKI without any mutations (n = 4). With NGS, all conventionally detected mutations were confirmed except for one L858R in group 2. Additional uncovered predictive mutations with NGS included one PIK3CA E542 K in group 2, two KRAS (G12 V and G12D), one PIK3CA E542 K, one concomitant PIK3CA and EGFR L858R in group 3, and one EGFR 19DEL in group 4.
Targeted NGS provided a more accurate and clinically useful molecular classification of NSLAs. It may improve the efficacy of EGFR-TKI therapy in lung cancer.
[Show abstract][Hide abstract] ABSTRACT: A reversible, carbon dioxide mediated chemical hydrogen storage was first demonstrated using a heterogeneous Pd catalyst supported on mesoporous graphitic carbon nitride (Pd/mpg-C3N4). The Pd nanoparticles were found to be uniformly dispersed onto mpg-C3N4 with an average size of 1.7 nm without any agglomeration and further exhibit superior activity for the dehydrogenation of formic acid with a turnover frequency of 144 h-1 even in the absence of external bases at room temperature. Initial DFT studies suggest that basic sites located at the mpg-C3N4 support play synergetic roles in stabilizing
reduced Pd nanoparticles without any surfactant as well as in initiating H2 -release by deprotonation of formic acid, and these potential interactions were further confirmed by X-ray absorption near edge structure (XANES). Along with dehydrogenation, Pd/mpg-C3N4
also proves to catalyze the regeneration of formic acid via CO2 hydrogenation. Governing factors on CO2 hydrogenation are further elucidated to increase the quantity of the desired formic acid with high selectivity.
[Show abstract][Hide abstract] ABSTRACT: Meniere's disease is an inner ear disorder that can manifest as fluctuating vertigo, sensorineural hearing loss, tinnitus, and aural fullness. However, the pathologic mechanism of Meniere's disease is still unclear. In this study, we evaluated autoimmunity as a potential cause of Meniere's disease. In addition we tried to find useful biomarker candidates for diagnosis. We investigated the protein composition of human inner ear fluid using liquid column mass spectrometry, the autoimmune reaction between circulating autoantibodies in patient serum and multiple antigens using the Protoarray system, the immune reaction between patient serum and mouse inner ear tissues using western blot analysis. Nine proteins, including immunoglobulin and its variants and interferon regulatory factor 7, were found only in the inner ear fluid of patients with Meniere's disease. Enhanced immune reactions with 18 candidate antigens were detected in patients with Meniere's disease in Protoarray analysis; levels of 8 of these antigens were more than 10-fold higher in patients than in controls. Antigen-antibody reactions between mouse inner ear proteins with molecular weights of 23-48 kDa and 63-75 kDa and patient sera were detected in 8 patients. These findings suggest that autoimmunity could be one of the pathologic mechanisms behind Meniere's disease. Multiple autoantibodies and antigens may be involved in the autoimmune reaction. Specific antigens that caused immune reactions with patient's serum in Protoarray analysis can be candidates for the diagnostic biomarkers of Meniere's disease.
PLoS ONE 01/2014; 9(10):e111039. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We have incorporated silicon nanoparticles (Si-nps) into organic–inorganic hybrid solar cells in place of the chalcogenide nanocrystals that are commonly employed in such devices. Poly(3,4-ethylenedioxy-thiophene):poly(styrene sulfonate) (PEDOT:PSS) and phenyl-C61-butyric acid methyl ester (PCBM) were employed as hole and electron transport layers, respectively. We used transmission electron microscopy, Raman spectroscopy, and ultraviolet–visible spectroscopy to fully characterize the Si-nps and relate their characteristics to the performance of the hybrid solar cells. We show that the open circuit voltage (VOC) was largely dependent on the size and amorphous volume fraction of Si-nps. Our findings imply that the amorphous phase and small size of Si-nps produce band gap widening that increases the VOC when coupled with PCBM as acceptor. The maximum VOC was up to 0.634 V in a hybrid device with 5.7 nm Si-nps.
Current Applied Physics 01/2014; 14(1):127–131. · 2.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462).
Journal of Korean medical science 01/2014; 29(1):61-8. · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study investigated the effect of Melissa officinalis extract on laser-induced choroidal neovascularization (CNV) in a rat model. The mechanism by which M. officinalis extract acted was also investigated.
PLoS ONE 01/2014; 9(10):e110109. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pendrin mutations cause enlarged vestibular aqueducts and various degrees of sensorineural hearing loss. The selective abolition of pendrin causes dilation of the membranous labyrinth known as endolymphatic hydrops, loss of the endocochlear potential, and consequently loss of hearing function. Because Na+ transport is one of the most important driving forces for fluid transport, the epithelial Na+ channel (ENaC) is believed to play an important role in fluid volume regulation in the inner ear. Therefore, the dysfunction of Na+ transport through ENaC by the acidification of endolymph in Pendred syndrome is one of the potential causes of endolymphatic hydrops. We investigated the changes of ENaC expression and function during the development of the pendrin knock-out mouse. In the cochlea, the expression of β and γENaC was significantly increased at P56 in Pds-/- mice compared with Pds+/+ mice. In the vestibule, the expression of βENaC was significantly increased at P56, and γENaC expression significantly increased from P6 to P56 in Pds-/- mice. The ENaC-dependent trans-epithelial current was not significantly different between Pds+/+ and Pds-/- mice in Reissner's membrane or the saccular extramacular roof epithelium at P0, but the current was significantly increased in Pds-/- mice at P56 compared with Pds+/+ mice. These findings indicate that the expression and function of ENaC were enhanced in Pds-/- mice after the development of endolymphatic hydrops as a compensatory mechanism. This result provides insight into the role of Na+ transport in the development and regulation of endolymphatic hydrops due to pendrin mutations.
PLoS ONE 01/2014; 9(4):e95730. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hexagonal Ba-ferrites are widely suggested as materials for small antennas. In this paper, the sintering behavior and magneto-electric properties of () ceramics were investigated for small antenna application. All samples of ceramics were prepared by the solid-state reaction method and sintered at . From the XRD patterns of the sintered ceramics, the Z-type phases were found to be the main phases. The real part of permittivity and permeability of the ceramics decreased with frequency. On the other hand, loss tangents of permittivity and permeability tended to behave opposite to real part of permittivity and permeability. The real part of permeability was affected by Mn additions. The real part of permittivity, the loss tangent of permittivity and the real part of permeability, the loss tangent of permeability of ceramics were 19.774, 0.176 and 15.183, 0.073, respectively, at 510 MHz. In order to investigate the effect of magneto-dielectric ceramics on antenna, PIFA (Planar Inverted F Antenna) was simulated with CST (Computer Simulation Technology). The operating frequency of antenna was decreased without considerable change of bandwidth by using the ceramics as the carrier.
Journal of Electrical Engineering and Technology 01/2014; 9(1). · 0.73 Impact Factor