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Sample records for a549 type ii

  1. Gold nanoparticles induce cytotoxicity in the alveolar type-II cell lines A549 and NCIH441

    PubMed Central

    Uboldi, Chiara; Bonacchi, Daniele; Lorenzi, Giada; Hermanns, M Iris; Pohl, Christine; Baldi, Giovanni; Unger, Ronald E; Kirkpatrick, C James

    2009-01-01

    Background During the last years engineered nanoparticles (NPs) have been extensively used in different technologies and consequently many questions have arisen about the risk and the impact on human health following exposure to nanoparticles. Nevertheless, at present knowledge about the cytotoxicity induced by NPs is still largely incomplete. In this context, we have investigated the cytotoxicity induced by gold nanoparticles (AuNPs), which differed in size and purification grade (presence or absence of sodium citrate residues on the particle surface) in vitro, in the human alveolar type-II (ATII)-like cell lines A549 and NCIH441. Results We found that the presence of sodium citrate residues on AuNPs impaired the viability of the ATII-like cell lines A549 and NCIH441. Interestingly, the presence of an excess of sodium citrate on the surface of NPs not only reduced the in vitro viability of the cell lines A549 and NCIH441, as shown by MTT assay, but also affected cellular proliferation and increased the release of lactate dehydrogenase (LDH), as demonstrated by Ki-67 and LDH-release assays respectively. Furthermore, we investigated the internalization of AuNPs by transmission electron microscopy (TEM) and we observed that particles were internalized by active endocytosis in the cell lines A549 and NCIH441 within 3 hr. In addition, gold particles accumulated in membrane-bound vesicles and were not found freely dispersed in the cytoplasm. Conclusion Our data suggest that the presence of contaminants, such as sodium citrate, on the surface of gold nanoparticles might play a pivotal role in inducing cytotoxicity in vitro, but does not influence the uptake of the particles in human ATII-like cell lines. PMID:19545423

  2. A Comprehensive Proteomic View of Responses of A549 Type II Alveolar Epithelial Cells to Human Respiratory Syncytial Virus Infection*

    PubMed Central

    Dave, Keyur A.; Norris, Emma L.; Bukreyev, Alexander A.; Headlam, Madeleine J.; Buchholz, Ursula J.; Singh, Toshna; Collins, Peter L.; Gorman, Jeffrey J.

    2014-01-01

    Human respiratory syncytial virus is a major respiratory pathogen for which there are no suitable antivirals or vaccines. A better understanding of the host cell response to this virus may redress this problem. The present report concerns analysis of multiple independent biological replicates of control and 24 h infected lysates of A549 cells by two different proteomic workflows. One workflow involved fractionation of lysates by in-solution protein IEF and individual fractions were digested using trypsin prior to capillary HPLC-LTQ-OrbitrapXL-MS/MS. A second workflow involved digestion of whole cell lysates and analysis by nanoUltraHPLC-LTQ-OrbitrapElite-MS/MS. Both workflows resulted in the quantification of viral proteins exclusively in lysates of infected cells in the relative abundances anticipated from previous studies. Unprecedented numbers (3247 - 5010) of host cell protein groups were also quantified and the infection-specific regulation of a large number (191) of these protein groups was evident based on a stringent false discovery rate cut-off (<1%). Bioinformatic analyses revealed that most of the regulated proteins were potentially regulated by type I, II, and III interferon, TNF-α and noncanonical NF-κB2 mediated antiviral response pathways. Regulation of specific protein groups by infection was validated by quantitative Western blotting and the cytokine-/key regulator-specific nature of their regulation was confirmed by comparable analyses of cytokine treated A549 cells. Overall, it is evident that the workflows described herein have produced the most comprehensive proteomic characterization of host cell responses to human respiratory syncytial virus published to date. These workflows will form the basis for analysis of the impacts of specific genes of human respiratory syncytial virus responses of A549 and other cell lines using a gene-deleted version of the virus. They should also prove valuable for the analysis of the impact of other infectious

  3. A comprehensive proteomic view of responses of A549 type II alveolar epithelial cells to human respiratory syncytial virus infection.

    PubMed

    Dave, Keyur A; Norris, Emma L; Bukreyev, Alexander A; Headlam, Madeleine J; Buchholz, Ursula J; Singh, Toshna; Collins, Peter L; Gorman, Jeffrey J

    2014-12-01

    Human respiratory syncytial virus is a major respiratory pathogen for which there are no suitable antivirals or vaccines. A better understanding of the host cell response to this virus may redress this problem. The present report concerns analysis of multiple independent biological replicates of control and 24 h infected lysates of A549 cells by two different proteomic workflows. One workflow involved fractionation of lysates by in-solution protein IEF and individual fractions were digested using trypsin prior to capillary HPLC-LTQ-OrbitrapXL-MS/MS. A second workflow involved digestion of whole cell lysates and analysis by nanoUltraHPLC-LTQ-OrbitrapElite-MS/MS. Both workflows resulted in the quantification of viral proteins exclusively in lysates of infected cells in the relative abundances anticipated from previous studies. Unprecedented numbers (3247 - 5010) of host cell protein groups were also quantified and the infection-specific regulation of a large number (191) of these protein groups was evident based on a stringent false discovery rate cut-off (<1%). Bioinformatic analyses revealed that most of the regulated proteins were potentially regulated by type I, II, and III interferon, TNF-α and noncanonical NF-κB2 mediated antiviral response pathways. Regulation of specific protein groups by infection was validated by quantitative Western blotting and the cytokine-/key regulator-specific nature of their regulation was confirmed by comparable analyses of cytokine treated A549 cells. Overall, it is evident that the workflows described herein have produced the most comprehensive proteomic characterization of host cell responses to human respiratory syncytial virus published to date. These workflows will form the basis for analysis of the impacts of specific genes of human respiratory syncytial virus responses of A549 and other cell lines using a gene-deleted version of the virus. They should also prove valuable for the analysis of the impact of other infectious

  4. Effect of exogenous surfactants on viability and DNA synthesis in A549, immortalized mouse type II and isolated rat alveolar type II cells

    PubMed Central

    2011-01-01

    Background In mechanically ventilated preterm infants with respiratory distress syndrome (RDS), exogenous surfactant application has been demonstrated both to decrease DNA-synthesis but also and paradoxically to increase epithelial cell proliferation. However, the effect of exogenous surfactant has not been studied directly on alveolar type II cells (ATII cells), a key cell type responsible for alveolar function and repair. Objective The aim of this study was to investigate the effects of two commercially available surfactant preparations on ATII cell viability and DNA synthesis. Methods Curosurf® and Alveofact® were applied to two ATII cell lines (human A549 and mouse iMATII cells) and to primary rat ATII cells for periods of up to 24 h. Cell viability was measured using the redox indicator resazurin and DNA synthesis was measured using BrdU incorporation. Results Curosurf® resulted in slightly decreased cell viability in all cell culture models. However, DNA synthesis was increased in A549 and rat ATII cells but decreased in iMATII cells. Alveofact® exhibited the opposite effects on A549 cells and had very mild effects on the other two cell models. Conclusion This study showed that commercially available exogenous surfactants used to treat preterm infants with RDS can have profound effects on cell viability and DNA synthesis. PMID:21324208

  5. Long Term Culture of the A549 Cancer Cell Line Promotes Multilamellar Body Formation and Differentiation towards an Alveolar Type II Pneumocyte Phenotype

    PubMed Central

    Cooper, James Ross; Abdullatif, Muhammad Bilal; Burnett, Edward C.; Kempsell, Karen E.; Conforti, Franco; Tolley, Howard; Collins, Jane E.; Davies, Donna E.

    2016-01-01

    Pulmonary research requires models that represent the physiology of alveolar epithelium but concerns with reproducibility, consistency and the technical and ethical challenges of using primary or stem cells has resulted in widespread use of continuous cancer or other immortalized cell lines. The A549 ‘alveolar’ cell line has been available for over four decades but there is an inconsistent view as to its suitability as an appropriate model for primary alveolar type II (ATII) cells. Since most work with A549 cells involves short term culture of proliferating cells, we postulated that culture conditions that reduced proliferation of the cancer cells would promote a more differentiated ATII cell phenotype. We examined A549 cell growth in different media over long term culture and then used microarray analysis to investigate temporal regulation of pathways involved in cell cycle and ATII differentiation; we also made comparisons with gene expression in freshly isolated human ATII cells. Analyses indicated that long term culture in Ham’s F12 resulted in substantial modulation of cell cycle genes to result in a quiescent population of cells with significant up-regulation of autophagic, differentiation and lipidogenic pathways. There were also increased numbers of up- and down-regulated genes shared with primary cells suggesting adoption of ATII characteristics and multilamellar body (MLB) development. Subsequent Oil Red-O staining and Transmission Electron Microscopy confirmed MLB expression in the differentiated A549 cells. This work defines a set of conditions for promoting ATII differentiation characteristics in A549 cells that may be advantageous for studies with this cell line. PMID:27792742

  6. Gliotoxin promotes Aspergillus fumigatus internalization into type II human pneumocyte A549 cells by inducing host phospholipase D activation.

    PubMed

    Jia, Xiaodong; Chen, Fangyan; Pan, Weihua; Yu, Rentao; Tian, Shuguang; Han, Gaige; Fang, Haiqin; Wang, Shuo; Zhao, Jingya; Li, Xianping; Zheng, Dongyu; Tao, Sha; Liao, Wanqing; Han, Xuelin; Han, Li

    2014-06-01

    The internalization of Aspergillus fumigatus into lung epithelial cells is critical for the infection process in the host. Gliotoxin is the most potent toxin produced by A. fumigatus. However, its role in A. fumigatus internalization into the lung epithelial cells is still largely unknown. In the present study, the deletion of the gliP gene regulating the production of gliotoxin in A. fumigatus suppressed the internalization of conidia into the A549 lung epithelial cells, and this suppression could be rescued by the exogenous addition of gliotoxin. At lower concentrations, gliotoxin enhanced the internalization of the conidia of A. fumigatus into A549 cells; in contrast, it inhibited the phagocytosis of J774 macrophages in a dose-dependent manner. Under a concentration of 100 ng/ml, gliotoxin had no effect on A549 cell viability but attenuated ROS production in a dose-dependent manner. Gliotoxin significantly stimulated the phospholipase D activity in the A549 cells at a concentration of 50 ng/ml. This stimulation was blocked by the pretreatment of host cells with PLD1- but not PLD2-specific inhibitor. Morphological cell changes induced by gliotoxin were observed in the A549 cells accompanying with obvious actin cytoskeleton rearrangement and a moderate alteration of phospholipase D distribution. Our data indicated that gliotoxin might be responsible for modulating the A. fumigatus internalization into epithelial cells through phospholipase D1 activation and actin cytoskeleton rearrangement.

  7. Infection of A549 human type II epithelial cells with Mycobacterium tuberculosis induces changes in mitochondrial morphology, distribution and mass that are dependent on the early secreted antigen, ESAT-6.

    PubMed

    Fine-Coulson, Kari; Giguère, Steeve; Quinn, Frederick D; Reaves, Barbara J

    2015-10-01

    Pulmonary infection by Mycobacterium tuberculosis (Mtb) involves the invasion of alveolar epithelial cells (AECs). We used Mitotracker Red(®) to assess changes in mitochondrial morphology/distribution and mass from 6 to 48 h post infection (hpi) by confocal microscopy and flow cytometry in Mtb-infected A549 type II AECs. During early infection there was no effect on mitochondrial morphology, however, by 48 hpi mitochondria appeared fragmented and concentrated around the nucleus. In flow cytometry experiments, the median fluorescence intensity (MFI) decreased by 44% at 48 hpi; double-labelling using antibodies to the integral membrane protein COXIV revealed that these changes were due to a decrease in mitochondrial mass. These changes did not occur with the apathogenic strain, Mycobacterium bovis BCG. ESAT-6 is a virulence factor present in Mtb Erdman but lacking in M. bovis BCG. We performed similar experiments using Mtb Erdman, an ESAT-6 deletion mutant and its complement. MFI decreased at 48 hpi in the parent and complemented strains versus uninfected controls by 52% and 36% respectively; no decrease was detected in the deletion mutant. These results indicate an involvement of ESAT-6 in the perturbation of mitochondria induced by virulent Mtb in AECs and suggest mitophagy may play a role in the infection process.

  8. Drug Transporter Protein Quantification of Immortalized Human Lung Cell Lines Derived from Tracheobronchial Epithelial Cells (Calu-3 and BEAS2-B), Bronchiolar-Alveolar Cells (NCI-H292 and NCI-H441), and Alveolar Type II-like Cells (A549) by Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Sakamoto, Atsushi; Matsumaru, Takehisa; Yamamura, Norio; Suzuki, Shinobu; Uchida, Yasuo; Tachikawa, Masanori; Terasaki, Tetsuya

    2015-09-01

    Understanding the mechanisms of drug transport in the human lung is an important issue in pulmonary drug discovery and development. For this purpose, there is an increasing interest in immortalized lung cell lines as alternatives to primary cultured lung cells. We recently reported the protein expression in human lung tissues and pulmonary epithelial cells in primary culture, (Sakamoto A, Matsumaru T, Yamamura N, Uchida Y, Tachikawa M, Ohtsuki S, Terasaki T. 2013. J Pharm Sci 102(9):3395-3406) whereas comprehensive quantification of protein expressions in immortalized lung cell lines is sparse. Therefore, the aim of the present study was to clarify the drug transporter protein expression of five commercially available immortalized lung cell lines derived from tracheobronchial cells (Calu-3 and BEAS2-B), bronchiolar-alveolar cells (NCI-H292 and NCI-H441), and alveolar type II cells (A549), by liquid chromatography-tandem mass spectrometry-based approaches. Among transporters detected, breast cancer-resistance protein in Calu-3, NCI-H292, NCI-H441, and A549 and OCTN2 in BEAS2-B showed the highest protein expression. Compared with data from our previous study,(Sakamoto A, Matsumaru T, Yamamura N, Uchida Y, Tachikawa M, Ohtsuki S, Terasaki T. 2013. J Pharm Sci 102(9):3395-3406) NCI-H441 was the most similar with primary lung cells from all regions in terms of protein expression of organic cation/carnitine transporter 1 (OCTN1). In conclusion, the protein expression profiles of transporters in five immortalized lung cell lines were determined, and these findings may contribute to a better understanding of drug transport in immortalized lung cell lines.

  9. Part II-mechanism of adaptation: A549 cells adapt to high concentration of nitric oxide through bypass of cell cycle checkpoints.

    PubMed

    Aqil, Madeeha; Deliu, Zane; Elseth, Kim M; Shen, Grace; Xue, Jiaping; Radosevich, James A

    2014-03-01

    Previous work has shown enhanced survival capacity in high nitric oxide (HNO)-adapted tumor cells. In Part I of this series of manuscripts, we have shown that A549-HNO cells demonstrate an improved growth profile under UV and X-ray radiation treatment. These cells exhibit increased expression of proteins involved in DNA damage recognition and repair pathway, both the non-homologous end joining pathway and homologous recombination. These include Ku80, DNA-PK, XLF ligase and MRN complex proteins. Further, the A549-HNO cells show high levels of ATM, ATR, Chk1 and Chk2, and phospho-p53. Activation of these molecules may lead to cell cycle arrest and apoptosis due to DNA damage. This is observed in parent A549 cells in response to NO donor treatment; however, the A549-HNO cells proliferate and inhibit apoptosis. Cell cycle analysis showed slowed progression through S phase which will allow time for DNA repair. Thus, to better understand the increased growth rate in A549-HNO when compared to the parent cell line A549, we studied molecular mechanisms involved in cell cycle regulation in A549-HNO cells. During the initial time period of NO donor treatment, we observe high levels of cyclin/Cdk complexes involved in regulating various stages of the cell cycle. This would lead to bypass of G1-S and G2-M checkpoints. The HNO cells also show much higher expression of Cdc25A. Cdc25A activates Cdk molecules involved in different phases of the cell cycle. In addition, there is enhanced phosphorylation of the Rb protein in HNO cells. This leads to inactivation of Rb/E2F checkpoint regulating G1-S transition. This may lead to faster progression in S phase. Thus, all of these perturbations in HNO cells lead to accelerated cell cycle progression and a higher growth rate. We also assessed expression of cell cycle inhibitors in HNO cells. Interestingly, the HNO cells show a significant decline in p21CIP1 at initial time points, but with prolonged exposure, the levels were much higher

  10. Transcriptome Profiles of Human Lung Epithelial Cells A549 Interacting with Aspergillus fumigatus by RNA-Seq

    PubMed Central

    Jia, Xiaodong; Wang, Shuo; Wang, Jing; Chen, Yong; Zhao, Jingya; Tian, Shuguang; Han, Xuelin; Han, Li

    2015-01-01

    Lung epithelial cells constitute the first defense line of host against the inhaled Aspergillus fumigatus; however, the transcriptional response of human alveolar type II epithelial cells was still unclear. Here we used RNA-Seq technology to assess the transcriptome profiles of A549 cells following direct interaction with conidia of A. fumigatus. The total number of identified genes was 19118. Compared with uninfected A549 cells, 459 genes were differentially expressed in cells co-incubated with conidia for 8 h, including 302 up-regulated genes and 157 down-regulated genes. GO and KEGG pathway enrichment analysis showed that most of the up-regulated genes were related to immune response, chemotaxis and inflammatory response and enriched in cytokine-cytokine receptor interaction, JAK-STAT and MAPK signaling pathways. The down-regulated genes were mainly enriched for terms associated with development, hemopoiesis and ion transport. Among them, EGR4 and HIST1H4J gene had the maximum of fold change in up-regulated and down-regulated genes, respectively. Fourteen up-regulated genes and three down-regulated genes were further validated and significant increase on expression of IL-6, IL-8 and TNF-α in A549 cells were confirmed by qRT-PCR during the interaction of A549 cells with A. fumigatus. Besides, western blot showed that expression of two proteins (ARC, EGR1) significantly increased in A549 cells during interaction with A. fumigatus conidia for 8h. Interference of endogenous expression of ARC or EGR1 protein in A549 cells reduced the internalization of A. fumigatus. These results provided important insights into dynamic changes of gene expression in lung epithelial cells, especially its strong immunological response against A. fumigatus infection. PMID:26273834

  11. Long-chain carboxychromanols are the major metabolites of tocopherols and tocotrienols in A549 lung epithelial cells but not HepG2 cells.

    PubMed

    You, Cha-Sook; Sontag, Timothy J; Swanson, Joy E; Parker, Robert S

    2005-02-01

    Human lung type II cell derived A549 epithelial cancer cells and HepG2 hepatocytes constitutively express cytochrome P4504F2, a P450 we previously identified as a tocopherol-omega-hydroxylase. To determine if A549 cells would metabolize tocochromanols via the omega-hydroxylase pathway, we compared the metabolism of tocopherols (alpha-, gamma-, delta-TOH) and tocotrienols (alpha-, gamma-, delta-T3) in these 2 cell lines. Cultures were incubated with alpha-, gamma-, or delta-TOH, or the analogous T3s, and synthesis of their metabolites quantitated by GC-MS. A549 cells metabolized all tocochromanols 2-3 times more extensively than HepG2 cells (P < 0.001) except alpha-TOH, a difference not related to cell uptake of substrate but rather was reflective of greater microsomal TOH-omega-hydroxylase enzyme activity. Notably, 9'-carboxychromanols were the major metabolites of all gamma- and delta-TOHs and T3s in A549 cultures, whereas 3'- and 5'-carboxychromanols predominated in HepG2 cultures. Accumulation of 9'-carboxychromanols in A549 cultures was due to their inefficient conversion to 7'-carboxychromanols relative to HepG2 cells. Sesamin inhibited tocochromanol metabolism in both cells types, and neither cell type exhibited evidence of alternative (sesamin-insensitive) pathways of metabolism. TOH-omega-hydroxylase activity was undetectable in rat primary lung type II cells, suggesting that expression of activity was associated with transformation of normal type II cells to cancer cells. Long-chain carboxychromanol metabolites of gamma-TOH and other forms of vitamin E can be biosynthesized in A549 cultures for assessment of their biological activity, including their potential inhibition of synthesis of inflammatory mediators.

  12. Solar Type II Radio Bursts and IP Type II Events

    NASA Technical Reports Server (NTRS)

    Cane, H. V.; Erickson, W. C.

    2005-01-01

    We have examined radio data from the WAVES experiment on the Wind spacecraft in conjunction with ground-based data in order to investigate the relationship between the shocks responsible for metric type II radio bursts and the shocks in front of coronal mass ejections (CMEs). The bow shocks of fast, large CMEs are strong interplanetary (IP) shocks, and the associated radio emissions often consist of single broad bands starting below approx. 4 MHz; such emissions were previously called IP type II events. In contrast, metric type II bursts are usually narrowbanded and display two harmonically related bands. In addition to displaying complete dynamic spectra for a number of events, we also analyze the 135 WAVES 1 - 14 MHz slow-drift time periods in 2001-2003. We find that most of the periods contain multiple phenomena, which we divide into three groups: metric type II extensions, IP type II events, and blobs and bands. About half of the WAVES listings include probable extensions of metric type II radio bursts, but in more than half of these events, there were also other slow-drift features. In the 3 yr study period, there were 31 IP type II events; these were associated with the very fastest CMEs. The most common form of activity in the WAVES events, blobs and bands in the frequency range between 1 and 8 MHz, fall below an envelope consistent with the early signatures of an IP type II event. However, most of this activity lasts only a few tens of minutes, whereas IP type II events last for many hours. In this study we find many examples in the radio data of two shock-like phenomena with different characteristics that occur simultaneously in the metric and decametric/hectometric bands, and no clear example of a metric type II burst that extends continuously down in frequency to become an IP type II event. The simplest interpretation is that metric type II bursts, unlike IP type II events, are not caused by shocks driven in front of CMEs.

  13. Bufalin inhibits TGF-β-induced epithelial-to-mesenchymal transition and migration in human lung cancer A549 cells by downregulating TGF-β receptors

    PubMed Central

    ZHAO, LEI; LIU, SHIZHOU; CHE, XIAOFANG; HOU, KEZUO; MA, YANJU; LI, CE; WEN, TI; FAN, YIBO; HU, XUEJUN; LIU, YUNPENG; QU, XIUJUAN

    2015-01-01

    The epithelial-to-mesenchymal transition (EMT) is a well-known prerequisite for cancer cells to acquire the migratory and invasive capacity, and to subsequently metastasize. Bufalin is one of the major active components of the traditional Chinese medicine Chan Su, and accumulating evidence has shown its anticancer effect in multipe types of cancer. However, the role of bufalin in transforming growth factor-β (TGF-β)-induced EMT and migration remains unclear. In the present study, the effect of bufalin on TGF-β-induced EMT and migration was investigated in human lung cancer A549 cells. TGF-β induced EMT in A549 cells and increased their migratory ability, which were markedly suppressed by bufalin. Additionally, TGF-β-induced upregulation of Twist2 and zinc finger E-box binding homeobox 2 (ZEB2), as well as the phosphorylation of Smad2 and Smad3 were also inhibited by bufalin. However, the Smad-independent signaling pathways were not affected. Further analysis showed that the TGF-β receptor I (TβRI) and TGF-β receptor II (TβRII) were downregulated in the presence of bufalin. Pretreatment with SB431542, a potent inhibitor of the phosphorylation of TβRI, significantly attenuated TGF-β-induced EMT, mimicking the effect of bufalin on A549 cells. Taken together, these results suggest that bufalin suppresses TGF-β-induced EMT and migration by downregulating TβRI and TβRII in A549 cells. PMID:26133118

  14. Achondrogenesis type II with polydactyly.

    PubMed

    Rittler, M; Orioli, I M

    1995-11-06

    We report on a newborn male infant who presented the typical findings of achondrogenesis type II (Langer-Saldino), and who also showed postaxial polydactyly on both feet and bilateral microtia. Polydactyly is frequently part of the short-rib syndromes, but has not been reported in achondrogenesis. The hypothesis of polydactyly as part of a contiguous gene syndrome is discussed.

  15. Light echoes - Type II supernovae

    NASA Technical Reports Server (NTRS)

    Schaefer, Bradley E.

    1987-01-01

    Type II supernovae (SNs) light curves show a remarkable range of shapes. Data have been collected for the 12 Type II SNs that have light curve information for more than four months past maximum. Contrary to previous reports, it is found that (1) the decay rate after 100 days past maximum varies by almost an order of magnitude and (2) the light curve shapes are not bimodally distributed, but actually form a continuum. In addition, it is found that the extinctions to the SNs are related to the light curve shapes. This implies that the absorbing dust is local to the SNs. The dust is likely to be part of a circumstellar shell emitted by the SN progenitor that Dwek (1983) has used to explain infrared echoes. The optical depth of the shell can get quite large. In such cases, it is found that the photons scattered and delayed by reflection off dust grains will dominate the light curve several months after peak brightness. This 'light echo' offers a straightforward explanation of the diversity of Type II SN light curves.

  16. Cathepsin L upregulation-induced EMT phenotype is associated with the acquisition of cisplatin or paclitaxel resistance in A549 cells

    PubMed Central

    Han, Mei-ling; Zhao, Yi-fan; Tan, Cai-hong; Xiong, Ya-jie; Wang, Wen-juan; Wu, Feng; Fei, Yao; Wang, Long; Liang, Zhong-qin

    2016-01-01

    model, the mice implanted with A549 cells overexpressing CTSL exhibited significantly reduced sensitivity to paclitaxel treatment, and increased expression of EMT-associated proteins and transcription factors in tumor tissues. Conclusion: Cisplatin and paclitaxel resistance is associated with CTSL upregulation-induced EMT in A549 cells. Thus, CTSL-mediated EMT may be exploited as a target to enhance the efficacy of cisplatin or paclitaxel against lung cancer and other types of malignancies. PMID:27840408

  17. In vitro cytotoxicity of gold nanorods in A549 cells.

    PubMed

    Tang, Ying; Shen, Yafeng; Huang, Libin; Lv, Gaojian; Lei, Changhai; Fan, Xiaoyan; Lin, Fangxing; Zhang, Yuxia; Wu, Lihui; Yang, Yongji

    2015-03-01

    Gold nanoparticles, which have unique physicochemical characteristics, are being used for an increasingly wide range of applications in biomedical research. In this study, gold nanorods (width of 25 nm, length of 52 nm) were found to be internalized by A549 cells and were primarily localized in the lysosomes and membranous vesicles. The integrity of the membranes of A549 cells exposed to gold nanorods for 4h was damaged, as indicated by laser scanning confocal microscopy (LSCM). Increased lactate dehydrogenase (LDH) leakage and decreased cell viability further indicated the concentration-dependent cytotoxicity of the gold nanorods to the A549 cells. Reactive oxygen species (ROS) production was induced in the A549 cells by the gold nanorods, and this effect was positively correlated with the concentration of the gold nanorods. The results of this study indicated that exposure to gold nanorods caused dose-dependent cytotoxicity in A549 cells and that oxidative stress may be the main factor causing cytotoxicity.

  18. Autophagy protects type II alveolar epithelial cells from Mycobacterium tuberculosis infection

    SciTech Connect

    Guo, Xu-Guang; Ji, Tian-Xing; Xia, Yong; Ma, Yue-Yun

    2013-03-08

    Highlights: ► We investigated the protective effect of autophagy pathway against MTB infection. ► MTB-infected A549 cells had higher LDH release. ► Inhibition of autophagy signaling significantly enhanced the MTB-induced necrosis. ► Autophagy prevents apoptosis and promotes cell survival in infected cells. -- Abstract: This study was designed to investigate the protective effect of the autophagy signaling pathway against Mycobacterium tuberculosis infection in type II alveolar epithelial cells. An in vitro M. tuberculosis system was established using human A549 cells. Infection-induced changes in the expression of the autophagic marker LC3 were assessed by reverse transcription-PCR and Western blotting. Morphological changes in autophagosomes were detected by transmission electron microscopy (TEM). The function of the autophagy signaling pathway during infection was assessed by measuring the level of cell death and the amount of lactate dehydrogenase (LDH) released in the presence or absence of the inhibitor 3-methyladenine (3-MA). In addition, effects on LDH release were assessed after the siRNA-mediated knockdown of the essential autophagosomal structural membrane protein Atg5. LC3 mRNA expression was significantly reduced in M.tuberculosis-infected A549 cells (16888.76 ± 1576.34 vs. uninfected: 12744.29 ± 1089.37; P < 0.05). TEM revealed M.tuberculosis bacilli-containing compartments that were surrounded by double membranes characteristic of the autophagic process. M.tuberculosis-infected A549 cells released more LDH (1.45 ± 0.12 vs. uninfected: 0.45 ± 0.04; P < 0.05). The inhibition of autophagy signaling significantly enhanced M.tuberculosis-induced necrosis (3-MA: 75 ± 5% vs. untreated: 15 ± 1%; P < 0.05) and LDH release (3-MA: 2.50 ± 0.24 vs. untreated: 0.45 ± 0.04; Atg5 knockdown: 3.19 ± 0.29 vs. untreated: 1.28 ± 0.11; P < 0.05). Our results indicate that autophagy signaling pathway prevents apoptosis in type II alveolar epithelial cells

  19. Moderately luminous Type II supernovae

    NASA Astrophysics Data System (ADS)

    Inserra, C.; Pastorello, A.; Turatto, M.; Pumo, M. L.; Benetti, S.; Cappellaro, E.; Botticella, M. T.; Bufano, F.; Elias-Rosa, N.; Harutyunyan, A.; Taubenberger, S.; Valenti, S.; Zampieri, L.

    2013-07-01

    Context. Core-collapse Supernovae (CC-SNe) descend from progenitors more massive than about 8 M⊙. Because of the young age of the progenitors, the ejecta may eventually interact with the circumstellar medium (CSM) via highly energetic processes detectable in the radio, X-ray, ultraviolet (UV) and, sometimes, in the optical domains. Aims: In this paper we present ultraviolet, optical and near infrared observations of five Type II SNe, namely SNe 2009dd, 2007pk, 2010aj, 1995ad, and 1996W. Together with few other SNe they form a group of moderately luminous Type II events. We investigate the photometric similarities and differences among these bright objects. We also attempt to characterise them by analysing the spectral evolutions, in order to find some traces of CSM-ejecta interaction. Methods: We collected photometry and spectroscopy with several telescopes in order to construct well-sampled light curves and spectral evolutions from the photospheric to the nebular phases. Both photometry and spectroscopy indicate a degree of heterogeneity in this sample. Modelling the data of SNe 2009dd, 2010aj and 1995ad allows us to constrain the explosion parameters and the properties of the progenitor stars. Results: The light curves have luminous peak magnitudes (-16.95 < MB < -18.70). The ejected masses of 56Ni for three SNe span a wide range of values (2.8 × 10-2 M⊙ < M(56Ni)< 1.4 × 10-1 M⊙), while for a fourth (SN 2010aj) we could determine a stringent upper limit (7 × 10-3 M⊙). Clues of interaction, such as the presence of high velocity (HV) features of the Balmer lines, are visible in the photospheric spectra of SNe 2009dd and 1996W. For SN 2007pk we observe a spectral transition from a Type IIn to a standard Type II SN. Modelling the observations of SNe 2009dd, 2010aj and 1995ad with radiation hydrodynamics codes, we infer kinetic plus thermal energies of about 0.2-0.5 foe, initial radii of 2-5 × 1013 cm and ejected masses of ~5.0-9.5 M⊙. Conclusions: These

  20. Human mast cells decrease SLPI levels in type II – like alveolar cell model, in vitro

    PubMed Central

    Hollander, Camilla; Nyström, Max; Janciauskiene, Sabina; Westin, Ulla

    2003-01-01

    Background Mast cells are known to accumulate at sites of inflammation and upon activation to release their granule content, e.g. histamine, cytokines and proteases. The secretory leukocyte protease inhibitor (SLPI) is produced in the respiratory mucous and plays a role in regulating the activity of the proteases. Result We have used the HMC-1 cell line as a model for human mast cells to investigate their effect on SLPI expression and its levels in cell co-culture experiments, in vitro. In comparison with controls, we found a significant reduction in SLPI levels (by 2.35-fold, p < 0.01) in a SLPI-producing, type II-like alveolar cell line, (A549) when co-cultured with HMC-1 cells, but not in an HMC-1-conditioned medium, for 96 hours. By contrast, increased SLPI mRNA expression (by 1.58-fold, p < 0.05) was found under the same experimental conditions. Immunohistochemical analysis revealed mast cell transmigration in co-culture with SLPI-producing A549 cells for 72 and 96 hours. Conclusion These results indicate that SLPI-producing cells may assist mast cell migration and that the regulation of SLPI release and/or consumption by mast cells requires interaction between these cell types. Therefore, a "local relationship" between mast cells and airway epithelial cells might be an important step in the inflammatory response. PMID:12952550

  1. Neurofibromatosis type II presenting as vertical diplopia.

    PubMed

    Sokwala, Ahmed; Knapp, Christopher; Gottlob, Irene

    2004-09-01

    Neurofibromatosis type II (NF II) is rare and most commonly presents with hearing loss, tinnitus and/or vestibular disturbance in the third decade of life. The authors describe a rare case presenting with NF II with vertical diplopia due to IV(th) nerve palsy. The patient was otherwise asymptomatic despite multiple extensive lesions on MRI.

  2. Fits, pyridoxine, and hyperprolinaemia type II.

    PubMed

    Walker, V; Mills, G A; Peters, S A; Merton, W L

    2000-03-01

    The rare inherited disorder hyperprolinaemia type II presents with fits in childhood, usually precipitated by infection. A diagnosis of hyperprolinaemia type II and vitamin B(6) deficiency was made in a well nourished child with fits. It is thought that pyridoxine deficiency was implicated in her fits and was the result of inactivation of the vitamin by the proline metabolite, pyrroline-5-carboxylate.

  3. Hearing Restoration in Neurofibromatosis Type II Patients

    PubMed Central

    Lee, Jeon Mi; Chang, Jin Woo; Choi, Jae Young

    2016-01-01

    Patients with neurofibromatosis type II will eventually succumb to bilateral deafness. For patients with hearing loss, modern medical science technology can provide efficient hearing restoration through a number of various methods. In this article, several hearing restoration methods for patients with neurofibromatosis type II are introduced. PMID:27189272

  4. Oxidative stress and inflammatory response to printer toner particles in human epithelial A549 lung cells.

    PubMed

    Könczöl, Mathias; Weiß, Adilka; Gminski, Richard; Merfort, Irmgard; Mersch-Sundermann, Volker

    2013-02-04

    Reports on adverse health effects related to occupational exposure to toner powder are still inconclusive. Therefore, we have previously conducted an in vitro-study to characterize the genotoxic potential of three commercially available black printer toner powders in A549 lung cells. In these cell-based assays it was clearly demonstrated that the tested toner powders damage DNA and induce micronucleus (MN) formation. Here, we have studied the cytotoxic and proinflammatory potential of these three types of printer toner particles and the influence of ROS and NF-κB induction in order to unravel the underlying mechanisms. A549 cells were exposed to various concentrations of printer toner particle suspensions for 24 h. The toner particles were observed to exert significant cytotoxic effects in the WST-1 and neutral red (NR)-assays, although to a varying extent. Caspase 3/7 activity increased, while the mitochondrial membrane potential (MMP) was not affected. Particles of all three printer toner powders induced concentration-dependent formation of reactive oxygen species (ROS), as measured in the DCFH-DA assay. Furthermore, toner particle exposure enhanced interleukin-6 and interleukin-8 production, which is in agreement with activation of the transcription factor NF-κB in A549 cells shown by the electrophoretic mobility shift assay (EMSA). Therefore, it can be concluded that exposure of A549 lung cells to three selected printer toner powders caused oxidative stress through induction of ROS. Increased ROS formation may trigger genotoxic effects and activate proinflammatory pathways.

  5. Genetic heterogeneity of Usher syndrome type II.

    PubMed Central

    Pieke Dahl, S; Kimberling, W J; Gorin, M B; Weston, M D; Furman, J M; Pikus, A; Möller, C

    1993-01-01

    Usher syndrome is an autosomal recessive disorder characterised by retinitis pigmentosa and congenital sensorineural hearing loss. A gene for Usher syndrome type II (USH2) has been localised to chromosome 1q32-q41. DNA from a family with four of seven sibs affected with clinical characteristics of Usher syndrome type II was genotyped using markers spanning the 1q32-1q41 region. These included D1S70 and D1S81, which are believed to flank USH2. Genotypic results and subsequent linkage analysis indicated non-linkage of this family to these markers. The A test analysis for heterogeneity with this family and 32 other Usher type II families was statistically significant at p < 0.05. Further clinical evaluation of this family was done in light of the linkage results to determine if any phenotypic characteristics would allow for clinical identification of the unlinked type. No clear phenotypic differences were observed; however, this unlinked family may represent a previously unreported subtype of Usher type II characterised by a milder form of retinitis pigmentosa and mild vestibular abnormalities. Heterogeneity of Usher syndrome type II complicates efforts to isolate and clone Usher syndrome genes using linkage analysis and limits the use of DNA markers in early detection of Usher type II. Images PMID:7901420

  6. Resistance domain in type II superconductors

    SciTech Connect

    Gurevich, A.V.; Mints, R.G.

    1980-01-05

    We show that traveling domains with a finite resistance can exist in type II superconductors in the presence of a transport current. An experiment in which this effect generates an alternating electric field and current is proposed.

  7. Achondrogenesis type II, abnormalities of extracellular matrix.

    PubMed

    Horton, W A; Machado, M A; Chou, J W; Campbell, D

    1987-09-01

    Immune and lectin histochemical and microchemical methods were employed to study growth cartilage from seven cases of achondrogenesis type II (Langer-Saldino). The normal architecture of the epiphyseal and growth plate cartilage was replaced by a morphologically heterogeneous tissue. Some areas were comprised of vascular canals surrounded by extensive fibrous tissue and enlarged cells that had the appearance and histochemical characteristics of hypertrophic chondrocytes. Other areas contained a mixture of cells ranging from small to the enlarged chondrocytes. The extracellular matrix in the latter areas was more abundant and had characteristics of both precartilage mesenchymal matrix and typical cartilage matrix; it contained types I and II collagen, cartilage proteoglycan, fibronectin, and peanut agglutinin binding glycoconjugate(s). Peptide mapping of cyanogen bromide cartilage collagen peptides revealed the presence of types I and II collagen. These observations could be explained by a defect in the biosynthesis of type II collagen or in chondrocyte differentiation.

  8. Antenatal diagnosis of achondrogenesis type II.

    PubMed

    Kodandapani, S; Ramkumar, V

    2009-01-01

    Achondrogenesis is a lethal congenital chondrodystrophy characterized by extreme micromelia, small thorax and polyhydramnios. We describe a case of achondrogenesis type II (Langer-Saldino achondrogenesis). Prenatal ultrasonography at 22-weeks gestation revealed a fetus with large head, short neck and chest, prominent abdomen and short limbs. Pregnancy was terminated. Radiologic examination of neonate revealed features of achondrogenesis type II. Routine ultrasound screening made early detection and timely management possible.

  9. Type II endometrial cancers: A case series

    PubMed Central

    Lobo, Flora D.; Thomas, Eliz

    2016-01-01

    Introduction: Endometrial carcinoma ranks 3rd in India among gynecological malignancies. Endometrial cancer (EC) can be classified into two distinct groups – type I and type II, based on histology, which differs in molecular, clinical and histopathological profiles. Type II is nonestrogen dependent, nonendometrioid, more aggressive and carries poor prognosis. Although type II cancers contribute only about 10% of EC incidence, they present at advanced age and cause approximately 50% recurrence and deaths with a low 5-year, overall survival rate. Type II EC are also characterized by genetic alterations in p53, human epidermal growth factor-2/neu, p16 and E-cadherin. Materials and Methods: Endometrial carcinomas diagnosed from endometrial biopsies and hysterectomy specimens received in the Department of Pathology, Kasturba Medical College, Mangalore, from January 2007 to June 2012 were included in the study. Clinicopathological analysis of the 84 cases of EC was done with emphasis on morphology. p53 immunostaining was performed in two cases of serous carcinoma. Results: Out of a total of 84 cases of EC, ten cases were of type II (11.9%). Out of which, eight were serous carcinoma (9.5%) and two clear cell (2.4%). p53 immunostain was strongly positive in the serous papillary carcinomas. The age of the patients ranged from 45 to 75 years. Myometrial invasion was more than half. Treatment was hysterectomy followed by aggressive chemotherapy. Conclusion: Of the type II EC, serous carcinoma is the most common type. Clinical presentation and prognosis differs in comparison to type I EC, thus the recognition of this type of EC is pivotal. PMID:27499593

  10. Jolkinolide A and Jolkinolide B Inhibit Proliferation of A549 Cells and Activity of Human Umbilical Vein Endothelial Cells

    PubMed Central

    Shen, Lei; Zhang, Shan-Qiang; Liu, Lei; Sun, Yu; Wu, Yu-Xuan; Xie, Li-Ping; Liu, Ji-Cheng

    2017-01-01

    Background Jolkinolide A (JA) and Jolkinolide B (JB) are diterpenoids extracted from the roots of Euphorbia fischeriana Steud and have been shown to have anti-tumor activity. However, their effects on the ability of tumor cells to invade blood vessels and metastasize remain largely unknown. Investigations into the effects of JA and JB on the angiogenesis of tumor tissues may facilitate the identification of new natural drugs with anti-tumor growth and metastasis activities. Material/Methods We used different concentrations of JA and JB (20 μg/ml, 40 μg/ml, 60 μg/ml, 80 μg/ml, and 100 μg/ml) to stimulate A549 cells and then studied the effects on the growth and metastasis of lung cancers. In addition, we used conditional media from A549 cells (A549-CM) stimulated by either JA or JB in different concentrations to culture human umbilical vein endothelial cells (HUVECs). Results We found that both JA and JB significantly inhibited the Akt-STAT3-mTOR signaling pathway and reduced the expression of VEGF in A549 cells, but JB exhibited more significant inhibitory effects than JA. The JB-stimulated A549 cell conditional media had a greater inhibitory effect on the proliferation and migration of HUVECs than did the conditional media of JA-stimulated A549 cells. This effect gradually increased with increasing concentrations of either type of Jolkinolide. Conclusions Our results suggest that JA and JB inhibited VEGF expression in A549 cells through the inhibition of the Akt-STAT3-mTOR signaling pathway, and directly inhibited the proliferation and migration of HUVECs. These findings are of great significance for the development of new plant-derived chemotherapy agents for the treatment of cancer. PMID:28087861

  11. Genetics Home Reference: distal hereditary motor neuropathy, type II

    MedlinePlus

    ... distal hereditary motor neuropathy, type II distal hereditary motor neuropathy, type II Enable Javascript to view the ... PDF Open All Close All Description Distal hereditary motor neuropathy, type II is a progressive disorder that ...

  12. Type II achondrogenesis-hypochondrogenesis: identification of abnormal type II collagen.

    PubMed

    Godfrey, M; Hollister, D W

    1988-12-01

    We have extended the study of a mild case of type II achondrogenesis-hypochondrogenesis to include biochemical analyses of cartilage, bone, and the collagens produced by dermal fibroblasts. Type I collagen extracted from bone and types I and III collagen produced by dermal fibroblasts were normal, as was the hexosamine ratio of cartilage proteoglycans. Hyaline cartilage, however, contained approximately equal amounts of types I and II collagen and decreased amounts of type XI collagen. Unlike the normal SDS-PAGE mobility. Two-dimensional SDS-PAGE revealed extensive overmodification of all type II cyanogen bromide peptides in a pattern consistent with heterozygosity for an abnormal pro alpha 1(II) chain which impaired the assembly and/or folding of type II collagen. This interpretation implies that dominant mutations of the COL2A1 gene may cause type II achondrogenesis-hypochondrogenesis. More generally, emerging data implicating defects of type II collagen in the type II achondrogenesis-hypochondrogenesis-spondyloepiphyseal dysplasia congenita spectrum and in the Kniest-Stickler syndrome spectrum suggest that diverse mutations of this gene may be associated with widely differing phenotypic outcome.

  13. DO GIANT PLANETS SURVIVE TYPE II MIGRATION?

    SciTech Connect

    Hasegawa, Yasuhiro; Ida, Shigeru E-mail: ida@geo.titech.ac.jp

    2013-09-10

    Planetary migration is one of the most serious problems to systematically understand the observations of exoplanets. We clarify that the theoretically predicted type II, migration (like type I migration) is too fast, by developing detailed analytical arguments in which the timescale of type II migration is compared with the disk lifetime. In the disk-dominated regime, the type II migration timescale is characterized by a local viscous diffusion timescale, while the disk lifetime is characterized by a global diffusion timescale that is much longer than the local one. Even in the planet-dominated regime where the inertia of the planet mass reduces the migration speed, the timescale is still shorter than the disk lifetime except in the final disk evolution stage where the total disk mass decays below the planet mass. This suggests that most giant planets plunge into the central stars within the disk lifetime, and it contradicts the exoplanet observations that gas giants are piled up at r {approx}> 1 AU. We examine additional processes that may arise in protoplanetary disks: dead zones, photoevaporation of gas, and gas flow across a gap formed by a type II migrator. Although they make the type II migration timescale closer to the disk lifetime, we show that none of them can act as an effective barrier for rapid type II migration with the current knowledge of these processes. We point out that gas flow across a gap and the fraction of the flow accreted onto the planets are uncertain and they may have the potential to solve the problem. Much more detailed investigation for each process may be needed to explain the observed distribution of gas giants in extrasolar planetary systems.

  14. Type II seesaw dominance in SO(10)

    SciTech Connect

    Melfo, Alejandra; Ramirez, Alba; Senjanovic, Goran

    2010-10-01

    Grand unified theories where the neutrino mass is given by type II seesaw have the potential to provide interesting connections between the neutrino and charged fermion sectors. We explore the possibility of having a dominant type II seesaw contribution in supersymmetric SO(10). We show that this can be achieved in the model where symmetry breaking is triggered by 54 and 45 dimensional representations, without the need for additional fields other than those already required to have a realistic charged fermion mass spectrum. Physical consequences, such as the implementation of the Bajc, Senjanovic, and Vissani mechanism, the possibility of the fields responsible for type II seesaw dominance being messengers of supersymmetry breaking, and the realization of baryo and leptogenesis in these theories, are discussed.

  15. [A case of type II achondrogenesis].

    PubMed

    Micheli, E; Perrone, C; Quarta Colosso, L; Vetrugno, M; Zecca, G; Indirli, G C; Greco, F; Elia, G; Ciancio, S

    1996-01-01

    We describe a rare case of type II achondrogenesis (gestational age = thirty-two weeks) dead forty-five minutes after birth. This congenital skeletal dysplasia is classified among the lethal osteochondrodysplasias. Clinical features were enough for diagnosis and autopsy added nothing to our clinical knowledges.

  16. Type II Technology Applications in Teacher Education:

    ERIC Educational Resources Information Center

    Chen Wang, Lih-Ching; Beasley, William

    2005-01-01

    The use of the Instant Messenger (IM) environment to carry out structured online class discussions in graduate teacher education courses is described. Properties of IM are delineated, and specific procedures in using IM as a vehicle for class discussions are discussed. Attributes of Type II technology applications are addressed directly, and the…

  17. Hyperoxia enhances VEGF release from A549 cells via post-transcriptional processes

    PubMed Central

    Shenberger, Jeffrey S.; Zhang, Lianqin; Powell, Richard J.; Barchowsky, Aaron

    2007-01-01

    Exposure of animals to hyperoxia decreases lung VEGF mRNA expression concomitant with an acute increase in VEGF protein within the epithelial lining fluid (ELF). The VEGF concentration in ELF is in excess of that found in the plasma, leading to the hypothesis that hyperoxia stimulates the release of VEGF protein from stores within the extracellular matrix. To test this hypothesis in a cell culture system, we exposed A549 cells to 95% O2 for 48 hrs followed by recovery in room air (RA) for 24 hrs. We found that Ox increased VEGF protein 2- to 3-fold within the medium at 48 hrs of exposure and during recovery. Heparin clearing revealed the medium to contain a 50:50 mixture of the heparin-binding (VEGF165) and heparin-non-binding (VEGF121) proteins and Ox to increase both proteins equally. Transcriptional activation of VEGF appears unlikely to explain the increase in VEGF protein as full-length and splice variant VEGF mRNA expression were unchanged by hyperoxia. Analysis of cell-associated VEGF proteins found that Ox increased the expression of VEGF121 and VEGF165 proteins. Blocking binding sites with exogenous heparin enhanced VEGF protein in the medium from RA grown cells while heparinase digestion of bound VEGF revealed a greater reserve of VEGF protein in RA cells. Collectively these findings indicate that hyperoxia enhances the expression of VEGF121/165 proteins and facilitates the release of VEGF165 from cell-associated stores. Increases in VEGF in ELF may represent an adaptive response fostering cell survival and type II cell proliferation in O2-induced lung injury. PMID:17664148

  18. Artesunate induces AIF-dependent apoptosis in A549 cells

    NASA Astrophysics Data System (ADS)

    Zhou, Chen-juan; Chen, Tong-Sheng

    2012-03-01

    Artesunate (ART), a semi-synthetic derivative of the sesquiterpene artemisinin extracted from the Chinese herb Artemisia annua, exerts a broad spectrum of clinical activity against human cancers. It has been shown that ART induces cancer cells death through apoptosis pathway. This study investigated whether ART treatment induced reactive oxygen species (ROS)-dependent cell death in the apoptosis fashion in human lung adenocarconoma A549 cell line and the proapoptotic protein apoptosis inducing factor (AIF) is involved in ART-induced apoptosis. Cells treated with ART exhibited typical apoptotic morphology as chromatin condensation, margination and shrunken nucleus. ART treatment also induced a loss of mitochondrial membrane potential and AIF release from mitochondria. Silencing AIF can remarkable attenuated ART-induced apoptosis. Collectively, ART induces apoptosis by caspase-independent intrinsic pathway in A549 cells.

  19. Pomegranate fruit extract inhibits prosurvival pathways in human A549 lung carcinoma cells and tumor growth in athymic nude mice.

    PubMed

    Khan, Naghma; Hadi, Naghma; Afaq, Farrukh; Syed, Deeba N; Kweon, Mee-Hyang; Mukhtar, Hasan

    2007-01-01

    Developing novel mechanism-based chemopreventive approaches for lung cancer through the use of dietary substances which humans can accept has become an important goal. In the present study, employing normal human bronchial epithelial cells (NHBE) and human lung carcinoma A549 cells, we first compared the growth inhibitory effects of pomegranate fruit extract (PFE). Treatment of PFE (50-150 microg/ml) for 72 h was found to result in a decrease in the viability of A549 cells but had only minimal effects on NHBE cells as assessed by the MTT and Trypan blue assays. PFE treatment of A549 cells also resulted in dose-dependent arrest of cells in G0-G1 phase of the cell cycle (as assessed by DNA cell cycle analysis). We further found that PFE treatment also resulted in (i) induction of WAF1/p21 and KIP1/p27, (ii) decrease in the protein expressions of cyclins D1, D2 and E, and (iii) decrease in cyclin-dependent kinase (cdk) 2, cdk4 and cdk6 expression. The treatment of cells with PFE inhibited (i) phosphorylation of MAPK proteins, (ii) inhibition of PI3K, (iii) phosphorylation of Akt at Thr308, (iv) NF-kappaB and IKKalpha, (v) degradation and phosphorylation of IkappaBalpha, and (vi) Ki-67 and PCNA. We also found that PFE treatment to A549 cells resulted in inhibition of NF-kappaB DNA-binding activity. Oral administration of PFE (0.1 and 0.2%, wt/vol) to athymic nude mice implanted with A549 cells resulted in a significant inhibition in tumor growth. Our results provide a suggestion that PFE can be a useful chemopreventive/chemotherapeutic agent against human lung cancer.

  20. Post-transcriptional silencing of CCR3 downregulates IL-4 stimulated release of eotaxin-3 (CCL26) and other CCR3 ligands in alveolar type II cells.

    PubMed

    Taka, Equar; Errahali, Younes J; Abonyo, Barack O; Bauer, David M; Heiman, Ann S

    2008-12-01

    Trafficking and inflammation in airway diseases are, in part, modulated by members of the CC chemokine family, eotaxin-1 (CCL11), eotaxin-2 (CCL24), and eotaxin-3 (CCL26), which transduce signals through their CCR3 receptor. In this context, we hypothesized that transfecting alveolar type II epithelial cells with CCR3-targeted siRNA or antisense (AS-ODN) sequences will downregulate cellular synthesis and release of the primary CCR3 ligands CCL26 and CCL24 and will modulate other CCR3 ligands. The human A549 alveolar type II epithelium-like cell culture model was used for transfection and subsequent effects on CCR3 agonists. siRNAs were particularly effective. PCR showed a 60-80% decrease in mRNA and immunoblots showed up to 75-84% reduction of CCR3 in siRNA treated cells. CCR3-siRNA treatments reduced IL-4 stimulated CCL26 release and constitutive CCL24 release by 65% and 80%, respectively. Release of four additional CCR3 agonists RANTES, MCP-2, MCP-3 and MCP-4 was also significantly reduced by CCR3-siRNA treatments of the alveolar type II cells. Activation of eosinophils, assessed as superoxide anion generation, was reduced when eosinophils were treated with supernatants of A549 cells pretreated with CCR3-targeted siRNAs or AS-ODNs. Collectively, the data suggest that post-transcriptional regulation of CCR3 receptors may be a potential therapeutic approach for interrupting proinflammatory signaling.

  1. Competency Based Vocational Education Typing I and Typing II.

    ERIC Educational Resources Information Center

    Brown, G. Lee; Mahan, Louise

    Materials are provided for two competency-based educational courses in Typing I and II for the community college level. The first course covers the touch method operation of the typewriter; the second covers the extension of the touch method and develops such skills as production of business letters, manuscripts, carbon copies, tabulation, tables,…

  2. The synergistic effect of resveratrol in combination with cisplatin on apoptosis via modulating autophagy in A549 cells.

    PubMed

    Hu, Song; Li, Xiaolin; Xu, Rongrong; Ye, Lingyun; Kong, Hui; Zeng, Xiaoning; Wang, Hong; Xie, Weiping

    2016-06-01

    Several studies have shown that combination treatment with natural products and chemotherapy agents can improve the sensitivity and cytotoxicity of chemotherapy agents. Resveratrol, a natural product, has many biological effects including antitumor and antiviral activities, as well as vascular protective effect. The aim of this study is to investigate the synergistic anticancer effect of resveratrol in combination with cisplatin and the potential anticancer mechanisms involved in A549 cells. The results obtained from Cell Counting Kit-8 and isobolographic analysis demonstrated that combination of resveratrol and cisplatin resulted in synergistic cytotoxic effects in A549 cells. Results from Hoechst staining, flow cytometry and western blot analysis suggested that resveratrol enhanced cisplatin-mediated apoptosis. Meanwhile, the changes of LC3-II and P62 levels and formation of autophagosome suggested that resveratrol in combination with cisplatin triggered autophagy. More importantly, inhibiting autophagy by 3-methyladenine markedly attenuated the apoptosis caused by combination of resveratrol and cisplatin in A549 cells. Taken together, our study provides the first evidence that resveratrol combined with cisplatin synergistically induce apoptosis via modulating autophagic cell death in A549 cells. These findings also help us to understand the role of natural products in combination with chemotherapy agents in lung cancer.

  3. Magnetization of anisotropic Type II superconductors

    SciTech Connect

    Mints, R.G.

    1989-04-10

    Peculiarities of magnetization of anisotropic type II superconductors are of considerable interest in view of the discovery of high-T/sub c/ superconductors characterized by strongly asymmetric layered structure. Specifics of the penetration of magnetic flux into an anisotropic type II superconductor were discussed in the literature. This analysis gave the distribution of induction in an isolated vortex, its energy, and critical magnetic field H/sub c1/. However, the magnetization curve of anisotropic superconductors was not considered. This paper deals with the magnetic moment of uniaxial London superconductor in the interval H/sub c1/ /le/ H/sub 0/ << H/sub c2/, where H/sub 0/ is the external magnetic field strength.

  4. Discovery of 2'-hydroxychalcones as autophagy inducer in A549 lung cancer cells.

    PubMed

    Wang, Fang-Wu; Wang, Sheng-Qing; Zhao, Bao-Xiang; Miao, Jun-Ying

    2014-05-21

    A series of 2'-hydroxychalcone derivatives was synthesized and the effects of all the compounds on growth of A549 lung cancer cell were investigated. The results showed that all compounds had inhibitory effects on the growth of A549 lung cancer cells and compound possessed the highest growth inhibitory effect and induced autophagy of A549 lung cancer cells.

  5. Novel curcumin analogue IHCH exhibits potent anti‑proliferative effects by inducing autophagy in A549 lung cancer cells.

    PubMed

    Zhou, Guang-Zhou; Xu, Su-Li; Sun, Gang-Chun; Chen, Xiao-Bing

    2014-07-01

    Curcumin is a natural polyphenolic compound that exhibits strong antioxidant and anticancer activities; however, low bioavailability has restricted its application in chemotherapeutic trials. The present study aimed to investigate the anticancer effect of the novel curcumin derivative 2E,6E‑2‑(1H‑indol‑3‑yl) methylene)‑6‑(4‑hydroxy‑3‑methoxy benzylidene)‑cyclohexanone (IHCH) on A549 lung cancer cells. Cells were treated with IHCH at different concentrations (1‑40 µM) for different time periods (1‑36 h). Microscopic analysis revealed that IHCH inhibited A549 cell growth and induced the formation of characteristic autophagolysosomes in a dose‑ and time‑dependent manner. Furthermore, the inhibitory rate of IHCH (40 µM) on A549 cell viability was 77.34% after 36 h of treatment. Acridine orange staining revealed an increase in autophagic vacuoles in the IHCH‑treated A549 cells. Monodansylcadaverine staining was used to analyze autophagy rate. Immunocytochemistry revealed an increase in light chain (LC) 3 protein expression in the IHCH‑treated cells and western blot analysis detected the conversion of LC3‑I to LC3‑II, as well as the recruitment of LC3 to autophagosomes in the cytoplasmatic compartment, suggesting the occurrence of autophagy. These findings show that IHCH induced autophagy in A549 cells, which is a novel cell death mechanism induced by curcumin derivatives.

  6. Headache and Decompression Sickness: Type I or Type II?

    DTIC Science & Technology

    2001-06-01

    neurological exam was normal. Recompression with 100% oxygen produced relief within fifteen minutes. Follow up revealed no recurrence . Case 2 A twenty-seven...Follow up revealed no recurrence . Both cases pose an intriguing question. Should headache always be considered Type II DCS? DCS has a wide range of...with the supporting basis for this alternative view. The background for this paper is based on orthodontic and osteopathic medicine. For years

  7. UBIQUITOUS TORSIONAL MOTIONS IN TYPE II SPICULES

    SciTech Connect

    De Pontieu, B.; Hansteen, V. H.; Carlsson, M.; Rouppe van der Voort, L. H. M.; Rutten, R. J.; Watanabe, H.

    2012-06-10

    Spicules are long, thin, highly dynamic features that jut out ubiquitously from the solar limb. They dominate the interface between the chromosphere and corona and may provide significant mass and energy to the corona. We use high-quality observations with the Swedish 1 m Solar Telescope to establish that so-called type II spicules are characterized by the simultaneous action of three different types of motion: (1) field-aligned flows of order 50-100 km s{sup -1}, (2) swaying motions of order 15-20 km s{sup -1}, and (3) torsional motions of order 25-30 km s{sup -1}. The first two modes have been studied in detail before, but not the torsional motions. Our analysis of many near-limb and off-limb spectra and narrowband images using multiple spectral lines yields strong evidence that most, if not all, type II spicules undergo large torsional modulation and that these motions, like spicule swaying, represent Alfvenic waves propagating outward at several hundred km s{sup -1}. The combined action of the different motions explains the similar morphology of spicule bushes in the outer red and blue wings of chromospheric lines, and needs to be taken into account when interpreting Doppler motions to derive estimates for field-aligned flows in spicules and determining the Alfvenic wave energy in the solar atmosphere. Our results also suggest that large torsional motion is an ingredient in the production of type II spicules and that spicules play an important role in the transport of helicity through the solar atmosphere.

  8. Effect of copper overload on the survival of HepG2 and A-549 human-derived cells.

    PubMed

    Arnal, N; de Alaniz, M J T; Marra, C A

    2013-03-01

    We investigated the effect of copper (Cu) overload (20-160 µM/24 h) in two cell lines of human hepatic (HepG2) and pulmonary (A-549) origin by determining lipid and protein damage and the response of the antioxidant defence system. A-549 cells were more sensitive to Cu overload than HepG2 cells. A marked increase was observed in both the cell lines in the nitrate plus nitrite concentration, protein carbonyls and thiobarbituric acid reactive substances (TBARS). The TBARS increase was consistent with an increment in saturated fatty acids at the expense of polyunsaturated acids in a Cu concentration-dependent fashion. Antioxidant enzymes were stimulated by Cu overload. Superoxide dismutase activity increased significantly in both the cell lines, with greater increases in HepG2 than in A-549 cells. A marked increase in ceruloplasmin and metallothionein content in both the cell types was also observed. Dose-dependent decreases in α-tocopherol and ferric reducing ability were observed. Total glutathione content was lower in A-549 cells and higher in HepG2. Calpain and caspase-3 were differentially activated in a dose-dependent manner under copper-induced reactive oxygen species production. We conclude that Cu exposure of human lung- and liver-derived cells should be considered a reliable experimental system for detailed study of mechanism/mechanisms by which Cu overload exerts its deleterious effects.

  9. Spectral modeling of Type II SNe

    NASA Astrophysics Data System (ADS)

    Dessart, Luc

    2015-08-01

    The red supergiant phase represents the final stage of evolution in the life of moderate mass (8-25Msun) massive stars. Hidden from view, the core changes considerably its structure, progressing through the advanced stages of nuclear burning, and eventually becomes degenerate. Upon reaching the Chandrasekhar mass, this Fe or ONeMg core collapses, leading to the formation of a proto neutron star. A type II supernova results if the shock that forms at core bounce, eventually wins over the envelope accretion and reaches the progenitor surface.The electromagnetic display of such core-collapse SNe starts with this shock breakout, and persists for months as the ejecta releases the energy deposited initially by the shock or continuously through radioactive decay. Over a timescale of weeks to months, the originally optically-thick ejecta thins out and turns nebular. SN radiation contains a wealth of information about the explosion physics (energy, explosive nucleosynthesis), the progenitor properties (structure and composition). Polarised radiation also offers signatures that can help constrain the morphology of the ejecta.In this talk, I will review the current status of type II SN spectral modelling, and emphasise that a proper solution requires a time dependent treatment of the radiative transfer problem. I will discuss the wealth of information that can be gleaned from spectra as well as light curves, from both the early times (photospheric phase) and late times (nebular phase). I will discuss the diversity of Type SNe properties and how they are related to the diversity of red supergiant stars from which they originate.SN radiation offers an alternate means of constraining the properties of red-supergiant stars. To wrap up, I will illustrate how SNe II-P can also be used as probes, for example to constrain the metallicity of their environment.

  10. INTERPLANETARY SHOCKS LACKING TYPE II RADIO BURSTS

    SciTech Connect

    Gopalswamy, N.; Kaiser, M. L.; Xie, H.; Maekelae, P.; Akiyama, S.; Yashiro, S.; Howard, R. A.; Bougeret, J.-L.

    2010-02-20

    We report on the radio-emission characteristics of 222 interplanetary (IP) shocks detected by spacecraft at Sun-Earth L1 during solar cycle 23 (1996 to 2006, inclusive). A surprisingly large fraction of the IP shocks ({approx}34%) was radio quiet (RQ; i.e., the shocks lacked type II radio bursts). We examined the properties of coronal mass ejections (CMEs) and soft X-ray flares associated with such RQ shocks and compared them with those of the radio-loud (RL) shocks. The CMEs associated with the RQ shocks were generally slow (average speed {approx}535 km s{sup -1}) and only {approx}40% of the CMEs were halos. The corresponding numbers for CMEs associated with RL shocks were 1237 km s{sup -1} and 72%, respectively. Thus, the CME kinetic energy seems to be the deciding factor in the radio-emission properties of shocks. The lower kinetic energy of CMEs associated with RQ shocks is also suggested by the lower peak soft X-ray flux of the associated flares (C3.4 versus M4.7 for RL shocks). CMEs associated with RQ CMEs were generally accelerating within the coronagraph field of view (average acceleration {approx}+6.8 m s{sup -2}), while those associated with RL shocks were decelerating (average acceleration {approx}-3.5 m s{sup -2}). This suggests that many of the RQ shocks formed at large distances from the Sun, typically beyond 10 Rs, consistent with the absence of metric and decameter-hectometric (DH) type II radio bursts. A small fraction of RL shocks had type II radio emission solely in the kilometric (km) wavelength domain. Interestingly, the kinematics of the CMEs associated with the km type II bursts is similar to those of RQ shocks, except that the former are slightly more energetic. Comparison of the shock Mach numbers at 1 AU shows that the RQ shocks are mostly subcritical, suggesting that they were not efficient in accelerating electrons. The Mach number values also indicate that most of these are quasi-perpendicular shocks. The radio-quietness is predominant

  11. Minkowski Flux Vacua of Type II Supergravities

    NASA Astrophysics Data System (ADS)

    Andriot, David; Blâbäck, Johan; Van Riet, Thomas

    2017-01-01

    We study flux compactifications of 10D type II supergravities to 4D Minkowski space-time, supported by parallel orientifold Op planes with 3 ≤p ≤8 . With some geometric restrictions, the 4D Ricci scalar can be written as a negative sum of squares involving Bogomol'nyi-Prasad-Sommerfield-like conditions. Setting all squares to zero provides automatically a solution to 10D equations of motion. This way we characterize a broad class, if not the complete set, of Minkowski flux vacua with parallel orientifolds. We conjecture an extension with nongeometric fluxes. None of our results rely on supersymmetry.

  12. Activity of interferon alpha, interleukin 6 and insulin in the regulation of differentiation in A549 alveolar carcinoma cells.

    PubMed

    McCormick, C; Freshney, R I; Speirs, V

    1995-02-01

    The differentiation of A549, a human tumour cell line from type II pneumocytes, can be induced by a crude fibroblast-derived factor (FDF) isolated from the conditioned medium of glucocorticoid-treated lung fibroblasts. In the present report, we have used alkaline phosphatase as a differentiation marker to investigate the activity of a number of growth factors as potential candidates for this paracrine activity. This showed that insulin, interleukin 6 (IL-6), and interferon alpha (IFN-alpha) could simulate the activity of conditioned medium. Their effects were dexamethasone (DX) dependent, additive and reversible with a half-life of 1 week. Transforming growth factor alpha and beta, IL-1 alpha and epidermal growth factor, were all inhibitory, and inhibition was opposed, partially or completely, by DX. The most potent inducer was IL-6, but as DX was shown to decrease the concentration of IL-6 in lung fibroblast-conditioned medium it seems an unlikely candidate for FDF. Unlike FDF, all of the positive-acting factors were shown to induce plasminogen activator. FDF has also been shown to be active in the absence of DX. This suggests that differentiation-inducing activity may be present in several paracrine factors, but that so far a candidate for FDF has not been identified.

  13. Activity of interferon alpha, interleukin 6 and insulin in the regulation of differentiation in A549 alveolar carcinoma cells.

    PubMed Central

    McCormick, C.; Freshney, R. I.; Speirs, V.

    1995-01-01

    The differentiation of A549, a human tumour cell line from type II pneumocytes, can be induced by a crude fibroblast-derived factor (FDF) isolated from the conditioned medium of glucocorticoid-treated lung fibroblasts. In the present report, we have used alkaline phosphatase as a differentiation marker to investigate the activity of a number of growth factors as potential candidates for this paracrine activity. This showed that insulin, interleukin 6 (IL-6), and interferon alpha (IFN-alpha) could simulate the activity of conditioned medium. Their effects were dexamethasone (DX) dependent, additive and reversible with a half-life of 1 week. Transforming growth factor alpha and beta, IL-1 alpha and epidermal growth factor, were all inhibitory, and inhibition was opposed, partially or completely, by DX. The most potent inducer was IL-6, but as DX was shown to decrease the concentration of IL-6 in lung fibroblast-conditioned medium it seems an unlikely candidate for FDF. Unlike FDF, all of the positive-acting factors were shown to induce plasminogen activator. FDF has also been shown to be active in the absence of DX. This suggests that differentiation-inducing activity may be present in several paracrine factors, but that so far a candidate for FDF has not been identified. PMID:7841035

  14. TGFβ upregulates PAR-1 expression and signalling responses in A549 lung adenocarcinoma cells

    PubMed Central

    Smoktunowicz, Natalia; Platé, Manuela; Stern, Alejandro Ortiz; D'Antongiovanni, Vanessa; Robinson, Eifion; Chudasama, Vijay; Caddick, Stephen; Scotton, Chris J.; Jarai, Gabor; Chambers, Rachel C.

    2016-01-01

    The major high-affinity thrombin receptor, proteinase activated receptor-1 (PAR-1) is expressed at low levels by the normal epithelium but is upregulated in many types of cancer, including lung cancer. The thrombin-PAR-1 signalling axis contributes to the activation of latent TGFβ in response to tissue injury via an αvβ6 integrin-mediated mechanism. TGFβ is a pleiotropic cytokine that acts as a tumour suppressor in normal and dysplastic cells but switches into a tumour promoter in advanced tumours. In this study we demonstrate that TGFβ is a positive regulator of PAR-1 expression in A549 lung adenocarcinoma cells, which in turn increases the sensitivity of these cells to thrombin signalling. We further demonstrate that this effect is Smad3-, ERK1/2- and Sp1-dependent. We also show that TGFβ-mediated PAR-1 upregulation is accompanied by increased expression of integrin αv and β6 subunits. Finally, TGFβ pre-stimulation promotes increased migratory potential of A549 to thrombin. These data have important implications for our understanding of the interplay between coagulation and TGFβ signalling responses in lung cancer. PMID:27566553

  15. Cytotoxicity of semiconductor nanoparticles in A549 cells is attributable to their intrinsic oxidant activity

    NASA Astrophysics Data System (ADS)

    Escamilla-Rivera, Vicente; Uribe-Ramirez, Marisela; Gonzalez-Pozos, Sirenia; Velumani, Subramaniam; Arreola-Mendoza, Laura; De Vizcaya-Ruiz, Andrea

    2016-04-01

    Copper indium gallium diselenide (CIGS) and cadmium sulfide (CdS) nanoparticles (NP) are next generation semiconductors used in photovoltaic cells (PV). They possess high quantum efficiency, absorption coefficient, and cheaper manufacturing costs compared to silicon. Due to their potential for an industrial development and the lack of information about the risk associated in their use, we investigated the influence of the physicochemical characteristics of CIGS (9 nm) and CdS (20 nm) in relation to the induction of cytotoxicity in human alveolar A549 cells through ROS generation and mitochondrial dysfunction. CIGS induced cytotoxicity in a dose dependent manner in lower concentrations than CdS; both NP were able to induce ROS in A549. Moreover, CIGS interact directly with mitochondria inducing depolarization that leads to the induction of apoptosis compared to CdS. Antioxidant pretreatment significantly prevented the loss of mitochondrial membrane potential and cytotoxicity, suggesting ROS generation as the main cytotoxic mechanism. These results demonstrate that semiconductor characteristics of NP are crucial for the type and intensity of the cytotoxic effects. Our work provides relevant information that may help guide the production of a safer NP-based PV technologies, and would be a valuable resource on future risk assessment for a safer use of nanotechnology in the development of clean sources of renewable energy.

  16. Type I, II, and III Interferons: Regulating Immunity to Mycobacterium tuberculosis Infection.

    PubMed

    Travar, Maja; Petkovic, Miroslav; Verhaz, Antonija

    2016-02-01

    Interferons (IFNs) are cytokines released by host cells in response to the presence of pathogens or tumor cells. The aim of this review was to present the previously known and new findings about the role of interferons type I and II, and recently discovered type III in Mycobacterium tuberculosis (M. tuberculosis) infection control. Infection of various cell types with M. tuberculosis induce both IFN-α and IFN-β synthesis. The majority of the studies support the findings that IFN type I actually promotes infection with M. tuberculosis. It has been well establish that IFN-γ has protective function against M. tuberculosis and the other mycobacteria and that the primary source of this cytokine are CD4(+) and CD8(+) T cells. Recently, it has been shown that also the innate lymphocytes, γδ T cells, natural killer (NK) T cells, and NK cells can also be the source of IFN-γ in response to mycobacterial infection. Several studies have shown that CD4(+) T cells protect mice against M. tuberculosis independently of IFN-γ. The balance between IFN-γ and different cytokines such as IL-10 and other Th2 cell cytokines is likely to influence disease outcome. Type I IFN appears to be detrimental through at least three separate, but overlapping, type I IFN-mediated mechanisms: induction of excessive apoptosis, specific suppression of Th1 and IFN-γ responses, and dampening of the immune response by strong IL-10 induction. Recently it has been found that M. tuberculosis infection in A549 lung epithelial cells stimulate up-regulation of IFN-λ genes in vitro. IFN-λs also have a role in modulation of Th1/Th2 response. IFN-λs are not essential for M. tuberculosis infection control, but can give some contribution in immune response to this pathogen.

  17. Enteropeptidase, a type II transmembrane serine protease.

    PubMed

    Zheng, X Long; Kitamoto, Yasunori; Sadler, J Evan

    2009-06-01

    Enteropeptidase, a type II transmembrane serine protease, is localized to the brush border of the duodenal and jejunal mucosa. It is synthesized as a zymogen (proenteropeptidase) that requires activation by another protease, either trypsin or possibly duodenase. Active enteropeptidase then converts the pancreatic precursor, trypsinogen, to trypsin by cleavage of the specific trypsinogen activation peptide, Asp-Asp-Asp-Asp-Lys- Ile that is highly conserved in vertebrates. Trypsin, in turn, activates other digestive zymogens such as chymotrypsinogen, proelastase, procarboxypeptidase and prolipase in the lumen of the gut. The important biological function of enteropeptidase is highlighted by the manifestation of severe diarrhea, failure to thrive, hypoproteinemia and edema as a result of congenital deficiency of enteropeptidase activity in the gut. Conversely, duodenopancreatic reflux of proteolytically active enteropeptidase may cause acute and chronic pancreatitis.

  18. Prenatal diagnosis of Pfeiffer syndrome type II.

    PubMed

    Blaumeiser, Bettina; Loquet, Philip; Wuyts, Wim; Nöthen, Markus M

    2004-08-01

    Pfeiffer syndrome is an autosomal dominant disorder characterized by coronal craniosynostosis, midface hypoplasia, broad thumbs and great toes. On the basis of clinical findings, three subtypes have been delineated. The clinical variability of Pfeiffer syndrome as well as other causes of craniosynostosis can make a prenatal diagnosis based on sonography alone difficult. We describe a fetus in whom sonographic findings (including 3D ultrasound) suggested a Pfeiffer syndrome type II and in which subsequent molecular analysis verified the diagnosis by identifying a de novo mutation in the FGFR2 gene. To the best of our knowledge, this is the first report of a prenatal molecular diagnosis of Pfeiffer syndrome in a patient without family history.

  19. Ordering dynamics in type-II superconductors.

    PubMed

    Guttenberg, Nicholas; Goldenfeld, Nigel

    2006-12-01

    We use analytic and numerical methods to analyze the dynamics of vortices following the quench of a type-II superconductor under the application of an external magnetic field. In three dimensions, in the absence of a field, the spacing between vortices scales with time t with an exponent phi=0.414+/-0.01, in a thin sheet of a superconductor, the scaling exponent is phi=0.294+/-0.01. When an external magnetic field h is applied, the vortices are confined with respect to the length scale of the Abrikosov lattice, leading to a crossover between the power-law scaling length scale and the lattice length scale. From this we suggest a one-parameter scaling of r with h and r that is consistent with numerical data.

  20. Waardenburg syndrome type II: phenotypic findings and diagnostic criteria.

    PubMed

    Liu, X Z; Newton, V E; Read, A P

    1995-01-02

    The Waardenburg syndrome (WS) consists of at least two distinct autosomal dominant hereditary disorders. WS Type I has been mapped to the distal part of chromosome 2q and the gene identified as PAX3. Other gene(s) are responsible for WS Type II. Mapping WS Type II requires accurate diagnosis within affected families. To establish diagnostic criteria for WS Type II, 81 individuals from 21 families with Type II WS were personally studied, and compared with 60 personally studied patients from 8 families with Type I and 253 cases of WS (Type I or II) from the literature. Sensorineural hearing loss (77%) and heterochromia iridum (47%) were the two most important diagnostic indicators for WS Type II. Both were more common in Type II than in Type I. Other clinical manifestations, such as white forelock and skin patches, were more frequent in Type I. We estimate the frequency of phenotypic traits and propose diagnostic criteria for WS Type II. In practice, a diagnosis of WS Type II can be made with confidence given a family history of congenital hearing loss and pigmentary disorders, where individuals have been accurately measured for ocular distances to exclude dystopia canthorum.

  1. Type II Migration and Giant Planet Survival

    NASA Technical Reports Server (NTRS)

    Ward, William R.

    2003-01-01

    Type II migration, in which a newly formed large planet opens a gap in its precursor circumstellar nebula and subsequently evolves with it, has been implicated as a delivery mechanism responsible for close stellar companions. Large scale migration is possible in a viscously spreading disk of surface density sigma (r,t) when most of it is sacrificed to the primary in order to promote a small portion of the disk to much higher angular momentum orbits. Embedded planets generally follow its evolution unless their own angular momentum is comparable to that of the disk. The fraction of the starting disk mass, M (sub d) = 2pi integral rsigma(r,0)dr, that is consumed by the star depends on the distance at which material escapes the disk's outer boundary. If the disk is allowed to expand indefinitely, virtually all of the disk will fall into the primary in order to send a vanishingly small portion to infinity. For such a case, it is difficult to explain the survival of any giant planets, including Jupiter and Saturn. Realistically, however, there are processes that could truncate a disk at a finite distance, r(sub d). Recent numerical modeling has illustrated that planets can survive in this case. We show here that much of these results can be understood by simple conservation arguments.

  2. Current Understanding of Usher Syndrome Type II

    PubMed Central

    Yang, Jun; Wang, Le; Song, Hongman; Sokolov, Maxim

    2012-01-01

    Usher syndrome is the most common deafness-blindness caused by genetic mutations. To date, three genes have been identified underlying the most prevalent form of Usher syndrome, the type II form (USH2). The proteins encoded by these genes are demonstrated to form a complex in vivo. This complex is localized mainly at the periciliary membrane complex in photoreceptors and the ankle-link of the stereocilia in hair cells. Many proteins have been found to interact with USH2 proteins in vitro, suggesting that they are potential additional components of this USH2 complex and that the genes encoding these proteins may be the candidate USH2 genes. However, further investigations are critical to establish their existence in the USH2 complex in vivo. Based on the predicted functional domains in USH2 proteins, their cellular localizations in photoreceptors and hair cells, the observed phenotypes in USH2 mutant mice, and the known knowledge about diseases similar to USH2, putative biological functions of the USH2 complex have been proposed. Finally, therapeutic approaches for this group of diseases are now being actively explored. PMID:22201796

  3. [Achondrogenesis type I and II and hypochondrogenesis (author's transl)].

    PubMed

    Bueno, M; Toledo, F; Toledo, J; Villegas, T; López, S; Remírez, J; García-Julián, G

    1980-10-01

    A study is made of achondrogenesis in relation to four observations of early fatal development. One case corresponds to type I (Parenti-Fraccaro); another to type II (Langer-Saldino); the final two, brothers, seem to come under the variation of hypochondrogenesis. In this study, authors stress the heterogenous nature of lethal, neonatal (short-limb) nanisms of which currently include: Type I and II achondrogenesis, hypochondrogenesis, homozygote achondroplasia, classical Torrance-type and San Diego-type thanatophoric dysplasia.

  4. Per2 participates in AKT-mediated drug resistance in A549/DDP lung adenocarcinoma cells.

    PubMed

    Chen, Bo; Tan, Yaoxi; Liang, Yan; Li, Yan; Chen, Lei; Wu, Shuangshuang; Xu, Wei; Wang, Yan; Zhao, Weihong; Wu, Jianqing

    2017-01-01

    Period2 (Per2) is a key mammalian circadian clock protein, and additionally has a tumor suppressive function. The present study aimed to investigate its role in drug resistance in A549/cisplatin (DDP) lung adenocarcinoma cells. Per2 knockdown and overexpression in A549/DDP cells were used to compare cell proliferation (by MTT assay), apoptosis (active-caspase 3 western blot) and clone forming assay. The activation of AKT/mechanistic target of rapamycin (mTOR) was investigated by a western blot assay. The Per2 expression level was decreased in A549/DDP cells compared with A549 cells. Per2 knockdown by short hairpin RNA protects A549/DDP cells from apoptosis, and promotes proliferation and migration. Per2 knockdown results in increased activation of the phosphoinositide 3-kinase (PI3K)/AKT/mTOR signaling pathway. Overexpression of Per2 in A549/DDP cells may reduce the activity of the PI3K/AKT/mTOR signaling pathway, and promote apoptosis of A549 cells. The results of the present study suggest that Per2 participates in AKT-mediated drug resistance in A549/DDP lung adenocarcinoma cells.

  5. Per2 participates in AKT-mediated drug resistance in A549/DDP lung adenocarcinoma cells

    PubMed Central

    Chen, Bo; Tan, Yaoxi; Liang, Yan; Li, Yan; Chen, Lei; Wu, Shuangshuang; Xu, Wei; Wang, Yan; Zhao, Weihong; Wu, Jianqing

    2017-01-01

    Period2 (Per2) is a key mammalian circadian clock protein, and additionally has a tumor suppressive function. The present study aimed to investigate its role in drug resistance in A549/cisplatin (DDP) lung adenocarcinoma cells. Per2 knockdown and overexpression in A549/DDP cells were used to compare cell proliferation (by MTT assay), apoptosis (active-caspase 3 western blot) and clone forming assay. The activation of AKT/mechanistic target of rapamycin (mTOR) was investigated by a western blot assay. The Per2 expression level was decreased in A549/DDP cells compared with A549 cells. Per2 knockdown by short hairpin RNA protects A549/DDP cells from apoptosis, and promotes proliferation and migration. Per2 knockdown results in increased activation of the phosphoinositide 3-kinase (PI3K)/AKT/mTOR signaling pathway. Overexpression of Per2 in A549/DDP cells may reduce the activity of the PI3K/AKT/mTOR signaling pathway, and promote apoptosis of A549 cells. The results of the present study suggest that Per2 participates in AKT-mediated drug resistance in A549/DDP lung adenocarcinoma cells. PMID:28123577

  6. Type-II Dirac surface states in topological crystalline insulators

    NASA Astrophysics Data System (ADS)

    Chiu, Ching-Kai; Chan, Y.-H.; Li, Xiao; Nohara, Y.; Schnyder, A. P.

    2017-01-01

    Recently, it has been realized that topological Weyl semimetals come in two different varieties: (i) with standard Weyl cones with pointlike Fermi surfaces (type I) and (ii) with tilted Weyl cones that appear at the contact of electron and hole pockets (type II). These two types of Weyl semimetals have very different physical properties, in particular, in their thermodynamics and magnetotransport. Here, we show that Dirac cone surface states of topological crystalline insulators can be distinguished in a similar way. We demonstrate this in terms of a general surface theory and then apply this knowledge to a family of antiperovskites of the form A3E O , where A denotes an alkaline earth metal, while E stands for Pb or Sn. Using ab initio DFT calculations, we investigate the bulk and surface topology of these antiperovskites and show that they exhibit type-I as well as type-II Dirac surface states protected by reflection symmetry. We find that the type-II Dirac states, as opposed to the type-I Dirac states, exhibit characteristic van Hove singularities in their dispersion, which lead to different thermodynamic properties, and which can serve as an experimental fingerprint of type-II surface states. The different magnetotransport characteristics between type-I and type-II surface states are discussed. In addition, we show that both type-I and type-II surface states exhibit an unusual helical spin polarization, which could lead to topological surface superconductivity.

  7. Surgical Treatment of Tubular Breast Type II

    PubMed Central

    Dabizha, Oleksii Y.; Kostenko, Alona A.; Gomolyako, Irina V.; Samko, Kristina A.; Borovyk, Denys V.

    2016-01-01

    Background: Tubular breasts are caused by connective tissue malformation and occur in puberty. The main clinical characteristics of the tubular breast are breast asymmetry, dense fibrous ring around the areola, hernia bulging of the areola, megaareola, and hypoplasia of quadrants of the breast. Pathology causes great psychological discomfort to patients. Methods: This study included 17 patients, aged 18 to 34 years, with tubular breast type II who had bilateral pathology and were treated from 2013 to 2016. They had surgical treatment by method of the clinic. Correction technique consisted of mobilization of the central part of the gland and formation of a glandular flap with vertical and horizontal scorings, which looks like a “chessboard,” that was sufficient to cover the lower pole of the implant. The flap was fixed to the submammary folds with stitches that prevented its reduction and accented a new submammary fold. To underscore the importance of the method and to study the structural features of the vascular bed of tubular breast tissue, a morphological study was conducted. Results: Mean follow-up time was 25 months (range between 13 and 37 mo). The proposed technique achieved good results. Complications (hematoma, circumareolar scarring, and “double-bubble” deformity) were identified in 4 patients. Conclusions: Our morphological study confirmed that tubular breast tissue has increased vascularity due to the vessels with characteristic minor malformation and due to the high restorative potential of the vascular bed. Therefore, an extended glandular flap could be freely mobilized without damaging its blood supply; thus, the flap in most cases covered the implant completely and good aesthetic results were achieved. PMID:27826461

  8. Type II superlattice technology for LWIR detectors

    NASA Astrophysics Data System (ADS)

    Klipstein, P. C.; Avnon, E.; Azulai, D.; Benny, Y.; Fraenkel, R.; Glozman, A.; Hojman, E.; Klin, O.; Krasovitsky, L.; Langof, L.; Lukomsky, I.; Nitzani, M.; Shtrichman, I.; Rappaport, N.; Snapi, N.; Weiss, E.; Tuito, A.

    2016-05-01

    SCD has developed a range of advanced infrared detectors based on III-V semiconductor heterostructures grown on GaSb. The XBn/XBp family of barrier detectors enables diffusion limited dark currents, comparable with MCT Rule-07, and high quantum efficiencies. This work describes some of the technical challenges that were overcome, and the ultimate performance that was finally achieved, for SCD's new 15 μm pitch "Pelican-D LW" type II superlattice (T2SL) XBp array detector. This detector is the first of SCD's line of high performance two dimensional arrays working in the LWIR spectral range, and was designed with a ~9.3 micron cut-off wavelength and a format of 640 x 512 pixels. It contains InAs/GaSb and InAs/AlSb T2SLs, engineered using k • p modeling of the energy bands and photo-response. The wafers are grown by molecular beam epitaxy and are fabricated into Focal Plane Array (FPA) detectors using standard FPA processes, including wet and dry etching, indium bump hybridization, under-fill, and back-side polishing. The FPA has a quantum efficiency of nearly 50%, and operates at 77 K and F/2.7 with background limited performance. The pixel operability of the FPA is above 99% and it exhibits a stable residual non uniformity (RNU) of better than 0.04% of the dynamic range. The FPA uses a new digital read-out integrated circuit (ROIC), and the complete detector closely follows the interfaces of SCD's MWIR Pelican-D detector. The Pelican- D LW detector is now in the final stages of qualification and transfer to production, with first prototypes already integrated into new electro-optical systems.

  9. Type II collagenopathies: Are there additional family members?

    SciTech Connect

    Freisinger, P.; Pontz, B.F.; Emmrich, P.; Stoess, H.; Bonaventure, J.

    1996-05-03

    The type II collagenopathies represent a group of chondrodysplasia sharing clinical and radiological manifestations which are expressed as a continuous spectrum of phenotypes, ranging from perinatally lethal to very mild conditions. Their common molecular bases are mutations in the type II collagen gene (COL2A1). We describe one case of lethal platyspondylic dysplasia, Torrance type, and a variant of lethal Kniest dysplasia, neither of which has been reported as a type II collagenopathy. Biochemical studies of cartilage collagens and morphological analysis of cartilage sections suggest that abnormalities of type II collagen structure and biosynthesis are the main pathogenetic factors in both cases. Thus, the phenotypic spectrum of type II collagenopathies might be greater than hitherto suspected. 20 refs., 6 figs.

  10. Generating controllable type-II Weyl points via periodic driving

    NASA Astrophysics Data System (ADS)

    Bomantara, Raditya Weda; Gong, Jiangbin

    2016-12-01

    Type-II Weyl semimetals are a novel gapless topological phase of matter discovered recently in 2015. Similar to normal (type-I) Weyl semimetals, type-II Weyl semimetals consist of isolated band touching points. However, unlike type-I Weyl semimetals which have a linear energy dispersion around the band touching points forming a three-dimensional (3D) Dirac cone, type-II Weyl semimetals have a tilted conelike structure around the band touching points. This leads to various novel physical properties that are different from type-I Weyl semimetals. In order to study further the properties of type-II Weyl semimetals and perhaps realize them for future applications, generating controllable type-II Weyl semimetals is desirable. In this paper, we propose a way to generate a type-II Weyl semimetal via a generalized Harper model interacting with a harmonic driving field. When the field is treated classically, we find that only type-I Weyl points emerge. However, by treating the field quantum mechanically, some of these type-I Weyl points may turn into type-II Weyl points. Moreover, by tuning the coupling strength, it is possible to control the tilt of the Weyl points and the energy difference between two Weyl points, which makes it possible to generate a pair of mixed Weyl points of type-I and type-II. We also discuss how to physically distinguish these two types of Weyl points in the framework of our model via the Landau level structures in the presence of an artificial magnetic field. The results are of general interest to quantum optics as well as ongoing studies of Floquet topological phases.

  11. Paracrine control of differentiation in the alveolar carcinoma, A549, by human foetal lung fibroblasts.

    PubMed

    Speirs, V; Ray, K P; Freshney, R I

    1991-10-01

    Synthesis of pulmonary surfactant (PS) is necessary for normal functioning of the lungs and its production is indicative of normal differentiated lung. The human alveolar carcinoma, A549, has been found to synthesis and secrete PS in vitro. The purpose of this study was to optimise the culture conditions for PS synthesis by A549 as well as to determine the potential role of foetal lung fibroblasts in the induction of PS by glucocorticoids. A549 cells growing in filter wells produced higher levels of PS in response to steroid, a 5-fold increase on the filter well compared to only a 1.5-fold increase when the cells were cultured on a conventional plastic substrate. A549 cells grown in filter wells responded to coculture with fibroblasts whether in direct contact or separated co-culture. A 20-fold increase in PS over control values was observed in separated steroid-treated co-cultures, suggesting the presence of a diffusible factor. A partially purified factor was isolated from fibroblast conditioned medium which was capable of inducing differentiation and other phenotypic changes in A549, namely induction of PS, reduction of plasminogen activator activity and reduction in the in vivo growth of A549 xenografts in nude mice. These results suggest that, under the correct conditions, A549 cells, although transformed, still retain the capacity to respond to differentiation-inducing signals from normal fibroblasts.

  12. Paracrine control of differentiation in the alveolar carcinoma, A549, by human foetal lung fibroblasts.

    PubMed Central

    Speirs, V.; Ray, K. P.; Freshney, R. I.

    1991-01-01

    Synthesis of pulmonary surfactant (PS) is necessary for normal functioning of the lungs and its production is indicative of normal differentiated lung. The human alveolar carcinoma, A549, has been found to synthesis and secrete PS in vitro. The purpose of this study was to optimise the culture conditions for PS synthesis by A549 as well as to determine the potential role of foetal lung fibroblasts in the induction of PS by glucocorticoids. A549 cells growing in filter wells produced higher levels of PS in response to steroid, a 5-fold increase on the filter well compared to only a 1.5-fold increase when the cells were cultured on a conventional plastic substrate. A549 cells grown in filter wells responded to coculture with fibroblasts whether in direct contact or separated co-culture. A 20-fold increase in PS over control values was observed in separated steroid-treated co-cultures, suggesting the presence of a diffusible factor. A partially purified factor was isolated from fibroblast conditioned medium which was capable of inducing differentiation and other phenotypic changes in A549, namely induction of PS, reduction of plasminogen activator activity and reduction in the in vivo growth of A549 xenografts in nude mice. These results suggest that, under the correct conditions, A549 cells, although transformed, still retain the capacity to respond to differentiation-inducing signals from normal fibroblasts. Images Figure 5 PMID:1654985

  13. Peptidoglycan-mediated IL-8 expression in human alveolar type II epithelial cells requires lipid raft formation and MAPK activation.

    PubMed

    Cheon, In Su; Woo, Sang Su; Kang, Seok-Seong; Im, Jintaek; Yun, Cheol-Heui; Chung, Dae Kyun; Park, Dong Ki; Han, Seung Hyun

    2008-03-01

    Staphylococcus aureus, a major sepsis-causing Gram-positive bacterium, invades pulmonary epithelial cells and causes lung diseases. In the lung, alveolar type II epithelial cells play an important role in innate immunity by secreting chemokines and antimicrobial peptides upon bacterial infection whereas type I cells mainly function in gas-exchange. In this study, we investigated the ability of S. aureus peptidoglycan (PGN) to induce expression of a chemokine, IL-8, in a human alveolar type II epithelial cell line, A549. PGN induces IL-8 mRNA and protein expression in a dose- and time-dependent manner. Supplementation of soluble CD14 further enhanced the PGN-induced IL-8 expression. Interestingly, PGN-induced IL-8 expression was inhibited by nystatin, a specific inhibitor for lipid rafts, but not by chlorpromazine, a specific inhibitor for clathrin-coated pits. Furthermore, PGN-induced IL-8 expression was attenuated by inhibitors for MAP kinases such as ERK, p38 kinase, and JNK/SAPK, whereas no inhibitory effect was observed by inhibitors for reactive oxygen species or protein kinase C. Electrophoretic mobility shift assay demonstrates that PGN increased the DNA binding of the transcription factors, AP-1 and NF-kappaB while minimally, NF-IL6, all of which are involved in the transcription of IL-8. Taken together, these results suggest that PGN induces IL-8 expression in a CD14-enhanced manner in human alveolar type II epithelial cells, through the formation of lipid rafts and the activation of MAP kinases, which ultimately leads to activation of AP-1, NF-kappaB, and NF-IL6.

  14. Anti-Proliferative and Apoptosis-Inducing Effect of Theabrownin against Non-small Cell Lung Adenocarcinoma A549 Cells

    PubMed Central

    Wu, Feifei; Zhou, Li; Jin, Wangdong; Yang, Weiji; Wang, Ying; Yan, Bo; Du, Wenlin; Zhang, Qiang; Zhang, Lei; Guo, Yonghua; Zhang, Jin; Shan, Letian; Efferth, Thomas

    2016-01-01

    With the highest cancer incidence rate, lung cancer, especially non-small cell lung cancer (NSCLC), is the leading cause of cancer death in the world. Tea (leaves of Camellia sinensis) has been widely used as a traditional beverage beneficial to human health, including anti-NSCLC activity. Theabrownin (TB) is one major kind of tea pigment responsible for the beneficial effects of tea liquor. However, its effect on NSCLC is unknown. The aim of the present study was to evaluate anti-proliferative and apoptosis-inducing effect of TB on NSCLC (A549) cells, using MTT assay, morphological observation (DAPI staining), in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and annexin-V/PI flow cytometry. Subsequently, the expression of several genes associated with cell proliferation and apoptosis were detected by real time PCR assay to explore its potential underlying mechanism. TB was revealed to inhibit cell proliferation of A549 cells in a concentration-dependent and time-dependent manner. Morphological observation, TUNEL assay and flow cytometric analysis evidenced an apoptosis-inducing effect of TB on A549 cells in a concentration-dependent manner. The real time PCR assay demonstrated that TB down-regulated the expression of TOPO I, TOPO II, and BCL-2, and up-regulated the expression of E2F1, P53, GADD45, BAX, BIM, and CASP 3,7,8,9, which suggests an activation of P53-mediated apoptotic (caspase-dependent) pathway in response to TB treatment. The western blot analysis showed a similar trend for the corresponding protein expression (P53, Bax, Bcl-2, caspase 3,9, and PARP) and further revealed DNA damage as a trigger of the apoptosis (phosphorylation of histone H2A.X). Accordingly, TB can be speculated as a DNA damage inducer and topoisomerase (Topo I and Topo II) inhibitor that can up-regulate P53 expression and subsequently modulate the expression of the downstream genes to induce cell proliferation inhibition and apoptosis of A549 cells

  15. Degree of polarization of type-II unpolarized light

    SciTech Connect

    Luis, Alfredo

    2007-05-15

    We address a quantitative determination of the degree of polarization of type-II unpolarized light via the computation of the distance between the polarization distribution and the uniform distribution associated with fully unpolarized light (i.e., type-I unpolarized light or natural light). We determine the maximum degree of polarization for type-II unpolarized light and the states reaching it. We show that the degree of polarization can be arbitrarily large, approaching complete polarization for increasing mean photon numbers.

  16. Prediction of Type II Burst Radiation for Large CME Events

    NASA Astrophysics Data System (ADS)

    Cairns, I. H.; Schmidt, J. M.

    2013-12-01

    Type IIs are associated with shocks in the corona and solar wind, either driven by CMEs or else blast waves. Recent quantitative theories for type II radiation show that the amount of radiation depends on the speed and spatial extent of the 3D shock, as well as on the background plasma, magnetic field configuration, and the number of superthermal electrons available for acceleration by the shock. In principle, then, Type II bursts may provide 1-3 day warnings of large and fast CMEs that might produce space weather at Earth. In this paper we couple the advanced 3D MHD BATS-R-US code of Toth, Gombosi, and colleagues with our new ``bolt-on'' theory for type II emission. The modeling includes initialization with coronal and active region magnetic fields reconstructed from solar magnetograms, coronal densities determined by 1 AU data, and CMEs modelled using STEREO coronagraph data. Two events with type IIs and strong CMEs are analyzed: 15 February 2011 and 7 March 2012. We demonstrate impressive accuracy in time, frequency, and intensity for both type II bursts. This strongly supports the type II theory, implies real understanding of the physics involved, and supports the near-term development of a capability to predict and track these events for space weather prediction.

  17. Herringbone bursts associated with type II solar radio emission

    NASA Technical Reports Server (NTRS)

    Cairns, I. H.; Robinson, R. D.

    1987-01-01

    Detailed observations of the herringbone (HB) fine structure on type II solar radio bursts are presented. Data from the Culgoora radiospectrograph, radiometer and radioheliograph are analyzed. The characteristic spectral profiles, frequency drift rates and exciter velocities, fluxes, source sizes, brightness temperatures, and polarizations of individual HB bursts are determined. Correlations between individual bursts within the characteristic groups of bursts and the properties of the associated type II bursts are examined. These data are compatible with HB bursts being radiation at multiples of the plasma frequency generated by electron streams accelerated by the type II shock. HB bursts are physically distinct phenomena from type II and type III bursts, differing significantly in emission processes and/or source conditions; this conclusion indicates that many of the presently available theoretical ideas for HB bursts are incorrect.

  18. Type II oestrogen binding sites in human colorectal carcinoma.

    PubMed Central

    Piantelli, M; Ricci, R; Larocca, L M; Rinelli, A; Capelli, A; Rizzo, S; Scambia, G; Ranelletti, F O

    1990-01-01

    Seven cases of colorectal adenocarcinomas were investigated for the presence of oestrogen receptors and progesterone receptors. The tumours specifically bound oestradiol. This binding almost exclusively resulted from the presence of high numbers of type II oestrogen binding sites. Oestrogen receptors were absent or present at very low concentrations. Immunohistochemical investigation of nuclear oestrogen receptors gave negative results. This indicates that antioestrogen receptor antibodies recognise oestrogen receptors but not type II oestrogen binding sites. The presence of specific type II oestrogen binding sites and progesterone binding offers further evidence for a potential role for these steroids and their receptors in colorectal carcinoma. PMID:2266171

  19. Type II achondrogenesis-hypochondrogenesis: morphologic and immunohistopathologic studies.

    PubMed

    Godfrey, M; Keene, D R; Blank, E; Hori, H; Sakai, L Y; Sherwin, L A; Hollister, D W

    1988-12-01

    A 32-wk-gestation female with type II achondrogenesis-hypochondrogenesis has been studied. The clinical features were typical, and radiographs revealed short ribs, hypoplastic ilia, absence of ossification of sacrum, pubis, ischia, tali, calcanei, and many vertebral bodies; the long bones were short with mild metaphyseal flaring. The femoral cylinder index was 6.3. Comparison with previous cases placed the patient toward the mild end of the achondrogenesis-hypochondrogenesis spectrum (Whitley-Gorlin prototype IV). Light microscopy revealed hypercellular cartilage with decreased matrix traversed by numerous fibrous vascular canals. The growth plate was markedly abnormal. Ultrastructural studies revealed prominently dilated rough endoplasmic reticulum containing a fine granular material with occasional fibrils in all chondrocytes. Immunohistologic studies indicated irregular large areas of cartilage matrix staining with monoclonal antibody to human type III collagen. The relative intensity of matrix staining for type II collagen appeared diminished. More striking, however, were intense focal accumulations of type II collagen within small rounded perinuclear structures of most chondrocytes but not other cell types. These results strongly suggest intracellular retention of type II collagen within vacuolar structures, probably within the dilated rough endoplasmic reticulum observed in all chondrocytes by electron microscopy (EM), and imply the presence of an abnormal, poorly secreted type II collagen molecule. Biochemical studies (see companion paper) suggest that this patient had a new dominant lethal disorder caused by a structural abnormality of type II collagen.

  20. Serum markers for type II diabetes mellitus

    DOEpatents

    Metz, Thomas O; Qian, Wei-Jun; Jacobs, Jon M; Polpitiya, Ashoka D; Camp, II, David G; Smith, Richard D

    2014-03-18

    A method for identifying persons with increased risk of developing type 2 diabetes mellitus utilizing selected biomarkers described hereafter either alone or in combination. The present invention allows for broad based, reliable, screening of large population bases and provides other advantages, including the formulation of effective strategies for characterizing, archiving, and contrasting data from multiple sample types under varying conditions.

  1. A COL2A1 mutation in achondrogenesis type II results in the replacement of type II collagen by type I and III collagens in cartilage.

    PubMed

    Chan, D; Cole, W G; Chow, C W; Mundlos, S; Bateman, J F

    1995-01-27

    An autosomal dominant mutation in the COL2A1 gene was identified in a fetus with achondrogenesis type II. A transition of G2853 to A in exon 41 produced a substitution of Gly769 by Ser within the triple helical domain of the alpha 1(II) chain of type II collagen, interrupting the mandatory Gly-X-Y triplet sequence required for the normal formation of stable triple helical type II collagen molecules, resulting in the complete absence of type II collagen in the cartilage, which had a gelatinous composition. Type I and III collagens were the major species found in cartilage tissue and synthesized by cultured chondrocytes along with cartilage type XI collagen. However, cultured chondrocytes produced a trace amount of type II collagen, which was retained within the cells and not secreted. In situ hybridization of cartilage sections showed that the chondrocytes produced both type II and type I collagen mRNA. As a result, it is likely that the chondrocytes produced type II collagen molecules, which were then degraded. The close proximity of the Gly769 substitution by Ser to the mammalian collagenase cleavage site at Gly775-Leu776 may have produced an unstable domain that was highly susceptible to proteolysis. The type I and III collagens that replaced type II collagen were unable to maintain the normal structure of the hyaline cartilage but did support chondrocyte maturation, evidenced by the expression of type X collagen in the hypertrophic zone of the growth plate cartilage.

  2. Tyrosine Hydroxylase Expression in Type II Cochlear Afferents in Mice.

    PubMed

    Vyas, Pankhuri; Wu, Jingjing Sherry; Zimmerman, Amanda; Fuchs, Paul; Glowatzki, Elisabeth

    2017-02-01

    Acoustic information propagates from the ear to the brain via spiral ganglion neurons that innervate hair cells in the cochlea. These afferents include unmyelinated type II fibers that constitute 5 % of the total, the majority being myelinated type I neurons. Lack of specific genetic markers of type II afferents in the cochlea has been a roadblock in studying their functional role. Unexpectedly, type II afferents were visualized by reporter proteins induced by tyrosine hydroxylase (TH)-driven Cre recombinase. The present study was designed to determine whether TH-driven Cre recombinase (TH-2A-CreER) provides a selective and reliable tool for identification and genetic manipulation of type II rather than type I cochlear afferents. The "TH-2A-CreER neurons" radiated from the spiral lamina, crossed the tunnel of Corti, turned towards the base of the cochlea, and traveled beneath the rows of outer hair cells. Neither the processes nor the somata of TH-2A-CreER neurons were labeled by antibodies that specifically labeled type I afferents and medial efferents. TH-2A-CreER-positive processes partially co-labeled with antibodies to peripherin, a known marker of type II afferents. Individual TH-2A-CreER neurons gave off short branches contacting 7-25 outer hair cells (OHCs). Only a fraction of TH-2A-CreER boutons were associated with CtBP2-immunopositive ribbons. These results show that TH-2A-CreER provides a selective marker for type II versus type I afferents and can be used to describe the morphology and arborization pattern of type II cochlear afferents in the mouse cochlea.

  3. Radiation-Induced Bystander Effects in A549 Cells Exposed to 6 MV X-rays.

    PubMed

    Yang, Shuning; Xu, Jing; Shao, Weixian; Geng, Chong; Li, Jia; Guo, Feng; Miao, Hui; Shen, Wenbin; Ye, Tao; Liu, Yazhou; Xu, Haiting; Zhang, Xuguang

    2015-07-01

    The aim of the study is to explore the bystander effects in A549 cells that have been exposed to 6MV X-ray. Control group, irradiated group, irradiated conditioned medium (ICM)-received group, and fresh medium group were designed in this study. A549 cells in the logarithmic growth phase were irradiated with 6MV X-ray at 0, 0.5, 1, 1.5, and 2. In ICM-received group, post-irradiation A549 cells were cultured for 3 h and were transferred into non-irradiated A549 cells for further cultivation. Clone forming test was applied to detect the survival fraction of cells. Annexin V-FITC/PI double-staining assay was used to detect the apoptosis of A549 cells 24, 48, 72, and 96 h after 2-Gy 6MV X-ray irradiation, and the curves of apoptosis were drawn. The changes in the cell cycles 4, 48, 72, and 96 h after 2-Gy 6MV X-ray irradiation were detected using PI staining flow cytometry. With the increase of irradiation dose, the survival fraction of A549 cells after the application of 0.5 Gy irradiation was decreasing continuously. In comparison to the control group, the apoptosis rate of the ICM-received group was increased in a time-dependent pattern, with the highest apoptosis rate observed at 72 h (p < 0.05). Cell count in G2/M stages was obviously increased compared with that of the control group (p < 0.05), with the highest count observed at 72 h, after which G2/M stage arrest was diminished. ICM can cause apparent A549 cell damage, indicating that 6MV X-ray irradiation can induce bystander effect on A549 cells, which reaches a peak at 72 h.

  4. Trichomonas vaginalis induces cytopathic effect on human lung alveolar basal carcinoma epithelial cell line A549.

    PubMed

    Salvador-Membreve, Daile Meek C; Jacinto, Sonia D; Rivera, Windell L

    2014-12-01

    Trichomonas vaginalis, the causative agent of trichomoniasis is generally known to inhabit the genitourinary tract. However, several case reports with supporting molecular and immunological identifications have documented its occurrence in the respiratory tract of neonates and adults. In addition, the reports have documented that its occurrence is associated with respiratory failures. The medical significance or consequence of this association is unclear. Thus, to establish the possible outcome from the interaction of T. vaginalis with lung cells, the cytopathic effects of the parasites were evaluated using monolayer cultures of the human lung alveolar basal carcinoma epithelial cell line A549. The possible effect of association of T. vaginalis with A549 epithelial cells was analyzed using phase-contrast, scanning electron microscopy and fluorescence microscopy. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), crystal-violet and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling) assays were conducted for cytotoxicity testing. The results demonstrate that T. vaginalis: (1) adheres to A549 epithelial cells, suggesting a density-dependent parasite-cell association; (2) adherence on A549 is through flagella, membrane and axostyle; (3) causes cell detachment and cytotoxicity (50-72.4%) to A549 and this effect is a function of parasite density; and (4) induces apoptosis in A549 about 20% after 6 h of incubation. These observations indicate that T. vaginalis causes cytopathic effects on A549 cell. To date, this is the first report showing a possible interaction of T. vaginalis with the lung cells using A549 monolayer cultures. Further studies are recommended to completely elucidate this association.

  5. Rab27A regulates exosome secretion from lung adenocarcinoma cells A549: involvement of EPI64.

    PubMed

    Li, Wenhai; Hu, Yunsheng; Jiang, Tao; Han, Yong; Han, Guoliang; Chen, Jiakuan; Li, Xiaofei

    2014-11-01

    Exosomes are small membrane vesicles secreted into the extracellular compartment by exocytosis. The unique composition of exosomes can be transported to other cells which allow cells to exert biological functions at distant sites. However, in lung cancer, the regulation of exosome secretion was poorly understood. In this study, we employed human lung adenocarcinoma A549 cells to determine the exosome secretion and involved regulation mechanism. We found that Rab27A was expressed in A549 cells and the reduction of Rab27A by Rab27A-specific shRNA could significantly decrease the secretion of exosome by A549 cells. EPI64, a candidate GAP that is specific for Rab27, was also detected in A549 cells. By pull-down assay, we found that EPI64 participated in the exosome secretion of A549 cells by acting as a specific GAP for Rab27A, not Rab27B. Overexpression of EPI64 enhanced exosome secretion. Taken together, in A549 cells, EPI64 could regulate the exosome secretion by functioning as a GAP specific for Rab27A.

  6. Achondrogenesis type II (Langer-Saldino)--a case report.

    PubMed

    Swar, M O; Srikrishna, B V

    1995-09-01

    Achondrogenesis is a lethal form of congenital chondrodystophy characterised by extreme micromelia. Definitive clinical and radiographic criteria have been established to differentiate Type II Achondrogenesis (Langer-Saldino) from type I Achondrogenesis (Parenti-Fraccaro). The mode of inheritance is autosomal recessive for both types. We are presenting a case of Type II Achondrogenesis, a still born male to consanguinous parents. The clinical features included an enlarged head, protuberant abdomen and short stubby limbs. The mother had earlier delivered two still born males presumably with similar features. Radiographic characteristics of absence of rib fractures and well ossified iliac bones with concave medial margins and absent or deficient ossification of the sacrum, ischiae, and pubic bones differentiated Type II Achondrogenesis from Type I Achondrogenesis.

  7. Achondrogenesis type II with normally developed extremities: a case report.

    PubMed

    Kocakoc, Ercan; Kiris, Adem

    2002-07-01

    We present a case of achondrogenesis type II with normally developed extremities that was confirmed with postmortem ultrasonographic and radiographic examination. The length of the long bones may vary and the diagnosis of achondrogenesis should not be ruled out with normally developed extremities. Intrauterine sonographic examination of the vertebrae is very important and the absence of vertebral body ossification may be the unique finding of achondrogenesis type II. Axial ultrasonographic images and postmortem plain radiographs are useful to clarify the pathology.

  8. Unsupervised Clustering of Type II Supernova Light Curves

    NASA Astrophysics Data System (ADS)

    Rubin, Adam; Gal-Yam, Avishay

    2016-09-01

    As new facilities come online, the astronomical community will be provided with extremely large data sets of well-sampled light curves (LCs) of transients. This motivates systematic studies of the LCs of supernovae (SNe) of all types, including the early rising phase. We performed unsupervised k-means clustering on a sample of 59 R-band SN II LCs and find that the rise to peak plays an important role in classifying LCs. Our sample can be divided into three classes: slowly rising (II-S), fast rise/slow decline (II-FS), and fast rise/fast decline (II-FF). We also identify three outliers based on the algorithm. The II-FF and II-FS classes are disjoint in their decline rates, while the II-S class is intermediate and “bridges the gap.” This may explain recent conflicting results regarding II-P/II-L populations. The II-FS class is also significantly less luminous than the other two classes. Performing clustering on the first two principal component analysis components gives equivalent results to using the full LC morphologies. This indicates that Type II LCs could possibly be reduced to two parameters. We present several important caveats to the technique, and find that the division into these classes is not fully robust. Moreover, these classes have some overlap, and are defined in the R band only. It is currently unclear if they represent distinct physical classes, and more data is needed to study these issues. However, we show that the outliers are actually composed of slowly evolving SN IIb, demonstrating the potential of such methods. The slowly evolving SNe IIb may arise from single massive progenitors.

  9. Acoustic Type-II Weyl Nodes from Stacking Dimerized Chains

    NASA Astrophysics Data System (ADS)

    Yang, Zhaoju; Zhang, Baile

    2016-11-01

    Lorentz-violating type-II Weyl fermions, which were missed in Weyl's prediction of nowadays classified type-I Weyl fermions in quantum field theory, have recently been proposed in condensed matter systems. The semimetals hosting type-II Weyl fermions offer a rare platform for realizing many exotic physical phenomena that are different from type-I Weyl systems. Here we construct the acoustic version of a type-II Weyl Hamiltonian by stacking one-dimensional dimerized chains of acoustic resonators. This acoustic type-II Weyl system exhibits distinct features in a finite density of states and unique transport properties of Fermi-arc-like surface states. In a certain momentum space direction, the velocity of these surface states is determined by the tilting direction of the type-II Weyl nodes rather than the chirality dictated by the Chern number. Our study also provides an approach of constructing acoustic topological phases at different dimensions with the same building blocks.

  10. Immunohistochemical analysis of lattice corneal dystrophies types I and II.

    PubMed Central

    Kivelä, T; Tarkkanen, A; McLean, I; Ghiso, J; Frangione, B; Haltia, M

    1993-01-01

    Corneal buttons from four patients with lattice corneal dystrophy (LD) type I, thought to be an isolated corneal amyloidosis, and from six patients with LD type II, part of systemic familial amyloidosis, Finnish type (FAF; Meretoja's syndrome), were studied by immunohistochemistry to determine the differential distribution in the amyloid deposits of amyloid P component (AP), mutated gelsolin specific for FAF, and native gelsolin. In both types of LD, antibodies to AP labelled lattice lines and a discontinuous layer of amyloid deposits under Bowman's layer. In LD type II, particularly, they also reacted with streak-like amyloid deposits between corneal almellae, especially in the limbal region. While the anti-FAF antiserum strongly labelled all amyloid deposits in LD type II, it failed to react unequivocally with them in LD type I. Both in LD type I and in two control specimens representing granular dystrophy, the monoclonal antibody (MAb) GS-2C4 to gelsolin faintly labelled some deposits, while in LD type II it reacted non-homogeneously with most amyloid deposits. In all specimens, MAb GS-2C4 labelled corneal epithelial cells and occasional stromal keratocytes and endothelial cells. The results suggest that Meretoja's syndrome, a systemic disease, can be diagnosed even retrospectively from corneal buttons subjected to histopathological study. Images PMID:8110676

  11. Origin of wide-band IP type II bursts

    NASA Astrophysics Data System (ADS)

    Pohjolainen, S.; Allawi, H.; Valtonen, E.

    2013-10-01

    Context. Different types of interplanetary (IP) type II bursts have been observed, where the more usual ones show narrow-band and patchy emissions, sometimes with harmonics, and which at intervals may disappear completely from the dynamic spectrum. The more unusual bursts are wide-band and diffuse, show no patches or breaks or harmonic emission, and often have long durations. Type II bursts are thought to be plasma emission, caused by propagating shock waves, but a synchrotron-emitting source has also been proposed as the origin for the wide-band type IIs. Aims: Our aim is to find out where the wide-band IP type II bursts originate and what is their connection to particle acceleration. Methods: We analyzed in detail 25 solar events that produced well-separated, wide-band IP type II bursts in 2001-2011. Their associations to flares, coronal mass ejections (CMEs), and solar energetic particle events (SEPs) were investigated. Results: Of the 25 bursts, 18 were estimated to have heights corresponding to the CME leading fronts, suggesting that they were created by bow shocks ahead of the CMEs. However, seven events were found in which the burst heights were significantly lower and which showed a different type of height-time evolution. Almost all the analyzed wide-band type II bursts were associated with very high-speed CMEs, originating from different parts of the solar hemisphere. In terms of SEP associations, many of the SEP events were weak, had poor connectivity due to the eastern limb source location, or were masked by previous events. Some of the events had precursors in specific energy ranges. These properties and conditions affected the intensity-time profiles and made the injection-time-based associations with the type II bursts difficult to interpret. In several cases where the SEP injection times could be determined, the radio dynamic spectra showed other features (in addition to the wide-band type II bursts) that could be signatures of shock fronts

  12. Perfluorocarbon reduces cell damage from blast injury by inhibiting signal paths of NF-κB, MAPK and Bcl-2/Bax signaling pathway in A549 cells

    PubMed Central

    Li, Huaidong; Li, Chunsun; Yang, Zhen; Li, Yanqin; She, Danyang; Cao, Lu; Wang, Wenjie; Liu, Changlin; Chen, Liangan

    2017-01-01

    Background and objective Blast lung injury is a common type of blast injury and has very high mortality. Therefore, research to identify medical therapies for blast injury is important. Perfluorocarbon (PFC) is used to improve gas exchange in diseased lungs and has anti-inflammatory functions in vitro and in vivo. The aim of this study was to determine whether PFC reduces damage to A549 cells caused by blast injury and to elucidate its possible mechanisms of action. Study design and methods A549 alveolar epithelial cells exposed to blast waves were treated with and without PFC. Morphological changes and apoptosis of A549 cells were recorded. PCR and enzyme-linked immunosorbent assay (ELISA) were used to measure the mRNA or protein levels of IL-1β, IL-6 and TNF-α. Malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity levels were detected. Western blot was used to quantify the expression of NF-κB, Bax, Bcl-2, cleaved caspase-3 and MAPK cell signaling proteins. Results A549 cells exposed to blast wave shrank, with less cell-cell contact. The morphological change of A549 cells exposed to blast waves were alleviated by PFC. PFC significantly inhibited the apoptosis of A549 cells exposed to blast waves. IL-1β, IL-6 and TNF-α cytokine and mRNA expression levels were significantly inhibited by PFC. PFC significantly increased MDA levels and decreased SOD activity levels. Further studies indicated that NF-κB, Bax, caspase-3, phospho-p38, phosphor-ERK and phosphor-JNK proteins were also suppressed by PFC. The quantity of Bcl-2 protein was increased by PFC. Conclusion Our research showed that PFC reduced A549 cell damage caused by blast injury. The potential mechanism may be associated with the following signaling pathways: 1) the signaling pathways of NF-κB and MAPK, which inhibit inflammation and reactive oxygen species (ROS); and 2) the signaling pathways of Bcl-2/Bax and caspase-3, which inhibit apoptosis. PMID:28323898

  13. Alveolar type II cell-fibroblast interactions, synthesis and secretion of surfactant and type I collagen.

    PubMed

    Griffin, M; Bhandari, R; Hamilton, G; Chan, Y C; Powell, J T

    1993-06-01

    During alveolar development and alveolar repair close contacts are established between fibroblasts and lung epithelial cells through gaps in the basement membrane. Using co-culture systems we have investigated whether these close contacts influence synthesis and secretion of the principal surfactant apoprotein (SP-A) by cultured rat lung alveolar type II cells and the synthesis and secretion of type I collagen by fibroblasts. The alveolar type II cells remained cuboidal and grew in colonies on fibroblast feeder layers and on Matrigel-coated cell culture inserts but were progressively more flattened on fixed fibroblast monolayers and plastic. Alveolar type II cells cultured on plastic released almost all their SP-A into the medium by 4 days. Alveolar type II cells cultured on viable fibroblasts or Matrigel-coated inserts above fibroblasts accumulated SP-A in the medium at a constant rate for the first 4 days, and probably recycle SP-A by endocytosis. The amount of mRNA for SP-A was very low after 4 days of culture of alveolar type II cells on plastic, Matrigel-coated inserts or fixed fibroblast monolayers: relatively, the amount of mRNA for SP-A was increased 4-fold after culture of alveolar type II cells on viable fibroblasts. Co-culture of alveolar type II cells with confluent human dermal fibroblasts stimulated by 2- to 3-fold the secretion of collagen type I into the culture medium, even after the fibroblasts' growth had been arrested with mitomycin C. Collagen secretion, by fibroblasts, also was stimulated 2-fold by conditioned medium from alveolar type II cells cultured on Matrigel. The amount of mRNA for type I collagen increased only modestly when fibroblasts were cultured in this conditioned medium. This stimulation of type I collagen secretion diminished as the conditioned medium was diluted out, but at high dilutions further stimulation occurred, indicating that a factor that inhibited collagen secretion also was being diluted out. The conditioned medium

  14. A sample of Type II-L supernovae

    NASA Astrophysics Data System (ADS)

    Faran, T.; Poznanski, D.; Filippenko, A. V.; Chornock, R.; Foley, R. J.; Ganeshalingam, M.; Leonard, D. C.; Li, W.; Modjaz, M.; Serduke, F. J. D.; Silverman, J. M.

    2014-11-01

    What are Type II-Linear supernovae (SNe II-L)? This class, which has been ill defined for decades, now receives significant attention - both theoretically, in order to understand what happens to stars in the ˜15-25 M⊙ range, and observationally, with two independent studies suggesting that they cannot be cleanly separated photometrically from the regular hydrogen-rich SNe II-P characterized by a marked plateau in their light curve. Here, we analyse the multiband light curves and extensive spectroscopic coverage of a sample of 35 SNe II and find that 11 of them could be SNe II-L. The spectra of these SNe are hydrogen deficient, typically have shallow Hα absorption, may show indirect signs of helium via strong O I λ7774 absorption, and have faster line velocities consistent with a thin hydrogen shell. The light curves can be mostly differentiated from those of the regular, hydrogen-rich SNe II-P by their steeper decline rates and higher luminosity, and we propose to define them based on their decline in the V band: SNe II-L decline by more than 0.5 mag from peak brightness by day 50 after explosion. Using our sample we provide template light curves for SNe II-L and II-P in four photometric bands.

  15. Alpha-tomatine inactivates PI3K/Akt and ERK signaling pathways in human lung adenocarcinoma A549 cells: effect on metastasis.

    PubMed

    Shih, Yuan-Wei; Shieh, Jiunn-Min; Wu, Pei-Fen; Lee, Yi-Chieh; Chen, Yi-Zhi; Chiang, Tai-An

    2009-08-01

    This study first investigates the anti-metastatic effect of alpha-tomatine in the human lung adenocarcinoma cell line: A549. In this study, we first noted alpha-tomatine inhibited A549 cells invasion and migration by wound-healing assay and Boyden chamber assay. The data also showed alpha-tomatine could inhibit phosphorylation of Akt and extracellular signal-regulated kinase 1 and 2 (ERK1/2), which is involved in the up-regulating matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) or urokinase-type plasminogen activator (u-PA), whereas it did not affect phosphorylation of c-Jun N-terminal kinase (JNK) and p38. Next, alpha-tomatine significantly decreased the nuclear levels of nuclear factor kappa B (NF-kappaB), c-Fos, and c-Jun. Also, treating A549 cells with alpha-tomatine also leads to a dose-dependent inhibition on the binding abilities of NF-kappaB and activator protein-1 (AP-1). Further, the treatment of inhibitors specific for PI3K (Wortmannin) or ERK (U0126) to A549 cells could cause reduced activities of MMP-2, MMP-9, and u-PA. These results showed alpha-tomatine could inhibit the metastatic ability of A549 cells by reducing MMP-2, MMP-9, and u-PA activities through suppressing phosphoinositide 3-kinase/Akt (PI3K/Akt) or ERK1/2 signaling pathway and inhibition NF-kappaB or AP-1 binding activities. These findings proved alpha-tomatine might be an anti-metastatic agent against human lung adenocarcinoma.

  16. Superinfection exclusion is absent during acute Junin virus infection of Vero and A549 cells

    PubMed Central

    Gaudin, Raphaël; Kirchhausen, Tomas

    2015-01-01

    Many viruses have evolved strategies of so-called “superinfection exclusion” to prevent re-infection of a cell that the same virus has already infected. Although Old World arenavirus infection results in down-regulation of its viral receptor and thus superinfection exclusion, whether New World arenaviruses have evolved such a mechanism remains unclear. Here we show that acute infection by the New World Junin virus (JUNV) failed to down-regulate the transferrin receptor and did not induce superinfection exclusion. We observed that Vero cells infected by a first round of JUNV (Candid1 strain) preserve an ability to internalize new incoming JUNV particles that is comparable to that of non-infected cells. Moreover, we developed a dual infection assay with the wild-type Candid1 JUNV and a recombinant JUNV-GFP virus to discriminate between first and second infections at the transcriptional and translational levels. We found that Vero and A549 cells already infected by JUNV were fully competent to transcribe viral RNA from a second round of infection. Furthermore, flow cytometry analysis of viral protein expression indicated that viral translation was normal, regardless of whether cells were previously infected or not. We conclude that in acutely infected cells, Junin virus lacks a superinfection exclusion mechanism. PMID:26549784

  17. Superinfection exclusion is absent during acute Junin virus infection of Vero and A549 cells.

    PubMed

    Gaudin, Raphaël; Kirchhausen, Tomas

    2015-11-09

    Many viruses have evolved strategies of so-called "superinfection exclusion" to prevent re-infection of a cell that the same virus has already infected. Although Old World arenavirus infection results in down-regulation of its viral receptor and thus superinfection exclusion, whether New World arenaviruses have evolved such a mechanism remains unclear. Here we show that acute infection by the New World Junin virus (JUNV) failed to down-regulate the transferrin receptor and did not induce superinfection exclusion. We observed that Vero cells infected by a first round of JUNV (Candid1 strain) preserve an ability to internalize new incoming JUNV particles that is comparable to that of non-infected cells. Moreover, we developed a dual infection assay with the wild-type Candid1 JUNV and a recombinant JUNV-GFP virus to discriminate between first and second infections at the transcriptional and translational levels. We found that Vero and A549 cells already infected by JUNV were fully competent to transcribe viral RNA from a second round of infection. Furthermore, flow cytometry analysis of viral protein expression indicated that viral translation was normal, regardless of whether cells were previously infected or not. We conclude that in acutely infected cells, Junin virus lacks a superinfection exclusion mechanism.

  18. Depression among patients with type-II diabetes mellitus.

    PubMed

    Khan, Mohammad Akmal; Sultan, Sayed Mohammad; Nazli, Rubina; Akhtar, Tasleem; Khan, Mudasar Ahmad; Sher, Nabila; Aslam, Hina

    2014-10-01

    This study aimed to determine the frequency of depression among patients with type-II diabetes mellitus in Peshawar at Khyber Teaching Hospital, Peshawar, from March to September 2010. Depression was assessed by using Beck Depressive Inventory-II (BDI-II). Out of 140 patients with type-II diabetes, 85 (61%) were women and 55 (39%) were men. Mean age was 45±7.45 years. Eighty four (60%) patients presented with severe depression. Depression was higher in females than males and widows. Depression was high in diabetic patients, especially in females and widows. It is of essence that psychiatric attention may be necessary to be incorporated in diabetes care both for prevention and treatment.

  19. Radix Tetrastigma hemsleyani flavone inhibits proliferation, migration, and invasion of human lung carcinoma A549 cells

    PubMed Central

    Zhong, Liangrui; Zheng, Junxian; Sun, Qianqian; Wei, Kemin; Hu, Yijuan

    2016-01-01

    Radix Tetrastigma hemsleyani flavone (RTHF) is widely used as a traditional herb and has detoxification and anti-inflammatory effects. In this study, we investigated the potential effects of RTHF on the growth and metastasis of human lung adenocarcinoma A549 cells and evaluated its mechanisms. A549 cells were treated with RTHF at various concentrations for different periods. In vitro Cell Counting Kit-8 assay and colony formation methods showed that RTHF had dose- and time-dependent antiproliferation effects on A549 cells. A cell adhesion assay showed that RTHF decreased A549 cell adhesion in a dose-dependent manner. Cell invasion and migration were investigated using the Transwell assay and observed using an inverted microscope; the results showed that cell metastasis was significantly lower in the treatment group than that in the control group (P<0.01). Expression of metastasis-related matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) was detected by real-time polymerase chain reaction and Western blotting. The results showed that the expression of MMP-2, MMP-9, and TIMP-1 decreased, while that of TIMP-2 increased significantly in the RTHF group when compared with the results of the control group. These results show that RTHF exhibits antigrowth and antimetastasis activity in lung cancer A549 cells by decreasing the expression of MMP-2/-9 and TIMP-1 and increasing that of TIMP-2. PMID:26893573

  20. Type II supernovae as probes of environment metallicity: observations of host H II regions

    NASA Astrophysics Data System (ADS)

    Anderson, J. P.; Gutiérrez, C. P.; Dessart, L.; Hamuy, M.; Galbany, L.; Morrell, N. I.; Stritzinger, M. D.; Phillips, M. M.; Folatelli, G.; Boffin, H. M. J.; de Jaeger, T.; Kuncarayakti, H.; Prieto, J. L.

    2016-05-01

    Context. Spectral modelling of type II supernova atmospheres indicates a clear dependence of metal line strengths on progenitor metallicity. This dependence motivates further work to evaluate the accuracy with which these supernovae can be used as environment metallicity indicators. Aims: To assess this accuracy we present a sample of type II supernova host H ii-region spectroscopy, from which environment oxygen abundances have been derived. These environment abundances are compared to the observed strength of metal lines in supernova spectra. Methods: Combining our sample with measurements from the literature, we present oxygen abundances of 119 host H ii regions by extracting emission line fluxes and using abundance diagnostics. These abundances are then compared to equivalent widths of Fe ii 5018 Å at various time and colour epochs. Results: Our distribution of inferred type II supernova host H ii-region abundances has a range of ~0.6 dex. We confirm the dearth of type II supernovae exploding at metallicities lower than those found (on average) in the Large Magellanic Cloud. The equivalent width of Fe ii 5018 Å at 50 days post-explosion shows a statistically significant correlation with host H ii-region oxygen abundance. The strength of this correlation increases if one excludes abundance measurements derived far from supernova explosion sites. The correlation significance also increases if we only analyse a "gold" IIP sample, and if a colour epoch is used in place of time. In addition, no evidence is found of a correlation between progenitor metallicity and supernova light-curve or spectral properties - except for that stated above with respect to Fe ii 5018 Å equivalent widths - suggesting progenitor metallicity is not a driving factor in producing the diversity that is observed in our sample. Conclusions: This study provides observational evidence of the usefulness of type II supernovae as metallicity indicators. We finish with a discussion of the

  1. Comparison of type I and type II bovine viral diarrhea virus infection in swine.

    PubMed Central

    Walz, P H; Baker, J C; Mullaney, T P; Kaneene, J B; Maes, R K

    1999-01-01

    Some isolates of type II bovine viral diarrhea virus (BVDV) are capable of causing severe clinical disease in cattle. Bovine viral diarrhea virus infection has been reported in pigs, but the ability of these more virulent isolates of type II BVDV to induce severe clinical disease in pigs is unknown. It was our objective to compare clinical, virologic, and pathologic findings between type I and type II BVDV infection in pigs. Noninfected control and BVDV-infected 2-month-old pigs were used. A noncytopathic type I and a noncytopathic type II BVDV isolate were chosen for evaluation in feeder age swine based upon preliminary in vitro and in vivo experiments. A dose titration study was performed using 4 groups of 4 pigs for each viral isolate. The groups were inoculated intranasally with either sham (control), 10(3), 10(5), or 10(7) TCID50 of virus. The pigs were examined daily and clinical findings were recorded. Antemortem and postmortem samples were collected for virus isolation. Neither the type I nor type II BVDV isolates resulted in clinical signs of disease in pigs. Bovine viral diarrhea virus was isolated from antemortem and postmortem samples from groups of pigs receiving the 10(5) and the 10(7) TCID50 dose of the type I BVDV isolate. In contrast, BVDV was only isolated from postmortem samples in the group of pigs receiving the 10(7) TCID50 dose of the type II BVDV isolate. Type I BVDV was able to establish infection in pigs at lower doses by intranasal instillation than type II BVDV. Infection of pigs with a type II isolate of BVDV known to cause severe disease in calves did not result in clinically apparent disease in pigs. PMID:10369569

  2. Asymptomatic type II hyperprolinaemia associated with hyperglycinaemia in three sibs.

    PubMed Central

    Pavone, L; Mollica, F; Levy, H L

    1975-01-01

    Three clinically normal sibs were discovered to have type II hyperprolinaemia in a routine serum amino acid screening programme in Sicily. In addition to the basic biochemical features of type II hyperprolinaemia, all 3 children had marked hyperglycinaemia, whereas their parents had both normal blood proline and glycine concentrations. Clinical normality in individuals with hyperprolinaemia may suggest that these two metabolic disorders (types I and II) are benign entities. Furthermore, the absence of clinical abnormality in these sibs, despite the presence of marked hyperprolinaemia and hyperglycinaemia, may suggest that neither of these findings alone causes brain damage. The hyperglycinaemia in these sibs is unexplained and is an unusual if not unique finding in association with hyperprolinaemia. PMID:1200680

  3. Realizing type-II Weyl points in an optical lattice

    NASA Astrophysics Data System (ADS)

    Shastri, Kunal; Yang, Zhaoju; Zhang, Baile

    2017-01-01

    The recent discovery of the Lorentz symmetry-violating "type-II" Weyl semimetal phase has renewed interest in the study of Weyl physics in condensed-matter systems. However, tuning the exceptional properties of this novel state has remained a challenge. Optical lattices, created using standing laser beams, provide a convenient platform to tune tunneling parameters continuously in time. In this paper, we propose a generalized two level system exhibiting type-II Weyl points that can be realized using ultracold atoms in an optical lattice. The system is engineered using a three-dimensional lattice with complex π phase tunneling amplitudes. Various unique properties of the type-II Weyl semimetal such as open Fermi surface, anomalous chirality, and topological Fermi arcs can be probed using the proposed optical lattice scheme.

  4. A TYPE II RADIO BURST WITHOUT A CORONAL MASS EJECTION

    SciTech Connect

    Su, W.; Cheng, X.; Ding, M. D.; Chen, P. F.; Sun, J. Q. E-mail: dmd@nju.edu.cn

    2015-05-10

    Type II radio bursts are thought to be a signature of coronal shocks. In this paper, we analyze a short-lived type II burst that started at 07:40 UT on 2011 February 28. By carefully checking white-light images, we find that the type II radio burst is not accompanied by a coronal mass ejection, only by a C2.4 class flare and narrow jet. However, in the EUV images provided by the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory, we find a wave-like structure that propagated at a speed of ∼600 km s{sup −1} during the burst. The relationship between the type II radio burst and the wave-like structure is, in particular, explored. For this purpose, we first derive the density distribution under the wave by the differential emission measure method, which is used to restrict the empirical density model. We then use the restricted density model to invert the speed of the shock that produces the observed frequency drift rate in the dynamic spectrum. The inverted shock speed is similar to the speed of the wave-like structure. This implies that the wave-like structure is most likely a coronal shock that produces the type II radio burst. We also examine the evolution of the magnetic field in the flare-associated active region and find continuous flux emergence and cancellation taking place near the flare site. Based on these facts, we propose a new mechanism for the formation of the type II radio burst, i.e., the expansion of the strongly inclined magnetic loops after reconnecting with a nearby emerging flux acts as a piston to generate the shock wave.

  5. Streptococcus pneumoniae ClpL Modulates Adherence to A549 Human Lung Cells through Rap1/Rac1 Activation

    PubMed Central

    Nguyen, Cuong Thach; Le, Nhat-Tu; Tran, Thao Dang-Hien; Kim, Eun-Hye; Park, Sang-Sang; Luong, Truc Thanh; Chung, Kyung-Tae; Pyo, Suhkneung

    2014-01-01

    Caseinolytic protease L (ClpL) is a member of the HSP100/Clp chaperone family, which is found mainly in Gram-positive bacteria. ClpL is highly expressed during infection for refolding of stress-induced denatured proteins, some of which are important for adherence. However, the role of ClpL in modulating pneumococcal virulence is poorly understood. Here, we show that ClpL impairs pneumococcal adherence to A549 lung cells by inducing and activating Rap1 and Rac1, thus increasing phosphorylation of cofilin (inactive form). Moreover, infection with a clpL mutant (ΔclpL) causes a greater degree of filopodium formation than D39 wild-type (WT) infection. Inhibition of Rap1 and Rac1 impairs filopodium formation and pneumococcal adherence. Therefore, ClpL can reduce pneumococcal adherence to A549 cells, likely via modulation of Rap1- and Rac1-mediated filopodium formation. These results demonstrate a potential role for ClpL in pneumococcal resistance to host cell adherence during infection. This study provides insight into further understanding the interactions between hosts and pathogens. PMID:24980975

  6. Oleifolioside B-mediated autophagy promotes apoptosis in A549 human non-small cell lung cancer cells.

    PubMed

    Jin, Cheng-Yun; Yu, Hai Yang; Park, Cheol; Han, Min Ho; Hong, Su Hyun; Kim, Kyoung-Sook; Lee, Young-Choon; Chang, Young-Chae; Cheong, Jaehun; Moon, Sung-Kwon; Kim, Gi-Young; Moon, Hyung-In; Kim, Wun-Jae; Lee, Jai-Heon; Choi, Yung Hyun

    2013-12-01

    The biochemical mechanisms of cell death by oleifolioside B (OB), a cycloartane-type triterpene glycoside isolated from Dendropanax morbifera Leveille, were investigated in A549 human lung carcinoma cells. Our data indicated that exposure to OB led to caspase activation and typical features of apoptosis; however, apoptotic cell death was not prevented by z-VAD-fmk, a pan-caspase inhibitor, demonstrating that OB-induced apoptosis was independent of caspase activation. Subsequently, we found that OB increased autophagy, as indicated by an increase in monodansylcadaverine fluorescent dye-labeled autophagosome formation and in the levels of the autophagic form of microtubule-associated protein 1 light chain 3 and Atg3, an autophagy-specific gene, which is associated with inhibiting phospho-nuclear factor erythroid 2-related factor 2 (Nrf2) expression. However, pretreatment with bafilomycin A1, an autophagy inhibitor, attenuated OB-induced apoptosis and dephosphorylation of Nrf2. The data suggest that OB-induced autophagy functions as a death mechanism in A549 cells and OB has potential as a novel anticancer agent capable of targeting apoptotic and autophagic cell death and the Nrf2 signaling pathway.

  7. Xylitol induces cell death in lung cancer A549 cells by autophagy.

    PubMed

    Park, Eunjoo; Park, Mi Hee; Na, Hee Sam; Chung, Jin

    2015-05-01

    Xylitol is a widely used anti-caries agent that has anti-inflammatory effects. We have evaluated the potential of xylitol in cancer treatment. It's effects on cell proliferation and cytotoxicity were measured by MTT assay and LDH assay. Cell morphology and autophagy were examined by immunostaining and immunoblotting. Xylitol inhibited cell proliferation in a dose-dependent manner in these cancer cells: A549, Caki, NCI-H23, HCT-15, HL-60, K562, and SK MEL-2. The IC50 of xylitol in human gingival fibroblast cells was higher than in cancer cells, indicating that it is more specific for cancer cells. Moreover, xylitol induced autophagy in A549 cells that was inhibited by 3-methyladenine, an autophagy inhibitor. These results indicate that xylitol has potential in therapy against lung cancer by inhibiting cell proliferation and inducing autophagy of A549 cells.

  8. Vortex liquid crystals in anisotropic type II superconductors.

    PubMed

    Carlson, E W; Castro Neto, A H; Campbell, D K

    2003-02-28

    In an isotropic type II superconductor in a moderate magnetic field, the transition to the normal state occurs by vortex lattice melting. In certain anisotropic cases, the vortices acquire elongated cross sections and interactions. Systems of anisotropic, interacting constituents generally exhibit liquid crystalline phases. We examine the possibility of a two step melting in homogeneous type II superconductors with anisotropic superfluid stiffness from a vortex lattice into first a vortex smectic and then a vortex nematic at high temperature and magnetic field. We find that fluctuations of the ordered phase favor an instability to an intermediate smectic-A in the absence of intrinsic pinning.

  9. Achondrogenesis type II (Langer-Saldino achondrogenesis): a case report.

    PubMed

    Lee, H S; Doh, J W; Kim, C J; Chi, J G

    2000-10-01

    Achondrogenesis is a lethal form of congenital chondrodystrophy characterized by extreme micromelia. We describe a case of achondrogenesis type II (Langer-Saldino achondrogenesis) detected by prenatal ultrasonography at 20-week gestation. A dwarfed fetus with large head, short neck and chest, prominent abdomen and short limbs was terminated transvaginally. Radiologic and histopathologic examination revealed features of mild form of achondrogenesis type II. Although the case had no known risk factor and the phenotypic abnormality was mild, modern development in prenatal screening made the early detection possible.

  10. Clinical and morphological features of Waardenburg syndrome type II.

    PubMed

    Mullaney, P B; Parsons, M A; Weatherhead, R G; Karcioglu, Z A

    1998-01-01

    Evaluation of 4-month-old girl who presented with congenital cataracts revealed heterochromia iridis, fundus hypopigmentation, residual white forelock and sensory neural hearing loss--findings consistent with Waardenburg syndrome type II. Bilateral peripheral iridectomies performed at lensectomy provided tissue for evaluation. Light microscopy revealed fewer melanocytes in the blue iris than in the brown. Electron microscopic examination showed a significant (p = 0.0001) reduction in melanosome size in the blue iris, and the nerve endings contained fewer vesicles. A defect in neural crest cell migration and melanin synthesis may be responsible for the heterochromia iridis seen in Waardenburg syndrome type II.

  11. Induction of p53-independent growth inhibition in lung carcinoma cell A549 by gypenosides

    PubMed Central

    Liu, Jung-Sen; Chiang, Tzu-Hsuan; Wang, Jinn-Shyan; Lin, Li-Ju; Chao, Wei-Chih; Inbaraj, Baskaran Stephen; Lu, Jyh-Feng; Chen, Bing-Huei

    2015-01-01

    The objectives of this study are to investigate antiproliferative effect and mechanisms of bioactive compounds from Gynostemma pentaphyllum (G. pentaphyllum) on lung carcinoma cell A549. Saponins, carotenoids and chlorophylls were extracted and fractionated by column chromatography, and were subjected to high-performance liquid chromatography-mass spectrometry analyses. The saponin fraction, which consisted mainly of gypenoside (Gyp) XXII and XXIII, rather than the carotenoid and chlorophyll ones, was effective in inhibiting A549 cell growth in a concentration- and a time-dependent manner as evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The estimated half maximal inhibitory concentration (IC50) of Gyp on A549 cells was 30.6 μg/ml. Gyp was further demonstrated to induce an apparent arrest of the A549 cell cycle at both the S phase and the G2/M phase, accompanied by a concentration- and a time-dependent increase in the proportions of both the early and late apoptotic cells. Furthermore, Gyp down-regulated cellular expression of cyclin A and B as well as BCL-2, while up-regulated the expression of BAX, DNA degradation factor 35 KD, poly [ADP-ribose] polymerase 1, p53, p21 and caspase-3. Nevertheless, both the treatment of a p53 inhibitor, pifithrin-α, and the small hairpin RNA-mediated p53 knockdown in the A549 cells did not alter the growth inhibition effect induced by Gyp. As a result, the cell cycle arrest and apoptosis of A549 cells induced by Gyp would most likely proceed through p53-independent pathway(s). PMID:25781909

  12. Towards a Cosmological Hubble Diagram for Type II-PSupernovae

    SciTech Connect

    Nugent, Peter; Sullivan, Mark; Ellis, Richard; Gal-Yam, Avishay; Leonard, Douglas C.; Howell, D. Andrew; Astier, Pierre; Carlberg, RaymondG.; Conley, Alex; Fabbro, Sebastien; Fouchez, Dominique; Neill, James D.; Pain, Reynald; Perrett, Kathy; Pritchet, Chris J; Regnault, Nicolas

    2006-03-20

    We present the first high-redshift Hubble diagram for Type II-P supernovae (SNe II-P) based upon five events at redshift upto z {approx}0.3. This diagram was constructed using photometry from the Canada-France-Hawaii Telescope Supernova Legacy Survey and absorption line spectroscopy from the Keck observatory. The method used to measure distances to these supernovae is based on recent work by Hamuy&Pinto (2002) and exploits a correlation between the absolute brightness of SNeII-P and the expansion velocities derived from the minimum of the Fe II 516.9 nm P-Cygni feature observed during the plateau phases. We present three refinements to this method which significantly improve the practicality of measuring the distances of SNe II-P at cosmologically interesting redshifts. These are an extinction correction measurement based on the V-I colors at day 50, across-correlation measurement for the expansion velocity and the ability to extrapolate such velocities accurately over almost the entire plateau phase. We apply this revised method to our dataset of high-redshift SNe II-P and find that the resulting Hubble diagram has a scatter of only 0.26 magnitudes, thus demonstrating the feasibility of measuring the expansion history, with present facilities, using a method independent of that based upon supernovae of Type Ia.

  13. Increased endocytotic and lysosomal activities in denervated type I and type II muscle fibres.

    PubMed

    Lawoko, G; Tågerud, S; Libelius, R

    1992-01-01

    Previous work has shown that increased endocytotic and lysosomal activities occur in the endplate region of denervated skeletal muscle fibres. This, however, does not engage all fibres of a muscle at a given time after denervation. The present study was carried out in order to determine if both type I (slow) and type II (fast) muscle fibres can react to denervation by increased endocytotic and lysosomal activities. Uptake of horseradish peroxidase as a marker for endocytosis was studied in conjunction with acid phosphatase staining for lysosomal activity in type I and type II fibres of the denervated mouse hemidiaphragm. Fibre typing was performed using a monoclonal antibody against fast skeletal myosin and by adenosine triphosphatase staining. The results show that increased endocytosis and lysosomal activation occur in both type I and type II fibres after denervation.

  14. SHAPING OF ACTION POTENTIALS BY TYPE I AND TYPE II BK CHANNELS

    PubMed Central

    Jaffe, David B.; Wang, Bin; Brenner, Robert

    2011-01-01

    The BK channel is a Ca2+ and voltage-gated conductance responsible for shaping action potential waveforms in many types of neurons. Type II BK channels are differentiated from type I channels by their pharmacology and slow gating kinetics. The β4 accessory subunit confers type II properties on BK α subunits. Empirically derived properties of BK channels, with and without the β4 accessory subunit, were obtained using a heterologous expression system under physiological ionic conditions. These data were then used to study how BK channels alone (type I) and with the accessory β4 subunit (type II) modulate action potential properties in biophysical neuron models. Overall, the models support the hypothesis that it is the slower kinetics provided by the β4 subunit that endows the BK channel with type II properties, which leads to broadening of action potentials and, secondarily, to greater recruitment of SK channels reducing neuronal excitability. Two regions of parameter space distinguished type II and type I effects; one where the range of BK-activating Ca2+ was high (>20 µM) and the other where BK-activating Ca2+ was low (~0.4–1.2 µM). The latter required an elevated BK channel density, possibly beyond a likely physiological range. BK-mediated sharpening of the spike waveform associated with the lack of the β4 subunit was sensitive to the properties of voltage-gated Ca2+ channels due to electrogenic effects on spike duration. We also found that depending on Ca2+ dynamics, type II BK channels may have the ability to contribute to the medium AHP, a property not generally ascribed to BK channels, influencing the frequency-current relationship. Finally, we show how the broadening of action potentials conferred by type II BK channels can also indirectly increase the recruitment of SK-type channels decreasing the excitability of the neuron. PMID:21723921

  15. Glycogen storage disease types I and II: Treatment updates

    PubMed Central

    Kishnani, P. S.; Chen, Y. T.

    2009-01-01

    Summary Prior to 2006 therapy for glycogen storage diseases consisted primarily of dietary interventions, which in the case of glycogen storage disease (GSD) type II (GSD II; Pompe disease) remained essentially palliative. Despite improved survival and growth, long-term complications of GSD type I (GSD I) have not responded to dietary therapy with uncooked cornstarch or continuous gastric feeding. The recognized significant risk of renal disease and liver malignancy in GSD I has prompted efforts towards curative therapy, including organ transplantation, in those deemed at risk. Results of clinical trials in infantile Pompe disease with alglucosidase alfa (Myozyme) showed prolonged survival reversal of cardiomyopathy, and motor gains. This resulted in broad label approval of Myozyme for Pompe disease in 2006. Furthermore, the development of experimental therapies, such as adeno-associated virus (AAV) vector-mediated gene therapy, holds promise for the availability of curative therapy in GSD I and GSD II/Pompe disease in the future. PMID:17308886

  16. Glycogen storage disease types I and II: treatment updates.

    PubMed

    Koeberl, D D; Kishnani, P S; Chen, Y T

    2007-04-01

    Prior to 2006 therapy for glycogen storage diseases consisted primarily of dietary interventions, which in the case of glycogen storage disease (GSD) type II (GSD II; Pompe disease) remained essentially palliative. Despite improved survival and growth, long-term complications of GSD type I (GSD I) have not responded to dietary therapy with uncooked cornstarch or continuous gastric feeding. The recognized significant risk of renal disease and liver malignancy in GSD I has prompted efforts towards curative therapy, including organ transplantation, in those deemed at risk. Results of clinical trials in infantile Pompe disease with alglucosidase alfa (Myozyme) showed prolonged survival reversal of cardiomyopathy, and motor gains. This resulted in broad label approval of Myozyme for Pompe disease in 2006. Furthermore, the development of experimental therapies, such as adeno-associated virus (AAV) vector-mediated gene therapy, holds promise for the availability of curative therapy in GSD I and GSD II/Pompe disease in the future.

  17. Antidepressants in type II versus type I bipolar depression: A randomized discontinuation trial

    PubMed Central

    Vöhringer, Paul A.; Ostacher, Michael J.; El-Mallakh, Rif S.; Holtzman, Niki S.; Thommi, Sairah B.; Whitham, Elizabeth A.; Sullivan, Matthew C.; Baldassano, Claudia F.; Goodwin, Fredrick K.; Baldessarini, Ross J.; Ghaemi, S. Nassir

    2015-01-01

    Background We sought to test the hypothesis that antidepressants (ADs) may show preferential efficacy and safety among type-II over type-I bipolar disorder (BD) patients. Methods DSM-IV BD-I (n=21) and -II patients (n=49) in acute major depressive episodes were treated with ADs plus mood-stabilizers to euthymia sustained for two months, and then randomized openly to continue or discontinue ADs for up to three years. Outcomes were episode-recurrences and changes in standardized symptom-ratings. Results In follow-up averaging 1.64±0.98 years, both subgroups showed improvement in depressive episode frequency with AD continuation, but contrary to the hypothesis, more improvement was seen in type I than in type II bipolar depression (for type II, mean decrease in depressive episodes per year 0.21 ± 0.26 [CI:0.05, 0.37]; for type I: mean decrease 0.35 ± 0.15 [CI:0.30, 0.41]). Type II subjects continued on ADs had slightly more depressive, but fewer manic/hypomanic, episodes than BD-I subjects. No notable differences were seen in either group in time to a recurrence of mood episodes or total time-in-remission. Conclusions The findings do not confirm the hypothesis that long-term AD treatment in BP-II has better outcomes than in BD-I patients, except somewhat lower risk of manic/hypomanic episodes. PMID:26267418

  18. Oro-facial-digital syndrome type II with otolaryngological manifestations.

    PubMed

    Havle, A; Shedge, S; Malashetti, S; Jain, V

    2015-01-01

    We present a case of oro-facial-digital syndrome type II (Mohr's syndrome) which is characterized by malformations of the oral cavity, face and digits. The facial and oral features include tongue nodules, cleft or high-arched palate, missing teeth, broad nose; cleft lip. The digital features include clinodactyly, polydactyly, syndactyly, brachydactyly and duplication of the hallux.

  19. 33 CFR 159.126 - Coliform test: Type II devices.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Coliform test: Type II devices. 159.126 Section 159.126 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION MARINE SANITATION DEVICES Design, Construction, and Testing § 159.126 Coliform...

  20. 33 CFR 159.126 - Coliform test: Type II devices.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Coliform test: Type II devices. 159.126 Section 159.126 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION MARINE SANITATION DEVICES Design, Construction, and Testing § 159.126 Coliform...

  1. 33 CFR 159.126 - Coliform test: Type II devices.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Coliform test: Type II devices. 159.126 Section 159.126 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION MARINE SANITATION DEVICES Design, Construction, and Testing § 159.126 Coliform...

  2. 33 CFR 159.126 - Coliform test: Type II devices.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Coliform test: Type II devices. 159.126 Section 159.126 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION MARINE SANITATION DEVICES Design, Construction, and Testing § 159.126 Coliform...

  3. Subcellular localization of mammalian type II membrane proteins.

    PubMed

    Aturaliya, Rajith N; Fink, J Lynn; Davis, Melissa J; Teasdale, Melvena S; Hanson, Kelly A; Miranda, Kevin C; Forrest, Alistair R R; Grimmond, Sean M; Suzuki, Harukazu; Kanamori, Mutsumi; Kai, Chikatoshi; Kawai, Jun; Carninci, Piero; Hayashizaki, Yoshihide; Teasdale, Rohan D

    2006-05-01

    Application of a computational membrane organization prediction pipeline, MemO, identified putative type II membrane proteins as proteins predicted to encode a single alpha-helical transmembrane domain (TMD) and no signal peptides. MemO was applied to RIKEN's mouse isoform protein set to identify 1436 non-overlapping genomic regions or transcriptional units (TUs), which encode exclusively type II membrane proteins. Proteins with overlapping predicted InterPro and TMDs were reviewed to discard false positive predictions resulting in a dataset comprised of 1831 transcripts in 1408 TUs. This dataset was used to develop a systematic protocol to document subcellular localization of type II membrane proteins. This approach combines mining of published literature to identify subcellular localization data and a high-throughput, polymerase chain reaction (PCR)-based approach to experimentally characterize subcellular localization. These approaches have provided localization data for 244 and 169 proteins. Type II membrane proteins are localized to all major organelle compartments; however, some biases were observed towards the early secretory pathway and punctate structures. Collectively, this study reports the subcellular localization of 26% of the defined dataset. All reported localization data are presented in the LOCATE database (http://www.locate.imb.uq.edu.au).

  4. Free flap transfer for complex regional pain syndrome type II

    PubMed Central

    Matsuda, Ken; Kikuchi, Mamoru; Murase, Tsuyoshi; Hosokawa, Ko; Shibata, Minoru

    2014-01-01

    Abstract A patient with complex regional pain syndrome type II was successfully treated using free anterolateral thigh flap transfer with digital nerve coaptation to the cutaneous nerve of the flap. Release of the scarred tissue and soft tissue coverage with targeted sensory nerve coaptation were useful in relieving severe pain. PMID:27252946

  5. 33 CFR 159.126 - Coliform test: Type II devices.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... follows: During each of the 10 test days, one sample must be taken at the beginning, middle and end of an 8-consecutive hour period with one additional sample taken immediately following the peak capacity... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Coliform test: Type II...

  6. Carbon and Silicate Dust Condensation in Type II Supernovae

    NASA Astrophysics Data System (ADS)

    Deneault, Ethan A.-N.; Morales, B.

    2012-01-01

    We investigate the chemistry of formation and destruction processes of molecules in the expanding and cooling ejecta of Type II Supernovae. In this work, we use a kinetic chemistry network to explore the parameters and conditions of the ejecta which are required for the condensation of graphite and silicon carbide grains.

  7. Type II (noninsulin-dependent) diabetes: new treatment options.

    PubMed

    Bodzin, B J

    1997-01-01

    Type II diabetes (noninsulin-dependent diabetes mellitus [NIDDM]) is a common primary and secondary diagnosis in home care patients. This article describes the pathophysiology of NIDDM, the new drugs that have been released for treatment, and the nursing implications inherent in using these new medications.

  8. Knowledge Is Power: Teaching Children about Type II Diabetes

    ERIC Educational Resources Information Center

    Feild-Berner, Natalie; Balgopal, Meena

    2011-01-01

    World Diabetes Day (November 14) offers a wonderful opportunity to educate elementary children about the power they have to control their health. First lady Michelle Obama has urged Americans to educate themselves about childhood obesity, which is often associated with the onset of type II diabetes (Rabin 2010). The authors developed activities to…

  9. Type II alveolar epithelial cell in vitro culture in aerobiosis.

    PubMed

    Aerts, C; Voisin, C; Wallaert, B

    1988-08-01

    A method of Type II alveolar epithelial cell culture in aerobiosis has been developed. Isolation of Type II cells was performed by digesting guinea-pig lung tissue with crude trypsin and elastase and using discontinuous Percoll density gradients. The Type II cells, as identified by light and electron microscopy, were cultured in aerobiosis for up to six days, in direct contact with the atmosphere in conditions mimicking those present in the lower respiratory tract. Significant activities of cellular superoxide dismutase (SOD), manganese dependent superoxide dismutase (Mn-SOD), catalase and glutathione peroxidase (GSH-Px) were found at the time of isolation. In contrast, cell glutathione content varied widely from one experiment to another. Changes of antioxidant enzymes were evaluated during cell culture in aerobiosis. SOD, Mn-SOD and catalase were significantly decreased after three days but were not significantly different between a three day and six day culture. Antioxidant changes did not influence the cell culture. In marked contrast, decrease in cell glutathione was associated with rapid cell death, whereas good cell survival was obtained at high levels of cell glutathione. Cell culture in aerobiosis will permit a precise evaluation of the effects of gases, particularly oxidant gases, on a primary culture of Type II alveolar epithelial cells.

  10. Type II restriction endonucleases--a historical perspective and more.

    PubMed

    Pingoud, Alfred; Wilson, Geoffrey G; Wende, Wolfgang

    2014-07-01

    This article continues the series of Surveys and Summaries on restriction endonucleases (REases) begun this year in Nucleic Acids Research. Here we discuss 'Type II' REases, the kind used for DNA analysis and cloning. We focus on their biochemistry: what they are, what they do, and how they do it. Type II REases are produced by prokaryotes to combat bacteriophages. With extreme accuracy, each recognizes a particular sequence in double-stranded DNA and cleaves at a fixed position within or nearby. The discoveries of these enzymes in the 1970s, and of the uses to which they could be put, have since impacted every corner of the life sciences. They became the enabling tools of molecular biology, genetics and biotechnology, and made analysis at the most fundamental levels routine. Hundreds of different REases have been discovered and are available commercially. Their genes have been cloned, sequenced and overexpressed. Most have been characterized to some extent, but few have been studied in depth. Here, we describe the original discoveries in this field, and the properties of the first Type II REases investigated. We discuss the mechanisms of sequence recognition and catalysis, and the varied oligomeric modes in which Type II REases act. We describe the surprising heterogeneity revealed by comparisons of their sequences and structures.

  11. Enhanced Replication of Hepatitis E Virus Strain 47832c in an A549-Derived Subclonal Cell Line

    PubMed Central

    Schemmerer, Mathias; Apelt, Silke; Trojnar, Eva; Ulrich, Rainer G.; Wenzel, Jürgen J.; Johne, Reimar

    2016-01-01

    Hepatitis E virus (HEV) is a human pathogen with increasing importance. The lack of efficient cell culture systems hampers systematic studies on its replication cycle, virus neutralization and inactivation. Here, several cell lines were inoculated with the HEV genotype 3c strain 47832c, previously isolated from a chronically infected transplant patient. At 14 days after inoculation the highest HEV genome copy numbers were found in A549 cells, followed by PLC/PRF/5 cells, whereas HepG2/C3A, Huh-7 Lunet BLR and MRC-5 cells only weakly supported virus replication. Inoculation of A549-derived subclone cell lines resulted in most cases in reduced HEV replication. However, the subclone A549/D3 was susceptible to lower virus concentrations and resulted in higher virus yields as compared to parental A549 cells. Transcriptome analysis indicated a downregulation of genes for carcinoembryonic antigen-related cell adhesion molecules (CEACAM) 5 and 6, and an upregulation of the syndecan 2 (SDC2) gene in A549/D3 cells compared to A549 cells. However, treatment of A549/D3 cells or A549 cells with CEACAM- or syndecan 2-specific antisera did not influence HEV replication. The results show that cells supporting more efficient HEV replication can be selected from the A549 cell line. The specific mechanisms responsible for the enhanced replication remain unknown. PMID:27690085

  12. Enhanced expression levels of aquaporin-1 and aquaporin-4 in A549 cells exposed to silicon dioxide.

    PubMed

    Hao, Xiaohui; Wang, Hongli; Liu, Wei; Liu, Shupeng; Peng, Zihe; Sun, Yue; Zhao, Jinyuan; Jiang, Qiujie; Liu, Heliang

    2016-09-01

    Aquaporins (AQPs), water channel proteins in the cell membranes of mammals, have been reported to be important in maintaining the water balance of the respiratory system. However, little is known regarding the role of AQP in occupational pulmonary diseases such as silicosis. The present study investigated the expression of AQP1 and AQP4 in the human A549 alveolar epithelial cell line stimulated by silica (SiO2). A549 cells were cultured and divided into four groups: Control, SiO2‑stimulated, AQP1 inhibitor and AQP4 inhibitor. The cells of the SiO2‑stimulated group were stimulated with SiO2 dispersed suspension (50 mg/ml). The cells of the inhibitor group were pretreated with mercury (II) chloride (HgCl2; a specific channel inhibitor of AQP1) and 2‑(nicotinamide)‑1,3,4‑thiadiazole (TGN‑020; a specific channel inhibitor of AQP4) and stimulated with SiO2. The mRNA expression levels of AQP1 and AQP4 were detected by reverse transcription‑quantitative polymerase chain reaction, and the protein expression levels of AQP1 and AQP4 were detected by western blotting and immunocytochemistry. Compared with the control group, the expression levels of AQP1 and AQP4 mRNA and protein in SiO2‑stimulated groups increased and subsequently decreased (AQP1 peaked at 2 h and AQP4 at 1h; both P<0.001 compared with control group). In the inhibitor group, expression levels were increased compared with controls; however, they were significantly decreased compared with the SiO2‑stimulated group at 2 h (AQP1; P<0.001) and 1 h (AQP4; P<0.001). The expression of AQP1 and AQP4 increased when exposed to SiO2, and this was inhibited by HgCl2 and TGN‑020, suggesting that AQP1 and AQP4 may contribute to A549 cell damage induced by SiO2. AQP1 and AQP4 may thus be involved in the initiation and development of silicosis.

  13. Comparing the host galaxies of type Ia, type II, and type Ibc supernovae

    SciTech Connect

    Shao, X.; Liang, Y. C.; Chen, X. Y.; Zhong, G. H.; Deng, L. C.; Zhang, B.; Shi, W. B.; Zhou, L.; Dennefeld, M.; Hammer, F.; Flores, H. E-mail: ycliang@bao.ac.cn

    2014-08-10

    We compare the host galaxies of 902 supernovae (SNe), including SNe Ia, SNe II, and SNe Ibc, which are selected by cross-matching the Asiago Supernova Catalog with the Sloan Digital Sky Survey (SDSS) Data Release 7. We selected an additional 213 galaxies by requiring the light fraction of spectral observations to be >15%, which could represent well the global properties of the galaxies. Among these 213 galaxies, 135 appear on the Baldwin-Phillips-Terlevich diagram, which allows us to compare the hosts in terms of whether they are star-forming (SF) galaxies, active galactic nuclei (AGNs; including composites, LINERs, and Seyfert 2s) or absorption-line galaxies (Absorps; i.e., their related emission lines are weak or non-existent). The diagrams related to the parameters D{sub n}(4000), Hδ{sub A}, stellar masses, star formation rates (SFRs), and specific SFRs for the SNe hosts show that almost all SNe II and most of the SNe Ibc occur in SF galaxies, which have a wide range of stellar masses and low D{sub n}(4000). The SNe Ia hosts as SF galaxies following similar trends. A significant fraction of SNe Ia occurs in AGNs and absorption-line galaxies, which are massive and have high D{sub n}(4000). The stellar population analysis from spectral synthesis fitting shows that the hosts of SNe II have a younger stellar population than hosts of SNe Ia. These results are compared with those of the 689 comparison galaxies where the SDSS fiber captures less than 15% of the total light. These comparison galaxies appear biased toward higher 12+log(O/H) (∼0.1 dex) at a given stellar mass. Therefore, we believe the aperture effect should be kept in mind when the properties of the hosts for different types of SNe are discussed.

  14. A universal characteristic of type II radio bursts

    NASA Astrophysics Data System (ADS)

    Aguilar-Rodriguez, E.; Gopalswamy, N.; MacDowall, R.; Yashiro, S.; Kaiser, M. L.

    2005-12-01

    We present a study on the spectral properties of interplanetary type II radio bursts observed by the Radio and Plasma Wave (WAVES) experiment on board the Wind spacecraft. We investigated the relative bandwidth of the type II radio bursts observed by WAVES from 1997 up to 2003. We obtained three sets of events, based on the frequency domain of occurrence: 109 events in the low-frequency domain (30 KHz to 1000 kHz, detected by the RAD1 receiver), 216 events in the high-frequency domain (1-14 MHz, observed by the RAD2 receiver), and 73 events that spanned both domains (RAD1 and RAD2). Statistical results show that the average bandwidth-to-frequency ratio (BFR) was 0.28 ± 0.15, 0.26 ± 0.16, and 0.32 ± 0.15 for RAD1, RAD2, and RAD1 + RAD2, respectively. We compared our results with those obtained for ISEE-3 type II bursts and found a difference in the average BFR, which seems to be due to a selection effect. The BFR of the WAVES type II bursts is similar to that of metric type II bursts reported in published works. This suggests that the BFR is a universal characteristic, irrespective of the spectral domain. Finally, we also studied the BFR evolution with heliocentric distance using white-light observation of the associated coronal mass ejections. We found that the BFR remains roughly constant in the SOHO/LASCO field of view (i.e., from 2.1 to 32 solar radii), while the bandwidth itself decreases.

  15. Monitoring of TGF-β 1-Induced Human Lung Adenocarcinoma A549 Cells Epithelial-Mesenchymal Transformation Process by Measuring Cell Adhesion Force with a Microfluidic Device.

    PubMed

    Li, Yuan; Gao, AnXiu; Yu, Ling

    2016-01-01

    The epithelial-mesenchymal transition (EMT) is a process in which epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties. It is believed that EMT is associated with initiation and completion of the invasion-metastasis cascade. In this study, an economic approach was developed to fabricate a microfluidic device with less instrumentation requirement for the investigation of EMT by quantifying cell adhesion force. Fluid shear force was precisely controlled by a homemade microfluidic perfusion apparatus and interface. The adhesion capability of the human lung adenocarcinoma cell line A549 on different types of extracellular matrix protein was studied. In addition, effects of transforming growth factor-β (TGF-β) on EMT in A549 cells were investigated by characterizing the adhesion force changes and on-chip fluorescent staining. The results demonstrate that the microfluidic device is a potential tool to characterize the epithelial-mesenchymal transition process by measuring cell adhesion force.

  16. Regulation of different components from Ophiopogon japonicus on autophagy in human lung adenocarcinoma A549Cells through PI3K/Akt/mTOR signaling pathway.

    PubMed

    Chen, Juan; Yuan, Jiarui; Zhou, Liqiang; Zhu, Maomao; Shi, Ziqi; Song, Jie; Xu, Qingyu; Yin, Guowen; Lv, You; Luo, Yi; Jia, Xiaobin; Feng, Liang

    2017-03-01

    Autophagy plays a dual role in the development of cancer, acting as both a tumor suppressor and a cell survival inducer. Ophiopogon japonicus (L.f) Ker-Gawl (OJ), as a traditional Chinese medicine, specially possesses remarkable anti-cancer activity in the clinical. Previously, studies have indicated that flavonoids (FOJ) and steroidal saponins (SSOJ) are the main active substances of OJ. However, the effects of FOJ and SSOJ on autophagy of A549 cells have not been fully elucidated. In this study, we found that the expressions of autophagy-related mediators (LC3-II/LC3-I ratio, Atg-3, Atg-7 and Beclin-1) were increased in A549 cells by the treatment with FOJ (7.9mg crude drug/mL) and SSOJ (12.2mg crude drug/mL). Meanwhile, FOJ or SSOJ could induce the up-regulation of LC3-II at both protein and mRNA levels. Moreover, we observed the cytoplasmic vaculoes which formed double-layered membranes and only some cytoplasmic organelles or myelin figures remained in FOJ or SSOJ-treated A549 cells for 24h by Transmission Electron Microscopy (TEM). Further detection about the PI3K/Akt/mTOR signaling pathway showed that the levels of PI3K, Akt and mTOR were significantly suppressed with the FOJ or SSOJ treatment. The 3-MA (an autophagy inhibitor) and LY294002 (a PI3K inhibitor) further confirmed the underlying mechanism in the FOJ or SSOJ-induced autophagy of A549 cells. Additionally, the pretreatment with FOJ and SSOJ increased the level of p53, whereas decreased the expression of Ki67. These findings suggested that FOJ or SSOJ could activate the autophagy of A549 cells, wherein the mechanism might be associated with their inhibition of PI3K/Akt/mTOR signaling pathway. Thus, FOJ or SSOJ could be a potential autophagy inducer to prevent the process of lung cancer.

  17. Cold stress increases reactive oxygen species formation via TRPA1 activation in A549 cells.

    PubMed

    Sun, Wenwu; Wang, Zhonghua; Cao, Jianping; Cui, Haiyang; Ma, Zhuang

    2016-03-01

    Reactive oxygen species (ROS) are responsible for lung damage during inhalation of cold air. However, the mechanism of the ROS production induced by cold stress in the lung is still unclear. In this work, we measured the changes of ROS and the cytosolic Ca(2+) concentration ([Ca(2+)]c) in A549 cell. We observed that cold stress (from 20 to 5 °C) exposure of A549 cell resulted in an increase of ROS and [Ca(2+)]c, which was completely attenuated by removing Ca(2+) from medium. Further experiments showed that cold-sensing transient receptor potential subfamily member 1 (TRPA1) agonist (allyl isothiocyanate, AITC) increased the production of ROS and the level of [Ca(2+)]c in A549 cell. Moreover, HC-030031, a TRPA1 selective antagonist, significantly inhibited the enhanced ROS and [Ca(2+)]c induced by AITC or cold stimulation, respectively. Taken together, these data demonstrated that TRPA1 activation played an important role in the enhanced production of ROS induced by cold stress in A549 cell.

  18. The role of PRRX1 in the apoptosis of A549 cells induced by cisplatin

    PubMed Central

    Zhu, Hongbin; Sun, Gengyun; Dong, Jiahui; Fei, Liming

    2017-01-01

    Paired related homeobox1 (PRRX1) was a newly identified Epithelial mesenchymal transition (EMT) inducer. It was found that the decreased expression of PRRX1 in breast cancer and liver cancer could enable tumor cells to obtain tumor stem cell characteristics in vitro studies. However, the role of PRRX1 in lung cancer was still unknown. The down-regulated PRRX1 gene in A549 cells was established by slow virus infection in this study. The apoptosis of A549 cells was observed after the treatment of different concentrations of cisplatin and the role of PRRX1 in the apoptosis of A549 cells was explored. MTT results showed that down-regulated PRRX1 gene could resist the inhibitory effect of cisplatin on cell proliferation. The results of flow cytometry assay showed that down-regulated PRRX1 gene could reduce the apoptosis and promote A549 cells to enter G2 phase. Mitochondrial membrane potential detection showed that PRRX1 gene could inhibit the decrease of mitochondrial membrane potential. Western blotting results showed that down-regulated PRRX1 gene could reduce the expression levels of Caspase3, caspase9, Apaf-1 and cytochrome C. In a word, down-regulation of PRRX1 could cause lung cancer cells to produce anti apoptotic ability and resistance to cisplatin, which maybe through caspase3 pathway. PMID:28337269

  19. Edaravone Decreases Paraquat Toxicity in A549 Cells and Lung Isolated Mitochondria

    PubMed Central

    Shokrzadeh, Mohammad; Shaki, Fatemeh; Mohammadi, Ebrahim; Rezagholizadeh, Neda; Ebrahimi, Fatemeh

    2014-01-01

    Edaravone, an antioxidant and radical scavenger, showed protective effects against oxidative stress-like condition. Paraquat (PQ) is toxic herbicide considerable evidence suggests that oxidative stress and mitochondrial dysfunction contribute to PQ toxicity. In this study, protective effect of edaravone against PQ induced toxicity and reactive oxygen species (ROS) generation in A549 cells and lung isolated mitochondria were evaluated. A549 cells and lung isolated mitochondria were divided into control group, PQ group, edaravone group and PQ plus edaravone-pretreated group. Cellular and mitochondrial viability assayed using MTT test and ROS generations in both cellular and mitochondrial fraction were determined by fluorometry using DCFH-DA as indicator. Our results showed that edaravone (5–100 µM) prevented PQ (500 µM) induced cytotoxicity in A549 cells that the best protective effect was observed at concentration of 50 µM of edaravone. In addition, PQ-induced ROS generation in A549 cells significantly inhibited by edaravone. Moreover, PQ decreased mitochondria viability and also increased ROS generation in lung isolated mitochondria that edaravone (25–400 µM) markedly inhibited these toxic effects. In overall, the results of this study suggest that lung mitochondria maintenance is essential for maintaining PQt cytotoxicity and Edaravone is a protective drug against PQ toxicity in-vitro. PMID:25237364

  20. Functional expression of nicotine influx transporter in A549 human alveolar epithelial cells.

    PubMed

    Tega, Yuma; Yuzurihara, Chihiro; Kubo, Yoshiyuki; Akanuma, Shin-ichi; Ehrhardt, Carsten; Hosoya, Ken-ichi

    2016-02-01

    Nicotine is a potent addictive alkaloid, and is rapidly absorbed through the alveoli of the lung. However, the transport mechanism of nicotine at the human alveolar epithelial barrier has not been investigated in great detail. In the present study, the transport mechanism of nicotine across alveolar epithelium was investigated in vitro using A549 cells, a human adenocarcinoma-derived cell line with an alveolar epithelial cell like phenotype. Nicotine uptake by A549 cells exhibited time-, temperature-, and concentration-dependence with a Km of 50.4 μM. These results suggest that a carrier-mediated transport process is involved in nicotine transport in human alveolar epithelial cells. Nicotine uptake by A549 cells was insensitive to change in extracellular pH. Moreover, nicotine uptake by A549 cells could be inhibited by organic cations such as verapamil and pyrilamine, but not typical substrates of organic cation transporters and β2-agonist. These results suggest that a novel, not yet molecularly identified, organic cation transporter plays a role in nicotine transport which is unlikely to interact with β2-agonist transport. This nicotine influx transporter in human alveolar epithelium might have implications for the rapid absorption of nicotine into the systemic circulation.

  1. Evaluation of a549 as a new vaccine cell substrate: digging deeper with massively parallel sequencing.

    PubMed

    Shabram, Paul; Kolman, John L

    2014-01-01

    In the past three decades, the use of tumorigenic cell substrates has been the topic of five Vaccine and Related Biological Products Advisory Committee (VRBPAC) meetings, including a review of the A549 cell line in September 2012. Over that period of time, major technological advances in biotechnology have improved our ability to assess the risk associated with using a tumorigenic cell line. As part of the September 2012 review, we assessed the history of A549 cells and evaluated the probable transforming event based on patterns of mutations to cancer genes. In addition, massively parallel sequencing was used to first screen then augment the characterization of A549 cells by searching for the presence of hidden viral threats using sequencing of the entire cellular transcriptome and comparing sequences to a curated viral sequence database. Based upon the combined results of next-generation sequencing technology along with standard cell characterization as outlined in published regulatory guidances, we believe that A549 cells pose no more risk than any other cell substrate for the manufacture of vaccines.

  2. Changes in the cellular proteins of A549 infected with Hepatitis E virus by proteomics analysis

    PubMed Central

    2014-01-01

    Background Our understanding of Hepatitis E virus (HEV) has changed enormously over the past 30 years, from a waterborne infection causing outbreaks of acute hepatitis in developing countries to an infection of global distribution causing a range of hepatic and extra-hepatic illness. However, the key proteins playing important parts in the virus infection were still unknown. Understanding the changes of cellular proteins in these cells exposed to HEV is helpful for elucidating molecular mechanisms associated with function alterations of HEV-infected susceptible cells. In the present study, a comparative gel-based proteomic analysis was employed to study the changes in cellular proteins of A549 exposed to HEV in vitro to provide novel information for understanding the functional alterations of A549 induced by HEV infection. Result Of 2 585-3 152 protein spots visualized on each gel using silver staining, a total of 31 protein spots were found to be differentially expressed in HEV-infected A549 cells compared with mock-infected A549, including 10 significantly up-regulated protein spots and 21 significantly down-regulated protein spots. Conclusion Our work is the first time regarding the proteomic analysis on the cellular responses to HEV infection. This work is helpful for investigating the molecular basis associated with the interaction between HEV and the host cells although more efforts should be required to discover the mechanisms. PMID:25175408

  3. Gain spectroscopy of a type-II VECSEL chip

    NASA Astrophysics Data System (ADS)

    Lammers, C.; Stein, M.; Berger, C.; Möller, C.; Fuchs, C.; Ruiz Perez, A.; Rahimi-Iman, A.; Hader, J.; Moloney, J. V.; Stolz, W.; Koch, S. W.; Koch, M.

    2016-12-01

    Using optical pump-white light probe spectroscopy, the gain dynamics is investigated for a vertical-external-cavity surface-emitting laser chip, which is based on a type-II heterostructure. The active region of the chip consists of a GaAs/(GaIn)As/Ga(AsSb)/(GaIn)As/GaAs multiple quantum well. For this structure, a fully microscopic theory predicts a modal room temperature gain at a wavelength of 1170 nm, which is confirmed by the experimental spectra. The results show a gain buildup on the type-II chip that is delayed relative to that of a type-I chip. This slower gain dynamics is attributed to a diminished cooling rate arising from the reduced electron-hole scattering.

  4. SPECTRA OF TYPE II CEPHEID CANDIDATES AND RELATED STARS

    SciTech Connect

    Schmidt, E. G.; Rogalla, Danielle; Thacker-Lynn, Lauren E-mail: drogall1@bigred.unl.edu

    2011-02-15

    We present low-resolution spectra for variable stars in the Cepheid period range from the ROTSE-I Demonstration Project and the All Sky Automated Survey, some of which were previously identified as type II Cepheid candidates. We have derived effective temperatures, gravities, and metallicities from the spectra. Based on this, three types of variables were identified: Cepheid strip stars, cool stars that lie along the red subgiant and giant branch, and cool main-sequence stars. Many fewer type II Cepheids were found than expected and most have amplitudes less than 0.4 mag. The cool variables include many likely binaries as well as intrinsic variables. Variation among the main-sequence stars is likely to be mostly due to binarity or stellar activity.

  5. Imaging and characterization of stretch-induced ATP release from alveolar A549 cells.

    PubMed

    Grygorczyk, Ryszard; Furuya, Kishio; Sokabe, Masahiro

    2013-03-01

    Abstract  Mechano-transduction at cellular and tissue levels often involves ATP release and activation of the purinergic signalling cascade. In the lungs, stretch is an important physical stimulus but its impact on ATP release, the underlying release mechanisms and transduction pathways are poorly understood. Here, we investigated the effect of unidirectional stretch on ATP release from human alveolar A549 cells by real-time luciferin-luciferase bioluminescence imaging coupled with simultaneous infrared imaging, to monitor the extent of cell stretch and to identify ATP releasing cells. In subconfluent (<90%) cell cultures, single 1 s stretch (10-40%)-induced transient ATP release from a small fraction (1.5%) of cells that grew in number dose-dependently with increasing extent of stretch. ATP concentration in the proximity (150 μm) of releasing cells often exceeded 10 μm, sufficient for autocrine/paracrine purinoreceptor stimulation of neighbouring cells. ATP release responses were insensitive to the putative ATP channel blockers carbenoxolone and 5-nitro-2-(3-phenylpropyl-amino) benzoic acid, but were inhibited by N-ethylmaleimide and bafilomycin. In confluent cell cultures, the maximal fraction of responding cells dropped to <0.2%, but was enhanced several-fold in the wound/scratch area after it was repopulated by new cells during the healing process. Fluo8 fluorescence experiments revealed two types of stretch-induced intracellular Ca(2+) responses, rapid sustained Ca(2+) elevations in a limited number of cells and delayed secondary responses in neighbouring cells, seen as Ca(2+) waves whose propagation was consistent with extracellular diffusion of released ATP. Our experiments revealed that a single >10% stretch was sufficient to initiate intercellular purinergic signalling in alveolar cells, which may contribute to the regulation of surfactant secretion and wound healing.

  6. Intrafibrillar Mineral May be Absent in Dentinogenesis Imperfecta Type II (DI-II)

    SciTech Connect

    Pople, John A.

    2001-03-29

    High-resolution synchrotron radiation computed tomography (SRCT) and small angle x-ray scattering (SAXS) were performed on normal and dentinogenesis imperfecta type II (DI-II) teeth. Three normal and three DI-II human third molars were used in this study. The normal molars were unerupted and had intact enamel; donors were female and ranged in age from 18-21y. The DI-II specimens, which were also unerupted with intact enamel, came from a single female donor age 20y. SRCT showed that the mineral concentration was 33% lower on average in the DI-II dentin with respect to normal dentin. The SAXS spectra from normal dentin exhibited low-angle diffraction peaks at harmonics of 67.6 nm, consistent with nucleation and growth of the apatite phase within gaps in the collagen fibrils (intrafibrillar mineralization). In contrast, the low-angle peaks were almost nonexistent in the DI-II dentin. Crystallite thickness was independent of location in both DI-II and normal dentin, although the crystallites were significantly thicker in DI-II dentin (6.8 nm (s.d. = 0.5) vs 5.1 nm (s.d. = 0.6)). The shape factor of the crystallites, as determined by SAXS, showed a continuous progression in normal dentin from roughly one-dimensional (needle-like) near the pulp to two-dimensional (plate-like) near the dentin-enamel junction. The crystallites in DI-II dentin, on the other hand, remained needle-like throughout. The above observations are consistent with an absence of intrafibrillar mineral in DI-II dentin.

  7. [Effect of two different acellular lung matrices on α-SMA expression in A549 cells].

    PubMed

    Chen, C; Wang, Z Y; Weng, J; Wang, Z B; Mei, J; Du, X H; Wang, L

    2017-01-24

    Objective: To explore the effect of acellular normal and fibrotic lung matrices on alpha smooth muscle actin (α-SMA) expression in human lung adenocarcinoma cell line A549. Methods: Twenty adult SD rats were randomly divided into normal group and idiopathic pulmonary fibrosis(IPF)group (n=10 each). The pulmonary fibrosis was induced by Bleomycin. Normal and fibrotic decellularized lungs were made, then sections with 500 μm thick were cut by a standard Vibratome. None scaffold was set as control group. A549 cells were seeded dropwise into different slices (normal and fibrotic scaffolds), and cultured for one week in vitro. The expression of α-SMA was measured by immunofluorescence staining and quantitative real time polymerase chain reaction (qRT-PCR). Results: In control group, the expression of α-SMA protein was positive in A549 cells by immunofluorescence staining. However, it expressed weakly both in normal and fibrotic scaffold group, and the fluorescence intensity in fibrotic scaffold group was significant lower than that in normal group (P<0.05). The relative expression amount of α-SMA mRNA in normal and fibrotic scaffold group were (0.70±0.11) and (0.55±0.12), which were significant lower than that of control group (1.28±0.21) (P<0.05). Moreover, the relative expression of α-SMA mRNA in fibrotic scaffold group was decreased compared to that in normal scaffold group (P<0.05). Conclusions: Acellular normal and fibrotic lung scaffold can downregulate the expression of α-SMA in human lung adenocarcinoma cell line A549. It may inhibit the movement of A549 cells in acellular normal and fibrotic lung matrices, especially in acellular fibrotic lung scaffold.

  8. Role of gambogic acid and NaI131 in A549/DDP cells

    PubMed Central

    Huang, Jing; Zhu, Xiaoli; Wang, Huan; Han, Shuhua; Liu, Lu; Xie, Yan; Chen, Daozhen; Zhang, Qiang; Zhang, Li; Hu, Yue

    2017-01-01

    Resistance to platinum in tumor tissue is a considerable barrier against effective lung cancer treatment. Radionuclide therapy is the primary adjuvant treatment, however, the toxic side effects limit its dosage in the clinical setting. Therefore, the present study aimed to determine whether an NaI131 radiosensitizer could help reduce the toxic side effects of radionuclide therapy. In vitro experiments were conducted to determine whether NaI131 can inhibit platinum resistance in A549/DDP cells, which are cisplatin-resistant non-small cell lung cancer cells, and whether gambogic acid (GA) is an effective NaI131 radiosensitizer. Cell proliferation following drug intervention was analyzed using MTT and isobolographic analysis. Apoptosis was assessed by flow cytometry. In addition, the mechanisms of drug intervention were analyzed by measuring the expression of P-glycoprotein (P-gP), B cell lymphoma 2 (Bcl-2), Bcl2-associated X protein (Bax) and P53 using western blot analysis and immunocytochemistry. According to isobolographic analysis, a low concentration of NaI131 combined with GA had a synergistic effect on the inhibition of A549/DDP cell proliferation, which was consistent with an increased rate of apoptosis. Furthermore, the overexpression of Bax, and the downregulation of P-gP, P53 and Bcl-2 observed demonstrated the potential mechanism(s) of NaI131 and GA intervention. NaI131 may induce apoptosis in A549/DDP cells by regulating apoptosis-related proteins. A low concentration combination of NaI131 and GA was able to significantly inhibit A549/DDP cell proliferation and induce cell apoptosis. Thus, the two drugs appear to have a synergistic effect on apoptosis of A549/DDP cells. PMID:28123519

  9. Rapamycin‐induced autophagy sensitizes A549 cells to radiation associated with DNA damage repair inhibition

    PubMed Central

    Li, Yong; Liu, Fen; Wang, Yong; Li, Donghai; Guo, Fei; Xu, Liyao; Zeng, Zhengguo; Zhong, Xiaojun

    2016-01-01

    Abstract Background Autophagy has been reported to increase in cancer cells after radiation. However, it remains unknown whether increased autophagy as a result of radiation affects DNA damage repair and sensitizes cancer cells. In this study, the radiosensitization effect of rapamycin, a mammalian target of rapamycin inhibitor that induces autophagy, on human lung adenocarcinoma A549 cells was investigated. Methods A549 cells were treated with different concentrations of rapamycin. Cell viability was evaluated by methyl‐thiazolyl‐tetrazolium assay. Survival fraction values of A549 cells after radiotherapy were detected by colony formation assay. Autophagosome was observed by a transmission electron microscope. Furthermore, Western blot was employed to examine alterations in autophagy protein LC3 and p62, DNA damage protein γ–H2AX, and DNA damage repair proteins Rad51, Ku70, and Ku80. Rad51, Ku70, and Ku80 messenger ribonucleic acid (mRNA) expression levels were examined by real‐time polymerase chain reaction. Results Rapamycin suppressed A549 cell proliferation in dose and time‐dependent manners. An inhibitory concentration (IC) 10 dose of rapamycin could induce autophagy in A549 cells. Rapamycin combined with radiation significantly decreased the colony forming ability of cells, compared with rapamycin or radiation alone. Rapamycin and radiation combined increased γ–H2AX expression levels and decreased Rad51 and Ku80 expression levels, compared with single regimens. However, rapamycin treatment did not induce any change in Rad51, Ku70, and Ku80 mRNA levels, regardless of radiation. Conclusions These findings indicate that increasing autophagy sensitizes lung cancer cells to radiation. PMID:27385978

  10. Coronal magnetic fields from multiple type II bursts

    NASA Astrophysics Data System (ADS)

    Honnappa, Vijayakumar; Raveesha, K. H.; Subramanian, K. R.

    Coronal magnetic fields from multiple type II bursts Vijayakumar H Doddamani1*, Raveesha K H2 and Subramanian3 1Bangalore University, Bangalore, Karnataka state, India 2CMR Institute of Technology, Bangalore, Karnataka state, India 3 Retd, Indian Institute of Astrophysics, Bangalore, Karnataka state, India Abstract Magnetic fields play an important role in the astrophysical processes occurring in solar corona. In the solar atmosphere, magnetic field interacts with the plasma, producing abundant eruptive activities. They are considered to be the main factors for coronal heating, particle acceleration and the formation of structures like prominences, flares and Coronal Mass Ejections. The magnetic field in solar atmosphere in the range of 1.1-3 Rsun is especially important as an interface between the photospheric magnetic field and the solar wind. Its structure and time dependent change affects space weather by modifying solar wind conditions, Cho (2000). Type II doublet bursts can be used for the estimation of the strength of the magnetic field at two different heights. Two type II bursts occur sometimes in sequence. By relating the speed of the type II radio burst to Alfven Mach Number, the Alfven speed of the shock wave generating type II radio burst can be calculated. Using the relation between the Alfven speed and the mean frequency of emission, the magnetic field strength can be determined at a particular height. We have used the relative bandwidth and drift rate properties of multiple type II radio bursts to derive magnetic field strengths at two different heights and also the gradient of the magnetic field in the outer corona. The magnetic field strength has been derived for different density factors. It varied from 1.2 to 2.5 gauss at a solar height of 1.4 Rsun. The empirical relation of the variation of the magnetic field with height is found to be of the form B(R) = In the present case the power law index ‘γ’ varied from -3 to -2 for variation of

  11. Isolinderalactone inhibits proliferation of A549 human non‑small cell lung cancer cells by arresting the cell cycle at the G0/G1 phase and inducing a Fas receptor and soluble Fas ligand-mediated apoptotic pathway.

    PubMed

    Chang, Wei-An; Lin, En-Shyh; Tsai, Ming-Ju; Huang, Ming-Shyan; Kuo, Po-Lin

    2014-05-01

    Lung cancer is currently the leading cause of cancer-related mortality worldwide. In Taiwan, lung cancer is also the type of malignancy that is the major cause of cancer-mortality. Investigating the mechanism of apoptosis of lung cancer cells is important in the treatment of lung cancer. In the present study, isolinderalactone was demonstrated to exhibit anticancer effects in A549 human non-small cell lung cancer cells. The effect of isolinderalactone on apoptosis, cell cycle distribution p21 levels and the Fas receptor and soluble Fas ligand (sFasL) were assayed in order to determine the mechanism underlying the anticancer effect of isolinderalactone. It was demonstrated that isolinderalactone may induce p21 expression and then cause the cell cycle arrest of A549 cells. The data of the present study also revealed that the Fas/sFasL apoptotic system is significant in the mechanism of isolinderalactone‑induced apoptosis of A549 cells. These novel findings demonstrated that isolinderalactone may cause the cell cycle arrest of A549 cells by induction of p21, and induce apoptosis of A549 human non-small-cell lung carcinoma cells through the Fas/sFasL apoptotic system.

  12. Refined genetic and physical mapping of BPES type II.

    PubMed

    Messiaen, L; Leroy, B P; De Bie, S; De Pauw, K; Van Roy, N; Speleman, F; Van Camp, G; De Paepe, A

    1996-01-01

    BPES is a genetic disorder including blepharophimosis, ptosis of the eyelids, epicanthus inversus and telecanthus. Type I is associated with female infertility, whereas type II presents without other symptoms. Both types I and II occur sporadically or are inherited as an autosomal dominant trait. We present a molecular genetic and cytogenetic study in a large four-generation Belgian family with BPES type II. Karyotype analysis on high-resolution banded chromosomes yielded normal results. Fluorescence in situ hybridization (FISH) with cosmid probes spanning 3q22-q24 revealed normal hybridization patterns. Sixteen polymorphic CA repeats encompassing region 3q13-q25 were analysed. Linkage analysis in this large four-generation family provides conclusive evidence for the presence of a BPES gene in this region. Two-point lod scores greater than 3.0 between the disease and the following markers were seen: D3S1589 (4.67), D3S1292 (3.52), D3S1290 (3.59) and D3S1549 (3.65). By FISH, D3S1290, D3S1292 and D3S1549 were assigned to chromosome 3q23 using YACs positive for these markers.

  13. Type II restriction endonucleases—a historical perspective and more

    PubMed Central

    Pingoud, Alfred; Wilson, Geoffrey G.; Wende, Wolfgang

    2014-01-01

    This article continues the series of Surveys and Summaries on restriction endonucleases (REases) begun this year in Nucleic Acids Research. Here we discuss ‘Type II’ REases, the kind used for DNA analysis and cloning. We focus on their biochemistry: what they are, what they do, and how they do it. Type II REases are produced by prokaryotes to combat bacteriophages. With extreme accuracy, each recognizes a particular sequence in double-stranded DNA and cleaves at a fixed position within or nearby. The discoveries of these enzymes in the 1970s, and of the uses to which they could be put, have since impacted every corner of the life sciences. They became the enabling tools of molecular biology, genetics and biotechnology, and made analysis at the most fundamental levels routine. Hundreds of different REases have been discovered and are available commercially. Their genes have been cloned, sequenced and overexpressed. Most have been characterized to some extent, but few have been studied in depth. Here, we describe the original discoveries in this field, and the properties of the first Type II REases investigated. We discuss the mechanisms of sequence recognition and catalysis, and the varied oligomeric modes in which Type II REases act. We describe the surprising heterogeneity revealed by comparisons of their sequences and structures. PMID:24878924

  14. On the nature of rapidly fading Type II supernovae

    NASA Astrophysics Data System (ADS)

    Moriya, Takashi J.; Pruzhinskaya, Maria V.; Ergon, Mattias; Blinnikov, Sergei I.

    2016-01-01

    It has been suggested that Type II supernovae with rapidly fading light curves (a.k.a. Type IIL supernovae) are explosions of progenitors with low-mass hydrogen-rich envelopes which are of the order of 1 M⊙. We investigate light-curve properties of supernovae from such progenitors. We confirm that such progenitors lead to rapidly fading Type II supernovae. We find that the luminosity of supernovae from such progenitors with the canonical explosion energy of 1051 erg and 56Ni mass of 0.05 M⊙ can increase temporarily shortly before all the hydrogen in the envelope recombines. As a result, a bump appears in their light curves. The bump appears because the heating from the nuclear decay of 56Ni can keep the bottom of hydrogen-rich layers in the ejecta ionized, and thus the photosphere can stay there for a while. We find that the light-curve bump becomes less significant when we make explosion energy larger (≳2 × 1051 erg), 56Ni mass smaller (≲0.01 M⊙), 56Ni mixed in the ejecta, or the progenitor radius larger. Helium mixing in hydrogen-rich layers makes the light-curve decline rates large but does not help reducing the light-curve bump. Because the light-curve bump we found in our light-curve models has not been observed in rapidly fading Type II supernovae, they may be characterized by not only low-mass hydrogen-rich envelopes but also higher explosion energy, larger degrees of 56Ni mixing, and/or larger progenitor radii than slowly fading Type II supernovae, so that the light-curve bump does not become significant.

  15. The transforming growth factor beta type II receptor can replace the activin type II receptor in inducing mesoderm.

    PubMed Central

    Bhushan, A; Lin, H Y; Lodish, H F; Kintner, C R

    1994-01-01

    The type II receptors for the polypeptide growth factors transforming growth factor beta (TGF-beta) and activin belong to a new family of predicted serine/threonine protein kinases. In Xenopus embryos, the biological effects of activin and TGF-beta 1 are strikingly different; activin induces a full range of mesodermal cell types in the animal cap assay, while TGF-beta 1 has no effects, presumably because of the lack of functional TGF-beta receptors. In order to assess the biological activities of exogenously added TGF-beta 1, RNA encoding the TGF-beta type II receptor was introduced into Xenopus embryos. In animal caps from these embryos, TGF-beta 1 and activin show similar potencies for induction of mesoderm-specific mRNAs, and both elicit the same types of mesodermal tissues. In addition, the response of animal caps to TGF-beta 1, as well as to activin, is blocked by a dominant inhibitory ras mutant, p21(Asn-17)Ha-ras. These results indicate that the activin and TGF-beta type II receptors can couple to similar signalling pathways and that the biological specificities of these growth factors lie in their different ligand-binding domains and in different competences of the responding cells. Images PMID:8196664

  16. Characteristics of Type-II Radio Bursts Associated with Flares and CMEs

    NASA Astrophysics Data System (ADS)

    Vasanth, V.; Umapathy, S.; Vršnak, Bojan; Anna Lakshmi, M.

    2011-10-01

    We present a statistical study of the characteristics of type-II radio bursts observed in the metric (m) and deca-hectometer (DH) wavelength range during 1997-2008. The collected events are divided into two groups: Group I contains the events of m-type-II bursts with starting frequency ≥ 100 MHz, and group II contains the events with starting frequency of m-type-II radio bursts < 100 MHz. We have analyzed both samples considering three different aspects: i) statistical properties of type-II bursts, ii) statistical properties of flares and CMEs associated with type-II bursts, and iii) time delays between type-II bursts, flares, and CMEs. We find significant differences in the properties of m-type-II bursts in duration, bandwidth, drift rate, shock speed and delay between m- and DH-type-II bursts. From the timing analysis we found that the majority of m-type-II bursts in both groups occur during the flare impulsive phase. On the other hand, the DH-type-II bursts in both groups occur during the decaying phase of the associated flares. Almost all m-DH-type-II bursts are found to be associated with CMEs. Our results indicate that there are two kinds of shock in which group I (high frequency) m-type-II bursts seem to be ignited by flares whereas group II (low frequency) m-type-II bursts are CME-driven.

  17. Exploring Type I and Type II Errors Using Rhizopus Sporangia Diameter Measurements.

    ERIC Educational Resources Information Center

    Smith, Robert A.; Burns, Gerard; Freud, Brian; Fenning, Stacy; Hoffman, Rosemary; Sabapathi, Durai

    2000-01-01

    Presents exercises in which students can explore Type I and Type II errors using sporangia diameter measurements as a means of differentiating between two species. Examines the influence of sample size and significance level on the outcome of the analysis. (SAH)

  18. Multicolor Oservations of the Type II Cepheid Prototype W Virginis

    NASA Astrophysics Data System (ADS)

    Templeton, Matthew R.; Henden, A. A.; Crawford, T.; James, R.; Bonnardeau, M.; Wells, D.

    2006-12-01

    We present preliminary results of the AAVSO's six-month photometric campaign on the bright, pulsating variable star W Virginis, class prototype of the Type II Cepheid variables. This campaign was organized in support of separate spectroscopic observations (Wallerstein et al., in preparation), but these photometric data also stand alone as a valuable, recent, multicolor light curve of this object. Observations were obtained by several amateur and professional observers using a variety of equipment; data are primarily in the V filter, but include two complete pulsation cycles in the BVRcIc filters. We present lightand color-curves of this star, and compare our results to previous observational and theoretical results on W Vir and the Type II Cepheids.

  19. THE CONNECTION OF TYPE II SPICULES TO THE CORONA

    SciTech Connect

    Judge, Philip G.; McIntosh, Scott W.; De Pontieu, Bart; Olluri, Kosovare

    2012-02-20

    We examine the hypothesis that plasma associated with 'Type II' spicules is heated to coronal temperatures, and that the upward moving hot plasma constitutes a significant mass supply to the solar corona. One-dimensional hydrodynamical models including time-dependent ionization are brought to bear on the problem. These calculations indicate that heating of field-aligned spicule flows should produce significant differential Doppler shifts between emission lines formed in the chromosphere, transition region, and corona. At present, observational evidence for the computed 60-90 km s{sup -1} differential shifts is weak, but the data are limited by difficulties in comparing the proper motion of Type II spicules with spectral and kinematic properties of an associated transition region and coronal emission lines. Future observations with the upcoming infrared interferometer spectrometer instrument should clarify if Doppler shifts are consistent with the dynamics modeled here.

  20. UBVRIz Light Curves of 51 Type II Supernovae

    NASA Astrophysics Data System (ADS)

    Galbany, Lluís; Hamuy, Mario; Phillips, Mark M.; Suntzeff, Nicholas B.; Maza, José; de Jaeger, Thomas; Moraga, Tania; González-Gaitán, Santiago; Krisciunas, Kevin; Morrell, Nidia I.; Thomas-Osip, Joanna; Krzeminski, Wojtek; González, Luis; Antezana, Roberto; Wishnjewski, Marina; McCarthy, Patrick; Anderson, Joseph P.; Gutiérrez, Claudia P.; Stritzinger, Maximilian; Folatelli, Gastón; Anguita, Claudio; Galaz, Gaspar; Green, Elisabeth M.; Impey, Chris; Kim, Yong-Cheol; Kirhakos, Sofia; Malkan, Mathew A.; Mulchaey, John S.; Phillips, Andrew C.; Pizzella, Alessandro; Prosser, Charles F.; Schmidt, Brian P.; Schommer, Robert A.; Sherry, William; Strolger, Louis-Gregory; Wells, Lisa A.; Williger, Gerard M.

    2016-02-01

    We present a compilation of UBVRIz light curves of 51 type II supernovae discovered during the course of four different surveys during 1986-2003: the Cerro Tololo Supernova Survey, the Calán/Tololo Supernova Program (C&T), the Supernova Optical and Infrared Survey (SOIRS), and the Carnegie Type II Supernova Survey (CATS). The photometry is based on template-subtracted images to eliminate any potential host galaxy light contamination, and calibrated from foreground stars. This work presents these photometric data, studies the color evolution using different bands, and explores the relation between the magnitude at maximum brightness and the brightness decline parameter (s) from maximum light through the end of the recombination phase. This parameter is found to be shallower for redder bands and appears to have the best correlation in the B band. In addition, it also correlates with the plateau duration, being shorter (longer) for larger (smaller) s values.

  1. New insights into bacterial type II polyketide biosynthesis

    PubMed Central

    Zhang, Zhuan; Pan, Hai-Xue; Tang, Gong-Li

    2017-01-01

    Bacterial aromatic polyketides, exemplified by anthracyclines, angucyclines, tetracyclines, and pentangular polyphenols, are a large family of natural products with diverse structures and biological activities and are usually biosynthesized by type II polyketide synthases (PKSs). Since the starting point of biosynthesis and combinatorial biosynthesis in 1984–1985, there has been a continuous effort to investigate the biosynthetic logic of aromatic polyketides owing to the urgent need of developing promising therapeutic candidates from these compounds. Recently, significant advances in the structural and mechanistic identification of enzymes involved in aromatic polyketide biosynthesis have been made on the basis of novel genetic, biochemical, and chemical technologies. This review highlights the progress in bacterial type II PKSs in the past three years (2013–2016). Moreover, novel compounds discovered or created by genome mining and biosynthetic engineering are also included. PMID:28299197

  2. Progression of Jackhammer Esophagus to Type II Achalasia

    PubMed Central

    Abdallah, Jason; Fass, Ronnie

    2016-01-01

    It has been suggested that patients with certain motility disorders may progress overtime to develop achalasia. We describe a 66 year-old woman who presented with dysphagia for solids and liquids for a period of 18 months. Her initial workup showed normal endoscopy and non-specific esophageal motility disorder on conventional manometry. Six months later, due to persistence of symptoms, the patient underwent a high resolution esophageal manometry (HREM) demonstrating jackhammer esophagus. The patient was treated with a high dose proton pump inhibitor but without resolution of her symptoms. During the last year, the patient reported repeated episodes of food regurgitation and a significant weight loss. A repeat HREM revealed type II achalasia. Multiple case reports, and only a few prospective studies have demonstrated progression from certain esophageal motility disorders to achalasia. However, this report is the first to describe a case of jackhammer esophagus progressing to type II achalasia. PMID:26717932

  3. On the Covariant Quantization of Type II Superstrings

    NASA Astrophysics Data System (ADS)

    Guttenberg, Sebastian; Knapp, Johanna; Kreuzer, Maximilian

    2004-06-01

    In a series of papers Grassi, Policastro, Porrati and van Nieuwenhuizen have introduced a new method to covariantly quantize the GS-superstring by constructing a resolution of the pure spinor constraint of Berkovits' approach. Their latest version is based on a gauged WZNW model and a definition of physical states in terms of relative cohomology groups. We first put the off-shell formulation of the type-II version of their ideas into a chirally split form and directly construct the free action of the gauged WZNW model, thus circumventing some complications of the super group manifold approach to type-II. Then we discuss the BRST charges that define the relative cohomology and the N=2 superconformal algebra. A surprising result is that nilpotency of the BRST charge requires the introduction of another quartet of ghosts.

  4. UBVRIz LIGHT CURVES OF 51 TYPE II SUPERNOVAE

    SciTech Connect

    Galbany, Lluis; Hamuy, Mario; Jaeger, Thomas de; Moraga, Tania; González-Gaitán, Santiago; Gutiérrez, Claudia P.; Phillips, Mark M.; Morrell, Nidia I.; Thomas-Osip, Joanna; Suntzeff, Nicholas B.; Maza, José; González, Luis; Antezana, Roberto; Wishnjewski, Marina; Krisciunas, Kevin; Krzeminski, Wojtek; McCarthy, Patrick; Anderson, Joseph P.; Stritzinger, Maximilian; Folatelli, Gastón; and others

    2016-02-15

    We present a compilation of UBVRIz light curves of 51 type II supernovae discovered during the course of four different surveys during 1986–2003: the Cerro Tololo Supernova Survey, the Calán/Tololo Supernova Program (C and T), the Supernova Optical and Infrared Survey (SOIRS), and the Carnegie Type II Supernova Survey (CATS). The photometry is based on template-subtracted images to eliminate any potential host galaxy light contamination, and calibrated from foreground stars. This work presents these photometric data, studies the color evolution using different bands, and explores the relation between the magnitude at maximum brightness and the brightness decline parameter (s) from maximum light through the end of the recombination phase. This parameter is found to be shallower for redder bands and appears to have the best correlation in the B band. In addition, it also correlates with the plateau duration, being shorter (longer) for larger (smaller) s values.

  5. Shock waves and nucleosynthesis in type II supernovae

    NASA Technical Reports Server (NTRS)

    Aufderheide, M. B.; Baron, E.; Thielemann, F.-K.

    1991-01-01

    In the study of nucleosynthesis in type II SN, shock waves are initiated artificially, since collapse calculations do not, as yet, give self-consistent shock waves strong enough to produce the SN explosion. The two initiation methods currently used by light-curve modelers are studied, with a focus on the peak temperatures and the nucleosynthetic yields in each method. The various parameters involved in artificially initiating a shock wave and the effects of varying these parameters are discussed.

  6. Study of interacting CMEs and DH type II radio bursts

    NASA Astrophysics Data System (ADS)

    Prasanna Subramanian, S.; Shanmugaraju, A.

    2013-04-01

    The subject of interaction between the Corona Mass Ejections (CMEs) is important in the concept of space-weather studies. In this paper, we analyzed a set of 15 interacting events taken from the list compiled by Manoharan et al. (in J. Geophys. Res. 109:A06109, 2004) and their associated DH type II radio bursts. The pre and primary CMEs, and their associated DH type II bursts are identified using the SOHO/LASCO catalog and Wind/WAVES catalog, respectively. All the primary CMEs are associated with shocks and interplanetary CMEs. These CMEs are found to be preceded by secondary slow CMEs. Most of primary CMEs are halo type CME and much faster (Mean speed = 1205 km s-1) than the pre CME (Mean speed = 450 km s-1). The average delay between the pre and primary CMEs, drift rate of DH type IIs and interaction height are found to be 211 min, 0.878 kHz/s and 17.87 Ro, respectively. The final observed distance (FOD) of all pre CMEs are found to be less than 15 Ro and it is seen that many of the pre CMEs got merged with the primary CMEs, and, they were not traced as separate CMEs in the LASCO field of view. Some radio signatures are identified for these events in the DH spectrum around the time of interaction. The interaction height obtained from the height-time plots of pre and primary CMEs is found to have correlations with (i) the time delay between the two CMEs and (ii) the central frequency of emission in the radio signatures in the DH spectrum around the time of interaction. The centre frequency of emission in the DH spectrum around the time of interaction seems to decrease when the interaction height increases. This result is compared with an interplanetary density model of Saito et al. (in Solar Phys. 55:121, 1977).

  7. Closed Timelike Curves in Type II Non-Vacuum Spacetime

    NASA Astrophysics Data System (ADS)

    Ahmed, Faizuddin

    2017-02-01

    Here we present a cyclicly symmetric non-vacuum spacetime, admitting closed timelike curves (CTCs) which appear after a certain instant of time, i.e., a time-machine spacetime. The spacetime is asymptotically flat, free-from curvature singularities and a four-dimensional extension of the Misner space in curved spacetime. The spacetime is of type II in the Petrov classification scheme and the matter field pure radiation satisfy the energy condition.

  8. Classification of SN2005dj, a Type II Supernova

    NASA Astrophysics Data System (ADS)

    Blanc, N.; Bongard, S.; Copin, Y.; Gangler, E.; Sauge, L.; Smadja, G.; Antilogus, P.; Garavini, G.; Gilles, S.; Pain, R.; Aldering, G.; Bailey, S.; Lee, B. C.; Loken, S.; Nugent, P.; Perlmutter, S.; Scalzo, R.; Thomas, R. C.; Wang, L.; Weaver, B. A.; Bonnaud, C.; Pecontal, E.; Kessler, R.; Baltay, C.; Rabinowitz, D.; Bauer, A.

    2005-08-01

    The Nearby Supernova Factory reports that a spectrum (range 320-1000 nm) of SN 2005dj (IAUC#8585), obtained August 19.6 UT with the Supernova Integral Field Spectrograph on the University of Hawaii 2.2-meter telescope, reveals P-Cygni H-alpha and H-beta, indicative of a Type II supernova. The observed redshift is consistent with that of the host UGC 3545 (z = 0.011508, Huchtmeier & Skillman 1998 via NED).

  9. Evaluation of nanoarchitectured collagen type II molecules on cartilage engineering.

    PubMed

    Kuo, Shyh Ming; Chiang, Ming Yu; Lan, Cheng Wen; Niu, Gregory Cheng-Chie; Chang, Shwu Jen

    2013-02-01

    Scaffold architecture, including the geometry and dimension of scaffolds, is an important parameter in cell adhesion, migration, proliferation, and differentiation. Following the characterization of collagen type II nanoarchitectured molecules, collagen fibrils (CNFs) and collagen spheres (CNPs) prepared using a high-voltage electric field in our laboratory, we proposed to use these nanoarchitectured molecules to assess their influence on the culturing of chondrocytes in stirred bioreactors. The results demonstrate that chondrocytes rapidly formed more and larger chondrocyte pellets (spheroids) after the addition of nanoarchitectured molecules into the culture medium. The maintenance of chondrocytes with round morphology and increased glycosaminoglycan secretion indicated that these spheroids contained viable and un-dedifferentiated chondrocytes. No significant increases in DNA content were detected. These results show that the introduction of these molecules did not affect chondrocyte proliferation during a 3-day culture period. After the addition of CNPs and CNFs into the culture medium, the expression levels of collagen type II and aggrecan genes in chondrocytes increased significantly as demonstrated by real-time PCR analysis. Interestingly, chondrocytes exhibited distinct collagen type II and aggrecan gene expression profiles in culture with CNPs and CNFs. The aggrecan gene expression level of the chondrocytes was 2.5-fold greater following CFN addition than following the addition of CNPs. In contrast, the collagen type II expression level of the chondrocytes was 2.2-fold greater following the addition of CNPs than following the addition of CNFs. The chondrocyte pellets rapidly restored defects in articular cartilage during a 1-month implantation period in a rabbit model.

  10. ACCELERATION OF TYPE II SPICULES IN THE SOLAR CHROMOSPHERE

    SciTech Connect

    Goodman, Michael L.

    2012-10-01

    A 2.5D, time-dependent magnetohydrodynamic model is used to test the proposition that observed type II spicule velocities can be generated by a Lorentz force under chromospheric conditions. It is found that current densities localized on observed space and time scales of type II spicules and that generate maximum magnetic field strengths {<=}50 G can generate a Lorentz force that accelerates plasma to terminal velocities similar to those of type II spicules. Maximum vertical flow speeds are {approx}150-460 km s{sup -1}, horizontally localized within {approx}2.5-10 km from the vertical axis of the spicule, and comparable to slow solar wind speeds, suggesting that significant solar wind acceleration occurs in type II spicules. Horizontal speeds are {approx}20 times smaller than vertical speeds. Terminal velocity is reached {approx}100 s after acceleration begins. The increase in the mechanical and thermal energy of the plasma during acceleration is (2-3) Multiplication-Sign 10{sup 22} ergs. The radial component of the Lorentz force compresses the plasma during the acceleration process by factors as large as {approx}100. The Joule heating flux generated during this process is essentially due to proton Pedersen current dissipation and can be {approx}0.1-3.7 times the heating flux of {approx}10{sup 6} ergs cm{sup -2} s{sup -1} associated with middle-upper chromospheric emission. About 84%-94% of the magnetic energy that accelerates and heats the spicules is converted into bulk flow kinetic energy.

  11. Type III intermediate filament peripherin inhibits neuritogenesis in type II spiral ganglion neurons in vitro

    PubMed Central

    Barclay, Meagan; Julien, Jean-Pierre; Ryan, Allen F.; Housley, Gary D.

    2010-01-01

    Peripherin, a type III intermediate filament protein, forms part of the cytoskeleton in a subset of neurons, most of which have peripheral fibre projections. Studies suggest a role for peripherin in axon outgrowth and regeneration, but evidence for this in sensory and brain tissues is limited. The exclusive expression of peripherin in a sub-population of primary auditory neurons, the type II spiral ganglion neurons (SGN) prompted our investigation of the effect of peripherin gene deletion (pphKO) on these neurons. We used confocal immunofluorescence to examine the establishment of the innervation of the cochlear outer hair cells by the type II SGN neurites in vivo and in vitro, in wildtype (WT) and pphKO mice, in the first postnatal week. The distribution of the type II SGN nerve fibres was normal in pphKO cochleae. However, using P1 spiral ganglion explants under culture conditions where the majority of neurites were derived from type II SGN, pphKO resulted in increased numbers of neurites/explant compared WT controls. Type II SGN neurites from pphKO explants extended ~ double the distance of WT neurites, and had reduced complexity based on greater distance between turning points. Addition of brain-derived neurotrophic factor (BDNF) to the culture media increased neurite number in WT and KO explants ~30-fold, but did not affect neurite length or distance between turning. These results indicate that peripherin may interact with other cytoskeletal elements to regulate outgrowth of the peripheral neurites of type II SGN, distinguishing these neurons from the type I SGN innervating the inner hair cells. PMID:20132868

  12. Comparison of oxycodone and morphine on the proliferation, apoptosis and expression of related molecules in the A549 human lung adenocarcinoma cell line

    PubMed Central

    Tian, Mi; Jin, Li; Li, Renqi; Zhu, Sihai; Ji, Muhuo; Li, Weiyan

    2016-01-01

    The present study aimed to compare the effects of oxycodone and morphine hydrochloride on the proliferation, apoptosis and migration of A549 lung cancer cells. A549 human lung cancer cells were cultured in vitro and treated with oxycodone or morphine at various concentrations (10, 20 and 40 µg/ml). Cell migration was determined using a wound healing assay, whereas apoptosis was detected using flow cytometry. Reverse transcription quantitative-polymerase chain reaction was performed in order to assess the apoptosis-related gene expression levels, including p53, B-cell lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax). The levels of vascular endothelial growth factor (VEGF) and urokinase-type plasminogen activator (uPA) were detected using enzyme-linked immunosorbent assays. The expression levels of intercellular cell adhesion molecule (ICAM)-1 were determined by immunofluorescence. In the present study, oxycodone and morphine induced apoptosis in A549 lung cancer cells with similar potency; however, >20 µg/ml oxycodone was more effective at inhibiting cell proliferation (P<0.05) and migration (P<0.05), as compared with morphine at the same concentration. Oxycodone induced a dose-dependent increase in the expression levels of p53 and Bax apoptosis-related genes, whereas it decreased the gene expression levels of Bcl-2. Furthermore, oxycodone decreased, whereas morphine increased, the expression levels of ICAM-1 in a concentration-dependent manner. In addition, at 40 µg/ml, the expression levels of VEGF and uPA in the morphine group were significantly higher than those demonstrated in the oxycodone group (P<0.05). In conclusion, oxycodone was more effective in inhibiting the proliferation and migration of A549 lung cancer cells, as compared with morphine. PMID:27446244

  13. Heat-modified citrus pectin induces apoptosis-like cell death and autophagy in HepG2 and A549 cancer cells.

    PubMed

    Leclere, Lionel; Fransolet, Maude; Cote, Francois; Cambier, Pierre; Arnould, Thierry; Van Cutsem, Pierre; Michiels, Carine

    2015-01-01

    Cancer is still one of the leading causes of death worldwide, and finding new treatments remains a major challenge. Previous studies showed that modified forms of pectin, a complex polysaccharide present in the primary plant cell wall, possess anticancer properties. Nevertheless, the mechanism of action of modified pectin and the pathways involved are unclear. Here, we show that citrus pectin modified by heat treatment induced cell death in HepG2 and A549 cells. The induced cell death differs from classical apoptosis because no DNA cleavage was observed. In addition, Z-VAD-fmk, a pan-caspase inhibitor, did not influence the observed cell death in HepG2 cells but appeared to be partly protective in A549 cells, indicating that heat-modified citrus pectin might induce caspase-independent cell death. An increase in the abundance of the phosphatidylethanolamine-conjugated Light Chain 3 (LC3) protein and a decrease in p62 protein abundance were observed in both cell types when incubated in the presence of heat-modified citrus pectin. These results indicate the activation of autophagy. To our knowledge, this is the first time that autophagy has been revealed in cells incubated in the presence of a modified form of pectin. This autophagy activation appears to be protective, at least for A549 cells, because its inhibition with 3-methyladenine increased the observed modified pectin-induced cytotoxicity. This study confirms the potential of modified pectin to improve chemotherapeutic cancer treatments.

  14. Type-II superlattice infrared detector technology at Fraunhofer IAF

    NASA Astrophysics Data System (ADS)

    Rehm, Robert; Daumer, Volker; Hugger, Tsvetelina; Kohn, Norbert; Luppold, Wolfgang; Müller, Raphael; Niemasz, Jasmin; Schmidt, Johannes; Rutz, Frank; Stadelmann, Tim; Wauro, Matthias; Wörl, Andreas

    2016-05-01

    For more than two decades, Antimony-based type-II superlattice photodetectors for the infrared spectral range between 3-15 μm are under development at the Fraunhofer Institute for Applied Solid State Physics (IAF). Today, Fraunhofer IAF is Germany's only national foundry for InAs/GaSb type-II superlattice detectors and we cover a wide range of aspects from basic materials research to small series production in this field. We develop single-element photodetectors for sensing systems as well as two-dimensional detector arrays for high-performance imaging and threat warning systems in the mid-wavelength and long-wavelength region of the thermal infrared. We continuously enhance our production capabilities by extending our in-line process control facilities. As a recent example, we present a semiautomatic wafer probe station that has developed into an important tool for electrooptical characterization. A large amount of the basic materials research focuses on the reduction of the dark current by the development of bandgap engineered device designs on the basis of heterojunction concepts. Recently, we have successfully demonstrated Europe's first LWIR InAs/GaSb type-II superlattice imager with 640x512 pixels with 15 μm pitch. The demonstrator camera already delivers a good image quality and achieves a thermal resolution better than 30 mK.

  15. Subcellular dynamics of type II PKA in neurons

    PubMed Central

    Zhong, Haining; Sia, Gek-Ming; Sato, Takashi R.; Gray, Noah W.; Mao, Tianyi; Khuchua, Zaza; Huganir, Richard L.; Svoboda, Karel

    2009-01-01

    SUMMARY Protein kinase A (PKA) plays multiple roles in neurons. The localization and specificity of PKA are largely controlled by A-kinase anchoring proteins (AKAPs). However, the dynamics of PKA in neurons, and the roles of specific AKAPs, are poorly understood. We imaged the distribution of type II PKA in hippocampal and cortical layer 2/3 pyramidal neurons in vitro and in vivo. PKA was concentrated in dendritic shafts compared to the soma, axons and dendritic spines. This spatial distribution was imposed by the microtubule-binding protein MAP2, indicating that MAP2 is the dominant AKAP in neurons. Following cAMP elevation, catalytic subunits dissociated from the MAP2-tethered regulatory subunits and rapidly moved to become enriched in nearby spines. The spatial gradient of type II PKA between dendritic shafts and spines was critical for the regulation of synaptic strength and long-term potentiation. The localization and activity-dependent translocation of type II PKA are therefore important determinants of PKA function. PMID:19447092

  16. Coronas Mass Ejections, Shocks, and Type II Radio Bursts

    NASA Technical Reports Server (NTRS)

    Gopalswamy, Natchimuthuk

    2010-01-01

    Coronal mass ejections (CMEs) are the most energetic phenomena in the interplanetary medium. Type II radio bursts are the earliest indicators of particle acceleration by CME-driven shocks. There is one-to-one correspondence between large solar energetic particle (SEP) events and long wavelength type II bursts because the same CME-driven shock is supposed to accelerate electrons and ions. However, there are some significant deviations: some CMEs lacking type II bursts (radio-quiet or RQ CMEs) are associated with small SEP events while some radioloud (RL) CMEs are not associated with SEP events, suggesting subtle differences in the acceleration of electrons and protons. Not all CME-driven shocks are radio loud: more than one third of the interplanetary shocks during solar cycle 23 were radio quiet. Some RQ shocks were associated with energetic storm particle (ESP) events, which are detected when the shocks arrive at the observing spacecraft. This paper attempts to explain these contradictory results in terms of the properties of CMEs, shocks, and the ambient medium.

  17. Perinatal lethal type II osteogenesis imperfecta: a case report.

    PubMed

    Ayadi, Imene Dahmane; Hamida, Emira Ben; Rebeh, Rania Ben; Chaouachi, Sihem; Marrakchi, Zahra

    2015-01-01

    We report a new case of osteogenesis imperfecta (OI) type II which is a perinatal lethal form. First trimester ultrasound didn't identified abnormalities. Second trimester ultrasound showed incurved limbs, narrow chest, with hypomineralization and multiple fractures of ribs and long bones. Parents refused pregnancy termination; they felt that the diagnosis was late. At birth, the newborn presented immediate respiratory distress. Postnatal examination and bone radiography confirmed the diagnosis of OI type IIA. Death occurred on day 25 of life related to respiratory failure.

  18. THE IMMUNOLOGICAL SPECIFICITY OF TYPE II PNEUMOCOCCUS AND ITS SEPARATION INTO PARTIAL SPECIFICITIES. II

    PubMed Central

    Heidelberger, Michael

    1960-01-01

    Quantitative data are given on the cross reactions in Type II antipneumococcal horse sera of plant gums and hemicelluloses containing multiple terminal groupings of glucuronic acid and/or 4-O-methylglucuronic acid. Great variability is shown both in the reactivities of the polysaccharides and in the antibodies in the sera of different animals immunized with the same antigen. The 4-O-methyl substituent on the glucuronic acid residues in a gum often appears to diminish cross-precipitation with antibodies to S II. PMID:13852209

  19. FGFR3 silencing by siRNA inhibits invasion of A549 cells

    PubMed Central

    Li, Yuhua; Liu, Xiguang; Zhang, Hongjun; Jiang, Tao; Xiao, Wenjing; Zhao, Shufen; Yu, Xiaoyun; Han, Fanjie

    2016-01-01

    The present study identified that fibroblast growth factor receptor 3 (FGFR3) was significantly upregulated in bone metastasis of lung adenocarcinoma. RNA interference (RNAi) is a powerful approach for treating a wide range of human diseases, including cancer, through downregulating the expression of selected genes. In the present study, the invasiveness of A549 cells cultured in vitro was altered by small interfering (si)RNA targeting FGFR3, and the regulatory effect of silencing FGFR3 on the expression levels of E-cadherin and matrix metalloproteinase (MMP)9 was investigated. Human lung adenocarcinoma A549 cells were transfected with synthetic specific siRNAs targeting a fragment of the FGFR3 gene (namely, siRNA-855, siRNA-1447 and siRNA-2076) or with negative control (NC) siRNA. Cells were divided into five groups (A, siRNA-855 group; B, siRNA-1447 group; C, siRNA-2076 group; D, NC-siRNA group; and E, blank control group). The effect of the above siRNAs targeting FGFR3 on the invasion capacity of A549 cells was detected by Transwell assay. siRNAs against FGFR3 were transfected into A549 cells with by Lipofectamine® 2000, and the expression levels of FGFR3, E-cadherin and MMP9 were measured by reverse transcription-quantitative polymerase chain reaction and western blot assay. The experimental findings indicated that the expression levels of FGFR3 and MMP9 were significantly reduced in the siRNA-FGFR3-transfected groups (A-C groups), compared with those in the D and E groups (P<0.01). In addition, the expression levels of E-cadherin were markedly elevated in the A-C groups, compared with those in the D and E groups (P<0.01). There was no significant difference in E-cadherin expression between the A-C groups, or between the D and E groups (P>0.05). These results indicated that siRNA-FGFR3 was able to decrease the invasiveness of A549 cells, inhibit the expression of MMP9 and increase the expression of E-cadherin by downregulating the expression of FGFR3. Taken

  20. Protection of A549 cells against the toxic effects of sulphur mustard by hexamethylenetetramine.

    PubMed

    Lindsay, C D; Hambrook, J L

    1997-02-01

    The A549 cell line was used as a model of the deep lung to study the toxicity and mechanism of action of sulphur mustard (HD), using the neutral red (NR) dye retention and gentian violet (GV) assays as indices of cell viability. It was found that exposure to concentrations in excess of 40 microM HD resulted in a rapid onset of toxicity. Exposure to 1000 microM HD reduced viability in A549 cell cultures to 61% after 2 h (control cultures = 100%), whereas exposure to 40 microM HD did not result in deleterious effects until 26 h at which point viability fell to only 84% (NR assay). Agarose gel electrophoresis of cell cultures exposed to 40 and 1000 microM HD and harvested at 4.5, 19 and 43 h after exposure to HD, indicated that cell death was due to necrosis, despite the observation that at the higher concentration of HD cells displayed many of the features common to cells undergoing apoptotic death. The ability of hexamethylenetetramine (HMT) to protect A549 cells against the effects of an LC50 challenge dose of HD was assessed using the GV and NR assays. It was found that HMT (15 mM) could protect cells against the effects of HD though HMT had to be present at the time of HD challenge. Cultures treated with HD only were 49% viable at 48 h after HD challenge, compared to 101% for protected cultures (NR assay) and 58% and 91% for unprotected and protected cultures respectively using the GV assay. Morphological observations of GV and NR stained cultures confirmed these findings. HMT concentrations of 2.5 to 25 mM were used. Maximal protection against the toxic effects of HD (LC50) was found at 10 to 25 mM HMT. Over this concentration range, HMT did not exert any toxic effects on A549 cells. Pretreatment of A549 cultures with HMT followed by its removal prior to HD challenge had no protective effect. Similarly, treating cultures with HD followed by addition of HMT did not increase the viability of the cultures, even if the HMT was added immediately after HD exposure

  1. A study of low-energy type II supernovae

    NASA Astrophysics Data System (ADS)

    Lisakov, Sergey M.; Dessart, Luc; Hillier, D. John; Waldman, Roni; Livne, Eli

    2015-08-01

    All stars with an initial mass greater than 8Msun, but not massive enough to encounter the pair-production instability, eventually form a degenerate core and collapse to form a compact object, either a neutron star or a black hole.At the lower mass end, these massive stars die as red-supergiant stars and give rise to Type II supernovae (SNe). The diversity of observed properties of SNe II suggests a range of progenitor mass, radii, but also explosion energy.We have performed a large grid simulations designed to cover this range of progenitor and explosion properties. Using MESA STAR, we compute a set of massive star models (12-30Msun) from the main sequence until core collapse. We then generate explosions with V1D to produce ejecta with a range of explosion energies and yields. Finally, all ejecta are evolved with CMFGEN to generate multi-band light curves and spectra.In this poster, we focus our attention on the properties of low-energy explosions that give rise to low-luminosity Type II Plateau (II-P) SNe. In particular, we present a detailed study of SN 2008bk, but also include other notorious low-energy SNe II-P like 2005cs, emphasising their non-standard properties by comparing to models that match well events like SN 1999em. Such low-energy explosions, characterised by low ejecta expansion rates, are more suitable for reliable spectral line identifications.Based on our models, we discuss the distinct signatures of low-energy explosions in lower and higher mass models. One important goal is to identify whether there is a progenitor-mass bias leading to such events.

  2. Effect of a misspecification of response rates on type I and type II errors, in a phase II Simon design.

    PubMed

    Baey, Charlotte; Le Deley, Marie-Cécile

    2011-07-01

    Phase-II trials are a key stage in the clinical development of a new treatment. Their main objective is to provide the required information for a go/no-go decision regarding a subsequent phase-III trial. In single arm phase-II trials, widely used in oncology, this decision relies on the comparison of efficacy outcomes observed in the trial to historical controls. The false positive rate generally accepted in phase-II trials, around 10%, contrasts with the very high attrition rate of new compounds tested in phase-III trials, estimated at about 60%. We assumed that this gap could partly be explained by the misspecification of the response rate expected with standard treatment, leading to erroneous hypotheses tested in the phase-II trial. We computed the false positive probability of a defined design under various hypotheses of expected efficacy probability. Similarly we calculated the power of the trial to detect the efficacy of a new compound for different expected efficacy rates. Calculations were done considering a binary outcome, such as the response rate, with a decision rule based on a Simon two-stage design. When analysing a single-arm phase-II trial, based on a design with a pre-specified null hypothesis, a 5% absolute error in the expected response rate leads to a false positive rate of about 30% when it is supposed to be 10%. This inflation of type-I error varies only slightly according to the hypotheses of the initial design. Single-arm phase-II trials poorly control for the false positive rate. Randomised phase-II trials should, therefore, be more often considered.

  3. Monoclonal antibodies against type II rat brain protein kinase

    SciTech Connect

    Nakabayashi, C.H.; Huang, K.P.

    1987-05-01

    Three monoclonal antibodies (8/1, 10/10, and 25/3) against rat brain type II protein kinase C (PKC) were used to carry out the immunochemical characterization of this kinase. These antibodies immunoprecipitated the type II PKC in a dose-dependent manner but did neither to type I nor type III isozyme. Purified type II PKC has a molecular weight of 82,000 and consists of heterogeneous isoelectric point species, all of which are cross reactive with these antibodies. Immunoblot analysis of the tryptic fragments from PKC revealed that all three antibodies recognized the 33-38-KDa fragments, the phospholipid/phorbol ester-binding domain, but not the 45-48-KDa fragments, the kinase catalytic domain. The immune complexes of the kinase and the antibodies retained the kinase activity which was dependent on Ca/sup 2 +/ and phosphatidylserine (PS) and further activated by diacylglycerol. With antibody 8/1, the apparent Km values of the kinase for Ca/sup 2 +/ and PS were not influenced. The initial rate and final extent of autophosphorylation were reduced. The concentration of PS required for half-maximal (/sup 3/H)phorbol 12,13-dibutyrate (PDBu) binding was increased and the total PDBu binding was reduced. In the presence of optimum concentrations of Ca/sup 2 +/ and PS, the Kd of PDBu was unaffected by the antibody but the total binding was reduced. These results demonstrate that the PS/PDBu-binding domain contains the major epitope for the antibodies and the antibody mainly influences the PS/PDBu binding to the kinase.

  4. EARLY-TYPE HOST GALAXIES OF TYPE II AND Ib SUPERNOVAE

    SciTech Connect

    Suh, Hyewon; Jeong, Hyunjin; Yi, Sukyoung K.; Yoon, Sung-chul

    2011-04-01

    Recent studies find that some early-type galaxies host Type II or Ibc supernovae (SNe II, Ibc). This may imply recent star formation activities in these SNe host galaxies, but a massive star origin of the SNe Ib so far observed in early-type galaxies has been questioned because of their intrinsic faintness and unusually strong Ca lines shown in the nebular phase. To address the issue, we investigate the properties of early-type SNe host galaxies using the data with Galaxy Evolution Explorer (GALEX) ultraviolet photometry and the Sloan Digital Sky Survey optical data. Our sample includes eight SNe II and one peculiar SN Ib (SN 2000ds) host galaxies as well as 32 SN Ia host galaxies. The host galaxy of SN 2005cz, another peculiar SN Ib, is also analyzed using the GALEX data and the NASA/IPAC Extragalactic Database optical data. We find that the NUV-optical colors of SN II/Ib host galaxies are systematically bluer than those of SN Ia host galaxies, and some SN II/Ib host galaxies with NUV - r colors markedly bluer than the others exhibit strong radio emission. We perform a stellar population synthesis analysis and find a clear signature of recent star formation activities in most of the SN II/Ib host galaxies. Our results generally support the association of the SNe II/Ib hosted in early-type galaxies with core collapse of massive stars. We briefly discuss implications for the progenitors of the peculiar SNe Ib 2000ds and 2005cz.

  5. Deciphering the role of the type II glyoxalase isoenzyme YcbL (GlxII-2) in Escherichia coli.

    PubMed

    Reiger, Matthias; Lassak, Jürgen; Jung, Kirsten

    2015-01-01

    In Escherichia coli, detoxification of methylglyoxal (MG) requires glyoxalases I and II. Glyoxalase I (gloA/GlxI) isomerizes the hemithioacetal, formed spontaneously from MG and glutathione (GSH) to S-lactoylglutathione (SLG), which is hydrolyzed by glyoxalase II (gloB/GlxII) to lactate and GSH. YcbL from Salmonella enterica serovar Typhimurium is an unusual type II glyoxalase whose role in MG detoxification has remained enigmatic. Here we show that YcbL (gloC/GlxII-2) acts as an accessory type II glyoxylase in E. coli. The two isoenzymes have additive effects and ensure maximal MG degradation.

  6. Cytotoxicity of carbon nanotube variants: a comparative in vitro exposure study with A549 epithelial and J774 macrophage cells.

    PubMed

    Kumarathasan, Prem; Breznan, Dalibor; Das, Dharani; Salam, Mohamed A; Siddiqui, Yunus; MacKinnon-Roy, Christine; Guan, Jingwen; de Silva, Nimal; Simard, Benoit; Vincent, Renaud

    2015-03-01

    While production of engineered carbon nanotubes (CNTs) has escalated in recent years, knowledge of risk associated with exposure to these materials remains unclear. We report on the cytotoxicity of four CNT variants in human lung epithelial cells (A549) and murine macrophages (J774). Morphology, metal content, aggregation/agglomeration state, pore volume, surface area and modifications were determined for the pristine and oxidized single-walled (SW) and multi-walled (MW) CNTs. Cytotoxicity was evaluated by cellular ATP content, BrdU incorporation, lactate dehydrogenase (LDH) release, and CellTiter-Blue (CTB) reduction assays. All CNTs were more cytotoxic than respirable TiO2 and SiO2 reference particles. Oxidation of CNTs removed most metallic impurities but introduced surface polar functionalities. Although slopes of fold changes for cytotoxicity endpoints were steeper with J774 compared to A549 cells, CNT cytotoxicity ranking in both cell types was assay-dependent. Based on CTB reduction and BrdU incorporation, the cytotoxicity of the polar oxidized CNTs was higher compared to the pristine CNTs. In contrast, pristine CNTs were more cytotoxic than oxidized CNTs when assessed for cellular ATP and LDH. Correlation analyses between CNTs' physico-chemical properties and average relative potency revealed the impact of metal content and surface area on the potency values estimated using ATP and LDH assays, while surface polarity affected the potency values estimated from CTB and BrdU assays. We show that in order to reliably estimate the risk posed by these materials, in vitro toxicity assessment of CNTs should be conducted with well characterized materials, in multiple cellular models using several cytotoxicity assays that report on distinct cellular processes.

  7. Preferential Type II Muscle Fiber Damage From Plyometric Exercise

    PubMed Central

    Macaluso, Filippo; Isaacs, Ashwin W.; Myburgh, Kathryn H.

    2012-01-01

    Context Plyometric training has been successfully used in different sporting contexts. Studies that investigated the effect of plyometric training on muscle morphology are limited, and results are controversial with regard to which muscle fiber type is mainly affected. Objective To analyze the skeletal muscle structural and ultrastructural change induced by an acute bout of plyometric exercise to determine which type of muscle fibers is predominantly damaged. Design Descriptive laboratory study. Setting Research laboratory. Patients or Other Participants Eight healthy, untrained individuals (age = 22 ± 1 years, height = 179.2 ± 6.4 cm, weight = 78.9 ± 5.9 kg). Intervention(s) Participants completed an acute bout of plyometric exercise (10 sets of 10 squat-jumps with a 1-minute rest between sets). Main Outcome Measure(s) Blood samples were collected 9 days and immediately before and 6 hours and 1, 2, and 3 days after the acute intervention. Muscle samples were collected 9 days before and 3 days after the exercise intervention. Blood samples were analyzed for creatine kinase activity. Muscle biopsies were analyzed for damage using fluorescent and electron transmission microscopy. Results Creatine kinase activity peaked 1 day after the exercise bout (529.0 ± 317.8 U/L). Immunofluorescence revealed sarcolemmal damage in 155 of 1616 fibers analyzed. Mainly fast-twitch fibers were damaged. Within subgroups, 7.6% of type I fibers, 10.3% of type IIa fibers, and 14.3% of type IIx fibers were damaged as assessed by losses in dystrophin staining. Similar damage was prevalent in IIx and IIa fibers. Electron microscopy revealed clearly distinguishable moderate and severe sarcomere damage, with damage quantifiably predominant in type II muscle fibers of both the glycolytic and oxidative subtypes (86% and 84%, respectively, versus only 27% of slow-twitch fibers). Conclusions We provide direct evidence that a single bout of plyometric exercise affected mainly type II muscle

  8. Mimulone-induced autophagy through p53-mediated AMPK/mTOR pathway increases caspase-mediated apoptotic cell death in A549 human lung cancer cells.

    PubMed

    An, Hyun-Kyu; Kim, Kyoung-Sook; Lee, Ji-Won; Park, Mi-Hyun; Moon, Hyung-In; Park, Shin-Ji; Baik, Ji-Sue; Kim, Cheorl-Ho; Lee, Young-Choon

    2014-01-01

    Anticancer properties and mechanisms of mimulone (MML), C-geranylflavonoid isolated from the Paulownia tomentosa fruits, were firstly elucidated in this study. MML prevented cell proliferation in a dose- and time-dependent way and triggered apoptosis through the extrinsic pathway in A549 human lung adenocarcinoma cells. Furthermore, MML-treated cells displayed autophagic features, such as the formation of autophagic vacuoles, a primary morphological feature of autophagy, and the accumulation of microtubule-associated protein 1 light chain 3 (LC3) puncta, another typical maker of autophagy, as determined by FITC-conjugated immunostaining and monodansylcadaverine (MDC) staining, respectively. The expression levels of LC3-I and LC3-II, specific markers of autophagy, were also augmented by MML treatment. Autophagy inhibition by 3-methyladenine (3-MA), pharmacological autophagy inhibitor, and shRNA knockdown of Beclin-1 reduced apoptotic cell death induced by MML. Autophagic flux was not significantly affected by MML treatment and lysosomal inhibitor, chloroquine (CQ) suppressed MML-induced autophagy and apoptosis. MML-induced autophagy was promoted by decreases in p53 and p-mTOR levels and increase of p-AMPK. Moreover, inhibition of p53 transactivation by pifithrin-α (PFT-α) and knockdown of p53 enhanced induction of autophagy and finally promoted apoptotic cell death. Overall, the results demonstrate that autophagy contributes to the cytotoxicity of MML in cancer cells harboring wild-type p53. This study strongly suggests that MML is a potential candidate for an anticancer agent targeting both autophagy and apoptotic cell death in human lung cancer. Moreover, co-treatment of MML and p53 inhibitor would be more effective in human lung cancer therapy.

  9. Mimulone-Induced Autophagy through p53-Mediated AMPK/mTOR Pathway Increases Caspase-Mediated Apoptotic Cell Death in A549 Human Lung Cancer Cells

    PubMed Central

    Lee, Ji-Won; Park, Mi-Hyun; Moon, Hyung-In; Park, Shin-Ji; Baik, Ji-Sue; Kim, Cheorl-Ho; Lee, Young-Choon

    2014-01-01

    Anticancer properties and mechanisms of mimulone (MML), C-geranylflavonoid isolated from the Paulownia tomentosa fruits, were firstly elucidated in this study. MML prevented cell proliferation in a dose- and time-dependent way and triggered apoptosis through the extrinsic pathway in A549 human lung adenocarcinoma cells. Furthermore, MML-treated cells displayed autophagic features, such as the formation of autophagic vacuoles, a primary morphological feature of autophagy, and the accumulation of microtubule-associated protein 1 light chain 3 (LC3) puncta, another typical maker of autophagy, as determined by FITC-conjugated immunostaining and monodansylcadaverine (MDC) staining, respectively. The expression levels of LC3-I and LC3-II, specific markers of autophagy, were also augmented by MML treatment. Autophagy inhibition by 3-methyladenine (3-MA), pharmacological autophagy inhibitor, and shRNA knockdown of Beclin-1 reduced apoptotic cell death induced by MML. Autophagic flux was not significantly affected by MML treatment and lysosomal inhibitor, chloroquine (CQ) suppressed MML-induced autophagy and apoptosis. MML-induced autophagy was promoted by decreases in p53 and p-mTOR levels and increase of p-AMPK. Moreover, inhibition of p53 transactivation by pifithrin-α (PFT-α) and knockdown of p53 enhanced induction of autophagy and finally promoted apoptotic cell death. Overall, the results demonstrate that autophagy contributes to the cytotoxicity of MML in cancer cells harboring wild-type p53. This study strongly suggests that MML is a potential candidate for an anticancer agent targeting both autophagy and apoptotic cell death in human lung cancer. Moreover, co-treatment of MML and p53 inhibitor would be more effective in human lung cancer therapy. PMID:25490748

  10. Isolation of eastern equine encephalitis virus in A549 and MRC-5 cell cultures.

    PubMed

    Sotomayor, E A; Josephson, S L

    1999-07-01

    Eastern equine encephalitis (EEE) has been diagnosed either serologically or by virus isolation. Until now, the recovery of EEE virus has been delegated to reference laboratories with the expertise and resources needed to amplify the virus in a susceptible vertebrate host and/or to isolate and identify the virus in cell culture. We report a case in which EEE virus was recovered directly from a patient's cerebrospinal fluid in A549 and MRC-5 cell cultures. Many clinical virology laboratories routinely use these cells to recover adenovirus, herpes simplex virus, and enterovirus. To the best of our knowledge, this is the first report of isolation of EEE virus in A549 cell culture. This report demonstrates the possibility of recovery of EEE virus in cell culture without the necessity of bioamplification or maintaining unusual cell lines.

  11. G4-Tetra DNA Duplex Induce Lung Cancer Cell Apoptosis in A549 Cells

    NASA Astrophysics Data System (ADS)

    Xu, Xiaobo; Zhao, YiZhuo; Lu, Hu; Fu, Cuiping; Li, Xiao; Jiang, Liyan; Li, Shanqun

    2016-10-01

    The specific DNA is typically impermeable to the plasma membrane due to its natural characters, but DNA tetra structures (DTNs) can be readily uptake by cells in the absence of transfection agents, providing a new strategy to deliver DNA drugs. In this research, the delivery efficiency of tetrahedral DNA nanostructures was measured on adenocarcinomic human alveolar basal epithelial (A549) cells via delivering AS1411 (G4). The DNA tetra-AS1411 complex was rapidly and abundantly uptake by A549 cells, and the induced apoptosis was enhanced. Furthermore, biodistribution in mouse proved the rapid clearance from non-targeted organs in vivo. This study improved the understanding of potential function in DNA-based drug delivery and proved that DTNs-AS1411 could be potentially useful for the treatment of lung cancer.

  12. Upregulation of AQP3 and AQP5 induced by dexamethasone and ambroxol in A549 cells.

    PubMed

    Ben, Yong; Chen, Jie; Zhu, Rong; Gao, Lei; Bai, Chunxue

    2008-04-30

    Aquaporins (AQPs) are membrane channel proteins that play roles in the regulation of water permeability in many tissues. AQP1 and AQP5 expressed in lung provide the principal route for osmotically driven water transport. In the airways, AQP3 and AQP4 facilitate water transport. Dexamethasone and ambroxol are often used to treat patients with pulmonary diseases accompanied by airway hypersecretion. The role of AQPs in these effective treatments has not been addressed. In this study, we analyzed the expression of AQPs in a human airway epithelial cell line (A549 cells) and showed that AQP3 and 5, but not AQP1 and 4, were expressed in A549 cells. Both dexamethasone and ambroxol stimulated the expression of AQP3 and 5 at the mRNA and protein levels. The data suggest potential roles of AQP3 and 5 in the regulation of airway hypersecretion, perhaps ultimately providing a target for treating such diseases.

  13. Deactivation of A549 cancer cells in vitro by a dielectric barrier discharge plasma needle

    NASA Astrophysics Data System (ADS)

    Huang, Jun; Chen, Wei; Li, Hui; Wang, Xing-Quan; Lv, Guo-Hua; Khohsa, M. Latif; Guo, Ming; Feng, Ke-Cheng; Wang, Peng-Ye; Yang, Si-Ze

    2011-03-01

    An inactivation mechanism study on A549 cancer cells by means of a dielectric barrier discharge plasma needle is presented. The neutral red uptake assay provides a quantitative estimation of cell viability after plasma treatment. Experimental results show that the efficiency of argon plasma for the inactivation process is very dependent on power and treatment time. A 27 W power and 120 s treatment time along with 900 standard cubic centimeter per minute Ar flow and a nozzle-to-sample separation of 3 mm are the best parameters of the process. According to the argon emission spectra of the plasma jet and the optical microscope images of the A549 cells after plasma treatment, it is concluded that the reactive species (for example, OH and O) in the argon plasma play a major role in the cell deactivation.

  14. Dynamics of keratin assembly: exogenous type I keratin rapidly associates with type II keratin in vivo

    PubMed Central

    1993-01-01

    Keratin intermediate filaments (IF) are obligate heteropolymers containing equal amounts of type I and type II keratin. We have previously shown that microinjected biotinylated type I keratin is rapidly incorporated into endogenous bundles of keratin IF (tonofilaments) of PtK2 cells. In this study we show that the earliest steps in the assembly of keratin subunits into tonofilaments involve the extremely rapid formation of discrete aggregates of microinjected keratin. These are seen as fluorescent spots containing both type I and type II keratins within 1 min post-injection as determined by double label immunofluorescence. These observations suggest that endogenous type II keratin subunits can be rapidly mobilized from their endogenous state to form complexes with the injected type I protein. Furthermore, confocal microscopy and immunogold electron microscopy suggest that the type I-type II keratin spots from in close association with the endogenous keratin IF network. When the biotinylated protein is injected at concentrations of 0.3-0.5 mg/ml, the organization of the endogenous network of tonofilaments remains undisturbed during incorporation into tonofilaments. However, microinjection of 1.5-2.0 mg/ml of biotinylated type I results in significant alterations in the organization and assembly state of the endogenous keratin IF network soon after microinjection. The results of this study are consistent with the existence of a state of equilibrium between keratin subunits and polymerized keratin IF in epithelial cells, and provide further proof that IF are dynamic elements of the cytoskeleton of mammalian cells. PMID:7686161

  15. Geochemistry of the alginite and amorphous organic matter from type II-S kerogens

    USGS Publications Warehouse

    Stankiewicz, B.A.; Kruge, M.A.; Mastalerz, Maria; Salmon, G.L.

    1996-01-01

    Maceral fractions of the Type II-S kerogens from the Monterey Formation (Miocene. California. U.S.A.) and Duwi Formation (Campanian/Maastrichtian, Egypt) were separated by density gradient centrifugation. The Monterey Fm. kerogen sample was comprised chiefly of light red-fluorescing amorphous organic matter (AOM), the flash pyrolyzate of which was characterized by a predominance of alkylbenzenes, alkylthiophenes and alkylpyrroles. In contrast, the pyrolyzates of its alginite concentrate showed a highly aliphatic character, typical of this maceral, with the series of n-alkenes and n-alkanes (C6- C26) predominating. The pyrolyzate of the dominant light brown-fluorescing AOM of the Duwi Fm. kerogen had a relatively high concentration of alkylbenzenes and alkylthiophenes, while its elginite concentrate showed a more aliphatic character upon pyrolysis. There was a marked enrichment of thiophenic sulfur in the light-colored AOM of both samples (and also pyrrolic nitrogen in the case of the Monterey) relative to the alginite. The results support a bacterially-mediated, degradative origin for Type II-S amorphous organic matter, with algal remains as the primary source of the kerogen.

  16. Early photocoagulation in patients with either type I or type II diabetes.

    PubMed Central

    Ferris, F

    1996-01-01

    OBJECTIVE: To determine the benefits of early photocoagulation in patients with type I versus type II diabetes. DESIGN: One eye of each of 3,711 patients was randomly assigned to early photocoagulation; the other was assigned to deferral of photocoagulation, with follow-up visits scheduled every 4 months and photocoagulation to be carried out promptly if high-risk proliferative retinopathy developed. Patients were categorized by age and type of diabetes. MAIN OUTCOME MEASURES: Best corrected visual acuity was measured at each study visit scheduled at 4-month intervals. Stereoscopic fundus photographs were taken and evaluated at baseline, 4 months, and yearly thereafter. Retinopathy severity was assessed from fundus photographs. Severe visual loss was defined as visual acuity of worse than 5/200 for at least two consecutive study visits. RESULTS: Previously published results of the Early Treatment Diabetic Retinopathy Study (ETDRS) demonstrated a statistically significant benefit of early photocoagulation in preventing severe vision loss. Further analyses demonstrate that this benefit of early photocoagulation is greater in patients with type II diabetes than in those with type I. The relative benefit of early photocoagulation in patients with type II diabetes is also seen for other outcomes (development of high-risk proliferative retinopathy, development of the combined end point [severe visual loss or vitrectomy], development of moderate visual loss, or development of legal blindness). The patients most likely to benefit from early photocoagulation had severe nonproliferative retinopathy or early proliferative retinopathy. Analyses from the Diabetic Retinopathy Study confirm the relative benefit of scatter photocoagulation for type II patients. Because of the high correlation between age and type of diabetes, analyses sub-grouped by age show similar results. CONCLUSION: These analyses suggest that patients with type II diabetes, or older patients with diabetes

  17. Tomatidine inhibits invasion of human lung adenocarcinoma cell A549 by reducing matrix metalloproteinases expression.

    PubMed

    Yan, Kun-Huang; Lee, Liang-Ming; Yan, Shao-Han; Huang, Hsiang-Ching; Li, Chia-Chen; Lin, Hui-Ting; Chen, Pin-Shern

    2013-05-25

    Tomatidine is an aglycone of glycoalkaloid tomatine in tomato. Tomatidine is found to possess anti-inflammatory properties and may serve as a chemosensitizer in multidrug-resistant tumor cells. However, the effect of tomatidine on cancer cell metastasis remains unclear. This study examines the effect of tomatidine on the migration and invasion of human lung adenocarcinoma A549 cell in vitro. The data demonstrates that tomatidine does not effectively inhibit the viability of A549 cells. When treated with non-toxic doses of tomatidine, cell invasion is markedly suppressed by Boyden chamber invasion assay, while cell migration is not affected. Tomatidine reduces the mRNA level of matrix metalloproteinase-2 (MMP-2), MMP-9 and increases the expression of reversion-inducing cysteine-rich protein with kazal motifs (RECK), as well as tissue inhibitor of metalloproteinase-1 (TIMP-1). The immunoblotting assays indicate that tomatidine is very effective in suppressing the phosphorylation of Akt and extracellular signal regulating kinase (ERK). In addition, tomatidine significantly decreases the nuclear level of nuclear factor kappa B (NF-κB), which suggests that tomatidine inhibits NF-κB activity. Furthermore, the treatment of inhibitors specific for PI3K/Akt (LY294002), ERK (U0126), or NF-κB (pyrrolidine dithiocarbamate) to A549 cells reduced cell invasion and MMP-2/9 expression. The results suggest that tomatidine inhibits the invasion of A549 cells by reducing the expression of MMPs. It also inhibits ERK and Akt signaling pathways and NF-κB activity. These findings demonstrate a new therapeutic potential for tomatidine in anti-metastatic therapy.

  18. TLE1 promotes EMT in A549 lung cancer cells through suppression of E-cadherin.

    PubMed

    Yao, Xin; Ireland, Shubha Kale; Pham, Tri; Temple, Brandi; Chen, Renwei; Raj, Madhwa H G; Biliran, Hector

    2014-12-12

    The Groucho transcriptional corepressor TLE1 protein has recently been shown to be a putative lung specific oncogene, but its underlying oncogenic activity in lung cancer has not been fully elucidated. In this report, we investigated whether TLE1 regulates lung cancer aggressiveness using the human lung adenocarcinoma cell line A549 as a model system. Through a combination of genetic approaches, we found that TLE1 potentiates epithelial-to-mesenchymal transition (EMT) in A549 cells in part through suppression of the tumor suppressor gene E-cadherin. Exogenous expression of TLE1 in A549 cells resulted in heightened EMT phenotypes (enhanced fibroblastoid morphology and increased cell migratory potential) and in molecular alterations characteristic of EMT (downregulation of the epithelial marker E-cadherin and upregulation of the mesenchymal marker Vimentin). Conversely, downregulation of endogenous TLE1 expression in these cells resulted in reversal of basal EMT characterized by a cuboidal-like epithelial cell phenotype, reduced cell motility, and upregulated E-cadherin expression. Mechanistic studies showed that TLE1 suppresses E-cadherin expression at the transcriptional level in part by recruiting histone deacetylase (HDAC) activity to the E-cadherin promoter. Consistently, the HDAC inhibitor TSA partially reversed the TLE1-induced E-cadherin downregulation and cell migration, suggesting a role for HDACs in TLE1-mediated transcriptional repression of E-cadherin and EMT function. These findings uncover a novel role of TLE1 in regulating EMT in A549 cells through its repressive effect on E-cadherin and provide a mechanism for TLE1 oncogenic activity in lung cancer.

  19. The common anesthetic, sevoflurane, induces apoptosis in A549 lung alveolar epithelial cells.

    PubMed

    Wei, Gui-Hua; Zhang, Juan; Liao, Da-Qing; Li, Zhuo; Yang, Jing; Luo, Nan-Fu; Gu, Yan

    2014-01-01

    Lung alveolar epithelial cells are the first barrier exposed to volatile anesthetics, such as sevoflurane, prior to reaching the targeted neuronal cells. Previously, the effects of volatile anesthetics on lung surfactant were studied primarily with physicochemical models and there has been little experimental data from cell cultures. Therefore it was investigated whether sevoflurane induces apoptosis of A549 lung epithelial cells. A549 cells were exposed to sevoflurane via a calibrated vaporizer with a 2 l/min flow in a gas‑tight chamber at 37˚C. The concentration of sevoflurane in Dulbecco's modified Eagle's medium was detected with gas chromatography. Untreated cells and cells treated with 2 µM daunorubicin hydrochloride (DRB) were used as negative and positive controls, respectively. Apoptosis factors, including the level of ATP, apoptotic‑bodies by terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling (TUNEL) assay, DNA damage and the level of caspase 3/7 were analyzed. Cells treated with sevoflurane showed a significant reduction in ATP compared with untreated cells. Effects in the DRB group were greater than in the sevoflurane group. The difference of TUNEL staining between the sevoflurane and untreated groups was statistically significant. DNA degradation was observed in the sevoflurane and DRB groups, however this was not observed in the untreated group. The sevoflurane and DRB groups induced increased caspase 3/7 activation compared with untreated cells. These results suggest that sevoflurane induces apoptosis in A549 cells. In conclusion, 5% sevoflurane induced apoptosis of A549 lung alveolar epithelial cells, which resulted in decreased cell viability, increased apoptotic bodies, impaired DNA integrality and increased levels of caspase 3/7.

  20. Fucoidan from Undaria pinnatifida induces apoptosis in A549 human lung carcinoma cells.

    PubMed

    Boo, Hye-Jin; Hyun, Jae-Hee; Kim, Sang-Cheol; Kang, Jung-Il; Kim, Min-Kyoung; Kim, Sun-Yeou; Cho, Heeyeong; Yoo, Eun-Sook; Kang, Hee-Kyoung

    2011-07-01

    Fucoidan, a sulfated polysaccharide, has various biological activities, such as anticancer, antiangiogenic and antiinflammatory effects; however, the mechanisms of action of fucoidan on anticancer activity have not been fully elucidated. The anticancer effects of fucoidan from Undaria pinnatifida on A549 human lung carcinoma cells were examined. Treatment of A549 cells with fucoidan resulted in potent antiproliferative activity. Also, some typical apoptotic characteristics, such as chromatin condensation and an increase in the population of sub-G1 hypodiploid cells, were observed. With respect to the mechanism underlying the induction of apoptosis, fucoidan reduced Bcl-2 expression, but the expression of Bax was increased in a dose-dependent manner compared with the controls. Furthermore, fucoidan induced caspase-9 activation, but decreased the level of procaspase-3. Cleavage of poly-ADP-ribose polymerase (PARP), a vital substrate of effector caspase, was found. The study further investigated the role of the MAPK and PI3K/Akt pathways with respect to the apoptotic effect of fucoidan, and showed that fucoidan activates ERK1/2 in A549 cells. Unlike ERK1/2, however, treatment with fucoidan resulted in the down-regulation of phospho-p38 expression. In addition, fucoidan resulted in the down-regulation of phospho-PI3K/Akt. Together, these results indicate that fucoidan induces apoptosis of A549 human lung cancer cells through down-regulation of p38, PI3K/Akt, and the activation of the ERK1/2 MAPK pathway.

  1. The biophysical property of A549 cells transferred by VEGF-D.

    PubMed

    Wang, Zhen; Wu, Xiu-Li; Wang, Xu; Tian, Hong-Xia; Chen, Zhi-Hong; Li, Yang-Qiu

    2014-01-01

    Vascular endothelial growth factor-D (VEGF-D) together with VEGF-C is considered to be associated with lymphangiogenesis and angiogenesis and involve in tumorization. This study aims to investigate the influence of exogenous VEGF-D gene on the biophysical property of cell surface of lung adenocarcinoma cell line. A panel of lung adenocarcinoma cell lines were examined the expression of VEGF-D and VEGF-C by real-time PCR. The VEGF-D recombinant plasmid containing enhanced green fluorescence protein (EGFP) was constructed and transfected to the cell line with no expression of VEGF-D and confirmed by real-time PCR and Western blot analysis. Topographic images of cells were obtained by using atomic force microscope (AFM) in contact mode. Unlike VEGF-C, VEGF-D was found to have a very low expression or undetectable expression in lung adenocarcinoma cell lines. The VEGF-D recombinant plasmid had been constructed successfully and was transferred into the human lung adenocarcinoma cell line A549 cells which had no endogenous expression of VEGF-D, and exogenous VEGF-D could be detected in mRNA and protein expression levels in the gene modified cells, while the VEGF-C gene expression had no change after VEGF-D transfection. After transfection, the irregular microspikes or nano clusters could observe on the surface of A549 cells, and VEGF-D transfected A549 cells became more rigid. The exogenous VEGF-D gene might cause the remarkable biophysical architectural changes in the A549 cells, which might as a novel biomarker for evaluation of its biological function.

  2. Oxidative stress mediated apoptosis induced by nickel ferrite nanoparticles in cultured A549 cells.

    PubMed

    Ahamed, Maqusood; Akhtar, Mohd Javed; Siddiqui, Maqsood A; Ahmad, Javed; Musarrat, Javed; Al-Khedhairy, Abdulaziz A; AlSalhi, Mohamad S; Alrokayan, Salman A

    2011-05-10

    Due to the interesting magnetic and electrical properties with good chemical and thermal stabilities, nickel ferrite nanoparticles are being utilized in many applications including magnetic resonance imaging, drug delivery and hyperthermia. Recent studies have shown that nickel ferrite nanoparticles produce cytotoxicity in mammalian cells. However, there is very limited information concerning the toxicity of nickel ferrite nanoparticles at the cellular and molecular level. The aim of this study was to investigate the cytotoxicity, oxidative stress and apoptosis induction by well-characterized nickel ferrite nanoparticles (size 26 nm) in human lung epithelial (A549) cells. Nickel ferrite nanoparticles induced dose-dependent cytotoxicity in A549 cells demonstrated by MTT, NRU and LDH assays. Nickel ferrite nanoparticles were also found to induce oxidative stress evidenced by generation of reactive oxygen species (ROS) and depletion of antioxidant glutathione (GSH). Further, co-treatment with the antioxidant L-ascorbic acid mitigated the ROS generation and GSH depletion due to nickel ferrite nanoparticles suggesting the potential mechanism of oxidative stress. Quantitative real-time PCR analysis demonstrated that following the exposure of A549 cells to nickel ferrite nanoparticles, the level of mRNA expressions of cell cycle checkpoint protein p53 and apoptotic proteins (bax, caspase-3 and caspase-9) were significantly up-regulated, whereas the expression of anti-apoptotic proteins (survivin and bcl-2) were down-regulated. Moreover, activities of caspase-3 and caspase-9 enzymes were also significantly higher in nickel ferrite nanoparticles exposed cells. To the best of our knowledge this is the first report showing that nickel ferrite nanoparticles induced apoptosis in A549 cells through ROS generation and oxidative stress via p53, survivin, bax/bcl-2 and caspase pathways.

  3. Effects of tanshinone nanoemulsion and extract on inhibition of lung cancer cells A549.

    PubMed

    Lee, W D; Liang, Y J; Chen, B H

    2016-12-09

    Danshen (Salvia miltiorrhiza), a Chinese medicinal herb, consists of several functional components including tanshinones responsible for prevention of several chronic diseases. This study intends to prepare tanshinone extract and nanoemulsion from danshen and determine their inhibition effect on lung cancer cells A549. A highly stable tanshinone nanoemulsion composed of Capryol 90, Tween 80, ethanol and deionized water with the mean particle size of 14.2 nm was successfully prepared. Tanshinone nanoemulsion was found to be more effective in inhibiting A549 proliferation than tanshinone extract. Both nanoemulsion and extract could penetrate into cytoplasm through endocytosis, with the former being more susceptible than the latter. A dose-dependent response in up-regulation of p-JNK, p53 and p21 and down-regulation of CDK2, cyclin D1 and cyclin E1 expressions was observed with the cell cycle arrested at G0/G1 phase. The cellular microcompartment change of A549 was also investigated. The study demonstrated that tanshinone nanoemulsion may be used as a botanic drug for treatment of lung cancer.

  4. Sinomenine inhibits A549 human lung cancer cell invasion by mediating the STAT3 signaling pathway

    PubMed Central

    Jiang, Shulong; Gao, Yebo; Hou, Wei; Liu, Rui; Qi, Xin; Xu, Xia; Li, Jie; Bao, Yanju; Zheng, Honggang; Hua, Baojin

    2016-01-01

    Increasing evidence suggests that the failure of lung cancer treatment may occur as a result of tumor invasion and metastasis. Signal transducer and activator of transcription 3 (STAT3), an epithelial-mesenchymal transition-inducing transcription factor, is a key signaling molecule involved in the proliferation, apoptosis, invasion and metastasis of tumor cells. Sinomenine is an alkaloid compound with an antineoplastic potential against a variety of cancer cells. The aim of the present study was to assess the antitumor mechanisms of sinomenine in the A549 human lung cancer cell line. The results demonstrated that sinomenine manifested dose-dependent cytotoxicity and induced apoptosis in A549 cells. The protein expression of Janus kinase 2, STAT3, phosphorylated-STAT3, Snail, N-cadherin and vimentin decreased in sinomenine-treated cells, while E-cadherin protein expression increased. The regulation of STAT3, N-cadherin and E-cadherin by sinomenine was further confirmed by reverse transcription-quantitative polymerase chain reaction and immunofluorescent staining. It was demonstrated that sinomenine exerts inhibitory effects on A549 human lung cancer cell invasion, possibly through the inhibition of STAT3 signaling. These results provide a novel insight into the role of sinomenine in the treatment of non-small cell lung cancer. PMID:27446441

  5. Wnt/{beta}-catenin signaling regulates cancer stem cells in lung cancer A549 cells

    SciTech Connect

    Teng, Ying; Wang, Xiuwen; Wang, Yawei; Ma, Daoxin

    2010-02-12

    Wnt/{beta}-catenin signaling plays an important role not only in cancer, but also in cancer stem cells. In this study, we found that {beta}-catenin and OCT-4 was highly expressed in cisplatin (DDP) selected A549 cells. Stimulating A549 cells with lithium chloride (LiCl) resulted in accumulation of {beta}-catenin and up-regulation of a typical Wnt target gene cyclin D1. This stimulation also significantly enhanced proliferation, clone formation, migration and drug resistance abilities in A549 cells. Moreover, the up-regulation of OCT-4, a stem cell marker, was observed through real-time PCR and Western blotting. In a reverse approach, we inhibited Wnt signaling by knocking down the expression of {beta}-catenin using RNA interference technology. This inhibition resulted in down-regulation of the Wnt target gene cyclin D1 as well as the proliferation, clone formation, migration and drug resistance abilities. Meanwhile, the expression of OCT-4 was reduced after the inhibition of Wnt/{beta}-catenin signaling. Taken together, our study provides strong evidence that canonical Wnt signaling plays an important role in lung cancer stem cell properties, and it also regulates OCT-4, a lung cancer stem cell marker.

  6. PVM/MA-shelled selol nanocapsules promote cell cycle arrest in A549 lung adenocarcinoma cells

    PubMed Central

    2014-01-01

    Background Selol is an oily mixture of selenitetriacylglycerides that was obtained as a semi-synthetic compound containing selenite. Selol is effective against cancerous cells and less toxic to normal cells compared with inorganic forms of selenite. However, Selol’s hydrophobicity hinders its administration in vivo. Therefore, the present study aimed to produce a formulation of Selol nanocapsules (SPN) and to test its effectiveness against pulmonary adenocarcinoma cells (A549). Results Nanocapsules were produced through an interfacial nanoprecipitation method. The polymer shell was composed of poly(methyl vinyl ether-co-maleic anhydride) (PVM/MA) copolymer. The obtained nanocapsules were monodisperse and stable. Both free Selol (S) and SPN reduced the viability of A549 cells, whereas S induced a greater reduction in non-tumor cell viability than SPN. The suppressor effect of SPN was primarily associated to the G2/M arrest of the cell cycle, as was corroborated by the down-regulations of the CCNB1 and CDC25C genes. Apoptosis and necrosis were induced by Selol in a discrete percentage of A549 cells. SPN also increased the production of reactive oxygen species, leading to oxidative cellular damage and to the overexpression of the GPX1, CYP1A1, BAX and BCL2 genes. Conclusions This study presents a stable formulation of PVM/MA-shelled Selol nanocapsules and provides the first demonstration that Selol promotes G2/M arrest in cancerous cells. PMID:25149827

  7. Effects of tanshinone nanoemulsion and extract on inhibition of lung cancer cells A549

    NASA Astrophysics Data System (ADS)

    Lee, W. D.; Liang, Y. J.; Chen, B. H.

    2016-12-01

    Danshen (Salvia miltiorrhiza), a Chinese medicinal herb, consists of several functional components including tanshinones responsible for prevention of several chronic diseases. This study intends to prepare tanshinone extract and nanoemulsion from danshen and determine their inhibition effect on lung cancer cells A549. A highly stable tanshinone nanoemulsion composed of Capryol 90, Tween 80, ethanol and deionized water with the mean particle size of 14.2 nm was successfully prepared. Tanshinone nanoemulsion was found to be more effective in inhibiting A549 proliferation than tanshinone extract. Both nanoemulsion and extract could penetrate into cytoplasm through endocytosis, with the former being more susceptible than the latter. A dose-dependent response in up-regulation of p-JNK, p53 and p21 and down-regulation of CDK2, cyclin D1 and cyclin E1 expressions was observed with the cell cycle arrested at G0/G1 phase. The cellular microcompartment change of A549 was also investigated. The study demonstrated that tanshinone nanoemulsion may be used as a botanic drug for treatment of lung cancer.

  8. NADPH:cytochrome c (P450) reductase activates tirapazamine (SR4233) to restore hypoxic and oxic cytotoxicity in an aerobic resistant derivative of the A549 lung cancer cell line

    PubMed Central

    Saunders, M P; Patterson, A V; Chinje, E C; Harris, A L; Stratford, I J

    2000-01-01

    Tirapazamine (TPZ, SR4233, WIN 59075) is a bioreductive drug that is activated in regions of low oxygen tension to a cytotoxic radical intermediate. This labile metabolite shows high selective toxicity towards hypoxic cells, such as those found in solid tumours. Under aerobic conditions, redox cycling occurs with subsequent generation of superoxide radicals, which are also cytotoxic. NADPH:cytochrome c (P450) reductase (P450R) is a one-electron reducing enzyme that efficiently activates TPZ. Recently a derivative of the A549 non-small cell lung cancer cell line (A549c50) was generated that showed substantially reduced P450R activity compared to its parental line (Elwell et al (1997) Biochem Pharmacol54: 249–257). Here, it is demonstrated that the A549c50 cells are markedly more resistant to TPZ under both aerobic and hypoxic conditions. In addition, these cells have a dramatically impaired ability to metabolize TPZ to its two-electron reduction product, SR4317, under hypoxic conditions when compared to wild-type cells. P450R activity in the A549c50 cells was reintroduced to similar levels as that seen in the parental A549 cells by transfection of the full-length cDNA for human P450R. These P450R over-expressing cells exhibit restored sensitivity to TPZ under both aerobic and hypoxic conditions, comparable to that found in the original parental A549 cells. Further, the ability of the transfected cells to metabolize TPZ to SR4317 under hypoxic conditions is also shown to be restored. This provides further evidence that P450R can play an important role in the activation, metabolism and toxicity of this lead bioreductive drug. © 2000 Cancer Research Campaign PMID:10682679

  9. Bauhinia variegata (Caesalpiniaceae) leaf extract: An effective treatment option in type I and type II diabetes.

    PubMed

    Kulkarni, Yogesh A; Garud, Mayuresh S

    2016-10-01

    Among various metabolic disorders, diabetes mellitus is one of the most common disorder. Present study was designed to evaluate the effectiveness of aqueous extract of Bauhinia variegata leaves (AE) in animal models of type I and type II diabetes. Type I diabetes was induced by streptozotocin at the dose of 55mg/kg (i.p.) in male Sprague Dawley rats while type II diabetes was induced by high fat diet and streptozotocin at the dose of 35mg/kg (i.p.). Diabetic animals were treated with AE at the dose of 250, 500 and 1000mg/kg. Glipizide (5mg/kg) was used as standard treatment drug. Treatment was given for 28days. Parameters evaluated were body weight, plasma glucose, cholesterol, triglyceride, aspartate aminotransferase, alanine transaminase, alkaline phosphatase, total proteins, albumin, creatinine and bun urea nitrogen. In type II diabetes, high density lipoprotein levels in plasma and plasma insulin level were also evaluated. Histopathological study of pancreases were carried out in type I study. AE showed significant decrease in plasma glucose significantly. AE was also found to decrease cholesterol, triglyceride, creatinine and blood urea nitrogen level in both types of diabetes. AE did not show any significant effect on plasma levels of aspartate aminotransferase, alanine transaminase, alkaline phosphatase. AE was found to increase the albumin and total protein levels. Histopathological study showed that AE decreases the necrotic changes in the pancreatic tissue. Aqueous extract of B. variegata leaves was found effective in treatment of both type I and type II diabetes.

  10. Flavonoids from Gynostemma pentaphyllum exhibit differential induction of cell cycle arrest in H460 and A549 cancer cells.

    PubMed

    Tsui, Ko-Chung; Chiang, Tzu-Hsuan; Wang, Jinn-Shyan; Lin, Li-Ju; Chao, Wei-Chih; Chen, Bing-Huei; Lu, Jyh-Feng

    2014-10-31

    Flavonoids, containing mainly kaempferol rhamnohexoside derivatives, were extracted from Gynostemma pentaphyllum (G. pentaphyllum) and their potential growth inhibition effects against H460 non-small cell lung cancer cells was explored and compared to that on A549 cells. The extracted flavonoids were found to exhibit antiproliferation effects against H460 cells (IC50 = 50.2 μg/mL), although the IC50 of H460 is 2.5-fold that of A549 cells (IC50 = 19.8 μg/mL). Further investigation revealed that H460 cells are more susceptible to kaempferol than A549, whereas A549 cell growth is better inhibited by kaempferol rhamnohexoside derivatives as compared with H460. In addition, flavonoids from G. pentaphyllum induced cell cycle arrest at both S and G2/M phases with concurrent modulated expression of the cellular proteins cyclin A, B, p53 and p21 in A549 cells, but not H460. On the contrary, apoptosis and concomitant alteration in balance of BCL-2 and BAX expression as well as activation of caspase-3 were equally affected between both cells by flavonoid treatment. These observations strongly suggest the growth inhibition discrepancy between H460 and A549 following flavonoid treatment can be attributed to the lack of cell cycle arrest in H460 cells and the differences between H460 and A549 cells may serve as contrasting models for further mechanistic investigations.

  11. Modeling fluid dynamics on type II quantum computers

    NASA Astrophysics Data System (ADS)

    Scoville, James; Weeks, David; Yepez, Jeffrey

    2006-03-01

    A quantum algorithm is presented for modeling the time evolution of density and flow fields governed by classical equations, such as the diffusion equation, the nonlinear Burgers equation, and the damped wave equation. The algorithm is intended to run on a type-II quantum computer, a parallel quantum computer consisting of a lattice of small type I quantum computers undergoing unitary evolution and interacting via information interchanges represented by an orthogonal matrices. Information is effectively transferred between adjacent quantum computers over classical communications channels because of controlled state demolition following local quantum mechanical qubit-qubit interactions within each quantum computer. The type-II quantum algorithm presented in this paper describes a methodology for generating quantum logic operations as a generalization of classical operations associated with finite-point group symmetries. The quantum mechanical evolution of multiple qubits within each node is described. Presented is a proof that the parallel quantum system obeys a finite-difference quantum Boltzman equation at the mesoscopic scale, leading in turn to various classical linear and nonlinear effective field theories at the macroscopic scale depending on the details of the local qubit-qubit interactions.

  12. On the Intrinsic Diversity of Type II-Plateau Supernovae

    NASA Astrophysics Data System (ADS)

    Pejcha, Ondřej; Prieto, Jose L.

    2015-06-01

    Hydrogen-rich Type II-Plateau supernovae (SNe) exhibit correlations between the plateau luminosity {L}{pl}, the nickel mass {M}{Ni}, the explosion energy {E}{exp}, and the ejecta mass {M}{ej}. Using our global, self-consistent, multi-band model of nearby well-observed SNe, we find that the covariances of these quantities are strong and that the confidence ellipsoids are oriented in the direction of the correlations, which reduces their significance. By proper treatment of the covariance matrix of the model, we discover a significant intrinsic width to the correlations between {L}{pl}, {E}{exp} and {M}{Ni}, where the uncertainties due to the distance and the extinction dominate. For fixed {E}{exp}, the spread in {M}{Ni} is about 0.25 dex, which we attribute to the differences in the progenitor internal structure. We argue that the effects of incomplete γ-ray trapping are not important in our sample. Similarly, the physics of the Type II-Plateau SN light curves leads to inherently degenerate estimates of {E}{exp} and {M}{ej}, which makes their observed correlation weak. Ignoring the covariances of SN parameters or the intrinsic width of the correlations causes significant biases in the slopes of the fitted relations. Our results imply that Type II-Plateau SN explosions are not described by a single physical parameter or a simple one-dimensional trajectory through the parameter space, but instead reflect the diversity of the core and surface properties of their progenitors. We discuss the implications for the physics of the explosion mechanism and possible future observational constraints.

  13. Effect of the type-I to type-II Weyl semimetal topological transition on superconductivity

    NASA Astrophysics Data System (ADS)

    Li, Dingping; Rosenstein, Baruch; Shapiro, B. Ya.; Shapiro, I.

    2017-03-01

    The influence of recently discovered topological transition between type-I and type-II Weyl semimetals on superconductivity is considered. A set of Gorkov equations for weak superconductivity in Weyl semimetal under topological phase transition is derived and solved. The critical temperature and superconducting gap both have spikes in the transition point as functions of the tilt parameter of the Dirac cone determined, in turn, by the material parameters like pressure. The spectrum of superconducting excitations is different in two phases: The sharp cone pinnacle is characteristic for type I, while two parallel almost flat bands, are formed in type II. Spectral density is calculated on both sides of transition to demonstrate the different weights of the bands. The superconductivity thus can be used as a clear indicator for the topological transformation. Results are discussed in the light of recent experiments.

  14. Tumor-targeting magnetic lipoplex delivery of short hairpin RNA suppresses IGF-1R overexpression of lung adenocarcinoma A549 cells in vitro and in vivo

    SciTech Connect

    Wang, Chunmao; Ding, Chao; Kong, Minjian; Dong, Aiqiang; Qian, Jianfang; Jiang, Daming; Shen, Zhonghua

    2011-07-08

    Highlights: {yields} We compared lipofection with magnetofection about difference of transfection efficiency on delivery a therapeutic gene in vitro and in vivo. {yields} We investigated the difference of shRNA induced by magnetofection and lipofection into A549 cell and subcutaneous tumor to knockdown IGF-1R overexpressed in A549 cell and A549 tumor. {yields} We investigated in vivo shRNA silenced IGF-1R overexpression 24, 48, and 72 h after shRNA intravenous injection into tumor-bearing mice by way of magnetofection and lipofection. {yields} Our results showed that magnetofection could achieve therapeutic gene targeted delivery into special site, which contributed to targeted gene therapy of lung cancers. -- Abstract: Liposomal magnetofection potentiates gene transfection by applying a magnetic field to concentrate magnetic lipoplexes onto target cells. Magnetic lipoplexes are self-assembling ternary complexes of cationic lipids with plasmid DNA associated with superparamagnetic iron oxide nanoparticles (SPIONs). Type1insulin-like growth factor receptor (IGF-1R), an important oncogene, is frequently overexpressed in lung cancer and mediates cancer cell proliferation and tumor growth. In this study, we evaluated the transfection efficiency (percentage of transfected cells) and therapeutic potential (potency of IGF-1R knockdown) of liposomal magnetofection of plasmids expressing GFP and shRNAs targeting IGF-1R (pGFPshIGF-1Rs) in A549 cells and in tumor-bearing mice as compared to lipofection using Lipofectamine 2000. Liposomal magnetofection provided a threefold improvement in transgene expression over lipofection and transfected up to 64.1% of A549 cells in vitro. In vitro, IGF-1R specific-shRNA transfected by lipofection inhibited IGF-1R protein by 56.1 {+-} 6% and by liposomal magnetofection by 85.1 {+-} 3%. In vivo delivery efficiency of the pGFPshIGF-1R plasmid into the tumor was significantly higher in the liposomal magnetofection group than in the

  15. Intracellular calcium promotes radioresistance of non-small cell lung cancer A549 cells through activating Akt signaling.

    PubMed

    Wang, Yiling; He, Jiantao; Zhang, Shenghui; Yang, Qingbo

    2017-03-01

    Radiotherapy is a major therapeutic approach in non-small cell lung cancer but is restricted by radioresistance. Although Akt signaling promotes radioresistance in non-small cell lung cancer, it is not well understood how Akt signaling is activated. Since intracellular calcium (Ca(2+)) could activate Akt in A549 cells, we investigated the relationship between intracellular calcium (Ca(2+)) and Akt signaling in radioresistant A549 cells by establishing radioresistant non-small cell lung cancer A549 cells. The radioresistant cell line A549 was generated by dose-gradient irradiation of the parental A549 cells. The cell viability, proliferation, and apoptosis were, respectively, assessed using the cell counting kit-8, EdU labeling, and flow cytometry analysis. The phosphorylation of Akt was evaluated by Western blotting, and the intracellular Ca(2+) concentration was assessed by Fluo 4-AM. The radioresistant A549 cells displayed mesenchymal morphology. After additional irradiation, the radioresistant A549 cells showed decreased cell viability and proliferation but increased apoptosis. Moreover, the intracellular Ca(2+) concentration and the phosphorylation level on the Akt473 site in radioresistant A549 cells were higher than those in original cells, whereas the percentage of apoptosis in radioresistant A549 cells was less. All these results could be reversed by verapamil. In conclusion, our study found that intracellular Ca(2+) could promote radioresistance of non-small cell lung cancer cells through phosphorylating of Akt on the 473 site, which contributes to a better understanding on the non-small cell lung cancer radioresistance, and may provide a new target for radioresistance management.

  16. Predicted continuum spectra of type II supernovae - LTE results

    NASA Technical Reports Server (NTRS)

    Shaviv, G.; Wehrse, R.; Wagoner, R. V.

    1985-01-01

    The continuum spectral energy distribution of the flux emerging from type II supernovae is calculated from quasi-static radiative transfer through a power-law density gradient, assuming radiative equilibrium and LTE. It is found that the Balmer jump disappears at high effective temperatures and low densities, while the spectrum resembles that of a dilute blackbody but is flatter with a sharper cutoff at the short-wavelength end. A significant UV excess is found in all models calculated. The calculation should be considered exploratory because of significant effects which are anticipated to arise from departure from LTE.

  17. Predictive data modeling of human type II diabetes related statistics

    NASA Astrophysics Data System (ADS)

    Jaenisch, Kristina L.; Jaenisch, Holger M.; Handley, James W.; Albritton, Nathaniel G.

    2009-04-01

    During the course of routine Type II treatment of one of the authors, it was decided to derive predictive analytical Data Models of the daily sampled vital statistics: namely weight, blood pressure, and blood sugar, to determine if the covariance among the observed variables could yield a descriptive equation based model, or better still, a predictive analytical model that could forecast the expected future trend of the variables and possibly eliminate the number of finger stickings required to montior blood sugar levels. The personal history and analysis with resulting models are presented.

  18. Interaction of ultrasound with vortices in type-II superconductors

    SciTech Connect

    Sonin, E.B.

    1996-04-01

    The theory of ultrasound in the mixed state of type-II superconductors is suggested which takes into account the Magnus force on vortices, the anti-Magnus force on ions, and diamagnetism of the mixed state. The acoustic Faraday effect (rotation of polarization of the transverse ultrasonic wave propagating along vortices) is linear in the Magnus force in any regime of the flux flow for wavelengths now used in the ultrasound experiments. Therefore, in contrast to previous predictions, the Faraday effect should be looked for only in clean superconductors with a strong Magnus force. {copyright} {ital 1996 The American Physical Society.}

  19. Type II strained layer superlattice: A potential future IR solution

    NASA Astrophysics Data System (ADS)

    Tidrow, Meimei Z.

    2009-11-01

    Type II strained layer superlattice (SLS) has been making tremendous progress in the past few years funded by the Missile Defense Agency Advanced Technology Directorate (MDA/DV) under the Passive EO/IR Program. SLS has shown great potential as a future solution for infrared military systems. In this presentation, the most recent progress in SLS development will be presented. The presentation will also discuss the comparison of SLS with mercury-cadmium-telluride (HgCdTe) using Rule 07, SLS minority carrier lifetime issues, and future directions.

  20. Biologic Activity of Type I and Type II Fusobacterium nucleatum Isolates from Clinically Characterized Sites,

    DTIC Science & Technology

    1984-07-26

    journal of choice is the Journal of Periodontology . 1 ncl JACK W. VINCENT as COL, DC Microbiology Branch SGRD-UDZ (19 Jul 84) TO COL Jack W. Vincent...Activitity of Type I and Type II Manuscript for Publication Fusobacterium nucleatum Isolates From Clinically Chatacterized Sites. 6. PERFORMING ONG...120) were obtained from subgingival plaque samples taken from 27 clinically characterized sites utilizing a selec- tive culture medium. All isolates

  1. Cognitive Dysfunction Is Worse among Pediatric Patients with Bipolar Disorder Type I than Type II

    ERIC Educational Resources Information Center

    Schenkel, Lindsay S.; West, Amy E.; Jacobs, Rachel; Sweeney, John A.; Pavuluri, Mani N.

    2012-01-01

    Background: Impaired profiles of neurocognitive function have been consistently demonstrated among pediatric patients with bipolar disorder (BD), and may aid in the identification of endophenotypes across subtypes of the disorder. This study aims to determine phenotypic cognitive profiles of patients with BD Type I and II. Methods: Subjects (N =…

  2. Dielectric barrier discharge plasma in Ar/O{sub 2} promoting apoptosis behavior in A549 cancer cells

    SciTech Connect

    Huang Jun; Li Hui; Chen Wei; Lv Guohua; Wang Xingquan; Zhang Guoping; Wang Pengye; Ostrikov, Kostya; Yang Size

    2011-12-19

    The Ar/O{sub 2} plasma needle in the induction of A549 cancer cells apoptosis process is studied by means of real-time observation. The entire process of programmed cell death is observed. The typical morphological changes of A549 apoptosis are detected by 4', 6-diamidino-2-phenylindole staining, for example, chromatin condensation and nuclear fragmentation. Cell viability is determined and quantified by neutral red uptake assay, and the survival rate of A549 from Ar/O{sub 2} plasmas is presented. Further spectral analysis indicates the reactive species, including O and OH play crucial roles in the cell inactivation.

  3. Dielectric barrier discharge plasma in Ar/O2 promoting apoptosis behavior in A549 cancer cells

    NASA Astrophysics Data System (ADS)

    Huang, Jun; Li, Hui; Chen, Wei; Lv, Guo-Hua; Wang, Xing-Quan; Zhang, Guo-Ping; Ostrikov, Kostya; Wang, Peng-Ye; Yang, Si-Ze

    2011-12-01

    The Ar/O2 plasma needle in the induction of A549 cancer cells apoptosis process is studied by means of real-time observation. The entire process of programmed cell death is observed. The typical morphological changes of A549 apoptosis are detected by 4', 6-diamidino-2-phenylindole staining, for example, chromatin condensation and nuclear fragmentation. Cell viability is determined and quantified by neutral red uptake assay, and the survival rate of A549 from Ar/O2 plasmas is presented. Further spectral analysis indicates the reactive species, including O and OH play crucial roles in the cell inactivation.

  4. 77 FR 60124 - Draft Guidance for Industry on Initial Completeness Assessments for Type II Active Pharmaceutical...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-02

    ... Assessments for Type II Active Pharmaceutical Ingredient Drug Master Files Under the Generic Drug User Fee... Amendments of 2012 (GDUFA), holders of certain drug master files, namely, Type II active...

  5. [Achondrogenesis type II-hypochondrogenesis: radiological features.Case report].

    PubMed

    Delgado Carrasco, J; Casanova Morcillo, A; Zabalza Alvillos, M; Ayala Garcés, A

    2001-12-01

    We present a case of lethal dysplasia in the neonatal period. The abnormality was suspected after ultrasonography of a pregnant woman presenting weak fetal movements revealed shortening of the extremities, voluminous cranium and polyhydramnios. Clinical and radiological findings showed platyspondylic dwarfism with short extremities, narrow thorax and hydropic appearance. The infant died on the third day of life from progressive respiratory distress. In the absence of histological, chondro-osseus and molecular studies, detailed clinical and radiological studies, as well as the lethal evolution during the neonatal period, guided the diagnosis of hypochondrogenesis. This entity, together with achondrogenesis II (and other dysplasias), forms part of the same spectrum of collagen type II abnormalities produced by a defect in the gene (COL2A1) that codifies collagen II, located in chromosome 12 I(12q13.1-13.2). When a heterozygote is produced, transmission is dominant autosomal. The phenotype shows wide variation and severity depends on the mechanism and location of the mutation. The definitive diagnosis is given by cytomolecular studies, while individualization of the different entities is based on histological data from the cartilage; clinical findings and skeletal radiology serve as a guide.

  6. Sodium orthovanadate affects growth of some human epithelial cancer cells (A549, HTB44, DU145).

    PubMed

    Klein, Andrzej; Holko, Przemyslaw; Ligeza, Janusz; Kordowiak, Anna M

    2008-01-01

    Within the concentration range of 1-20 microM, orthovanadate (Na3VO4) demonstrated a time and dose-dependent inhibition of autocrine growth of the human carcinoma cell lines A549 (lung), HTB44 (kidney) and DU145 (prostate), as compared to appropriate controls (without Na3VO4). The investigation was conducted by two methods: staining with N-hexa-methylpararosaniline (crystal violet=CV) or bromide3-(4,5-dimethyltio-azo-2)-2,5-diphenyl-tetrazole (MTT). In 5, 10 and 20 microM of Na3VO4 in serum-free medium, the mean values of these two tests for A549 were approximately 40%, 45% or 65% as compared to the appropriate controls. HTB44 had the greatest opportunity (statistically insignificant) at lower vanadium concentrations (up to 10 microM), whereas at 20 microM growth inhibition of these cells was approximately 50% of the controls. DU145 showed approximately 33%, 65% and 98% growth inhibition for 5, 10 and 20 microM of Na3VO4, respectively Additionally, hypothetical curves obtained by a MANOVA test based on the CV results after 72 h incubation with Na3VO4 in serum-free medium, and an example of a time-dependent effect of Na3VO4 on A549 cells, were also presented. Sodium orthovanadate was also examined for its cytotoxic capabilities, especially its ability to induce tumor cell apoptosis; the results were compared with the effect of paclitaxel. The target cells were dyed by differential staining (HOECHST33258 and propidium iodide) after 3 h and 24 h (DU145) or 3 h and 72 h (A549) of incubation with the vanadium compound. Contrary to the two cancer cell lines (viable, apoptotic or necrotic in experimental conditions), the renal HTB44 cells were insensitive up to 15 microM Na3VO4 concentrations. After 3 h incubation with Na3VO4, both lung (A549) and prostate (DU145) cancer cells showed a slight but significant reduction in the percentage of viable cells, and an increased amount of apoptotic cells. In contrast to the lung cells, DU145 prostate cells after 24 h were more

  7. Identification of inositol polyphosphate 4-phosphatase type II as a novel tumor resistance biomarker in human laryngeal cancer HEp-2 cells.

    PubMed

    Kim, Jae-Sung; Yun, Hong Shik; Um, Hong-Duck; Park, Jong Kuk; Lee, Kee-Ho; Kang, Chang-Mo; Lee, Su-Jae; Hwang, Sang-Gu

    2012-11-01

    Although tumor resistance remains a significant impediment to successful radiotherapy, associated regulatory markers and detailed molecular mechanisms underlying this phenomenon are not well defined. In this study, we identified inositol polyphosphate 4-phosphatase type II (INPP4B) as a novel marker of radioresistance by systematically analyzing Unigene libraries of laryngeal cancer. INPP4B was highly expressed in radioresistant laryngeal cancer cells and was induced by treatment with either radiation or anticancer drugs in various types of cancer cells. Ectopic INPP4B overexpression increased radioresistance and anticancer drug resistance by suppressing apoptosis in HEp-2 cells. Conversely, INPP4B depletion with small interfering RNA resensitized HEp-2 as well as A549 and H1299 cells to radiation- and anticancer drug-induced apoptosis. Furthermore, radiation-induced INPP4B expression was blocked by inhibition of extracellular signal-regulated kinase (ERK). INPP4B depletion significantly attenuated radiation-induced increases in Akt phosphorylation, indicating an association of INPP4B-mediated radioresistance with Akt survival signaling. Taken together, our data suggest that ERK-dependent induction of INPP4B triggers the development of a tumor-resistance phenotype via Akt signaling and identify INPP4B as a potentially important target molecule for resolving the radioresistance of cancer cells.

  8. Type-II Bursts in Meter and Deca - Hectometer Wavelengths and Their Relation to Flares and CMEs: II

    NASA Astrophysics Data System (ADS)

    Prakash, O.; Umapathy, S.; Shanmugaraju, A.; Pappa Kalaivani, P.; Vršnak, Bojan

    2010-09-01

    A study of the relationship between 38 type-II bursts recorded in meter and deca-hectometer (hereinafter m and DH) wavelength range and the associated flares and CMEs observed during the years 2000 - 2005 was carried out by Prakash et al. (2009). These events were divided into two classes: i) Class I, representing events where DH-type-II bursts are not a continuation of m-type-II bursts and ii) Class II, where DH-type-II bursts are a continuation of m-type-II bursts. In the present work, we extend the analysis of this sample of 38 events in three different steps: i) statistical properties of m- and DH-type-II bursts; ii) analysis of time lags between onsets of flares and CMEs associated with type-II bursts; and iii) statistical properties and relation between flares and CMEs of Class I and Class II events. We found a significant difference between the properties of m- and DH-type-II bursts of Class I and Class II events. For example, there are significant differences in starting and ending frequencies, bandwidth and speed. From the time delay analysis, we found the following. i) In 64% of Class I events, flares start after the onset of CMEs and the remaining 36% of flares start before the onset of CMEs. On the other hand, in the case of Class II events, the values are 83% and 17%, respectively. ii) The difference between the mean values of delay between flare start and DH start has high statistical significance (probability P of null hypothesis <1%). The time delays between the start of m-type-II burst and the CME onset are considerably larger for Class I events ( P=7%) than Class II events. iii) There are notable differences in: (a) delay between the flare and CME onset times ( P<1%); (b) flare rise time of Class I and Class II events ( P<5%). iv) While the flare rise time is well correlated with the lag between the flare start and the CME onset in Class I events, there is no such correlation for Class II events.

  9. A-current and type I/type II transition determine collective spiking from common input.

    PubMed

    Barreiro, Andrea K; Thilo, Evan L; Shea-Brown, Eric

    2012-09-01

    The mechanisms and impact of correlated, or synchronous, firing among pairs and groups of neurons are under intense investigation throughout the nervous system. A ubiquitous circuit feature that can give rise to such correlations consists of overlapping, or common, inputs to pairs and populations of cells, leading to common spike train responses. Here, we use computational tools to study how the transfer of common input currents into common spike outputs is modulated by the physiology of the recipient cells. We focus on a key conductance, g(A), for the A-type potassium current, which drives neurons between "type II" excitability (low g(A)), and "type I" excitability (high g(A)). Regardless of g(A), cells transform common input fluctuations into a tendency to spike nearly simultaneously. However, this process is more pronounced at low g(A) values. Thus, for a given level of common input, type II neurons produce spikes that are relatively more correlated over short time scales. Over long time scales, the trend reverses, with type II neurons producing relatively less correlated spike trains. This is because these cells' increased tendency for simultaneous spiking is balanced by an anticorrelation of spikes at larger time lags. These findings extend and interpret prior findings for phase oscillators to conductance-based neuron models that cover both oscillatory (superthreshold) and subthreshold firing regimes. We demonstrate a novel implication for neural signal processing: downstream cells with long time constants are selectively driven by type I cell populations upstream and those with short time constants by type II cell populations. Our results are established via high-throughput numerical simulations and explained via the cells' filtering properties and nonlinear dynamics.

  10. Type-II Weyl cone transitions in driven semimetals

    NASA Astrophysics Data System (ADS)

    Chan, Ching-Kit; Oh, Yun-Tak; Han, Jung Hoon; Lee, Patrick A.

    2016-09-01

    Periodically driven systems provide tunable platforms to realize interesting Floquet topological phases and phase transitions. In electronic systems with Weyl dispersions, the band crossings are topologically protected even in the presence of time-periodic perturbations. This robustness permits various routes to shift and tilt the Weyl spectra in the momentum and energy space using circularly polarized light of sufficient intensity. We show that type-II Weyl fermions, in which the Weyl dispersions are tilted with the appearance of pocketlike Fermi surfaces, can be induced in driven Dirac semimetals and line node semimetals. Under a circularly polarized drive, both semimetal systems immediately generate Weyl node pairs whose types can be further controlled by the driving amplitude and direction. The resultant phase diagrams demonstrate experimental feasibilities.

  11. Exotic dual of type II double field theory

    NASA Astrophysics Data System (ADS)

    Bergshoeff, Eric A.; Hohm, Olaf; Riccioni, Fabio

    2017-04-01

    We perform an exotic dualization of the Ramond-Ramond fields in type II double field theory, in which they are encoded in a Majorana-Weyl spinor of O (D , D). Starting from a first-order master action, the dual theory in terms of a tensor-spinor of O (D , D) is determined. This tensor-spinor is subject to an exotic version of the (self-)duality constraint needed for a democratic formulation. We show that in components, reducing O (D , D) to GL (D), one obtains the expected exotically dual theory in terms of mixed Young tableaux fields. To this end, we generalize exotic dualizations to self-dual fields, such as the 4-form in type IIB string theory.

  12. Feeding problems and malnutrition in spinal muscular atrophy type II.

    PubMed

    Messina, Sonia; Pane, Marika; De Rose, Paola; Vasta, Isabella; Sorleti, Domenica; Aloysius, Annie; Sciarra, Federico; Mangiola, Fortunato; Kinali, Maria; Bertini, Enrico; Mercuri, Eugenio

    2008-05-01

    The aim of the study was to conduct a survey using a dedicated questionnaire to assess feeding difficulties and weight gain in a population of 122 Spinal Muscular Atrophy (SMA) type II patients, aged between 1 and 47 years. All the answers were entered in a database and were analysed subdividing the cohort into age groups (1-5, 6-10, 11-14, 15-19, 20-29, and 30-50 years). Six out of our 122 patients (5%), all younger than 11 years, had weights more than 2SD above the median for age matched controls, whilst 45 (37%) had weights less than 2SD below the median. Chewing difficulties were reported in 34 of the 122 patients (28%) and limitation in the ability to open the mouth in 36 (30%) and both were increasingly more frequent with age. Swallowing difficulties were reported in 30 patients (25%). The results of our survey suggest that a number of patients with SMA type II have limited jaw opening, and chewing and swallowing difficulties. Our findings raise a few issues concerning standards of care that should be implemented in the monitoring and management of feeding difficulties and weight gain.

  13. Model light curves of linear Type II supernovae

    SciTech Connect

    Swartz, D.A.; Wheeler, J.C.; Harkness, R.P. )

    1991-06-01

    Light curves computed from hydrodynamic models of supernova are compared graphically with the average observed B and V-band light curves of linear Type II supernovae. Models are based on the following explosion scenarios: carbon deflagration within a C + O core near the Chandrasekhar mass, electron-capture-induced core collapse of an O-Ne-Mg core of the Chandrasekhar mass, and collapse of an Fe core in a massive star. A range of envelope mass, initial radius, and composition is investigated. Only a narrow range of values of these parameters are consistent with observations. Within this narrow range, most of the observed light curve properties can be obtained in part, but none of the models can reproduce the entire light curve shape and absolute magnitude over the full 200 day comparison period. The observed lack of a plateau phase is explained in terms of a combination of small envelope mass and envelope helium enhancement. The final cobalt tail phase of the light curve can be reproduced only if the mass of explosively synthesized radioactive Ni-56 is small. The results presented here, in conjunction with the observed homogeneity among individual members of the supernova subclass, argue favorably for the O-Ne-Mg core collapse mechanism as an explanation for linear Type II supernovae. The Crab Nebula may arisen from such an explosion. Carbon deflagrations may lead to brighter events like SN 1979C. 62 refs.

  14. Type II intermediate-luminosity optical transients (ILOTs)

    NASA Astrophysics Data System (ADS)

    Kashi, Amit; Soker, Noam

    2017-01-01

    We propose that in a small fraction of intermediate luminosity optical transients (ILOTs) powered by a strongly interacting binary system, the ejected mass in the equatorial plane can block the central source from our line of sight. We can therefore observe only radiation that is reprocessed by polar outflow, much as in type II active galactic nuclei (AGN). An ejection of M_ej,e=10^{-4} M_⊙ (1 M_⊙) at 30 degrees from the equatorial plane and at a velocity of v_e = 100 {km} {s}^{-1} will block the central source in the NIR for about 5 years (500 years). During that period of time the object might disappear in the visible band, and be detected only in the IR band due to polar dust. We raise the possibility that the recently observed disappearance of a red giant in the visible, designated N6946-BH1, is a type II ILOT rather than a failed supernova. For this case we estimate that the ejected mass in the polar direction was M_ej,p≈ 10^{-3} M_⊙. Our scenario predicts that this event should reinstate its visible emission in several decades.

  15. Isolation and molecular characterization of type I and type II feline coronavirus in Malaysia

    PubMed Central

    2012-01-01

    Background Feline infectious peritonitis virus (FIPV) and feline enteric coronavirus (FECV) are two important coronaviruses of domestic cat worldwide. Although FCoV is prevalent among cats; the fastidious nature of type I FCoV to grow on cell culture has limited further studies on tissue tropism and pathogenesis of FCoV. While several studies reported serological evidence for FCoV in Malaysia, neither the circulating FCoV isolated nor its biotypes determined. This study for the first time, describes the isolation and biotypes determination of type I and type II FCoV from naturally infected cats in Malaysia. Findings Of the total number of cats sampled, 95% (40/42) were RT-PCR positive for FCoV. Inoculation of clinical samples into Crandell feline kidney cells (CrFK), and Feline catus whole fetus-4 cells (Fcwf-4), show cytopathic effect (CPE) characterized by syncytial cells formation and later cell detachment. Differentiation of FCoV biotypes using RT-PCR assay revealed that, 97.5% and 2.5% of local isolates were type I and type II FCoV, respectively. These isolates had high sequence homology and phylogenetic similarity with several FCoV isolates from Europe, South East Asia and USA. Conclusions This study reported the successful isolation of local type I and type II FCoV evident with formation of cytopathic effects in two types of cell cultures namely the CrFK and Fcwf-4 , where the later cells being more permissive. However, the RT-PCR assay is more sensitive in detecting the antigen in suspected samples as compared to virus isolation in cell culture. The present study indicated that type I FCoV is more prevalent among cats in Malaysia. PMID:23171743

  16. Supernova 1993J as a spectroscopic link between type II and type Ib supernovae

    NASA Technical Reports Server (NTRS)

    Swartz, D. A.; Clocchiatti, A.; Benjamin, R.; Lester, D. F.; Wheeler, J. C.

    1993-01-01

    Supernova 1993J in the nearby galaxy M81 is one of the closest - and hence brightest - supernovae to be witnessed this century. The early spectrum of SN1993J showed the characteristic hydrogen signature of type II supernovae, but its subsequent evolution is atypical for this class of supernova. Here we present optical and infrared spectra of SN1993J up to 43 days after outburst, which reveal the onset of the helium absorption and emission features more commonly associated with hydrogen-free type Ib supernovae. Corresponding model spectra show that the progenitor star must have possessed an unusually thin (for type II supernovae) hydrogen-rich envelope overlying a helium-rich mantle. Moreover, the supernova ejecta must have remained compositionally stratified, with little transport of the hydrogen-rich material down into the underlying helium layer or mixing of heavier elements outwards. SN1993J therefore represents a transition object between hydrogen-dominated type II supernovae, and hydrogen-free, helium-dominated type Ib supernovae.

  17. Magnetic description of the Fermi arc in type-I and type-II Weyl semimetals

    NASA Astrophysics Data System (ADS)

    Tchoumakov, Serguei; Civelli, Marcello; Goerbig, Mark O.

    2017-03-01

    We consider finite-sized interfaces of a Weyl semimetal and show that the corresponding confinement potential is similar to the application of a magnetic field. Among the numerous states, which can be labeled by indices n like in Landau levels, the n =0 surface state describes the Weyl semimetal Fermi arc at a given chemical potential. Moreover, the analogy with a magnetic field shows that an external in-plane magnetic field can be used to distort the Fermi arc and would explain some features of magnetotransport in Weyl semimetals. We derive the Fermi arc for type-I and type-II Weyl semimetals where we deal with the tilt anisotropy by the use of Lorentz boosts. In the case of type-II Weyl semimetals, this leads to many additional topologically trivial surface states at low energy. Finally, we extend the Aharonov-Casher argument and demonstrate the stability of the Fermi arc over fluctuations of the surface potential.

  18. Piezoelectricity in collagen type II fibrils measured by scanning probe microscopy

    NASA Astrophysics Data System (ADS)

    Denning, D.; Kilpatrick, J. I.; Hsu, T.; Habelitz, S.; Fertala, A.; Rodriguez, B. J.

    2014-08-01

    The converse piezoelectric effect in collagen type II fibrils, the main collagen constituent in cartilage, was investigated using piezoresponse force microscopy. The fibrils exhibited shear piezoelectric behavior similar to that previously reported in collagen type I fibrils and followed the same cantilever-fibril angle dependence present for type I. A uniform polarization directed from the amine to carboxyl termini, as seen for collagen type I, was observed in all type II fibrils studied. The shear piezoelectric coefficient, d15, however, for type II was roughly 28-32% of the value measured for type I fibrils. Possible explanations for the reduced piezoelectric coefficient of type II collagen are provided.

  19. Neutrinos from type II supernovae - The first 100 milliseconds

    NASA Technical Reports Server (NTRS)

    Myra, Eric S.; Burrows, Adam

    1990-01-01

    The collapse of a 1.17 solar mass iron core is numerically followed through infall to 100 ms past core bounce, and the emergent neutrino spectra during each phase are highlighted. It is found that, even with fairly optimistic conditions for producing a strong, sustained core-bounce shock wave, the prompt shock stalls within 9 ms of core bounce at a radius of less than 250 km. It appears that a radical change in the character of the progenitor core or in our understanding of the relevant physics of stellar collapse is needed before the direct mechanism for type II supernovae can become viable. Expanding the number of neutrino types from one to six magnifies the debilitating effect of neutrino loss on shock propagation. At shock breakout, prompt bursts of all neutrino types are observed. The luminosities of the nonelectron types show a sudden turn-on in luminosity while that of the electron neutrinos steadily increases throughout infall as a result of accelerating electron capture.

  20. Migration-stimulating factor (MSF) is over-expressed in non-small cell lung cancer and promotes cell migration and invasion in A549 cells over-expressing MSF

    SciTech Connect

    Deng, Xuefeng; Ma, Qunfeng; Zhang, Bo; Jiang, Hong; Zhang, Zhipei; Wang, Yunjie

    2013-10-15

    Migration-stimulating factor (MSF), an oncofetal truncated isoform of fibronectin, is a potent stimulator of cell invasion. However, its distribution and motogenic role in non-small cell lung cancer (NSCLC) have never been identified. In this study, real-time PCR and immunohistochemical staining (IHC) were performed to detect MSF mRNA and protein levels in tumor tissues and matched adjacent tumor-free tissues. Furthermore, to examine the effect of MSF on invasiveness, MSF was upregulated in A549 cells. The invasiveness and viability of A549 cells were then determined using a transwell migration assay and the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assays, respectively. The expression level of MSF in NSCLC tissue was markedly higher than in matched adjacent tumor-free tissue. Additionally, the level of MSF protein expression in stage III and IV NSCLC samples was higher than in stage I and II NSCLC samples. More importantly, we also demonstrated that migration and invasion of A549 cells increased substantially after upregulating MSF, although proliferation remained unchanged. Meanwhile, we found no correlation between increasing motility and invasiveness of MSF-overexpressing cells and expression levels and activities of matrix metalloprotease MMP-2 and MMP-9. Our current study shows that MSF plays a role in migration and invasion of A549 cells and suggests that MSF may be a potential biomarker of NSCLC progression. - Highlights: • MSF expression was upregulated in NSCLC and correlated with TNM stages. • MSF may be a new biomarker for NSCLC progression. • MSF promoted migration and invasion in A549 cells, independent of MMP-2/MMP-9 expression.

  1. Therapeutic effects of sorafenib on the A549/DDP human lung adenocarcinoma cell line in vitro.

    PubMed

    Chen, Xiang-Qi; Wang, Yu-Lan; Li, Zhi-Ying; Lin, Ting-Yan

    2014-07-01

    The aim of the present study was to observe the effects of sorafenib on the proliferation, apoptosis and invasion of A549/DDP cisplatin-resistant lung adenocarcinoma cells cultured in vitro. The A549/DDP cisplatin-resistant lung adenocarcinoma cell strain was cultured in vitro, the cell culture group incubated in culture medium only was set as the control group (Group S0) and the four concentration gradients of sorafenib were added to the culture groups as the experimental groups: S1, 2 µmol/l; S2, 4 µmol/l; S3, 8 µmol/l; and S4, 16 µmol/l. The MTT assay was used to determine the growth inhibition rate of the cells, which were respectively subjected to sorafenib treatment for 24, 48 and 72 h. Flow cytometry was used to determine the rate of apoptosis of cells in each group following sorafenib treatment for 72 h. Furthermore, the Transwell invasion experiment was used to determine the effect on A549/DDP cell invasion following sorafenib treatment for 24 h. Based on the MTT assay, it was found that the inhibition rates of A549/DDP cisplatin-resistant lung adenocarcinoma cells in groups S1-4 following sorafenib treatment for 24 h were 4.58±2.82, 14.93±2.62, 37.58±7.13 and 58.39±8.15%, respectively. For 48 h, inhibition rates in S1-4 were 14.98±2.93, 26.28±7.31, 63.00±3.05 and 78.84±3.96%, respectively, and for 72 h, inhibition rates were 18.80±2.82, 32.71±2.55, 75.51±4.73 and 87.50±3.36%, respectively. The difference in the inhibition rates of cells among the experimental groups for the same incubation time showed statistical significance (P<0.05). Flow cytometric analysis indicated that the rate of apoptosis in the control group was 8.88±0.81% following sorafenib treatment for 72 h, and the rates of apoptosis in groups S1-4 were, 12.84±0.24, 17.27±0.78, 21.98±0.75 and 49.67±1.38%, respectively. The rate of apoptosis in each experimental group was higher compared with that in the control group (P<0.05). The difference in the rate of apoptosis

  2. In vitro and in vivo antitumor activity of scutebarbatine A on human lung carcinoma A549 cell lines.

    PubMed

    Yang, Xiao-Kun; Xu, Ming-Yuan; Xu, Gui-Sen; Zhang, Yu-Lan; Xu, Zhao-Xia

    2014-06-25

    During our systematic study on the anticancer activities of Scutellaria barbata, scutebarbatine A (SBT-A), one of the major alkaloids in S. barbata, was found to have antitumor effects on A549 cells. Thus, we designed the present study to investigate in detail the antitumor effects of SBT-A. The cytotoxic effect of SBT-A on A549 in vitro were determined by an MTT assay and evaluated by IC50 values. Furthermore, results of Hoechst 33258 and Annexin V/PI staining assays demonstrated that SBT-A had significant antitumor effects on A549 cells via apoptosis, in a concentration-dependent manner. What's more, the mechanism was explored by western blotting, and our study revealed that SBT-A can up-regulate the expressions of cytochrome c, caspase-3 and 9, and down-regulate the levels of Bcl-2 in A549 cells. Finally, the antitumor effects of SBT-A were evaluated in vivo by using transplanted tumor nude mice, and the results confirmed that SBT-A has a notable antitumor effect on A549 cancer via mitochondria-mediated apoptosis. Collectively, our results demonstrated that SBT-A showed significant antitumor effects on A549 cells in vivo and in vitro via mitochondria-mediated apoptosis by up-regulating expressions of caspase-3 and 9, and down-regulating Bcl-2.

  3. Xanthohumol induces apoptosis and S phase cell cycle arrest in A549 non-small cell lung cancer cells

    PubMed Central

    Yong, Wai Kuan; Ho, Yen Fong; Malek, Sri Nurestri Abd

    2015-01-01

    Background: Xanthohumol, a major prenylated chalcone found in female hop plant, Humulus lupulus, was reported to have various chemopreventive and anti-cancer properties. However, its apoptotic effect on human alveolar adenocarcinoma cell line (A549) of non-small cell lung cancer (NSCLC) was unknown. Objective: This study aimed to investigate the effects of xanthohumol on apoptosis in A549 human NSCLC cells. Materials and Methods: A549 cell proliferation was determined by sulforhodamine B assay. Morphological changes of the cells were studied via phase contrast and fluorescent microscopy. Induction of apoptosis was assessed by Annexin-V fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) staining, DNA fragmentation (TUNEL) assay mitochondrial membrane potential assay, cell cycle analysis, and caspase activity studies. Results: Xanthohumol was found to decrease cell proliferation in A549 cells but had relatively low cytotoxicity on normal human lung fibroblast cell line (MRC-5). Typical cellular and nuclear apoptotic features were also observed in A549 cells treated with xanthohumol. Onset of apoptosis in A549 cells was further confirmed by externalization of phosphatidylserine, changes in mitochondrial membrane potential, and DNA fragmentation in the cells after treatment. Xanthohumol induced accumulation of cells in sub G1 and S phase based on cell cycle analysis and also increased the activities of caspase-3, -8, and -9. Conclusion: This work suggests that xanthohumol as an apoptosis inducer, may be a potent therapeutic compound for NSCLC. PMID:26664015

  4. Effects of Alpha Particle and Proton Beam Irradiation as Putative Cross-Talk between A549 Cancer Cells and the Endothelial Cells in a Co-Culture System

    PubMed Central

    Riquier, Hélène; Abel, Denis; Wera, Anne-Catherine; Heuskin, Anne-Catherine; Genard, Géraldine; Lucas, Stéphane; Michiels, Carine

    2015-01-01

    Background: High-LET ion irradiation is being more and more often used to control tumors in patients. Given that tumors are now considered as complex organs composed of multiple cell types that can influence radiosensitivity, we investigated the effects of proton and alpha particle irradiation on the possible radioprotective cross-talk between cancer and endothelial cells. Materials and Methods: We designed new irradiation chambers that allow co-culture study of cells irradiated with a particle beam. A549 lung carcinoma cells and endothelial cells (EC) were exposed to 1.5 Gy of proton beam or 1 and 2 Gy of alpha particles. Cell responses were studied by clonogenic assays and cell cycle was analyzed by flow cytometry. Gene expression studies were performed using Taqman low density array and by RT-qPCR. Results: A549 cells and EC displayed similar survival fraction and they had similar cell cycle distribution when irradiated alone or in co-culture. Both types of irradiation induced the overexpression of genes involved in cell growth, inflammation and angiogenesis. Conclusions: We set up new irradiation chamber in which two cell types were irradiated together with a particle beam. We could not show that tumor cells and endothelial cells were able to protect each other from particle irradiation. Gene expression changes were observed after particle irradiation that could suggest a possible radioprotective inter-cellular communication between the two cell types but further investigations are needed to confirm these results. PMID:25794049

  5. HTLV type I and HTLV type II infection among Indians and natives from Argentina.

    PubMed

    Bouzas, M B; Zapiola, I; Quiruelas, S; Gorvein, D; Panzita, A; Rey, J; Carnese, F P; Corral, R; Perez, C; Zala, C

    1994-11-01

    Endemic foci for HTLV-II infection have been identified in several Amerindian populations. To determine HTLV-I and/or HTLV-II infection among Amerindians living in Argentina we studied 454 sera or plasmas from Indians and natives from different areas of our country. All samples were tested by the particle agglutination technique, and positive reactions were confirmed by the immunofluorescence assay (IFA). IFA titration was used to differentiate HTLV-I and HTLV-II antibodies. Twenty-three of 222 samples (10.4%) were found positive among the Tobas Indians; 22 samples were typed as HTLV-II and 1 as HTLV-I. Antibodies for HTLV-I were found in the serum and CSF of three natives from Salta with a TSP diagnosis. No positive samples were found among 96 Mapuche Indians and 133 natives from San Luis. Our results indicate that HTLV-II is endemic among the Tobas Indians. In this study, infection by these retroviruses in Argentinian Amerindians seems to have a marked geographic distribution.

  6. The importance of type II error and falsifiability.

    PubMed

    Matsuda, Hiroyuki

    2004-01-01

    Before intergovernmental consensus under the Rio Declaration in 1992, ignorance of type I errors had been disfavored in science. However, the Precautionary Principle (PP) counsels the avoidance of type II errors, rather than of type I errors. We need a new academic code for the PP. The risk of extinction has usually been evaluated based on conservative estimates of the present population size. I define the weight of evidence as the extinction risk of Japanese vascular plants based on unbiased estimates. Catch quotas in the fisheries are usually decided by precautionary approach. I calculate the long-term yield and risk of stock collapse under a simple stock dynamics model. The weight of evidence depends on the frequency of grids with size unknown. In a few plant species, rankings based on conservative estimates have differed from rankings based on unbiased estimates. In fishery management, a catch quota based on a precautionary approach proved neither sufficient nor necessary to avoid stock collapse. The precautionary approach is one of the reasons that prevent us from maximizing a sustainable yield. We need to clarify the end-point of risks, and check whether it is necessary to adopt a PP. We can obtain the weight of evidence that is measured under unbiased estimates, while the risk based on a PP is measured under conservative estimates.

  7. Proposal for strained type II superlattice infrared detectors

    NASA Astrophysics Data System (ADS)

    Smith, D. L.; Mailhiot, C.

    1987-09-01

    It is shown that strained type II superlattices made of InAs-Ga(1-x)In(x)Sb(x) about 0.4 have favorable optical properties for infrared detection. By adjusting the layer thicknesses and the alloy composition, a wide range of wavelengths can be reached. Optical absorption calculations for a case where the cutoff wavelength is about 10 microns show that, near threshold, the absorption is as good as for the HgCdTe alloy with the same band gap. The electron effective mass is nearly isotropic and equal to 0.04 m. This effective mass should give favorable electrical properties, such as small diode tunneling currents and good mobilities, and diffusion lengths.

  8. Type II seesaw model and multilepton signatures at hadron colliders

    NASA Astrophysics Data System (ADS)

    Mitra, Manimala; Niyogi, Saurabh; Spannowsky, Michael

    2017-02-01

    We investigate multilepton signatures, arising from the decays of doubly charged and singly charged Higgs bosons in the Type II seesaw model. Depending on the vacuum expectation value of the triplet vΔ , the doubly and singly charged Higgs bosons can decay into a large variety of multilepton final states. We explore all possible decay modes corresponding to different regimes of vΔ that generate distinguishing four and five leptonic signatures. We focus on the 13 TeV Large Hadron Collider (LHC) and further extend the study to a very high energy proton-proton collider (VLHC) with a center-of-mass energy of 100 TeV. We find that a doubly charged Higgs boson of masses around 375 GeV can be discovered at immediate LHC runs. A heavier mass of 630 GeV can instead be discovered at the high-luminosity run of the LHC or at the VLHC with 30 fb-1 .

  9. Sweet taste and diet in type II diabetes.

    PubMed

    Tepper, B J; Hartfiel, L M; Schneider, S H

    1996-07-01

    The relationship between sweet taste function and dietary intake was studied in 21 patients with type II diabetes mellitus and 16 age-, weight-, and sex-matched controls. Subjects rated the sweetness intensity and pleasantness of a series of beverage samples sweetened with sucrose: 1.5-24%, fructose: 1-18%, or aspartame: 0.25-4%. They also kept 7-day food records. No group differences were found in sweet taste perception, pleasantness ratings, daily energy intakes, or macronutrient composition of the diets. However, subjects with diabetes consumed less sucrose but 3.5 times more alternative sweeteners than did controls. Peak pleasantness ratings for the beverage samples were positively correlated with dietary sweetness content in the subjects with diabetes but not the controls. These findings suggest that in diabetes, hedonic ratings for a sweetened beverage were related to dietary sweetness intake rather than changes in sweet taste perception.

  10. Type II congenital pulmonary airway malformation in an esophageal lung

    PubMed Central

    Martínez-Martínez, Blanca Estela; Furuya, María Elena Yuriko; Martínez-Muñiz, Irma; Vargas, Mario H; Flores-Salgado, Rosalinda

    2013-01-01

    A seven-month-old girl, born prematurely (birth weight 1000 g) from a twin pregnancy, was admitted to hospital due to recurrent pneumonia and atelectasis. She experienced cough and respiratory distress during feeding. The right hemithorax was smaller than the left, with diminished breath sounds and dullness. Chest x-rays revealed decreased lung volume and multiple radiolucent images in the right lung, as well as overdistention of the left lung. An esophagogram revealed three bronchial branches arising from the lower one-third of the esophagus, corresponding to the right lung and ending in a cul-de-sac. A diagnosis of esophageal lung was established. On bronchography, the right lung was absent and the trachea only continued into the left main bronchus. Echocardiography and angiotomography revealed agenesis of the pulmonary artery right branch. The surgical finding was an esophageal right lung, which was removed; the histopathological diagnosis was type II congenital pulmonary airway malformation in an esophageal lung. PMID:23762890

  11. Vorticity and magnetic shielding in a type-II superconductor.

    PubMed

    Cardoso, Marco; Bicudo, Pedro; Sacramento, Pedro D

    2006-09-20

    We study in detail, solving the Bogoliubov-de Gennes equations, the magnetic field, supercurrent and order parameter profiles originated by a solenoid or magnetic whisker inserted in a type-II superconductor. We consider solutions of different vorticities, n, in the various cases. The results confirm the connection between the vorticity, the internal currents and the boundstates in a self-consistent way. The number of boundstates is given by the vorticity of the phase of the gap function as in the case with no external solenoid. In the limiting case of an infinitely thin solenoid, like a Dirac string, the solution is qualitatively different. The quasiparticle spectrum and wavefunctions are a function of n-n(ext), where n(ext) is the vorticity of the solenoid. The flux is in all cases determined by the vorticity of the gap function.

  12. Unusual approach for the treatment of a type II endoleak.

    PubMed

    Ciampi Dopazo, J J; Gastaldo, F; Lanciego Pérez, C

    2016-01-01

    This case presentation is about an 88 years-old male patient with previous endovascular aortic aneurysm repairment history and aortic endoleak type II (EL2). The direct lumbar artery catheterization was considered an alternative to solve EL2, associated with aortic endovascular prosthesis and due to an incomplete sealing or exclusion of the aneurysmal sac or a vascular segment demonstrated by imaging studies, when other treatment alternative failed (transarterial embolization) to control the aneurysm growing. Performing translumbar approach was decided by puncturing the artery lumbar (L4) left, previously the lumbar arteries (L4) were evaluated in the abdominal CT arterial phase to guide a puncture/access under flouroscopy control. Diagnostic angiogram clearly demonstrated the median sacral and right lumbar arteries inflow into the aneurysm sac. Transcatheter embolization with fibered platinum microcoils was performed of the median sacral artery and lumbar left and right arteries (L4), showing satisfactory endoleak devascularization.

  13. Type II Diabetes Mellitus in Arabic-Speaking Countries

    PubMed Central

    Badran, Mohammad; Laher, Ismail

    2012-01-01

    The global epidemic of diabetes has not spared the Arabic-speaking countries, which have some of the highest prevalence of type II diabetes. This is particularly true of the Arab Gulf, a conglomerate of high income, oil-producing countries where prevalence rates are the highest. The prevalence rates among adults of the Arabic speaking countries as a whole range between 4%–21%, with the lowest being in Somalia and the highest in Kuwait. As economic growth has accelerated, so has the movement of the populations to urban centers where people are more likely to adopt lifestyles that embrace increased high-calorie food consumption and sedentary lifestyles. These factors likely contribute to the increased prevalence of obesity and diabetes in the Arabic speaking countries. PMID:22851968

  14. Type II congenital cystic pulmonary malformation in an esophageal lung.

    PubMed

    Martínez-Martínez, Blanca E; Furuya, María Elena Yuriko; Martínez-Muñiz, Irma; Vargas, Mario H; Flores-Salgado, Rosalinda

    2013-01-01

    A seven-month-old girl, born prematurely (birth weight 1000 g) from a twin pregnancy, was admitted to hospital due to recurrent pneumonia and atelectasis. She experienced cough and respiratory distress during feeding. The right hemithorax was smaller than the left, with diminished breath sounds and dullness. Chest x-rays revealed decreased lung volume and multiple radiolucent images in the right lung, as well as overdistention of the left lung. An esophagogram revealed three bronchial branches arising from the lower one-third of the esophagus, corresponding to the right lung and ending in a cul-de-sac. A diagnosis of esophageal lung was established. On bronchography, the right lung was absent and the trachea only continued into the left main bronchus. Echocardiography and angiotomography revealed agenesis of the pulmonary artery right branch. The surgical finding was an esophageal right lung, which was removed; the histopathological diagnosis was type II congenital pulmonary airway malformation in an esophageal lung.

  15. Majewski osteodysplastic primordial dwarfism type II (MOPD II): expanding the vascular phenotype.

    PubMed

    Bober, Michael B; Khan, Nadia; Kaplan, Jennifer; Lewis, Kristi; Feinstein, Jeffrey A; Scott, Charles I; Steinberg, Gary K

    2010-04-01

    Majewski Osteodysplastic Primordial Dwarfism, Type II (MOPD II) is a rare, autosomal recessive disorder. Features include severe intrauterine growth retardation (IUGR), poor postnatal growth (adult stature approximately 100 cm), severe microcephaly, skeletal dysplasia, characteristic facial features, and normal or near normal intelligence. An Institutional Review Board (IRB) approved registry was created and currently follows 25 patients with a diagnosis of MOPD II. Based on previous studies, a neurovascular screening program was implemented and 13 (52%) of these patients have been found to have cerebral neurovascular abnormalities including moyamoya angiopathy and/or intracranial aneurysms. The typical moyamoya pathogenesis begins with vessel narrowing in the supraclinoid internal carotid artery, anterior cerebral (A1) or middle cerebral (M1) artery segments. The narrowing may predominate initially on one side, progresses to bilateral stenosis, with subsequent occlusion of the vessels and collateral formation. We present four patients who, on neurovascular screening, were found to have cerebrovascular changes. Two were asymptomatic, one presented with a severe headache and projectile vomiting related to a ruptured aneurysm, and one presented after an apparent decline in cognitive functioning. Analysis of the registry suggests screening for moyamoya disease be performed at the time of MOPD II diagnosis and at least every 12-18 months using MRA or computerized tomographic angiography (CTA). We believe this is imperative. If diagnosed early enough, re-vascularization and aneurysm treatment in skilled hands can be performed safely and prevent or minimize long-term sequelae in this population. Emergent evaluation is also needed when other neurologic or cardiac symptoms are present.

  16. Type-II superlattice materials for mid-infrared detection

    NASA Astrophysics Data System (ADS)

    Brown, Gail J.; Haugan, Heather; Szmulowicz, Frank; Mahalingam, Krishnamur; Grazulis, L.; Houston, Shanee

    2005-03-01

    Type-II superlattices composed of alternating thin layers of InAs and GaSb, have been shown to be a highly flexible infrared materials system in which the energy band gap can be adjusted anywhere between 360 meV and 40 meV. These superlattices (SLs) are the III-V equivalent to the well established HgxCd1-xTe alloys used for infrared detection in the short, mid and long wavelength bands of the infrared spectrum. There are many possible designs for these superlattices that will produce the same narrow band gap by adjusting individual layer thicknesses and interface composition. Systematic growth and characterization studies were performed to determine optimum superlattice designs suitable for infrared detection in the 3 to 5 μm wavelength band. For these studies the individual layer thicknesses were less than 35Å. The effects of adding different thickness InSb-like interfaces were also studied. Through precision molecular beam epitaxy, design changes as small as 3Å to the SL layers could be studied. Significant changes were observed in the infrared photoresponse spectra of the various SL samples. The infrared properties of the various designs of these type-II superlattices were modeled using an 8-band Envelope Function Approximation. The infrared photoresponse spectra, combined with quantum mechanical modeling of predicted absorption spectra, were a key factor in the design optimization of the InAs/GaSb superlattices with band gaps in the range of 200 to 360 meV.

  17. Bilateral internal auditory canal gangliogliomas mimicking neurofibromatosis Type II

    PubMed Central

    Hooten, Kristopher G.; Oliveria, Seth F.; Sadrameli, Saeed S.; Gandhi, Shashank; Yachnis, Anthony T.; Lewis, Stephen B.

    2016-01-01

    Background: Gangliogliomas are rare low grade, typically well-differentiated, tumors that are composed of mature ganglion cells and neoplastic glial cells. These tumors can appear at virtually any location along the neuroaxis but classically occur in the temporal lobe of young patients. In a small number of cases, gangliogliomas have presented as masses in the brainstem or involving cranial nerves. With the exception of vestibular schwannomas, bilateral tumors in the region of the internal auditory canal (IAC) or cerebellopontine angle (CPA) are exceedingly rare. Case Description: We report a case of a 58-year-old male who presented with hearing loss, tinnitus, and vertigo. Initial magnetic resonance imaging revealed bilateral nonenhancing IAC/CPA tumors. Based on this finding, a presumptive diagnosis of neurofibromatosis Type II was made, which was initially managed conservatively with close observation. He returned for follow-up with worsening vertigo and tinnitus, thus prompting the decision to proceed with surgical resection of the symptomatic mass. Intriguingly, pathological study demonstrated a WHO Grade I ganglioglioma. Description: We report a case of a 58-year-old male who presented with hearing loss, tinnitus, and vertigo. Initial magnetic resonance imaging revealed bilateral nonenhancing IAC/CPA tumors. Based on this finding, a presumptive diagnosis of neurofibromatosis Type II was made, which was initially managed conservatively with close observation. He returned for follow-up with worsening vertigo and tinnitus, thus prompting the decision to proceed with surgical resection of the symptomatic mass. Intriguingly, pathological study demonstrated a WHO Grade I ganglioglioma. Conclusion: This is the first reported case of bilateral IAC/CPA gangliogliomas. When evaluating bilateral IAC/CPA lesions with unusual imaging characteristics, ganglioglioma should be included in the differential diagnosis. PMID:27127704

  18. Type II collagen defects in the chondrodysplasias. I. Spondyloepiphyseal dysplasias.

    PubMed Central

    Murray, L W; Bautista, J; James, P L; Rimoin, D L

    1989-01-01

    The spondyloepiphyseal dysplasias (SEDs) and spondyloepimetaphyseal dysplasias (SEMDs) are a heterogeneous group of skeletal dysplasias (dwarfing disorders) characterized by abnormal epiphyses, with and without varying degrees of metaphyseal irregularities, flattened vertebral bodies, and myopia. To better define the underlying cause of these disorders, we have analyzed the collagens from costal cartilage from several of these patients, using SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and high-performance liquid chromatography (HPLC) of intact chains and cyanogen bromide (CNBr) peptides and amino acid analysis. In almost all of the patients in this study group, the type II collagen exhibited a slower electrophoretic mobility when compared with that in normal controls. The mobility of many, but not all, of the CNBr peptides was also retarded. Peptides near the amino terminus were almost always altered, while the mobility of peptides close to the carboxyl terminus were normal in all but the severely affected cases. Analysis of the CNBr peptides on an HPLC sieving column confirmed that the electrophoretically abnormal peptides were of a higher molecular weight than were control peptides. Amino acid analysis indicated that the abnormal collagens have a higher ratio of hydroxylysine to lysine than does control collagen, suggesting that overmodification may be involved in the altered mobility. Our results are consistent with a defect in the collagen helix that results in overmodification of the molecule from that point toward the amino terminus. We propose that some forms of SED and SEMD are associated with abnormalities in type II collagen that results in delayed helix formation and consequent overmodification of the collagen. Cases of SED fit onto a continuous spectrum of clinical severity that correlates positively with both the extent of alteration and the proximity of the defect to the carboxyl terminus. Images Figure 1 Figure 2 PMID:2741952

  19. Phospholipid-transfer activities in cytosols from lung, isolated alveolar type II cells and alveolar type II cell-derived adenomas.

    PubMed Central

    Pool, G L; Bubacz, D G; Lumb, R H; Mason, R J

    1983-01-01

    We have examined phospholipid-transfer activities in cytosols from rat and mouse whole lung, isolated rat alveolar type II cells and alveolar type II cell-derived mouse pulmonary adenomas. We report an enrichment in phosphatidylcholine and phosphatidylglycerol (but not phosphatidylinositol) protein-catalysed transfer in the type II cell and adenoma cytosols compared with the whole-lung cytosols. The activities from these cytosols were resolved using column chromatofocusing, which clearly demonstrated the presence of a phosphatidylcholine-specific transfer protein in each of the four tissues. In addition, two proteins (rat) or three proteins (mouse) catalysing both phosphatidylcholine and phosphatidylglycerol transfer were resolved from whole lung, whereas in both the rat isolated alveolar type II cells and the mouse type II cell-derived adenomas one of these less specific proteins is not present. PMID:6661189

  20. Localization of pro-collagen type II mRNA and collagen type II in the healing tooth socket of the rat.

    PubMed

    Devlin, H; Hoyland, J; Freemont, A J; Sloan, P

    1995-03-01

    Sprague-Dawley rats (50 days old) were anaesthetized and the maxillary right molars extracted. The rats were killed at 2, 3, 6, 8 and 10 days after extraction. The maxillae were dissected and prepared for either routine histology, in situ hybridization for pro-collagen type II mRNA, or immunohistochemical detection of collagen type II. Pro-collagen type II mRNA was expressed maximally in the healing tooth socket at 8 days after the extractions, but the protein was not expressed at any time. This suggests that the translation of pro-collagen type II mRNA does not occur in osteoblasts following tooth extraction. Ossification was present in the socket at 6 days after the extractions, which is consistent with the suggestion that an early feature of osteoblastic differentiation may be the expression of type II pro-collagen mRNA.

  1. Rescue of Isolated GH Deficiency Type II (IGHD II) via Pharmacologic Modulation of GH-1 Splicing.

    PubMed

    Miletta, Maria Consolata; Petkovic, Vibor; Eblé, Andrée; Flück, Christa E; Mullis, Primus-E

    2016-10-01

    Isolated GH deficiency (IGHD) type II, the autosomal dominant form of GHD, is mainly caused by mutations that affect splicing of GH-1. When misspliced RNA is translated, it produces a toxic 17.5-kDa GH isoform that reduces the accumulation and secretion of wild-type-human GH (wt-hGH). Usually, isolated GHD type II patients are treated with daily injections of recombinant human GH in order to maintain normal growth. However, this type of replacement therapy does not prevent toxic effects of the 17.5-kDa GH isoform on the pituitary gland, which can eventually lead to other hormonal deficiencies. Here, we tested the possibility to restore the constitutive splicing pattern of GH-1 by using butyrate, a drug that mainly acts as histone deacetylase inhibitor. To this aim, wt-hGH and/or different hGH-splice site mutants (GH-IVS3+2, GH-IVS3+6, and GH-ISE+28) were transfected in rat pituitary cells expressing human GHRH receptor (GHRHR) (GC-GHRHR). Upon butyrate treatment, GC-GHRHR cells coexpressing wt-hGH and each of the mutants displayed increased GH transcript level, intracellular GH content, and GH secretion when compared with the corresponding untreated condition. The effect of butyrate was most likely mediated by the alternative splicing factor/splicing factor 2. Overexpression of alternative ASF/SF2 in the same experimental setting, indeed, promoted the amount of full-length transcripts thus increasing synthesis and secretion of the 22-kDa GH isoform. In conclusion, our results support the hypothesis that modulation of GH-1 splicing pattern to increase the 22-kDa GH isoform levels can be clinically beneficial and hence a crucial challenge in GHD research.

  2. Prenylation of Rab8 GTPase by type I and type II geranylgeranyl transferases.

    PubMed Central

    Wilson, A L; Erdman, R A; Castellano, F; Maltese, W A

    1998-01-01

    Rab GTPases are post-translationally modified by addition of geranylgeranyl moieties to carboxyl-terminal cysteine residues. For Rab proteins ending with xxCC xCxC and CCxx motifs this modification is catalysed by geranylgeranyltransferase type II (GGTaseII), and is entirely dependent on the Rab substrate being bound to Rab escort protein (REP). Several Rab proteins contain carboxyl-terminal CaaL prenylation motifs typical of members of the Rho family, which are modified in a REP-independent manner by geranylgeranyltransferase type I (GGTaseI). The present studies show that one such Rab protein (Rab8), which ends with a CVLL motif, is uniquely able to serve as a substrate for either REP/GGTaseII or GGTaseI in cell-free assays. The modification of Rab8 by GGTaseI did not require REP, indicating that a REP-induced conformational change is not essential for exposure of the Rab carboxyl-terminal cysteine prenylation site. To determine whether one enzyme plays a predominant role in Rab8 prenylation in vivo, the incorporation of [3H]mevalonate into Rab8 was measured in human embryonal kidney 293 cells under conditions where the activity of GGTaseI, but not GGTaseII, was blocked by the peptidomimetic inhibitor GGTI-298. The GGTaseI inhibitor did not prevent prenylation of either overexpressed Myc-tagged Rab8 or endogenous Rab8, whereas prenylation of a known GGTaseI substrate with the same carboxyl-terminal motif, Cdc42Hs, was completely blocked. To rule out the possibility that the apparent prenylation of Rab8 by GGTaseII occurs only when GGTaseI activity is eliminated, metabolic labelling studies were carried out in the absence of the GGTaseI inhibitor, using a REP-binding-deficient Rab8 construct (Y78D) that cannot serve as a substrate for GGTaseII, but is indistinguishable from wild-type Rab8 as a substrate for GGTaseI. Prenylation of the Y78D mutant was reduced by 60-70% in intact cells, consistent with the conclusion that the majority of Rab8 is prenylated by the

  3. Magnetization studies of II-VI semiconductor columnar quantum dots with type-II band alignment

    NASA Astrophysics Data System (ADS)

    Eginligil, M.; Sellers, I. R.; McCombe, B. D.; Chou, W.-C.; Kuskovsky, I. L.

    2009-03-01

    We report SQUID magnetization measurements of MBE-grown type-II, II-VI semiconductor quantum dot (QD) samples, with and without Mn incorporation. In all samples, the easy axis is out-of-plane, possibly due to columnar QD formation that arises from strain interaction between adjacent thin dot-containing layers. In addition, both types of QDs display a non-zero spontaneous magnetic ordering at 300 K. One set of samples consists of five-layers of (Zn,Mn)Te/ZnSe with a nominal (Zn,Mn)Te thickness of 3 nm, and ZnSe spacer thickness of 5 nm and 20 nm. These magnetic QD samples show magnetization vs. temperature behavior that can be interpreted in terms of two independent FM phases characterized by transition temperatures TC1 < TC2. A sample containing no Mn consists of 130 ZnTe/ZnSe layers, which forms Zn(Se,Te) QD layers separated by ZnSe spacers. Evidence of ferromagnetism is also seen in this structure, but the spontaneous magnetization is much weaker. For this sample only one phase is seen with TC above 300 K. Results will be discussed in terms of magneto-polaronic effects and defect-level induced ferromagnetism.

  4. Magnetic-Field-Induced Relativistic Properties in Type-I and Type-II Weyl Semimetals

    NASA Astrophysics Data System (ADS)

    Tchoumakov, Serguei; Civelli, Marcello; Goerbig, Mark O.

    2016-08-01

    We investigate Weyl semimetals with tilted conical bands in a magnetic field. Even when the cones are overtilted (type-II Weyl semimetal), Landau-level quantization can be possible as long as the magnetic field is oriented close to the tilt direction. Most saliently, the tilt can be described within the relativistic framework of Lorentz transformations that give rise to a rich spectrum, displaying new transitions beyond the usual dipolar ones in the optical conductivity. We identify particular features in the latter that allow one to distinguish between semimetals of different types.

  5. Molecular determinants on the insect sodium channel for the specific action of type II pyrethroid insecticides

    SciTech Connect

    Du Yuzhe; Nomura, Yoshiko; Luo Ningguang; Liu Zhiqi; Lee, Jung-Eun; Khambay, Bhupinder; Dong Ke

    2009-01-15

    Pyrethroid insecticides are classified as type I or type II based on their distinct symptomology and effects on sodium channel gating. Structurally, type II pyrethroids possess an {alpha}-cyano group at the phenylbenzyl alcohol position, which is lacking in type I pyrethroids. Both type I and type II pyrethroids inhibit deactivation consequently prolonging the opening of sodium channels. However, type II pyrethroids inhibit the deactivation of sodium channels to a greater extent than type I pyrethroids inducing much slower decaying of tail currents upon repolarization. The molecular basis of a type II-specific action, however, is not known. Here we report the identification of a residue G{sup 1111} and two positively charged lysines immediately downstream of G{sup 1111} in the intracellular linker connecting domains II and III of the cockroach sodium channel that are specifically involved in the action of type II pyrethroids, but not in the action of type I pyrethroids. Deletion of G{sup 1111}, a consequence of alternative splicing, reduced the sodium channel sensitivity to type II pyrethroids, but had no effect on channel sensitivity to type I pyrethroids. Interestingly, charge neutralization or charge reversal of two positively charged lysines (Ks) downstream of G{sup 1111} had a similar effect. These results provide the molecular insight into the type II-specific interaction of pyrethroids with the sodium channel at the molecular level.

  6. XIAP acts as a switch between type I and type II FAS-induced apoptosis signalling

    PubMed Central

    Jost, Philipp J.; Grabow, Stephanie; Gray, Daniel; McKenzie, Mark D.; Nachbur, Ueli; Huang, David C.S.; Bouillet, Philippe; Thomas, Helen E.; Borner, Christoph; Silke, John; Strasser, Andreas; Kaufmann, Thomas

    2010-01-01

    FAS (APO-1/CD95) and its physiological ligand, FASL, regulate apoptotic death of unwanted or dangerous cells in many tissues, functioning as a guardian against autoimmunity and cancer development1-4. Distinct cell types differ in the mechanisms by which the ‘death receptor’ FAS triggers their apoptosis1-4. In type I cells, such as lymphocytes, activation of ‘effector caspases’ by FAS-induced activation of caspase-8 suffices for cell killing whereas in type II cells, including hepatocytes and pancreatic β-cells, amplification of the caspase cascade through caspase-8 mediated activation of the pro-apoptotic BCL-2 family member BID5 is essential6-8. Here we show, that loss of X-chromosome linked inhibitor of apoptosis (XIAP)9,10 function by gene-targeting or treatment with a second mitochondria-derived activator of caspases (SMAC11, also called DIABLO12: direct IAP binding protein with low pI) mimetic drug rendered hepatocytes independent of BID for FAS-induced apoptosis signalling. These results show that XIAP is the critical discriminator between type I versus type II apoptosis signalling and suggest that IAP inhibitors should be used with caution in cancer patients with underlying liver conditions. PMID:19626005

  7. XIAP discriminates between type I and type II FAS-induced apoptosis.

    PubMed

    Jost, Philipp J; Grabow, Stephanie; Gray, Daniel; McKenzie, Mark D; Nachbur, Ueli; Huang, David C S; Bouillet, Philippe; Thomas, Helen E; Borner, Christoph; Silke, John; Strasser, Andreas; Kaufmann, Thomas

    2009-08-20

    FAS (also called APO-1 and CD95) and its physiological ligand, FASL, regulate apoptosis of unwanted or dangerous cells, functioning as a guardian against autoimmunity and cancer development. Distinct cell types differ in the mechanisms by which the 'death receptor' FAS triggers their apoptosis. In type I cells, such as lymphocytes, activation of 'effector caspases' by FAS-induced activation of caspase-8 suffices for cell killing, whereas in type II cells, including hepatocytes and pancreatic beta-cells, caspase cascade amplification through caspase-8-mediated activation of the pro-apoptotic BCL-2 family member BID (BH3 interacting domain death agonist) is essential. Here we show that loss of XIAP (X-chromosome linked inhibitor of apoptosis protein) function by gene targeting or treatment with a second mitochondria-derived activator of caspases (SMAC, also called DIABLO; direct IAP-binding protein with low pI) mimetic drug in mice rendered hepatocytes and beta-cells independent of BID for FAS-induced apoptosis. These results show that XIAP is the critical discriminator between type I and type II apoptosis signalling and suggest that IAP inhibitors should be used with caution in cancer patients with underlying liver conditions.

  8. Previous heat shock treatment inhibits Mayaro virus replication in human lung adenocarcinoma (A549) cells.

    PubMed

    Virgilio, P L; Godinho-Netto, M C; Carvalho Mda, G

    1997-01-01

    Human lung adenocarcinoma cells (A549) were submitted to mild or severe heat shock (42 degrees C or 44 degrees C) for 1 h, while another group of cells was double-heat-shocked (submitted to 42 degrees C for 1 h, returned to 37 degrees C for 3 h, then exposed to 44 degrees C for 1 h). After each heat treatment, the cells were infected with Mayaro virus for 24 h and incubated at 37 degrees C. The results showed that the double-heat-shocked thermotolerant cells exhibited a 10(4)-fold virus titre inhibition, despite the recovery of protein synthesis and original morphology 24 h post-infection. In contrast, cells submitted to mild or severe heat shock exhibited weaker inhibition of Mayaro virus titre (10(2)-fold). The mildly heat-shocked cells also presented a full recovery in protein synthesis, which was not observed in severely heat-shocked cells. These results indicate that exposure of A549 cells to a mild or to a double heat shock treatment before Mayaro virus infection induces an antiviral state.

  9. Middle infrared radiation induces G2/M cell cycle arrest in A549 lung cancer cells.

    PubMed

    Chang, Hsin-Yi; Shih, Meng-Her; Huang, Hsuan-Cheng; Tsai, Shang-Ru; Juan, Hsueh-Fen; Lee, Si-Chen

    2013-01-01

    There were studies investigating the effects of broadband infrared radiation (IR) on cancer cell, while the influences of middle-infrared radiation (MIR) are still unknown. In this study, a MIR emitter with emission wavelength band in the 3-5 µm region was developed to irradiate A549 lung adenocarcinoma cells. It was found that MIR exposure inhibited cell proliferation and induced morphological changes by altering the cellular distribution of cytoskeletal components. Using quantitative PCR, we found that MIR promoted the expression levels of ATM (ataxia telangiectasia mutated), ATR (ataxia-telangiectasia and Rad3-related and Rad3-related), TP53 (tumor protein p53), p21 (CDKN1A, cyclin-dependent kinase inhibitor 1A) and GADD45 (growth arrest and DNA-damage inducible), but decreased the expression levels of cyclin B coding genes, CCNB1 and CCNB2, as well as CDK1 (Cyclin-dependent kinase 1). The reduction of protein expression levels of CDC25C, cyclin B1 and the phosphorylation of CDK1 at Thr-161 altogether suggest G(2)/M arrest occurred in A549 cells by MIR. DNA repair foci formation of DNA double-strand breaks (DSB) marker γ-H2AX and sensor 53BP1 was induced by MIR treatment, it implies the MIR induced G(2)/M cell cycle arrest resulted from DSB. This study illustrates a potential role for the use of MIR in lung cancer therapy by initiating DSB and blocking cell cycle progression.

  10. Apoptosis inducing ability of silver decorated highly reduced graphene oxide nanocomposites in A549 lung cancer.

    PubMed

    Khan, Merajuddin; Khan, Mujeeb; Al-Marri, Abdulhadi H; Al-Warthan, Abdulrahman; Alkhathlan, Hamad Z; Siddiqui, Mohammed Rafiq H; Nayak, Vadithe Lakshma; Kamal, Ahmed; Adil, Syed F

    2016-01-01

    Recently, graphene and graphene-based materials have been increasingly used for various biological applications due to their extraordinary physicochemical properties. Here, we demonstrate the anticancer properties and apoptosis-inducing ability of silver doped highly reduced graphene oxide nanocomposites synthesized by employing green approach. These nano composites (PGE-HRG-Ag) were synthesized by using Pulicaria glutinosa extract (PGE) as a reducing agent and were evaluated for their anticancer properties against various human cancer cell lines with tamoxifen as the reference drug. A correlation between the amount of Ag nanoparticles on the surface of highly reduced graphene oxide (HRG) and the anticancer activity of nanocomposite was observed, wherein an increase in the concentration of Ag nanoparticles on the surface of HRG led to the enhanced anticancer activity of the nanocomposite. The nanocomposite PGE-HRG-Ag-2 exhibited more potent cytotoxicity than standard drug in A549 cells, a human lung cancer cell line. A detailed investigation was undertaken and Fluorescence activated cell sorting (FACS) analysis demonstrated that the nanocomposite PGE-HRG-Ag-2 showed G0/G1 phase cell cycle arrest and induced apoptosis in A549 cells. Studies such as, measurement of mitochondrial membrane potential, generation of reactive oxygen species (ROS) and Annexin V-FITC staining assay suggested that this compound induced apoptosis in human lung cancer cells.

  11. Cimicifuga foetida L. inhibited human respiratory syncytial virus in HEp-2 and A549 cell lines.

    PubMed

    Wang, Kuo Chih; Chang, Jung San; Chiang, Lien Chai; Lin, Chun Ching

    2012-01-01

    Human respiratory syncytial virus (HRSV) causes serious pediatric infection of the lower respiratory tract without effective therapeutic modality. Sheng-Ma-Ge-Gen-Tang (SMGGT; Shoma-kakkon-to) has been proven to be effective at inhibiting HRSV-induced plaque formation, and Cimicifuga foetida is the major constituent of SMGGT. We tested the hypothesis that C. foetida effectively inhibited the cytopathic effects of HRSV by a plaque reduction assay in both human upper (HEp2) and lower (A549) respiratory tract cell lines. Its ability to stimulate anti-viral cytokines was evaluated by an enzyme-linked immunosorbent assay (ELISA). C. foetida dose-dependently inhibited HRSV-induced plaque formation (p < 0.0001) before and after viral inoculation, especially in A549 cells (p < 0.0001). C. foetida dose-dependently inhibited viral attachment (p < 0.0001) and could increase heparins effect on viral attachment. In addition, C. foetida time-dependently and dose-dependently (p < 0.0001) inhibited HRSV internalization. C. foetida could stimulate epithelial cells to secrete IFN-β to counteract viral infection. However, C. foetida did not stimulate TNF-α secretion. Therefore, C. foetida could be useful in managing HRSV infection. This is the first evidence to support that C. foetida possesses antiviral activity.

  12. Silica nanoparticles and biological dispersants: genotoxic effects on A549 lung epithelial cells

    NASA Astrophysics Data System (ADS)

    Brown, David M.; Varet, Julia; Johnston, Helinor; Chrystie, Alison; Stone, Vicki

    2015-10-01

    Silica nanoparticle exposure could be intentional (e.g. medical application or food) or accidental (e.g. occupational inhalation). On entering the body, particles become coated with specific proteins depending on the route of entry. The ability of silica particles of different size and charge (non-functionalized 50 and 200 nm and aminated 50 and 200 nm) to cause genotoxic effects in A549 lung epithelial cells was investigated. Using the modified comet assay and the micronucleus assay, we examined the effect of suspending the particles in different dispersion media [RPMI or Hanks' balanced salt solution (HBSS), supplemented with bovine serum albumin (BSA), lung lining fluid (LLF) or serum] to determine if this influenced the particle's activity. Particle characterisation suggested that the particles were reasonably well dispersed in the different media, with the exception of aminated 50 nm particles which showed evidence of agglomeration. Plain 50, 200 nm and aminated 50 nm particles caused significant genotoxic effects in the presence of formamidopyrimidine-DNA glycosylase when dispersed in HBSS or LLF. These effects were reduced when the particles were dispersed in BSA and serum. There was no significant micronucleus formation produced by any of the particles when suspended in any of the dispersants. The data suggest that silica particles can produce a significant genotoxic effect according to the comet assay in A549 cells, possibly driven by an oxidative stress-dependent mechanism which may be modified depending on the choice of dispersant employed.

  13. COPD promotes migration of A549 lung cancer cells: the role of chemokine CCL21.

    PubMed

    Kuźnar-Kamińska, Barbara; Mikuła-Pietrasik, Justyna; Sosińska, Patrycja; Książek, Krzysztof; Batura-Gabryel, Halina

    2016-01-01

    Patients with COPD develop lung cancer more frequently than healthy smokers. At the same time, molecular mediators promoting various aspects of cancer cell progression are still elusive. In this report, we examined whether COPD can be coupled with increased migration of non-small-cell lung cancer cells A549 and, if so, whether this effect may be related to altered production and activity of chemokines CCL21, CXCL5, and CXCL12. The study showed that the migration of A549 cells through the polycarbonate membrane and basement membrane extract toward a chemotactic gradient elicited by serum from patients with COPD was markedly higher as compared with serum from healthy donors. The concentration of CCL21 and CXCL12, but not CXCL5, in serum from patients with COPD was also increased. Experiments in which CCL21- and CXCL12-dependent signaling was blocked revealed that increased migration of the cancer cells upon treatment with serum from patients with COPD was mediated exclusively by CCL21. Collectively, our results indicate that COPD may contribute to the progression of lung cancer via CCL21-dependent intensification of cancer cell migration.

  14. Complex Type-II Interband Cascade MQW Photodetectors

    NASA Technical Reports Server (NTRS)

    Yang, Rui

    2007-01-01

    Multiple-quantum-well (MQW) photodetectors of a proposed type would contain active regions comprising multiple superlattice subregions. These devices would have complex structures: The superlattice of each subregion would be designed for enhanced absorption of photons in a desired wavelength band (typically in the infrared) and multiple subregions of different design would be cascaded for multicolor operation. The designs of these photodetectors would take advantage of the characteristic alignment of the edges of the electron-energy bands in type-II quantum-well structures: Within each finite superlattice, interband transitions would be used for detecting photons, and between finite superlattices, intraband relaxation and interband tunneling would be used for transport of charge carriers, all such as to enable detection of normally incident photons. Absorption of photons in the active region of a photodetector according to the proposal could be significantly enhanced by designing the superlattice/MQW structures to contain closely spaced energy states. The photodetector could be operated with a small bias to facilitate transport of charge carriers. The superlattices could be somewhat chirped, with a preferred transport direction.

  15. Adjuvant arthritis pretreatment with type II collagen and Mycobacterium butyricum.

    PubMed

    Franch, A; Cassany, S; Castellote, C; Castell, M

    1992-11-01

    A treatment previous to adjuvant arthritis induction has been performed with type II collagen (CII) or Mycobacterium butyricum (Mb), which is the inducer of the pathology. Pretreatment was administered in two different ways: a) subcutaneously or intradermally 14 days before arthritis induction, and b) intravenously 3 days before induction. In order to relate the change in inflammation to the corresponding antigen immune response, serum antibodies and delayed type hypersensitivity (DTH) against CII or Mb were studied. Pretreatment with s.c. CII 14 days before induction produced slight protection against arthritis and significantly delayed its onset; systemic inflammation showed good positive correlation with anti-CII antibodies. The CII administered i.v. 3 days before arthritic challenge did not significantly modify the inflammatory process. The use of i.d. subarthritogenic doses of Mb 14 days before induction protected a high percentage of the animals from the posterior arthritic challenge; this protection was accompanied by high anti-Mb antibody titers and DTH reaction. When Mb was given i.v. 3 days before induction, a partial protection of inflammation was observed; arthritis was milder and its onset was delayed. These changes were accompanied by reduced humoral and cellular response to Mb.

  16. RNA interference-mediated knockdown of Aurora-B alters the metastatic behavior of A549 cells via modulation of the phosphoinositide 3-kinase/Akt signaling pathway.

    PubMed

    Zhou, Long Dian; Xiong, Xu; Long, Xin Hua; Liu, Zhi Li; Huang, Shan Hu; Zhang, Wei

    2014-11-01

    Accumulating evidence has revealed that an elevated expression level of Aurora-B is associated with metastasis in various types of malignant tumor. However, it is currently unclear whether this molecule is involved in non-small lung cancer (NSCLC) metastasis, and the molecular mechanisms associated with Aurora-B and metastasis remain unknown. In the present study, in order to investigate whether Aurora-B is involved in the development and metastasis of NSCLC, the Aurora-B protein expression in NSCLC tissues was detected by immunohistochemistry and its association with metastasis was analyzed. The results revealed that the expression levels of the Aurora-B protein in tissues obtained from NSCLC patients with lymph node metastasis were significantly higher than those without metastatic disease. Furthermore, the effect of Aurora-B inhibition on A549 cell migration and invasion, as well as the activity of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway was evaluated. Aurora-B was inhibited in the A549 cells using short hairpin RNA, and the cell migration and invasion rates were investigated using wound healing and Transwell invasion assays. In addition, the expression of the main proteins in the PI3K/Akt/nuclear factor-κB (NF-κB) signaling pathway, and matrix metalloproteinase (MMP)-2 and -9 were measured by western blot analysis. The results demonstrated that cell migration and invasion were decreased as a result of silencing Aurora-B. Furthermore, the activity of the PI3K/Akt/NF-κB signaling pathway and the expression of MMP-2 and -9 protein were suppressed by silencing Aurora-B. The results of the present study indicate that the knockdown of Aurora-B suppresses A549 cell invasion and migration via the inhibition of the PI3K/Akt signaling pathway in vitro and thus, targeting Aurora-B may present a potential treatment strategy for NSCLC.

  17. RNA interference-mediated knockdown of Aurora-B alters the metastatic behavior of A549 cells via modulation of the phosphoinositide 3-kinase/Akt signaling pathway

    PubMed Central

    ZHOU, LONG DIAN; XIONG, XU; LONG, XIN HUA; LIU, ZHI LI; HUANG, SHAN HU; ZHANG, WEI

    2014-01-01

    Accumulating evidence has revealed that an elevated expression level of Aurora-B is associated with metastasis in various types of malignant tumor. However, it is currently unclear whether this molecule is involved in non-small lung cancer (NSCLC) metastasis, and the molecular mechanisms associated with Aurora-B and metastasis remain unknown. In the present study, in order to investigate whether Aurora-B is involved in the development and metastasis of NSCLC, the Aurora-B protein expression in NSCLC tissues was detected by immunohistochemistry and its association with metastasis was analyzed. The results revealed that the expression levels of the Aurora-B protein in tissues obtained from NSCLC patients with lymph node metastasis were significantly higher than those without metastatic disease. Furthermore, the effect of Aurora-B inhibition on A549 cell migration and invasion, as well as the activity of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway was evaluated. Aurora-B was inhibited in the A549 cells using short hairpin RNA, and the cell migration and invasion rates were investigated using wound healing and Transwell invasion assays. In addition, the expression of the main proteins in the PI3K/Akt/nuclear factor-κB (NF-κB) signaling pathway, and matrix metalloproteinase (MMP)-2 and -9 were measured by western blot analysis. The results demonstrated that cell migration and invasion were decreased as a result of silencing Aurora-B. Furthermore, the activity of the PI3K/Akt/NF-κB signaling pathway and the expression of MMP-2 and -9 protein were suppressed by silencing Aurora-B. The results of the present study indicate that the knockdown of Aurora-B suppresses A549 cell invasion and migration via the inhibition of the PI3K/Akt signaling pathway in vitro and thus, targeting Aurora-B may present a potential treatment strategy for NSCLC. PMID:25295091

  18. Relative potencies of Type I and Type II pyrethroids for inhibition of spontaneous firing in neuronal networks.

    EPA Science Inventory

    Pyrethroids insecticides commonly used in pest control disrupt the normal function of voltage-sensitive sodium channels. We have previously demonstrated that permethrin (a Type I pyrethroid) and deltamethrin (a Type II pyrethroid) inhibit sodium channel-dependent spontaneous netw...

  19. Evaporation and recondensation of sodium in Semarkona Type II chondrules

    NASA Astrophysics Data System (ADS)

    Hewins, Roger H.; Zanda, Brigitte; Bendersky, Claire

    2012-02-01

    We have investigated the Na distributions in Semarkona Type II chondrules by electron microprobe, analyzing olivine and melt inclusions in it, mesostasis and bulk chondrule, to see whether they indicate interactions with an ambient gas during chondrule formation. Sodium concentrations of bulk chondrule liquids, melt inclusions and mesostases can be explained to a first approximation by fractional crystallization of olivine ± pyroxene. The most primitive olivine cores in each chondrule are mostly between Fa 8 and Fa 13, with 0.0022-0.0069 ± 0.0013 wt.% Na 2O. Type IIA chondrule olivines have consistently higher Na contents than olivines in Type IIAB chondrules. We used the dependence of olivine-liquid Na partitioning on FeO in olivine as a measure of equilibration. Extreme olivine rim compositions are ˜Fa 35 and 0.03 wt.% Na 2O and are close to being in equilibrium with the mesostasis glass. Olivine cores compared with the bulk chondrule compositions, particularly in IIA chondrules, show very high apparent D Na, indicating disequilibrium and suggesting that chondrule initial melts were more Na-rich than present chondrule bulk compositions. The apparent D Na values correlate with the Na concentrations of the olivine, but not with concentrations in the bulk melt. We use equilibrium D Na to find the Na content of the true parent liquid and estimate that Type IIA chondrules lost more than half their Na and recondensation was incomplete, whereas Type IIAB chondrules recovered most of theirs in their mesostases . Glass inclusions in olivine have lower Na than expected from fractionation of bulk composition liquids, and mesostases have higher Na than expected in calculated daughter liquids formed by fractional crystallization alone. These observations also require open system behavior of chondrules, specifically evaporation of Na before formation of melt inclusions followed by recondensation of Na in mesostases. Within this record of evaporation followed by

  20. Genistein inhibits A549 human lung cancer cell proliferation via miR-27a and MET signaling

    PubMed Central

    Yang, Yang; Zang, Aimin; Jia, Youchao; Shang, Yanhong; Zhang, Zhuoqi; Ge, Kun; Zhang, Jinchao; Fan, Wufang; Wang, Bei

    2016-01-01

    Genistein is a soybean isoflavone; in its aglycone it has various biological activities. Animal experiments, clinical studies and epidemiological investigations suggest that genistein has preventative and curative functions for a number of diseases, particularly in cancer. The present study explored the potential anti-cancer effect of genistein by observing its role in inhibiting A549 human lung cancer cell proliferation and investigating the possible mechanism. A549 cells were exposed to various concentrations of genistein (0, 10, 25, 50, 100 and 200 µM; dissolved in physiological saline) for 1, 2 and 3 days. Subsequently, the viability of A549 cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell apoptosis was examined using a flow cytometer, caspase 3/9 activity was measured using commercial kits, reverse transcription quantitative polymerase chain reaction was used to analyze the miR-27a expression and western blotting was used to investigate MET protein expression. The results suggested a significant inhibition of A549 cell growth following treatment with genistein in a time- and dose-dependent manner. The current study also indicated that treatment with genistein significantly induces cell apoptosis and promotes caspase-3/9 activation of A549 cells in a dose-dependent manner. Further functional assays revealed that the anti-cancer effect of genistein activated microRNA-27a (miR-27a) expression levels and reduced MET protein expression in A549 cells. In conclusion, the present study demonstrates that genistein inhibits A549 human lung cancer cell proliferation. Furthermore, this study reports, for the first time, a correlation between the anti-cancer effect of genistein and miR-27a-mediated MET signaling. PMID:27602162

  1. Solar flares associated coronal mass ejections in case of type II radio bursts

    NASA Astrophysics Data System (ADS)

    Bhatt, Beena; Prasad, Lalan; Chandra, Harish; Garia, Suman

    2016-08-01

    We have statistically studied 220 events from 1996 to 2008 (i.e. solar cycle 23). Two set of flare-CME is examined one with Deca-hectometric (DH) type II and other without DH type II radio burst. Out of 220 events 135 (flare-halo CME) are accompanied with DH type II radio burst and 85 are without DH type II radio burst. Statistical analysis is performed to examine the distribution of solar flare-halo CME around the solar disk and to investigate the relationship between solar flare and halo CME parameters in case of with and without DH type II radio burst. In our analysis we have observed that: (i) 10-20° latitudinal belt is more effective than the other belts for DH type II and without DH type II radio burst. In this belt, the southern region is more effective in case of DH type II radio burst, whereas in case of without DH type II radio burst dominance exits in the northern region. (ii) 0-10° longitudinal belt is more effective than the other belts for DH type II radio burst and without DH type II radio burst. In this belt, the western region is more effective in case of DH type II radio burst, while in case of without DH type II radio burst dominance exits in the eastern region. (iii) Mean speed of halo CMEs (1382 km/s) with DH type II radio burst is more than the mean speed of halo CMEs (775 km/s) without DH type II radio burst. (iv) Maximum number of M-class flares is found in both the cases. (v) Average speed of halo CMEs in each class accompanied with DH type II radio burst is higher than the average speed of halo CMEs in each class without DH type II radio burst. (vi) Average speed of halo CMEs, associated with X-class flares, is greater than the other class of solar flares in both the cases.

  2. Human primary bronchial epithelial cells respond differently to titanium dioxide nanoparticles than the lung epithelial cell lines A549 and BEAS-2B.

    PubMed

    Ekstrand-Hammarström, Barbro; Akfur, Christine M; Andersson, Per Ola; Lejon, Christian; Osterlund, Lars; Bucht, Anders

    2012-09-01

    We have compared the cellular uptake and responses of five preparations of nanocrystalline titanium dioxide (TiO(2)) between normal human bronchial epithelial (NHBE) cells and epithelial cell lines (A549 and BEAS-2B). The P25 nanoparticles, containing both anatase and rutile modifications, induced reactive oxygen species (ROS) and secretion of the neutrophil chemoattractant IL-8 in all three cell types used. Pure anatase and rutile particles provoked differential IL-8 response in A549 and no response in BEAS-2B cells despite similar formation of ROS. The pure TiO(2) modifications also provoked release of the inflammatory mediators: IL-6, G-CSF and VEGF, in NHBE cells but not in the two cell lines. We conclude that the responsiveness of lung epithelial cells is strongly dependent on both the physicochemical properties of TiO(2) nanoparticles and the type of responder cells. The differential pro-inflammatory responsiveness of primary lung epithelial cells compared with immortalized cell lines should be considered in the assessment of adverse reactions to inhaled nanoparticles.

  3. Determination of adsorption affinity of nanoparticles for interleukin-8 secreted from A549 cells by in vitro cell-free and cell-based assays.

    PubMed

    Lee, Yun-Geon; Jeong, Jiyoung; Raftis, Jennifer; Cho, Wan-Seob

    2015-01-01

    The evaluation of the potential of nanoparticles (NP) for adsorbing biomolecules and use of control approaches are important for accurate presentation of in vitro analytical data. In this study, seven types of NP including carbon black (CB), cerium dioxide (CeO2), copper oxide (CuO), indium trioxide (In2O3), nickel oxide (NiO), silicon dioxide (SiO2), and titanium dioxide (TiO2) were used for determining the adsorption ability of interleukin-8 (IL-8) under either (1) a cell-free condition where NP were incubated with supernatant of A549 cells, or (2) a cell-based condition, where cells were treated with NP. Under the cell-free condition, CB and TiO2 NP showed a high adsorption affinity for IL-8 in supernatants of both lipopolysaccharide (LPS)-stimulated and unstimulated A549 cells. In contrast, SiO2 and In2O3 NP displayed a relatively low adsorption affinity. Further, IL-8 adsorption was markedly reduced when NP were predispersed in fetal bovine serum. The results obtained under cell-based conditions using both stimulated and unstimulated cells were consistent with those of the cell-free condition. Data indicate that adsorption of IL-8 onto NP surface is variable depending on type of NP, preparation method of NP, and cellular inflammatory state. Thus, the cell-free adsorption assay may be utilized for reliable interpretation of data produced by in vitro cell-based methodology.

  4. miR-129b suppresses cell proliferation in the human lung cancer cell lines A549 and H1299.

    PubMed

    Zheng, L; Qi, Y X; Liu, S; Shi, M L; Yang, W P

    2016-10-17

    Lung cancer is one of the most prevalent malignant tumors, and is one of the primary causes of cancer-associated deaths. In 2002, an estimated 1.18 million lung cancer-associated deaths were recorded, accounting for 18% of cancer-related deaths and 2% of total mortality. Despite the great progress that has been made in lung cancer therapies, the mechanisms underlying lung cancer formation and development remain largely unknown. Meanwhile, the microRNA miR-129 has been shown to be involved in the formation of many types of cancer. Therefore, this study aims to investigate whether miR129b could suppress proliferation of lung cancer cell lines. NSCLC tissue samples were collected from the Department of Respiratory Medicine between April 2013 and December 2015. Ten normal health individuals were recruited as controls. Lung cancer cell lines A549 and H1299 were used to examine the suppressive effects of miR129b. Quantitative real-time PCR was used to detect miR129b expression. The MTT assay was used to analyze cell proliferation. Results indicated that miR-129b is down-regulated in lung cancer cell lines and NSCLC tissues. Furthermore, overexpression of miR-129b inhibited proliferation of lung cancer cells. In conclusion, miR-129b suppresses lung cancer cell proliferation, and can be a potential therapeutic target for treatment of lung cancers.

  5. Characteristics of DH type II bursts, CMEs and flares with respect to the acceleration of CMEs

    NASA Astrophysics Data System (ADS)

    Prakash, O.; Umapathy, S.; Shanmugaraju, A.; Pappa Kalaivani, P.; Vršnak, Bojan

    2012-01-01

    A detailed investigation on DH-type-II radio bursts recorded in Deca-Hectometer (hereinafter DH-type-II) wavelength range and their associated CMEs observed during the year 1997-2008 is presented. The sample of 212 DH-type-II associated with CMEs are classified into three populations: (i) Group I (43 events): DH-type-II associated CMEs are accelerating in the LASCO field view ( a>15 m s-2); (ii) Group II (99 events): approximately constant velocity CMEs (-15< a<15 m s-2) and (iii) Group III (70 events): represents decelerating CMEs ( a<-15 m s-2). Our study consists of three steps: (i) statistical properties of DH-type-II bursts of Group I, II and III events; (ii) analysis of time lags between onsets of flares and CMEs associated with DH-type-II bursts and (iii) statistical properties of flares and CMEs of Group I, II and III events. We found statistically significant differences between the properties of DH-type-II bursts of Group I, II and III events. The significance ( P a ) is found using the one-way ANOVA-test to examine the differences between means of groups. For example, there is significant difference in the duration ( P a =5%), ending frequency ( P a =4%) and bandwidth ( P a =4%). The accelerating and decelerating CMEs have more kinetic energy than the constant speed CMEs. There is a significant difference between the nose height of CMEs at the end time of DH-type-IIs ( P a ≪1%). From the time delay analysis, we found: (i) there is no significant difference in the delay (flare start—DH-type-II start and flare peak—DH-type-II start); (ii) small differences in the time delay between the CME onset and DH-type-II start, delay between the flare start and CME onset times. However, there are high significant differences in: flare duration ( P a =1%), flare rise time ( P a =0.5%), flare decay time ( P a =5%) and CMEs speed ( P a ≪1%) of Group I, II and III events. The general LASCO CMEs have lower width and speeds when compared to the DH CMEs. It seems

  6. Type I and type II fatty acid biosynthesis in Eimeria tenella: enoyl reductase activity and structure.

    PubMed

    Lu, J Z; Muench, S P; Allary, M; Campbell, S; Roberts, C W; Mui, E; McLeod, R L; Rice, D W; Prigge, S T

    2007-12-01

    Apicomplexan parasites of the genus Eimeria are the major causative agent of avian coccidiosis, leading to high economic losses in the poultry industry. Recent results show that Eimeria tenella harbours an apicoplast organelle, and that a key biosynthetic enzyme, enoyl reductase, is located in this organelle. In related parasites, enoyl reductase is one component of a type II fatty acid synthase (FAS) and has proven to be an attractive target for antimicrobial compounds. We cloned and expressed the mature form of E. tenella enoyl reductase (EtENR) for biochemical and structural studies. Recombinant EtENR exhibits NADH-dependent enoyl reductase activity and is inhibited by triclosan with an IC50 value of 60 nm. The crystal structure of EtENR reveals overall similarity with other ENR enzymes; however, the active site of EtENR is unoccupied, a state rarely observed in other ENR structures. Furthermore, the position of the central beta-sheet appears to block NADH binding and would require significant movement to allow NADH binding, a feature not previously seen in the ENR family. We analysed the E. tenella genomic database for orthologues of well-characterized bacterial and apicomplexan FAS enzymes and identified 6 additional genes, suggesting that E. tenella contains a type II FAS capable of synthesizing saturated, but not unsaturated, fatty acids. Interestingly, we also identified sequences that appear to encode multifunctional type I FAS enzymes, a feature also observed in Toxoplasma gondii, highlighting the similarity between these apicomplexan parasites.

  7. Schisandrin B inhibits the proliferation of human lung adenocarcinoma A549 cells by inducing cycle arrest and apoptosis

    PubMed Central

    Lv, Xue-Jiao; Zhao, Li-Jing; Hao, Yu-Qiu; Su, Zhen-Zhong; Li, Jun-Yao; Du, Yan-Wei; Zhang, Jie

    2015-01-01

    Lung cancer is the leading cause of cancer death in the world. Schizandrin B (Sch B) is one of the main dibenzocyclooctadiene lignans present in the fruit of Schisandra chinensis (Schisandraceae). Sch B has multiple functions against cancer. The aim of this study was to determine the effect of Sch B on the proliferation, cell cycling, apoptosis and invasion of lung adenocarcinoma A549 cells by MTT, flow cytometry, wound healing and transwell invasion assays. Treatment with Sch B inhibited the proliferation of A549 cells in a dose-dependent manner. Sch B induced cell cycle arrest at G0/G1 phase by down-regulating the expression of cyclin D1, cyclin-dependent kinase (CDK)4, and CDK6, but up-regulating p53 and p21 expression in A549 cells. Furthermore, Sch B triggered A549 cell apoptosis by increasing Bax, cleaved caspase-3, 9, Cyto C, but decreasing Bcl-2 and PCNA expression. In addition, Sch B inhibited the invasion and migration of A549 cells by down-regulating the expressions of HIF-1, VEGF, MMP-9 and MMP-2. Therefore, Sch B has potent anti-tumor activity and may be a promising traditional Chinese medicine for human lung carcinoma. PMID:26221229

  8. Psoralen reverses docetaxel-induced multidrug resistance in A549/D16 human lung cancer cells lines.

    PubMed

    Hsieh, Ming-Ju; Chen, Mu-Kuan; Yu, Ya-Yen; Sheu, Gwo-Tarng; Chiou, Hui-Ling

    2014-06-15

    Chemotherapy is the recommended treatment for advanced-stage cancers. However, the emergence of multidrug resistance (MDR), the ability of cancer cells to become simultaneously resistant to different drugs, limits the efficacy of chemotherapy. Previous studies have shown that herbal medicine or natural food may be feasible for various cancers as potent chemopreventive drug. This study aims to explore the capablility of reversing the multidrug resistance of docetaxel (DOC)-resistant A549 cells (A549/D16) of psoralen and the underlying mechanisms. In this study, results showed that the cell viability of A549/D16 subline is decreased when treated with psoralen plus DOC, while psoralen has no effect on the cell proliferation on A549 and A549/D16 cells. Furthermore, mRNA and proteins levels of ABCB1 were decreased in the presence of psoralen, while decreased ABCB1 activity was also revealed by flow cytometry. Based on these results, we believe that psoralen may be feasible for reversing the multidrug resistance by inhibiting ABCB1 gene and protein expression. Such inhibition will lead to a decrease in ABCB1 activity and anti-cancer drug efflux, which eventually result in drug resistance reversal and therefore, sensitizing drug-resistant cells to death in combination with chemotherapeutic drugs.

  9. Wheatgrass Extract Ameliorates Hypoxia-induced Mucin Gene Expression in A549 cells

    PubMed Central

    Sim, Ju hwan; Choi, Moon-Hee; Shin, Hyun-Jae; Lee, Ji-Eun

    2017-01-01

    Background: Wheatgrass is known to have antioxidant, antiaging, and anti-inflammatory effect. However, its protective effect against hypoxia is not yet evaluated. Objective: In this study, we evaluated the protective and anti-inflammatory effect of wheatgrass against the hypoxia in airway epithelial cells. Materials and Methods: A549 human lung adenocarcinoma cells were incubated in a hypoxic condition (CO2 5%/O2 1%) for 24 hr in the presence of different concentration of wheatgrass 50, 75, 100, and 150 μg/mL, and the magnitude of each immunologic response produced by the A549 cells was compared. The mRNA expression level of mucin gene (MUC), 5A, 5B, 8, GM-CSF, TNF-α, and VEGF were evaluated by using real-time polymerase chain reaction. The MUC proteins level before and after knocking out the hypoxia-inducible factor (hif)-1α via short interfering (si) RNA transfection were assessed by immunoblot analysis. Accordingly, the involved cell signaling pathway was evaluated by immunoblot analysis. Results: The inflammatory cytokines (GM-CSF, TNF- α) and the expressions of MUC 5A, 5B, and 8 were augmented by hypoxia. The augmented MUC expression was decreased by the wheatgrass extract administration. Hif-1α gene expression after hypoxia exposure was decreased by wheatgrass. Knockdown of hif-1α by siRNA reduced the mucin gene expression and which was more enhanced by wheatgrass extract. Conclusion: Theses results suggest that wheatgrass may be useful in the treatment of sinonasal disease by inhibiting mucus hypersecretion in airway epithelium. SUMMARY Wheatgrass extract decreases the hypoxia-induced MUC 5A, 5B and 8 expression.Hif-1α gene expression after hypoxia exposure was decreased by wheatgrass.Wheatgrass inhibits p44/42 phosphorylation in hypoxia-exposed airway epithelial cells. Abbreviations used: A549: human lung adenocarcinoma cells, GM-CSF: granulocyte-macrophage colony stimulating factor, HIF: hypoxia inducible factor, IL: interleukin, MUC: mucin, MTT: 3

  10. [Influence of Berberine on Cisplatin Antineoplastic Effect in A549 Cells].

    PubMed

    Jiang, Guojun; Li, Li; Wu, Xiaoxiang; Dong, Shuying; Tong, Xuhui

    2015-08-01

    背景与目的 以顺铂为基础的化疗方案是晚期非小细胞肺癌的一线化疗方案,但是由于顺铂的不良反应严重及耐药性的产生均限制了它的临床应用,本研究采用联合用药的方式观察黄连素对顺铂抗肿瘤作用的影响,并探讨其可能机制。方法 分别观察黄连素对肺腺癌细胞A549细胞中总Cx43蛋白、细胞膜Cx43蛋白的表达以及细胞缝隙连接功能的改变,通过标准细胞集落克隆实验观察黄连素对顺铂细胞毒性的影响;并观察PKC激酶的表达。结果 黄连素在0 μM-10 μM浓度范围内对细胞无毒性,通过增加细胞内总Cx43蛋白和胞膜Cx43蛋白的表达而增强细胞缝隙连接功能,0.1 μM、1 μM、10 μM黄连素可以显著增强细胞间的荧光传递,与空白对照组相比,黄连素预处理后的细胞间荧光传递功能分别增加了33.3% (P=0.002,3)、67.0% (P<0.001)、160.0% (P<0.001),这种作用与PKC的活性被抑制相关,抑制PKC活性可以进一步增加顺铂对A549细胞的毒性作用。结论 黄连素可通过增加A549细胞的缝隙连接功能而明显增强顺铂的细胞毒性。.

  11. Type II topoisomerases--inhibitors, repair mechanisms and mutations.

    PubMed

    Heisig, Peter

    2009-11-01

    Type II topoisomerases are ubiquitous enzymes that play an essential role in the control of replicative DNA synthesis and share structural and functional homology among different prokaryotic and eukaryotic organisms. Antibacterial fluoroquinolones target prokaryotic topoisomerases at concentrations 100- to 1000-fold lower than mammalian enzymes, the preferred targets of anticancer drugs such as etoposide. The mechanisms of action of both of these types of inhibitors involve the fixation of an intermediate reaction step, where the enzyme is covalently bound to an enzyme-mediated DNA double-strand break (DSB). The resulting ternary drug-enzyme-DNA complexes can then be converted to cleavage complexes that block further movement of the DNA replication fork, subsequently inducing stress responses. In haploid prokaryotic cells, stress responses include error-free and error-prone DNA damage repair pathways, such as homologous recombination and translesion synthesis, respectively. The latter can result in the acquisition of point mutations. Diploid mammalian cells are assumed to preferentially use recombination mechanisms for the repair of DSBs, an example of which, non-homologous end joining, is a major error-prone repair mechanism associated with an increased frequency of detectable small deletions, insertions and translocations. However, results obtained from safety testing of novel fluoroquinolones at high concentrations indicate that point mutations may also occur in mammalian cells. Recent data provide evidence for translesion synthesis catalysed by error-prone repair polymerases as a damage-tolerance repair mechanism of DSBs in eukaryotic cells. This paper discusses possible roles of different mechanisms for the repair of DSBs operating in both eukaryotic and prokaryotic cells that result in recombinational rearrangements, deletions/insertions as well as point mutations.

  12. Bolometric Lightcurves of Peculiar Type II-P Supernovae

    NASA Astrophysics Data System (ADS)

    Lusk, Jeremy A.; Baron, Edward A.

    2017-01-01

    We examine the bolometric lightcurves of five Type II-P supernovae (SNe 1998A, 2000cb, 2006V, 2006au and 2009E) which are thought to originate from blue supergiant progenitors using a new python package named SuperBoL. With this code, we calculate SNe lightcurves using three different techniques common in the literature: the quasi-bolometric method, which integrates the observed photometry, the direct integration method, which additionally corrects for unobserved flux in the UV and IR, and the bolometric correction method, which uses correlations between observed colors and V-band bolometric corrections. We present here the lightcurves calculated by SuperBoL along with previously published lightcurves, as well as peak luminosities and 56Ni yields. We find that the direct integration and bolometric correction lightcurves largely agree with previously published lightcurves, but with what we believe to be more robust error calculations, with 0.2 ≤ δL/L ≤ 0.5. Peak luminosities and 56Ni masses are similarly comparable to previous work. SN 2000cb remains an unusual member of this sub-group, owing to the faster rise and flatter plateau than the other supernovae in the sample. Initial comparisons with the NLTE atmosphere code PHOENIX show that the direct integration technique reproduces the luminosity of a model supernova spectrum to ˜5% when given synthetic photometry of the spectrum as input. Our code is publicly available. The ability to produce bolometric lightcurves from observed sets of broad-band light curves should be helpful in the interpretation of other types of supernovae, particularly those that are not well characterized, such as extremely luminous supernovae and faint fast objects.

  13. Bolometric Light Curves of Peculiar Type II-P Supernovae

    NASA Astrophysics Data System (ADS)

    Lusk, Jeremy A.; Baron, E.

    2017-04-01

    We examine the bolometric light curves of five Type II-P supernovae (SNe 1998A, 2000cb, 2006V, 2006au, and 2009E), which are thought to originate from blue supergiant progenitors like that of SN 1987A, using a new python package named SuperBoL. With this code, we calculate SNe light curves using three different common techniques common from the literature: the quasi-bolometric method, which integrates the observed photometry, the direct integration method, which additionally corrects for unobserved flux in the UV and IR, and the bolometric correction method, which uses correlations between observed colors and V-band bolometric corrections. We present here the light curves calculated by SuperBoL, along with previously published light curves, as well as peak luminosities and 56Ni yields. We find that the direct integration and bolometric correction light curves largely agree with previously published light curves, but with what we believe to be more robust error calculations, with 0.2≲ δ {L}{bol}/{L}{bol}≲ 0.5. Peak luminosities and 56Ni masses are similarly comparable to previous work. SN 2000cb remains an unusual member of this sub-group, owing to the faster rise and flatter plateau than the other supernovae in the sample. Initial comparisons with the NLTE atmosphere code PHOENIX show that the direct integration technique reproduces the luminosity of a model supernova spectrum to ∼5% when given synthetic photometry of the spectrum as input. Our code is publicly available. The ability to produce bolometric light curves from observed sets of broadband light curves should be helpful in the interpretation of other types of supernovae, particularly those that are not well characterized, such as extremely luminous supernovae and faint fast objects.

  14. Isolation of cDNA and genomic DNA clones encoding type II collagen.

    PubMed Central

    Young, M F; Vogeli, G; Nunez, A M; Fernandez, M P; Sullivan, M; Sobel, M E

    1984-01-01

    A cDNA library constructed from total chick embryo RNA was screened with an enriched fraction of type II collagen mRNA. Two overlapping cDNA clones were characterized and shown to encode the COOH propeptide of type II collagen. In addition, a type II collagen clone was isolated from a Charon 4A library of chick genomic fragments. Definitive identification of the clones was based on DNA sequence analysis. The 3' end of the type II collagen gene appears to be similar to that of other interstitial collagen genes. Northern hybridization data indicates that there is a marked decrease in type II collagen mRNA levels in chondrocytes treated with the dedifferentiating agent 5-bromodeoxyuridine. The major type II collagen mRNA species is 5300 bases long, similar to that of other interstitial collagen RNAs. Images PMID:6203098

  15. Alternative Splicing of Type II Procollagen: IIB or not IIB?

    PubMed Central

    McAlinden, Audrey

    2015-01-01

    Over two decades ago, two isoforms of the type II procollagen gene (COL2A1) were discovered. These isoforms, named IIA and IIB, are generated in a developmentally-regulated manner by alternative splicing of exon 2. Chondroprogenitor cells synthesize predominantly IIA isoforms (containing exon 2) while differentiated chondrocytes produce mainly IIB transcripts (devoid of exon 2). Importantly, this IIA-to-IIB alternative splicing switch occurs only during chondrogenesis. More recently, two other isoforms have been reported (IIC and IID) that also involve splicing of exon 2; these findings highlight the complexities involving regulation of COL2A1 expression. The biological significance of why different isoforms of COL2A1 exist within the context of skeletal development and maintenance is still not completely understood. This review will provide current knowledge on COL2A1 isoform expression during chondrocyte differentiation and what is known about some of the mechanisms that control exon 2 alternative splicing. Utilization of mouse models to address the biological significance of Col2a1 alternative splicing in vivo will also be discussed. From the knowledge acquired to date, some new questions and concepts are now being proposed on the importance of Col2a1 alternative splicing in regulating extracellular matrix assembly and how this may subsequently affect cartilage and endochondral bone quality and function. PMID:24669942

  16. Type II supernovae as a significant source of interstellar dust.

    PubMed

    Dunne, Loretta; Eales, Stephen; Ivison, Rob; Morgan, Haley; Edmunds, Mike

    2003-07-17

    Large amounts of dust (>10(8)M(o)) have recently been discovered in high-redshift quasars and galaxies corresponding to a time when the Universe was less than one-tenth of its present age. The stellar winds produced by stars in the late stages of their evolution (on the asymptotic giant branch of the Hertzsprung-Russell diagram) are thought to be the main source of dust in galaxies, but they cannot produce that dust on a short enough timescale (&<1 Gyr) to explain the results in the high-redshift galaxies. Supernova explosions of massive stars (type II) are also a potential source, with models predicting 0.2-4M(o) of dust. As massive stars evolve rapidly, on timescales of a few Myr, these supernovae could be responsible for the high-redshift dust. Observations of supernova remnants in the Milky Way, however, have hitherto revealed only 10(-7)-10(-3)M(o) each, which is insufficient to explain the high-redshift data. Here we report the detection of approximately 2-4M(o) of cold dust in the youngest known Galactic supernova remnant, Cassiopeia A. This observation implies that supernovae are at least as important as stellar winds in producing dust in our Galaxy and would have been the dominant source of dust at high redshifts.

  17. Inert dark matter in type-II seesaw

    NASA Astrophysics Data System (ADS)

    Chen, Chuan-Hung; Nomura, Takaaki

    2014-09-01

    Weakly interacting massive particle (WIMP) as a dark matter (DM) candidate is further inspired by recent AMS-02 data, which confirm the excess of positron fraction observed earlier by PAMELA and Fermi-LAT experiments. Additionally, the excess of positron+electron flux is still significant in the measurement of Fermi-LAT. For solving the problems of massive neutrinos and observed excess of cosmic-ray, we study the model with an inert Higgs doublet (IHD) in the framework of type-II seesaw model by imposing a Z 2 symmetry on the IHD, where the lightest particle of IHD is the DM candidate and the neutrino masses originate from the Yukawa couplings of Higgs triplet and leptons. We calculate the cosmic-ray production in our model by using three kinds of neutrino mass spectra, which are classified by normal ordering, inverted ordering and quasi-degeneracy. We find that when the constraints of DM relic density and comic-ray antiproton spectrum are taken into account, the observed excess of positron/electron flux could be explained well in normal ordered neutrino mass spectrum. Moreover, excess of comic-ray neutrinos is implied in our model. We find that our results on < σv> are satisfied with and close to the upper limit of IceCube analysis. More data from comic-ray neutrinos could test our model.

  18. Identification of type II and III DDR2 inhibitors.

    PubMed

    Richters, André; Nguyen, Hoang D; Phan, Trang; Simard, Jeffrey R; Grütter, Christian; Engel, Julian; Rauh, Daniel

    2014-05-22

    Discoidin domain-containing receptors (DDRs) exhibit a unique mechanism of action among the receptor tyrosine kinases (RTKs) because their catalytic activity is induced by extracellular collagen binding. Moreover, they are essential components in the assimilation of extracellular signals. Recently, DDRs were reported to be significantly linked to tumor progression in breast cancer by facilitating the processes of invasion, migration, and metastasis. Here, we report the successful development of a fluorescence-based, direct binding assay for the detection of type II and III DFG-out binders for DDR2. Using sequence alignments and homology modeling, we designed a DDR2 construct appropriate for fluorescent labeling. Successful assay development was validated by sensitive detection of a reference DFG-out binder. Subsequent downscaling led to convenient application to high-throughput screening formats. Screening of a representative compound library identified high-affinity DDR2 ligands validated by orthogonal activity-based assays, and a subset of identified compounds was further investigated with respect to DDR1 inhibition.

  19. Type II dehydroquinase: molecular replacement with many copies

    PubMed Central

    Stewart, Kirsty Anne; Robinson, David Alexander; Lapthorn, Adrian Jonathan

    2008-01-01

    Type II dehydroquinase is a small (150-amino-acid) protein which in solution packs together to form a dodecamer with 23 cubic symmetry. In crystals of this protein the symmetry of the biological unit can be coincident with the crystallographic symmetry, giving rise to cubic crystal forms with a single monomer in the asymmetric unit. In crystals where this is not the case, multiple copies of the monomer are present, giving rise to significant and often confusing noncrystallographic symmetry in low-symmetry crystal systems. These different crystal forms pose a variety of challenges for solution by molecular replacement. Three examples of structure solutions, including a highly unusual triclinic crystal form with 16 dodecamers (192 monomers) in the unit cell, are described. Four commonly used molecular-replacement packages are assessed against two of these examples, one of high symmetry and the other of low symmetry; this study highlights how program performance can vary significantly depending on the given problem. In addition, the final refined structure of the 16-dodecamer triclinic crystal form is analysed and shown not to be a superlattice structure, but rather an F-centred cubic crystal with frustrated crystallographic symmetry. PMID:18094474

  20. Health perceptions among urban American Indians with type II diabetes.

    PubMed

    Patel, Sachin; Davila, Javier; Patel, Sonam; Norman, Dennis

    2014-01-01

    Since the 1940s, American Indians (AIs) have increasingly urbanized, moving off of reservations in large part due to federal policies of tribal termination and relocation. Though previous AI research has largely focused on reservation-associated challenges, many of these same challenges persist among urban AI populations. One mutual concern is the growing prevalence and incidence of type II diabetes mellitus (T2DM). While behavioral, genetic, and socioeconomic determinants of T2DM have been explored, much less is known about the influence of cultural and psychosocial factors. Recent studies suggest that the way AIs perceive diabetes may affect their health trajectory and explain their poor prognosis. Through the use of the Illness Perception Questionnaire, we explored this hypothesis in a pilot study of urban AI with T2DM living in Los Angeles County. We found that the majority of participants have a neutral perception about their diabetes: They view their condition to be long lasting yet treatable and indicate reasonable understanding of its symptoms and progression. We also identified "personal control," the level of perceived control one has over his or her disease, as a strong correlate of overall illness perception and, thus, a potentially useful psychological metric.

  1. Balneotherapy and platelet glutathione metabolism in type II diabetic patients

    NASA Astrophysics Data System (ADS)

    Ohtsuka, Yoshinori; Yabunaka, Noriyuki; Watanabe, Ichiro; Noro, Hiroshi; Agishi, Yuko

    1996-09-01

    Effects of balneotherapy on platelet glutathione metabolism were investigated in 12 type II (non-insulin-dependent) diabetic patients. Levels of the reduced form of glutathione (GSH) on admission were well correlated with those of fasting plasma glucose (FPG; r=0.692, P<0.02). After 4 weeks of balneotherapy, the mean level of GSH showed no changes; however, in well-controlled patients (FPG <150 mg/dl), the level increased ( P<0.01) and in poorly controlled patients (FPG >150 mg/dl), the value decreased ( P<0.05). There was a negative correlation between glutathione peroxidase (GPX) activities and the levels of FPG ( r=-0.430, P<0.05). After balneotherapy, the activity increased in 5 patients, decreased in 3 patients and showed no changes (alteration within ±3%) in all the other patients. From these findings in diabetic patients we concluded: (1) platelet GSH synthesis appeared to be induced in response to oxidative stress; (2) lowered GPX activities indicated that the antioxidative defense system was impaired; and (3) platelet glutathione metabolism was partially improved by 4 weeks balneotherapy, an effect thought to be dependent on the control status of plasma glucose levels. It is suggested that balneotherapy is beneficial for patients whose platelet antioxidative defense system is damaged, such as those with diabetes mellitus and coronary heart disease.

  2. Simvastatin enhances bone morphogenetic protein receptor type II expression

    SciTech Connect

    Hu Hong; Sung, Arthur; Zhao, Guohua; Shi, Lingfang; Qiu Daoming; Nishimura, Toshihiko; Kao, Peter N. . E-mail: peterkao@stanford.edu

    2006-01-06

    Statins confer therapeutic benefits in systemic and pulmonary vascular diseases. Bone morphogenetic protein (BMP) receptors serve essential signaling functions in cardiovascular development and skeletal morphogenesis. Mutations in BMP receptor type II (BMPR2) are associated with human familial and idiopathic pulmonary arterial hypertension, and pathologic neointimal proliferation of vascular endothelial and smooth muscle cells within small pulmonary arteries. In severe experimental pulmonary hypertension, simvastatin reversed disease and conferred a 100% survival advantage. Here, modulation of BMPR2 gene expression by simvastatin is characterized in human embryonic kidney (HEK) 293T, pulmonary artery smooth muscle, and lung microvascular endothelial cells (HLMVECs). A 1.4 kb BMPR2 promoter containing Egr-1 binding sites confers reporter gene activation in 293T cells which is partially inhibited by simvastatin. Simvastatin enhances steady-state BMPR2 mRNA and protein expression in HLMVEC, through posttranscriptional mRNA stabilization. Simvastatin induction of BMPR2 expression may improve BMP-BMPR2 signaling thereby enhancing endothelial differentiation and function.

  3. ``N'' structure for type-II superlattice photodetectors

    NASA Astrophysics Data System (ADS)

    Salihoglu, Omer; Muti, Abdullah; Kutluer, Kutlu; Tansel, Tunay; Turan, Rasit; Ergun, Yuksel; Aydinli, Atilla

    2012-08-01

    In the quest to raise the operating temperature and improve the detectivity of type II superlattice (T2SL) photodetectors, we introduce a design approach that we call the "N structure." N structure aims to improve absorption by manipulating electron and hole wavefunctions that are spatially separated in T2SLs, increasing the absorption while decreasing the dark current. In order to engineer the wavefunctions, we introduce a thin AlSb layer between InAs and GaSb layers in the growth direction which also acts as a unipolar electron barrier. Unlike the symmetrical insertion of AlSb into GaSb layers, N design aims to exploit the shifting of the electron and hole wavefunctions under reverse bias. With cutoff wavelength of 4.3 μm at 77 K, temperature dependent dark current and detectivity measurements show that the dark current density is 3.6 × 10-9 A/cm2, under zero bias. Photodetector reaches background limited infrared photodetection (BLIP) condition at 125 K with the BLIP detectivity (D*BLIP) of 2.6 × 1010 Jones under 300 K background and -0.3 V bias voltage.

  4. Type II Radio Bursts as an Indicator of CME Location

    NASA Astrophysics Data System (ADS)

    Quirk, C. A.; St Cyr, O. C.; Henning, C.; Xie, H.; Gilbert, H. R.; Orlove, M.; Gopalswamy, N.; Odstrcil, D.

    2011-12-01

    We examined a subset of nine low-frequency radio events with type II radio bursts that drifted below 2 megahertz and were detected by the WAVES investigation on the WIND spacecraft. For each event, we identified the associated coronal mass ejection (CME) and derived the electron density using a model of solar wind plasma frequency (fp ≈ 9 * ne1/2, where fp is plasma frequency in kHz and ne is electron density in cm-3) . We also used the pb_inverter program in SolarSoft developed by Howard and Hayes to examine the electron density structure. Expanding on the Van De Hulst process of inverting polarized brightness measurements, the program inverts total brightness measurements from SOHO LASCO images to extract electron density information. From the electron density inferred from radio spectra, we derived the location of the CME using five standard electron density to height models (Leblanc, 1996; Saito, 1977; Bougeret, 1984; Alvarez, 1973; and Fainberg, 1971). Using images from the LASCO instrument on SOHO and the SECCHI instrument on STEREO, we extracted locations of the leading edge of the CME and compared the heights and velocities to those found using the frequency data. For the lowest frequency events, we also compared our results to the outputs of ENLIL, a time-dependent, three-dimensional, MHD model of the heliosphere hosted by the Community Coordinated Modeling Center (CCMC) at NASA Goddard Space Flight Center.

  5. Redesigning the type II' β-turn in green fluorescent protein to type I': implications for folding kinetics and stability.

    PubMed

    Madan, Bharat; Sokalingam, Sriram; Raghunathan, Govindan; Lee, Sun-Gu

    2014-10-01

    Both Type I' and Type II' β-turns have the same sense of the β-turn twist that is compatible with the β-sheet twist. They occur predominantly in two residue β-hairpins, but the occurrence of Type I' β-turns is two times higher than Type II' β-turns. This suggests that Type I' β-turns may be more stable than Type II' β-turns, and Type I' β-turn sequence and structure can be more favorable for protein folding than Type II' β-turns. Here, we redesigned the native Type II' β-turn in GFP to Type I' β-turn, and investigated its effect on protein folding and stability. The Type I' β-turns were designed based on the statistical analysis of residues in natural Type I' β-turns. The substitution of the native "GD" sequence of i+1 and i+2 residues with Type I' preferred "(N/D)G" sequence motif increased the folding rate by 50% and slightly improved the thermodynamic stability. Despite the enhancement of in vitro refolding kinetics and stability of the redesigned mutants, they showed poor soluble expression level compared to wild type. To overcome this problem, i and i + 3 residues of the designed Type I' β-turn were further engineered. The mutation of Thr to Lys at i + 3 could restore the in vivo soluble expression of the Type I' mutant. This study indicates that Type II' β-turns in natural β-hairpins can be further optimized by converting the sequence to Type I'.

  6. Higgs potential in the type II seesaw model

    SciTech Connect

    Arhrib, A.; Benbrik, R.; Chabab, M.; Rahili, L.; Ramadan, J.; Moultaka, G.; Peyranere, M. C.

    2011-11-01

    The standard model Higgs sector, extended by one weak gauge triplet of scalar fields with a very small vacuum expectation value, is a very promising setting to account for neutrino masses through the so-called type II seesaw mechanism. In this paper we consider the general renormalizable doublet/triplet Higgs potential of this model. We perform a detailed study of its main dynamical features that depend on five dimensionless couplings and two mass parameters after spontaneous symmetry breaking, and highlight the implications for the Higgs phenomenology. In particular, we determine (i) the complete set of tree-level unitarity constraints on the couplings of the potential and (ii) the exact tree-level boundedness from below constraints on these couplings, valid for all directions. When combined, these constraints delineate precisely the theoretically allowed parameter space domain within our perturbative approximation. Among the seven physical Higgs states of this model, the mass of the lighter (heavier) CP{sub even} state h{sup 0} (H{sup 0}) will always satisfy a theoretical upper (lower) bound that is reached for a critical value {mu}{sub c} of {mu} (the mass parameter controlling triple couplings among the doublet/triplet Higgses). Saturating the unitarity bounds, we find an upper bound m{sub h}{sup 0} or approx. {mu}{sub c} and {mu} < or approx. {mu}{sub c}. In the first regime the Higgs sector is typically very heavy, and only h{sup 0} that becomes SM-like could be accessible to the LHC. In contrast, in the second regime, somewhat overlooked in the literature, most of the Higgs sector is light. In particular, the heaviest state H{sup 0} becomes SM-like, the lighter states being the CP{sub odd} Higgs, the (doubly) charged Higgses, and a decoupled h{sup 0}, possibly

  7. Halothane-induced alterations in cellular structure and proliferation of A549 cells.

    PubMed

    Stephanova, E; Topouzova-Hristova, T; Hazarosova, R; Moskova, V

    2008-12-01

    Genotoxicity, cytotoxicity or teratogenicity are among the well-known detrimental effects of the volatile anaesthetics. The aim of the present work was to study the structural changes, proliferative activity and the possibility of alveolar A549 cells to recover after in vitro exposure to halothane at 1.5 and 2.1mM concentrations. Our data indicated significant reduction of viability, suppression of mitotic activity more than 60%, and that these alterations were accompanied by disturbances of nuclear and nucleolar structures. The most prominent negative effect was the destruction of the lamellar bodies, the main storage organelles of pulmonary surfactant, substantial for the lung physiology. In conclusion, halothane applied at clinically relevant concentrations exerts genotoxic and cytotoxic effect on the alveolar cells in vitro, most likely as a consequence of stress-induced apoptosis, thus modulating the respiratory function.

  8. In vitro anticancer activity of fucoidan from Turbinaria conoides against A549 cell lines.

    PubMed

    Marudhupandi, Thangapandi; Ajith Kumar, Thipramalai Thankappan; Lakshmanasenthil, Shanmugaasokan; Suja, Gunasekaran; Vinothkumar, Thirumalairaj

    2015-01-01

    The present study was conducted to evaluate the anticancer activity of fucoidan isolated from brown seaweed Turbinaria conoides. Extracted fucoidan contained 53 ± 0.69% of fucose and 38 ± 0.42% of sulphate, respectively. Functional groups and structural characteristics of the fucoidan were analyzed by FT-IR and NMR. In vitro anticancer effect was studied on A549 cell line. Fucoidan inhibited the growth of cancer cells in a dose-dependent manner and potent anticancer activities were 24.9-73.5% in the concentrations of 31.25-500 μg/ml. The CTC50 value against the cancer cell was found to be 45 μg/ml and the CTC50 value of normal Vero cell line is 325 μg/ml. This study suggests that the fucoidan from T. conoides could be significantly improved if the active component is further purified and tested for further investigation in various cancer cell lines.

  9. Proteomic response to 5,6-dimethylxanthenone 4-acetic acid (DMXAA, vadimezan) in human non-small cell lung cancer A549 cells determined by the stable-isotope labeling by amino acids in cell culture (SILAC) approach.

    PubMed

    Pan, Shu-Ting; Zhou, Zhi-Wei; He, Zhi-Xu; Zhang, Xueji; Yang, Tianxin; Yang, Yin-Xue; Wang, Dong; Qiu, Jia-Xuan; Zhou, Shu-Feng

    2015-01-01

    5,6-Dimethylxanthenone 4-acetic acid (DMXAA), also known as ASA404 and vadimezan, is a potent tumor blood vessel-disrupting agent and cytokine inducer used alone or in combination with other cytotoxic agents for the treatment of non-small cell lung cancer (NSCLC) and other cancers. However, the latest Phase III clinical trial has shown frustrating outcomes in the treatment of NSCLC, since the therapeutic targets and underlying mechanism for the anticancer effect of DMXAA are not yet fully understood. This study aimed to examine the proteomic response to DMXAA and unveil the global molecular targets and possible mechanisms for the anticancer effect of DMXAA in NSCLC A549 cells using a stable-isotope labeling by amino acids in cell culture (SILAC) approach. The proteomic data showed that treatment with DMXAA modulated the expression of 588 protein molecules in A549 cells, with 281 protein molecules being up regulated and 306 protein molecules being downregulated. Ingenuity pathway analysis (IPA) identified 256 signaling pathways and 184 cellular functional proteins that were regulated by DMXAA in A549 cells. These targeted molecules and signaling pathways were mostly involved in cell proliferation and survival, redox homeostasis, sugar, amino acid and nucleic acid metabolism, cell migration, and invasion and programed cell death. Subsequently, the effects of DMXAA on cell cycle distribution, apoptosis, autophagy, and reactive oxygen species (ROS) generation were experimentally verified. Flow cytometric analysis showed that DMXAA significantly induced G1 phase arrest in A549 cells. Western blotting assays demonstrated that DMXAA induced apoptosis via a mitochondria-dependent pathway and promoted autophagy, as indicated by the increased level of cytosolic cytochrome c, activation of caspase 3, and enhanced expression of beclin 1 and microtubule-associated protein 1A/1B-light chain 3 (LC3-II) in A549 cells. Moreover, DMXAA significantly promoted intracellular ROS

  10. Cytokines from the tumor microenvironment modulate sirtinol cytotoxicity in A549 lung carcinoma cells.

    PubMed

    Pal, Shyama; Shankar, Bhavani S; Sainis, Krishna B

    2013-10-01

    Cytokines in tumor microenvironment play an important role in the success or failure of molecular targeted therapies. We have chosen tumor necrosis factor α (TNF-α), TNF related apoptosis inducing ligand (TRAIL), insulin-like growth factor 1 (IGF-1) and transforming growth factor β (TGF-β) as representative pro-inflammatory, pro-apoptotic, anti-apoptotic and anti-inflammatory tumor derived cytokines. Analysis of Oncomine database revealed the differential expression of these cytokines in a subset of cancer patients. The effects of these cytokines on cytotoxicity of FDA approved drugs - cisplatin and taxol and inhibitors of epidermal growth factor receptor - AG658, Janus kinase - AG490 and SIRT1 - sirtinol were assessed in A549 lung cancer cells. TRAIL augmented cytotoxicity of sirtinol and IGF-1 had a sparing effect. Since TRAIL and IGF-1 differentially modulated sirtinol cytotoxicity, further studies were carried out to identify the mechanisms. Sirtinol or knockdown of SIRT1 increased the expression of death receptors DR4 and DR5 and sensitized A549 cells to TRAIL. Increased cell death in presence of TRAIL and sirtinol was caspase independent and demonstrated classical features of necroptosis. Inhibition of iNOS increased caspase activity and switched the mode of cell death to caspase mediated apoptosis. Interestingly, sirtinol or SIRT1 knockdown did not increase IGF-1R expression. Instead, it abrogated ligand induced downregulation of IGF-1R and increased cell survival through PI3K-AKT pathway. In conclusion, these findings reveal that the tumor microenvironment contributes to modulation of cytotoxicity of drugs and that combination therapy, with agents that increase TRAIL signaling and suppress IGF-1 pathway may potentiate anticancer effect.

  11. High Throughput Determination of TGFβ1/SMAD3 Targets in A549 Lung Epithelial Cells

    PubMed Central

    Kaplan, Tommy; Yu, Haiying; Bais, Abha S.; Richards, Thomas; Pandit, Kusum V.; Zeng, Qilu; Benos, Panayiotis V.; Friedman, Nir; Eickelberg, Oliver; Kaminski, Naftali

    2011-01-01

    Background Transforming growth factor beta 1 (TGFβ1) plays a major role in many lung diseases including lung cancer, pulmonary hypertension, and pulmonary fibrosis. TGFβ1 activates a signal transduction cascade that results in the transcriptional regulation of genes in the nucleus, primarily through the DNA-binding transcription factor SMAD3. The objective of this study is to identify genome-wide scale map of SMAD3 binding targets and the molecular pathways and networks affected by the TGFβ1/SMAD3 signaling in lung epithelial cells. Methodology We combined chromatin immunoprecipitation with human promoter region microarrays (ChIP-on-chip) along with gene expression microarrays to study global transcriptional regulation of the TGFβ1/SMAD3 pathway in human A549 alveolar epithelial cells. The molecular pathways and networks associated with TGFβ1/SMAD3 signaling were identified using computational approaches. Validation of selected target gene expression and direct binding of SMAD3 to promoters were performed by quantitative real time RT-PCR and electrophoretic mobility shift assay on A549 and human primary lung epithelial cells. Results and Conclusions Known TGFβ1 target genes such as SERPINE1, SMAD6, SMAD7, TGFB1 and LTBP3, were found in both ChIP-on-chip and gene expression analyses as well as some previously unrecognized targets such as FOXA2. SMAD3 binding of FOXA2 promoter and changed expression were confirmed. Computational approaches combining ChIP-on-chip and gene expression microarray revealed multiple target molecular pathways affected by the TGFβ1/SMAD3 signaling. Identification of global targets and molecular pathways and networks associated with TGFβ1/SMAD3 signaling allow for a better understanding of the mechanisms that determine epithelial cell phenotypes in fibrogenesis and carcinogenesis as does the discovery of the direct effect of TGFβ1 on FOXA2. PMID:21625455

  12. Calcium is not required for triggering volume restoration in hypotonically challenged A549 epithelial cells.

    PubMed

    Ponomarchuk, Olga; Boudreault, Francis; Orlov, Sergei N; Grygorczyk, Ryszard

    2016-11-01

    Maintenance of cell volume is a fundamental housekeeping function in eukaryotic cells. Acute cell swelling activates a regulatory volume decrease (RVD) process with poorly defined volume sensing and intermediate signaling mechanisms. Here, we analyzed the putative role of Ca(2+) signaling in RVD in single substrate-adherent human lung epithelial A549 cells. Acute cell swelling was induced by perfusion of the flow-through imaging chamber with 50 % hypotonic solution at a defined fluid turnover rate. Changes in cytosolic Ca(2+) concentration ([Ca(2+)]i) and cell volume were monitored simultaneously with ratiometric Fura-2 fluorescence and 3D reconstruction of stereoscopic single-cell images, respectively. Hypotonic challenge caused a progressive swelling peaking at ∼20 min and followed, during the next 20 min, by RVD of 60 ± 7 % of the peak volume increase. However, at the rate of swelling used in our experiments, these processes were not accompanied by a measurable increment of [Ca(2+)]i. Loading with intracellular Ca(2+) chelator BAPTA slightly delayed peak of swelling but did not prevent RVD in 82 % of cells. Further, electrophysiology whole-cell patch-clamp experiments showed that BAPTA did not block activation of volume-regulated anion channel (VRAC) measured as swelling-induced outwardly rectifying 5-nitro-2-(3-phenylpropyl-amino) benzoic acid sensitive current. Together, our data suggest that intracellular Ca(2+)-mediated signaling is not essential for VRAC activation and subsequent volume restoration in A549 cells.

  13. Blocking the NOTCH pathway can inhibit the growth of CD133-positive A549 cells and sensitize to chemotherapy.

    PubMed

    Liu, Juntao; Mao, Zhangfan; Huang, Jie; Xie, Songping; Liu, Tianshu; Mao, Zhifu

    2014-02-21

    Cancer stem cells (CSCs) are believed to play an important role in tumor growth and recurrence. These cells exhibit self-renewal and proliferation properties. CSCs also exhibit significant drug resistance compared with normal tumor cells. Finding new treatments that target CSCs could significantly enhance the effect of chemotherapy and improve patient survival. Notch signaling is known to regulate the development of the lungs by controlling the cell-fate determination of normal stem cells. In this study, we isolated CSCs from the human lung adenocarcinoma cell line A549. CD133 was used as a stem cell marker for fluorescence-activated cell sorting (FACS). We compared the expression of Notch signaling in both CD133+ and CD133- cells and blocked Notch signaling using the γ-secretase inhibitor DAPT (GSI-IX). The effect of combining GSI and cisplatin (CDDP) was also examined in these two types of cells. We observed that both CD133+ and CD133- cells proliferated at similar rates, but the cells exhibited distinctive differences in cell cycle progression. Few CD133+ cells were observed in the G2/M phase, and there were half as many cells in S phase compared with the CD133- cells. Furthermore, CD133+ cells exhibited significant resistance to chemotherapy when treated with CDDP. The expression of Notch signaling pathway members, such as Notch1, Notch2 and Hes1, was lower in CD133+ cells. GSI slightly inhibited the proliferation of both cell types and exhibited little effect on the cell cycle. The inhibitory effects of DPP on these two types of cells were enhanced when combined with GSI. Interestingly, this effect was especially significant in CD133+ cells, suggesting that Notch pathway blockade may be a useful CSC-targeted therapy in lung cancer.

  14. Salvianolic acid A positively regulates PTEN protein level and inhibits growth of A549 lung cancer cells

    PubMed Central

    BI, LEI; CHEN, JIANPING; YUAN, XIAOJING; JIANG, ZEQUN; CHEN, WEIPING

    2013-01-01

    Salvianolic acid A (Sal A) is an effective compound extracted from Salvia miltiorrhiza which has been used in the treatment of various diseases. Preliminary data indicate that Sal A treatment has a specific anti-lung cancer effect. However, the manner in which Sal A regulates cancer growth remains unknown. In this study, the A549 lung cancer cell line and its response to Sal A treatment was examined. Results showed that Sal A treatment significantly decreased A549 cell growth, promoted partial apoptosis and increased mitochondrial membrane permeability. Western blot analysis showed that Sal A upregulated the phosphatase and tensin homolog (PTEN) protein level, while consistently downregulating Akt phosphorylation. These results indicate that Sal A negatively mediates A549 lung cancer cell line growth or apoptosis, most likely by positively regulating PTEN protein level. PMID:24648921

  15. 46 CFR 171.070 - Subdivision requirements--Type II.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... have a collision bulkhead. (d) Paragraph (c) of this section applies to a ferry vessel that— (1) Is 150... other main transverse watertight bulkhead; (ii) The collision bulkhead; and (iii) The aftermost point on... transverse watertight bulkhead; (ii) The collision bulkhead; and (iii) The aftermost point on the...

  16. 46 CFR 171.070 - Subdivision requirements--Type II.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... have a collision bulkhead. (d) Paragraph (c) of this section applies to a ferry vessel that— (1) Is 150... other main transverse watertight bulkhead; (ii) The collision bulkhead; and (iii) The aftermost point on... transverse watertight bulkhead; (ii) The collision bulkhead; and (iii) The aftermost point on the...

  17. 5-allyl-7-gen-difluoromethoxychrysin enhances TRAIL-induced apoptosis in human lung carcinoma A549 cells

    PubMed Central

    2011-01-01

    Background 5-allyl-7-gen-difluoromethoxychrysin (AFMC) is a novel synthetic analogue of chrysin that has been reported to inhibit proliferation in various cancer cell lines. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer agent. Methods The cytotoxicity of A549 and WI-38 cells were determined using colorimetry. Apoptosis was detected by flow cytometry (FCM) after propidium iodide (PI) fluorescence staining and agarose gel electrophoresis. Caspase activities were evaluated using enzyme-linked immunosorbent assay (ELISA).The expressions of DR4 and DR5 were analyzed using FCM and western blot. Results Subtoxic concentrations of AFMC sensitize human non-small cell lung cancer (NSCLC) A549 cells to TRAIL-mediated apoptosis. Combined treatment of A549 cells with AFMC and TRAIL significantly activated caspase-3, -8 and -9. The caspase-3 inhibitor zDEVD-fmk and the caspase-8 inhibitor zIETD-fmk blocked the apoptosis of A549 cells induced by co-treatment with AFMC and TRAIL. In addition, we found that treatment of A549 cells with AFMC significantly induced the expression of death receptor 5 (DR5). AFMC-mediated sensitization of A549 cells to TRAIL was efficiently reduced by administration of a blocking antibody or small interfering RNAs against DR5. AFMC also caused increase of the Sub-G1 cells by TRAIL treatment and increased the expression levels of DR5 in other NSCLC H460 and H157 cell lines. In contrast, AFMC-mediated induction of DR5 expression was not observed in human embryo lung WI-38 cells, and AFMC did not sensitize WI-38 cells to TRAIL-induced apoptosis. Conclusions AFMC synergistically enhances TRAIL-mediated apoptosis in NSCLC cells through up-regulating DR5 expression. PMID:21801359

  18. ACTIVE IMMUNIZATION OF MICE WITH THE POLYSACCHARIDES OF PNEUMOCOCCI TYPES I, II AND III

    PubMed Central

    Zozaya, José; Clark, Janet

    1933-01-01

    1. Pneumococcus polysaccharides Types I, II and III adsorbed on collodion particles, and Types I and III adsorbed on carbon (norit) are antigenic in mice. 2. Unadsorbed pneumococcus polysaccharide of Type I is antigenic in mice in proper dilution. One preparation of Type II polysaccharide was not antigenic, while another one immunized against Types I and II. Type III polysaccharide was only slightly antigenic against Type III but immunized against Type I. 3. The antigenicity of pneumococcus polysaccharide in optimal dosage is tentatively explained by an adsorption phenomenon taking place in the body in instances in which the polysaccharides had not been adsorbed before injection. 4. The aggressin-like action of large doses of pneumococcus polysaccharides Types I, II and III is further established. PMID:19870119

  19. Matrix composition of cartilaginous anlagen in achondrogenesis type II (Langer-Saldino).

    PubMed

    Dertinger, Susanne; Söeder, Stephan; Bösch, Hubert; Aigner, Thomas

    2005-01-01

    Skeletal dysplasias represent in vivo models of genetic defects. Achondrogenesis type II (Langer-Saldino), caused by a genetic defect in the major cartilage matrix protein, collagen type II, is a rare and severe skeletal dysplasia. It comprises a severe derangement of the fetal growth plate cartilage with subsequent ossification defects. In this study, we analyzed the matrix composition and cell differentiation pattern in 3 relatives with achondrogenesis type II. Most strikingly we found a strongly reduced collagen type II and moderately reduced aggrecan proteoglycan content in the dysplastic cartilage matrix. Type II collagen is, at least to some extent, replaced by collagens type I III, and VI. Ultrastructural analysis of the dysplastic cartilage matrix demonstrated a distended rER (rough endoplasmic reticulum), which is typical for this condition and most likely related to improper processing and retention of genetically altered type II collagen. Immunostaining for type IIA and X collagens suggest a severe delay in chondrocyte maturation. Thus, the genetic defect in the present cases leads most likely to a severe retention of collagen type II in the rER and, therefore, a strongly reduced collagen deposition and replacement by other interstitial collagens. However, the latter are less efficient in binding aggrecan proteoglycans in the dysplastic cartilage matrix. Additionally, a delay in chondrocyte maturation appears to be important in achondrogenesis type II.

  20. Investigation of resistive losses in type II superconductors

    NASA Astrophysics Data System (ADS)

    Benapfl, Brendan W.

    For low-TC materials, the superconducting transition temperature (TC) is depressed by the application of a magnetic field. In contrast, one of the remarkable features of cuprate high-TC materials is that the superconducting transition is broadened by the application of a magnetic field. Tinkham presented a model for the field-dependent resistive transition of high-T C materials, arising from "phase slippage at a complicated network of channels." Coffey & Clem did not include this field-broadening effect in their sophisticated model for the field and temperature dependence of the surface resistance in type-II superconductors. From the model by Lee & Stroud, treating Josephson Junction-coupled superconducting segments, it is concluded that doped, layered superconductors are certain to have a field-broadened superconducting transition. This effect can be identified by measurements of the resistivity as a function of temperature, magnetic field strength, angle of field with respect to the crystal axis as well as with respect to an induced current density. The iron pnictide materials such as Ba0.6K0.4Fe2As2 (BaK122) have chemical layers with different compositions, differentiating them from elemental type-II superconductors such as niobium, and also from cuprates, by the absence of copper. Experimental data on BaK122 indicate a field-broadened transition in conjunction with a field-depressed superconducting transition temperature. In this work, techniques associated with Electron Spin Resonance (ESR) spectroscopy were used to measure the temperature and field-induced changes in the surface resistance of single-crystal BaK122 samples. In addition, polycrystalline foils of niobium and a NbTi (70/30) alloy were measured using the same techniques to provide comparison. Measurements were taken as a function of applied magnetic field, temperature, rf field intensity, and angle of the applied field with respect to the rf-induced current. BaK122 sample field-dependent surface

  1. Unusual compactness of a polyproline type II structure

    PubMed Central

    Zagrovic, Bojan; Lipfert, Jan; Sorin, Eric J.; Millett, Ian S.; van Gunsteren, Wilfred F.; Doniach, Sebastian; Pande, Vijay S.

    2005-01-01

    Polyproline type II (PPII) helix has emerged recently as the dominant paradigm for describing the conformation of unfolded polypeptides. However, most experimental observables used to characterize unfolded proteins typically provide only short-range, sequence-local structural information that is both time- and ensemble-averaged, giving limited detail about the long-range structure of the chain. Here, we report a study of a long-range property: the radius of gyration of an alanine-based peptide, Ace-(diaminobutyric acid)2-(Ala)7-(ornithine)2-NH2. This molecule has previously been studied as a model for the unfolded state of proteins under folding conditions and is believed to adopt a PPII fold based on short-range techniques such as NMR and CD. By using synchrotron radiation and small-angle x-ray scattering, we have determined the radius of gyration of this peptide to be 7.4 ± 0.5 Å, which is significantly less than the value expected from an ideal PPII helix in solution (13.1 Å). To further study this contradiction, we have used molecular dynamics simulations using six variants of the AMBER force field and the GROMOS 53A6 force field. However, in all cases, the simulated ensembles underestimate the PPII content while overestimating the experimental radius of gyration. The conformational model that we propose, based on our small angle x-ray scattering results and what is known about this molecule from before, is that of a very flexible, fluctuating structure that on the level of individual residues explores a wide basin around the ideal PPII geometry but is never, or only rarely, in the ideal extended PPII helical conformation. PMID:16085707

  2. Non-insulin-dependent (type II) diabetes mellitus.

    PubMed Central

    Rodger, W

    1991-01-01

    Non-insulin-dependent (type II) diabetes mellitus is an inherited metabolic disorder characterized by hyperglycemia with resistance to ketosis. The onset is usually after age 40 years. Patients are variably symptomatic and frequently obese, hyperlipidemic and hypertensive. Clinical, pathological and biochemical evidence suggests that the disease is caused by a combined defect of insulin secretion and insulin resistance. Goals in the treatment of hyperglycemia, dyslipidemia and hypertension should be appropriate to the patient's age, the status of diabetic complications and the safety of the regimen. Nonpharmacologic management includes meal planning to achieve a suitable weight, such that carbohydrates supply 50% to 60% of the daily energy intake, with limitation of saturated fats, cholesterol and salt when indicated, and physical activity appropriate to the patient's age and cardiovascular status. Follow-up should include regular visits with the physician, access to diabetes education, self-monitoring of the blood or urine glucose level and laboratory-based measurement of the plasma levels of glucose and glycated hemoglobin. If unacceptably high plasma glucose levels (e.g., 8 mmol/L or more before meals) persist the use of orally given hypoglycemic agents (a sulfonylurea agent or metformin or both) is indicated. Temporary insulin therapy may be needed during intercurrent illness, surgery or pregnancy. Long-term insulin therapy is recommended in patients with continuing symptoms or hyperglycemia despite treatment with diet modification and orally given hypoglycemic agents. The risk of pancreatitis may be reduced by treating severe hypertriglyceridemia (fasting serum level greater than 10 mmol/L) and atherosclerotic disease through dietary and, if necessary, pharmacologic management of dyslipidemia. Antihypertensive agents are available that have fewer adverse metabolic effects than thiazides and beta-adrenergic receptor blockers. New drugs are being developed that

  3. Screening of three Usher syndrome type II candidate genes

    SciTech Connect

    Bloemker, B.K.; Swaroop, A.; Kimberling, W.J.

    1994-09-01

    Usher syndrome type II (US2) is an autosomal recessive disorder that results in blindness due to retinitis pigmentosa and congenital hearing loss. The disease affects approximately 1 in 20,000 individuals in the general population and is responsible for over 50% of all cases of deafness with blindness. The underlying US2 defect is unknown. The US2 gene has been localized to the 1q41 region of chromosome 1 by linkage studies. Three genes previously localized to 1q were analyzed to assess their candidacy as the US2 gene. These were evaluated by PCR assays using DNA from a YAC contig spanning the US2 region on chromosome 1. The first gene evaluated was the human choroideremia-like gene (hCHML), which had been mapped to chromosome 1q. The sequence on 1q is a homologue of the human choroideremia gene on chromosome X. Choroideremia is a degenerative disorder causing ocular pathology similar to that observed in US2 patients. Therefore, hCHML is a candidate for the US2 gene. Two cDNAs (A and B) from an enriched human retinal pigment epithelium library have been mapped to 1q41 by in situ hybridization. Both cDNAs are considered good candidates. The hCHML and cDNA A were ruled out as candidates for the US2 gene based on negative results from PCR assays performed on YACs spanning the US2 region. cDNA B could not be ruled out as a candidate for the US2 gene by these assays. Answers to many clinical questions regarding US2 will only be resolved after the gene is identified and characterized. Eventually, understanding the function and expression of the US2 gene will provide a basis for the development of therapy.

  4. Radiation-hydrodynamical modelling of underluminous Type II plateau supernovae

    NASA Astrophysics Data System (ADS)

    Pumo, M. L.; Zampieri, L.; Spiro, S.; Pastorello, A.; Benetti, S.; Cappellaro, E.; Manicò, G.; Turatto, M.

    2017-01-01

    With the aim of improving our knowledge about the nature of the progenitors of low-luminosity Type II plateau supernovae (LL SNe IIP), we made radiation-hydrodynamical models of the well-sampled LL SNe IIP 2003Z, 2008bk and 2009md. For these three SNe, we infer explosion energies of 0.16-0.18 foe, radii at explosion of 1.8-3.5 × 1013 cm and ejected masses of 10-11.3 M⊙. The estimated progenitor mass on the main sequence is in the range ˜13.2-15.1 M⊙ for SN 2003Z and ˜11.4-12.9 M⊙ for SNe 2008bk and 2009md, in agreement with estimates from observations of the progenitors. These results together with those for other LL SNe IIP modelled in the same way enable us also to conduct a comparative study on this SN sub-group. The results suggest that (a) the progenitors of faint SNe IIP are slightly less massive and have less energetic explosions than those of intermediate-luminosity SNe IIP; (b) both faint and intermediate-luminosity SNe IIP originate from low-energy explosions of red (or yellow) supergiant stars of low to intermediate mass; (c) some faint objects may also be explained as electron-capture SNe from massive super-asymptotic giant branch stars; and (d) LL SNe IIP form the underluminous tail of the SNe IIP family, where the main parameter `guiding' the distribution seems to be the ratio of the total explosion energy to the ejected mass. Further hydrodynamical studies should be performed and compared to a more extended sample of LL SNe IIP before drawing any conclusion on the relevance of fall-back to this class of events.

  5. Macrovascular complications in Mexican Americans with type II diabetes.

    PubMed

    Haffner, S M; Mitchell, B D; Stern, M P; Hazuda, H P

    1991-07-01

    Mexican Americans have a threefold greater prevalence of non-insulin-dependent (type II) diabetes mellitus than non-Hispanic whites in the San Antonio Heart Study, a population-based study of diabetes. In addition, Mexican-American diabetic subjects (n = 365) have greater fasting glycemia than non-Hispanic white diabetic subjects (P less than 0.001). Despite these findings, and despite a higher prevalence of microvascular complications among Mexican Americans, there does not appear to be a marked difference in prevalence of macrovascular complications between Mexican-American and non-Hispanic white diabetic subjects. Mexican-American diabetic subjects have only a moderate excess of peripheral vascular disease (as judged by ankle-arm blood pressure ratios) relative to non-Hispanic white diabetic subjects (sex-adjusted Mantel-Haenszel odds ratio 1.84, 95% confidence interval 0.75-4.49). Mexican-American diabetic subjects actually reported fewer myocardial infarctions than non-Hispanic white diabetic subjects (sex-adjusted Mantel-Haenszel odds ratio 0.73, 95% confidence interval 0.31-1.71). Duration was not associated with either peripheral vascular disease or myocardial infarction. Severity of glycemia was only mildly associated with presence of peripheral vascular disease and negatively associated with self-reported myocardial infarction. This latter finding may represent a survival bias in that more severe diabetic subjects have already died and are not ascertained in a prevalence study. The absence of an ethnic difference in the prevalence of macrovascular disease contrasts with our previous reports from the San Antonio Heart Study, in which the prevalence of both retinopathy and proteinuria was observed to be higher in Mexican-American diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Analytic Approximation of Carbon Condensation Issues in Type ii Supernovae

    NASA Astrophysics Data System (ADS)

    Clayton, Donald D.

    2013-01-01

    I present analytic approximations for some issues related to condensation of graphite, TiC, and silicon carbide in oxygen-rich cores of supernovae of Type II. Increased understanding, which mathematical analysis can support, renders researchers more receptive to condensation in O-rich supernova gases. Taking SN 1987A as typical, my first analysis shows why the abundance of CO molecules reaches an early maximum in which free carbon remains more abundant than CO. This analysis clarifies why O-rich gas cannot oxidize C if 56Co radioactivity is as strong as in SN 1987A. My next analysis shows that the CO abundance could be regarded as being in chemical equilibrium if the CO molecule is given an effective binding energy rather than its laboratory dissociation energy. The effective binding energy makes the thermal dissociation rate of CO equal to its radioactive dissociation rate. This preserves possible relevance for the concept of chemical equilibrium. My next analysis shows that the observed abundances of CO and SiO molecules in SN 1987A rule out frequent suggestions that equilibrium condensation of SUNOCONs has occurred following atomic mixing of the He-burning shell with more central zones in such a way as to reproduce roughly the observed spectrum of isotopes in SUNOCONs while preserving C/O > 1. He atoms admixed along with the excess carbon would destroy CO and SiO molecules, leaving their observed abundances unexplained. The final analysis argues that a chemical quasiequilibrium among grains (but not gas) may exist approximately during condensation, so that its computational use is partially justified as a guide to which mineral phases would be stable against reactions with gas. I illustrate this point with quasiequilibrium calculations by Ebel & Grossman that have shown that graphite is stable even when O/C >1 if prominent molecules are justifiably excluded from the calculation of chemical equilibrium.

  7. Identification of Unique Type II Polyketide Synthase Genes in Soil

    PubMed Central

    Wawrik, Boris; Kerkhof, Lee; Zylstra, Gerben J.; Kukor, Jerome J.

    2005-01-01

    Many bacteria, particularly actinomycetes, are known to produce secondary metabolites synthesized by polyketide synthases (PKS). Bacterial polyketides are a particularly rich source of bioactive molecules, many of which are of potential pharmaceutical relevance. To directly access PKS gene diversity from soil, we developed degenerate PCR primers for actinomycete type II KSα (ketosynthase) genes. Twenty-one soil samples were collected from diverse sources in New Jersey, and their bacterial communities were compared by terminal restriction fragment length polymorphism (TRFLP) analysis of PCR products generated using bacterial 16S rRNA gene primers (27F and 1525R) as well as an actinomycete-specific forward primer. The distribution of actinomycetes was highly variable but correlated with the overall bacterial species composition as determined by TRFLP. Two samples were identified to contain a particularly rich and unique actinomycete community based on their TRFLP patterns. The same samples also contained the greatest diversity of KSα genes as determined by TRFLP analysis of KSα PCR products. KSα PCR products from these and three additional samples with interesting TRFLP pattern were cloned, and seven novel clades of KSα genes were identified. Greatest sequence diversity was observed in a sample containing a moderate number of peaks in its KSα TRFLP. The nucleotide sequences were between 74 and 81% identical to known sequences in GenBank. One cluster of sequences was most similar to the KSα involved in ardacin (glycopeptide antibiotic) production by Kibdelosporangium aridum. The remaining sequences showed greatest similarity to the KSα genes in pathways producing the angucycline-derived antibiotics simocyclinone, pradimicin, and jasomycin. PMID:15870305

  8. The Three-Dimensional Structural Basis of Type II Hyperprolinemia

    SciTech Connect

    Srivastava, Dhiraj; Singh, Ranjan K.; Moxley, Michael A.; Henzl, Michael T.; Becker, Donald F.; Tanner, John J.

    2012-08-31

    Type II hyperprolinemia is an autosomal recessive disorder caused by a deficiency in {Delta}{sup 1}-pyrroline-5-carboxylate dehydrogenase (P5CDH; also known as ALDH4A1), the aldehyde dehydrogenase that catalyzes the oxidation of glutamate semialdehyde to glutamate. Here, we report the first structure of human P5CDH (HsP5CDH) and investigate the impact of the hyperprolinemia-associated mutation of Ser352 to Leu on the structure and catalytic properties of the enzyme. The 2. 5-{angstrom}-resolution crystal structure of HsP5CDH was determined using experimental phasing. Structures of the mutant enzymes S352A (2.4 {angstrom}) and S352L (2.85 {angstrom}) were determined to elucidate the structural consequences of altering Ser352. Structures of the 93% identical mouse P5CDH complexed with sulfate ion (1.3 {angstrom} resolution), glutamate (1.5 {angstrom}), and NAD{sup +} (1.5 {angstrom}) were determined to obtain high-resolution views of the active site. Together, the structures show that Ser352 occupies a hydrophilic pocket and is connected via water-mediated hydrogen bonds to catalytic Cys348. Mutation of Ser352 to Leu is shown to abolish catalytic activity and eliminate NAD{sup +} binding. Analysis of the S352A mutant shows that these functional defects are caused by the introduction of the nonpolar Leu352 side chain rather than the removal of the Ser352 hydroxyl. The S352L structure shows that the mutation induces a dramatic 8-{angstrom} rearrangement of the catalytic loop. Because of this conformational change, Ser349 is not positioned to interact with the aldehyde substrate, conserved Glu447 is no longer poised to bind NAD{sup +}, and Cys348 faces the wrong direction for nucleophilic attack. These structural alterations render the enzyme inactive.

  9. The three-dimensional structural basis of type II hyperprolinemia.

    PubMed

    Srivastava, Dhiraj; Singh, Ranjan K; Moxley, Michael A; Henzl, Michael T; Becker, Donald F; Tanner, John J

    2012-07-13

    Type II hyperprolinemia is an autosomal recessive disorder caused by a deficiency in Δ(1)-pyrroline-5-carboxylate dehydrogenase (P5CDH; also known as ALDH4A1), the aldehyde dehydrogenase that catalyzes the oxidation of glutamate semialdehyde to glutamate. Here, we report the first structure of human P5CDH (HsP5CDH) and investigate the impact of the hyperprolinemia-associated mutation of Ser352 to Leu on the structure and catalytic properties of the enzyme. The 2. 5-Å-resolution crystal structure of HsP5CDH was determined using experimental phasing. Structures of the mutant enzymes S352A (2.4 Å) and S352L (2.85 Å) were determined to elucidate the structural consequences of altering Ser352. Structures of the 93% identical mouse P5CDH complexed with sulfate ion (1.3 Å resolution), glutamate (1.5 Å), and NAD(+) (1.5 Å) were determined to obtain high-resolution views of the active site. Together, the structures show that Ser352 occupies a hydrophilic pocket and is connected via water-mediated hydrogen bonds to catalytic Cys348. Mutation of Ser352 to Leu is shown to abolish catalytic activity and eliminate NAD(+) binding. Analysis of the S352A mutant shows that these functional defects are caused by the introduction of the nonpolar Leu352 side chain rather than the removal of the Ser352 hydroxyl. The S352L structure shows that the mutation induces a dramatic 8-Å rearrangement of the catalytic loop. Because of this conformational change, Ser349 is not positioned to interact with the aldehyde substrate, conserved Glu447 is no longer poised to bind NAD(+), and Cys348 faces the wrong direction for nucleophilic attack. These structural alterations render the enzyme inactive.

  10. Ring A of nukacin ISK-1: a lipid II-binding motif for type-A(II) lantibiotic.

    PubMed

    Islam, Mohammad R; Nishie, Mami; Nagao, Jun-ichi; Zendo, Takeshi; Keller, Sandro; Nakayama, Jiro; Kohda, Daisuke; Sahl, Hans-Georg; Sonomoto, Kenji

    2012-02-29

    Ring A of nukacin ISK-1, which is also present in different type-A(II) lantibiotics, resembles a lipid II-binding motif (TxS/TxD/EC, x denotes undefined residues) similar to that present in mersacidin (type-B lantibiotics), which suggests that nukacin ISK-1 binds to lipid II as a docking molecule. Results from our experiments on peptidoglycan precursor (UDP-MurNAc-pp) accumulation and peptide antagonism assays clearly indicated that nukacin ISK-1 inhibits cell-wall biosynthesis, accumulating lipid II precursor inside the cell, and the peptide activity can be repressed by lipid I and lipid II. Interaction analysis of nukacin ISK-1 and different ring A variants with lipid II revealed that nukacin ISK-1 and nukacin D13E (a more active variant) have a high affinity (K(D) = 0.17 and 0.19 μM, respectively) for lipid II, whereas nukacin D13A (a less active variant) showed a lower affinity, and nukacin C14S (a negative variant lacking the ring A structure) exhibited no interaction. Therefore, on the basis of the structural similarity and positional significance of the amino acids in this region, we concluded that nukacin ISK-1 binds lipid II via its ring A region and may lead to the inhibition of cell-wall biosynthesis.

  11. Direct and in vitro observation of growth hormone receptor molecules in A549 human lung epithelial cells by nanodiamond labeling

    NASA Astrophysics Data System (ADS)

    Cheng, C.-Y.; Perevedentseva, E.; Tu, J.-S.; Chung, P.-H.; Cheng, C.-L.; Liu, K.-K.; Chao, J.-I.; Chen, P.-H.; Chang, C.-C.

    2007-04-01

    This letter presents direct observation of growth hormone receptor in one single cancer cell using nanodiamond-growth hormone complex as a specific probe. The interaction of surface growth hormone receptor of A549 human lung epithelial cells with growth hormone was observed using nanodiamond's unique spectroscopic signal via confocal Raman mapping. The growth hormone molecules were covalent conjugated to 100nm diameter carboxylated nanodiamonds, which can be recognized specifically by the growth hormone receptors of A549 cell. The Raman spectroscopic signal of diamond provides direct and in vitro observation of growth hormone receptors in physiology condition in a single cell level.

  12. Use of Enterally Delivered Angiotensin II Type Ia Receptor Antagonists to Reduce the Severity of Colitis

    PubMed Central

    Okawada, Manabu; Koga, Hiroyuki; Larsen, Scott D.; Showalter, Hollis D.; Turbiak, Anjanette J.; Jin, Xiaohong; Lucas, Peter C.; Lipka, Elke; Hillfinger, John; Kim, Jae Seung

    2011-01-01

    Background Renin-angiotensin system blockade reduces inflammation in several organ systems. Having found a fourfold increase in angiotensin II type Ia receptor expression in a dextran sodium sulfate colitis model, we targeted blockade with angiotensin II type Ia receptor antagonists to prevent colitis development. Because hypotension is a major complication of angiotensin II type Ia receptor antagonists use, we hypothesized that use of angiotensin II type Ia receptor antagonists compounds which lack cell membrane permeability, and thus enteric absorption, would allow for direct enteral delivery at far higher concentrations than would be tolerated systemically, yet retain efficacy. Methods Based on the structure of the angiotensin II type Ia receptor antagonist losartan, deschloro-losartan was synthesized, which has extremely poor cell membrane permeability. Angiotensin II type Ia receptor antagonist efficacy was evaluated by determining the ability to block NF-κB activation in vitro. Dextran sodium sulfate colitis was induced in mice and angiotensin II type Ia receptor antagonist efficacy delivered transanally was assessed. Results In vitro, deschloro-losartan demonstrated near equal angiotensin II type Ia receptor blockade compared to losartan as well as another angiotensin II type Ia receptor antagonist, candesartan. In the dextran sodium sulfate model, each compound significantly improved clinical and histologic scores and epithelial cell apoptosis. Abundance of TNF-α, IL-1β, and IL6 mRNA were significantly decreased with each compound. In vitro and in vivo intestinal drug absorption, as well as measures of blood pressure and mucosal and colonic blood flow, showed significantly lower uptake of deschloro-losartan compared to losartan and candesartan. Conclusions This study demonstrated efficacy of high-dose angiotensin II type Ia receptor antagonists in this colitis model. We postulate that a specially designed angiotensin II type Ia receptor antagonist with

  13. [Extraction, purification and identification of type II collagen from Agkistrodon acutus].

    PubMed

    Gu, Heng-Cun; Hu, Jin-Bo; Ding, Zhi-Shan; Fan, Yong-Sheng; Ding, Xing-Hong

    2013-11-01

    The object of the research was to extract, purify and identify the type II collagen of Agkistrodon acutus. Type II collagen of A. acutus was extracted by enzyme decomposition method, and purified by ion exchange column chromatography. It was characterized by SDS-PAGE gel electrophoresis, ultraviolet spectrophotometry, infrared absorption spectroscopy and mass spectroscopy. The results showed that the size of C II was about 130 kDa. It absorbed at 223 nm. IR spectrum obtained showed that the triple helical domains of amino-acid sequences were characterized by the repetition of triplets Gly-X-Y. The MS spectrum graphically stated that C II extracted from cow and A. acutus have the similar peptides. The C II of A. acutus was obtained by extraction and purification. Appraisal analysis by SDS-PAGE, UV, IR and MS, C II of A. acutus was consistent with the standard C II of cow. It was proved that the extracted protein was C II.

  14. Shaping of action potentials by type I and type II large-conductance Ca²+-activated K+ channels.

    PubMed

    Jaffe, D B; Wang, B; Brenner, R

    2011-09-29

    The BK channel is a Ca(2+) and voltage-gated conductance responsible for shaping action potential waveforms in many types of neurons. Type II BK channels are differentiated from type I channels by their pharmacology and slow gating kinetics. The β4 accessory subunit confers type II properties on BK α subunits. Empirically derived properties of BK channels, with and without the β4 accessory subunit, were obtained using a heterologous expression system under physiological ionic conditions. These data were then used to study how BK channels alone (type I) and with the accessory β4 subunit (type II) modulate action potential properties in biophysical neuron models. Overall, the models support the hypothesis that it is the slower kinetics provided by the β4 subunit that endows the BK channel with type II properties, which leads to broadening of action potentials and, secondarily, to greater recruitment of SK channels reducing neuronal excitability. Two regions of parameter space distinguished type II and type I effects; one where the range of BK-activating Ca(2+) was high (>20 μM) and the other where BK-activating Ca(2+) was low (∼0.4-1.2 μM). The latter required an elevated BK channel density, possibly beyond a likely physiological range. BK-mediated sharpening of the spike waveform associated with the lack of the β4 subunit was sensitive to the properties of voltage-gated Ca(2+) channels due to electrogenic effects on spike duration. We also found that depending on Ca(2+) dynamics, type II BK channels may have the ability to contribute to the medium AHP, a property not generally ascribed to BK channels, influencing the frequency-current relationship. Finally, we show how the broadening of action potentials conferred by type II BK channels can also indirectly increase the recruitment of SK-type channels decreasing the excitability of the neuron.

  15. Differential properties of type I and type II benzodiazepine receptors in mammalian CNS neurones.

    PubMed Central

    Yakushiji, T.; Shirasaki, T.; Munakata, M.; Hirata, A.; Akaike, N.

    1993-01-01

    1. The effects of benzodiazepine receptor (BZR) partial agonists, Y-23684 and CL218,872, were compared with its full agonist, diazepam, on gamma-aminobutyric acid (GABA)-induced Cl- current (ICl) in acutely dissociated rat cerebral cortex (CTX), cerebellar Purkinje (CPJ) and spinal ventral horn (SVH) neurones, by the whole-cell mode patch-clamp technique. 2. The GABA-induced responses were essentially the same in both SVH and CPJ neurones, but the KD value of the GABA response in CTX neurone was lower than those in the other two brain regions. 3. Enhancement of the GABA response by the two partial agonists was about one-third of that by diazepam in the SVH neurones (where type II subtype of BZR, BZ2, is predominant), whereas these partial agonists potentiated the GABA response as much as diazepam in CPJ neurones (where the type I subtype of BZR, BZ1, is predominant). In CTX neurones where both type I and II variants are expressed, the augmentation ratio of the GABA response by diazepam was between the values in CPJ and SVH neurones. 4. In concentration-response relationships of BZR partial agonists, the threshold concentrations, KD values and maximal augmentation ratio of the GABA response were similar in all CTX, CPJ and SVH neurones. Also, in all preparations, the threshold concentration and KD values of diazepam action were 10 fold less than those induced by partial agonists. 5. All BZR agonists shifted the concentration-response relationship for GABA to the left without changing the maximum current amplitude, indicating that activation of both BZ1 and BZ2 increase the affinity of the GABAA receptor for GABA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8395299

  16. Differential properties of type I and type II benzodiazepine receptors in mammalian CNS neurones.

    PubMed

    Yakushiji, T; Shirasaki, T; Munakata, M; Hirata, A; Akaike, N

    1993-07-01

    1. The effects of benzodiazepine receptor (BZR) partial agonists, Y-23684 and CL218,872, were compared with its full agonist, diazepam, on gamma-aminobutyric acid (GABA)-induced Cl- current (ICl) in acutely dissociated rat cerebral cortex (CTX), cerebellar Purkinje (CPJ) and spinal ventral horn (SVH) neurones, by the whole-cell mode patch-clamp technique. 2. The GABA-induced responses were essentially the same in both SVH and CPJ neurones, but the KD value of the GABA response in CTX neurone was lower than those in the other two brain regions. 3. Enhancement of the GABA response by the two partial agonists was about one-third of that by diazepam in the SVH neurones (where type II subtype of BZR, BZ2, is predominant), whereas these partial agonists potentiated the GABA response as much as diazepam in CPJ neurones (where the type I subtype of BZR, BZ1, is predominant). In CTX neurones where both type I and II variants are expressed, the augmentation ratio of the GABA response by diazepam was between the values in CPJ and SVH neurones. 4. In concentration-response relationships of BZR partial agonists, the threshold concentrations, KD values and maximal augmentation ratio of the GABA response were similar in all CTX, CPJ and SVH neurones. Also, in all preparations, the threshold concentration and KD values of diazepam action were 10 fold less than those induced by partial agonists. 5. All BZR agonists shifted the concentration-response relationship for GABA to the left without changing the maximum current amplitude, indicating that activation of both BZ1 and BZ2 increase the affinity of the GABAA receptor for GABA. 6. The results are important in clarifying the mechanism of anxiety and might explain the anxioselectivity of BZR partial agonists.

  17. 33 CFR 159.126a - Suspended solids test: Type II devices.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Suspended solids test: Type II... Suspended solids test: Type II devices. During the sewage processing test (§ 159.121) 40 effluent samples... suspended solids in accordance with 40 CFR Part 136. The arithmetic mean of the total suspended solids in...

  18. 33 CFR 159.126a - Suspended solids test: Type II devices.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Suspended solids test: Type II... Suspended solids test: Type II devices. During the sewage processing test (§ 159.121) 40 effluent samples... suspended solids in accordance with 40 CFR part 136. The arithmetic mean of the total suspended solids in...

  19. Interband cascade light emitting devices based on type-II quantum wells

    SciTech Connect

    Yang, Rui Q.; Lin, C.H.; Murry, S.J.

    1997-06-01

    The authors discuss physical processes in the newly developed type-II interband cascade light emitting devices, and review their recent progress in the demonstration of the first type-II interband cascade lasers and the observation of interband cascade electroluminescence up to room temperature in a broad mid-infrared wavelength region (extended to 9 {mu}m).

  20. Characteristics of coronal mass ejections associated with solar frontside and backside metric Type II bursts

    NASA Technical Reports Server (NTRS)

    Kahler, S. W.; Cliver, E. W.; Sheeley, N. R.; Howard, R. A.; Michels, D. J.; Koomen, M. J.

    1985-01-01

    Fast velocities of 500 km/s or greater coronal mass ejections (CME's) are compared with reported metric type II bursts to study the properties of CME's associated with coronal shocks. An earlier report of fast frontside CME's with no associated metric type II bursts is confirmed, and it is calculated that 33 + or - 15 percent of all fast frontside CME's are not associated with such bursts. Faster CME's are more likely to be associated with type II bursts, as expected from the hypothesis of piston-driven shocks. However, CME brightness and associated peak 3-cm burst intensity are also important factors, as might be inferred from the Wagner and MacQueen (1983) view of type II shocks decoupled from associated CME's. The equal visibility of solar frontside and backside CME's is used to deduce the observability of backside type II bursts. It is calculated that 23 + or - 7 percent of all backside type II bursts associated with fast CME's can be observed at the earth and that 13 + or - 4 percent of all type II bursts originate in backside flares. CME speed again is the most important factor in the obervability of backside type II bursts.

  1. Characterization of cloned cells from an immortalized fetal pulmonary type II cell line

    SciTech Connect

    Henderson, R.F.; Waide, J.J.; Lechner, J.F.

    1995-12-01

    A cultured cell line that maintained expression of pulmonary type II cell markers of differentiation would be advantageous to generate a large number of homogenous cells in which to study the biochemical functions of type II cells. Type II epithelial cells are the source of pulmonary surfactant and a cell of origin for pulmonary adenomas. Last year our laboratory reported the induction of expression of two phenotypic markers of pulmonary type II cells (alkaline phosphatase activity and surfactant lipid synthesis) in cultured fetal rat lung epithelial (FRLE) cells, a spontaneously immortalized cell line of fetal rat lung type II cell origin. Subsequently, the induction of the ability to synthesize surfactant lipid became difficult to repeat. We hypothesized that the cell line was heterogenuous and some cells were more like type II cells than others. The purpose of this study was to test this hypothesis and to obtain a cultured cell line with type II cell phenotypic markers by cloning several FRLE cells and characterizing them for phenotypic markers of type II cells (alkaline phosphatase activity and presence of surfactant lipids). Thirty cloned cell lines were analyzed for induced alkaline phosphatase activity (on x-axis) and for percent of phospholipids that were disaturated (i.e., surfactant).

  2. The effect of type II collagen on MSC osteogenic differentiation and bone defect repair.

    PubMed

    Chiu, Li-Hsuan; Lai, Wen-Fu T; Chang, Shwu-Fen; Wong, Chin-Chean; Fan, Cheng-Yu; Fang, Chia-Lang; Tsai, Yu-Hui

    2014-03-01

    The function of type II collagen in cartilage is well documented and its importance for long bone development has been implicated. However, the involvement of type II collagen in bone marrow derived mesenchymal stem cell (BMSC) osteogenesis has not been well investigated. This study elucidated the pivotal role of type II collagen in BMSC osteogenesis and its potential application to bone healing. Type II collagen-coated surface was found to accelerate calcium deposition, and the interaction of osteogenic medium-induced BMSCs with type II collagen-coated surface was mainly mediated through integrin α2β1. Exogenous type II collagen directly activated FAK-JNK signaling and resulted in the phosphorylation of RUNX2. In a segmental defect model in rats, type II collagen-HA/TCP-implanted rats showed significant callus formation at the reunion site, and a higher SFI (sciatic function index) scoring as comparing to other groups were also observed at 7, 14, and 21 day post-surgery. Collectively, type II collagen serves as a better modulator during early osteogenic differentiation of BMSCs by facilitating RUNX2 activation through integrin α2β1-FAK-JNK signaling axis, and enhance bone defect repair through an endochondral ossification-like process. These results advance our understanding about the cartilaginous ECM-BMSC interaction, and provide perspective for bone defect repair strategies.

  3. 46 CFR 171.072 - Calculation of permeability for Type II subdivision.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Calculation of permeability for Type II subdivision. 171... permeability for Type II subdivision. When doing calcualtions to show compliance with § 171.070, the following uniform average permeabilities must be assumed: (a) 85 percent in the machinery space. (b) 60 percent...

  4. 46 CFR 171.072 - Calculation of permeability for Type II subdivision.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Calculation of permeability for Type II subdivision. 171... Calculation of permeability for Type II subdivision. When doing calcualtions to show compliance with § 171.070, the following uniform average permeabilities must be assumed: (a) 85 percent in the machinery...

  5. Stimulation of DNA synthesis in cultured rat alveolar type II cells

    SciTech Connect

    Leslie, C.C.; McCormick-Shannon, K.; Robinson, P.C.; Mason, R.J.

    1985-01-01

    Restoration of the alveolar epithelium after injury is thought to be dependent on the proliferation of alveolar type II cells. To understand the factors that may be involved in promoting type II cell proliferation in vivo, we determined the effect of potential mitogens and culture substrata on DNA synthesis in rat alveolar type II cells in primary culture. Type II cells cultured in basal medium containing 10% fetal bovine serum (FBS) exhibited essentially no DNA synthesis. Factors that stimulated /sup 3/H-thymidine incorporation included cholera toxin, epidermal growth factor, and rat serum. The greatest degree of stimulation was achieved by plating type II cells on an extracellular matrix prepared from bovine corneal endothelial cells and then by culturing the pneumocytes in medium containing rat serum, cholera toxin, insulin, and epidermal growth factor. Under conditions of stimulation of /sup 3/H-thymidine incorporation there was an increased DNA content per culture dish but no increase in cell number. The ability of various culture conditions to promote DNA synthesis in type II cells was verified by autoradiography. Type II cells were identified by the presence of cytoplasmic inclusions, which were visualized by tannic acid staining before autoradiography. These results demonstrate the importance of soluble factors and culture substratum in stimulating DNA synthesis in rat alveolar type II cells in primary culture.

  6. Rules for distinguishing toxicants that cause type I and type II narcosis syndromes

    SciTech Connect

    Veith, G.D.; Broderius, S.J. )

    1990-07-01

    Narcosis is a nonspecific reversible state of arrested activity of protoplasmic structures caused by a wide variety of organic chemicals. The vast majority of industrial organic chemicals can be characterized by a baseline structure-toxicity relationship as developed for diverse aquatic organisms, using only the n-octanol/water partition coefficient as a descriptor. There are, however, many apparent narcotic chemicals that are more toxic than baseline narcosis predicts. Some of these chemicals have been distinguished as polar narcotics. Joint toxic theory and isobole diagrams were used to show that chemicals strictly additive with phenol were generally more toxic than predicted by narcosis I models and characterized by a different mode of action called narcosis II syndrome. This type of toxicity is exemplified by certain amides, amines, phenols, and nitrogen heterocycles. Evidence is provided that suggests that narcosis II syndrome may result from the presence of a strong hydrogen bonding group on the molecule, and narcosis I syndrome results from hydrophobic bonding of the chemical to enzymes and/or membranes. This shift in toxic action is apparently indistinguishable for narcotic chemicals with log P greater than about 2.7. General rules for selecting the appropriate models are proposed.

  7. Nucleosynthesis in the accretion disks of Type II collapsars

    NASA Astrophysics Data System (ADS)

    Banerjee, Indrani; Mukhopadhyay, Banibrata

    2013-09-01

    We investigate nucleosynthesis inside the gamma-ray burst (GRB) accretion disks formed by the Type II collapsars. In these collapsars, the core collapse of massive stars first leads to the formation of a proto-neutron star. After that, an outward moving shock triggers a successful supernova. However, the supernova ejecta lacks momentum and within a few seconds the newly formed neutron star gets transformed to a stellar mass black hole via massive fallback. The hydrodynamics of such an accretion disk formed from the fallback material of the supernova ejecta has been studied extensively in the past. We use these well-established hydrodynamic models for our accretion disk in order to understand nucleosynthesis, which is mainly advection dominated in the outer regions. Neutrino cooling becomes important in the inner disk where the temperature and density are higher. The higher the accretion rate (dot M) is, the higher the density and temperature are in the disks. We deal with accretion disks with relatively low accretion rates: 0.001 Msolar s-1 ≲ dot M ≲ 0.01 Msolar s-1 and hence these disks are predominantly advection dominated. We use He-rich and Sirich abundances as the initial condition of nucleosynthesis at the outer disk, and being equipped with the disk hydrodynamics and the nuclear network code, we study the abundance evolution as matter inflows and falls into the central object. We investigate the variation in the nucleosynthesis products in the disk with the change in the initial abundance at the outer disk and also with the change in the mass accretion rate. We report the synthesis of several unusual nuclei like 31P, 39K, 43Sc, 35Cl and various isotopes of titanium, vanadium, chromium, manganese and copper. We also confirm that isotopes of iron, cobalt, nickel, argon, calcium, sulphur and silicon get synthesized in the disk, as shown by previous authors. Much of these heavy elements thus synthesized are ejected from the disk via outflows and hence they

  8. Investigation of the Geoeffectiveness of CMEs Associated with IP Type II Radio Bursts

    NASA Astrophysics Data System (ADS)

    Vasanth, V.; Chen, Y.; Kong, X. L.; Wang, B.

    2015-06-01

    We perform a statistical analysis of the geoeffectiveness of coronal mass ejections (CMEs) that are associated with interplanetary (IP) type II bursts in Solar Cycle 23 during the period 1997 - 2008. About 47 % (109 out of 232) of IP type II bursts are found to be associated with geomagnetic storms. Of these 47 %, 27 % are associated with moderate, 14 % with intense, and 6 % with severe geomagnetic storms. We find that the IP type II bursts and their corresponding end frequencies can be used as indicators of CME geoeffectiveness: the lower the type II burst end frequency, the higher the possibility of having a stronger storm. In addition, we show that various combinations of CME remote-sensing and IP type II parameters can be used to improve geomagnetic storm forecasting.

  9. Organotypic culture of fetal lung type II alveolar epithelial cells: applications to pulmonary toxicology.

    PubMed Central

    Shami, S G; Aghajanian, J D; Sanders, R L

    1984-01-01

    Techniques for isolation and culture of fetal Type II alveolar epithelial cells, as well as the morphologic and biochemical characteristics of these histotypic cultures, are described. Type II alveolar epithelial cells can be isolated from fetal rat lungs and grown in an organotypic culture system as described in this review. The fetal Type II cells resemble differentiated rat Type II cells in morphology, biochemistry, and karyotype as they grow in culture for up to 5 weeks. The cells of the mature organotypic cultures form alveolarlike structures while growing on a gelatin sponge matrix. The Type II cells also synthesize and secrete pulmonary surfactant similar in biochemical composition to that produced in vivo. This system has been used to study the effects of hormones on surfactant production and composition. The organotypic model has many potential applications to the study of pulmonary toxicology. Images FIGURE 1. FIGURE 2. PMID:6548184

  10. Treatment of Type II Endoleaks After Endovascular Repair of Abdominal Aortic Aneurysms: Transcaval Approach

    SciTech Connect

    Mansueto, Giancarlo Cenzi, Daniela; D'Onofrio, Mirko; Petrella, Enrico; Gumbs, Andrew A.; Mucelli, Roberto Pozzi

    2005-06-15

    The purpose of the note is to describe a new technique for type II endoleak treatment, using an alternative approach through femoral venous access. Three patients who developed type II endoleak after endovascular repair of abdominal aortic aneurysm were treated with direct transcaval puncture and embolization inside the aneurysm sac. The detailed technique is described. All patients were treated without any complications and discharged 48 hours after the treatment. At 1 month follow-up the computed tomograph scan did not show a recurrence of a type II endoleak. The management of patients with type II endoleak is a controversial issue and different techniques have been proposed. We suggest an alternative technique for type II endoleak treatment. The feasibility and the advantages of this approach can offer new possibilities for the diagnosis as well as for the treatment of this complication.

  11. Notch maintains Drosophila type II neuroblasts by suppressing expression of the Fez transcription factor Earmuff.

    PubMed

    Li, Xiaosu; Xie, Yonggang; Zhu, Sijun

    2016-07-15

    Notch signaling is crucial for maintaining neural stem cell (NSC) self-renewal and heterogeneity; however, the underlying mechanism is not well understood. In Drosophila, loss of Notch prematurely terminates the self-renewal of larval type II neuroblasts (NBs, the Drosophila NSCs) and transforms type II NBs into type I NBs. Here, we demonstrate that Notch maintains type II NBs by suppressing the activation of earmuff (erm) by Pointed P1 (PntP1). We show that loss of Notch or components of its canonical pathway leads to PntP1-dependent ectopic Erm expression in type II NBs. Knockdown of Erm significantly rescues the loss-of-Notch phenotypes, and misexpression of Erm phenocopies the loss of Notch. Ectopically expressed Erm promotes the transformation of type II NBs into type I NBs by inhibiting PntP1 function and expression in type II NBs. Our work not only elucidates a key mechanism of Notch-mediated maintenance of type II NB self-renewal and identity, but also reveals a novel function of Erm.

  12. Overexpression of Bcl-2–Associated Death Inhibits A549 Cell Growth In Vitro and In Vivo

    PubMed Central

    Huang, Na; Zhu, Jing; Liu, Dan; Li, Ya-Lun; Chen, Bo-Jiang; He, Yan-Qi; Liu, Kun; Mo, Xian-Ming

    2012-01-01

    Abstract The importance of apoptosis during the process of inhibiting tumorigenesis has been recognized. The role of BH3-only proapoptotic protein Bcl-2–associated death (BAD) in tumor growth remains controversial. The aim of this study was to explore the role of BAD in lung cancer cells. Our study showed that expression of BAD was upregulated in A549 cells by a recombinant lentivirus overexpressing BAD. In vitro, BAD overexpression significantly inhibited A549 cell proliferation and induced apoptosis in cell proliferation and apoptosis assays, respectively. The effect of BAD on A549 cells was studied in tumor xenograft of nude mice and the results showed that the tumor volume in the experimental group was smaller than the control groups. Further, immunohistochemical technique was used to determine the cell proliferation and apoptosis status of the lung tumor xenograft cells. This demonstrated that the in vivo and in vitro results were consistent. Taken together, our results indicate that overexpression of BAD inhibits the growth of A549 cells in vitro and in vivo, through inhibiting cell proliferation and inducing apoptosis. Thus, BAD could be a potential therapeutic target. PMID:22011203

  13. Molecular mechanisms underlying mangiferin-induced apoptosis and cell cycle arrest in A549 human lung carcinoma cells

    PubMed Central

    SHI, WEI; DENG, JIAGANG; TONG, RONGSHENG; YANG, YONG; HE, XIA; LV, JIANZHEN; WANG, HAILIAN; DENG, SHAOPING; QI, PING; ZHANG, DINGDING; WANG, YI

    2016-01-01

    Mangiferin, which is a C-glucosylxanthone (1,3,6,7-tetrahydroxyxanthone-C2-β-D-glucoside) purified from plant sources, has recently gained attention due to its various biological activities. The present study aimed to determine the apoptotic effects of mangiferin on A549 human lung adenocarcinoma cells. In vitro studies demonstrated that mangiferin exerted growth-inhibitory and apoptosis-inducing effects against A549 cells. In addition, mangiferin exhibited anti-tumor properties in A549 xenograft mice in vivo. Mangiferin triggered G2/M phase cell cycle arrest via down-regulating the cyclin-dependent kinase 1-cyclin B1 signaling pathway, and induced apoptotic cell death by inhibiting the protein kinase C-nuclear factor-κB pathway. In addition, mangiferin was able to enhance the antiproliferative effects of cisplatin on A549 cells, thus indicating the potential for a combined therapy. Notably, mangiferin exerted anticancer effects in vivo, where it was able to markedly decrease the volume and weight of subcutaneous tumor mass, and expand the lifespan of xenograft mice. The present study clarified the molecular mechanisms underlying mangiferin-induced antitumor activities, and suggested that mangiferin may be considered a potential antineoplastic drug for the future treatment of cancer. PMID:26935347

  14. Enhanced production of nitric oxide in A549 cells through activation of TRPA1 ion channel by cold stress.

    PubMed

    Sun, Wenwu; Wang, Zhonghua; Cao, Jianping; Wang, Xu; Han, Yaling; Ma, Zhuang

    2014-08-31

    The respiratory epithelium is exposed to the external environment, and inhalation of cold air is common during the season of winter. In addition, the lung is a major source of nitric oxide (NO). However, the effect of cold stress on the production of NO is still unclear. In the present work, We measured the change of NO in single cell with DACF-DA and the change in cytosolic Ca(2+) concentration ([Ca(2+)]c) in A549 cell. We observed that cold stress (from 20 °C to 5 °C) induced an increase of NO in A549 cell, which was completely abolished by applying an extracellular Ca(2+) free medium. Further experiments showed that cold-sensing transient receptor potential subfamily member 1 (TRPA1) channel agonist (allyl isothiocyanate, AITC) increased the production of NO and the level of [Ca(2+)]c in A549 cell. Additionally, TRPA1 inhibitor, Ruthenium red (RR) and camphor, significantly blocked the enhanced production of NO and the rise of [Ca(2+)]c induced by AITC or cold stimulation, respectively. Taken together, these data indicated that cold-induced TRPA1 activation was responsible for the enhanced production of NO in A549 cell.

  15. Enhancement of radiosensitivity by CpG-oligodeoxyribonucleotide-7909 in human non-small cell lung cancer A549 cells.

    PubMed

    Zha, Lin; Qiao, Tiankui; Yuan, Sujuan; Lei, Linjie

    2010-04-01

    CpG-oligodeoxyribonucleotides (CpG-ODNs), which induce signaling through the toll-like receptor 9, are currently under investigation as immunity stimulators against cancer. It has recently been suggested that CpG-ODNs may also enhance sensitivity to traditional therapies including chemotherapy in certain cancer-cell lines. The purpose of this study was to define the activity of CpG-ODN7909 in increasing radiosensitivity of the human non-small cell lung cancer cell line A549 in vitro. First, a dose- and time-dependent inhibitory effect on cell viability was observed after A549 cells were treated with different concentrations of CpG-ODN7909 (5, 10, 30, and 60 microg/mL). Second, decreased cell clonogenic survival, enhanced cell apoptotic index, accumulated percentage of cells in the G2/M phase, and increased tumor necrosis factor (TNF)-alpha secretion were found after combined treatments with 10 microg/mL of CpG-ODN7909 and radiation compared to either treatment alone (p < 0.05). Furthermore, the toll-like receptor 9 mRNA was found to express in A549. The results suggest that CpG-ODN7909 can increase the radiosensitivity of human non-small cell lung cancer A549 cells, which may be associated with reduced cell clonogenic survival, enhanced apoptosis, prolonged cell-cycle arrest in G2/M, and stimulation of TNF-alpha secretion.

  16. Green tea polyphenol EGCG reverse cisplatin resistance of A549/DDP cell line through candidate genes demethylation.

    PubMed

    Zhang, Youwei; Wang, Xiang; Han, Liang; Zhou, Yizhou; Sun, Sanyuan

    2015-02-01

    Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, has been extensively studied as a potential demethylating agent. Our hypothesis is that EGCG could resensitize non-small-cell lung cancer (NSCLC) cells to cisplatin (DDP) through candidate genes demethylation. The A549/DDP cell line was established by continuous exposure of A549 cells to increasing concentrations of DDP. MTT, colony formation assay, flow cytometric analysis, Hoechst staining, real time-PCR, quantitative methylation-specific PCR and in vivo experiments were performed in this study. EGCG+DDP treatment significantly caused proliferation inhibition, cell cycle arrest in G1 phase, increase of apoptosis in A549/DDP cells, along with inhibition of DNA methyltransferase (DNMT) activity and histone deacetylase (HDAC) activity, reversal of hypermethylated status and downregulated expression of GAS1, TIMP4, ICAM1 and WISP2 gene in A549/DDP cells. Furthermore, pre-treatment with EGCG followed by DDP caused significant tumor inhibition in vivo. Methylation levels of GAS1, TIMP4, ICAM1 and WISP2 were decreased and their expression levels were increased in EGCG-treatment groups, but only combinatorial treatment group caused growth inhibition. In conclusion, we identified EGCG pretreatment resensitized cells to DDP, along with the demethylation and restoration of expression of candidate genes.

  17. Winter fine particulate matter from Milan induces morphological and functional alterations in human pulmonary epithelial cells (A549).

    PubMed

    Gualtieri, Maurizio; Mantecca, Paride; Corvaja, Viviana; Longhin, Eleonora; Perrone, Maria Grazia; Bolzacchini, Ezio; Camatini, Marina

    2009-07-10

    Samples of PM(2.5) were gravimetrically collected during the winter 2005/2006 in the urban area of Milan (North Italy). Samples were chemically characterized and the particles were detached from filters to determine their cytotoxic effects on the A549 cell line. Based on the potential toxicological relevance of its components, Milan winter PM(2.5) contained high concentrations of pro-oxidant transition metals and PAHs, while re-suspended particles showed a relatively high frequency of dimensional classes ranging from 40 nm to 300 nm. A549 cells exposed to particle suspensions showed a concentration-dependent decrease in viability, starting from 10 microg/cm(2). Phagocytosis of particles by A549 cells and particle aggregates were morphologically characterized and seemed to depend on both particle concentration and exposure time, with the majority of particles being engulfed in membrane-bound vacuoles after 24h of exposure. The ability of ultrafine particles to penetrate and spread throughout the cells was also verified. Cell membrane lysis and mitochondrial ultrastructural disruption appeared to be the main modifications induced by PM(2.5) on A549 cells. Concomitantly to the adverse effects observed in terms of cell mortality and ultrastructural lesions, a significant intracellular production of reactive oxygen species (ROS) was observed, suggesting that the cytotoxicity, exerted by the winter PM(2.5) in Milan, derived also from its oxidative potential, probably associated with particle-adsorbed metals and PAHs.

  18. Transcriptome Sequencing Reveals Key Pathways and Genes Associated with Cisplatin Resistance in Lung Adenocarcinoma A549 Cells

    PubMed Central

    Fang, Yani; Zhang, Cheng; Wu, Tong; Wang, Qi; Liu, Jinhui; Dai, Penggao

    2017-01-01

    Acquired resistance to cisplatin-based chemotherapy frequently occurs in patients with non-small cell lung cancer, and the underlying molecular mechanisms are not well understood. The aim of this study was to investigate whether a distinct gene expression pattern is associated with acquired resistance to cisplatin in human lung adenocarcinoma. Whole-transcriptome sequencing was performed to compare the genome-wide gene expression patterns of the human lung adenocarcinoma A549 cisplatin-resistant cell line A549/DDP with those of its progenitor cell line A549. A total of 1214 differentially expressed genes (DEGs) were identified, 656 of which were upregulated and 558 were downregulated. Functional annotation of the DEGs in the Kyoto Encyclopedia of Genes and Genomes database revealed that most of the identified genes were enriched in the PI3K/AKT, mitogen-activated protein kinase, actin cytoskeleton regulation, and focal adhesion pathways in A549/DDP cells. These results support previous studies demonstrating that the pathways regulating cell proliferation and invasion confer resistance to chemotherapy. Furthermore, the results proved that cell adhesion and cytoskeleton regulation is associated with cisplatin resistance in human lung cancer. Our study provides new promising biomarkers for lung cancer prognosis and potential therapeutic targets for lung cancer treatment. PMID:28114404

  19. Diverse effects of type II collagen on osteogenic and adipogenic differentiation of mesenchymal stem cells.

    PubMed

    Chiu, Li-Hsuan; Yeh, Tien-Shun; Huang, Huei-Mei; Leu, Sy-Jye; Yang, Charng-Bin; Tsai, Yu-Hui

    2012-06-01

    Type II collagen is known to modulate chondrogenesis of mesenchymal stem cells (MSCs). In this study, MSCs from human bone marrow aspirates were used to study the modulating effects of type II collagen on MSC differentiation during the early stages of osteogenesis and adipogenesis. With osteogenic induction, MSCs cultured on the type II collagen-coated surface showed an enhanced calcium deposition level with increasing mRNA expressions of RUNX2, osteocalcin, and alkaline phosphatase. A synthetic integrin binding peptide, which specifically interacts with the I-domain of α(1)β(1)/α(2)β(1) integrins significantly blocks the mineralization-enhancing effect of type II collagen. MSCs attached on the type II collagen-coated plates exhibited expanded cell morphology with increasing spreading area, and the pretreatment of cells with integrin α(1)β(1) or α(2)β(1)-blocking antibody reduced the effect. The phosphorylation levels of FAK, ERK, and JNK significantly increased in the MSCs that attached on the type II collagen-coated plates. On the contrary, the mineralization-enhancing effect of type II collagen was diminished by JNK and MEK inhibitors. Furthermore, type II collagen blocked the adipogenic differentiation of MSCs, and this effect is rescued by JNK and MEK inhibitors. In conclusion, type II collagen facilitates osteogenesis and suppresses adipogenesis during early stage MSC differentiation. Such effects are integrin binding-mediated and conducted through FAK-JNK and/or FAK-ERK signaling cascades. These results inspire a novel strategy encompassing type II collagen in bone tissue engineering.

  20. Regional differences of type II collagen synthesis in the human temporomandibular joint disc: immunolocalization study of carboxy-terminal type II procollagen peptide (chondrocalcin).

    PubMed

    Kondoh, Toshirou; Hamada, Yoshiki; Iino, Mitsuyoshi; Takahashi, Tetsu; Kikuchi, Toshiyuki; Fujikawa, Kyousuke; Seto, Kannichi

    2003-09-01

    The purpose of this study was to determine the regional differences of distribution of the carboxy-terminal type II procollagen peptide (pCOL-II-C; chondrocalcin) as markers of cartilaginous expression in the human temporomandibular joint (TMJ) disc. Twelve human TMJ discs without morphologic abnormalities were obtained from 12 fresh cadavers. All specimens were analysed for pCOL-II-C expression using polyclonal rabbit anti-human pCOL-II-C antibody in avidin-biotin-peroxidase complex staining. The results were demonstrated that the percentage of pCOL-II-C immunoreactive disc cells was significantly higher in the outer part (the articular surfaces) than in the inner part (the deep central areas) of the disc. These findings suggest that the tissue heterogeneity of cartilaginous expression reflects the functional demands of the remodelling process in the human TMJ disc.

  1. Multifunctional polyamidoamine-modified selenium nanoparticles dual-delivering siRNA and cisplatin to A549/DDP cells for reversal multidrug resistance.

    PubMed

    Zheng, Wenjing; Cao, Chengwen; Liu, Yanan; Yu, Qianqian; Zheng, Chuping; Sun, Dongdong; Ren, Xiaofan; Liu, Jie

    2015-01-01

    Multidrug resistance (MDR) is a major barrier against effective cancer treatment. Dual-delivering a therapeutic small interfering RNA (siRNA) and chemotherapeutic agents has been developed to reverse drug resistance in tumor cells. In this study, amine-terminated generation 5 polyamidoamine (PAMAM) dendrimers (G5.NH2)-modified selenium nanoparticles (G5@Se NP) were synthesized for the systemic dual-delivery of mdr1 siRNA and cisplatin (cis-diamminedichloroplatinum-(II), DDP), which was demonstrated to enhance siRNA loading, releasing efficiency and gene-silencing efficacy. When the mdr1 siRNA was conjugated with G5@Se NP via electrostatic interaction, a significant down-regulation of P-glycoprotein and multidrug resistance-associated protein expression was observed; G5@Se-DDP-siRNA arrested A549/DDP cells at G1 phase and led to enhanced cytotoxicity in A549/DDP cells through induction of apoptosis involving the AKT and ERK signaling pathways. Interestingly, G5@Se-DDP NP were much less reactive than DDP in the reactions with both MT and GSH, indicating that loading of DDP in a nano-delivery system could effectively prevent cell detoxification. Furthermore, animal studies demonstrated that the new delivery system of G5@Se-DDP-siRNA significantly enhanced the anti-tumor effect on tumor-bearing nude mice, with no appreciable abnormality in the major organs. These results suggest that G5@Se NP could be a potential platform to combine chemotherapy and gene therapy technology in the treatment of human disease.

  2. Oxidative damage induced in A549 cells by physically and chemically characterized air particulate matter (PM2.5) collected in Abidjan, Côte d'Ivoire.

    PubMed

    Kouassi, Kouakou S; Billet, Sylvain; Garçon, Guillaume; Verdin, Anthony; Diouf, Amadou; Cazier, Fabrice; Djaman, Joseph; Courcot, Dominique; Shirali, Pirouz

    2010-05-01

    Exposure to high levels of air pollution particulate matter (PM) is strongly associated with increased pulmonary morbidity and mortality. However, the underlying mechanisms of action whereby PM cause adverse health effects are still unclear. In developing countries, like in the sub-Saharian region of Africa, people are often exposed to high PM levels. Hence, three PM(2.5) samples were collected in the District of Abidjan (Côte d'Ivoire), under rural, urban or industrial influences. Their most toxicologically relevant physical and chemical characteristics were determined--thereby showing that most of them were equal or smaller than 2.5 microm--and the influence of both natural (Ca, Na, Mg, Ti, etc.) and anthropic (Al, Fe, Mn, Cr, Pb, Zn, Cu, Ni, benzene and its derivatives, paraffins, etc.) emission sources. The toxicity induced by the three PM samples was studied through 5-bromodeoxyuridine incorporation to DNA, mitochondrial dehydrogenase activity and extracellular lactate dehydrogenase activity. Hence, effect concentrations at 10 and 50% (EC(10) and EC(50), respectively) were as follows: (i) rural PM--EC(10) = 5.91 microg cm(-2) and EC(50) = 29.55 microg cm(-2); (ii) urban PM--EC(10) = 5.45 microg cm(-2) and EC(50) = 27.23 microg cm(-2); and (iii) industrial PM--EC(10) = 6.86 microg cm(-2) and EC(50) = 34.29 microg cm(-2). Moreover, PM-induced oxidative damage in A549 cells was observed through the induction of lipid peroxidation, the alteration of superoxide dismutase activity, and the disruption of glutathione status. Both the transition metals and the organic chemicals within the three collected PM samples under study might be involved in the oxidative damage and, therefore, the toxicity they induced in A549 cells.

  3. Angiotensin-II mediates ACE2 Internalization and Degradation through an Angiotensin-II type I receptor-dependent mechanism

    PubMed Central

    Lazartigues, Eric; Filipeanu, Catalin M.

    2014-01-01

    Angiotensin Converting Enzyme type 2 (ACE2) is a pivotal component of the renin-angiotensin system, promoting the conversion of Angiotensin (Ang)-II to Ang-(1-7). We previously reported that decreased ACE2 expression and activity contribute to the development of Ang-II-mediated hypertension in mice. The present study aimed to investigate the mechanisms involved in ACE2 down-regulation during neurogenic hypertension. In ACE2-transfected Neuro-2A cells, Ang-II treatment resulted in a significant attenuation of ACE2 enzymatic activity. Examination of the subcellular localization of ACE2 revealed that Ang-II treatment leads to ACE2 internalization and degradation into lysosomes. These effects were prevented by both the Ang-II type 1 receptor (AT1R) blocker losartan and the lysosomal inhibitor leupeptin. In contrast, in HEK293T cells, which lack endogenous AT1R, Ang-II failed to promote ACE2 internalization. Moreover, this effect could be induced after AT1R transfection. Further, co-immunoprecipitation experiments demonstrated that AT1R and ACE2 form complexes and these interactions were decreased by Ang-II treatment, which also enhanced ACE2 ubiquitination. In contrast, ACE2 activity was not changed by transfection of AT2 or Mas receptors. In vivo, Ang-II-mediated hypertension was blunted by chronic infusion of leupeptin in wildtype C57Bl/6, but not in ACE2 knockout mice. Overall, this is the first demonstration that elevated Ang-II levels reduce ACE2 expression and activity by stimulation of lysosomal degradation through an AT1R-dependent mechanism. PMID:25225202

  4. Inhibition of lung cancer cells A549 and H460 by curcuminoid extracts and nanoemulsions prepared from Curcuma longa Linnaeus

    PubMed Central

    Chang, Hong-Bin; Chen, Bing-Huei

    2015-01-01

    The objectives of this study were to explore the inhibition mechanism of lung cancer cells A549 and H460 by curcuminoid extracts and nanoemulsions prepared from Curcuma longa Linnaeus. In addition, human bronchus epithelial cell line BEAS-2B (normal cell) was selected for comparison. A high-performance liquid chromatography (HPLC) method was developed to separate and quantify the various curcuminoids in C. longa extract, including curcumin (1,714.5 μg/mL), demethoxycurcumin (1,147.4 μg/mL), and bisdemethoxycurcumin (190.2 μg/mL). A high-stability nanoemulsion composed of Tween 80, water, and curcuminoid extract was prepared, with mean particle size being 12.6 nm. The cell cycle was retarded at G2/M for both the curcuminoid extract and nanoemulsion treatments; however, the inhibition pathway may be different. H460 cells were more susceptible to apoptosis than A549 cells for both curcuminoid extract and nanoemulsion treatments. Growth of BEAS-2B remained unaffected for both the curcuminoid extract and nanoemulsion treatments, with a concentration range from 1 to 4 μg/mL. Also, the activities of caspase-3, caspase-8, and caspase-9 followed a dose-dependent increase for both A549 and H460 cells for both the treatments, accompanied by a dose-dependent increase in cytochrome C expression and a dose-dependent decrease in CDK1 expression. Interestingly, a dose-dependent increase in cyclin B expression was shown for A549 cells for both the treatments, while a reversed trend was found for H460 cells. Both mitochondria and death receptor pathways may be responsible for apoptosis of both A549 and H460 cells. PMID:26345201

  5. Capsaicin-induced genotoxic stress does not promote apoptosis in A549 human lung and DU145 prostate cancer cells.

    PubMed

    Lewinska, Anna; Jarosz, Paulina; Czech, Joanna; Rzeszutek, Iwona; Bielak-Zmijewska, Anna; Grabowska, Wioleta; Wnuk, Maciej

    2015-02-01

    Capsaicin is the major pungent component of the hot chili peppers of the genus Capsicum, which are consumed worldwide as a food additive. More recently, the selective action of capsaicin against cancer cells has been reported. Capsaicin was found to induce apoptosis and inhibit proliferation of a wide range of cancer cells in vitro, whereas being inactive against normal cells. As data on capsaicin-induced genotoxicity are limited and the effects of capsaicin against human lung A549 and DU145 prostate cancer cells were not explored in detail, we were interested in determining whether capsaicin-associated genotoxicity may also provoke A549 and DU145 cell death. Capsaicin-induced decrease in metabolic activity and cell proliferation, and changes in the cell cycle were limited to high concentrations used (≥ 100 μM), whereas, at lower concentrations, capsaicin stimulated both DNA double strand breaks and micronuclei production. Capsaicin was unable to provoke apoptotic cell death when used up to 250 μM concentrations. Capsaicin induced oxidative stress, but was ineffective in provoking the dissipation of the mitochondrial inner transmembrane potential. A different magnitude of p53 binding protein 1 (53BP1) recruitment contributed to diverse capsaicin-induced genotoxic effects in DU145 and A549 cells. Capsaicin was also found to be a DNA hypermethylating agent in A549 cells. In summary, we have shown that genotoxic effects of capsaicin may contribute to limited susceptibility of DU145 and A549 cancer cells to apoptosis in vitro, which may question the usefulness of capsaicin-based anticancer therapy, at least in a case of lung and prostate cancer.

  6. MicroRNA-490-3p inhibits proliferation of A549 lung cancer cells by targeting CCND1

    SciTech Connect

    Gu, Haihua; Yang, Tao; Fu, Shaozi; Chen, Xiaofan; Guo, Lei; Ni, Yiming

    2014-01-31

    Highlights: • We examined the level of miR-490-3p in A549 lung cancer cells compared with normal bronchial epithelial cell line. • We are the first to show the function of miR-490-3p in A549 lung cancer cells. • We demonstrate CCND1 may be one of the targets of miR-490-3p. - Abstract: MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate the translation of messenger RNAs by binding their 3′-untranslated region (3′UTR). In this study, we found that miR-490-3p is significantly down-regulated in A549 lung cancer cells compared with the normal bronchial epithelial cell line. To better characterize the role of miR-490-3p in A549 cells, we performed a gain-of-function analysis by transfecting the A549 cells with chemically synthesized miR-490-3P mimics. Overexpression of miR-490-3P evidently inhibits cell proliferation via G1-phase arrest. We also found that forced expression of miR-490-3P decreased both mRNA and protein levels of CCND1, which plays a key role in G1/S phase transition. In addition, the dual-luciferase reporter assays indicated that miR-490-3P directly targets CCND1 through binding its 3′UTR. These findings indicated miR-490-3P could be a potential suppressor of cellular proliferation.

  7. Inhibition of lung cancer cells A549 and H460 by curcuminoid extracts and nanoemulsions prepared from Curcuma longa Linnaeus.

    PubMed

    Chang, Hong-Bin; Chen, Bing-Huei

    2015-01-01

    The objectives of this study were to explore the inhibition mechanism of lung cancer cells A549 and H460 by curcuminoid extracts and nanoemulsions prepared from Curcuma longa Linnaeus. In addition, human bronchus epithelial cell line BEAS-2B (normal cell) was selected for comparison. A high-performance liquid chromatography (HPLC) method was developed to separate and quantify the various curcuminoids in C. longa extract, including curcumin (1,714.5 μg/mL), demethoxycurcumin (1,147.4 μg/mL), and bisdemethoxycurcumin (190.2 μg/mL). A high-stability nanoemulsion composed of Tween 80, water, and curcuminoid extract was prepared, with mean particle size being 12.6 nm. The cell cycle was retarded at G2/M for both the curcuminoid extract and nanoemulsion treatments; however, the inhibition pathway may be different. H460 cells were more susceptible to apoptosis than A549 cells for both curcuminoid extract and nanoemulsion treatments. Growth of BEAS-2B remained unaffected for both the curcuminoid extract and nanoemulsion treatments, with a concentration range from 1 to 4 μg/mL. Also, the activities of caspase-3, caspase-8, and caspase-9 followed a dose-dependent increase for both A549 and H460 cells for both the treatments, accompanied by a dose-dependent increase in cytochrome C expression and a dose-dependent decrease in CDK1 expression. Interestingly, a dose-dependent increase in cyclin B expression was shown for A549 cells for both the treatments, while a reversed trend was found for H460 cells. Both mitochondria and death receptor pathways may be responsible for apoptosis of both A549 and H460 cells.

  8. Uterine type II estrogen-binding sites are not of eosinophil origin

    SciTech Connect

    Not Available

    1986-01-05

    A recent report suggested that nuclear type II sites in the rat uterus are of eosinophil origin and may represent (/sup 3/H)estradiol binding to eosinophil peroxidase. To further evaluate this hypothesis the authors examined the response of nuclear type II sites to estrogen under conditions where eosinophils are not present. Results of the experiments show that physiological levels of estradiol-17..beta.. (10 nM for 72 h) will stimulate nuclear type II sites in highly purified cultures of rat uterine stromal and myometrial cells. The magnitude of the response of type II sites to estradiol in these stromal (4-fold) and myometrial (80-fold) cell cultures was essentially identical to that observed in the uterine cell types following in vivo estrogen treatment. Since these highly purified cultures of uterine cells were prepared from the uterus of a 21-day ovariectomized rat which is devoid of eosinophils, it was concluded that estradiol stimulation of nuclear type II sites is a direct intracellular response to estrogen which occurs independent of eosinophil accumulation. Furthermore, it was found that type II sites in the rat uterus are not peroxidase. Stimulation of cytosol and nuclear type II sites by estrogen in the rat uterus is a direct intracellular response to the hormone unrelated to eosinophil accumulation and/or peroxidase activity.

  9. Cardiac angiotensin II type I and type II receptors are increased in rats submitted to experimental hypothyroidism

    PubMed Central

    Carneiro-Ramos, M S; Diniz, G P; Almeida, J; Vieira, R L P; Pinheiro, S V B; Santos, R A; Barreto-Chaves, M L M

    2007-01-01

    This study assessed the behaviour of angiotensin II (Ang II) receptors in an experimental hypothyroidism model in male Wistar rats. Animals were subjected to thyroidectomy and resting for 14 days. The alteration of cardiac mass was evaluated by total heart weight (HW), right ventricle weight (RVW), left ventricle weight (LVW), ratio of HW, RVW and LVW to body weight (BW) and atrial natriuretic factor (ANF) expression. Cardiac and plasma Ang II levels and serum T3 and T4 were determined. The mRNA and protein levels of Ang II receptors were investigated by RT-PCR and Western blotting, respectively. Functional analyses were performed using binding assays. T3 and T4 levels and the haemodynamic parameters confirmed the hypothyroid state. HW/BW, RVW/BW and LVW/BW ratios and the ANF expression were lower than those of control animals. No change was observed in cardiac or plasma Ang II levels. Both AT1/AT2 mRNA and protein levels were increased in the heart of hypothyroid animals due to a significant increase of these receptors in the RV. Experiments performed in cardiomyocytes showed a direct effect promoted by low thyroid hormone levels upon AT1 and AT2 receptors, discarding possible influence of haemodynamic parameters. Functional assays showed that both receptors are able to bind Ang II. Herein, we have identified, for the first time, a close and direct relation of elevated Ang II receptor levels in hypothyroidism. Whether the increase in these receptors in hypothyroidism is an alternative mechanism to compensate the atrophic state of heart or whether it may represent a potential means to the progression of heart failure remains unknown. PMID:17540701

  10. Interfacial strain effect on type-I and type-II core/shell quantum dots

    NASA Astrophysics Data System (ADS)

    Gheshlaghi, Negar; Pisheh, Hadi Sedaghat; Karim, M. Rezaul; Malkoc, Derya; Ünlü, Hilmi

    2016-09-01

    A comparative experimental and theoretical study on the calculation of capped core diameter in ZnSe/ZnS, CdSe/Cd(Zn)S type-I and ZnSe/CdS type-II core/shell nanocrystals is presented. The lattice mismatch induced interface strain between core and shell was calculated from continuum elastic theory and applied in effective mass approximation method to obtain the corresponding capped core diameter. The calculated results were compared with diameter of bare cores (CdSe and ZnSe) from transmission electron microscopy images to obtain the amount of the stretched or squeezed core after deposition of tensile or compressive shells. The result of the study showed that the core is squeezed in ZnSe/ZnS and CdSe/Cd(Zn)S after compressive shell and stretched in ZnSe/CdS after tensile shell deposition. The stretched and squeezed amount of the capped core found to be in proportion with lattice mismatch amount in the core/shell structure.

  11. Proteolysis of synaptobrevin, syntaxin, and SNAP-25 in alveolar epithelial type II cells.

    PubMed

    Zimmerman, U J; Malek, S K; Liu, L; Li, H L

    1999-10-01

    Synaptobrevin-2, syntaxin-1, and SNAP-25 were identified in rat alveolar epithelial type II cells by Western blot analysis. Synaptobrevin-2 was localized in the lamellar bodies, and syntaxin-1 and SNAP-25 were found in 0.4% Nonidet P40-soluble and -insoluble fractions, respectively, of the type II cells. When the isolated type II cells were stimulated for secretion with calcium ionophore A23187 or with phorbol 12-myristate 13-acetate, these proteins were found to have been proteolyzed. Preincubation of cells with calpain inhibitor II (N-acetylleucylleucylmethionine), however, prevented the proteolysis. Treatment of the cell lysate with exogenous calpain resulted in a time-dependent decrease of these proteins. The data suggest that synaptobrevin, syntaxin, and SNAP-25 are subject to proteolytic modification by activated calpain in intact type II cells stimulated for secretion.

  12. Raw and thermally treated cement asbestos exerts different cytotoxicity effects on A549 cells in vitro.

    PubMed

    Pugnaloni, Armanda; Lucarini, Guendalina; Rubini, Corrado; Smorlesi, Arianna; Tomasetti, Marco; Strafella, Elisabetta; Armeni, Tatiana; Gualtieri, Alessandro F

    2015-01-01

    Raw cement asbestos (RCA) undergoes a complete solid state transformation when heated at high temperatures. The secondary raw material produced, high temperatures-cement asbestos (HT-CA) is composed of newly-formed crystals in place of the asbestos fibers present in RCA. Our previous study showed that HT-CA exerts lower cytotoxic cell damage compared to RCA. Nevertheless further investigations are needed to deepen our understanding of pathogenic pathways involving oxidative and nitrative damage. Our aim is to deepen the understanding of the biological effects on A549 cells of these materials regarding DNA damage related proteins (p53, its isoform p73 and TRAIL) and nitric oxide (NO) production during inducible nitric oxide synthase (iNOS)-mediated inflammation. Increments of p53/p73 expression, iNOS positive cells and NO concentrations were found with RCA, compared to HT-CA and controls mainly at 48 h. Interestingly, ferrous iron causing reactive oxygen species (ROS)-mediated DNA damage was found in RCA as a contaminant. HT-CA thermal treatment induces a global recrystallization with iron in a crystal form poorly released in media. HT-CA slightly interferes with genome expression and exerts lower inflammatory potential compared to RCA on biological systems. It could represent a safe approach for storing or recycling asbestos and an environmentally friendly alternative to asbestos waste.

  13. Biosynthesis of gold nanoparticles and related cytotoxicity evaluation using A549 cells.

    PubMed

    Sathishkumar, M; Pavagadhi, S; Mahadevan, A; Balasubramanian, R

    2015-04-01

    Biosynthesis of gold nanoparticles (AuNPs) has become an attractive area of research as it is environmentally benign. The toxicity of AuNPs synthesized by chemical routes has been widely studied. However, little is known about the toxicity associated with the biological synthesis of AuNPs. The present study was carried out to synthesize AuNPs using star anise (Illicium verum; a commercially available spice in abundance)and evaluate its toxicity using human epithelial lung cells (A549) in comparison with AuNPs synthesized by the traditional chemical methods (using sodium citrate and sodium borohydride). Apart from cell viability, markers of oxidative stress (reduced glutathione) and cell death (caspases) were also evaluated to understand the mechanisms of toxicity. Cell viability was observed to be 65.7 percent and 72.3 percent in cells exposed to chemically synthesized AuNPs at the highest dose (200nM) as compared to 80.2 percent for biologically synthesized AuNPs. Protective coating/capping of AuNPs by various polyphenolic compounds present in star anise extract appears to be a major contributor to lower toxicity observed in biologically synthesized AuNPs.

  14. Study of gaseous benzene effects upon A549 lung epithelial cells using a novel exposure system.

    PubMed

    Mascelloni, Massimiliano; Delgado-Saborit, Juana Maria; Hodges, Nikolas J; Harrison, Roy M

    2015-08-19

    Volatile organic compounds (VOCs) are ubiquitous pollutants known to be present in both indoor and outdoor air arising from various sources. Indoor exposure has increasingly become a major cause of concern due to the effects that such pollutants can have on health. Benzene, along with toluene, is one of the main components of the VOC mixture and is a known carcinogen due to its genotoxic effects. The aim of this study was to test the feasibility of an in vitro model to study the short-term effects of exposure of lung cells to airborne benzene. We studied the effects of exposure on DNA and the production of reactive oxygen species (ROS) in A549 cells, exposed to various concentrations of benzene (0.03; 0.1; 0.3 ppm) in gaseous form using a custom designed cell exposure chamber. Results showed a concentration-dependent increase of DNA breaks and an increase of ROS production, confirming the feasibility of the experimental procedure and validating the model for further in vitro studies of exposure to other VOCs.

  15. Role of cytoskeleton network in anisosmotic volume changes of intact and permeabilized A549 cells.

    PubMed

    Platonova, Alexandra; Ponomarchuk, Olga; Boudreault, Francis; Kapilevich, Leonid V; Maksimov, Georgy V; Grygorczyk, Ryszard; Orlov, Sergei N

    2015-10-01

    Recently we found that cytoplasm of permeabilized mammalian cells behaves as a hydrogel displaying intrinsic osmosensitivity. This study examined the role of microfilaments and microtubules in the regulation of hydrogel osmosensitivity, volume-sensitive ion transporters, and their contribution to volume modulation of intact cells. We found that intact and digitonin-permeabilized A549 cells displayed similar rate of shrinkage triggered by hyperosmotic medium. It was significantly slowed-down in both cell preparations after disruption of actin microfilaments by cytochalasin B, suggesting that rapid water release by intact cytoplasmic hydrogel contributes to hyperosmotic shrinkage. In hyposmotic swelling experiments, disruption of microtubules by vinblastine attenuated the maximal amplitude of swelling in intact cells and completely abolished it in permeabilized cells. The swelling of intact cells also triggered ~10-fold elevation of furosemide-resistant (86)Rb+ (K+) permeability and the regulatory volume decrease (RVD), both of which were abolished by Ba2+. Interestingly, RVD and K+ permeability remained unaffected in cytocholasin/vinblastine treated cells demonstrating that cytoskeleton disruption has no direct impact on Ba2+-sensitive K+-channels involved in RVD. Our results show, for the first time, that the cytoskeleton network contributes directly to passive cell volume adjustments in anisosmotic media via the modulation of the water retained by the cytoplasmic hydrogel.

  16. Taxol-induced paraptosis-like A549 cell death is not senescence

    NASA Astrophysics Data System (ADS)

    Wang, Chao-yang; Chen, Tong-Sheng

    2011-03-01

    Our previous studies have shown that taxol, a potent anticancer agent, induces caspase-independent cell death and cytoplasmic vacuolization in human lung cancer cells. However, the mechanisms of taxol-induced cytoplasmic vacuolization are poorly understood. Cytoplasmic vacuolization have been reported to be a characteristic of cell senescence. Here, we employed confocal fluorescence microscopy imaging to study the reversibility of taxol-induced cytoplasmic vacuolization and whether taxol triggers senescence in A549 cells. We found that taxol-induced cytoplasmic vacuolization at 6 or 9 h after treatment with taxol did not decrease but increase at 24 h or 72 h after refreshing the culture medium without taxol, indicating taxol-induced cytoplasmic vacuolization is irreversible. We used SA-β-Gal (senescence-associated β-galactosidase) to assess whether taxol-induced cell death in cytoplasmic vacuolization fashion is senescence, and found that hydrogen peroxide (H2O2)-treated, but not taxol-treated cells is significantly stained by the SA-β-Gal, a senescence testing kit, indicating that the form of taxol-induced cell death is not senescence.

  17. In vivo evaluation of curcumin-loaded nanoparticles in a A549 xenograft mice model.

    PubMed

    Yin, Hai-Tao; Zhang, De-Geng; Wu, Xiao-Li; Huang, Xin-En; Chen, Gang

    2013-01-01

    Curcumin (Cum) has been reported to have potential chemo-preventive and chemotherapeutic activity through influencing various processes, inducing cell cycle arrest, differentiation and apoptosis in a series of cancers. However, the poor solubility of Cum limits its further applications in the treatment of cancer. We have previously reported Cum-loaded nanoparticles (Cum-NPs) prepared with amphilic methoxy poly(ethylene glycol)-polycaprolactone (mPEG-PCL) block copolymers. The current study demonstrated superior antitumor efficacy of Cum-NPs over free Cum in the treatment of lung cancer. In vivo evaluation further demonstrated superior anticancer effects of Cum-NPs by delaying tumor growth compared to free Cum in an established A549 transplanted mice model. Moreover, Cum-NPs showed little toxicity to normal tissues including bone marrow, liver and kidney at a therapeutic dose. These results suggest that Cum-NPs are effective to inhibit the growth of human lung cancer with little toxicity to normal tissues, and could provide a clinically useful therapeutic regimen. They thus merit more research to evaluate the feasibility of clinical application.

  18. Pinus massoniana bark extract inhibits migration of the lung cancer A549 cell line

    PubMed Central

    Mao, Ping; Zhang, Ershao; Chen, Yang; Liu, Likun; Rong, Daqing; Liu, Qingfeng; Li, Weiling

    2017-01-01

    The bark of Pinus massoniana is a traditional Chinese medicine for the treatment of various health disorders. Previous studies have demonstrated that P. massoniana bark extract (PMBE) may induce the apoptosis of hepatoma and cervical cancer cells. However, whether PMBE is able to inhibit the migration of lung cancer cells requires further investigation. In the current study, the effects of PMBE on the viability of human lung cancer A549 cells were detected using an MTT assay. The migration of lung cancer cells following exposure to PMBE were quantified using wound healing and Transwell assays, respectively. The expression levels of matrix metalloproteinase (MMP)-9 were determined using western blotting. The results revealed that PMBE significantly inhibited the growth of the lung cancer cells. In addition, the wound closure rate and the migration of the lung cancer cells were suppressed by PMBE. Furthermore, the expression levels of MMP-9 were reduced. These findings indicated that PMBE is able to restrict the migration and invasion of lung cancer cells, and that PMBE may serve as a novel therapeutic agent for patients with metastatic lung cancer in the future. PMID:28356994

  19. Combined toxic effect of airborne heavy metals on human lung cell line A549.

    PubMed

    Choi, Yeowool; Park, Kihong; Kim, Injeong; Kim, Sang D

    2016-11-25

    Many studies have demonstrated that heavy metals existing as a mixture in the atmospheric environment cause adverse effects on human health and are important key factors of cytotoxicity; however, little investigation has been conducted on a toxicological study of a metal mixture from atmospheric fine particulate matter. The objective of this study was to predict the combined effects of heavy metals in aerosol by using in vitro human cells and obtain a suitable mixture toxicity model. Arsenic, nickel, and lead were selected for mixtures exposed to A549 human lung cancer cells. Cell proliferation (WST-1), glutathione (GSH), and interleukin (IL)-8 inhibition were observed and applied to the prediction models of mixture toxicity, concentration addition (CA) and independent action (IA). The total mixture concentrations were set by an IC10-fixed ratio of individual toxicity to be more realistic for mortality and enzyme inhibition tests. The results showed that the IA model was statistically closer to the observed results than the CA model in mortality, indicating dissimilar modes of action. For the GSH inhibition, the results predicted by the IA and CA models were highly overestimated relative to mortality. Meanwhile, the IL-8 results were stable with no significant change in immune reaction related to inflammation. In conclusion, the IA model is a rapid prediction model in heavy metals mixtures; mortality, as a total outcome of cell response, is a good tool for demonstrating the combined toxicity rather than other biochemical responses.

  20. Nanoparticles of Selaginella doederleinii leaf extract inhibit human lung cancer cells A549

    NASA Astrophysics Data System (ADS)

    Syaefudin; Juniarti, A.; Rosiyana, L.; Setyani, A.; Khodijah, S.

    2016-01-01

    The aim of the present study is to evaluate cytotoxicity effect of nanoparticles of Selaginella doederleinii (S. doederleinii) leaves extract. S. doederleinii was extracted by maceration method using 70%(v/v) ethanol as solvent. Phytochemical content was analyzed qualitatively by using Harborne and Thin Layer Chromatography (TLC) methods. Nanoparticle extract was prepared by ionic gelation using chitosan as encapsulant agent. Anticancer activity was performed by using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The results showed that S. doederleinii contains of flavonoids. Nanoparticle of S. doederleinii leaves extract greatly inhibited A549 cells growth (cancer cells), with IC50 of 3% or 1020 μg/ml. These nanoparticles extract also inhibited the growth of Chang cells (normal cells), with IC50 of 4% or 1442 μg/ml. The effective concentration of nanoparticles extract which inhibits cancer cells without harming the normal cells is 0.5% or 167 μg/ml. Further studies are needed to obtain the concentration of nanoparticles extract which can selectively suppress cancer cells.

  1. Receptor for detection of a Type II sex pheromone in the winter moth Operophtera brumata

    PubMed Central

    Zhang, Dan-Dan; Wang, Hong-Lei; Schultze, Anna; Froß, Heidrun; Francke, Wittko; Krieger, Jürgen; Löfstedt, Christer

    2016-01-01

    How signal diversity evolves under stabilizing selection in a pheromone-based mate recognition system is a conundrum. Female moths produce two major types of sex pheromones, i.e., long-chain acetates, alcohols and aldehydes (Type I) and polyenic hydrocarbons and epoxides (Type II), along different biosynthetic pathways. Little is known on how male pheromone receptor (PR) genes evolved to perceive the different pheromones. We report the identification of the first PR tuned to Type II pheromones, namely ObruOR1 from the winter moth, Operophtera brumata (Geometridae). ObruOR1 clusters together with previously ligand-unknown orthologues in the PR subfamily for the ancestral Type I pheromones, suggesting that O. brumata did not evolve a new type of PR to match the novel Type II signal but recruited receptors within an existing PR subfamily. AsegOR3, the ObruOR1 orthologue previously cloned from the noctuid Agrotis segetum that has Type I acetate pheromone components, responded significantly to another Type II hydrocarbon, suggesting that a common ancestor with Type I pheromones had receptors for both types of pheromones, a preadaptation for detection of Type II sex pheromone. PMID:26729427

  2. Receptor for detection of a Type II sex pheromone in the winter moth Operophtera brumata.

    PubMed

    Zhang, Dan-Dan; Wang, Hong-Lei; Schultze, Anna; Froß, Heidrun; Francke, Wittko; Krieger, Jürgen; Löfstedt, Christer

    2016-01-05

    How signal diversity evolves under stabilizing selection in a pheromone-based mate recognition system is a conundrum. Female moths produce two major types of sex pheromones, i.e., long-chain acetates, alcohols and aldehydes (Type I) and polyenic hydrocarbons and epoxides (Type II), along different biosynthetic pathways. Little is known on how male pheromone receptor (PR) genes evolved to perceive the different pheromones. We report the identification of the first PR tuned to Type II pheromones, namely ObruOR1 from the winter moth, Operophtera brumata (Geometridae). ObruOR1 clusters together with previously ligand-unknown orthologues in the PR subfamily for the ancestral Type I pheromones, suggesting that O. brumata did not evolve a new type of PR to match the novel Type II signal but recruited receptors within an existing PR subfamily. AsegOR3, the ObruOR1 orthologue previously cloned from the noctuid Agrotis segetum that has Type I acetate pheromone components, responded significantly to another Type II hydrocarbon, suggesting that a common ancestor with Type I pheromones had receptors for both types of pheromones, a preadaptation for detection of Type II sex pheromone.

  3. Achondrogenesis: a review with special consideration of achondrogenesis type II (Langer-Saldino).

    PubMed

    Chen, H; Liu, C T; Yang, S S

    1981-01-01

    We describe two dwarfed infants with large head, short neck and chest, prominent abdomen, and short limbs. Both died neonatally. Radiographic and morphologic characteristics identified the Langer-Saldino form of achondrogenesis (type II). Review of type II achondrogenesis documented distinctive clinical and anthropometric manifestations (fewer stillbirths, longer survival time and gestation period, larger size of the baby, longer limbs, and characteristic craniofacial features) as compared with type I achondrogenesis (Parenti-Fraccaro).

  4. Alteration of sequence specificity of the type II restriction endonuclease HincII through an indirect readout mechanism.

    PubMed

    Joshi, Hemant K; Etzkorn, Christopher; Chatwell, Lorentz; Bitinaite, Jurate; Horton, Nancy C

    2006-08-18

    The functional and structural consequences of a mutation of the DNA intercalating residue of HincII, Q138F, are presented. Modeling has suggested that the DNA intercalation by Gln-138 results in DNA distortions potentially used by HincII in indirect readout of its cognate DNA, GTYRAC (Y = C or T, R = A or G) (Horton, N. C., Dorner, L. F., and Perona, J. J. (2002) Nat. Struct. Biol. 9, 42-47). Kinetic data presented here indicate that the mutation of glutamine 138 to phenylalanine (Q138F) results in a change in sequence specificity at the center two base pairs of the cognate recognition site. We show that the preference of HincII for cutting, but not binding, the three cognate sites differing in the center two base pairs has been altered by the mutation Q138F. Five new crystal structures are presented including Q138F HincII bound to GTTAAC and GTCGAC both with and without Ca2+ as well as the structure of wild type HincII bound to GTTAAC. The Q138F HincII/DNA structures show conformational changes in the protein, bound DNA, and at the protein-DNA interface, consistent with the formation of adaptive complexes. Analysis of these structures and the effect of Ca2+ binding on the protein-DNA interface illuminates the origin of the altered specificity by the mutation Q138F in the HincII enzyme.

  5. Development of type-I/type-II hybrid dye sensitizer with both pyridyl group and catechol unit as anchoring group for type-I/type-II dye-sensitized solar cell.

    PubMed

    Ooyama, Yousuke; Furue, Kensuke; Enoki, Toshiaki; Kanda, Masahiro; Adachi, Yohei; Ohshita, Joji

    2016-11-09

    A type-I/type-II hybrid dye sensitizer with a pyridyl group and a catechol unit as the anchoring group has been developed and its photovoltaic performance in dye-sensitized solar cells (DSSCs) is investigated. The sensitizer has the ability to adsorb on a TiO2 electrode through both the coordination bond at Lewis acid sites and the bidentate binuclear bridging linkage at Brønsted acid sites on the TiO2 surface, which makes it possible to inject an electron into the conduction band of the TiO2 electrode by the intramolecular charge-transfer (ICT) excitation (type-I pathway) and by the photoexcitation of the dye-to-TiO2 charge transfer (DTCT) band (type-II pathway). It was found that the type-I/type-II hybrid dye sensitizer adsorbed on TiO2 film exhibits a broad photoabsorption band originating from ICT and DTCT characteristics. Here we reveal the photophysical and electrochemical properties of the type-I/type-II hybrid dye sensitizer bearing a pyridyl group and a catechol unit, along with its adsorption modes onto TiO2 film, and its photovoltaic performance in type-I/type-II DSSC, based on optical (photoabsorption and fluorescence spectroscopy) and electrochemical measurements (cyclic voltammetry), density functional theory (DFT) calculation, FT-IR spectroscopy of the dyes adsorbed on TiO2 film, photocurrent-voltage (I-V) curves, incident photon-to-current conversion efficiency (IPCE) spectra, and electrochemical impedance spectroscopy (EIS) for DSSC.

  6. Polyelectrolytes Multilayers to Modulate Cell Adhesion: A Study of the Influence of Film Composition and Polyelectrolyte Interdigitation on the Adhesion of the A549 Cell Line.

    PubMed

    Muzzio, Nicolás E; Pasquale, Miguel A; Gregurec, Danijela; Diamanti, Eleftheria; Kosutic, Marija; Azzaroni, Omar; Moya, Sergio E

    2016-04-01

    Polyelectrolyte multilayers (PEMs) with different polycation/polyanion pairs are fabricated by the layer-by-layer technique employing synthetic, natural, and both types of polyelectrolytes. The impact of the chemical composition of PEMs on cell adhesion is assessed by studying cell shape, spreading area, focal contacts, and cell proliferation for the A549 cell line. Cells exhibit good adhesion on PEMs containing natural polycations and poly(sodium 4-styrenesulfonate) (PSS) as polyanion, but limited adhesion is observed on PEMs fabricated from both natural polyelectrolytes. PEMs are then assembled, depositing a block of natural polyelectrolytes on top of a stiffer block with PSS as polyanion. Cell adhesion is enhanced on top of the diblock PEMs compared to purely natural PEMs. This fact could be explained by the interdigitation between polyelectrolytes from the two blocks. Diblock PEM assembly provides a simple means to tune cell adhesion on biocompatible PEMs.

  7. Functionalized fullerenes mediate photodynamic killing of cancer cells: Type I versus Type II photochemical mechanism

    PubMed Central

    Mroz, Pawel; Pawlak, Anna; Satti, Minahil; Lee, Haeryeon; Wharton, Tim; Gali, Hariprasad; Sarna, Tadeusz; Hamblin, Michael R.

    2007-01-01

    Photodynamic therapy (PDT) employs the combination of non-toxic photosensitizers (PS) and harmless visible light to generate reactive oxygen species (ROS) and kill cells. Most clinically studied PS are based on the tetrapyrrole structure of porphyrins, chlorins and related molecules, but new non-tetrapyrrole PS are being sought. Fullerenes are soccer-ball shaped molecules composed of sixty or seventy carbon atoms and have attracted interest in connection with the search for biomedical applications of nanotechnology. Fullerenes are biologically inert unless derivatized with functional groups, whereupon they become soluble and can act as PS. We have compared the photodynamic activity of six functionalized fullerenes with 1, 2, or 3 hydrophilic or 1, 2, or 3 cationic groups. The octanol-water partition coefficients were determined and the relative contributions of Type I photochemistry (photogeneration of superoxide in the presence of NADH) and Type II photochemistry (photogeneration of singlet oxygen) were studied by measurement of oxygen consumption, 1270-nm luminescence and EPR spin-trapping of the superoxide product. We studied three mouse cancer cell lines: (J774, LLC and CT26) incubated for 24 h with fullerenes and illuminated with white light. The order of effectiveness as PS was inversely proportional to the degree of substitution of the fullerene nucleus for both the neutral and cationic series. The mono-pyrrolidinium fullerene was the most active PS against all cell lines and induced apoptosis 4–6 hours after illumination. It produced diffuse intracellular fluorescence when dichlorodihydrofluorescein was added as an ROS probe suggesting a Type I mechanism for phototoxicity. We conclude that certain functionalized fullerenes have potential as novel PDT agents and phototoxicity may be mediated both by superoxide and by singlet oxygen. PMID:17664135

  8. Characteristics of flares producing metric type II bursts and coronal mass ejections

    NASA Technical Reports Server (NTRS)

    Kahler, S.; Sheeley, N. R., Jr.; Howard, R. A.; Michels, D. J.; Koomen, M. J.

    1984-01-01

    An attempt is made to study the origin of coronal shocks by comparing several flare characteristics for two groups of flares: those with associated metric type II bursts and coronal mass ejections (CMEs) and those with associated metric type II bursts but no CMEs. CMEs accompany about 60 percent of all flares with type II bursts for solar longitudes greater than 30 deg, where CMEs are well observed with the NRL Solwind coronagraph. H-alpha flare areas, 1-8 A X-ray fluxes, and impulsive 3-cm fluxes are all statistically smaller for events with no CMEs than for events with CMEs. It appears that both compact and large mass ejection flares are associated with type II bursts. The events with no CMEs imply that at least many type II shocks are not piston-driven, but the large number of events of both groups with small 3 cm bursts does not support the usual assumption that type II shocks are produced by large energy releases in flare impulsive phases. The poor correlation between 3 cm burst fluxes and the occurrence of type II bursts may be due to large variations in the coronal Alfven velocity.

  9. THE CONNECTIONS BETWEEN THE UV AND OPTICAL Fe ii EMISSION LINES IN TYPE 1 AGNs

    SciTech Connect

    Kovacević-Dojcinović, Jelena; Popović, Luka Č. E-mail: lpopovic@aob.bg.ac.rs

    2015-12-15

    We investigate the spectral properties of the UV (λλ2650–3050 Å) and optical (λλ4000–5500 Å) Fe ii emission features in a sample of 293 Type 1 active galactic nuclei (AGNs) from the Sloan Digital Sky Survey database. We explore different correlations between their emission line properties, as well as the correlations with other emission lines from the spectral range. We find several interesting correlations and outline the most interesting results as follows. (i) There is a kinematical connection between the UV and optical Fe ii lines, indicating that the UV and optical Fe ii lines originate from the outer part of the broad line region, the so-called intermediate line region. (ii) The unexplained anticorrelations of the optical Fe ii equivalent width (EW Fe ii{sub opt}) versus EW [O iii] 5007 Å and EW Fe ii{sub opt} versus FWHM Hβ have not been detected for the UV Fe ii lines. (iii) The significant averaged redshift in the UV Fe ii lines, which is not present in optical Fe ii, indicates an inflow in the UV Fe ii emitting clouds, and probably their asymmetric distribution. (iv) Also, we confirm the anticorrelation between the intensity ratio of the optical and UV Fe ii lines and the FWHM of Hβ, and we find the anticorrelations of this ratio with the widths of Mg ii 2800 Å, optical Fe ii, and UV Fe ii. This indicates a very important role for the column density and microturbulence in the emitting gas. We discuss the starburst activity in high-density regions of young AGNs as a possible explanation of the detected optical Fe ii correlations and intensity line ratios of the UV and optical Fe ii lines.

  10. Effectiveness of cervical hemilaminectomy in canine Hansen Type I and Type II disc disease: a retrospective study.

    PubMed

    Schmied, Oliver; Golini, Lorenzo; Steffen, Frank

    2011-01-01

    Medical records of 41 dogs, including 15 small breed dogs (<15 kg) and 26 large breed dogs (>15 kg), with cervical intervertebral disc disease (IVDD) that underwent a hemilaminectomy were reviewed. Dogs were diagnosed using myelography, computed tomography/myelography, or MRI, and dogs were classified as having either Hansen Type I disc extrusion or Hansen Type II disc protrusion located ventrally, ventrolaterally, or laterally within the cervical spinal canal. The most common clinical presentation was ambulatory tetraparesis and/or lameness (44%). The most affected sites for cervical IVDD were between the sixth and seventh cervical vertebrae (C6-C7; 78% of Hansen Type II discs) and C2-C3 (86% of Hansen Type I discs). Treatment was effective in 88% of dogs. Five large breed dogs (12%) did not improve. In dogs with a Hansen Type I disc extrusion, clinical signs improved in 96% of the cases. In dogs with a Hansen Type II disc protrusion, an excellent and good outcome was seen in 47% and 32% of cases, respectively. Outcome was significantly better for small breed dogs and dogs with Hansen Type I disc disease compared with large breed dogs and dogs with Hansen Type II disc disease.

  11. Computer simulation of vortex pinning in type II superconductors. II. Random point pins

    NASA Astrophysics Data System (ADS)

    Brandt, E. H.

    1983-10-01

    Pinning of vortices in a type II superconductor by randomly positioned identical point pins is simulated using the two-dimensional method described in a previous paper (Part I). The system is characterized by the vortex and pin numbers ( N v , N p ), the vortex and pin interaction ranges ( R v , R p ), and the amplitude of the pin potential A p . The computation is performed for many cases: dilute or dense, sharp or soft, attractive or repulsive, weak or strong pins, and ideal or amorphous vortex lattice. The total pinning force F as a function of the mean vortex displacement X increases first linearly (over a distance usually much smaller than the vortex spacing and than R p ) and then saturates, fluctuating about its averagebar F. We interpretbar F as the maximum pinning force j c B of a large specimen. For weak pins the prediction of Larkin and Ovchinnikov for two-dimensional collective pinning is confirmed:bar F=const·bar W/ R p c 66, wherebar W is the mean square pinning force and c 66 is the shear modulus of the vortex lattice. If the initial vortex lattice is chosen highly defective (“amorphous”) the constant is 1.3 3 times larger than for the ideal triangular lattice. This finding may explain the often observed “history effect”. The functionbar F( A p ) exhibits a jump, which for dilute, sharp, attractive pins occurs close to the “threshold value” predicted for isolated pins by Labusch. This jump reflects the onset of plastic deformation of the vortex lattice, and in some cases of vortex trapping, but is not a genuine threshold. For strong pinsbar F˜( N p bar W)1/2 approaches the direct summation limit. For both weak and strong pinning j c B is related to the mean square actual (not maximum) force of each pin. This mean square in general is not proportional to A {/p 2} but, due to relaxation of the vortex lattice, may be smaller or larger than its rigid-lattice limit. Therefore, simple power laws j c ˜ n p A {/p 2} or j c ˜ n p A p in

  12. Shock-associated kilometric radio emission and solar metric type II bursts

    NASA Technical Reports Server (NTRS)

    Kahler, S. W.; Cliver, E. W.; Cane, H. V.

    1989-01-01

    New criteria are used here to select and study the properties of shock-associated (SA) kilometric bursts. Nearly half of all intense metric type II bursts were temporally associated with 1980 kHz emission which was not attributable to metric type III bursts. A quarter of all intense type II bursts are not associated with any significant 1980 kHz emission and another quarter are accompanied by 1980 kHz emission presumed due to type II bursts. The SA bursts are generally not well correlated with microwave flux-density profiles but compare more closely with the most intense and structured parts of the profiles of metric type II bursts. These results imply that the SA emission is due primarily to energetic electrons accelerated at the associated shock.

  13. Quantum cascade light emitting diodes based on type-II quantum wells

    SciTech Connect

    Lin, C.H.; Yang, R.Q.; Zhang, D.; Murry, S.J.; Pei, S.S.; Allerman, A.A.; Kurtz, S.R.

    1997-01-21

    The authors have demonstrated room-temperature CW operation of type-II quantum cascade (QC) light emitting diodes at 4.2 {micro}m using InAs/InGaSb/InAlSb type-II quantum wells. The type-II QC configuration utilizes sequential multiple photon emissions in a staircase of coupled type-II quantum wells. The device was grown by molecular beam epitaxy on a p-type GaSb substrate and was compared of 20 periods of active regions separated by digitally graded quantum well injection regions. The maximum average output power is about 250 {micro}W at 80 K, and 140 {micro}W at 300 K at a repetition rate of 1 kHz with a duty cycle of 50%.

  14. Type-II AGN population from the zCOSMOS survey

    NASA Astrophysics Data System (ADS)

    Bongiorno, A.; Mignoli, M.; Zamorani, G.; Zcosmos Team

    2008-10-01

    I'll present the first results on the type-II AGN population isolated from the zCOSMOS bright sample which consists of 10k sources, purely magnitude selected at I=22.5. The selected type-II AGN sample consists of about 200 AGN, selected using the diagnostic diagrams up to redshift ~1.0. I'll present the properties of this sample (i.e. SED and morphology) and some preliminary results on the evolution of type-II AGN, as well as on the evolution of their fraction with respect to the total AGN population (Type-I + Type-II), as a function of both luminosity and redshift.

  15. Femtosecond Dynamics of Norrish Type-II Reactions: Nonconcerted Hydrogen-Transfer and Diradical Intermediacy.

    PubMed

    De Feyter S; Diau; Zewail

    2000-01-01

    Norrish type-II and McLafferty rearrangements, which both involve an intramolecular transfer of a gamma H atom, can be differentiated on the femtosecond time scale. The McLafferty rearrangement results in ion fragmentation of the parent ketone, whereas the Norrish type-II reaction leads to a diradical species, which then either cyclizes or fragments (see scheme). For Norrish type-II reactions, the reaction time for the transfer of the hydrogen atom is within 70 - 90 fs, and the lifetime of the diradical intermediate is in the range of 400 - 700 ps at the total energy studied.

  16. Blocking the NOTCH pathway can inhibit the growth of CD133-positive A549 cells and sensitize to chemotherapy

    SciTech Connect

    Liu, Juntao; Mao, Zhangfan; Huang, Jie; Xie, Songping; Liu, Tianshu; Mao, Zhifu

    2014-02-21

    Highlights: • Notch signaling pathway members are expressed lower levels in CD133+ cells. • CD133+ cells are not as sensitive as CD133− cells to chemotherapy. • GSI could inhibit the growth of both CD133+ and CD133− cells. • Blockade of Notch signaling pathway enhanced the effect of chemotherapy with CDDP. • DAPT/CDDP co-therapy caused G2/M arrest and elimination in CD133+ cells. - Abstract: Cancer stem cells (CSCs) are believed to play an important role in tumor growth and recurrence. These cells exhibit self-renewal and proliferation properties. CSCs also exhibit significant drug resistance compared with normal tumor cells. Finding new treatments that target CSCs could significantly enhance the effect of chemotherapy and improve patient survival. Notch signaling is known to regulate the development of the lungs by controlling the cell-fate determination of normal stem cells. In this study, we isolated CSCs from the human lung adenocarcinoma cell line A549. CD133 was used as a stem cell marker for fluorescence-activated cell sorting (FACS). We compared the expression of Notch signaling in both CD133+ and CD133− cells and blocked Notch signaling using the γ-secretase inhibitor DAPT (GSI-IX). The effect of combining GSI and cisplatin (CDDP) was also examined in these two types of cells. We observed that both CD133+ and CD133− cells proliferated at similar rates, but the cells exhibited distinctive differences in cell cycle progression. Few CD133+ cells were observed in the G{sub 2}/M phase, and there were half as many cells in S phase compared with the CD133− cells. Furthermore, CD133+ cells exhibited significant resistance to chemotherapy when treated with CDDP. The expression of Notch signaling pathway members, such as Notch1, Notch2 and Hes1, was lower in CD133+ cells. GSI slightly inhibited the proliferation of both cell types and exhibited little effect on the cell cycle. The inhibitory effects of DPP on these two types of cells were

  17. Oligomeric State Regulated Trafficking of Human Platelet-Activating Factor Acetylhydrolase Type-II

    PubMed Central

    Monillas, Elizabeth S.; Caplan, Jeffrey L.; Thévenin, Anastasia F.; Bahnson, Brian J.

    2015-01-01

    The intracellular enzyme platelet-activating factor acetylhydrolase type-II (PAFAH-II) hydrolyzes platelet-activating factor and oxidatively fragmented phospholipids. PAFAH-II in its resting state is mainly cytoplasmic, and it responds to oxidative stress by becoming increasingly bound to endoplasmic reticulum and Golgi membranes. Numerous studies have indicated that this enzyme is essential for protecting cells from oxidative stress induced apoptosis. However, the regulatory mechanism of the oxidative stress response by PAFAH-II has not been fully resolved. Here, changes to the oligomeric state of human PAFAH-II were investigated as a potential regulatory mechanism toward enzyme trafficking. Native PAGE analysis in vitro and photon counting histogram within live cells showed that PAFAH-II is both monomeric and dimeric. A Gly-2-Ala site-directed mutation of PAFAH-II demonstrated that the N-terminal myristoyl group is required for homodimerization. Additionally, the distribution of oligomeric PAFAH-II is distinct within the cell; homodimers of PAFAH-II were localized to the cytoplasm while monomers were associated to the membranes of the endoplasmic reticulum and Golgi. We propose that the oligomeric state of PAFAH-II drives functional protein trafficking. PAFAH-II localization to the membrane is critical for substrate acquisition and effective oxidative stress protection. It is hypothesized that the balance between monomer and dimer serves as a regulatory mechanism of a PAFAH-II oxidative stress response. PMID:25707358

  18. Oligomeric state regulated trafficking of human platelet-activating factor acetylhydrolase type-II.

    PubMed

    Monillas, Elizabeth S; Caplan, Jeffrey L; Thévenin, Anastasia F; Bahnson, Brian J

    2015-05-01

    The intracellular enzyme platelet-activating factor acetylhydrolase type-II (PAFAH-II) hydrolyzes platelet-activating factor and oxidatively fragmented phospholipids. PAFAH-II in its resting state is mainly cytoplasmic, and it responds to oxidative stress by becoming increasingly bound to endoplasmic reticulum and Golgi membranes. Numerous studies have indicated that this enzyme is essential for protecting cells from oxidative stress induced apoptosis. However, the regulatory mechanism of the oxidative stress response by PAFAH-II has not been fully resolved. Here, changes to the oligomeric state of human PAFAH-II were investigated as a potential regulatory mechanism toward enzyme trafficking. Native PAGE analysis in vitro and photon counting histogram within live cells showed that PAFAH-II is both monomeric and dimeric. A Gly-2-Ala site-directed mutation of PAFAH-II demonstrated that the N-terminal myristoyl group is required for homodimerization. Additionally, the distribution of oligomeric PAFAH-II is distinct within the cell; homodimers of PAFAH-II were localized to the cytoplasm while monomers were associated to the membranes of the endoplasmic reticulum and Golgi. We propose that the oligomeric state of PAFAH-II drives functional protein trafficking. PAFAH-II localization to the membrane is critical for substrate acquisition and effective oxidative stress protection. It is hypothesized that the balance between monomer and dimer serves as a regulatory mechanism of a PAFAH-II oxidative stress response.

  19. Type II collagen is transiently expressed during avian cardiac valve morphogenesis.

    PubMed

    Swiderski, R E; Daniels, K J; Jensen, K L; Solursh, M

    1994-08-01

    We present new evidence of the temporal and spatial expression of type II collagen in the embryonic chick heart during the very early stages of its development. In particular, we emphasize the distribution of its mRNA and protein during valve formation. Type II collagen as well as several other fibrillar collagens (types I, III, and V) are present in stage 18 endocardial cushion mesenchymal cells. At stage 23, alpha 1 (II) collagen transcripts and the cognate polypeptide colocalize in the atrioventricular valves. As development proceeds, the relative abundance of alpha 1 (II) collagen transcripts decreases during the stages studied (stages 22 to 45; day 3.5 to day 19) as assayed by RNA blotting of extracts of whole hearts. Type II collagen protein was immunologically undetectable in stage 38 (day 12) hearts, although collagens I, III, and V persisted and localize in the valve regions, in the endothelial lining of the heart, and in the epicardium. In keeping with other observations of type II collagen expression in non-chondrogenic regions of a variety of vertebrate embryos, the avian heart also exhibits transient type II collagen expression.

  20. Halo Coronal Mass Ejections and Their Relation to DH Type-II Radio Bursts

    NASA Astrophysics Data System (ADS)

    Shanmugaraju, A.; Bendict Lawrance, M.

    2015-10-01

    A set of 88 halo CMEs observed by the Solar and Heliospheric Observatory/ Large Angle Solar Coronagraph (SOHO/LASCO) during the period 2005 to 2010 is considered to study the relationship of these halo CMEs with Type-II radio bursts in the deca-hectametric (DH) wavelength range observed by Wind/(Plasma and Radio Waves: WAVES). Among the 88 events, 39 halo CMEs are found to be associated with DH Type-II radio bursts and their characteristics are analyzed with the following results: i) The heights of the CME leading edge at the time of the starting frequencies of many of the selected DH Type-II events (74 %) are in the range (2 - 10 R_{⊙}) where the shocks are formed. ii) The mean speed of DH-associated halo CMEs (1610 km s-1) is nearly twice the mean speed (853 km s-1) of halo CMEs without DH Type-II radio bursts, implying that the peak of the Alfvén speed profile in the outer corona where DH Type-II radio bursts start might be around 800 km s-1. iii) The shock speed of DH Type-II radio bursts calculated using the heights of shock signatures of the corresponding CME events is found to be slightly higher than the CME speed. iv) The CME speed plays a major role in the determination of the ending frequency of DH Type-II radio bursts but not the starting frequency. v) The relationship between the characteristics of DH Type-II radio bursts and CMEs is explained in the context of the universal drift-rate spectrum.

  1. Acute high-dose X-radiation-induced genomic changes in A549 cells.

    PubMed

    Muradyan, A; Gilbertz, K; Stabentheiner, S; Klause, S; Madle, H; Meineke, V; Ullmann, R; Scherthan, H

    2011-06-01

    Accidents with ionizing radiation often involve single, acute high-dose exposures that can lead to acute radiation syndrome and late effects such as carcinogenesis. To study such effects at the cellular level, we investigated acute ionizing radiation-induced chromosomal aberrations in A549 adenocarcinoma cells at the genome-wide level by exposing the cells to an acute dose of 6 Gy 240 kV X rays. One sham-irradiated clone and four surviving irradiated clones were recovered by minimal dilution and further expanded and analyzed by chromosome painting and tiling-path array CGH, with the nonirradiated clone 0 serving as the control. Acute X-ray exposure induced specific translocations and changes in modal chromosome number in the four irradiated clones. Array CGH disclosed unique and recurrent genomic changes, predominantly losses, and revealed that the fragile sites FRA3B and FRA16D were preferential regions of genomic alterations in all irradiated clones, which is likely related to radioresistant S-phase progression and genomic stress. Furthermore, clone 4 displayed an increased radiosensitivity at doses >5 Gy. Pairwise comparisons of the gene expression patterns of all irradiated clones to the sham-irradiated clone 0 revealed an enrichment of the Gene Ontology term "M Phase" (P = 6.2 × 10(-7)) in the set of differentially expressed genes of clone 4 but not in those of clones 1-3. Ionizing radiation-induced genomic changes and fragile site expression highlight the capacity of a single acute radiation exposure to affect the genome of exposed cells by inflicting genomic stress.

  2. PM10-biogenic fraction drives the seasonal variation of proinflammatory response in A549 cells.

    PubMed

    Camatini, Marina; Corvaja, Viviana; Pezzolato, Eleonora; Mantecca, Paride; Gualtieri, Maurizio

    2012-02-01

    PM10 was collected in a Milan urban site, representative of the city air quality, during winter and summer 2006. Mean daily PM10 concentration was 48 μg m(-3) during summer and 148 μg m(-3) during winter. Particles collected on Teflon filters were chemically characterized and the endotoxin content determined by the LAL test. PM10-induced cell toxicity, assessed with MTT and LDH methods, and proinflammatory potential, monitored by IL-6 and IL-8 cytokines release, were investigated on the human alveolar epithelial cell line A549 exposed to increasing doses of PM. Besides untreated cells, exposure to inert carbon particles (2-12 μm) was also used as additional control. Both cell toxicity and proinflammatory potency resulted to be higher for summer PM10 with respect of winter PM10, with IL-6 showing the highest dose-dependent release. The relevance of biogenic components adsorbed onto PM10 in eliciting the proinflammatory mediators release was investigated by inhibition experiments. Polymixin B (Poly) was used to inhibit particle-bind LPS while Toll-like receptor-2 antibody (a-TLR2) to specifically block the activation of this receptor. While cell viability was not modulated in cells coexposed to PM10 and Poly or a-TLR2 or both, inflammatory response did it, with IL-6 release being the most inhibited. In conclusion, Milan PM10-induced seasonal-dependent biological effects, with summer particles showing higher cytotoxic and proinflammatory potential. Cytotoxicity seemed to be unaffected by the PM biogenic components, while inflammation was significantly reduced after the inhibition of some biogenic activated pathways. Besides, the PM-associated biogenic activity does not entirely justify the PM-induced inflammatory effects. © 2010 Wiley Periodicals, Inc. Environ Toxicol 2012.

  3. Suitable parameter choice on quantitative morphology of A549 cell in epithelial–mesenchymal transition

    PubMed Central

    Ren, Zhou-Xin; Yu, Hai-Bin; Li, Jian-Sheng; Shen, Jun-Ling; Du, Wen-Sen

    2015-01-01

    Evaluation of morphological changes in cells is an integral part of study on epithelial to mesenchymal transition (EMT), however, only a few papers reported the changes in quantitative parameters and no article compared different parameters for demanding better parameters. In the study, the purpose was to investigate suitable parameters for quantitative evaluation of EMT morphological changes. A549 human lung adenocarcinoma cell line was selected for the study. Some cells were stimulated by transforming growth factor-β1 (TGF-β1) for EMT, and other cells were as control without TGF-β1 stimulation. Subsequently, cells were placed in phase contrast microscope and three arbitrary fields were captured and saved with a personal computer. Using the tools of Photoshop software, some cells in an image were selected, segmented out and exchanged into unique hue, and other part in the image was shifted into another unique hue. The cells were calculated with 29 morphological parameters by Image Pro Plus software. A parameter between cells with or without TGF-β1 stimulation was compared statistically and nine parameters were significantly different between them. Receiver operating characteristic curve (ROC curve) of a parameter was described with SPSS software and F-test was used to compare two areas under the curves (AUCs) in Excel. Among them, roundness and radius ratio were the most AUCs and were significant higher than the other parameters. The results provided a new method with quantitative assessment of cell morphology during EMT, and found out two parameters, roundness and radius ratio, as suitable for quantification. PMID:26182364

  4. DNA double-strand breaks activate ATM independent of mitochondrial dysfunction in A549 cells.

    PubMed

    Kalifa, Lidza; Gewandter, Jennifer S; Staversky, Rhonda J; Sia, Elaine A; Brookes, Paul S; O'Reilly, Michael A

    2014-10-01

    Excessive nuclear or mitochondrial DNA damage can lead to mitochondrial dysfunction, decreased energy production, and increased generation of reactive oxygen species (ROS). Although numerous cell signaling pathways are activated when cells are injured, the ataxia telangiectasia mutant (ATM) protein has emerged as a major regulator of the response to both mitochondrial dysfunction and nuclear DNA double-strand breaks (DSBs). Because mitochondrial dysfunction is often a response to excessive DNA damage, it has been difficult to determine whether nuclear and/or mitochondrial DNA DSBs activate ATM independent of mitochondrial dysfunction. In this study, mitochondrial and nuclear DNA DSBs were generated in the A549 human lung adenocarcinoma cell line by infecting with retroviruses expressing the restriction endonuclease PstI fused to a mitochondrial targeting sequence (MTS) or nuclear localization sequence (NLS) and a hemagglutinin antigen epitope tag (HA). Expression of MTS-PstI-HA or NLS-PstI-HA activated the DNA damage response defined by phosphorylation of ATM, the tumor suppressor protein p53 (TP53), KRAB-associated protein (KAP)-1, and structural maintenance of chromosomes (SMC)-1. Phosphorylated ATM and SMC1 were detected in nuclear fractions, whereas phosphorylated TP53 and KAP1 were detected in both mitochondrial and nuclear fractions. PstI also enhanced expression of the cyclin-dependent kinase inhibitor p21 and inhibited cell growth. This response to DNA damage occurred in the absence of detectable mitochondrial dysfunction and excess production of ROS. These findings reveal that DNA DSBs are sufficient to activate ATM independent of mitochondrial dysfunction and suggest that the activated form of ATM and some of its substrates are restricted to the nuclear compartment, regardless of the site of DNA damage.

  5. Type-II Dirac fermions in the PtSe2 class of transition metal dichalcogenides

    NASA Astrophysics Data System (ADS)

    Huang, Huaqing; Zhou, Shuyun; Duan, Wenhui

    2016-09-01

    Recently, a new "type-II" Weyl fermion, which exhibits exotic phenomena, such as an angle-dependent chiral anomaly, was discovered in a new phase of matter where electron and hole pockets contact at isolated Weyl points [Nature (London) 527, 495 (2015), 10.1038/nature15768]. This raises an interesting question about whether its counterpart, i.e., a type-II Dirac fermion, exists in real materials. Here, we predict the existence of symmetry-protected type-II Dirac fermions in a class of transition metal dichalcogenide materials. Our first-principles calculations on PtSe2 reveal its bulk type-II Dirac fermions which are characterized by strongly tilted Dirac cones, novel surface states, and exotic doping-driven Lifshitz transition. Our results show that the existence of type-II Dirac fermions in PtSe2-type materials is closely related to its structural P 3 ¯m 1 symmetry, which provides useful guidance for the experimental realization of type-II Dirac fermions and intriguing physical properties distinct from those of the standard Dirac fermions known before.

  6. Expression of collagen types I and II on articular cartilage in a rat knee contracture model.

    PubMed

    Hagiwara, Yoshihiro; Ando, Akira; Chimoto, Eiichi; Tsuchiya, Masahiro; Takahashi, Ichiro; Sasano, Yasuyuki; Onoda, Yoshito; Suda, Hideaki; Itoi, Eiji

    2010-01-01

    The purpose of our study was to clarify the expression patterns of collagen types I and II on articular cartilage after immobilization in a rat knee contracture model in 3 specific areas (noncontact area, transitional area, contact area). The unilateral knee joints of adult male rats were rigidly immobilized at 150 degrees of flexion using screws and a rigid plastic plate. Sham-operated animals had holes drilled in the femur and the tibia and screws inserted but were not plated. The expression patterns of collagen types I and II in each area were evaluated by in situ hybridization (ISH), immunohistochemistry (IHC), and quantitative real-time polymerase chain reaction (qPCR). The expression of collagen type II in the noncontact area was decreased by ISH but appeared unchanged when examined by IHC. In the transitional and contact areas, the expression of collagen type II was initially shown to have decreased and then increased at the hypertrophic chondrocytes by ISH but appeared decreased by IHC. Quantitative PCR revealed the decreased expression of type II collagen in the contact area. Immunostaining of collagen type I was increased at the noncontact area and transitional areas. Alterations of collagen types I and II expression may also affect the degeneration of articular cartilage after immobilization and the changes were different in the three areas.

  7. Organization of the human keratin type II gene cluster at 12q13

    SciTech Connect

    Yoon, S.J.; LeBlanc-Straceski, J.; Krauter, K.

    1994-12-01

    Keratin proteins constitute intermediate filaments and are the major differentiation products of mammalian epithelial cells. The epithelial keratins are classified into two groups, type I and type II, and one member of each group is expressed in a given epithelial cell differentiation stage. Mutations in type I and type II keratin genes have now been implicated in three different human genetic disorders, epidermolysis bullosa simplex, epidermolytic hyperkeratosis, and epidermolytic palmoplantar keratoderma. Members of the type I keratins are mapped to human chromosome 17, and the type II keratin genes are mapped to chromosome 12. To understand the organization of the type II keratin genes on chromosome 12, we isolated several yeast artificial chromosomes carrying these keratin genes and examined them in detail. We show that eight already known type II keratin genes are located in a cluster at 12q13, and their relative organization reflects their evolutionary relationship. We also determined that a type I keratin gene, KRT8, is located next to its partner, KRT18, in this cluster. Careful examination of the cluster also revealed that there may be a number of additional keratin genes at this locus that have not been described previously. 41 refs., 3 figs., 1 tab.

  8. Genetics Home Reference: hereditary sensory and autonomic neuropathy type II

    MedlinePlus

    ... Diseases Clinical Research Network: The Inherited Neuropathies Consortium Educational Resources (2 links) Orphanet: Hereditary sensory and autonomic neuropathy type 2 University of Chicago Center for Peripheral Neuropathy Patient Support ...

  9. Tissue-specific expression of the human type II collagen gene in mice

    SciTech Connect

    Lovell-Badge, R.H.; Bygrave, A.; Bradley, A.; Robertson, E.; Tilly, R.; Cheah, K.S.E.

    1987-05-01

    Type II collagen is crucial to the development of form in vertebrates as it is the major protein of cartilage. To study the factors regulating its expression the authors introduced a cosmid containing the human type II collagen gene, including 4.5 kilobases of 5' and 2.2 kilobases of 3' flanking DNA, into embryonic stem cells in vitro. The transformed cells contribute to all tissues in chimeric mice allowing the expression of the exogenous gene to be studied in vivo. Human type II collagen mRNA is restricted to tissues showing transcription from the endogenous gene and human type II collagen is found in extracellular matrix surrounding chondrocytes in cartilage. The results indicate that the cis-acting requirements for correct temporal and spatial regulation of the gene are contained with the introduced DNA.

  10. Alzheimer type II astrocytes in the brains of pigs with salt poisoning (water deprivation/intoxication).

    PubMed

    Finnie, J W; Blumbergs, P C; Williamson, M M

    2010-10-01

    The finding of Alzheimer type II astrocytes, in addition to the pathognomonic combination of laminar cerebrocortical necrosis and eosinophil infiltration, in the brains of pigs is reported for the first time in cases of indirect salt poisoning following water deprivation.

  11. Quantitative prediction of type II solar radio emission from the Sun to 1 AU

    NASA Astrophysics Data System (ADS)

    Schmidt, J. M.; Cairns, Iver H.

    2016-01-01

    Coronal mass ejections (CMEs) are frequently associated with shocks and type II solar radio bursts. Despite involving fundamental plasma physics and being the archetype for collective radio emission from shocks, type II bursts have resisted detailed explanation for over 60 years. Between 29 November and 1 December 2013 the two widely separated spacecraft STEREO A and B observed a long lasting, intermittent, type II radio burst from ≈4 MHz to 30 kHz (harmonic), including an intensification when the CME-driven shock reached STEREO A. We demonstrate the first accurate and quantitative simulation of a type II burst from the high corona (near 11 solar radii) to 1 AU for this event with a combination of a data-driven three-dimensional magnetohydrodynamic simulation for the CME and plasma background and an analytic quantitative kinetic model for the radio emission.

  12. Enhanced proliferation of primary rat type II pneumocytes by Jaagsiekte sheep retrovirus envelope protein

    SciTech Connect

    Johnson, Chassidy; Jahid, Sohail; Voelker, Dennis R.; Fan Hung

    2011-04-10

    Jaagsiekte sheep retrovirus (JSRV) is the causative agent of a contagious lung cancer in sheep. The envelope protein (Env) is the oncogene, as it can transform cell lines in culture and induce tumors in animals, although the mechanisms for transformation are not yet clear because a system to perform transformation assays in differentiated type II pneumocytes does not exist. In this study we report culture of primary rat type II pneumocytes in conditions that favor prolonged expression of markers for type II pneumocytes. Env-expressing cultures formed more colonies that were larger in size and were viable for longer periods of time compared to vector control samples. The cells that remained in culture longer were confirmed to be derived from type II pneumocytes because they expressed surfactant protein C, cytokeratin, displayed alkaline phosphatase activity and were positive for Nile red. This system will be useful to study JSRV Env in the targets of transformation.

  13. Chromosomal localization and structure of the human type II IMP dehydrogenase gene

    SciTech Connect

    Glesne, D.; Huberman, E. |; Collart, F.; Varkony, T.; Drabkin, H.

    1994-05-01

    We determined the chromosomal localization and structure of the gene encoding human type II inosine 5{prime}-monophosphate dehydrogenase (IMPDH, EC 1.1.1.205), an enzyme associated with cellular proliferation, malignant transformation, and differentiation. Using polymerase chain reaction (PCR) primers specific for type II IMPDH, we screened a panel of human-Chinese hamster cell somatic hybrids and a separate deletion panel of chromosome 3 hybrids and localized the gene to 3p21.1{yields}p24.2. Two overlapping yeast artificial chromosome clones containing the full gene for type II IMPDH were isolated and a physical map of 117 kb of human genomic DNA in this region of chromosome 3 was constructed. The gene for type II IMPDH was localized and oriented on this map and found to span no more than 12.5 kb.

  14. Dynamic investigation of DNA bending and wrapping by type II topoisomerases

    NASA Astrophysics Data System (ADS)

    Shao, Qing; Finzi, Laura; Dunlap, David

    2009-11-01

    Type II topoisomerases catalyze DNA decatenation and unwinding which is crucial for cell division, and therefore type II topoisomerases are some of the main targets of anti-cancer drugs. A recent crystal structure shows that, during the catalytic cycle, a yeast type II topoimerase can bend a 10 base pair DNA segment by up to 150 degrees. Bacterial gyrase, another type II topoisomerase, can wrap DNA into a tight 180 degree turn. Bending a stiff polymer like DNA requires considerable energy and could represent the rate limiting step in the catalytic (topological) cycle. Using modified deoxyribonucleotides in PCR reactions, stiffer DNA fragments have been produced and used as substrates for topoisomerase II-mediated relaxation of plectonemes introduced in single molecules using magnetic tweezers. The wrapping ability of gyrase decreases for diamino-purine-substituted DNA in which every base pair has three hydrogen-bonds. The overall rate of relaxation of plectonemes by recombinant human topoisomerase II alpha also decreases. These results reveal the dynamic properties of DNA bending and wrapping by type II topisomerases and suggest that A:T base pair melting is a rate determining step for bending and wrapping.

  15. Opsonic effect of jacalin and human immunoglobulin A on type II group B streptococci.

    PubMed Central

    Payne, N R; Concepcion, N F; Anthony, B F

    1990-01-01

    This study examined the effect of immunoglobulin A (IgA) and the IgA-binding lectin jacalin on the phagocytosis of type II group B streptococci (GBS). Strains possessing the trypsin-sensitive and trypsin-resistant components of the c protein (II/c) and type II GBS lacking the c protein (II) were examined by radiolabeled bacterial uptake, bactericidal assays, and electron microscopy. Type II/c GBS resisted phagocytosis by monocytes (4.9% +/- 0.8% uptake, mean +/- SE, n = 25) compared with type II GBS (8.5% +/- 1.4% uptake, n = 14, P = 0.03). Phagocytic killing by polymorphonuclear leukocytes was also less for the type II/c strain 78-471 than for the type II strain 79-176 (68% +/- 5% versus 86% +/- 4% reduction in CFU at 45 min, P = 0.03). IgA binding did not explain the resistance of type II/c GBS to phagocytosis. The uptake of type II/c GBS was not significantly different after opsonization in cord sera lacking endogenous IgA (5.93% +/- 1.4%) than in the same cord sera after addition of exogenous IgA (5.48% +/- 1.4%, P = 0.69, n = 9). Attempts to remove serum IgA with the IgA-binding lectin jacalin resulted in the binding of IgA-jacalin complexes to II/c GBS. This combination of nonspecific IgA and jacalin increased uptake of II/c GBS from 4.9% +/- 0.8% to 11.8% +/- 1.9% (P = 0.002). Jacalin also combined with specific, immune, monoclonal IgA bound to the surface of Haemophilus influenzae and promoted the uptake of these bacteria. Jacalin and IgA mediated phagocytosis of II/c GBS via receptors that were not dependent on divalent cations and that were not modulated by plating monocytes on antigen-antibody complexes. Images PMID:2228238

  16. Iron Kα emission in type-I and type-II active galactic nuclei

    NASA Astrophysics Data System (ADS)

    Ricci, C.; Ueda, Y.; Paltani, S.; Ichikawa, K.; Gandhi, P.; Awaki, H.

    2014-07-01

    The narrow Fe Kα line is one of the main signatures of the reprocessing of X-ray radiation from the material surrounding supermassive black holes, and it has been found to be omnipresent in the X-ray spectra of active galactic nuclei (AGN). In this work, we study the characteristics of the narrow Fe Kα line in different types of AGN. Using the results of a large Suzaku study, we find that Seyfert 2s have on average lower Fe Kα luminosities than Seyfert 1s for the same 10-50 keV continuum luminosity. Simulating dummy Seyfert 1s and Seyfert 2s populations using physical torus models of X-ray reflected emission, we find that this difference can be explained by means of different average inclination angles with respect to the torus, as predicted by the unified model. Alternative explanations include differences in the intensities of Compton humps, in the photon index distributions or in the average iron abundances. We show that the ratio between the flux of the broad and narrow Fe Kα line in the 6.35-6.45 keV range depends on the torus geometry considered, and is on average <25 per cent and <15 per cent for type-I and type-II AGN, respectively. We find evidence of absorption of the narrow Fe Kα line flux in Compton-thick AGN, which suggests that part of the reflecting material is obscured. We estimate that on average in obscured AGN the reflected radiation from neutral material is seen through a column density which is 1/4 of that absorbing the primary X-ray emission. This should be taken into account in synthesis models of the CXB and when studying the luminosity function of heavily obscured AGN. We detect the first evidence of the X-ray Baldwin effect in Seyfert 2s, with the same slope as that found for Seyfert 1s, which suggests that the mechanism responsible for the decrease of the equivalent width with the continuum luminosity is the same in the two classes of objects.

  17. Comparative physicochemical and biological characterization of NIST Interim Reference Material PM2.5 and SRM 1648 in human A549 and mouse RAW264.7 cells.

    PubMed

    Mitkus, Robert J; Powell, Jan L; Zeisler, Rolf; Squibb, Katherine S

    2013-12-01

    The epidemiological association between exposure to fine particulate matter (PM2.5) and adverse health effects is well-known. Here we report the size distribution, metals content, endotoxin content, and biological activity of National Institute of Standards and Technology (NIST) Interim Reference Material (RM) PM2.5. Biological activity was measured in vitro by effects on cell viability and the release of four inflammatory immune mediators, from human A549 alveolar epithelial cells or murine RAW264.7 monocytes. A dose range covering three orders of magnitude (1-1000μg/mL) was tested, and biological activity was compared to an existing Standard Reference Material (SRM) for urban PM (NIST SRM 1648). Robust release of IL-8 and MCP-1 from A549 cells was observed in response to IRM PM2.5 exposures. Significant TNF-α, but not IL-6, secretion from RAW264.7 cells was observed in response to both IRM PM2.5 and SRM 1648 particle types. Cytokine or chemokine release at high doses often occurred in the presence of cytotoxicity, likely as a result of externalization of preformed mediator. Our results are consistent with a local cytotoxic and pro-inflammatory mechanism of response to exposure to inhaled ambient PM2.5 and reinforce the continued relevance of in vitro assays for mechanistic research in PM toxicology. Our study furthers the goal of developing reference samples of environmentally relevant particulate matter of various sizes that can be used for hypothesis testing by multiple investigators.

  18. E2F1 enhances 8-chloro-adenosine-induced G2/M arrest and apoptosis in A549 and H1299 lung cancer cells.

    PubMed

    Duan, Hong-Ying; Cao, Ji-Xiang; Qi, Jun-Juan; Wu, Guo-Sheng; Li, Shu-Yan; An, Guo-Shun; Jia, Hong-Ti; Cai, Wang-Wei; Ni, Ju-Hua

    2012-03-01

    The E2F1 transcription factor is a well known regulator of cell proliferation and apoptosis, but its role in response to DNA damage is less clear. 8-Chloro-adenosine (8-Cl-Ado), a nucleoside analog, can inhibit proliferation in a variety of human tumor cells. However, it is still elusive how the agent acts on tumors. Here we show that A549 and H1299 cells formed DNA double-strand breaks after 8-Cl-Ado exposure, accompanied by E2F1 upregulation at protein level. Overexpressed wild-type (E2F1-wt) colocalized with double-strand break marker γ-H2AX and promoted G2/M arrest in 8-Cl-Ado-exposed A549 and H1299, while expressed S31A mutant of E2F1 (E2F1-mu) significantly reduced ability to accumulate at sites of DNA damage and G2/M arrest, suggesting that E2F1 is required for activating G2/M checkpoint pathway upon DNA damage. Transfection of either E2F1-wt or E2F1-mu plasmid promoted apoptosis in 8-Cl-Ado-exposed cells, indicating that 8-Cl-Ado may induce apoptosis in E2F1-dependent and E2F1-independent ways. These findings demonstrate that E2F1 plays a crucial role in 8-Cl-Ado-induced G2/M arrest but is dispensable for 8-Cl-Ado-induced apoptosis. These data also suggest that the mechanism of 8-Cl-Ado action is complicated.

  19. Reproducible isolation of type II pneumocytes from fetal and adult rat lung using nycodenz density gradients.

    PubMed

    Viscardi, R M; Ullsperger, S; Resau, J H

    1992-01-01

    Isolating fresh, relatively pure type II pneumocytes from the lung, particularly of fetal origin, is a difficult process. Separation by buoyant density gradient centrifugation has been used successfully to isolate adult type II cells. There is concern, however, that Percoll, a gradient medium that is commonly used for type II cell isolation, may be toxic to cells. We evaluated a new gradient medium, Nycodenz, that is (1) a true solution, (2) transparent, (3) not metabolized by cells, and (4) nontoxic to cells. Type II pneumocytes were isolated from 19- and 21-day gestation fetal and adult rat lung by elastase digestion and separated on preformed isotonic Nycodenz gradients (2 mL each of 27.6, 20.7, 13.8, and 4.6 (w/v) solutions). Type II pneumocytes were recovered from the density range 1.057-1.061 and identified by binding of FITC-conjugated and gold-complexed Maclura pomifera lectin. Cells derived from 19-day fetal lung contained abundant glycogen and reacted with a monoclonal antibody to the cytokeratins 8 and 18, which are markers of the fetal type II cell. Adult type II cells reacted with antibodies to cytokeratins 8, 18, and 19. Type II cell purity was 79.7 +/- 2.4%, 83.8 +/- 2.8%, and 82.6 +/- 1.8% (means +/- SEM) for 19- and 21-day gestation fetal and adult lung preparations, respectively. Cell viability was greater than 95%. The final cell yield for adult preparations was 17.8 +/- 2.7 x 10(6)/rat (means +/- SEM). To determine if the freshly isolated type II pneumocytes were functionally active, the incorporation of [3H]choline into phosphatidylcholine was measured. The percent saturation of phosphatidylcholine was high for both populations of freshly isolated cells. However, adult type II pneumocytes incorporated [3H]choline into phosphatidylcholine more rapidly than 21-day gestation fetal cells (5.97 x 10(-3) dpm/10(6) cells/h vs. 0.32 x 10(-3) dpm/10(6) cells/h, P less than .005). We have demonstrated that, using the Nycodenz isolation method, it is

  20. Positions of type II fundamental and harmonic sources in the 30-100 MHZ range

    NASA Technical Reports Server (NTRS)

    Sawant, H. S.; Gergely, T. E.; Kundu, M. R.

    1982-01-01

    An excellent example of a type III-V burst followed by a type II burst with fundamental and harmonic bands was observed on June 18, 1979 at the Clark Lake Radio Observatory. The observations are described in detail and their implications are discussed with regard to the problem of directionality with respect to the magnetic field lines of the collisionless MHD shock wave generated at the start of the flash phase. It is found that the positions of type III and type II (F) bursts at a number of frequencies are essentially the same, which implies that the shock responsible for the type II radiation follows the path of the type III exciter, that is, the shock propagates along the open field lines.

  1. MACHO observations of Type II cepheids and RV Tauri Stars in the LMC

    SciTech Connect

    Alcock, C.; Pollard, K.A.; Alisman, R.A.

    1996-07-01

    We report the of the existence of RV Tauri stars in the Large Magellanic Cloud (LMC). This class of variable star has hitherto been unidentified in the Magellanic Clouds. In light and color curve behavior the RV Tauri stars appear to be an extension of the Type II Cepheids to longer periods. A single period-luminosity-color relationship is seen to describe both the Type II Cepheids and the RV Tauri stars in the LMC.

  2. Black hole and hawking radiation by type-II Weyl fermions

    NASA Astrophysics Data System (ADS)

    Volovik, G. E.

    2016-11-01

    The type-II Weyl and type-II Dirac fermions may emerge behind the event horizon of black holes. Correspondingly, the black hole can be simulated by creation of the region with overtilted Weyl or Dirac cones. The filling of the electronic states inside the "black hole" is accompanied by Hawking radiation. The Hawking temperature in the Weyl semimetals can reach the room temperature, if the black hole region is sufficiently small, and thus the effective gravity at the horizon is large.

  3. The Relation Between Large-Scale Coronal Propagating Fronts and Type II Radio Bursts

    NASA Astrophysics Data System (ADS)

    Nitta, Nariaki V.; Liu, Wei; Gopalswamy, Nat; Yashiro, Seiji

    2014-12-01

    Large-scale, wave-like disturbances in extreme-ultraviolet (EUV) and type II radio bursts are often associated with coronal mass ejections (CMEs). Both phenomena may signify shock waves driven by CMEs. Taking EUV full-disk images at an unprecedented cadence, the Atmospheric Imaging Assembly (AIA) onboard the Solar Dynamics Observatory has observed the so-called EIT waves or large-scale coronal propagating fronts (LCPFs) from their early evolution, which coincides with the period when most metric type II bursts occur. This article discusses the relation of LCPFs as captured by AIA with metric type II bursts. We show examples of type II bursts without a clear LCPF and fast LCPFs without a type II burst. Part of the disconnect between the two phenomena may be due to the difficulty in identifying them objectively. Furthermore, it is possible that the individual LCPFs and type II bursts may reflect different physical processes and external factors. In particular, the type II bursts that start at low frequencies and high altitudes tend to accompany an extended arc-shaped feature, which probably represents the 3D structure of the CME and the shock wave around it, and not just its near-surface track, which has usually been identified with EIT waves. This feature expands and propagates toward and beyond the limb. These events may be characterized by stretching of field lines in the radial direction and may be distinct from other LCPFs, which may be explained in terms of sudden lateral expansion of the coronal volume. Neither LCPFs nor type II bursts by themselves serve as necessary conditions for coronal shock waves, but these phenomena may provide useful information on the early evolution of the shock waves in 3D when both are clearly identified in eruptive events.

  4. Knockdown of Aurora-B inhibits the growth of non-small cell lung cancer A549 cells.

    PubMed

    Yu, Jing Jing; Zhou, Long Dian; Zhao, Tian Tian; Bai, Wei; Zhou, Jing; Zhang, Wei

    2015-09-01

    Elevated expression of Aurora-B affects cell apoptosis and proliferation in a variety of solid tumors. However, the role of Aurora-B has been poorly evaluated in non-small cell lung cancer (NSCLC). In the present study, it was found that Aurora-B was overexpressed in tissue specimens obtained from 174 patients with lung cancer. It was also demonstrated that knockdown of Aurora-B induces apoptosis and inhibits the growth of lung cancer A549 cells in vitro and in vivo. Furthermore, it was found that silencing Aurora-B decreased the activity of the phosphoinositide 3-kinase (PI3K)/AKT pathway. Therefore, it was concluded that knockdown of Aurora-B induces apoptosis and inhibits growth in NSCLC A549 cells, in addition to inhibiting the activity of the PI3K/AKT signaling pathway. Targeting Aurora-B may provide a novel target for lung cancer therapy.

  5. Flux tubes and the type-I/type-II transition in a superconductor coupled to a superfluid

    SciTech Connect

    Alford, Mark G.; Good, Gerald

    2008-07-01

    We analyze magnetic-flux tubes at zero temperature in a superconductor that is coupled to a superfluid via both density and gradient ('entrainment') interactions. The example we have in mind is high-density nuclear matter, which is a proton superconductor and a neutron superfluid, but our treatment is general and simple, modeling the interactions as a Ginzburg-Landau effective theory with four-fermion couplings, including only s-wave pairing. We numerically solve the field equations for flux tubes with an arbitrary number of flux quanta and compare their energies. This allows us to map the type-I/type-II transition in the superconductor, which occurs at the conventional {kappa}{identical_to}{lambda}/{xi}=1/{radical}(2) if the condensates are uncoupled. We find that a density coupling between the condensates raises the critical {kappa} and, for a sufficiently high neutron density, resolves the type-I/type-II transition line into an infinite number of bands corresponding to 'type-II(n)' phases, in which n, the number of quanta in the favored flux tube, steps from 1 to infinity. For lower neutron density, the coupling creates spinodal regions around the type-I/type-II boundary, in which metastable flux configurations are possible. We find that a gradient coupling between the condensates lowers the critical {kappa} and creates spinodal regions. These exotic phenomena may not occur in nuclear matter, which is thought to be deep in the type-II region but might be observed in condensed-matter systems.

  6. CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms

    PubMed Central

    Meyer, Sara C.; Keller, Matthew D.; Chiu, Sophia; Koppikar, Priya; Guryanova, Olga A.; Rapaport, Franck; Xu, Ke; Manova, Katia; Pankov, Dmitry; O’Reilly, Richard J.; Kleppe, Maria; McKenney, Anna Sophia; Shih, Alan H.; Shank, Kaitlyn; Ahn, Jihae; Papalexi, Eftymia; Spitzer, Barbara; Socci, Nick; Viale, Agnes; Mandon, Emeline; Ebel, Nicolas; Andraos, Rita; Rubert, Joëlle; Dammassa, Ernesta; Romanet, Vincent; Dölemeyer, Arno; Zender, Michael; Heinlein, Melanie; Rampal, Rajit; Weinberg, Rona Singer; Hoffman, Ron; Sellers, William R.; Hofmann, Francesco; Murakami, Masato; Baffert, Fabienne; Gaul, Christoph; Radimerski, Thomas; Levine, Ross L.

    2015-01-01

    Summary Although clinically tested JAK inhibitors reduce splenomegaly and systemic symptoms, molecular responses are not observed in most myeloproliferative neoplasms (MPN) patients. We previously demonstrated that MPN cells become persistent to type I JAK inhibitors that bind the active conformation of JAK2. We investigated if CHZ868, a type II JAK inhibitor, would demonstrate activity in JAK inhibitor persistent cells, murine MPN models, and MPN patient samples. JAK2- and MPL-mutant cell lines were sensitive to CHZ868, including type I JAK inhibitor persistent cells. CHZ868 showed significant activity in murine MPN models and induced reductions in mutant allele burden not observed with type I JAK inhibitors. These data demonstrate that type II JAK inhibition is a viable therapeutic approach for MPN patients. PMID:26175413

  7. Statistical Study of Shocks and CMEs Associated With Interplanetary Type II Bursts

    NASA Astrophysics Data System (ADS)

    Aguilar-Rodriguez, E.; Gopalswamy, N.; MacDowall, R.; Yashiro, S.; Kaiser, M. L.

    2005-05-01

    We present a study of some spectral properties associated with interplanetary Type II radio emission. Type II radio bursts are signatures of violent eruptions from the Sun that result in shock waves propagating through the corona and the interplanetary medium. We investigated the relative bandwidth of all the type II bursts observed by the Radio and Plasma Wave Experiment (WAVES) on board the Wind spacecraft from 1997 up to 2003. We obtained three sets of events, based on the frequency domain of occurrence: 109 events in the low frequency domain (30 KHz to 1000 kHz detected by the RAD1 receiver), 216 events in the high frequency domain (1-14 MHz, observed by the RAD2 receiver), and 73 events that spanned both domains (RAD1 and RAD2). We present statistical results for the bandwidth-to-frequency ratio (BFR) in the three subsets as well as a comparision of our results with the Type II solar radio bursts observed by ISEE-3 radio experiment, which is similar to WAVES/RAD1. We analyzed the bandwidth and BFR evolution with the heliocentric distance as well as an analysis of drift rate magnitude of type II radio bursts and its starting frequency. We also present some properties of shocks and coronal mass ejections associated with interplanetary type II bursts. This work is partially supported by NSF/SHINE (ATM 0204588)

  8. Production of human type II collagen using an efficient baculovirus-silkworm multigene expression system.

    PubMed

    Qi, Qi; Yao, Lunguang; Liang, Zhisheng; Yan, Donghua; Li, Zhuo; Huang, Yadong; Sun, Jingchen

    2016-12-01

    Human type II collagen is a macromolecular protein found throughout the human body. The baculovirus expression vector system is one of the most ideal systems for the routine production and display of recombinant eukaryotic proteins in insect, larvae, and mammalian cells. We use this system to express a full-length gene, human type II collagen cDNA (4257 bp), in cultured Spodoptera frugiperda 9 cells (Sf9), Bombyx mori cells, and silkworm larvae. In this study, the expression of human type II collagen gene in both insect cells and silkworm larvae was purified by nickel column chromatography, leading to 300-kDa bands in SDS-PAGE and western blotting indicative of collagen α-chains organized in a triple-helical structure. About 1 mg/larva human type II collagen is purified from silkworm skin, which shows a putative large scale of collagen production way. An activity assay of recombinant human type II collagen expressed by silkworm larvae demonstrated that the recombinant protein has considerable bioactive properties. Scanning electron microscopy of purified proteins clearly reveals randomly distributed and pitted structures. We conclude that the baculovirus-silkworm multigene expression system can be used as an efficient platform for express active human type II collagen and other complicated eukaryotic proteins.

  9. Exploring the unified class of Type II Supernovae with the Las Cumbres Observatory Global Telescope Network

    NASA Astrophysics Data System (ADS)

    Valenti, Stefano; Howell, Dale Andrew; Sand, David J.; Arcavi, Iair; Hosseinzadeh, Griffin; McCully, Curtis

    2015-01-01

    Traditionally Type II supernovae (SNe) have been separated into two distinct classes based on the shape of their light curves after peak: Type II plateau (IIP) and Type II linear (IIL) SNe. Recent works suggest that Type II SNe form a continuum of objects from a single progenitor system. Here we present data for a set of Type II SNe collected with the Las Cumbres Observatory Global Telescope (LCOGT) Network and observed simultaneously with UVOT-Swift. In the growing sample of Type II SNe, we search for clear evidence to distinguish the two classes. SNe IIL show a similar drop at the end of their short steep plateau that resemble the drop visible in SNe IIP. We show that also at early phase SNe IIP and IIL are similar both in the UV and in the optical. Our analysis is consistent with the scenario that SNe IIP and IIL come from similar progenitors but with SN IIL progenitors having been stripped of their hydrogen envelope before explosion. While SNe IIL are on average more luminous than SNe IIP, we show that they both produce a comparable amount of nickel.

  10. Seasonal plasticity of auditory saccular sensitivity in "sneaker" type II male plainfin midshipman fish, Porichthys notatus.

    PubMed

    Bhandiwad, Ashwin A; Whitchurch, Elizabeth A; Colleye, Orphal; Zeddies, David G; Sisneros, Joseph A

    2017-02-28

    Adult female and nesting (type I) male midshipman fish (Porichthys notatus) exhibit an adaptive form of auditory plasticity for the enhanced detection of social acoustic signals. Whether this adaptive plasticity also occurs in "sneaker" type II males is unknown. Here, we characterize auditory-evoked potentials recorded from hair cells in the saccule of reproductive and non-reproductive "sneaker" type II male midshipman to determine whether this sexual phenotype exhibits seasonal, reproductive state-dependent changes in auditory sensitivity and frequency response to behaviorally relevant auditory stimuli. Saccular potentials were recorded from the middle and caudal region of the saccule while sound was presented via an underwater speaker. Our results indicate saccular hair cells from reproductive type II males had thresholds based on measures of sound pressure and acceleration (re. 1 µPa and 1 ms(-2), respectively) that were ~8-21 dB lower than non-reproductive type II males across a broad range of frequencies, which include the dominant higher frequencies in type I male vocalizations. This increase in type II auditory sensitivity may potentially facilitate eavesdropping by sneaker males and their assessment of vocal type I males for the selection of cuckoldry sites during the breeding season.

  11. Suppression of SCARA5 by Snail1 is essential for EMT-associated cell migration of A549 cells

    PubMed Central

    Liu, J; Hu, G; Chen, D; Gong, A-Y; Soori, G S; Dobleman, T J; Chen, X-M

    2013-01-01

    Accumulating evidence indicates that epithelial-to-mesenchymal transition (EMT) might be a key event for cancer progression. The upregulation of Snail1, one of the most extensively studied EMT regulators, has been implicated in cancer metastasis, but the underlying mechanisms remain unclear. This study aims to identify that Snail1 targets regulating EMT-associated cancer cell migration. Human lung carcinoma A549 cells were treated with transforming growth factor beta 1 (TGF-β1), and EMT-associated phenotypic and functional alterations were monitored. TGF-β1 induced typical EMT-like morphological changes, ‘cadherin switching' and cell migration in A549 cells. TGF-β1 stimulation induced rapid and persistent upregulation of Snail1. Moreover, Snail1 upregulation was required for EMT-associated cell migration. Several metastasis suppressors with putative Snail1-binding sites in their promoters were dramatically repressed in A549 cells during TGF-β1-induced EMT. Gain- and loss-of Snail1 function experiments demonstrated that scavenger receptor class A member 5 (SCARA5) was negatively regulated by Snail1. Importantly, SCARA5 downregulation was essential for EMT-induced migration in A549 cells. The chromatin immunoprecipitation assay revealed that Snail1 could bind to the E-box elements in SCARA5 promoter, implying that SCARA5 is a direct Snail1 target modulating cancer cell mobility during EMT. In addition, we showed that DNA methyltransferase 1 was physically associated with Snail1 to silence SCARA5 expression with an unidentified DNA methylation-independent mechanism, suggesting the complexity of Snail1-mediated epigenetic regulation. Collectively, our data demonstrated that EMT-regulator Snail1 suppresses the expression of SCARA5 to promote cancer progression, highlighting the possibility to target Snail1 and SCARA5 for cancer treatment. PMID:24061576

  12. Suppression of SCARA5 by Snail1 is essential for EMT-associated cell migration of A549 cells.

    PubMed

    Liu, J; Hu, G; Chen, D; Gong, A-Y; Soori, G S; Dobleman, T J; Chen, X-M

    2013-09-23

    Accumulating evidence indicates that epithelial-to-mesenchymal transition (EMT) might be a key event for cancer progression. The upregulation of Snail1, one of the most extensively studied EMT regulators, has been implicated in cancer metastasis, but the underlying mechanisms remain unclear. This study aims to identify that Snail1 targets regulating EMT-associated cancer cell migration. Human lung carcinoma A549 cells were treated with transforming growth factor beta 1 (TGF-β1), and EMT-associated phenotypic and functional alterations were monitored. TGF-β1 induced typical EMT-like morphological changes, 'cadherin switching' and cell migration in A549 cells. TGF-β1 stimulation induced rapid and persistent upregulation of Snail1. Moreover, Snail1 upregulation was required for EMT-associated cell migration. Several metastasis suppressors with putative Snail1-binding sites in their promoters were dramatically repressed in A549 cells during TGF-β1-induced EMT. Gain- and loss-of Snail1 function experiments demonstrated that scavenger receptor class A member 5 (SCARA5) was negatively regulated by Snail1. Importantly, SCARA5 downregulation was essential for EMT-induced migration in A549 cells. The chromatin immunoprecipitation assay revealed that Snail1 could bind to the E-box elements in SCARA5 promoter, implying that SCARA5 is a direct Snail1 target modulating cancer cell mobility during EMT. In addition, we showed that DNA methyltransferase 1 was physically associated with Snail1 to silence SCARA5 expression with an unidentified DNA methylation-independent mechanism, suggesting the complexity of Snail1-mediated epigenetic regulation. Collectively, our data demonstrated that EMT-regulator Snail1 suppresses the expression of SCARA5 to promote cancer progression, highlighting the possibility to target Snail1 and SCARA5 for cancer treatment.

  13. Lysyl oxidase mediates hypoxia-induced radioresistance in non-small cell lung cancer A549 cells

    PubMed Central

    Gong, Chongwen; Gu, Runxia; Jin, Honglin; Sun, Yao; Li, Zhenyu; Wu, Gang

    2016-01-01

    Hypoxia-induced radioresistance has been well known as the main obstacle in cancer radiotherapy. Lysyl oxidase (LOX) was previously demonstrated to play an important role in hypoxia-induced biological behaviors, such as metastasis and angiogenesis, through hypoxia-inducible factor-1α (HIF-1α), which is an important contributing factor to radioresistance in tumor cells. However, how LOX plays a role in hypoxia-induced radioresistance has yet to be determined. Here, we found that LOX expression was in accordance with HIF-1α expression, and LOX expression at the mRNA and protein level, and enzymatic activity were remarkably upregulated in the hypoxic A549 cells, compared with normoxic A549 cells. Inhibition of LOX resulted in the reduction of the ability to repair double-stranded breaks (DSBs), promotion of apoptosis, relief of G2/M cycle arrest, and eventually reduction of hypoxia-induced radioresistance in the hypoxic A549 cells. This suggests that LOX may play an important role in hypoxia-induced radioresistance. Together, our results might suggest a novel potential therapeutic target in the management of non-small cell lung cancer (NSCLC). PMID:26515140

  14. 13-Methyl-palmatrubine induces apoptosis and cell cycle arrest in A549 cells in vitro and in vivo

    PubMed Central

    Chen, Jingxian; Lu, Xingang; Lu, Chenghua; Wang, Chunying; Xu, Haizhu; Xu, Xiaoli; Gou, Haixin; Zhu, Bing; Du, Wangchun

    2016-01-01

    Corydalis yanhusuo, a well-known herbaceous plant, is commonly used in the treatment of inflammation, injury and pain. One natural agent isolated from Corydalis yanhusuo, 13-methyl-palmatrubine, was found to have a cytotoxic effect on cancer cells as reported in published studies. In the present study, we synthesized a potential anti-lung tumor agent, 13-methyl-palmatrubine and analyzed its activity. 13-Methyl-palmatrubine exhibited a cytotoxic effect on a panel of cancer cell lines in a time- and concentration-dependent manner. Among all the tested cancer cell lines, lung cancer A549 cells were most sensitive to 13-methyl-palmatrubine treatment. Meanwhile 13-methyl-palmatrubine showed less cytotoxicity in human normal cells. Our investigation revealed that 13-methyl-palmatrubine induced apoptosis and cell cycle arrest in A549 cells in a dose-dependent manner. Furthermore, 13-methyl-palmatrubine treatment caused activation of P38 and JNK pathways and blocked the EGFR pathway. In conclusion, our findings demonstrated that 13-methyl-palmatrubine inhibited the growth of A549 cells mediated by blocking of the EGFR signaling pathway and activation of the MAPK signaling pathway and provides a better understanding of the molecular mechanisms of 13-methyl-palmatrubine. PMID:27633656

  15. Over expression of miR-200c suppresses invasion and restores methotrexate sensitivity in lung cancer A549 cells.

    PubMed

    Shan, Wulin; Zhang, Xiaolei; Li, Ming; Deng, Fang; Zhang, Jing

    2016-11-30

    MicroRNAs have become recognized as key players in the development of malignancy. MiR-200c can function as a tumor suppressor gene. However, the effect of miR-200c on methotrexate resistance remains unclear to date. This study aims to evaluate the function of miR-200c in lung cancer A549 cells. The data presented in our study demonstrated that the expression of miR-200c was down-regulated in methotrexate-resistant A549 cells. Over expression of miR-200c could significantly inhibit cell proliferation, induce G0/G1 cell cycle arrest and induce cell apoptosis. RT-PCR and Western blot assays showed that the expression of P53 and P21 were significantly increased with miR-200c overexpression. These results indicated that over expression of miR-200c might enhance the sensitivity of A549 cells to methotrexate through the P53/P21 pathway. Furthermore, miR-200c overexpression significantly inhibited cell migration and invasion with increasing the expression of E-cad and decreasing the expression of EZH2. In consequence, we provide a mechanism of acquired resistance to methotrexate that is caused by the loss of miR-200c in lung cancer cells. Along with this, our study demonstrates the complex network of microRNA mediated chemoresistance.

  16. Effects of green tea extract on lung cancer A549 cells: proteomic identification of proteins associated with cell migration.

    PubMed

    Lu, Qing-Yi; Yang, Yanan; Jin, Yu Sheng; Zhang, Zuo-Feng; Heber, David; Li, Frederick P; Dubinett, Steven M; Sondej, Melissa A; Loo, Joseph A; Rao, Jian Yu

    2009-02-01

    Green tea polyphenols exhibit multiple antitumor activities, and the mechanisms of action are not completely understood. Previously, we reported that green tea extract (GTE)-induced actin remolding is associated with increased cell adhesion and decreased motility in A549 lung cancer cells. To identify the cellular targets responsible for green tea-induced actin remodeling, we performed 2-DE LC-MS/MS of A549 cells before and after GTE exposure. We have identified 14 protein spots that changed in expression (> or =2-fold) after GTE treatment. These proteins are involved in calcium-binding, cytoskeleton and motility, metabolism, detoxification, or gene regulation. In particular we found upregulation of several genes that modulate actin remodeling and cell migration, including lamin A/C. Our data indicated that GTE-induced lamin A/C upregulation appears to be at the transcriptional level and the increased expression results in the decrease in cell motility, as confirmed by siRNA. The result of the study demonstrates that GTE alters the levels of many proteins involved in growth, motility and apoptosis of A549 cells and their identification may explain the multiple antitumor activities of GTE.

  17. A novel polysaccharide from Sargassum integerrimum induces apoptosis in A549 cells and prevents angiogensis in vitro and in vivo

    PubMed Central

    Liu, Ge; Kuang, Shan; Wu, Shimei; Jin, Weihua; Sun, Chaomin

    2016-01-01

    Many polysaccharides isolated from plants have exhibited promising antitumor activities. The aim of this study is to investigate the antitumor activity of the novel polysaccharide named SPS from Sargassum integerrimum, elucidate the underlying anticancer mechanism in a human lung cancer cell line A549, and evaluate its anti-angiogenic activity both in vitro and in vivo. The results show that SPS significantly reduces A549 cells viability in a dose- and time-dependent manner via MTT method. Flow cytometry analysis indicates that SPS could induce cell apoptosis, the loss of mitochondrial membrane potential (MMP), generation of reactive oxygen species (ROS) and G2/M phase cell cycle arrest of A549 cells. Up-regulation of the expressions of P53 and Bax, down-regulation of the expression of Bcl-2, and activation of cleaved caspase-3, caspase-9 and PARP are also detected by western blotting after the treatment of SPS. In addition, SPS inhibits the proliferation, migration and cord formation of human umbilical vein endothelial cells (HUVECs) in vitro, and prevents the vascular development of zebrafish embryos in vivo. Altogether, our data prove the anticancer and anti-angiogenesis properties of SPS, and provide further insights into the potential pharmacological application of SPS as antitumor and anti-angiogenic agent against lung cancer. PMID:27216943

  18. The effects of Davallic acid from Davallia divaricata Blume on apoptosis induction in A549 lung cancer cells.

    PubMed

    Cheng, An-Sheng; Chang, We-Chang; Cheng, Yu-Hsiang; Chen, Kai-Yu; Chen, Kai-Hsien; Chang, Tsu-Liang

    2012-11-01

    Traditional or folk medicinal herbs continue to be prescribed in the treatment of various diseases and conditions in many cultures. Recent scientific efforts have focused on the potential roles of extracts of traditional herbs as alternative and complementary medications for cancer treatment. In Taiwan, Davallia divaricata Blume has been traditionally employed in folk medicine for therapy of lung cancer, davallic acid being the major active compound of D. divaricata Blume. In this study, we investigated the inhibitory activity of davallic acid on the proliferation of A549 lung cancer cells. Davallic acid was extracted from D. divaricata Blume, and its effects on cell viability, cell cycle distribution, ROS level, and apoptotic protein expression in A549 cells were determined. Davallic acid significantly induced reactive oxygen species (ROS) generation as well as caspase-3, -8, and -9 activation, thereby repressing A549 cell growth and elevating apoptotic activity. Since lung cancer has a high incidence of recurrence, these results indicate that davallic acid may have the potential to be a natural anti-lung cancer compound, and may provide a basis for further study of its use in combating cancer.

  19. Silver nanoparticles induce apoptosis and G2/M arrest via PKCζ-dependent signaling in A549 lung cells.

    PubMed

    Lee, Young Sook; Kim, Dong Woon; Lee, Young Ho; Oh, Jung Hwa; Yoon, Seokjoo; Choi, Mi Sun; Lee, Sung Kyu; Kim, Ji Won; Lee, Kyuhong; Song, Chang-Woo

    2011-12-01

    The use of silver nanoparticles is one of the fastest growing product categories in the nanotechnology industry, with a focus on antimicrobial activity. However, thus far, toxicity data for silver nanoparticles are limited. In this study, we investigated the cytotoxic effects of silver nanoparticles (Ag NPs) and the pathway by which they affect A549 lung epithelial cells. The effects of Ag NPs on cell survival, cell cycle progression, and mRNA and protein alterations of selected cell cycle- and apoptosis-related genes were studied using formazan dye and LDH release assays, flow cytometric analysis, semi-quantitative RT-PCR, and Western blot analysis. Ag NPs reduced cell viability, increased LDH release, and modulated cell cycle distribution through the accumulation of cells at G2/M and sub-G1 phases (cell death), with a concurrent decrease in cells at G1. Ag NP treatment increased Bax and Bid mRNA levels and downregulated Bcl-2 and Bcl-w mRNAs in a dose-dependent manner. Furthermore, Ag NPs altered the mRNA levels of protein kinase C (PKC) family members. In particular, ectopic overexpression of PKCζ led to the enhancement of cellular proliferation and reduced sensitivity to Ag NPs in A549 cells. Together, these results suggest that Ag NPs induce strong toxicity and G2/M cell cycle arrest by a mechanism involving PKCζ downregulation in A549 cells.

  20. Effect of silencing SATB1 on proliferation, invasion and apoptosis of A549 human lung adenocarcinoma cells

    PubMed Central

    Huang, Bo; Zhou, Hongli; Wang, Siwang; Lang, Xian Ping; Wang, Xiaodong

    2016-01-01

    The present study aimed to explore the clinical characteristics of special adenine-thymine-rich sequence-binding protein 1 (SATB1) in lung adenocarcinoma and its role in the proliferation, invasion, migration and apoptosis of the lung adenocarcinoma cell line A549. The expression of SATB1 was first studied in tumor tissues of lung adenocarcinoma and adjacent non-tumor tissues. The siRNA green fluorescent protein expression vector of SATB1 was constructed and transfected into the lung adenocarcinoma cell line A549, then a fluorescence microscope was used to study the transfection efficiency. Western blot analysis was adopted to measure the silencing efficiency. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Transwell and scratch assays were used to study cell proliferation, invasion and migration activity, and the apoptosis rate was tested by flow cytometry. SATB1 expression was low in the adjacent non-tumor tissues but high in lung adenocarcinoma tissues, and it was reversely proportional to the differentiation degree. Following transfection with SATB1-siRNA, the expression of SATB1 in A549 cells was blocked (P<0.01). In addition, the proliferation, invasion and migration abilities of cells decreased significantly while the apoptosis rate increased significantly (P<0.01). In conclusion SATB1 is closely associated with the pathogenesis and development of lung adenocarcinoma. PMID:27895736

  1. Induction of apoptosis in human lung carcinoma A549 epithelial cells with an ethanol extract of Tremella mesenterica.

    PubMed

    Chen, Nan-Yin; Lai, Hsi-Huai; Hsu, Tai-Hao; Lin, Fang-Yi; Chen, Jian-Zhi; Lo, Hui-Chen

    2008-05-01

    Tremella mesenterica (TM) is a common food and folk medicine widely used in several Asian countries as a tonic for the lungs. In the present study, we compared the effects of extracellular polysaccharides (EPS), intracellular polysaccharides (IPS), and ethanol extract (EE) of Tremella mesenterica on the induction of apoptosis into human lung carcinoma A549 epithelial cells. The EE, but not the EPS or the IPS, almost completely inhibited the growth of A549 cells. The results of Annexin V-FITC/PI staining and flow cytometric analysis indicated that the percentage of Annexin V(+)/PI(-) cells in EE-treated cells increased to 32.8%. The results of further investigation showed a disruption of mitochondrial transmembrane potential (DeltaPsi(m)), the production of reactive oxygen species (ROS), and the activation of caspase-3 protein in EE-treated cells. These findings suggest that EE can decrease cell viability and induce apoptosis in A549 cell lines by activating a mitochondrial pathway.

  2. Todani choledochal cyst type II: case report and review.

    PubMed

    Farías Molina, Solange Marcela; Castillo Machado, Rafael Lisandro; Sanhueza Palma, Natalia Carolina; Calzadilla Riveras, Jeannette Alejandra

    2016-10-20

    Choledochal cyst is a rare pathological condition, which represents 1% of benign diseases of the biliary tract. It is seen with significant frequency in childhood, with a higher prevalence in females, and a greater diagnostic incidence in Asia. Diagnosis is primarily based on clinical suspicion. Its symptoms are variable, and its treatment, depending on the type, is surgical.

  3. Personal Educational Tools (PETs) for Type II Learning

    ERIC Educational Resources Information Center

    Christensen, Rhonda; Overall, Theresa; Knezek, Gerald

    2006-01-01

    This article introduces the concept of Personal Educational Tools (PETs) and places these tools within the context of existing rationales for using technology for teaching, learning, and instruction. An identification of the distinguishing characteristics of these devices is followed by the conjecture that these types of classifying…

  4. Human Blood Typing: A Forensic Science Approach: Part II. Experiments.

    ERIC Educational Resources Information Center

    Kobilinsky, Lawrence; Sheehan, Francis X.

    1988-01-01

    Describes several experiments that explore the methodology available to the forensic serologist for typing a human bloodstain in the ABH grouping system. Presents ABO blood group of wet blood, Lattes Crust test procedure, and the absorption-elution procedure. Uses outdated blood; equipment requirements are minimal. (ML)

  5. Differential effect of cholesterol on type I and II feline coronavirus infection.

    PubMed

    Takano, Tomomi; Satomi, Yui; Oyama, Yuu; Doki, Tomoyoshi; Hohdatsu, Tsutomu

    2016-01-01

    Feline infectious peritonitis (FIP) is a fatal disease of domestic and wild felidae that is caused by feline coronavirus (FCoV). FCoV has been classified into types I and II. Since type I FCoV infection is dominant in the field, it is necessary to develop antiviral agents and vaccines against type I FCoV infection. However, few studies have been conducted on type I FCoV. Here, we compare the effects of cholesterol on types I and II FCoV infections. When cells were treated methyl-β-cyclodextrin (MβCD) and inoculated with type I FCoV, the infection rate decreased significantly, and the addition of exogenous cholesterol to MβCD-treated cells resulted in the recovery of the infectivity of type I FCoV. Furthermore, exogenous cholesterol increased the infectivity of type I FCoV. In contrast, the addition of MβCD and exogenous cholesterol had little effect on the efficiency of type II FCoV infection. These results strongly suggest that the dependence of infection by types I and II FCoV on cholesterol differs.

  6. Water-soluble undenatured type II collagen ameliorates collagen-induced arthritis in mice.

    PubMed

    Yoshinari, Orie; Shiojima, Yoshiaki; Moriyama, Hiroyoshi; Shinozaki, Junichi; Nakane, Takahisa; Masuda, Kazuo; Bagchi, Manashi

    2013-11-01

    Earlier studies have reported the efficacy of type II collagen (C II) in treating rheumatoid arthritis (RA). However, a few studies have investigated the ability of the antigenic collagen to induce oral tolerance, which is defined as active nonresponse to an orally administered antigen. We hypothesized that water-soluble undenatured C II had a similar effect as C II in RA. The present study was designed to examine the oral administration of a novel, water-soluble, undenatured C II (commercially known as NEXT-II) on collagen-induced arthritis (CIA) in mice. In addition, the underlying mechanism of NEXT-II was also identified. After a booster dose (collagen-Freund's complete adjuvant), mice were assigned to control CIA group, or NEXT-II treatment group, to which saline and NEXT-II were administered, respectively. The arthritis index in the NEXT-II group was significantly lower compared with the CIA group. Serum IL-6 levels in the NEXT-II group were significantly lower compared with the CIA group, while serum IL-2 level was higher. Furthermore, oral administration of NEXT-II enhanced the proportion of CD4+CD25+T (Treg) cells, and gene expressions of stimulated dendritic cells induced markers for regulatory T cells such as forkhead box p3 (Foxp3), transforming growth factor (TGF)-β1, and CD25. These results demonstrated that orally administered water-soluble undenatured C II (NEXT-II) is highly efficacious in the suppression of CIA by inducing CD4+CD25+ Treg cells.

  7. Self-consistent calculations of optical properties of type I and type II quantum heterostructures

    NASA Astrophysics Data System (ADS)

    Shuvayev, Vladimir A.

    In this Thesis the self-consistent computational methods are applied to the study of the optical properties of semiconductor nanostructures with one- and two-dimensional quantum confinements. At first, the self-consistent Schrodinger-Poisson system of equations is applied to the cylindrical core-shell structure with type II band alignment without direct Coulomb interaction between carriers. The electron and hole states and confining potential are obtained from a numerical solution of this system. The photoluminescence kinetics is theoretically analyzed, with the nanostructure size dispersion taken into account. The results are applied to the radiative recombination in the system of ZnTe/ZnSe stacked quantum dots. A good agreement with both continuous wave and time-resolved experimental observations is found. It is shown that size distribution results in the photoluminescence decay that has essentially non-exponential behavior even at the tail of the decay where the carrier lifetime is almost the same due to slowly changing overlap of the electron and hole wavefunctions. Also, a model situation applicable to colloidal core-shell nanowires is investigated and discussed. With respect to the excitons in type I quantum wells, a new computationally efficient and flexible approach of calculating the characteristics of excitons, based on a self-consistent variational treatment of the electron-hole Coulomb interaction, is developed. In this approach, a system of self-consistent equations describing the motion of an electron-hole pair is derived. The motion in the growth direction of the quantum well is separated from the in-plane motion, but each of them occurs in modified potentials found self-consistently. This approach is applied to a shallow quantum well with the delta-potential profile, for which analytical expressions for the exciton binding energy and the ground state eigenfunctions are obtained, and to the quantum well with the square potential profile with several

  8. Angiotensin II-induced angiotensin II type I receptor lysosomal degradation studied by fluorescence lifetime imaging microscopy

    NASA Astrophysics Data System (ADS)

    Li, Hewang; Yu, Peiying; Felder, Robin A.; Periasamy, Ammasi; Jose, Pedro A.

    2009-02-01

    Upon activation, the angiotensin (Ang) II type 1 receptor (AT1Rs) rapidly undergoes endocytosis. After a series of intracellular processes, the internalized AT1Rs recycle back to the plasma membrane or are trafficked to proteasomes or lysosomes for degradation. We recently reported that AT1Rs degrades in proteasomes upon stimulation of the D5 dopamine receptor (D5R) in human renal proximal tubule and HEK-293 cells. This is in contrast to the degradation of AT1R in lysosomes upon binding Ang II. However, the dynamic regulation of the AT1Rs in lysosomes is not well understood. Here we investigated the AT1Rs lysosomal degradation using FRET-FLIM in HEK 293 cells heterologously expressing the human AT1R tagged with EGFP as the donor fluorophore. Compared to its basal state, the lifetime of AT1Rs decreased after a 5-minute treatment with Ang II treatment and colocalized with Rab5 but not Rab7 and LAMP1. With longer Ang II treatment (30 min), the AT1Rs lifetime decreased and co-localized with Rab5, as well as Rab7 and LAMP1. The FLIM data are corroborated with morphological and biochemical co-immunoprecipitation studies. These data demonstrate that Ang II induces the internalization of AT1Rs into early sorting endosomes prior to trafficking to late endosomes and subsequent degradation in lysosomes.

  9. Curcumin promotes apoptosis in A549/DDP multidrug-resistant human lung adenocarcinoma cells through an miRNA signaling pathway

    SciTech Connect

    Zhang, Jian; Zhang, Tao; Ti, Xinyu; Shi, Jieran; Wu, Changgui; Ren, Xinling; Yin, Hong

    2010-08-13

    Research highlights: {yields} Curcumin had anti-cancer effects on A549/DDP multidrug-resistant human lung adenocarcinoma cells {yields} Curcumin promotes apoptosis in A549/DDP cells through a miRNA signaling pathway {yields} Curcumin induces A549/DDP cell apoptosis by downregulating miR-186* {yields} miR-186* may serve as a potential gene therapy target for refractory lung cancer that is sensitive to curcumin -- Abstract: Curcumin extracted from the rhizomes of Curcuma longa L. has been shown to have inhibitory effects on cancers through its anti-proliferative and pro-apoptotic activities. Emerging evidence demonstrates that curcumin can overcome drug resistance to classical chemotherapies. Thus, the mechanisms underlying the anti-tumor activities of curcumin require further study. In our study, we first demonstrated that curcumin had anti-cancer effects on A549/DDP multidrug-resistant human lung adenocarcinoma cells. Further studies showed that curcumin altered miRNA expression; in particular, significantly downregulated the expression of miR-186* in A549/DDP. In addition, transfection of cells with a miR-186* inhibitor promoted A549/DDP apoptosis, and overexpression of miR-186* significantly inhibited curcumin-induced apoptosis in A549/DDP cells. These observations suggest that miR-186* may serve as a potential gene therapy target for refractory lung cancer that is sensitive to curcumin.

  10. Clinical and immunohistochemical characteristics of type II and type I focal cortical dysplasia

    PubMed Central

    Yao, Kun; Duan, Zejun; Zhou, Jian; Li, Lin; Zhai, Feng; Dong, Yanting; Wang, Xiaoyan; Ma, Zhong; Bian, Yu; Qi, Xueling; Li, Liang

    2016-01-01

    Focal cortical dysplasia (FCD) II and I are major causes for drug-resistant epilepsy. In order to gain insight into the possible correlations between FCD II and FCD I, different clinical characteristics and immunohistochemical expression characteristics in FCD I and II were analyzed. The median age of onset and duration of epilepsy in FCD I and FCD II patients were 2.1 years and 5.3 years vs 2.4 years and 4.5 years. Therefore, the median age of onset and duration of epilepsy were similar in the two groups. Pathological lesions were predominantly located in frontal lobe in FCD II and temporal in FCD I. Significantly more signal abnormalities in FLAIR and T2 images were demonstrated in FCD II than FCD I. The rate of satisfied seizure outcome was relative higher in FCDII patients (95.12%) than that in FCDI group (84.6%). Furthermore, we detected expressions of progenitor cell proteins and the mammalian target of rapamycin (mTOR) cascade activation protein in FCDs. Results showed that sex-determiningregion Y-box 2(SOX2), Kruppel-likefactor 4 (KLF4) and phospho-S6 ribosomal proteins (ser240/244 or ser235/236) were expressed in FCDII group but not in FCD I. Overall, this study unveils FCD I and II exhibit distinct clinical and immunohistochemical expression characteristics, revealing different pathogenic mechanisms. PMID:27811355

  11. Type II NKT Cells in Inflammation, Autoimmunity, Microbial Immunity, and Cancer

    PubMed Central

    Marrero, Idania; Ware, Randle; Kumar, Vipin

    2015-01-01

    Natural killer T cells (NKT) recognize self and microbial lipid antigens presented by non-polymorphic CD1d molecules. Two major NKT cell subsets, type I and II, express different types of antigen receptors (TCR) with distinct mode of CD1d/lipid recognition. Though type II NKT cells are less frequent in mice and difficult to study, they are predominant in human. One of the major subsets of type II NKT cells reactive to the self-glycolipid sulfatide is the best characterized and has been shown to induce a dominant immune regulatory mechanism that controls inflammation in autoimmunity and in anti-cancer immunity. Recently, type II NKT cells reactive to other self-glycolipids and phospholipids have been identified suggesting both promiscuous and specific TCR recognition in microbial immunity as well. Since the CD1d pathway is highly conserved, a detailed understanding of the biology and function of type II NKT cells as well as their interplay with type I NKT cells or other innate and adaptive T cells will have major implications for potential novel interventions in inflammatory and autoimmune diseases, microbial immunity, and cancer. PMID:26136748

  12. Characterization of the Type III restriction endonuclease PstII from Providencia stuartii.

    PubMed

    Sears, Alice; Peakman, Luke J; Wilson, Geoffrey G; Szczelkun, Mark D

    2005-01-01

    A new Type III restriction endonuclease designated PstII has been purified from Providencia stuartii. PstII recognizes the hexanucleotide sequence 5'-CTGATG(N)(25-26/27-28)-3'. Endonuclease activity requires a substrate with two copies of the recognition site in head-to-head repeat and is dependent on a low level of ATP hydrolysis ( approximately 40 ATP/site/min). Cleavage occurs at just one of the two sites and results in a staggered cut 25-26 nt downstream of the top strand sequence to generate a two base 5'-protruding end. Methylation of the site occurs on one strand only at the first adenine of 5'-CATCAG-3'. Therefore, PstII has characteristic Type III restriction enzyme activity as exemplified by EcoPI or EcoP15I. Moreover, sequence asymmetry of the PstII recognition site in the T7 genome acts as an historical imprint of Type III restriction activity in vivo. In contrast to other Type I and III enzymes, PstII has a more relaxed nucleotide specificity and can cut DNA with GTP and CTP (but not UTP). We also demonstrate that PstII and EcoP15I cannot interact and cleave a DNA substrate suggesting that Type III enzymes must make specific protein-protein contacts to activate endonuclease activity.

  13. Prevalence and risk factors of type II endoleaks after endovascular aneurysm repair: A meta-analysis

    PubMed Central

    Zhao, Jichun; Ma, Yukui; Huang, Bin; Yuan, Ding; Yang, Yi; Zeng, Guojun; Xiong, Fei

    2017-01-01

    Objectives This systematic review and meta-analysis aims to determine the current evidence on risk factors for type II endoleaks after endovascular aneurysm repair (EVAR). Materials and methods A systematic literature search was carried out for studies that evaluated the association of demographic, co-morbidity, and other patient-determined factors with the onset of type II endoleaks. Pooled prevalence of type II endoleaks after EVAR was updated. Results Among the 504 studies screened, 45 studies with a total of 36,588 participants were included in this review. The pooled prevalence of type II endoleaks after EVAR was 22% [95% confidence interval (CI), 19%–25%]. The main factors consistently associated with type II endoleaks included age [pooled odds ratio (OR), 0.37; 95% CI, 0.31–0.43; P<0.001], smoking (pooled OR, 0.71; 95% CI, 0.55–0.92; P<0.001), patent inferior mesenteric artery (pooled OR, 1.98; 95% CI, 1.06–3.71; P = 0.012), maximum aneurysm diameter (pooled OR, 0.23; 95% CI, 0.17–0.30; P<0.001), and number of patent lumbar arteries (pooled OR, 3.07; 95% CI, 2.81–3.33; P<0.001). Sex, diabetes, hypertension, anticoagulants, antiplatelet, hyperlipidemia, chronic renal insufficiency, types of graft material, and chronic obstructive pulmonary diseases (COPD) did not show any association with the onset of type II endoleaks. Conclusions Clinicians can use the identified risk factors to detect and manage patients at risk of developing type II endoleaks after EVAR. However, further studies are needed to analyze a number of potential risk factors. PMID:28182753

  14. Type-II second-harmonic-generation properties of YCOB and GdCOB single crystals.

    PubMed

    Liu, Yanqing; Qi, Hongwei; Lu, Qingming; Yu, Fapeng; Wang, Zhengping; Xu, Xinguang; Zhao, Xian

    2015-02-09

    As excellent nonlinear optical (NLO) crystals, YCa(4)O(BO(3))(3) (YCOB) and GdCa(4)O(BO(3))(3) (GdCOB) have been paid much attention since their first appearance in 1990's. From that time to now, almost all of related researches and applications have focused on their type-I phase-matching (PM) configurations which possess large effective NLO coefficient (d(eff)). In this paper, type-II second-harmonic-generation (SHG) properties of these two crystals are reported, including PM curve, d(eff), angular acceptance and walk-off angle. Both of the type-II SHG experiments for 1064 and 1320 nm have indicated that the optimum directions which have maximum d(eff) locate in the second octant, i.e. (90° < θ< 180°, 0° < ϕ < 90°). For a (112°, 81.3°)-cut, 24 mm long YCOB crystal, the largest type-II SHG conversion efficiency of a 1064 nm Nd:YAG pico-second laser is 55%, which reaches the same level of the optimum type-I sample. To our knowledge this is the first time that type-II SHG performance of YCOB and GdCOB crystals is investigated intensively. Our research has shown that the smaller d(eff) of type-II PM can be compensated by its larger angular acceptance and less beam walk-off. The same level SHG conversion efficiency implies for such type crystals the type-II components have the potential to replace type-I ones and obtain important NLO applications in the future.

  15. Type-II Weyl points in three-dimensional cold-atom optical lattices

    NASA Astrophysics Data System (ADS)

    Xu, Yong; Duan, L.-M.

    2016-11-01

    Topological Lifshitz phase transition characterizes an abrupt change of the topology of the Fermi surface through a continuous deformation of parameters. Recently, Lifshitz transition has been predicted to separate two types of Weyl points: type-I and type-II (or called structured Weyl points), which has attracted considerable attention in various fields. Although recent experimental investigation has seen a rapid progress on type-II Weyl points, it still remains a significant challenge to observe their characteristic Lifshitz transition. Here, we propose a scheme to realize both type-I and type-II Weyl points in three-dimensional ultracold atomic gases by introducing an experimentally feasible configuration based on current spin-orbit coupling technology. In the resultant Hamiltonian, we find three degenerate points: two Weyl points carrying a Chern number -1 and a fourfold degenerate point carrying a Chern number 2. Remarkably, by continuous tuning of a convenient experimental knob, all these degenerate points can transition from type-I to type-II, thereby providing an ideal platform to study different types of Weyl points and directly probe their Lifshitz phase transition.

  16. Comparison of the relative toxicities of Shiga-like toxins type I and type II for mice.

    PubMed Central

    Tesh, V L; Burris, J A; Owens, J W; Gordon, V M; Wadolkowski, E A; O'Brien, A D; Samuel, J E

    1993-01-01

    In earlier studies using a streptomycin-treated mouse model of infection caused by enterohemorrhagic Escherichia coli (EHEC), animals fed Shiga-like toxin type II (SLT-II)-producing strains developed acute renal cortical necrosis and died, while mice fed Shiga-like toxin type I (SLT-I)-producing clones did not die (E. A. Wadolkowski, L. M. Sung, J. A. Burris, J. E. Samuel, and A. D. O'Brien, Infect. Immun. 58:3959-3965, 1990). To examine the bases for the differences we noted between the two toxins in the murine infection model, we injected mice with purified toxins and carried out histopathological examinations. Despite the genetic and structural similarities between the two toxins, SLT-II had a 50% lethal dose (LD50) which was approximately 400 times lower than that of SLT-I when injected intravenously or intraperitoneally into mice. Histopathologic examination of toxin-injected mice revealed that detectable damage was limited to renal cortical tubule epithelial cells. Passive administration of anti-SLT-II antibodies protected mice from SLT-II-mediated kidney damage and death. Immunofluorescence staining of normal murine kidney sections incubated with purified SLT-I or SLT-II demonstrated that both toxins bound to cortical tubule and medullary duct epithelial cells. Compared with SLT-I, SLT-II was more heat and pH stable, suggesting that SLT-II is a relatively more stable macromolecule. Although both toxins bound to globotriaosylceramide, SLT-I bound with a higher affinity in a solid-phase binding assay. Differences in enzymatic activity between the two toxins were not detected. These data suggest that structural/functional differences between the two toxins, possibly involving holotoxin stability and/or receptor affinity, may contribute to the differential LD50s in mice. Images PMID:8335369

  17. Moringa oleifera Gold Nanoparticles Modulate Oncogenes, Tumor Suppressor Genes, and Caspase-9 Splice Variants in A549 Cells.

    PubMed

    Tiloke, Charlette; Phulukdaree, Alisa; Anand, Krishnan; Gengan, Robert M; Chuturgoon, Anil A

    2016-10-01

    Gold nanoparticles (AuNP's) facilitate cancer cell recognition and can be manufactured by green synthesis using nutrient rich medicinal plants such as Moringa oleifera (MO). Targeting dysregulated oncogenes and tumor suppressor genes is crucial for cancer therapeutics. We investigated the antiproliferative effects of AuNP synthesized from MO aqueous leaf extracts (MLAuNP ) in A549 lung and SNO oesophageal cancer cells. A one-pot green synthesis technique was used to synthesise MLAuNP . A549, SNO cancer cells and normal peripheral blood mononuclear cells (PBMCs) were exposed to MLAuNP and CAuNP to evaluate cytotoxicity (MTT assay); apoptosis was measured by phosphatidylserine (PS) externalization, mitochondrial depolarization (ΔΨm) (flow cytometry), caspase-3/7, -9 activity, and ATP levels (luminometry). The mRNA expression of c-myc, p53, Skp2, Fbw7α, and caspase-9 splice variants was determined using qPCR, while relative protein expression of c-myc, p53, SRp30a, Bax, Bcl-2, Smac/DIABLO, Hsp70, and PARP-1 were determined by Western blotting. MLAuNP and CAuNP were not cytotoxic to PBMCs, whilst its pro-apoptotic properties were confirmed in A549 and SNO cells. MLAuNP significantly increased caspase activity in SNO cells while MLAuNP significantly increased PS externalization, ΔΨm, caspase-9, caspase-3/7 activities, and decreased ATP levels in A549 cells. Also, p53 mRNA and protein levels, SRp30a (P = 0.428), Bax, Smac/DIABLO and PARP-1 24 kDa fragment levels were significantly increased. Conversely, MLAuNP significantly decreased Bcl-2, Hsp70, Skp2, Fbw7α, c-myc mRNA, and protein levels and activated alternate splicing with caspase-9a splice variant being significantly increased. MLAuNP possesses antiproliferative properties and induced apoptosis in A549 cells by activating alternate splicing of caspase-9. J. Cell. Biochem. 117: 2302-2314, 2016. © 2016 Wiley Periodicals, Inc.

  18. Optogenetic Stimulation Shifts the Excitability of Cerebral Cortex from Type I to Type II: Oscillation Onset and Wave Propagation

    PubMed Central

    Rule, Michael; Truccolo, Wilson; Ermentrout, Bard

    2017-01-01

    Constant optogenetic stimulation targeting both pyramidal cells and inhibitory interneurons has recently been shown to elicit propagating waves of gamma-band (40–80 Hz) oscillations in the local field potential of non-human primate motor cortex. The oscillations emerge with non-zero frequency and small amplitude—the hallmark of a type II excitable medium—yet they also propagate far beyond the stimulation site in the manner of a type I excitable medium. How can neural tissue exhibit both type I and type II excitability? We investigated the apparent contradiction by modeling the cortex as a Wilson-Cowan neural field in which optogenetic stimulation was represented by an external current source. In the absence of any external current, the model operated as a type I excitable medium that supported propagating waves of gamma oscillations similar to those observed in vivo. Applying an external current to the population of inhibitory neurons transformed the model into a type II excitable medium. The findings suggest that cortical tissue normally operates as a type I excitable medium but it is locally transformed into a type II medium by optogenetic stimulation which predominantly targets inhibitory neurons. The proposed mechanism accounts for the graded emergence of gamma oscillations at the stimulation site while retaining propagating waves of gamma oscillations in the non-stimulated tissue. It also predicts that gamma waves can be emitted on every second cycle of a 100 Hz oscillation. That prediction was subsequently confirmed by re-analysis of the neurophysiological data. The model thus offers a theoretical account of how optogenetic stimulation alters the excitability of cortical neural fields. PMID:28118355

  19. Repression of host RNA polymerase II transcription by herpes simplex virus type 1.

    PubMed Central

    Spencer, C A; Dahmus, M E; Rice, S A

    1997-01-01

    Lytic infection of mammalian cells with herpes simplex virus type 1 (HSV-1) results in rapid repression of host gene expression and selective activation of the viral genome. This transformation in gene expression is thought to involve repression of host transcription and diversion of the host RNA polymerase (RNAP II) transcription machinery to the viral genome. However, the extent of virus-induced host transcription repression and the mechanisms responsible for these major shifts in transcription specificities have not been examined. To determine how HSV-1 accomplishes repression of host RNAP II transcription, we assayed transcription patterns on several cellular genes in cells infected with mutant and wild-type HSV-1. Our results suggest that HSV-1 represses RNAP II transcription on most cellular genes. However, each cellular gene we examined responds differently to the transcription repressive effects of virus infection, both quantitatively and with respect to the involvement of viral gene products. Virus-induced shutoff of host RNAP II transcription requires expression of multiple immediate-early genes. In contrast, expression of delayed-early and late genes and viral DNA replication appear to contribute little to repression of host cell RNAP II transcription. Modification of RNAP II to the intermediately phosphorylated (II(I)) form appears unlinked to virus-induced repression of host cell transcription. However, full repression of host transcription is correlated with depletion of the hyperphosphorylated (IIO) form of RNAP II. PMID:9032335

  20. Angiotensin II Type 1 Receptor-Dependent GLP-1 and PYY Secretion in Mice and Humans

    PubMed Central

    Pais, Ramona; Rievaj, Juraj; Larraufie, Pierre

    2016-01-01

    Angiotensin II (Ang II) is the key hormone mediator of the renin angiotensin system, which regulates blood pressure and fluid and electrolyte balance in the body. Here we report that in the colonic epithelium, the Ang II type 1 receptor is highly and exclusively expressed in enteroendocrine L cells, which produce the gut hormones glucagon-like peptide-1 and peptide YY (PYY). Ang II stimulated glucagon-like peptide-1 and PYY release from primary cultures of mouse and human colon, which was antagonized by the specific Ang II type 1 receptor blocker candesartan. Ang II raised intracellular calcium levels in L cells in primary cultures, recorded by live-cell imaging of L cells specifically expressing the fluorescent calcium sensor GCaMP3. In Ussing chamber recordings, Ang II reduced short circuit currents in mouse distal colon preparations, which was antagonized by candesartan or a specific neuropeptide Y1 receptor inhibitor but insensitive to amiloride. We conclude that Ang II stimulates PYY secretion, in turn inhibiting epithelial anion fluxes, thereby reducing net fluid secretion into the colonic lumen. Our findings highlight an important role of colonic L cells in whole-body fluid homeostasis by controlling water loss through the intestine. PMID:27447725

  1. Prediction of Type II Radio Bursts Associated with Large CME Events

    NASA Astrophysics Data System (ADS)

    Cairns, Iver; Schmidt, Joachim

    Type II radio bursts are associated with shocks in the corona and solar wind, either driven by CMEs or else by blast waves. Recently we coupled the advanced 3D MHD BATS-R-US code of Toth, Gombosi, and colleagues with our kinetic ``bolt-on'' theory for type II emission. Initialising the simulation code with event specific coronal and CME data, the combined code can be used to predict the dynamic spectrum of type II emission for a specific radio event. We demonstrate very good agreement with Wind spacecraft observations for three typ