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Sample records for satheesh sk moorthy

  1. COVERING RACE AND RELIGION: THE MOORTHY AND NYONYA TAHIR CASES IN FOUR MALAYSIAN NEWSPAPERS

    Directory of Open Access Journals (Sweden)

    Ngu Teck Hua

    2006-01-01

    Full Text Available Reporting on issues like race and religion in a multi-racial and multi-religious society is not an easy media responsibility. In a country like Malaysia where racial and religious sensitivities abound, the media have to constantly tread on precarious ground, balancing between what to write and how to write it. Much of the concern over the reporting of sensitive issues stems from the belief that a wrong move may have dire consequences, as seen in the recent controversy and furore over the Prophet Muhammad caricature published in the Danish newspaper, Jyllands-Posten.This study analyses two recent racial/religious issues – M. Moorthy and Nyonya Tahir cases – as reported in the New Straits Times (NST, Utusan Malaysia (UM, Malaysia Nanban (MN and Sin Chew Daily (SCD. The former case caused a stir when there was a tussle between Moorthy’s Indian/Hindu family and the Federal Territory Islamic Affairs Council which argued that Moorthy had converted to Islam when he was alive without the family’s knowledge. The latter was a case of a Malay/Muslim woman who, while alive, had denounced Islam and lived as a Chinese practising Buddhism.This study analyses how the two race and religion-related controversial issues were treated in the various language newspapers in Malaysia. A preliminary finding showed that, true to the communal nature of the Malaysian press, there was an apparent slant in how the ethnic press covered these two issues. For instance, in terms of prominence given to the stories, SCD, while downplaying the Moorthy story, dedicated more space to the Nyonya Tahir case. Similarly, MN highlighted the Moorthy story and downplayed the Nyonya Tahir case. The different newspapers were also seen to ''favour'' the subject they covered according to the ethnicity.

  2. Skífan

    OpenAIRE

    Elín Ólafsdóttir

    2011-01-01

    Skífan er eina fyrirtækið hér á landi sem sérhæfir sig í sölu á tónlist, mynddiskum, tölvuleikjum og leikjatölvum. Sú atvinnugrein sem Skífan tilheyrir hefur fengið að finna töluvert fyrir þróun internetsins þar sem mögulegt er að hlaða þessu efni niður hvort sem er með löglegum eða ólöglegum hætti. Markmið verkefnisins var að skoða hver áhrif sviðsmynda væru á rekstrarlíkan Skífunnar. Höfundur fór í gegnum atvinnuvega- og samkeppnisgreiningu með aðstoð eiganda og rekstrarstjóra Skífunnar...

  3. Sk@m i cyberspace

    DEFF Research Database (Denmark)

    Holm, Claus

    2009-01-01

    Terapi på nettet er en ny mulighed. Men hjælper den klienter med at tale om skambelagte temaer, eller risikerer den at skabe en uansvarlig og skamløs terapisituation? Den norske forfatter, psykiater og psykoterapeut Finn Skårderud vurderer fordele og ulemper ved terapi i cyberspace....

  4. Measurements of the branching fractions for $D^+\\to K^0_SK^0_SK^+$, $K^0_SK^0_S\\pi^+$ and $D^0\\to K^0_SK^0_S$, $K^0_SK^0_SK^0_S$

    CERN Document Server

    Ablikim, M; Ahmed, S; Ai, X C; Albayrak, O; Albrecht, M; Ambrose, D J; Amoroso, A; An, F F; An, Q; Bai, J Z; Ferroli, R Baldini; Ban, Y; Bennett, D W; Bennett, J V; Berger, N; Bertani, M; Bettoni, D; Bian, J M; Bianchi, F; Boger, E; Boyko, I; Briere, R A; Cai, H; Cai, X; Cakir, O; Calcaterra, A; Cao, G F; Cetin, S A; Chai, J; Chang, J F; Chelkov, G; Chen, G; Chen, H S; Chen, J C; Chen, M L; Chen, S; Chen, S J; Chen, X; Chen, X R; Chen, Y B; Cheng, H P; Chu, X K; Cibinetto, G; Dai, H L; Dai, J P; Dbeyssi, A; Dedovich, D; Deng, Z Y; Denig, A; Denysenko, I; Destefanis, M; DeMori, F; Ding, Y; Dong, C; Dong, J; Dong, L Y; Dong, M Y; Dou, Z L; Du, S X; Duan, P F; Fan, J Z; Fang, J; Fang, S S; Fang, X; Fang, Y; Farinelli, R; Fava, L; Fedorov, O; Feldbauer, F; Felici, G; Feng, C Q; Fioravanti, E; Fritsch, M; Fu, C D; Gao, Q; Gao, X L; Gao, Y; Gao, Z; Garzia, I; Goetzen, K; Gong, L; Gong, W X; Gradl, W; Greco, M; Gu, M H; Gu, Y T; Guan, Y H; Guo, A Q; Guo, L B; Guo, R P; Guo, Y; Guo, Y P; Haddadi, Z; Hafner, A; Han, S; Hao, X Q; Harris, F A; He, K L; Heinsius, F H; Held, T; Heng, Y K; Holtmann, T; Hou, Z L; Hu, C; Hu, H M; Hu, J F; Hu, T; Hu, Y; Huang, G S; Huang, J S; Huang, X T; Huang, X Z; Huang, Y; Huang, Z L; Hussain, T; Ji, Q; Ji, Q P; Ji, X B; Ji, X L; Jiang, L W; Jiang, X S; Jiang, X Y; Jiao, J B; Jiao, Z; Jin, D P; Jin, S; Johansson, T; Julin, A; Kalantar-Nayestanaki, N; Kang, X L; Kang, X S; Kavatsyuk, M; Ke, B C; Kiese, P; Kliemt, R; Kloss, B; Kolcu, O B; Kopf, B; Kornicer, M; Kupsc, A; Kuhn, W; Lange, J S; Lara, M; Larin, P; Leithoff, H; Leng, C; Li, C; Li, Cheng; Li, D M; Li, F; Li, F Y; Li, G; Li, H B; Li, H J; Li, J C; Li, Jin; Li, K; Li, K; Li, Lei; Li, P R; Li, Q Y; Li, T; Li, W D; Li, W G; Li, X L; Li, X N; Li, X Q; Li, Y B; Li, Z B; Liang, H; Liang, Y F; Liang, Y T; Liao, G R; Lin, D X; Liu, B; Liu, B J; Liu, C X; Liu, D; Liu, F H; Liu, Fang; Liu, Feng; Liu, H B; Liu, H H; Liu, H H; Liu, H M; Liu, J; Liu, J B; Liu, J P; Liu, J Y; Liu, K; Liu, K Y; Liu, L D; Liu, P L; Liu, Q; Liu, S B; Liu, X; Liu, Y B; Liu, Y Y; Liu, Z A; Liu, Zhiqing; Loehner, H; Lou, X C; Lu, H J; Lu, J G; Lu, Y; Lu, Y P; Luo, C L; Luo, M X; Luo, T; Luo, X L; Lyu, X R; Ma, F C; Ma, H L; Ma, L L; Ma, M M; Ma, Q M; Ma, T; Ma, X N; Ma, X Y; Ma, Y M; Maas, F E; Maggiora, M; Malik, Q A; Mao, Y J; Mao, Z P; Marcello, S; Messchendorp, J G; Mezzadri, G; Min, J; Mitchell, R E; Mo, X H; Mo, Y J; Morales, C Morales; Muchnoi, N Yu; Muramatsu, H; Musiol, P; Nefedov, Y; Nerling, F; Nikolaev, I B; Ning, Z; Nisar, S; Niu, S L; Niu, X Y; Olsen, S L; Ouyang, Q; Pacetti, S; Pan, Y; Patteri, P; Pelizaeus, M; Peng, H P; Peters, K; Pettersson, J; Ping, J L; Ping, R G; Poling, R; Prasad, V; Qi, H R; Qi, M; Qian, S; Qiao, C F; Qin, L Q; Qin, N; Qin, X S; Qin, Z H; Qiu, J F; Rashid, K H; Redmer, C F; Ripka, M; Rong, G; Rosner, Ch; Ruan, X D; Sarantsev, A; Savri, M; Schnier, C; Schoenning, K; Schumann, S; Shan, W; Shao, M; Shen, C P; Shen, P X; Shen, X Y; Sheng, H Y; Shi, M; Song, W M; Song, X Y; Sosio, S; Spataro, S; Sun, G X; Sun, J F; Sun, S S; Sun, X H; Sun, Y J; Sun, Y Z; Sun, Z J; Sun, Z T; Tang, C J; Tang, X; Tapan, I; Thorndike, E H; Tiemens, M; Uman, I; Varner, G S; Wang, B; Wang, B L; Wang, D; Wang, D Y; Wang, K; Wang, L L; Wang, L S; Wang, M; Wang, P; Wang, P L; Wang, S G; Wang, W; Wang, W P; Wang, X F; Wang, Y; Wang, Y D; Wang, Y F; Wang, Y Q; Wang, Z; Wang, Z G; Wang, Z H; Wang, Z Y; Wang, Z Y; Weber, T; Wei, D H; Wei, J B; Weidenkaff, P; Wen, S P; Wiedner, U; Wolke, M; Wu, L H; Wu, L J; Wu, Z; Xia, L; Xia, L G; Xia, Y; Xiao, D; Xiao, H; Xiao, Z J; Xie, Y G; Xiu, Q L; Xu, G F; Xu, J J; Xu, L; Xu, Q J; Xu, Q N; Xu, X P; Yan, L; Yan, W B; Yan, W C; Yan, Y H; Yang, H J; Yang, H X; Yang, L; Yang, Y X; Ye, M; Ye, M H; Yin, J H; Yu, B X; Yu, C X; Yu, J S; Yuan, C Z; Yuan, W L; Yuan, Y; Yuncu, A; Zafar, A A; Zallo, A; Zeng, Y; Zeng, Z; Zhang, B X; Zhang, B Y; Zhang, C; Zhang, C C; Zhang, D H; Zhang, H H; Zhang, H Y; Zhang, J; Zhang, J J; Zhang, J L; Zhang, J Q; Zhang, J W; Zhang, J Y; Zhang, J Z; Zhang, K; Zhang, L; Zhang, S Q; Zhang, X Y; Zhang, Y; Zhang, Y H; Zhang, Y N; Zhang, Y T; Zhang, Yu; Zhang, Z H; Zhang, Z P; Zhang, Z Y; Zhao, G; Zhao, J W; Zhao, J Y; Zhao, J Z; Zhao, Lei; Zhao, Ling; Zhao, M G; Zhao, Q; Zhao, Q W; Zhao, S J; Zhao, T C; Zhao, Y B; Zhao, Z G; Zhemchugov, A; Zheng, B; Zheng, J P; Zheng, W J; Zheng, Y H; Zhong, B; Zhou, L; Zhou, X; Zhou, X K; Zhou, X R; Zhou, X Y; Zhu, K; Zhu, K J; Zhu, S; Zhu, S H; Zhu, X L; Zhu, Y C; Zhu, Y S; Zhu, Z A; Zhuang, J; Zotti, L; Zou, B S; Zou, J H

    2016-01-01

    By analyzing $2.93\\ \\rm fb^{-1}$ of data taken at the $\\psi(3770)$ resonance peak with the BESIII detector, we measure the branching fractions for the hadronic decays $D^+\\to K^0_SK^0_S K^+$, $D^+\\to K^0_SK^0_S \\pi^+$, $D^0\\to K^0_S K^0_S$ and $D^0\\to K^0_SK^0_SK^0_S$. They are determined to be ${\\mathcal B}(D^+\\to K^0_SK^0_SK^+)=(2.54 \\pm 0.05_{\\rm stat.} \\pm 0.12_{\\rm sys.})\\times 10^{-3}$, ${\\mathcal B}(D^+\\to K^0_SK^0_S\\pi^+)=(2.70 \\pm 0.05_{\\rm stat.} \\pm 0.12_{\\rm sys.})\\times 10^{-3}$, ${\\mathcal B}(D^0\\to K^0_SK^0_S)=(1.67 \\pm 0.11_{\\rm stat.} \\pm 0.11_{\\rm sys.})\\times 10^{-4}$ and ${\\mathcal B}(D^0\\to K^0_SK^0_SK^0_S)=(7.21 \\pm 0.33_{\\rm stat.} \\pm 0.44_{\\rm sys.})\\times 10^{-4}$, where the second one is measured for the first time and the others are measured with significantly improved precision over the previous measurements.

  5. Pharmacological modulation of SK3 channels

    DEFF Research Database (Denmark)

    Grunnet, M; Jespersen, Thomas; Angelo, K

    2001-01-01

    of 512 microM and 6 microM, respectively) at concentrations lower than those used for brain slice recordings. Riluzole, a potent neuroprotective drug with anti-ischemic, anticonvulsant and sedative effects currently used in the treatment of amyotrophic lateral sclerosis, activates SK3 channels...

  6. Antiarrhythmic Mechanisms of SK Channel Inhibition in the Rat Atrium

    DEFF Research Database (Denmark)

    Skibsbye, Lasse; Wang, Xiaodong; Axelsen, Lene Nygaard

    2015-01-01

    remains unclear. OBJECTIVES: We speculated that together with a direct inhibition of repolarizing SK current, the previously observed depolarization of the atrial resting membrane potential (RMP) after SK channel inhibition reduces sodium channel availability thereby prolonging the effective refractory...

  7. Skærmens samfund/Screen Society

    DEFF Research Database (Denmark)

    Fausing, Bent

    Udgivelsen skal komme dels i en danks udgave og i en engelsk oversættelse. Der er skærme overalt i samfundet. Det er vanskeligere at finde et rum uden end et med en skærm. Hvad betyder det, at vi får oplevelser via skærme? Hvordan er skærmens æstetik og dens visualiseringer? Hvordan interagerer v...

  8. 7SK-BAF axis controls pervasive transcription at enhancers.

    Science.gov (United States)

    Flynn, Ryan A; Do, Brian T; Rubin, Adam J; Calo, Eliezer; Lee, Byron; Kuchelmeister, Hannes; Rale, Michael; Chu, Ci; Kool, Eric T; Wysocka, Joanna; Khavari, Paul A; Chang, Howard Y

    2016-03-01

    RNA functions at enhancers remain mysterious. Here we show that the 7SK small nuclear RNA (snRNA) inhibits enhancer transcription by modulating nucleosome position. 7SK occupies enhancers and super enhancers genome wide in mouse and human cells, and it is required to limit enhancer-RNA initiation and synthesis in a manner distinct from promoter pausing. Clustered elements at super enhancers uniquely require 7SK to prevent convergent transcription and DNA-damage signaling. 7SK physically interacts with the BAF chromatin-remodeling complex, recruits BAF to enhancers and inhibits enhancer transcription by modulating chromatin structure. In turn, 7SK occupancy at enhancers coincides with that of Brd4 and is exquisitely sensitive to the bromodomain inhibitor JQ1. Thus, 7SK uses distinct mechanisms to counteract the diverse consequences of pervasive transcription that distinguish super enhancers, enhancers and promoters.

  9. Solar Neutrino Measurement at SK-III

    CERN Document Server

    Yang, B S

    2009-01-01

    The full Super-Kamiokande-III data-taking period, which ran from August of 2006 through August of 2008, yielded 298 live days worth of solar neutrino data with a lower total energy threshold of 4.5 MeV. During this period we made many improvements to the experiment's hardware and software, with particular emphasis on its water purification system and Monte Carlo simulations. As a result of these efforts, we have significantly reduced the low energy backgrounds as compared to earlier periods of detector operation, cut the systematic errors by nearly a factor of two, and achieved a 4.5 MeV energy threshold for the solar neutrino analysis. In this presentation, I will present the preliminary SK-III solar neutrino measurement results.

  10. Elektrooniline maksekäsk kiirendab kohtumenetlust / Marko Aavik

    Index Scriptorium Estoniae

    Aavik, Marko, 1977-

    2008-01-01

    Eesti kohtusüsteemist ning maksekäsumenetlusest. Ilmunud ka Valgamaalane 17. juuni 2008, lk. 2 ; Harju Ekspress 20. juuni 2008, lk. 6 ; Meie Maa 2. juuli 2008, lk. 5 ; Nädaline 1. juuli 2008, lk. 5 ; Severnoje Poberezhje 2. juuli 2008, lk. 2 (Melnitsõ pravosudija stali molot bõstreje) ; Sakala 18. juuli 2008, lk. 2 ; Vooremaa : Jõgeva Valla Teataja 4. okt. 2008, lk. 2 ; Meie Maa 8. okt. 2008, lk. 6, pealkiri kujul: e-maksekäsk lahendab võlanõude kiiresti ; Vooremaa 7. okt. 2008, lk. 2, pealkiri kujul: e-maksekäsk lahendab võlanõuded kiiresti ; Koit 9. okt. 2008, lk. 3, pealkiri kujul: e-maksekäsk säästab aega ja raha ; Virumaa Teataja 9. okt. 2008, lk. 7, pealkiri kujul: e-maksekäsk lahendab võlanõuded kiiresti ; Kuulutaja 10. okt. 2008, lk. 4, pealkiri kujul: e-maksekäsk lahendab võlanõuded kiiresti ; Nädaline 14. okt. 2008, lk. 10, pealkiri kujul: e-maksekäsk lahendab võlanõuded kiiresti ; Lääne Elu 14. okt. 2008, lk. 5, pealkiri kujul: e-maksekäsk lahendab võlanõuded kiiresti ; Pärnu Postimees 18. okt. 2008, lk. 19, pealkiri kujul: e-maksekäsk lahendab võlanõuded kiiresti

  11. Elektrooniline maksekäsk kiirendab kohtumenetlust / Marko Aavik

    Index Scriptorium Estoniae

    Aavik, Marko, 1977-

    2008-01-01

    Eesti kohtusüsteemist ning maksekäsumenetlusest. Ilmunud ka Valgamaalane 17. juuni 2008, lk. 2 ; Harju Ekspress 20. juuni 2008, lk. 6 ; Meie Maa 2. juuli 2008, lk. 5 ; Nädaline 1. juuli 2008, lk. 5 ; Severnoje Poberezhje 2. juuli 2008, lk. 2 (Melnitsõ pravosudija stali molot bõstreje) ; Sakala 18. juuli 2008, lk. 2 ; Vooremaa : Jõgeva Valla Teataja 4. okt. 2008, lk. 2 ; Meie Maa 8. okt. 2008, lk. 6, pealkiri kujul: e-maksekäsk lahendab võlanõude kiiresti ; Vooremaa 7. okt. 2008, lk. 2, pealkiri kujul: e-maksekäsk lahendab võlanõuded kiiresti ; Koit 9. okt. 2008, lk. 3, pealkiri kujul: e-maksekäsk säästab aega ja raha ; Virumaa Teataja 9. okt. 2008, lk. 7, pealkiri kujul: e-maksekäsk lahendab võlanõuded kiiresti ; Kuulutaja 10. okt. 2008, lk. 4, pealkiri kujul: e-maksekäsk lahendab võlanõuded kiiresti ; Nädaline 14. okt. 2008, lk. 10, pealkiri kujul: e-maksekäsk lahendab võlanõuded kiiresti ; Lääne Elu 14. okt. 2008, lk. 5, pealkiri kujul: e-maksekäsk lahendab võlanõuded kiiresti ; Pärnu Postimees 18. okt. 2008, lk. 19, pealkiri kujul: e-maksekäsk lahendab võlanõuded kiiresti

  12. Charting Class ${\\cal S}_k$ Territory

    CERN Document Server

    Franco, Sebastian; Uranga, Angel

    2015-01-01

    We extend the investigation of the recently introduced class ${\\cal S}_k$ of 4d $\\mathcal{N}=1$ SCFTs, by considering a large family of quiver gauge theories within it, which we denote $\\mathcal{S}^1_k$. These theories admit a realization in terms of $\\mathbb{Z}_k$ orbifolds of Type IIA configurations of D4-branes stretched among relatively rotated sets of NS-branes. This fact permits a systematic investigation of the full family, which exhibits new features such as non-trivial anomalous dimensions differing from free field values and novel ways of gluing theories. We relate these ingredients to properties of compactification of the 6d (1,0) superconformal ${\\cal T}_N^k$ theories on spheres with different kinds of punctures. We describe the structure of dualities in this class of theories upon exchange of punctures, including transformations that correspond to Seiberg dualities, and exploit the computation of the superconformal index to check the invariance of the theories under them.

  13. Skønhed - En engel gik forbi

    DEFF Research Database (Denmark)

    Jørgensen, Dorthe

    Hvorfor spilde tiden på skønhed i en verden fuld af problemer? Med dette provokerende spørgsmål indleder filosof og idéhistoriker Dorthe Jørgensen sin undersøgelse af, hvad skønhed er, og hvordan den kan hjælpe os i vor søgen efter det gode liv. Hun fortæller ikke bare om, hvad kunstnere og tænke...

  14. Skønhed - En engel gik forbi

    DEFF Research Database (Denmark)

    Jørgensen, Dorthe

    Hvorfor spilde tiden på skønhed i en verden fuld af problemer? Med dette provokerende spørgsmål indleder filosof og idéhistoriker Dorthe Jørgensen sin undersøgelse af, hvad skønhed er, og hvordan den kan hjælpe os i vor søgen efter det gode liv. Hun fortæller ikke bare om, hvad kunstnere og tænke...

  15. Solar neutrino measurement in SK and larger detector

    Energy Technology Data Exchange (ETDEWEB)

    Koshio, Y. [Kamioka observatory, ICRR, Univ. of Tokyo, Higashi-Mozumi, Kamioka cho, Hida city, Gifu pref (Japan)

    2005-08-15

    The results of solar neutrino data from the first phase of Super-Kamiokande (SK-I) are presented. Super-Kamiokande can measure not only the solar neutrino flux but also its energy spectrum and time variations such as day-night and seasonal differences. The detail oscillation analysis using those information is appeared. Combining all the solar and KamLAND reactor data, the obtained oscillation parameters are determined as {delta}m{sup 2}=8.3x10{sup -5}eV{sup 2} and tan{sup 2}{theta}=0.38. The recent results in the second phase of SK (SK-II) are also presented, and its flux, spectrum and time variation are consistent with SK-I. The possibility of future water Cherenkov detectors, such as SK-III and Mega-ton class detector, are described. If the current neutrino oscillation parameter is assumed, its spectrum has deficit in the lower energy region. And the possibility of the day-night asymmetry is also discussed.

  16. Branching fraction and CP asymmetries of B0-->K0(S)K0(S)K0(S).

    Science.gov (United States)

    Aubert, B; Barate, R; Boutigny, D; Couderc, F; Karyotakis, Y; Lees, J P; Poireau, V; Tissserand, V; Zghiche, A; Grauges-Pous, E; Palano, A; Pompili, A; Chen, J C; Qi, N D; Rong, G; Wang, P; Zhu, Y S; Eigen, G; Ofte, I; Stugu, B; Abrams, G S; Borgland, A W; Breon, A B; Brown, D N; Button-Shafer, J; Cahn, R N; Charles, E; Day, C T; Gill, M S; Gritsan, A V; Groysman, Y; Jacobsen, R G; Kadel, R W; Kadyk, J; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Lynch, G; Mir, L M; Oddone, P J; Orimoto, T J; Pripstein, M; Roe, N A; Ronan, M T; Wenzel, W A; Barrett, M; Ford, K E; Harrison, T J; Hart, A J; Hawkes, C M; Morgan, S E; Watson, A T; Fritsch, M; Goetzen, K; Held, T; Koch, H; Lewandowski, B; Pelizaeus, M; Peters, K; Schroeder, T; Steinke, M; Boyd, J T; Burke, J P; Chevalier, N; Cottingham, W N; Kelly, M P; Latham, T E; Wilson, F F; Cuhadar-Donszelmann, T; Hearty, C; Knecht, N S; Mattison, T S; McKenna, J A; Thiessen, D; Khan, A; Kyberd, P; Teodorescu, L; Blinov, A E; Blinov, V E; Druzhinin, V P; Golubev, V B; Ivanchenko, V N; Kravchenko, E A; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Yushkov, A N; Best, D; Bruinsma, M; Chao, M; Eschrich, I; Kirkby, D; Lankford, A J; Mandelkern, M; Mommsen, R K; Roethel, W; Stoker, D P; Buchanan, C; Hartfiel, B L; Weinstein, A J R; Foulkes, S D; Gary, J W; Long, O; Shen, B C; Wang, K; del Re, D; Hadavand, H K; Hill, E J; MacFarlane, D B; Paar, H P; Rahatlou, Sh; Sharma, V; Berryhill, J W; Campagnari, C; Cunha, A; Dahmes, B; Hong, T M; Lu, A; Mazur, M A; Richman, J D; Verkerke, W; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Nesom, G; Schalk, T; Schumm, B A; Seiden, A; Spradlin, P; Williams, D C; Wilson, M G; Albert, J; Chen, E; Dubois-Felsmann, G P; Dvoretskii, A; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Ryd, A; Samuel, A; Yang, S; Jayatilleke, S; Mancinelli, G; Meadows, B T; Sokoloff, M D; Blanc, F; Bloom, P; Chen, S; Ford, W T; Nauenberg, U; Olivas, A; Rankin, P; Ruddick, W O; Smith, J G; Ulmer, K A; Zhang, J; Zhang, L; Chen, A; Eckhart, E A; Harton, J L; Soffer, A; Toki, W H; Wilson, R J; Zeng, Q; Spaan, B; Altenburg, D; Brandt, T; Brose, J; Dickopp, M; Feltresi, E; Hauke, A; Lacker, H M; Maly, E; Nogowski, R; Otto, S; Petzold, A; Schott, G; Schubert, J; Schubert, K R; Schwierz, R; Sundermann, J E; Bernard, D; Bonnneaud, G R; Grenier, P; Schrenk, S; Thiebaux, Ch; Vasileiadis, G; Verderi, M; Bard, D J; Clark, P J; Muheim, F; Playfer, S; Xie, Y; Andreotti, M; Azzolini, V; Bettoni, D; Bozzi, C; Calabrese, R; Cibinetto, G; Luppi, E; Negrini, M; Piemontese, L; Sarti, A; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Patteri, P; Peruzzi, I M; Piccolo, M; Zallo, A; Buzzo, A; Capra, R; Contri, R; Crosetti, G; Lo Vetere, M; Macri, M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Bailey, S; Brandenburg, G; Chaisanguanthum, K S; Morii, M; Won, E; Dubitzky, R S; Langenegger, U; Marks, J; Uwer, U; Bhimji, W; Bowerman, D A; Dauncey, P D; Egede, U; Gaillard, J R; Morton, G W; Nash, J A; Nikolich, M B; Taylor, G P; Charles, M J; Grenier, G J; Mallik, U; Mohapatra, A K; Cochran, J; Crawley, H B; Lamsa, J; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Yi, J; Arnaud, N; Davier, M; Giroux, X; Grosdidier, G; Höcker, A; Le Diberder, F; Lepeltier, V; Lutz, A M; Petersen, T C; Pierini, M; Plaszczynski, S; Schune, M H; Wormser, G; Cheng, C H; Lange, D J; Simani, M C; Wright, D M; Bevan, A J; Chavez, C A; Coleman, J P; Forster, I J; Fry, J R; Gabathuler, E; Gamet, R; Hutchhcroft, D E; Parry, R J; Payne, D J; Touramanis, C; Cormack, C M; Di Lodovico, F; Brown, C L; Cowan, G; Flack, R L; Flaecher, H U; Green, M G; Jackson, P S; McMahon, T R; Ricciardi, S; Salvatore, F; Winter, M A; Brown, D; Davis, C L; Allison, J; Barlow, N R; Barlow, R J; Hodgkinson, M C; Lafferty, G D; Naisbit, M T; Williams, J C; Chen, C; Farbin, A; Hulsbergen, W D; Jawahery, A; Kovalskyi, D; Lae, C K; Lillard, V; Roberts, D A; Blaylock, G; Dallapiccola, C; Hertzbach, S S; Kofler, R; Koptchev, V B; Moore, T B; Saremi, S; Staengle, H; Willocq, S; Cowan, R; Koeneke, K; Sciolla, G; Sekula, S J; Taylor, F; Yamamoto, R K; Patel, P M; Robertson, S H; Lazzaro, A; Lombardo, V; Palombo, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Reidy, J; Sanders, D A; Summers, D J; Zhao, H W; Brunet, S; Côté, D; Taras, P; Nicholson, H; Cavallo, N; Fabozzi, F; Gatto, C; Lista, L; Monorchio, D; Paolucci, P; Piccolo, D; Sciacca, C; Baak, M; Bulten, H; Raven, G; Snoek, H L; Wilden, L; Jessop, C P; LoSecco, J M; Allmendinger, T; Bennelli, G; Gan, K K; Honscheid, K; Hufnagel, D; Kagan, H; Kass, R; Pulliam, T; Rahimi, A M; Ter-Antonyan, R; Wong, Q K; Brau, J; Frey, R; Igonkina, O; Lu, M; Potter, C T; Sinev, N B; Strom, D; Torrence, E; Colecchia, F; Dorigo, A; Galeazzi, F; Margoni, M; Morandin, M; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Benayoun, M; Briand, H; Chauveau, J; David, P; Del Buono, L; de la Vaissière, Ch; Hamon, O; John, M J J; Leruste, Ph; Malclès, J; Ocariz, J; Roos, L; Therin, G; Behera, P K; Gladney, L; Guo, Q H; Panetta, J; Biasini, M; Covarelli, R; Pioppi, M; Angelini, C; Batignani, G; Bettarini, S; Bondioli, M; Bucci, F; Calderini, G; Carpinelli, M; Forti, F; Giorgi, M A; Lusiani, A; Marchiori, G; Morganti, M; Neri, N; Paoloni, E; Rama, M; Rizzo, G; Simi, G; Walsh, J; Haire, M; Judd, D; Paick, K; Wagoner, D E; Danielson, N; Elmer, P; Lau, Y P; Lu, C; Miftakov, V; Olsen, J; Smith, A J S; Telnov, A V; Bellini, F; Cavoto, G; D'Orazio, A; Di Marco, E; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Li Gioi, L; Mazzoni, M A; Morganti, S; Piredda, G; Polci, F; Safai Tehrani, F; Voena, C; Christ, S; Schröder, H; Wagner, G; Waldi, R; Adye, T; De Groot, N; Franek, B; Gopal, G P; Olaiya, E O; Aleksan, R; Emery, S; Gaidot, A; Ganzhur, S F; Giraud, P-F; Hamel de Monchenault, G; Kozanecki, W; Legendre, M; London, G W; Mayer, B; Vasseur, G; Yèche, Ch; Zito, M; Purohit, M V; Weidemann, A W; Wilson, J R; Yumiceva, F X; Abe, T; Aston, D; Bartoldus, R; Berger, N; Boyarski, A M; Buchmueller, O L; Claus, R; Convery, M R; Cristinziani, M; De Nardo, G; Dingfelder, J C; Dong, D; Dorfan, J; Dujmic, D; Dunwoodie, W; Fan, S; Field, R C; Glanzman, T; Gowdy, S J; Hadig, T; Halyo, V; Hast, C; Hrny'ova, T; Innes, W R; Kelsey, M H; Kim, P; Kocian, M L; Leith, D W G S; Libby, J; Luitz, S; Luth, V; Lynch, H L; Marsiske, H; Messner, R; Muller, D R; O'Grady, C P; Ozcan, V E; Perazzo, A; Perl, M; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Snyder, A; Soha, A; Stelzer, J; Strube, J; Su, D; Sullivan, M K; Va'vra, J; Wagner, S R; Weaver, M; Wisniewski, W J; Wittgen, M; Wright, D H; Yarritu, A K; Young, C C; Burchat, P R; Edwards, A J; Majewski, S A; Petersen, B A; Roat, C; Ahmed, M; Ahmed, S; Alam, M S; Ernst, J A; Saeed, M A; Saleem, M; Wappler, F R; Bugg, W; Krishnamurthy, M; Spanier, S M; Eckmann, R; Kim, H; Ritchie, J L; Satpathy, A; Schwitters, R F; Izen, J M; Kitayama, I; Lou, X C; Ye, S; Bianchi, F; Bona, M; Gallo, F; Gamba, D; Bosisio, L; Cartaro, C; Cossutti, F; Della Ricca, G; Dittongo, S; Grancagnolo, S; Lanceri, L; Poropat, P; Vitale, L; Vuagnin, G; Martinez-Vidal, F; Panvini, R S; Banerjee, Sw; Bhuyan, B; Brown, C M; Fortin, D; Hamano, K; Jackson, P D; Kowalewski, R; Roney, J M; Sobie, R J; Back, J J; Harrison, P F; Mohanty, G B; Band, H R; Chen, X; Cheng, B; Dasu, S; Datta, M; Eichenbaum, A M; Flood, K T; Graham, M; Hollar, J J; Johnson, J R; Kutter, P E; Li, H; Liu, R; Mihalyi, A; Pan, Y; Prepost, R; Tan, P; von Wimmersperg-Toeller, J H; Wu, J; Wu, S L; Yu, Z; Greene, M G; Neal, H

    2005-07-01

    We present measurements of the branching fraction and time-dependent CP-violating asymmetries in B0-->K0(S)K0(S)K0(S) decays based on 227 x 10(6) Upsilon4S-->BB decays collected with the BABAR detector at the PEP-II asymmetric-energy B factory at SLAC. We obtain a branching fraction of (6.9(+0.9)(-0.8)+/-0.6) x 10(-6), and CP asymmetries C=-0.34(+0.28)(-0.25)+/-0.05 and S=-0.71(+0.38)(-0.32)+/-0.04, where the first uncertainties are statistical and the second systematic.

  17. Global features of the Alcanivorax borkumensis SK2 genome

    DEFF Research Database (Denmark)

    Reva, Oleg N.; Hallin, Peter Fischer; Willenbrock, Hanni

    2008-01-01

    The global feature of the completely sequenced Alcanivorax borkumensis SK2 type strain chromosome is its symmetry and homogeneity. The origin and terminus of replication are located opposite to each other in the chromosome and are discerned with high signal to noise ratios by maximal oligonucleot...

  18. En "skælvsættende" dom?

    DEFF Research Database (Denmark)

    Lauta, Kristian Cedervall

    2012-01-01

    Sanktioner imod bevidste undladelser eller uprofessionelle skøn er en måde at opretholde tilliden til ingeniører på, og det samme gælder seismologer. ... Sagen illustrerer de fundamentale forandringer, der de sidste 30 år er sket med vores forståelse af, hvad en ' naturkatastrofe' er. Katastrofer...

  19. Analysis of Future KamLAND and Gadolinium Doped SK

    Energy Technology Data Exchange (ETDEWEB)

    Choubey, Sandhya [INFN and SISSA, Trieste (Italy)

    2005-12-15

    We probe in detail the precision expected in the measurement of {delta}m{sub 21}{sup 2} and sin{sup 2}{theta}{sub 12} in the SNO, KamLAND, the proposed SK-Gd and a reactor experiment tuned to the SPMIN.

  20. Uncovering a Role for SK2 in Angelman Syndrome

    Directory of Open Access Journals (Sweden)

    Sofia B. Lizarraga

    2015-07-01

    Full Text Available Angelman syndrome is a severe neurodevelopmental disorder caused by mutations in UBE3A. Sun et al. (2015 report SK2 as a UBE3A substrate and provide insight into the molecular mechanisms that might underlie impaired neuronal function in individuals affected by Angelman syndrome.

  1. Identification and characterization of a novel, shorter isoform of the small conductance Ca(2+)-activated K(+) channel SK2

    NARCIS (Netherlands)

    Murthy, Saravana R. K.; Teodorescu, Georgeta; Nijholt, Ingrid M.; Dolga, Amalia; Grissmer, Stephan; Spiess, Joachim; Blank, Thomas

    2008-01-01

    Throughout the CNS, small conductance Ca(2+)-activated potassium (SK) channels modulate firing frequency and neuronal excitability. We have identified a novel, shorter isoform of standard SK2 (SK2-std) in mouse brain which we named SK2-sh. SK2-sh is alternatively spliced at exon 3 and therefore lack

  2. Characteristics of glycosylated streptokinase secreted from Pichia pastoris: enhanced resistance of SK to proteolysis by glycosylation.

    Science.gov (United States)

    Pratap, J; Rajamohan, G; Dikshit, K L

    2000-04-01

    Degradation of streptokinase (SK) has been frequently observed during large-scale protein production. An enhanced susceptibility of SK to degradation has been correlated with its existence in a partially unfolded state. The influence of the carbohydrate moiety on the stability and functional characteristics of SK has been examined by obtaining the glycoform of SK following its secretion through the methylotrophic yeast Pichia pastoris. Secretion of the protein product was achieved by replacing the native secretion signal codons of SK with those from alpha-factor leader peptide and expressing the fusion construct under the control of the methanol-inducible alcohol oxidase (ox) promoter of P. pastoris after its integration into the host chromosome. Western blot and zymographic analysis of proteins secreted from the recombinant P. pastoris indicated that SK was glycosylated by the host cells, which resulted in the appearance of a SK species migrating slowly, corresponding to a 55-kDa protein product as compared to the 47-kDa native SK. The glycosylated SK retained a plasminogen activation capability identical to that of its unglycosylated counterpart. Glycoform SK exhibited an enhanced stability profile at 25 degrees C and 37 degrees C and improved resistance towards protease treatment compared to unglycosylated SK secreted through P. pastoris after tunicamycin treatment or that secreted from the recombinant Escherichia coli. The results presented thus illustrate that N-linked glycosylation of SK results in 30-40% enhancement of the protein stability and resistance towards degradation but does not interfere with its fibrinolytic function.

  3. File list: His.Brs.20.AllAg.SK-BR-3 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Brs.20.AllAg.SK-BR-3 hg19 Histone Breast SK-BR-3 SRX750665,SRX750660,SRX469107,...SRX469108 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Brs.20.AllAg.SK-BR-3.bed ...

  4. File list: Oth.Brs.10.AllAg.SK-BR-3 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Brs.10.AllAg.SK-BR-3 hg19 TFs and others Breast SK-BR-3 SRX155755,SRX128102,SRX...155754 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Brs.10.AllAg.SK-BR-3.bed ...

  5. File list: Oth.Brs.20.AllAg.SK-BR-3 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Brs.20.AllAg.SK-BR-3 hg19 TFs and others Breast SK-BR-3 SRX155755,SRX128102,SRX...155754 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Brs.20.AllAg.SK-BR-3.bed ...

  6. File list: His.Brs.05.AllAg.SK-BR-3 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Brs.05.AllAg.SK-BR-3 hg19 Histone Breast SK-BR-3 SRX750660,SRX750665,SRX469108,...SRX469107 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Brs.05.AllAg.SK-BR-3.bed ...

  7. File list: Oth.Brs.50.AllAg.SK-BR-3 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Brs.50.AllAg.SK-BR-3 hg19 TFs and others Breast SK-BR-3 SRX128102,SRX155755,SRX...155754 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Brs.50.AllAg.SK-BR-3.bed ...

  8. File list: Oth.Brs.05.AllAg.SK-BR-3 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Brs.05.AllAg.SK-BR-3 hg19 TFs and others Breast SK-BR-3 SRX155754,SRX155755,SRX...128102 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Brs.05.AllAg.SK-BR-3.bed ...

  9. File list: His.Brs.10.AllAg.SK-BR-3 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Brs.10.AllAg.SK-BR-3 hg19 Histone Breast SK-BR-3 SRX750660,SRX750665,SRX469108,...SRX469107 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Brs.10.AllAg.SK-BR-3.bed ...

  10. The legacy of Maria Curie Skłodowska

    Science.gov (United States)

    Sosnowski, Ryszard

    2011-01-01

    Maria Skłodowska Curie left us a great legacy. Her discovery of polonium and radium was incomparably greater than the mere discovery of new elements. Its significance lay in the discovery of a new form of matter, namely radioactive one, but also in her unveiling of the internal property of its atoms. Subsequently emitted radiation went on to play the role of a "natural accelerator" for both scientific research and in medical radiotherapy. It was thanks to these discoveries that the field of nuclear physics arose just a few decades later. As importantly the work of Maria Curie Skłodowska during the Great War demonstrated how important pure scientific discovery can be for society and its welfare.

  11. Pääsküla raamatukogu / Maris Takk

    Index Scriptorium Estoniae

    Takk, Maris

    2006-01-01

    Pääsküla raamatukogu (Tallinn, Pärnu mnt. 480A) sisekujundus, mille eest sisekujundajad Katrin Kaevats ja Peeter Pere (AB Muru & Pere) pälvisid Eesti Sisearhitektide Liidu 2005. a. ühiskondliku interjööri preemia. Ehitaja: OÜ SCE Grupp. K. Kaevatsist, tema tähtsamad tööd. P. Perest, valik AB Muru & Pere projektidest. Ill.: kaks korruste plaani, 17 värv. vaadet, K. Kaevatsi ja P. Pere fotod

  12. Pääsküla raamatukogu / Maris Takk

    Index Scriptorium Estoniae

    Takk, Maris

    2006-01-01

    Pääsküla raamatukogu (Tallinn, Pärnu mnt. 480A) sisekujundus, mille eest sisekujundajad Katrin Kaevats ja Peeter Pere (AB Muru & Pere) pälvisid Eesti Sisearhitektide Liidu 2005. a. ühiskondliku interjööri preemia. Ehitaja: OÜ SCE Grupp. K. Kaevatsist, tema tähtsamad tööd. P. Perest, valik AB Muru & Pere projektidest. Ill.: kaks korruste plaani, 17 värv. vaadet, K. Kaevatsi ja P. Pere fotod

  13. CP Violation in $D^0\\rightarrow K_SK_S$

    CERN Document Server

    Nierste, Ulrich

    2015-01-01

    The direct CP asymmetry $a_{CP}^{\\mathrm{dir}}(D^0\\rightarrow K_SK_S)$ involves exchange diagrams which are induced at tree-level in the Standard Model. Since the corresponding topological amplitude $E_{KK}$ can be large, $D^0\\rightarrow K_SK_S$ is a promising discovery channel for charm CP violation. We estimate the penguin annihilation amplitude with a perturbative calculation and extract the exchange amplitude $E_{KK}$ from a global fit to $D$ branching ratios. Our results are further used to predict the size of mixing-induced CP violation. We obtain $\\vert a_{CP}^{\\mathrm{dir}}(D^0\\rightarrow K_SK_S)\\vert \\leq 1.1\\%$ (95\\% C.L.). The same bound applies to the nonuniversal part of the phase between the $D\\!-\\overline{\\!D}\\,$ mixing and decay amplitudes. If future data exceed our predictions, this will point to new physics or an enhancement of the penguin annihilation amplitude by QCD dynamics. We briefly discuss the implications of these possibilities for other CP asymmetries.

  14. Mitochondrial small conductance SK2 channels prevent glutamate-induced oxytosis and mitochondrial dysfunction.

    Science.gov (United States)

    Dolga, Amalia M; Netter, Michael F; Perocchi, Fabiana; Doti, Nunzianna; Meissner, Lilja; Tobaben, Svenja; Grohm, Julia; Zischka, Hans; Plesnila, Nikolaus; Decher, Niels; Culmsee, Carsten

    2013-04-12

    Small conductance calcium-activated potassium (SK2/K(Ca)2.2) channels are known to be located in the neuronal plasma membrane where they provide feedback control of NMDA receptor activity. Here, we provide evidence that SK2 channels are also located in the inner mitochondrial membrane of neuronal mitochondria. Patch clamp recordings in isolated mitoplasts suggest insertion into the inner mitochondrial membrane with the C and N termini facing the intermembrane space. Activation of SK channels increased mitochondrial K(+) currents, whereas channel inhibition attenuated these currents. In a model of glutamate toxicity, activation of SK2 channels attenuated the loss of the mitochondrial transmembrane potential, blocked mitochondrial fission, prevented the release of proapoptotic mitochondrial proteins, and reduced cell death. Neuroprotection was blocked by specific SK2 inhibitory peptides and siRNA targeting SK2 channels. Activation of mitochondrial SK2 channels may therefore represent promising targets for neuroprotective strategies in conditions of mitochondrial dysfunction.

  15. Mitochondrial Small Conductance SK2 Channels Prevent Glutamate-induced Oxytosis and Mitochondrial Dysfunction*

    Science.gov (United States)

    Dolga, Amalia M.; Netter, Michael F.; Perocchi, Fabiana; Doti, Nunzianna; Meissner, Lilja; Tobaben, Svenja; Grohm, Julia; Zischka, Hans; Plesnila, Nikolaus; Decher, Niels; Culmsee, Carsten

    2013-01-01

    Small conductance calcium-activated potassium (SK2/KCa2.2) channels are known to be located in the neuronal plasma membrane where they provide feedback control of NMDA receptor activity. Here, we provide evidence that SK2 channels are also located in the inner mitochondrial membrane of neuronal mitochondria. Patch clamp recordings in isolated mitoplasts suggest insertion into the inner mitochondrial membrane with the C and N termini facing the intermembrane space. Activation of SK channels increased mitochondrial K+ currents, whereas channel inhibition attenuated these currents. In a model of glutamate toxicity, activation of SK2 channels attenuated the loss of the mitochondrial transmembrane potential, blocked mitochondrial fission, prevented the release of proapoptotic mitochondrial proteins, and reduced cell death. Neuroprotection was blocked by specific SK2 inhibitory peptides and siRNA targeting SK2 channels. Activation of mitochondrial SK2 channels may therefore represent promising targets for neuroprotective strategies in conditions of mitochondrial dysfunction. PMID:23430260

  16. Solar Neutrino flare detection in Hyperkamiokande and SK

    Science.gov (United States)

    Fargion, Daniele

    2016-07-01

    The possible buid and near activity of a Megaton neutrino detection in HyperKamiokande and the older SK implementation by Gadolinium liqid might open to future detection of largest solar flare (pion trace at tens MeV) electron neutrino and antineutrino. The multiwave detection of X-gamma and neutrino event might offer a deep view of such solar acelleration and of neutrino flavor mix along its flight. The possoble near future discover of such events will open a third neutrino astronomy windows after rarest SN 1987A and persistent Solar nuclear signals.

  17. Hepatoma SK Hep-1 cells exhibit characteristics of oncogenic mesenchymal stem cells with highly metastatic capacity.

    Directory of Open Access Journals (Sweden)

    Jong Ryeol Eun

    Full Text Available BACKGROUND: SK Hep-1 cells (SK cells derived from a patient with liver adenocarcinoma have been considered a human hepatoma cell line with mesenchymal origin characteristics, however, SK cells do not express liver genes and exhibit liver function, thus, we hypothesized whether mesenchymal cells might contribute to human liver primary cancers. Here, we characterized SK cells and its tumourigenicity. METHODS AND PRINCIPAL FINDINGS: We found that classical mesenchymal stem cell (MSC markers were presented on SK cells, but endothelial marker CD31, hematopoietic markers CD34 and CD45 were negative. SK cells are capable of differentiate into adipocytes and osteoblasts as adipose-derived MSC (Ad-MSC and bone marrow-derived MSC (BM-MSC do. Importantly, a single SK cell exhibited a substantial tumourigenicity and metastatic capacity in immunodefficient mice. Metastasis not only occurred in circulating organs such as lung, liver, and kidneys, but also in muscle, outer abdomen, and skin. SK cells presented greater in vitro invasive capacity than those of Ad-MSC and BM-MSC. The xenograft cells from subcutaneous and metastatic tumors exhibited a similar tumourigenicity and metastatic capacity, and showed the same relatively homogenous population with MSC characteristics when compared to parental SK cells. SK cells could unlimitedly expand in vitro without losing MSC characteristics, its tumuorigenicity and metastatic capacity, indicating that SK cells are oncogenic MSC with enhanced self-renewal capacity. We believe that this is the first report that human MSC appear to be transformed into cancer stem cells (CSC, and that their derivatives also function as CSCs. CONCLUSION: Our findings demonstrate that SK cells represent a transformation mechanism of normal MSC into an enhanced self-renewal CSC with metastasis capacity, SK cells and their xenografts represent a same relative homogeneity of CSC with substantial metastatic capacity. Thus, it represents a

  18. Longitudinal epitope mapping in MuSK myasthenia gravis: implications for disease severity.

    Science.gov (United States)

    Huijbers, Maartje G; Vink, Anna-Fleur D; Niks, Erik H; Westhuis, Ruben H; van Zwet, Erik W; de Meel, Robert H; Rojas-García, Ricardo; Díaz-Manera, Jordi; Kuks, Jan B; Klooster, Rinse; Straasheijm, Kirsten; Evoli, Amelia; Illa, Isabel; van der Maarel, Silvère M; Verschuuren, Jan J

    2016-02-15

    Muscle weakness in MuSK myasthenia gravis (MG) is caused predominantly by IgG4 antibodies which block MuSK signalling and destabilize neuromuscular junctions. We determined whether the binding pattern of MuSK IgG4 antibodies change throughout the disease course ("epitope spreading"), and affect disease severity or treatment responsiveness. We mapped the MuSK epitopes of 255 longitudinal serum samples of 53 unique MuSK MG patients from three independent cohorts with ELISA. Antibodies against the MuSK Iglike-1 domain determine disease severity. Epitope spreading outside this domain did not contribute to disease severity nor to pyridostigmine responsiveness. This provides a rationale for epitope specific treatment strategies.

  19. Subtype-specific, bi-component inhibition of SK channels by low internal pH

    DEFF Research Database (Denmark)

    Peitersen, Torben; Jespersen, Thomas; Jorgensen, Nanna K;

    2006-01-01

    The effects of low intracellular pH (pH(i) 6.4) on cloned small-conductance Ca2+-activated K+ channel currents of all three subtypes (SK1, SK2, and SK3) were investigated in HEK293 cells using the patch-clamp technique. In 400 nM internal Ca2+ [Ca2+]i, all subtypes were inhibited by pH(i) 6...

  20. Characterization of CD4 and CD8 T Cell Responses in MuSK Myasthenia Gravis

    OpenAIRE

    Yi, JS; Guidon, A; Sparks, S.; Osborne, R.; Juel, VC; Massey, JM; Sanders, DB; Weinhold, KJ; Guptill, JT

    2013-01-01

    Muscle specific tyrosine kinase myasthenia gravis (MuSK MG) is a form of autoimmune MG that predominantly affects women and has unique clinical features, including prominent bulbar weakness, muscle atrophy, and excellent response to therapeutic plasma exchange. Patients with MuSK MG have predominantly IgG4 autoantibodies directed against MuSK on the postsynaptic muscle membrane. Lymphocyte functionality has not been reported in this condition. The goal of this study was to characterize T-cell...

  1. File list: ALL.Brs.10.AllAg.SK-BR-3 [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  2. File list: ALL.Brs.50.AllAg.SK-BR-3 [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. File list: ALL.Brs.20.AllAg.SK-BR-3 [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  4. File list: ALL.Brs.05.AllAg.SK-BR-3 [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. CyPPA, a positive SK3/SK2 modulator, reduces activity of dopaminergic neurons, inhibits dopamine release, and counteracts hyperdopaminergic behaviors induced by methylphenidate

    Directory of Open Access Journals (Sweden)

    Kjartan F. Herrik

    2012-02-01

    Full Text Available Dopamine (DA containing midbrain neurons play critical roles in several psychiatric and neurological diseases, including schizophrenia and attention deficit hyperactivity disorder (ADHD, and the substantia nigra pars compacta neurons selectively degenerate in Parkinson’s disease. Pharmacological modulation of DA receptors and transporters are well established approaches for treatment of DA-related disorders. Direct modulation of the DA system by influencing the discharge pattern of these autonomously firing neurons has yet to be exploited as a potential therapeutic strategy. Small conductance Ca2+-activated K+ channels (SK channels, in particular the SK3 subtype, are important in the physiology of DA neurons, and agents modifying SK channel activity could potentially affect DA-signaling and DA-related behaviors. Here we show that CyPPA (cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl-6-methyl-pyrimidin-4-yl]-amine, a subtype-selective positive modulator of SK channels (SK3 > SK2 >>> SK1, IK, decreased spontaneous firing rate, increased the duration of the apamin-sensitive, medium duration afterhyperpolarization (mAHP, and caused an activity-dependent inhibition of current-evoked action potentials in DA neurons from both mouse and rat midbrain slices. Using a immunohistochemically and pharmacologically validated DA release assay employing cultured DA neurons from rats, we show that CyPPA repressed DA release in a concentration-dependent manner with a maximal effect equal to the D2 receptor agonist quinpirole. In vivo studies revealed that systemic administration of CyPPA attenuated methylphenidate-induced hyperactivity and stereotypic behaviors in mice. Taken together, the data accentuate the important role played by SK3 channels in the physiology of DA neurons, and indicate that their facilitation by CyPPA profoundly influences physiological as well as pharmacologically induced hyperdopaminergic behavior.

  6. Mitochondria-targeted antioxidant SkQ1 improves impaired dermal wound healing in old mice.

    Science.gov (United States)

    Demyanenko, Ilya A; Popova, Ekaterina N; Zakharova, Vlada V; Ilyinskaya, Olga P; Vasilieva, Tamara V; Romashchenko, Valeria P; Fedorov, Artem V; Manskikh, Vasily N; Skulachev, Maxim V; Zinovkin, Roman A; Pletjushkina, Olga Yu; Skulachev, Vladimir P; Chernyak, Boris V

    2015-07-01

    The process of skin wound healing is delayed or impaired in aging animals. To investigate the possible role of mitochondrial reactive oxygen species (mtROS) in cutaneous wound healing of aged mice, we have applied the mitochondria-targeted antioxidant SkQ1. The SkQ1 treatment resulted in accelerated resolution of the inflammatory phase, formation of granulation tissue, vascularization and epithelization of the wounds. The wounds of SkQ1-treated mice contained increased amount of myofibroblasts which produce extracellular matrix proteins and growth factors mediating granulation tissue formation. This effect resembled SkQ1-induced differentiation of fibroblasts to myofibroblast, observed earlierin vitro. The Transforming Growth Factor beta (TGFb) produced by SkQ1-treated fibroblasts was found to stimulated motility of endothelial cells in vitro, an effect which may underlie pro-angiogenic action of SkQ1 in the wounds. In vitro experiments showed that SkQ1 prevented decomposition of VE-cadherin containing contacts and following increase in permeability of endothelial cells monolayer, induced by pro-inflammatory cytokine TNF. Prevention of excessive reaction of endothelium to the pro-inflammatory cytokine(s) might account for anti-inflammatory effect of SkQ1. Our findings point to an important role of mtROS in pathogenesis of age-related chronic wounds.

  7. SK2 channels regulate mitochondrial respiration and mitochondrial Ca2+ uptake

    NARCIS (Netherlands)

    Honrath, Birgit; Matschke, Lina; Meyer, Tammo; Magerhans, Lena; Perocchi, Fabiana; Ganjam, Goutham K; Zischka, Hans; Krasel, Cornelius; Gerding, Albert; Bakker, Barbara M; Bünemann, Moritz; Strack, Stefan; Decher, Niels; Culmsee, Carsten; Dolga, Amalia M

    Mitochondrial calcium ([Ca(2+)]m) overload and changes in mitochondrial metabolism are key players in neuronal death. Small conductance calcium-activated potassium (SK) channels provide protection in different paradigms of neuronal cell death. Recently, SK channels were identified at the inner

  8. Skønhedens metamorfose - De æstetiske idéers historie

    DEFF Research Database (Denmark)

    Jørgensen, Dorthe

    Hvorfor findes der kunst? Hvad vil guderne os? Hvordan forholder kunst, skønhed og guddommelighed sig til hinanden? Disse spørgsmål er blevet diskuteret siden antikken. Og lige så tit der er blevet formuleret nye svar, lige så ofte er skønhedsopfattelsen undergået en metamorfose. Det er dog gammel...

  9. Effects of the mitochondria-targeted antioxidant SkQ1 on lifespan of rodents

    Science.gov (United States)

    Anisimov, Vladimir N.; Egorov, Maxim V.; Krasilshchikova, Marina S.; Lyamzaev, Konstantin G.; Manskikh, Vasily N.; Moshkin, Mikhail P.; Novikov, Evgeny A.; Popovich, Irina G.; Rogovin, Konstantin A.; Shabalina, Irina G.; Shekarova, Olga N.; Skulachev, Maxim V.; Titova, Tatiana V.; Vygodin, Vladimir A.; Vyssokikh, Mikhail Yu.; Yurova, Maria N.; Zabezhinsky, Mark A.; Skulachev, Vladimir P.

    2011-01-01

    The effect of the mitochondria-targeted, plastoquinone-containing antioxidant SkQ1 on the lifespan of outbred mice and of three strains of inbred mice was studied. To this end, low pathogen (LP) or specific pathogen free (SPF) vivaria in St. Petersburg, Moscow, and Stockholm were used. For comparison, we also studied mole-voles and dwarf hamsters, two wild species of small rodents kept under simulated natural conditions. It was found that substitution of a LP vivarium for a conventional (non-LP) one doubled the lifespan of female outbred mice, just as SkQ1 did in a non-LP vivarium. SkQ1 prevented age-dependent disappearance of estrous cycles of outbred mice in both LP and non-LP vivaria. In the SPF vivarium in Moscow, male BALB/c mice had shorter lifespan than females, and SkQ1 increased their lifespan to the values of the females. In the females, SkQ1 retarded development of such trait of aging as heart mass increase. Male C57Bl/6 mice housed individually in the SPF vivarium in Stockholm lived as long as females. SkQ1 increased the male lifespan, the longevity of the females being unchanged. SkQ1 did not change food intake by these mice. Dwarf hamsters and mole-voles kept in outdoor cages or under simulated natural conditions lived longer if treated with SkQ1. The effect of SkQ1 on longevity of females is assumed to mainly be due to retardation of the age-linked decline of the immune system. For males under LP or SPF conditions, SkQ1 increased the lifespan, affecting also some other system(s) responsible for aging. PMID:22166671

  10. SkTech:俄罗斯工程教育的模式创新%SkTech: An Innovative Model of Engineering Education in Russia

    Institute of Scientific and Technical Information of China (English)

    孔寒冰; 吴婧姗; 李文

    2012-01-01

    The Skolkovo Institute of Science and Technology(SkTech) is a new Russian research university in an international context built in Skolkovo recently.With the participation and support of MIT,it provides graduate programs in science and engineering.This paper briefly describes profound context of SkTech,Innovation Entrepreneurship(IE) ideas and practice,novel organization and culture,and the unique development model as well.It is worthwhile to notice that SkTech innovation mode is a triple helix of integrating Research-Education-IE.This also represents the important essence of SkTech innovative model and its key role in Skolkovo innovation ecosystem.%俄罗斯的SkTech(斯科尔科沃理工学院)是在MIT的鼎力支持下新近创办的一所理工科研究生大学。本文简要介绍它的建校背景、先进的办学理念、新颖的组织架构与文化,以及独特的办学模式与实践。SkTech创新模式的精彩之处,在于它的"研究、教育、创业创新"三重螺旋集成的协同创新。这也是Sk-Tech将在斯科尔科沃创新生态系统中发挥关键作用的重要机制。

  11. An SK3 channel/nWASP/Abi-1 complex is involved in early neurogenesis.

    Directory of Open Access Journals (Sweden)

    Stefan Liebau

    Full Text Available BACKGROUND: The stabilization or regulated reorganization of the actin cytoskeleton is essential for cellular structure and function. Recently, we could show that the activation of the SK3-channel that represents the predominant SK-channel in neural stem cells, leads to a rapid local outgrowth of long filopodial processes. This observation indicates that the rearrangement of the actin based cytoskeleton via membrane bound SK3-channels might selectively be controlled in defined micro compartments of the cell. PRINCIPAL FINDINGS: We found two important proteins for cytoskeletal rearrangement, the Abelson interacting protein 1, Abi-1 and the neural Wiskott Aldrich Syndrome Protein, nWASP, to be in complex with SK3- channels in neural stem cells (NSCs. Moreover, this interaction is also found in spines and postsynaptic compartments of developing primary hippocampal neurons and regulates neurite outgrowth during early phases of differentiation. Overexpression of the proteins or pharmacological activation of SK3 channels induces obvious structural changes in NSCs and hippocampal neurons. In both neuronal cell systems SK3 channels and nWASP act synergistic by strongly inducing filopodial outgrowth while Abi-1 behaves antagonistic to its interaction partners. CONCLUSIONS: Our results give good evidence for a functional interplay of a trimeric complex that transforms incoming signals via SK3-channel activation into the local rearrangement of the cytoskeleton in early steps of neuronal differentiation involving nWASP and Abi-1 actin binding proteins.

  12. Pharmacokinetic/Toxicity Properties of the New Anti-Staphylococcal Lead Compound SK-03-92

    Directory of Open Access Journals (Sweden)

    William R. Schwan

    2015-11-01

    Full Text Available Because of the potential of a new anti-staphylococcal lead compound SK-03-92 as a topical antibiotic, a patch, or an orally active drug, we sought to determine its safety profile and oral bioavailability. SK-03-92 had a high IC50 (125 μg/mL in vitro against several mammalian cell lines, and mice injected intraperiteonally at the highest dose did not exhibit gross toxicity (e.g., altered gait, ungroomed, significant weight loss. Single dose (100 μg/g pharmacokinetic (PK analysis with formulated SK-03-92 showed that peak plasma concentration (1.64 μg/mL was achieved at 20–30 min. Oral relative bioavailability was 8%, and the drug half-life was 20–30 min, demonstrating that SK-03-92 is likely not a candidate for oral delivery. Five-day and two-week PK analyses demonstrated that SK-03-92 plasma levels were low. Multi-dose analysis showed no gross adverse effects to the mice and a SK-03-92 peak plasma concentration of 2.12 μg/mL with the presence of significant concentrations of breakdown products 15 min after dosing. SK-03-92 appeared to be very safe based on tissue culture and mouse gross toxicity determinations, but the peak plasma concentration suggests that a pro-drug of SK-03-92 or preparation of analogs of SK-03-92 with greater bioavailability and longer half-lives are warranted.

  13. Pharmacokinetics and tissue distribution of a novel PDE5 inhibitor,SK-3530, in rats

    Institute of Scientific and Technical Information of China (English)

    Hye-hyun YOO; Nam-sun KIM; Guang-jin Im; Dong-hyun KIM

    2007-01-01

    Aim: To investigate the pharmacokinetic profile and tissue distribution of a novel phosphodiesterase type 5 inhibitor, 5-ethyl-2-{5-[4-(2-hydroxy-ethyl)-piperazine-1-sulfonyl]-2-propoxy-phenyl }-7-propyl-3,5-dihydro-pyrrolo(3,2-d)pyrimidin-4-one (SK-3530), in rats after administration of the 14C-labeled compound. Methods:The pharmacokinetic parameters of SK-3530 were measured based on the total radioactivity and parent SK-3530 concentration in rat plasma after intravenous and oral administration. The tissue distribution of total radioactivity after a single oral administration of [14C]SK-3530 at a dose of 40 mg/kg was assayed. The plasma protein binding rates of SK-3530 were assessed by in vitro and ex vivo assay. Results: The total radioactivity profiles showed linear pharmacokinetics.The maximum plasma concentration and area under the curve of the parent SK3530 were 10%-20% compared to those of the total radioactivity. After the oral admin-istration of [14C]SK-3530, the radioactivity was widely distributed in all tissues,and the tissue/plasma ratio of the radioactivity 1 h after administration was calcu-lated as 0.5-2.6 with the exception of excretory organs. A relatively high penetra-tion was shown in the adrenal glands, liver, and lung. In vitro and ex vivo plasma protein binding assay by ultrafiltration showed a considerably high binding rate of more than 97%. Conclusion: SK-3530 was relatively well absorbed in the gas-trointestinal tract and showed linear pharmacokinetics over the investigated dose range. SK-3530 had low oral bioavailability due to a high, first-pass metabolism.

  14. File list: InP.Brs.10.AllAg.SK-BR-3 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Brs.10.AllAg.SK-BR-3 hg19 Input control Breast SK-BR-3 SRX750675,SRX155756,SRX4...69109 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Brs.10.AllAg.SK-BR-3.bed ...

  15. File list: InP.Brs.20.AllAg.SK-BR-3 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Brs.20.AllAg.SK-BR-3 hg19 Input control Breast SK-BR-3 SRX750675,SRX155756,SRX4...69109 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Brs.20.AllAg.SK-BR-3.bed ...

  16. File list: InP.Brs.05.AllAg.SK-BR-3 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Brs.05.AllAg.SK-BR-3 hg19 Input control Breast SK-BR-3 SRX750675,SRX155756,SRX4...69109 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Brs.05.AllAg.SK-BR-3.bed ...

  17. File list: InP.Brs.50.AllAg.SK-BR-3 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Brs.50.AllAg.SK-BR-3 hg19 Input control Breast SK-BR-3 SRX750675,SRX469109,SRX1...55756 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Brs.50.AllAg.SK-BR-3.bed ...

  18. Therapeutic doses of SkQ1 do not induce cytochromes P450 in rat liver.

    Science.gov (United States)

    Myasoedova, K N; Silachev, D N

    2014-10-01

    The effect of SkQ1 (a mitochondria-targeted antioxidant) on the level of cytochromes P450 in rat liver was studied. It was found that administration of therapeutic dose of SkQ1 with drinking water for 5 days (250 nmol/kg of body weight per day) did not alter the level of cytochromes P450. Under the same conditions, the standard dose of phenobarbital used for the induction of cytochromes P450 caused the 2.7-fold increase in the content of these cytochromes. We conclude that therapeutic doses of SkQ1 do not induce cytochromes P450 in rats.

  19. Expression of postsynaptic Ca2+-activated K+ (SK) channels at C-bouton synapses in mammalian lumbar α-motoneurons

    Science.gov (United States)

    Deardorff, Adam S; Romer, Shannon H; Deng, Zhihui; Bullinger, Katie L; Nardelli, Paul; Cope, Timothy C; Fyffe, Robert E W

    2013-01-01

    Small-conductance calcium-activated potassium (SK) channels mediate medium after-hyperpolarization (AHP) conductances in neurons throughout the central nervous system. However, the expression profile and subcellular localization of different SK channel isoforms in lumbar spinal α-motoneurons (α-MNs) is unknown. Using immunohistochemical labelling of rat, mouse and cat spinal cord, we reveal a differential and overlapping expression of SK2 and SK3 isoforms across specific types of α-MNs. In rodents, SK2 is expressed in all α-MNs, whereas SK3 is expressed preferentially in small-diameter α-MNs; in cats, SK3 is expressed in all α-MNs. Function-specific expression of SK3 was explored using post hoc immunostaining of electrophysiologically characterized rat α-MNs in vivo. These studies revealed strong relationships between SK3 expression and medium AHP properties. Motoneurons with SK3-immunoreactivity exhibit significantly longer AHP half-decay times (24.67 vs. 11.02 ms) and greater AHP amplitudes (3.27 vs. 1.56 mV) than MNs lacking SK3-immunoreactivity. We conclude that the differential expression of SK isoforms in rat and mouse spinal cord may contribute to the range of medium AHP durations across specific MN functional types and may be a molecular factor distinguishing between slow- and fast-type α-MNs in rodents. Furthermore, our results show that SK2- and SK3-immunoreactivity is enriched in distinct postsynaptic domains that contain Kv2.1 channel clusters associated with cholinergic C-boutons on the soma and proximal dendrites of α-MNs. We suggest that this remarkably specific subcellular membrane localization of SK channels is likely to represent the basis for a cholinergic mechanism for effective regulation of channel function and cell excitability. PMID:23129791

  20. Influence of source batch Sk dispersion on dosimetry for prostate cancer treatment with permanent implants

    DEFF Research Database (Denmark)

    Nunez-Cumplido, Eduardo; Perez-Calatayud, J; Casares-Magaz, O;

    2015-01-01

    PURPOSE: In clinical practice, specific air kerma strength (SK) value is used in treatment planning system (TPS) permanent brachytherapy implant calculations with (125)I and (103)Pd sources; in fact, commercial TPS provide only one SK input value for all implanted sources and the certified shipment...... is to examine the impact of SK dispersion on typical implant parameters that are used to evaluate the dose volume histogram (DVH) for both planning target volume (PTV) and organs at risk (OARs). METHODS: The authors have developed a new algorithm to compute dose distributions with different SK values for each...... source. Three different prostate volumes (20, 30, and 40 cm(3)) were considered and two typical commercial sources of different radionuclides were used. Using a conventional TPS, clinically accepted calculations were made for (125)I sources; for the palladium, typical implants were simulated. To assess...

  1. Control of sexuality by the sk1-encoded UDP-glycosyltransferase of maize.

    Science.gov (United States)

    Hayward, Andrew P; Moreno, Maria A; Howard, Thomas P; Hague, Joel; Nelson, Kimberly; Heffelfinger, Christopher; Romero, Sandra; Kausch, Albert P; Glauser, Gaétan; Acosta, Ivan F; Mottinger, John P; Dellaporta, Stephen L

    2016-10-01

    Sex determination in maize involves the production of staminate and pistillate florets from an initially bisexual floral meristem. Pistil elimination in staminate florets requires jasmonic acid signaling, and functional pistils are protected by the action of the silkless 1 (sk1) gene. The sk1 gene was identified and found to encode a previously uncharacterized family 1 uridine diphosphate glycosyltransferase that localized to the plant peroxisomes. Constitutive expression of an sk1 transgene protected all pistils in the plant, causing complete feminization, a gain-of-function phenotype that operates by blocking the accumulation of jasmonates. The segregation of an sk1 transgene was used to effectively control the production of pistillate and staminate inflorescences in maize plants.

  2. Characterization of CD4 and CD8 T cell responses in MuSK myasthenia gravis.

    Science.gov (United States)

    Yi, J S; Guidon, A; Sparks, S; Osborne, R; Juel, V C; Massey, J M; Sanders, D B; Weinhold, K J; Guptill, J T

    2014-08-01

    Muscle specific tyrosine kinase myasthenia gravis (MuSK MG) is a form of autoimmune MG that predominantly affects women and has unique clinical features, including prominent bulbar weakness, muscle atrophy, and excellent response to therapeutic plasma exchange. Patients with MuSK MG have predominantly IgG4 autoantibodies directed against MuSK on the postsynaptic muscle membrane. Lymphocyte functionality has not been reported in this condition. The goal of this study was to characterize T cell responses in patients with MuSK MG. Intracellular production of IFN-gamma, TNF-alpha, IL-2, IL-17, and IL-21 by CD4+ and CD8+ T cells was measured by polychromatic flow cytometry in peripheral blood samples from 11 Musk MG patients and 10 healthy controls. Only one MuSK MG patient was not receiving immunosuppressive therapy. Regulatory T cells (Treg) were also included in our analysis to determine if changes in T cell function were due to altered Treg frequencies. CD8+ T cells from MuSK MG patients had higher frequencies of polyfunctional responses than controls, and CD4+ T cells had higher IL-2, TNF-alpha, and IL-17. MuSK MG patients had a higher percentage of CD4+ T cells producing combinations of IFN-gamma/IL-2/TNF-gamma, TNF-alpha/IL-2, and IFN-gamma/TNF-alpha. Interestingly, Treg numbers and CD39 expression were not different from control values. MuSK MG patients had increased frequencies of Th1 and Th17 cytokines and were primed for polyfunctional proinflammatory responses that cannot be explained by a defect in CD39 expression or Treg number.

  3. Efficacy and Safety of Intacs SK in Moderate to Severe Keratoconus

    OpenAIRE

    El-Moatassem Kotb, Ahmed M.; Mohamed Hantera

    2013-01-01

    Purpose: To examine the safety and efficacy of Intacs SK for moderate to severe keratoconus (KC) using femtosecond technology. Materials and Methods: This prospective, non-comparative study included 37 contact lens intolerant keratoconic eyes (stage II-III) of 24 patients who underwent femtosecond-assisted Intacs SK implantation. Inclusion criteria were mean K readings 400 μm at the incision site, mesopic pupil

  4. The Analgesic Effect of the Mitochondria-Targeted Antioxidant SkQ1 in Pancreatic Inflammation

    Directory of Open Access Journals (Sweden)

    Maximilian Weniger

    2016-01-01

    Full Text Available Background. Chronic pancreatitis is one of the main risk factors for pancreatic cancer. In acute and chronic pancreatitis, oxidative stress is thought to play a key role. In this respect, the recently described mitochondria-targeted antioxidant SkQ1 effectively scavenges reactive oxygen species at nanomolar concentrations. Therefore, we aimed to characterize the influence of SkQ1 on tissue injury and pain in acute and chronic pancreatitis. Methods. Both acute and chronic pancreatitis were induced in C57BL/6 mice by intraperitoneal cerulein injections and treatment with SkQ1 was carried out by peroral applications. Hyperalgesia was assessed by behavioral observation and measurement of abdominal mechanical sensitivity. Blood serum and pancreatic tissue were harvested for analysis of lipase and histology. Results. SkQ1 did not influence pain, serological, or histological parameters of tissue injury in acute pancreatitis. In chronic pancreatitis, a highly significant reduction of pain-related behavior (p<0.0001 was evident, but histological grading revealed increased tissue injury in SkQ1-treated animals (p=0.03. Conclusion. After SkQ1 treatment, tissue injury is not ameliorated in acute pancreatitis and increased in chronic pancreatitis. However, we show an analgesic effect in chronic pancreatitis. Further studies will need to elucidate the risks and benefits of mitochondria-targeted antioxidants as an analgesic.

  5. Sustaining sleep spindles through enhanced SK2 channel activity consolidates sleep and elevates arousal threshold

    Science.gov (United States)

    Wimmer, Ralf D.; Astori, Simone; Bond, Chris T.; Rovó, Zita; Chatton, Jean-Yves; Adelman, John P.; Franken, Paul; Lüthi, Anita

    2013-01-01

    Sleep spindles are synchronized 11–15 Hz electroencephalographic (EEG) oscillations predominant during non-rapid-eye-movement sleep (NREMS). Rhythmic bursting in the reticular thalamic nucleus (nRt), arising from interplay between Cav3.3-type Ca2+ channels and Ca2+-dependent small-conductance-type 2 (SK2) K+ channels, underlies spindle generation. Correlative evidence indicates that spindles contribute to memory consolidation and protection against environmental noise in human NREMS. Here, we describe a molecular mechanism through which spindle power is selectively extended and we probed the actions of intensified spindling in the naturally sleeping mouse. Using electrophysiological recordings in acute brain slices from SK2 channel-over-expressing (SK2-OE) mice, we found that nRt bursting was potentiated and thalamic circuit oscillations were prolonged. Moreover, nRt cells showed greater resilience to transit from burst to tonic discharge in response to gradual depolarization, mimicking transitions out of NREMS. Compared to wild-type littermates, chronic EEG recordings of SK2-OE mice contained less fragmented NREMS, while the NREMS EEG power spectrum was conserved. Furthermore, EEG spindle activity was prolonged at NREMS exit. Finally, when exposed to white noise, SK2-OE mice needed stronger stimuli to arouse. Increased nRt bursting thus strengthens spindles and improves sleep quality through mechanisms independent of EEG slow-waves (< 4 Hz), suggesting SK2 signaling as a new potential therapeutic target for sleep disorders and for neuropsychiatric diseases accompanied by weakened sleep spindles. PMID:23035101

  6. Sustaining sleep spindles through enhanced SK2-channel activity consolidates sleep and elevates arousal threshold.

    Science.gov (United States)

    Wimmer, Ralf D; Astori, Simone; Bond, Chris T; Rovó, Zita; Chatton, Jean-Yves; Adelman, John P; Franken, Paul; Lüthi, Anita

    2012-10-03

    Sleep spindles are synchronized 11-15 Hz electroencephalographic (EEG) oscillations predominant during nonrapid-eye-movement sleep (NREMS). Rhythmic bursting in the reticular thalamic nucleus (nRt), arising from interplay between Ca(v)3.3-type Ca(2+) channels and Ca(2+)-dependent small-conductance-type 2 (SK2) K(+) channels, underlies spindle generation. Correlative evidence indicates that spindles contribute to memory consolidation and protection against environmental noise in human NREMS. Here, we describe a molecular mechanism through which spindle power is selectively extended and we probed the actions of intensified spindling in the naturally sleeping mouse. Using electrophysiological recordings in acute brain slices from SK2 channel-overexpressing (SK2-OE) mice, we found that nRt bursting was potentiated and thalamic circuit oscillations were prolonged. Moreover, nRt cells showed greater resilience to transit from burst to tonic discharge in response to gradual depolarization, mimicking transitions out of NREMS. Compared with wild-type littermates, chronic EEG recordings of SK2-OE mice contained less fragmented NREMS, while the NREMS EEG power spectrum was conserved. Furthermore, EEG spindle activity was prolonged at NREMS exit. Finally, when exposed to white noise, SK2-OE mice needed stronger stimuli to arouse. Increased nRt bursting thus strengthens spindles and improves sleep quality through mechanisms independent of EEG slow waves (<4 Hz), suggesting SK2 signaling as a new potential therapeutic target for sleep disorders and for neuropsychiatric diseases accompanied by weakened sleep spindles.

  7. Mitochondria-Targeted Antioxidant SkQ1 Improves Dermal Wound Healing in Genetically Diabetic Mice.

    Science.gov (United States)

    Demyanenko, Ilya A; Zakharova, Vlada V; Ilyinskaya, Olga P; Vasilieva, Tamara V; Fedorov, Artem V; Manskikh, Vasily N; Zinovkin, Roman A; Pletjushkina, Olga Yu; Chernyak, Boris V; Skulachev, Vladimir P; Popova, Ekaterina N

    2017-01-01

    Oxidative stress is widely recognized as an important factor in the delayed wound healing in diabetes. However, the role of mitochondrial reactive oxygen species in this process is unknown. It was assumed that mitochondrial reactive oxygen species are involved in many wound-healing processes in both diabetic humans and animals. We have applied the mitochondria-targeted antioxidant 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) to explore the role of mitochondrial reactive oxygen species in the wound healing of genetically diabetic mice. Healing of full-thickness excisional dermal wounds in diabetic C57BL/KsJ-db(-)/db(-) mice was significantly enhanced after long-term (12 weeks) administration of SkQ1. SkQ1 accelerated wound closure and stimulated epithelization, granulation tissue formation, and vascularization. On the 7th day after wounding, SkQ1 treatment increased the number of α-smooth muscle actin-positive cells (myofibroblasts), reduced the number of neutrophils, and increased macrophage infiltration. SkQ1 lowered lipid peroxidation level but did not change the level of the circulatory IL-6 and TNF. SkQ1 pretreatment also stimulated cell migration in a scratch-wound assay in vitro under hyperglycemic condition. Thus, a mitochondria-targeted antioxidant normalized both inflammatory and regenerative phases of wound healing in diabetic mice. Our results pointed to nearly all the major steps of wound healing as the target of excessive mitochondrial reactive oxygen species production in type II diabetes.

  8. The Jurassic of Denmark and Greenland: The Jurassic of Skåne, southern Sweden

    Directory of Open Access Journals (Sweden)

    Sivhed, Ulf

    2003-10-01

    Full Text Available In Sweden, Jurassic strata are restricted to Skåne and adjacent offshore areas. Jurassic sedimentary rocks predominantly comprise sandy to muddy siliciclastics, with subordinate coal beds andfew carbonate-rich beds. During Mesozoic times, block-faulting took place in the Sorgenfrei–Tornquist Zone, a tectonic zone which transects Skåne in a NW–SE direction. The Jurassic depositionalenvironments in Skåne were thus strongly influenced by uplift and downfaulting, and to some extent by volcanism. Consequently, the sedimentary record reveals evidence of numerous transgressions, regressions and breaks in sedimentation. Relative sea-level changes played a significant role in controlling the facies distribution, as deposition mainly took place in coastal plain to shallow shelf environments.The alluvial deposits in Skåne include floodplain palaeosols, autochthonous coals, overbank sandstones, and stream channel pebbly sandstones. Restricted marine strata comprise intertidalheteroliths with mixed freshwater and marine trace fossil assemblages, and intertidal delta distributary channel sandstones. Shallow marine sediments encompass subtidal and shoreface sandstoneswith herringbone structures, and bioturbated mudstones with tempestite sandstones. Offshore deposits typically comprise extensively bioturbated muddy sandstones.Floral remains, palaeopedology, clay mineralogy and arenite maturity indicate a warm and humid climate in Skåne throughout the Jurassic, possibly with slightly increasing aridity towards the end of the period. Most Jurassic strata in Skåne have been subjected to mild burial diagenesis, and the petroleum generative window has rarely been reached.

  9. UBE3A Regulates Synaptic Plasticity and Learning and Memory by Controlling SK2 Channel Endocytosis

    Directory of Open Access Journals (Sweden)

    Jiandong Sun

    2015-07-01

    Full Text Available Gated solely by activity-induced changes in intracellular calcium, small-conductance potassium channels (SKs are critical for a variety of functions in the CNS, from learning and memory to rhythmic activity and sleep. While there is a wealth of information on SK2 gating, kinetics, and Ca2+ sensitivity, little is known regarding the regulation of SK2 subcellular localization. We report here that synaptic SK2 levels are regulated by the E3 ubiquitin ligase UBE3A, whose deficiency results in Angelman syndrome and overexpression in increased risk of autistic spectrum disorder. UBE3A directly ubiquitinates SK2 in the C-terminal domain, which facilitates endocytosis. In UBE3A-deficient mice, increased postsynaptic SK2 levels result in decreased NMDA receptor activation, thereby impairing hippocampal long-term synaptic plasticity. Impairments in both synaptic plasticity and fear conditioning memory in UBE3A-deficient mice are significantly ameliorated by blocking SK2. These results elucidate a mechanism by which UBE3A directly influences cognitive function.

  10. Network excitability in a model of chronic temporal lobe epilepsy critically depends on SK channel-mediated AHP currents.

    Science.gov (United States)

    Schulz, Robert; Kirschstein, Timo; Brehme, Hannes; Porath, Katrin; Mikkat, Ulrike; Köhling, Rüdiger

    2012-01-01

    Hippocampal CA1 pyramidal neurons generate an after-hyperpolarization (AHP) whose medium component is thought to be generated by small-conductance Ca(2+)-activated K(+) channels (SK channels). Neuronal excitability is increased in epilepsy, and the AHP in turn is fundamentally involved in regulation of cellular excitability. We therefore investigated the involvement of the SK channel-mediated AHP in controlling cell and network excitability in the pilocarpine model epilepsy. Both acutely isolated CA1 pyramidal cells and isolated hippocampal slices were investigated in terms of the impact of SK channel-mediated AHP on hyperexcitability. Our findings show that pilocarpine-treated chronically epileptic rats exhibit significantly reduced SK channel-mediated hyperpolarizing outward current which was accompanied by a significant decrease in the somatic AHP. Paradoxically, inhibiting SK channels strongly exacerbated 0-Mg(2+)-induced epileptiform activity in slices from pilocarpine-treated animals, while having a significantly smaller effect in control tissue. This suggests that in chronically epileptic tissue, network excitability very critically depends on the remaining SK-channel mediated AHP. Additional real-time RT-PCR and semiquantitative Western blot experiments revealed that both the SK2 channel transcript and protein were significantly downregulated in the epileptic CA1 region. We conclude that SK2 channels are down-regulated in chronic epilepsy underlying the impaired SK channel function in CA1 pyramidal cells, and a further reduction of the remaining critical mass of SK channels results in an acute network decompensation.

  11. Genetic deficit of SK3 and IK1 channels disrupts the endothelium-derived hyperpolarizing factor vasodilator pathway and causes hypertension

    DEFF Research Database (Denmark)

    Brähler, Sebastian; Kaistha, Anuradha; Schmidt, Volker J;

    2009-01-01

    SK3 and IK1 in IK1(-/-)/SK3(T/T) mice was characterized by patch-clamp, membrane potential measurements, pressure myography, and intravital microscopy. Blood pressure was measured in conscious mice by telemetry. Combined IK1/SK3 deficiency in IK1(-/-)/SK3(T/T) (+doxycycline) mice abolished......-mediated vasodilation and lowered elevated blood pressure. The IK1-opener SKA-31 enhanced EDHF-mediated vasodilation and lowered blood pressure in SK3-deficient IK1(+/+)/SK3(T/T) (+doxycycline) mice to normotensive levels. CONCLUSIONS: Our study demonstrates that endothelial SK3 and IK1 channels have distinct stimulus...

  12. Is MuSK myasthenia gravis linked to IgG4-related disease?

    Science.gov (United States)

    Raibagkar, Pooja; Ferry, Judith A; Stone, John H

    2017-04-15

    Immunoglobulin (Ig) G4-related disease (IgG4-RD) is an immune-mediated inflammatory condition that affects a wide variety of sites, including the nervous system, where it can involve the meninges or the pituitary gland, and cause perineural mass lesions. A large subset of acetylcholine receptor antibody (Ab)-negative myasthenia gravis (MG) patients has muscle-specific tyrosine kinase (MuSK) Abs, generally of the IgG4 subclass. There has not been any association found between IgG4-RD and MuSK MG yet. We report the first case of MuSK MG associated with lymphadenopathy with histopathology consistent with IgG4-RD. A 54-year-old woman with MuSK MG developed eight compression fractures related to steroid therapy. Eighteen months after initial presentation she was found to have retroperitoneal lymphadenopathy with biopsy findings consistent with IgG4-RD. She was started on rituximab with clinical improvement and ability to taper immunomodulatory agents for the first time. Our case raises number of questions regarding a potential link between MuSK MG and IgG4-RD which may shed further light on the pathophysiology and management of these diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Comparison of Visual, Refractive and Topographic Keratometry Outcomes of Intacs and Intacs SK in Mild to Moderate Keratoconus Eyes

    OpenAIRE

    Abdulrahman Al Muammar

    2015-01-01

    Purpose: The purpose was to evaluate and compare the visual and refractive outcomes, topographic keratometry (K) and complications of Intacs and Intacs SK for mild to moderate keratoconus. Methods: In this retrospective study, all mild to moderate keratoconus eyes that underwent implantation of Intacs (Intacs group) or Intacs SK (Intacs SK group) with minimum follow-up of 12 months were included. Preoperative and postoperative uncorrected distance visual acuity (UDVA), corrected distance ...

  14. Experimental Evaluation Of A Herbal Cream (SK-AC On Acetylated Lanolin Alcohol-Induced ACNE In Rabbit

    Directory of Open Access Journals (Sweden)

    Mitra S K

    1998-01-01

    Full Text Available Experimental studies were conducted in four groups of rabbits using external ear canal for inducing comedogenesis and its correction by a herbal formulation, viz., SK-AC cream. The result brought out that the SK-AC cream restricted the comedogenesis induced by acetylated lanolin alcohol when compared with other defined groups. Microcomedo being the basic pathology of acne, the outcome of this experiment pointed out the usefulness of SK-AC cream for the treatment of acne.

  15. SkData: data sets and algorithm evaluation protocols in Python

    Science.gov (United States)

    Bergstra, James; Pinto, Nicolas; Cox, David D.

    2015-01-01

    Machine learning benchmark data sets come in all shapes and sizes, whereas classification algorithms assume sanitized input, such as (x, y) pairs with vector-valued input x and integer class label y. Researchers and practitioners know all too well how tedious it can be to get from the URL of a new data set to a NumPy ndarray suitable for e.g. pandas or sklearn. The SkData library handles that work for a growing number of benchmark data sets (small and large) so that one-off in-house scripts for downloading and parsing data sets can be replaced with library code that is reliable, community-tested, and documented. The SkData library also introduces an open-ended formalization of training and testing protocols that facilitates direct comparison with published research. This paper describes the usage and architecture of the SkData library.

  16. Mitochondria-Targeted Antioxidant SkQ1 Improves Dermal Wound Healing in Genetically Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Ilya A. Demyanenko

    2017-01-01

    Full Text Available Oxidative stress is widely recognized as an important factor in the delayed wound healing in diabetes. However, the role of mitochondrial reactive oxygen species in this process is unknown. It was assumed that mitochondrial reactive oxygen species are involved in many wound-healing processes in both diabetic humans and animals. We have applied the mitochondria-targeted antioxidant 10-(6′-plastoquinonyldecyltriphenylphosphonium (SkQ1 to explore the role of mitochondrial reactive oxygen species in the wound healing of genetically diabetic mice. Healing of full-thickness excisional dermal wounds in diabetic C57BL/KsJ-db−/db− mice was significantly enhanced after long-term (12 weeks administration of SkQ1. SkQ1 accelerated wound closure and stimulated epithelization, granulation tissue formation, and vascularization. On the 7th day after wounding, SkQ1 treatment increased the number of α-smooth muscle actin-positive cells (myofibroblasts, reduced the number of neutrophils, and increased macrophage infiltration. SkQ1 lowered lipid peroxidation level but did not change the level of the circulatory IL-6 and TNF. SkQ1 pretreatment also stimulated cell migration in a scratch-wound assay in vitro under hyperglycemic condition. Thus, a mitochondria-targeted antioxidant normalized both inflammatory and regenerative phases of wound healing in diabetic mice. Our results pointed to nearly all the major steps of wound healing as the target of excessive mitochondrial reactive oxygen species production in type II diabetes.

  17. Dexamethasone blocks the migration of the human neuroblastoma cell line SK-N-SH

    Directory of Open Access Journals (Sweden)

    L.A. Casulari

    2006-09-01

    Full Text Available Glucocorticoids (Gc influence the differentiation of neural crest-derived cells such as those composing sympathoadrenal tumors like pheochromocytomas, as well as neuroblastomas and gangliomas. In order to obtain further information on the effects of Gc on cells evolving from the neural crest, we have used the human neuroblastoma cell line SK-N-SH to analyze: 1 the presence and the binding characteristics of Gc receptors in these cells, 2 the effect of dexamethasone (Dex on the migration of SK-N-SH cells, and 3 the effect of Dex on the organization of the cytoskeleton of SK-N-SH cells. We show that: 1 receptors that bind [³H]-Dex with high affinity and high capacity (Kd of 9.6 nM, Bmax of 47 fmol/mg cytosolic protein, corresponding to 28,303 sites/cell are present in cytosolic preparations of SK-N-SH cells, and 2 treatment with Dex (in the range of 10 nM to 1 µM has an inhibitory effect (from 100% to 74 and 43%, respectively on the chemotaxis of SK-N-SH cells elicited by fetal bovine serum. This inhibition is completely reversed by the Gc receptor antagonist RU486 (1 µM, and 3 as demonstrated by fluorescent phalloidin-actin detection, the effect of Dex (100 nM on SK-N-SH cell migration is accompanied by modifications of the cytoskeleton organization that appear with stress fibers. These modifications did not take place in the presence of 1 µM RU486. The present data demonstrate for the first time that Dex affects the migration of neuroblastoma cells as well as their cytoskeleton organization by interacting with specific receptors. These findings provide new insights on the mechanism(s of action of Gc on cells originating in the neural crest.

  18. Dexamethasone blocks the migration of the human neuroblastoma cell line SK-N-SH

    Directory of Open Access Journals (Sweden)

    L.A. Casulari

    Full Text Available Glucocorticoids (Gc influence the differentiation of neural crest-derived cells such as those composing sympathoadrenal tumors like pheochromocytomas, as well as neuroblastomas and gangliomas. In order to obtain further information on the effects of Gc on cells evolving from the neural crest, we have used the human neuroblastoma cell line SK-N-SH to analyze: 1 the presence and the binding characteristics of Gc receptors in these cells, 2 the effect of dexamethasone (Dex on the migration of SK-N-SH cells, and 3 the effect of Dex on the organization of the cytoskeleton of SK-N-SH cells. We show that: 1 receptors that bind [³H]-Dex with high affinity and high capacity (Kd of 9.6 nM, Bmax of 47 fmol/mg cytosolic protein, corresponding to 28,303 sites/cell are present in cytosolic preparations of SK-N-SH cells, and 2 treatment with Dex (in the range of 10 nM to 1 µM has an inhibitory effect (from 100% to 74 and 43%, respectively on the chemotaxis of SK-N-SH cells elicited by fetal bovine serum. This inhibition is completely reversed by the Gc receptor antagonist RU486 (1 µM, and 3 as demonstrated by fluorescent phalloidin-actin detection, the effect of Dex (100 nM on SK-N-SH cell migration is accompanied by modifications of the cytoskeleton organization that appear with stress fibers. These modifications did not take place in the presence of 1 µM RU486. The present data demonstrate for the first time that Dex affects the migration of neuroblastoma cells as well as their cytoskeleton organization by interacting with specific receptors. These findings provide new insights on the mechanism(s of action of Gc on cells originating in the neural crest.

  19. In vitro probiotic properties of Lactobacillus fermentum SK5 isolated from vagina of a healthy woman.

    Science.gov (United States)

    Kaewnopparat, Sanae; Dangmanee, Nattakan; Kaewnopparat, Nattha; Srichana, Teerapol; Chulasiri, Malyn; Settharaksa, Sukanya

    2013-08-01

    A lactobacillus strain isolated from a vaginal tract of a healthy woman was examined in vitro for its probiotic potential. This strain, identified as Lactobacillus fermentum SK5, was able to survive at pH 3-4 and 0.1-0.2% bile, and unaffected by pepsin (3 g l(-1)) and pancreatin (1 g l(-1)), but was susceptible to all tested antibiotics except metronidazole. L. fermentum SK5 had an antimicrobial potential against gastrointestinal pathogenic Escherichia coli and vaginal pathogenic Gardnerella vaginalis. The effective substance was suspected to be a bacteriocin-like compound with a molecular weight of more than 10 kDa, but hydrogen peroxide was also detected. Further studies revealed that L. fermentum SK5 had good autoaggregation characteristic and a high surface hydrophobicity that enhanced its adhesion ability to epithelial cells and for biofilm formation. This lactobacillus showed coaggregation with E. coli and G. vaginalis to affect their adhesion and colonization. The adhesion of L. fermentum SK5 to HeLa, HT-29 and Caco-2 cells and its inhibition of E. coli and G. vaginalis adherence to these cells were demonstrated. These incidences provided evidence of the possible colonization of L. fermentum SK5 that would prevent binding and growth of E. coli and G. vaginalis onto intestinal and vaginal epithelial cells. On the basis of the ability of L. fermentum SK5 to inhibit pathogenic microorganisms through coaggregation and antimicrobial substances, it is likely that this lactobacillus strain could be a potential probiotic candidate for beneficial use in protecting against gastrointestinal and vaginal microbial infections. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Anti-MuSK-Positive Myasthenia Gravis in a Patient with Parkinsonism and Cognitive Impairment

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    S. Lanfranconi

    2011-01-01

    Full Text Available Muscle-specific tyrosine kinase- (MuSK- antibodies-positive Myasthenia Gravis accounts for about one third of Seronegative Myasthenia Gravis and is clinically characterized by early onset of prominent bulbar, neck, shoulder girdle, and respiratory weakness. The response to medical therapy is generally poor. Here we report a case of late-onset MuSK-antibodies-positive Myasthenia Gravis presenting with signs of cognitive impairment and parkinsonism in addition to bulbar involvement and external ophthalmoplegia. The pattern of involvement of both peripheral and central nervous system dysfunction might suggest a common pathogenic mechanism, involving impaired cholinergic transmission.

  1. Cloning and characterization of SK2 channel from chicken short hair cells.

    Science.gov (United States)

    Matthews, T M; Duncan, R K; Zidanic, M; Michael, T H; Fuchs, P A

    2005-06-01

    In the inner ear of birds, as in mammals, reptiles and amphibians, acetylcholine released from efferent neurons inhibits hair cells via activation of an apamin-sensitive, calcium-dependent potassium current. The particular potassium channel involved in avian hair cell inhibition is unknown. In this study, we cloned a small-conductance, calcium-sensitive potassium channel (gSK2) from a chicken cochlear library. Using RT-PCR, we demonstrated the presence of gSK2 mRNA in cochlear hair cells. Electrophysiological studies on transfected HEK293 cells showed that gSK2 channels have a conductance of approximately 16 pS and a half-maximal calcium activation concentration of 0.74+/-0.17 microM. The expressed channels were blocked by apamin (IC(50)=73.3+/-5.0 pM) and d-tubocurarine (IC(50)=7.6+/-1.0 microM), but were insensitive to charybdotoxin. These characteristics are consistent with those reported for acetylcholine-induced potassium currents of isolated chicken hair cells, suggesting that gSK2 is involved in efferent inhibition of chicken inner ear. These findings imply that the molecular mechanisms of inhibition are conserved in hair cells of all vertebrates.

  2. New metabolic activity of the nonsulfated sulfakinin Zopat-SK-1 in the insect fat body.

    Science.gov (United States)

    Slocinska, Malgorzata; Marciniak, Pawel; Jarmuszkiewicz, Wieslawa; Rosinski, Grzegorz

    2015-06-01

    Insect sulfakinins are multifunctional neuropeptides homologous to vertebrate gastrin/cholecystokin (CCK) neuropeptide hormones. We investigated the action of the nonsulfated sulfakinin Zopat-SK-1 (pETSDDYGHLRFa) on the levels of chosen metabolites in the Zophobas atratus beetle fat body. Samples of fat body were collected 2h and 24h after hormone injection. The administration of 20pmol of Zopat-SK-1 to feeding larvae significantly increased concentrations of lipids and proteins and decreased the content of glycogen in fat body tissue in the 24h experimental group. In contrast, the only increase in total lipid concentration in prepupal fat bodies was observed 24h after Zopat-SK-1 treatment. Simultaneously, changes in the quality and quantity of free sugars in the hemolymph were measured. In larval hemolymph, a marked increase in free sugar concentration and a decrease in glucose content were observed 24h and 2h after Zopat-SK-1 application, respectively. No changes in the prepupal stage were observed. For the first time we show potent metabolic activity of sulfakinin in the fat body tissue of an insect. Our findings imply a physiological function of the nonsulfated form of sulfakinin in energy storage and release processes in fat body tissue of larvae and prepupae was indicated. We suggest a role for sulfakinin signaling in the regulation of energy metabolism in insect tissues. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. 7SK small nuclear RNA inhibits cancer cell proliferation through apoptosis induction.

    Science.gov (United States)

    Keramati, Farid; Seyedjafari, Ehsan; Fallah, Parviz; Soleimani, Masoud; Ghanbarian, Hossein

    2015-04-01

    7SK small nuclear RNA (snRNA) is a 331-333-bp non-coding RNA, which recruits HEXIM 1/2 protein to inhibit positive elongation factor b (P-TEFb) activity. P-TEFb is an essential factor in alleviating promoter-proximal paused RNA polymerase II (Pol II) and initiating the productive elongation phase of gene transcription. Without this protein, Pol II will remain in its hypophosphorylated state, and no transcription occurs. In this study, we inhibited P-TEFb activity by over-expressing 7SK snRNA in human embryonic kidney (HEK) 293T cancer cell line. This inhibition led to a significant decrease in cell viability, which can be due to the transcription inhibition. Moreover, 7SK snRNA over-expression promoted apoptosis in cancerous cells. Our results suggest 7SK snRNA as a potential endogenous anti-cancer agent, and to the best of our knowledge, this is the first study that uses a long non-coding RNA's over-expression against cancer cell growth and proliferation.

  4. SK channels mediate NADPH oxidase-independent reactive oxygen species production and apoptosis in granulocytes.

    Science.gov (United States)

    Fay, Alex J; Qian, Xiang; Jan, Yuh Nung; Jan, Lily Yeh

    2006-11-14

    Neutrophils are immune cells that bind to, engulf, and destroy bacterial and fungal pathogens in infected tissue, and their clearance by apoptosis is essential for the resolution of inflammation. Killing involves both oxidative and nonoxidative processes, the oxidative pathway requiring electrogenic production of superoxide by the membrane-bound NADPH oxidase complex. A variety of stimuli, from bacterial chemotactic peptides to complement- or IgG-opsonized microbes, can induce the production of reactive oxygen species (ROS) by neutrophils, presumably by means of NADPH oxidase. We report here that 1-ethyl-2-benzimidazolinone (1-EBIO), an activator of Ca2+-activated potassium channels of small conductance (SK) and intermediate conductance (IK), causes production of superoxide and hydrogen peroxide by neutrophils and granulocyte-differentiated PLB-985 cells. This response can be partially inhibited by the SK blocker apamin, which inhibits a Ca2+-activated K+ current in these cells. Analysis of RNA transcripts indicates that channels encoded by the SK3 gene carry this current. The effects of 1-EBIO and apamin are independent of the NADPH oxidase pathway, as demonstrated by using a PLB-985 cell line lacking the gp91phox subunit. Rather, 1-EBIO and apamin modulate mitochondrial ROS production. Consistent with the enhanced ROS production and K+ efflux mediated by 1-EBIO, we found that this SK opener increased apoptosis of PLB-985 cells. Together, these findings suggest a previously uncharacterized mechanism for the regulation of neutrophil ROS production and programmed cell death.

  5. Hvem sidder dér bag skærmen?

    DEFF Research Database (Denmark)

    Werlauff, Erik; Schaumburg-Müller, Peer

    2009-01-01

    Med udgangspunkt i nutidens daytrader, der sidder ´"bag skærmen" og foretager talrige daglige køb og salg af børsnoterede aktier mv., analyseres det i artiklen, hvornår en sådan lovlig daytrading udarter til strafbar kursmanipulation. Nogle daytradere har ment, at hvis en ikke-professionel invest...

  6. Bifurcation diagram globally underpinning neuronal firing behaviors modified by SK conductance

    Science.gov (United States)

    Chen, Meng-Jiao; Ling, Heng-Li; Liu, Yi-Hui; Qu, Shi-Xian; Ren, Wei

    2014-02-01

    Neurons in the brain utilize various firing trains to encode the input signals they have received. Firing behavior of one single neuron is thoroughly explained by using a bifurcation diagram from polarized resting to firing, and then to depolarized resting. This explanation provides an important theoretical principle for understanding neuronal biophysical behaviors. This paper reports the novel experimental and modeling results of the modification of such a bifurcation diagram by adjusting small conductance potassium (SK) channel. In experiments, changes in excitability and depolarization block in nucleus accumbens shell and medium-spiny projection neurons are explored by increasing the intensity of injected current and blocking the SK channels by apamin. A shift of bifurcation points is observed. Then, a Hodgkin—Huxley type model including the main electrophysiological processes of such neurons is developed to reproduce the experimental results. The reduction of SK channel conductance also shifts the bifurcations, which is in consistence with experiment. A global bifurcation paradigm of this shift is obtained by adjusting two parameters, intensity of injected current and SK channel conductance. This work reveals the dynamics underpinning modulation of neuronal firing behaviors by biologically important ionic conductance. The results indicate that small ionic conductance other than that responsible for spike generation can modify bifurcation points and shift the bifurcation diagram and, thus, change neuronal excitability and adaptation.

  7. Control of Ca2+ Influx and Calmodulin Activation by SK-Channels in Dendritic Spines.

    Directory of Open Access Journals (Sweden)

    Thom Griffith

    2016-05-01

    Full Text Available The key trigger for Hebbian synaptic plasticity is influx of Ca2+ into postsynaptic dendritic spines. The magnitude of [Ca2+] increase caused by NMDA-receptor (NMDAR and voltage-gated Ca2+ -channel (VGCC activation is thought to determine both the amplitude and direction of synaptic plasticity by differential activation of Ca2+ -sensitive enzymes such as calmodulin. Ca2+ influx is negatively regulated by Ca2+ -activated K+ channels (SK-channels which are in turn inhibited by neuromodulators such as acetylcholine. However, the precise mechanisms by which SK-channels control the induction of synaptic plasticity remain unclear. Using a 3-dimensional model of Ca2+ and calmodulin dynamics within an idealised, but biophysically-plausible, dendritic spine, we show that SK-channels regulate calmodulin activation specifically during neuron-firing patterns associated with induction of spike timing-dependent plasticity. SK-channel activation and the subsequent reduction in Ca2+ influx through NMDARs and L-type VGCCs results in an order of magnitude decrease in calmodulin (CaM activation, providing a mechanism for the effective gating of synaptic plasticity induction. This provides a common mechanism for the regulation of synaptic plasticity by neuromodulators.

  8. Tee Toompealt Pääskülani ja Tallinna saras / Tõnu Raid

    Index Scriptorium Estoniae

    Raid, Tõnu, 1939-

    2009-01-01

    Keskaegses Tallinnas puudus maamõõtja. Esimese säilinud Tallinna linnaplaani valmistas 1680. aastal Tallinna gümnaasiumi professor Heinrich Julius Woltemate. 1807. aastal loodi linna maamõõtja koht. Kõrgepea nuki asukohast. Pärnu maanteest esimestel kaartidel. Pärnu maantee üleviimisest. Muinasaja teest Pääskülast Tallinna.

  9. SK2 channel modulation contributes to compartment-specific dendritic plasticity in cerebellar Purkinje cells.

    Science.gov (United States)

    Ohtsuki, Gen; Piochon, Claire; Adelman, John P; Hansel, Christian

    2012-07-12

    Small-conductance Ca(2+)-activated K(+) channels (SK channels) modulate excitability and curtail excitatory postsynaptic potentials (EPSPs) in neuronal dendrites. Here, we demonstrate long-lasting plasticity of intrinsic excitability (IE) in dendrites that results from changes in the gain of this regulatory mechanism. Using dendritic patch-clamp recordings from rat cerebellar Purkinje cells, we find that somatic depolarization or parallel fiber (PF) burst stimulation induce long-term amplification of synaptic responses to climbing fiber (CF) or PF stimulation and enhance the amplitude of passively propagated sodium spikes. Dendritic plasticity is mimicked and occluded by the SK channel blocker apamin and is absent in Purkinje cells from SK2 null mice. Triple-patch recordings from two dendritic sites and the soma and confocal calcium imaging studies show that local stimulation limits dendritic plasticity to the activated compartment of the dendrite. This plasticity mechanism allows Purkinje cells to adjust the SK2-mediated control of dendritic excitability in an activity-dependent manner.

  10. Acquired resistance to oxaliplatin is not directly associated with increased resistance to DNA damage in SK-N-ASrOXALI4000, a newly established oxaliplatin-resistant sub-line of the neuroblastoma cell line SK-N-AS

    Science.gov (United States)

    Saintas, Emily; Abrahams, Liam; Ahmad, Gulshan T.; Ajakaiye, Anu-Oluwa M.; AlHumaidi, Abdulaziz S. H. A. M.; Ashmore-Harris, Candice; Clark, Iain; Dura, Usha K.; Fixmer, Carine N.; Ike-Morris, Chinedu; Mato Prado, Mireia; Mccullough, Danielle; Mishra, Shishir; Schöler, Katia M. U.; Timur, Husne; Williamson, Maxwell D. C.; Alatsatianos, Markella; Bahsoun, Basma; Blackburn, Edith; Hogwood, Catherine E.; Lithgow, Pamela E.; Rowe, Michelle; Yiangou, Lyto; Rothweiler, Florian; Cinatl, Jindrich; Zehner, Richard; Baines, Anthony J.; Garrett, Michelle D.; Gourlay, Campbell W.; Griffin, Darren K.; Gullick, William J.; Hargreaves, Emma; Howard, Mark J.; Lloyd, Daniel R.; Rossman, Jeremy S.; Smales, C. Mark; Tsaousis, Anastasios D.; von der Haar, Tobias; Wass, Mark N.

    2017-01-01

    The formation of acquired drug resistance is a major reason for the failure of anti-cancer therapies after initial response. Here, we introduce a novel model of acquired oxaliplatin resistance, a sub-line of the non-MYCN-amplified neuroblastoma cell line SK-N-AS that was adapted to growth in the presence of 4000 ng/mL oxaliplatin (SK-N-ASrOXALI4000). SK-N-ASrOXALI4000 cells displayed enhanced chromosomal aberrations compared to SK-N-AS, as indicated by 24-chromosome fluorescence in situ hybridisation. Moreover, SK-N-ASrOXALI4000 cells were resistant not only to oxaliplatin but also to the two other commonly used anti-cancer platinum agents cisplatin and carboplatin. SK-N-ASrOXALI4000 cells exhibited a stable resistance phenotype that was not affected by culturing the cells for 10 weeks in the absence of oxaliplatin. Interestingly, SK-N-ASrOXALI4000 cells showed no cross resistance to gemcitabine and increased sensitivity to doxorubicin and UVC radiation, alternative treatments that like platinum drugs target DNA integrity. Notably, UVC-induced DNA damage is thought to be predominantly repaired by nucleotide excision repair and nucleotide excision repair has been described as the main oxaliplatin-induced DNA damage repair system. SK-N-ASrOXALI4000 cells were also more sensitive to lysis by influenza A virus, a candidate for oncolytic therapy, than SK-N-AS cells. In conclusion, we introduce a novel oxaliplatin resistance model. The oxaliplatin resistance mechanisms in SK-N-ASrOXALI4000 cells appear to be complex and not to directly depend on enhanced DNA repair capacity. Models of oxaliplatin resistance are of particular relevance since research on platinum drugs has so far predominantly focused on cisplatin and carboplatin. PMID:28192521

  11. Survivin selective inhibitor YM155 induce apoptosis in SK-NEP-1 Wilms tumor cells

    Directory of Open Access Journals (Sweden)

    Tao Yan-Fang

    2012-12-01

    Full Text Available Abstract Background Survivin, a member of the family of inhibitor of apoptosis proteins, functions as a key regulator of mitosis and programmed cell death. YM155, a novel molecular targeted agent, suppresses survivin, which is overexpressed in many tumor types. The aim of this study was to determine the antitumor activity of YM155 in SK-NEP-1 cells. Methods SK-NEP-1 cell growth in vitro and in vivo was assessed by MTT and nude mice experiments. Annexin V/propidium iodide staining followed by flow cytometric analysis was used to detect apoptosis in cell culture. Then gene expression profile of tumor cells treated with YM155 was analyzed with real-time PCR arrays. We then analyzed the expression data with MEV (Multi Experiment View cluster software. Datasets representing genes with altered expression profile derived from cluster analyses were imported into the Ingenuity Pathway Analysis tool. Results YM155 treatment resulted in inhibition of cell proliferation of SK-NEP-1cells in a dose-dependent manner. Annexin V assay, cell cycle, and activation of caspase-3 demonstrates that YM155 induced apoptosis in SK-NEP-1 cells. YM155 significantly inhibited growth of SK-NEP-1 xenografts (YM155 5 mg/kg: 1.45 ± 0.77 cm3; YM155 10 mg/kg: 0.95 ± 0.55 cm3 compared to DMSO group (DMSO: 3.70 ± 2.4 cm3 or PBS group cells (PBS: 3.78 ± 2.20 cm3, ANOVA P Conclusions The present study demonstrates that YM155 treatment resulted in apoptosis and inhibition of cell proliferation of SK-NEP-1cells. YM155 had significant role and little side effect in the treatment of SK-NEP-1 xenograft tumors. Real-time PCR array analysis firstly showed expression profile of genes dyes-regulated after YM155 treatment. IPA analysis also represents new molecule mechanism of YM155 treatment, such as NR3C1 and dexamethasone may be new target of YM155. And our results may provide new clues of molecular mechanism of apoptosis induced by YM155.

  12. Skórna postać leiszmaniozy u pacjenta powracającego z Maroka

    Directory of Open Access Journals (Sweden)

    Aleksander Garlicki

    2010-09-01

    Full Text Available Wprowadzenie: Leiszmanioza jest tropikalną chorobą pasożytniczą,wywołaną przez pierwotniaki z rodzaju Leishmania. RezerwuaremLeishmania są ludzie i zwierzęta, a wektorem przenoszącym pasożytakomary z rodzaju Phlebotomus i Lutzomyia. Wyróżnia się trzy postaciechoroby: skórną, śluzówkowo-skórną i trzewną. Cel pracy: Zwrócenie uwagi na narastający problem zawlekaniachorób z krajów tropikalnych i trudności w rozpoznaniu skórnej lei szmaniozy. Opis przypadku: Pacjent, lat 29, został przyjęty do Kliniki z powoduowrzodzenia II palca stopy lewej po powrocie z 16-dniowego pobytuw Maroku. Początkowo był diagnozowany w miejscu zamieszkania,gdzie wykluczono leiszmaniozę, opierając się na negatywnych wynikachbadań zeskrobin skórnych i testów serologicznych. Po przyjęciudo Kliniki pobrano wycinek ze zmiany skórnej palca do badania histopatologicznego,w którym stwierdzono zmiany sugerujące tę chorobę.Do leczenia włączono ketokonazol na 4 tygodnie, uzyskując niewielkąpoprawę. Po tej terapii obserwowano stałą, choć wolną, poprawę miejscowąi po kolejnych 3 miesiącach doszło do całkowitego wygojeniazmian skórnych. Wnioski: W procesie diagnostycznym skórnej leiszmaniozy należyuwzględnić ocenę histopatologiczną wycinka ze zmiany. W związkuz coraz częstszymi wyjazdami do stref występowania leiszmaniozynależy oczekiwać zwiększenia liczby przypadków tej choroby w Polsce.

  13. THE PROBLEM OF COMMON SLAVIC OPPOSITION X ~ SK ~ ŠČ

    Directory of Open Access Journals (Sweden)

    A. K. Shaposhnikov

    2015-01-01

    Full Text Available This article deals with Common Slavic rows of lexical oppositions with x ~ sk ~ šč, going back to primordial Indo-European sound clusters *sk or *ks, and presents an attempt at establishing laws and rules of their occurrence. There is one more Indo-European language, namely Albanian, in which there was a similar regular transition of etymological *sk, *ks into *h in initial, intervocal and final positions in the words. All examples of similar opposition known nowadays from ESSJA and other accessible publications are presented for further consideration of the similar phenomena. About 160 examples of different degrees of reliability  are submitted. The author deduces some rules on the basis of comparisons: 1 etymological initial *skregularly passed into *xbefore back vowels. Reconstruction of forms with s mobile is an anachronism. 2 etymological initial *skhas regularly changed into *ščbefore front vowels. 3 Etymological initial *skwas kept only after a prefix *ob-. 4 It is possible to explain preservation of etymological initial *skin some cases by a loss of a prefixal morpheme: *skъrbь  from *obskъrbь.  The mechanism of mutation seems to be as follows: skhas changed into ks(this stage of development: Sanskrit kṣoda  and Greek , and then by the notorious rule of RUKI kshas changed into khand later into x-. The etymological confluence skbefore a back vowel is kept only after prefix *ob(*obskalъ, *obskǫděti, *obskomina. Regular opposition initial x-: initial  šč-, can never  be sk-: šč-, therefore ščel’, ščyolka  correlate with oskal but skala,  skol  < *sъkala, *sъkolъ. In this case we have an etymological opposition *xo-: *sъ-ko-.

  14. Disease specific enrichment of circulating let-7 family microRNA in MuSK+ myasthenia gravis.

    Science.gov (United States)

    Punga, Tanel; Bartoccioni, Emanuela; Lewandowska, Marta; Damato, Valentina; Evoli, Amelia; Punga, Anna Rostedt

    2016-03-15

    Myasthenia gravis (MG) patients with antibodies against the muscle specific tyrosine kinase (MuSK+) have predominantly involvement of cranio-bulbar muscles and do not display thymus pathology, as do acetylcholine receptor antibody seropositive (AChR+) MG patients. In search of novel biomarkers for MuSK+ MG, we evaluated circulating serum microRNAs. Four analyzed microRNAs were specifically elevated in MuSK+ MG patient serum samples: let-7a-5p, let-7f-5p, miR-151a-3p and miR-423-5p. The circulating microRNA profile in MuSK+ MG differs from the profile previously observed in the serum of AChR+ MG, thus indicating the etiological difference between these two entities. We propose that the identified microRNAs could serve as potential serum biomarkers for MuSK+ MG.

  15. α-actinin2增加SK2通道在HEK293膜蛋白的表达%α-Actinin 2 increases membrane protein expression of SK2 channel in HEK293 cell

    Institute of Scientific and Technical Information of China (English)

    李涛; 陈桂兰; 黄文俊; 毛亮; 李畅; 杨艳; 曾晓荣

    2014-01-01

    目的:证实α-Actinin 2与小电导钙激活钾通道(Small Conductance Ca2+-activated K+Channels, SK)的共同表达增加SK2在HEK293细胞膜上的表达。方法:HEK293细胞用RPMI 1640培养基培养。将HEK293细胞分为两组,对照组细胞转染pIRES-SK2质粒,实验组细胞共转染pIRES-SK2和pcDNA3-α-actinin2质粒。免疫荧光共聚焦显微镜和蛋白印迹技术检测SK2通道蛋白在HEK293细胞膜上的表达。结果:免疫荧光共聚焦显微镜检测到转染pIRES-SK2质粒的HEK293细胞膜上有SK2通道蛋白的表达。蛋白印迹技术显示实验组蛋白条带亮度明显高于对照组。结论:α-Actinin 2能增加SK2在HEK293细胞膜上的表达。%Objective:To confirm whether the protein expression of SK2 channel in HEK293 cell membrane is increased by the co-expression of α-Actinin2. Methods:HEK293 cells were cultured and randomly divided into control group, transfected with plasmid pIRES-SK2,and experimental group,transfected with plasmid pIRES-SK2 plus pcDNA3-α-Actinin2. Immunofluorescence confocal microscopy and western-blotting were used to test the membrane protein expression of SK2 channel in HEK293 cell. Results: SK2 channel protein was detected in the membrane of HEK293 by immunofluorescence confocal microscopy ,and he protein expression level in the experimental group was much higher than that in the control group. Conclusion:α-Actinin2 can increase SK2 channel membrane protein expression in HEK293 cell.

  16. Magmatic evolution of the Early Pliocene Etrüsk stratovolcano, Eastern Anatolian Collision Zone, Turkey

    Science.gov (United States)

    Oyan, Vural; Keskin, Mehmet; Lebedev, Vladimir A.; Chugaev, Andrey V.; Sharkov, Evgenii V.

    2016-07-01

    The Pliocene Etrüsk stratovolcano, located in the northeast of Lake Van (Eastern Anatolia; Turkey), is one of the important volcanic centres in the Eastern Anatolian collision zone. Mt. Etrüsk overlies a widespread volcanic plateau, consisting of basaltic and hawaiitic lavas formed by fissure eruptions between 4.9-4.5 Ma. These basic lavas contain a phenocryst phase consisting of olivine, plagioclase and clinopyroxene. Trace element ratio diagrams imply that these basic magmas were generated from a mantle that contained a clear subduction component that is related to the subducted sediments rather than fluids or altered oceanic crust. Results of the melting models on the basaltic plateau lavas indicate that there was a marked variation both in the mantle source mineralogy (i.e. the ratio of garnet peridotite to spinel peridotite in the source varies between 60/40% and 40/60%) and the degree of melting (i.e. F between 0.8-4%). This can be explained by a model in which magmas were generated by partial melting of both metasomatised lithospheric and deeper asthenospheric mantle sources in an extensional setting in response to the partial delamination of the lithospheric mantle of Eastern Anatolia and then mixed with each other during Pliocene times. Central eruptions that formed the Etrüsk volcano lasted ~ 600 kyr between 4.3-3.7 Ma during Zanclean times. The estimated depth of the Etrüsk magma chamber is ~ 9-12 km. The volcano erupted lavas with a rather narrow compositional range from latite to rhyolite, which are either transitional or mildly alkaline in character. The Etrüsk lavas contain plagioclase, clino- and orthopyroxene, biotite, K-feldspar and rarely, minor amounts of olivine and amphibole in the phenocryst phase. A composite chemo-stratigraphic section of the volcano and petrological models indicate that the evolved lavas of the Etrüsk volcano differentiated from a parental magma composition, which is similar to that of the most primitive plateau

  17. Isolation, characterization and anti-cancer activity of SK84, a novel glycine-rich antimicrobial peptide from Drosophila virilis.

    Science.gov (United States)

    Lu, Jie; Chen, Zheng-wang

    2010-01-01

    We report herein the isolation and characterization of a novel glycine-rich antimicrobial peptide purified from the larvae of Drosophila virilis. A range of chromatographic methods was used for isolation and its antibacterial activity against Bacillus subtilis was employed to screen for the most active fractions. The peptide, termed SK84 due to its N-terminal serine, C-terminal lysine and a total of 84 residues, was completed sequenced using RT-PCR cDNA cloning. SK84 contains a high level of glycine (15.5%) and a hexaglycine cluster motif in the N-terminal part. SK84 displayed antibacterial activity against the tested Gram-positive bacteria (B. subtilis, Bacillus thuringiensis and Staphylococcus aureus), but had no effect on Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli) and fungi (Saccharomyces cerevisiae, Candida albicans). SK84 had specific inhibitory effects on the proliferation of several cancer cell lines (Human leukemia THP-1, liver cancer HepG2, and breast cancer MCF-7 cells), but no hemolytic activity. The results from scanning electron microscopy observations revealed that SK84 killed THP-1 cells by destroying the cell membranes. Alignment results show that SK84 is a mature protein processed from the pseudoprotein GJ19999 from D. virilis, and is very similar to several pseudoproteins from different Drosophila species. Our results show that SK84 represents a novel glycine-rich peptide family in Drosophila species with antimicrobial and anti-cancer cell activities.

  18. Effect of cationic plastoquinone SkQ1 on electron transfer reactions in chloroplasts and mitochondria from pea seedlings.

    Science.gov (United States)

    Samuilov, V D; Kiselevsky, D B

    2015-04-01

    Plastoquinone bound with decyltriphenylphosphonium cation (SkQ1) penetrating through the membrane in nanomolar concentrations inhibited H2O2 generation in cells of epidermis of pea seedling leaves that was detected by the fluorescence of 2',7'-dichlorofluorescein. Photosynthetic electron transfer in chloroplasts isolated from pea leaves is suppressed by SkQ1 at micromolar concentrations: the electron transfer in chloroplasts under the action of photosystem II or I (with silicomolybdate or methyl viologen as electron acceptors, respectively) is more sensitive to SkQ1 than under the action of photosystem II + I (with ferricyanide or p-benzoquinone as electron acceptors). SkQ1 reduced by borohydride is oxidized by ferricyanide, p-benzoquinone, and, to a lesser extent, by silicomolybdate, but not by methyl viologen. SkQ1 is not effective as an electron acceptor supporting O2 evolution from water in illuminated chloroplasts. The data on suppression of photosynthetic O2 evolution or consumption show that SkQ1, similarly to phenazine methosulfate, causes conversion of the chloroplast redox-chain from non-cyclic electron transfer mode to the cyclic mode without O2 evolution. Oxidation of NADH or succinate in mitochondria isolated from pea roots is stimulated by SkQ1.

  19. Detection of Large Color Variation of Potentially Hazardous Asteroid (297274) 1996 SK

    CERN Document Server

    Lin, Chien-Hsien; Lin, Zhong-Yi; Yoshida, Fumi; Cheng, Yu-Chi

    2013-01-01

    Low-inclination Near-Earth Asteroid (297274) 1996 SK, which is also classified as a Potentially Hazardous Asteroid, has a highly eccentric orbit. It was studied by multi-wavelength photometry within the framework of an NEA color survey at the Lulin Observatory. We report here the finding of large color variation across the surface of (297274) 1996 SK within one asteroidal rotation period of $4.656\\pm0.122$ hours and classify it as a S-type asteroid according to its average colors of $B-V=0.767\\pm0.033$, $V-R=0.482\\pm0.021$, $V-I=0.801\\pm0.025$ and the corresponding relative reflectance spectrum. It might be indicative of differential space weathering effect or compositional inhomogeneity of the surface materials.

  20. Muscle-Specific Receptor Tyrosine Kinase (MuSK) Myasthenia Gravis.

    Science.gov (United States)

    Hurst, Rebecca L; Gooch, Clifton L

    2016-07-01

    Autoimmune myasthenia gravis (MG) is the prototypic, antibody-mediated neuromuscular disease and is characterized by a decrease in the number of functional acetylcholine receptors (AChR) within the muscle end plate zone of the neuromuscular junction (NMJ). Although the pathophysiology of AChR-mediated myasthenia gravis has been extensively studied over the last 40 years since its original description by Patrick and Lindstrom (Science 180:871-872, 1973), less is known about the much more recently described muscle-specific kinase (MuSK) antibody-mediated MG. MuSK-MG has features clinically distinct from Ach-R MG, as well as a different pattern of response to treatment and a unique immunopathogenesis.

  1. Astronomical journey to the Skåne district in Sweden

    Science.gov (United States)

    Nakamura, Tsuko

    2006-09-01

    In September of 2005, we had a chance to travel to the Skåe district of Sweden. This short paper briefly reports what we saw there, along with historical episodes relating to Lund Observatory, the medieval astronomical clock preserved at the Lund Cathedral, and the Hven island where Tycho Brahe constructed in the late 16th century the first modern astronomical observatory called Uraniborg.

  2. Skærmstilling og underplantning af rødgran i Gludsted Plantage

    DEFF Research Database (Denmark)

    Brunner, Andreas; Sørensen, Ib Holmgård; Skovsgaard, Jens Peter

    Konvertering af rødgran til mere stabile blandingsbevoksninger er blevet et vigtigt mål i mange skove og betragtes som regel som et led i indførelsen af naturnær skovdrift. Rapporten beskriver et forsøg med skærmstilling og underplantning af rødgran in Gludsted Plantage og første resultater fra f...

  3. EarthLink和SK Telecom的合资公司正式成立

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    美国网络服务提供商EarthLink和韩国最大的通信公司韩国电信(SK Telecom)合资成立的移动虚拟网络运营商(Mobile Virtual Network Operator,MVNO)已组建完成,这家名称为SK—EarthLink的合资企业即将进人美国的无线服务市场。

  4. Observation of the decay B¯s0→ψ(2SK+π−

    Directory of Open Access Journals (Sweden)

    R. Aaij

    2015-07-01

    Full Text Available The decay B¯s0→ψ(2SK+π− is observed using a data set corresponding to an integrated luminosity of 3.0 fb−1 collected by the LHCb experiment in pp collisions at centre-of-mass energies of 7 and 8 TeV. The branching fraction relative to the B0→ψ(2SK+π− decay mode is measured to beB(B¯s0→ψ(2SK+π−B(B0→ψ(2SK+π−=5.38±0.36(stat±0.22(syst±0.31(fs/fd%, where fs/fd indicates the uncertainty due to the ratio of probabilities for a b quark to hadronise into a Bs0 or B0 meson. Using an amplitude analysis, the fraction of decays proceeding via an intermediate K⁎(8920 meson is measured to be 0.645±0.049(stat±0.049(syst and its longitudinal polarisation fraction is 0.524±0.056(stat±0.029(syst. The relative branching fraction for this component is determined to be B(B¯s0→ψ(2SK⁎(8920B(B0→ψ(2SK⁎(8920=5.58±0.57(stat±0.40(syst±0.32(fs/fd%. In addition, the mass splitting between the Bs0 and B0 mesons is measured as M(Bs0−M(B0=87.45±0.44(stat±0.09(syst MeV/c2.

  5. MaSK: A visualization tool for teaching and research in computational chemistry

    Science.gov (United States)

    Podolyan, Yevgeniy; Leszczynski, Jerzy

    The number of researchers using computational chemistry tools is growing every year. There are multiple programs used for calculation of various molecular and electronic properties such as optimized geometry, energy, vibrational spectra, and so forth. Another set of programs is used for the visualization of these properties. However, such programs are either too complex for a beginner or too simple for an intermediate user for everyday use. Molecular Modeling and Simulation Kit (MaSK) is designed to fill this gap by presenting an easy-to-use intuitive interface to quantum chemical programs such as GAMESS and Gaussian with an array of advanced tools. The program can be used as a postprocessor to visualize calculated properties or as a preprocessor to prepare the input files for quantum chemical programs. In addition, some properties such as the surfaces of molecular orbitals, electron and spin densities, and molecular electrostatic potentials are actually calculated by MaSK. If MaSK is combined with PC GAMESS, the preparation of the input, running of the calculations, and the display of the results can all be done without leaving the program's interface.

  6. Structural basis of agrin-LRP4-MuSK signaling

    Energy Technology Data Exchange (ETDEWEB)

    Zong, Yinong; Zhang, Bin; Gu, Shenyan; Lee, Kwangkook; Zhou, Jie; Yao, Guorui; Figueiredo, Dwight; Perry, Kay; Mei, Lin; Jin, Rongsheng [Cornell; (GSHU); (Sanford-Burnham)

    2012-06-27

    Synapses are the fundamental units of neural circuits that enable complex behaviors. The neuromuscular junction (NMJ), a synapse formed between a motoneuron and a muscle fiber, has contributed greatly to understanding of the general principles of synaptogenesis as well as of neuromuscular disorders. NMJ formation requires neural agrin, a motoneuron-derived protein, which interacts with LRP4 (low-density lipoprotein receptor-related protein 4) to activate the receptor tyrosine kinase MuSK (muscle-specific kinase). However, little is known of how signals are transduced from agrin to MuSK. Here, we present the first crystal structure of an agrin-LRP4 complex, consisting of two agrin-LRP4 heterodimers. Formation of the initial binary complex requires the z8 loop that is specifically present in neuronal, but not muscle, agrin and that promotes the synergistic formation of the tetramer through two additional interfaces. We show that the tetrameric complex is essential for neuronal agrin-induced acetylcholine receptor (AChR) clustering. Collectively, these results provide new insight into the agrin-LRP4-MuSK signaling cascade and NMJ formation and represent a novel mechanism for activation of receptor tyrosine kinases.

  7. Antioxidative and neuroprotective activities of peanut sprout extracts against oxidative stress in SK-N-SH cells

    Directory of Open Access Journals (Sweden)

    Pranee Lertkaeo

    2017-01-01

    Conclusions: PSE has neuroprotective activities against oxidative stress in SK-N-SH cells induced by PQ, suggesting that PSE is a highly promising agent in the prevention of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.

  8. Outcomes of Single Segment Implantation of Conventional Intacs versus Intacs SK for Keratoconus

    Directory of Open Access Journals (Sweden)

    Mohammad Nasser Hashemian

    2014-01-01

    Full Text Available Purpose: To compare the visual, refractive, and keratometric outcomes of single-segment conventional and severe keratoconus (SK types of Intacs for correction of inferior keratoconus (KCN. Methods: A total number of 41 consecutive eyes of 23 patients with a diagnosis of inferior KCN underwent Intacs implantation. Eight eyes were excluded due to postoperative complications (4 eyes and loss to follow-up (4 eyes and finally 33 eyes underwent statistical analysis. Two groups were created according to Intacs type insertion; conventional group (17 eyes and SK groups (16 eyes. Intracorneal ring segments (ICRS implantation was indicated in keratoconic patients with contact-lens intolerance or reduced best spectacle-corrected visual acuity (BSCVA. Results: In the conventional group, mean uncorrected distance visual acuity (UCDVA improved from 0.45 ± 0.41 preoperatively to 0.69 ± 0.39 six months after surgery representing a gain of 2 Snellen lines, and in the SK group mean UCDVA changed from 0.40 ± 0.35 preoperatively to 0.58 ± 0.48 equivalent to two Snellen lines improvement 6 months after operation (P = 0.48. Mean preoperative BSCVA in the conventional group improved from 0.72 ± 0.41 to 0.86 ± 0.39 (2 lines improvement postoperatively and in the SK group improved from 0.71 ± 0.69 to 0.75 ± 0.45 (0.50 line improvement ( P = 0.29. Mean preoperative spherical equivalent (SE decreased from −4.86 ± 2.26 D to −3.57 ± 2.21 D (conventional group and from −4.20 ± 1.82 D to −3.60 ± 1.89 D (P = 0.34, mean astigmatism (AST decreased from −5.20 ± 2.07 D and −4.50 ± 2.26 D to −4.02 ± 2.57 D and − 3.18 ± 2.14 D in the conventional and SK groups, respectively (P = 0.68. Finally, mean K min decreased from 47.11 ± 2.51 D to 45.40 ± 3.30 D in the conventional group and from 45.05 ± 2.59 D to 44 ± 3.88 D in the SK group (P = 0.63 and mean K max was decreased from 52.82 ± 3.23 D to 50.52 ± 3.57 D and from 49.72 ± 3.17 D to 48.55 ± 4

  9. The Small-Conductance Ca2+-Activated Potassium Channel, Subtype SK3, in the Human Myometrium Is Downregulated in Early Stages of Pregnancy

    Directory of Open Access Journals (Sweden)

    M. Rahbek

    2013-01-01

    Full Text Available The human myometrium is mainly relaxed during pregnancy, but, up to term, contractions become more coordinated and forceful in order to initiate delivery. Small conductance Ca2+-activated K+ channels (SK channels in human myometrium have been shown to be downregulated in late pregnancy. The aim was to investigate the presence of SK2 and SK3 in the human myometrium from nonpregnant women, pregnant women at term, and pregnancies delivered preterm and, in addition, to characterize the time of downregulation of these channels. Using qRT-PCR, we observed significantly lower levels of mRNA for SK2 than for SK3 in the nonpregnant tissue. The mRNA levels of SK3 were significantly reduced in tissue from pregnancies at term and pregnancies resulting in preterm deliveries, whereas no downregulation for SK2 was observed. Western blotting confirmed the qRT-PCR results. Using immunohistochemical staining, both SK2 and SK3 were detected in endometrial glandular epithelium. We conclude that SK3 mRNA is downregulated early in pregnancy—at least among those that result in preterm deliveries. Furthermore, we find that SK channels are expressed not only in the uterine smooth muscle but also in the endometrial epithelium.

  10. The SK-N-AS human neuroblastoma cell line develops osteolytic bone metastases with increased angiogenesis and COX-2 expression

    Directory of Open Access Journals (Sweden)

    Takahiro Tsutsumimoto

    2014-11-01

    Full Text Available Neuroblastoma (NB, which arises from embryonic neural crest cells, is the most common extra-cranial solid tumor of childhood. Approximately half of NB patients manifest bone metastasis accompanied with bone pain, fractures and bone marrow failure, leading to disturbed quality of life and poor survival. To study the mechanism of bone metastasis of NB, we established an animal model in which intracardiac inoculation of the SK-N-AS human NB cells in nude mice developed osteolytic bone metastases with increased osteoclastogenesis. SK-N-AS cells induced the expression of receptor activator of NF-κB ligand and osteoclastogenesis in mouse bone marrow cells in the co-culture. SK-N-AS cells expressed COX-2 mRNA and produced substantial amounts of prostaglandin E2 (PGE2. In contrast, the SK-N-DZ and SK-N-FI human NB cells failed to develop bone metastases, induce osteoclastogenesis, express COX-2 mRNA and produce PGE2. Immunohistochemical examination of SK-N-AS bone metastasis and subcutaneous tumor showed strong expression of COX-2. The selective COX-2 inhibitor NS-398 inhibited PGE2 production and suppressed bone metastases with reduced osteoclastogenesis. NS-398 also inhibited subcutaneous SK-N-AS tumor development with decreased angiogenesis and vascular endothelial growth factor-A expression. Of interest, metastasis to the adrenal gland, a preferential site for NB development, was also diminished by NS-398. Our results suggest that COX2/PGE2 axis plays a critical role in the pathophysiology of osteolytic bone metastases and tumor development of the SK-NS-AS human NB. Inhibition of angiogenesis by suppressing COX-2/PGE2 may be an effective therapeutic approach for children with NB.

  11. Identification of Staphylococcus aureus Cellular Pathways Affected by the Stilbenoid Lead Drug SK-03-92 Using a Microarray.

    Science.gov (United States)

    Schwan, William R; Polanowski, Rebecca; Dunman, Paul M; Medina-Bielski, Sara; Lane, Michelle; Rott, Marc; Lipker, Lauren; Wescott, Amy; Monte, Aaron; Cook, James M; Baumann, Douglas D; Tiruveedhula, V V N Phani Babu; Witzigmann, Christopher M; Mikel, Cassandra; Rahman, Md Toufiqur

    2017-09-11

    The mechanism of action for a new lead stilbene compound coded SK-03-92 with bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) is unknown. To gain insight into the killing process, transcriptional profiling was performed on SK-03-92 treated vs. untreated S. aureus. Fourteen genes were upregulated and 38 genes downregulated by SK-03-92 treatment. Genes involved in sortase A production, protein metabolism, and transcriptional regulation were upregulated, whereas genes encoding transporters, purine synthesis proteins, and a putative two-component system (SACOL2360 (MW2284) and SACOL2361 (MW2285)) were downregulated by SK-03-92 treatment. Quantitative real-time polymerase chain reaction analyses validated upregulation of srtA and tdk as well as downregulation of the MW2284/MW2285 and purine biosynthesis genes in the drug-treated population. A quantitative real-time polymerase chain reaction analysis of MW2284 and MW2285 mutants compared to wild-type cells demonstrated that the srtA gene was upregulated by both putative two-component regulatory gene mutants compared to the wild-type strain. Using a transcription profiling technique, we have identified several cellular pathways regulated by SK-03-92 treatment, including a putative two-component system that may regulate srtA and other genes that could be tied to the SK-03-92 mechanism of action, biofilm formation, and drug persisters.

  12. Possible mechanism of leptin on human SK-BR-3 breast cancer cells%瘦素作用于人乳腺癌SK-BR-3细胞的可能机制

    Institute of Scientific and Technical Information of China (English)

    曾繁余; 刘菁; 黄颖; 骆耐香

    2013-01-01

    Objective To explore the possible mechanism of leptin on human SK-BR-3 breast cancer cells, cell proliferation and vascular endothelial growth factor ( VEGF) expression. Methods SK-BR-3 cells were treated with different concentration of leptin for different hours in vitro, respectively. Cell proliferation was evaluated by CCK-8 method. The expression of VEGF mRNA and protein were detected in SK-BR-3 by real time PCR and western blot, respectively. Results Cell proliferation of SK-BR-3 was in a dose and time-dependent way in vitro (P < 0. 05 ). The expression level of VEGF mRNA and protein were increased significantly in a leptin dose-dependent manner ( P < 0. 05 ). Conclusions Leptin promotes the growth of human SK-BR-3 breast cancer cells in vitro, which plays a role in the mechanism of angiogenesis and metastasis by increasing the expression of VEGF.%目的 观察瘦素对人乳腺癌SK-BR-3细胞增殖及对VEGF表达的影响,探讨其可能机制.方法 不同浓度瘦素与人乳腺癌SK-BR-3细胞共同培养后,CCK-8法检测其对人乳腺癌SK-BR-3细胞增殖的影响,实时荧光定量PCR法及Western印迹法检测VEGF mRNA及蛋白表达情况.结果 在一定范围内,瘦素呈时间、剂量依赖性促进SK-BR-3细胞的生长(P<0.05);细胞受不同浓度瘦素作用后VEGF mRNA及蛋白表达量明显增加并具有剂量依赖性(P<0.05).结论 在体外瘦素对人乳腺癌SK-BR-3细胞有明显增殖作用,通过促进VEGF的表达,在促进血管的生成及肿瘤转移机制中可能发挥一定作用.

  13. Effects of PDGF-BB on migration and proliferation of SK-BR-3 mammary carcinoma cells%PDGF-BB 对 SK-BR-3乳腺癌细胞迁移、增殖的影响

    Institute of Scientific and Technical Information of China (English)

    步玉辉; 史建红; 崔乃鹏; 何欢; 王冰; 陈保平

    2014-01-01

    目的:观察血小板源性生长因子(PDGF)-BB对乳腺癌SK-BR-3细胞迁移、增殖的促进作用。方法分别以0.5、1、2、4ng/mL质量浓度的PDGF-BB干预对数期SK-BR-3乳腺癌细胞,细胞计数法和內盐法(MTS)检测细胞增殖情况,细胞迁移试验检测细胞迁移能力。结果与未加入任何药物的SK-BR-3乳腺癌细胞相比,4ng/mL的PDGF-BB对SK-BR-3乳腺癌细胞的迁移及增殖有明显促进作用,该促进作用与药物质量浓度呈正相关。结论在一定质量浓度范围内,PDGF-BB能明显促进人源性SK-BR-3细胞的迁移和增殖。%Objective To explore the effects of platelet-derived growth factor ( PDGF)-BB on the migration and prolif-eration of SK-BR-3 mammary carcinoma cells .Methods SK-BR-3 mammary carcinoma cells in logarithm growth stage were treated with different concentrations of PDGF-BB (0.5, 1, 2, 4 ng/mL).The proliferation was determined by cytom-etry and MTS assay , and the migration ability was detected by cell migration assay .Results Compared with SK-BR-3 mammary carcinoma cells without any drug , 4 ng/mL PDGF-BB promoted the migration and proliferation of SK-BR-3 mam-mary cells and it was positively associated with the drug concentration .Conclusions The PDGF-BB can promote the mi-gration and proliferation of human SK-BR-3 cells in a specific concentration range .

  14. Leczenie pierwotnych chłoniaków skóry. Rekomendacje Sekcji Chłoniaków Skóry Polskiej Grupy Badawczej Chłoniaków (PLRG

    Directory of Open Access Journals (Sweden)

    Jan Walewski

    2010-09-01

    Full Text Available Pierwotne chłoniaki skóry stanowią heterogenną grupę nowotworówukładu limfoidalnego, wśród których około 75% wywodzi się z limfocytówT i których pierwotnym i dominującym klinicznie umiejscowieniemjest skóra. Pierwotne chłoniaki skóry cechuje odmienny przebiegkliniczny i rokowanie w porównaniu z chłoniakami układowymi.Chłoniaki skóry mają najczęściej przebieg przewlekły, ale całkowitewyleczenie chorego rzadko jest możliwe. Diagnostyka i leczenie pierwotnychchłoniaków skóry jest zagadnieniem interdyscyplinarnym,w które powinni być zaangażowani, obok dermatologów, równieżonkolodzy, hematolodzy i patomorfolodzy. Powstała w 2009 roku SekcjaChłoniaków Skóry Polskiej Grupy Badawczej Chłoniaków podjęłapróbę opracowania jednolitych zaleceń terapeutycznych, które byłybyuznane i stosowane w środowiskach wszystkich zaangażowanych specjalności.Są one oparte na dostępnych europejskich i światowych rekomendacjachoraz na doświadczeniu polskich ośrodków dermatologicznychi hematoonkologicznych w zakresie leczenia chłoniaków skóry.

  15. Effect of Trastuzumab on Notch-1 Signaling Pathway in Breast Cancer SK-BR3 Cells

    Institute of Scientific and Technical Information of China (English)

    Ming Han; Hua-yu Deng; Rong Jiang

    2012-01-01

    Objective:To investigate the effects and mechanisms of trastuzumab on Notch-1 pathway in breast cancer cells,recognizing the significance of Notch-1 signaling pathway in trastuzumab resistance.Methods:Immunocytochemistry staining and Western blotting were employed to justify the expression of Notch-1 protein in HER2-overexpressing SK-BR3 cells and HER2-non-overexpressing breast cancer MDA-MB-231 cells.Western blotting and reverse transcription PCR (RT-PCR) were used to detect the activated Notch-1 and Notch-1 target gene HES-1 mRNA expression after SK-BR3 cells were treated with trastuzumab.Double immunofluorescence staining and co-immunoprecipitation were used to analyze the relationship of Notch-1 and HER2 proteins.Results:The level of Notch-1 nuclear localization and activated Notch-1 proteins in HER2-overexpressing cells were significantly lower than in HER2-non-overexpressing cells (P<0.01),and the expressions of activated Notch-1 and HES-1 mRNA were obviously increased after trastuzumab treatment (P<1.05),but HER2 expression did not change significantly for trastuzumab treating (P>0.05).Moreover,Notch-1 was discovered to co-localize and interact with HER2 in SK-BR3 cells.Conclusion:Overexpression of HER2 decreased Notch-1 activity by the formation of a HER2-Notch1 complex,and trastuzumab can restore the activity of Notch-1 signaling pathway,which could be associated with cell resistance to trastuzumab.

  16. How does ethanol induce apoptotic cell death of SK-N-SH neuroblastoma cells?*

    Institute of Scientific and Technical Information of China (English)

    Yong Moon; Yongil Kwon; Shun Yu

    2013-01-01

    A body of evidence suggests that ethanol can lead to damage of neuronal cel s. However, the me-chanism underlying the ethanol-induced damage of neuronal cel s remains unclear. The role of mi-togen-activated protein kinases in ethanol-induced damage was investigated in SK-N-SH neurob-lastoma cel s. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide cel viability assay, DNA fragmentation detection, and flow cytometric analysis showed that ethanol induced apoptotic cel death and cel cycle arrest, characterized by increased caspase-3 activity, DNA fragmentation, nuclear disruption, and G 1 arrest of cel cycle of the SK-N-SH neuroblastoma cel s. In addition, western blot analysis indicated that ethanol induced a lasting increase in c-Jun N-terminal protein kinase activity and a transient increase in p38 kinase activity of the neuroblastoma cel s. c-Jun N-terminal protein kinase or p38 kinase inhibitors significantly reduced the ethanol-induced cel death. Ethanol also increased p53 phosphorylation, fol owed by an increase in p21 tumor sup-pressor protein and a decrease in phospho-Rb (retinoblastoma) protein, leading to alterations in the expressions and activity of cyclin dependent protein kinases. Our results suggest that ethanol me-diates apoptosis of SK-N-SH neuroblastoma cel s by activating p53-related cel cycle arrest possibly through activation of the c-Jun N-terminal protein kinase-related cel death pathway.

  17. Northern settlement family-style: labor planning and population policy in Noril'sk.

    Science.gov (United States)

    Bond, A R

    1985-01-01

    This paper reviews labor planning and population policies in Noril'sk, a mining and metallurgical settlement in northern Siberia. When the settlement was established in 1935, planners were lacking in ideas about how to recruit workers to staff the mines and smelters and how to retain the labor force once it was in place. From 1935-79, planners followed a forced labor policy dependent upon the labor of prisoners. However, this solution was not adequate for meeting the manpower needs of an economy undergoing rapid technological sophistication. Northern wage increments were introduced after 1945 to recruit skilled workers from other regions. These increments built up over a 4-year period to a maximum of 80% of base pay. A special cost of living bonus was also awarded. Although these inducements facilitated labor recruitment, labor retention remained a major problem. Surveys indicated that workers would prefer improvements in housing and social services to further wage increases. Thus, policy was directed at the housing shortages, poor medical care, and inadequate child care facilities in Noril'sk. Such improvements facilitated labor retention but also contributed to overpopulation. The population doubled between 1956-80, exceeding 180,000 in the latter year. In the early 1980s, selective measures toward population control were implemented to ensure maintenance of living standards (e.g., encouragement of older workers to leave the area upon retirement, more careful screening of recruits). The goal is to stabilize city size at around 250,000. The Noril'sk case illustrates that quality of life investments can alleviate labor retention problems even in the harshest physical environments. Recent policies have advocated productivity-enriching technologies that do not require increments in the labor force.

  18. Food truck som ett nytt fenomen i Skåne

    OpenAIRE

    Fromell, Hilda; Winter, Regina

    2016-01-01

    Food truck is a mobile restaurant business which originates from the United States, and can now be seen also in Sweden. There are specific guidelines regarding the food that are served from the food trucks rolling the streets of Skåne from 2013. For example the food should be ecological, which is in keeping with the other municipal goals regarding food and meal. The concept is communicated and marketed through social media, which makes it possible to effectively reach many people. Four food t...

  19. Aplikace marketingu na trhu rybářských potřeb

    OpenAIRE

    Skalický, Karel

    2009-01-01

    This bachelor thesis focuses on the marketing mixture of the fishing tackle. The aim of this thesis is to introduce the market of these particular products and its marketing specifics and to get the general idea of the marketing activities of the company Rybářské centrum s.r.o. Another aim is also to recommend and suggest new marketing strategies that help to develop the company. The theoretical part deals with all the important terminology concerning the marketing and marketing mix. The fish...

  20. Inclusive K0SK0S resonance production in ep collisions at HERA

    CERN Document Server

    AUTHOR|(CDS)2076592; Magill, S.; Musgrave, B.; Nicholass, D.; Repond, J.; Yoshida, R.; Mattingly, M.C.K.; Antonioli, P.; Bari, G.; Bellagamba, L.; Boscherini, D.; Bruni, A.; Bruni, G.; Cindolo, F.; Corradi, M.; Iacobucci, G.; Margotti, A.; Nania, R.; Polini, A.; Antonelli, S.; Basile, M.; Bindi, M.; Cifarelli, L.; Contin, A.; De Pasquale, S.; Sartorelli, G.; Zichichi, A.; Bartsch, D.; Brock, I.; Hartmann, H.; Hilger, E.; Jakob, H.P.; Jungst, M.; Nuncio-Quiroz, A.E.; Paul, E.; Samson, U.; Schonberg, V.; Shehzadi, R.; Wlasenko, M.; Brook, N.H.; Heath, G.P.; Morris, J.D.; Capua, M.; Fazio, S.; Mastroberardino, A.; Schioppa, M.; Susinno, G.; Tassi, E.; Kim, J.Y.; Ibrahim, Z.A.; Kamaluddin, B.; Wan Abdullah, W.A.T.; Ning, Y.; Ren, Z.; Sciulli, F.; Chwastowski, J.; Eskreys, A.; Figiel, J.; Galas, A.; Gil, M.; Olkiewicz, K.; Stopa, P.; Zawiejski, L.; Adamczyk, L.; Bold, T.; Grabowska-Bold, I.; Kisielewska, D.; Lukasik, J.; Przybycien, M.; Suszycki, L.; Kotanski, A.; Slominski, W.; Behrens, U.; Blohm, C.; Bonato, A.; Borras, K.; Ciesielski, R.; Coppola, N.; Fang, S.; Fourletova, J.; Geiser, A.; Gottlicher, P.; Grebenyuk, J.; Gregor, I.; Haas, T.; Hain, W.; Huttmann, A.; Januschek, F.; Kahle, B.; Katkov, I.I.; Klein, U.; Kotz, U.; Kowalski, H.; Lobodzinska, E.; Lohr, B.; Mankel, R.; Melzer-Pellmann, I.A.; Miglioranzi, S.; Montanari, A.; Namsoo, T.; Notz, D.; Parenti, A.; Rinaldi, L.; Roloff, P.; Rubinsky, I.; Santamarta, R.; Schneekloth, U.; Spiridonov, A.; Szuba, D.; Szuba, J.; Theedt, T.; Wolf, G.; Wrona, K.; Yagues Molina, A.G.; Youngman, C.; Zeuner, W.; Drugakov, V.; Lohmann, W.; Schlenstedt, S.; Barbagli, G.; Gallo, E.; Pelfer, P.G.; Bamberger, A.; Dobur, D.; Karstens, F.; Vlasov, N.N.; Bussey, P.J.; Doyle, A.T.; Dunne, W.; Forrest, M.; Rosin, M.; Saxon, D.H.; Skillicorn, I.O.; Gialas, I.; Papageorgiu, K.; Holm, U.; Klanner, R.; Lohrmann, E.; Schleper, P.; Schorner-Sadenius, T.; Sztuk, J.; Stadie, H.; Turcato, M.; Foudas, C.; Fry, C.; Long, K.R.; Tapper, A.D.; Matsumoto, T.; Nagano, K.; Tokushuku, K.; Yamada, S.; Yamazaki, Y.; Barakbaev, A.N.; Boos, E.G.; Pokrovskiy, N.S.; Zhautykov, B.O.; Aushev, V.; Borodin, M.; Kadenko, I.; Kozulia, A.; Libov, V.; Lisovyi, M.; Lontkovskyi, D.; Makarenko, I.; Sorokin, Iu.; Verbytskyi, A.; Volynets, O.; Son, D.; de Favereau, J.; Piotrzkowski, K.; Barreiro, F.; Glasman, C.; Jimenez, M.; Labarga, L.; del Peso, J.; Ron, E.; Soares, M.; Terron, J.; Zambrana, M.; Corriveau, F.; Liu, C.; Schwartz, J.; Walsh, R.; Zhou, C.; Tsurugai, T.; Antonov, A.; Dolgoshein, B.A.; Gladkov, D.; Sosnovtsev, V.; Stifutkin, A.; Suchkov, S.; Dementiev, R.K.; Ermolov, P.F.; Gladilin, L.K.; Golubkov, Yu.A.; Khein, L.A.; Korzhavina, I.A.; Kuzmin, V.A.; Levchenko, B.B.; Lukina, O.Yu.; Proskuryakov, A.S.; Shcheglova, L.M.; Zotkin, D.S.; Abt, I.; Caldwell, A.; Kollar, D.; Reisert, B.; Schmidke, W.B.; Grigorescu, G.; Keramidas, A.; Koffeman, E.; Kooijman, P.; Pellegrino, A.; Tiecke, H.; Vazquez Acosta, Monica Luisa; Wiggers, L.; Brummer, N.; Bylsma, B.; Durkin, L.S.; Lee, A.; Ling, T.Y.; Allfrey, Philip Daniel; Bell, M.A.; Cooper-Sarkar, A.M.; Devenish, R.C.E.; Ferrando, J.; Foster, B.; Korcsak-Gorzo, K.; Oliver, K.; Robertson, A.; Uribe-Estrada, C.; Walczak, R.; Bertolin, A.; Dal Corso, F.; Dusini, S.; Longhin, A.; Stanco, L.; Bellan, P.; Brugnera, R.; Carlin, R.; Garfagnini, A.; Limentani, S.; Oh, B.Y.; Raval, A.; Ukleja, J.; Whitmore, J.J.; Iga, Y.; D'Agostini, G.; Marini, G.; Nigro, A.; Cole, J.E.; Hart, J.C.; Abramowicz, H.; Ingbir, R.; Kananov, S.; Levy, A.; Stern, A.; Kuze, M.; Maeda, J.; Hori, R.; Kagawa, S.; Okazaki, N.; Shimizu, S.; Tawara, T.; Hamatsu, R.; Kaji, H.; Kitamura, S.; Ota, O.; Ri, Y.D.; Costa, M.; Ferrero, M.I.; Monaco, V.; Sacchi, R.; Solano, A.; Arneodo, M.; Ruspa, M.; Fourletov, S.; Martin, J.F.; Stewart, T.P.; Boutle, S.K.; Butterworth, J.M.; Gwenlan, C.; Jones, T.W.; Loizides, J.H.; Wing, M.; Brzozowska, B.; Ciborowski, J.; Grzelak, G.; Kulinski, P.; Luzniak, P.; Malka, J.; Nowak, R.J.; Pawlak, J.M.; Tymieniecka, T.; Ukleja, A.; zarnecki, A.F.; Adamus, M.; Plucinski, P.; Eisenberg, Y.; Hochman, D.; Karshon, U.; Brownson, E.; Danielson, T.; Everett, A.; Kcira, D.; Reeder, D.D.; Ryan, P.; Savin, A.A.; Smith, W.H.; Wolfe, H.; Bhadra, S.; Catterall, C.D.; Cui, Y.; Hartner, G.; Menary, S.; Noor, U.; Standage, J.; Whyte, J.

    2008-01-01

    Inclusive K0SK0S production in ep collisions at HERA was studied with the ZEUS detector using an integrated luminosity of 0.5 fb-1. Enhancements in the mass spectrum were observed and are attributed to the production of f2(1270)/a02(1320), f'2(1525) and f0(1710). The f0(1710) state was observed with a statistical significance of 5 standard deviations. Masses and widths were obtained using a fit which takes into account theoretical predictions based on SU(3) symmetry arguments.

  1. Altered active zones, vesicle pools, nerve terminal conductivity, and morphology during experimental MuSK myasthenia gravis.

    Science.gov (United States)

    Patel, Vishwendra; Oh, Anne; Voit, Antanina; Sultatos, Lester G; Babu, Gopal J; Wilson, Brenda A; Ho, Mengfei; McArdle, Joseph J

    2014-01-01

    Recent studies demonstrate reduced motor-nerve function during autoimmune muscle-specific tyrosine kinase (MuSK) myasthenia gravis (MG). To further understand the basis of motor-nerve dysfunction during MuSK-MG, we immunized female C57/B6 mice with purified rat MuSK ectodomain. Nerve-muscle preparations were dissected and neuromuscular junctions (NMJs) studied electrophysiologically, morphologically, and biochemically. While all mice produced antibodies to MuSK, only 40% developed respiratory muscle weakness. In vitro study of respiratory nerve-muscle preparations isolated from these affected mice revealed that 78% of NMJs produced endplate currents (EPCs) with significantly reduced quantal content, although potentiation and depression at 50 Hz remained qualitatively normal. EPC and mEPC amplitude variability indicated significantly reduced number of vesicle-release sites (active zones) and reduced probability of vesicle release. The readily releasable vesicle pool size and the frequency of large amplitude mEPCs also declined. The remaining NMJs had intermittent (4%) or complete (18%) failure of neurotransmitter release in response to 50 Hz nerve stimulation, presumably due to blocked action potential entry into the nerve terminal, which may arise from nerve terminal swelling and thinning. Since MuSK-MG-affected muscles do not express the AChR γ subunit, the observed prolongation of EPC decay time was not due to inactivity-induced expression of embryonic acetylcholine receptor, but rather to reduced catalytic activity of acetylcholinesterase. Muscle protein levels of MuSK did not change. These findings provide novel insight into the pathophysiology of autoimmune MuSK-MG.

  2. Altered active zones, vesicle pools, nerve terminal conductivity, and morphology during experimental MuSK myasthenia gravis.

    Directory of Open Access Journals (Sweden)

    Vishwendra Patel

    Full Text Available Recent studies demonstrate reduced motor-nerve function during autoimmune muscle-specific tyrosine kinase (MuSK myasthenia gravis (MG. To further understand the basis of motor-nerve dysfunction during MuSK-MG, we immunized female C57/B6 mice with purified rat MuSK ectodomain. Nerve-muscle preparations were dissected and neuromuscular junctions (NMJs studied electrophysiologically, morphologically, and biochemically. While all mice produced antibodies to MuSK, only 40% developed respiratory muscle weakness. In vitro study of respiratory nerve-muscle preparations isolated from these affected mice revealed that 78% of NMJs produced endplate currents (EPCs with significantly reduced quantal content, although potentiation and depression at 50 Hz remained qualitatively normal. EPC and mEPC amplitude variability indicated significantly reduced number of vesicle-release sites (active zones and reduced probability of vesicle release. The readily releasable vesicle pool size and the frequency of large amplitude mEPCs also declined. The remaining NMJs had intermittent (4% or complete (18% failure of neurotransmitter release in response to 50 Hz nerve stimulation, presumably due to blocked action potential entry into the nerve terminal, which may arise from nerve terminal swelling and thinning. Since MuSK-MG-affected muscles do not express the AChR γ subunit, the observed prolongation of EPC decay time was not due to inactivity-induced expression of embryonic acetylcholine receptor, but rather to reduced catalytic activity of acetylcholinesterase. Muscle protein levels of MuSK did not change. These findings provide novel insight into the pathophysiology of autoimmune MuSK-MG.

  3. 相依误差线性模型中的主成分 s-K 估计%Principal Components s-K Class Estimator in the Linear Model with Correlated Errors

    Institute of Scientific and Technical Information of China (English)

    周玲; 何道江

    2015-01-01

    为同时克服线性回归模型的自相关性和回归变量间的复共线性,通过融合主成分回归估计和 s-K 估计,提出一类新估计,称为主成分 s-K 估计;并在均方误差阵意义下,得到了这类估计分别优于广义最小二乘估计、主成分估计、r-k 和 s-K 估计的充要条件。 Monto Carlo 数值模拟表明,新估计是一种同时克服自相关性和复共线性的有效方法。%To combat autocorrelation in errors and multicollinearity among the regressors in linear regression model,we proposed a new estimator by combining the principal components regression (PCR)estimator and the s-K estimator.Then necessary and sufficient conditions for the superiority of the new estimator over the GLS,the PCR,the r-k and the s-K estimators were derived by the mean squared error matrix criterion.Finally,a Monte Carlo simulation study was carried out to investigate the performance of the proposed estimator.

  4. Clinical findings in MuSK-antibody positive myasthenia gravis: a U.S. experience.

    Science.gov (United States)

    Pasnoor, Mamatha; Wolfe, Gil I; Nations, Sharon; Trivedi, Jaya; Barohn, Richard J; Herbelin, Laura; McVey, April; Dimachkie, Mazen; Kissel, John; Walsh, Ronan; Amato, Anthony; Mozaffar, Tahseen; Hungs, Marcel; Chui, Luis; Goldstein, Jonathan; Novella, Steven; Burns, Ted; Phillips, Lawrence; Claussen, Gwendolyn; Young, Angela; Bertorini, Tulio; Oh, Shin

    2010-03-01

    We performed a retrospective chart review on 53 muscle-specific kinase antibody (MuSK-Ab)-positive myasthenia gravis (MG) patients at nine university-based centers in the U.S. Of these, 66% were Caucasian, 85% were women, and age of onset was 9-79 years. Twenty-seven patients were nonresponsive to anticholinesterase therapy. Myasthenia Gravis Foundation of America improvement status was achieved in 53% patients on corticosteroids, 51% with plasma exchange, and in 20% on intravenous immunoglobulin (IVIG). Thymectomy was beneficial in 7/18 patients at 3 years. Long-term (> or =3 years) outcome was very favorable in 58% of patients who achieved remission and/or minimal manifestation status. Overall, 73% improved. There was one MG-related death. This survey reinforces several cardinal features of MuSK-Ab-positive MG, including prominent bulbar involvement and anticholinesterase nonresponsiveness. Facial or tongue atrophy was rare. Most patients respond favorably to immunotherapy. The best clinical response was to corticosteroids and plasma exchange, and the poorest response was to IVIG. Long-term outcome is favorable in about 60% of cases.

  5. A dehydrin-dehydrin interaction: the case of SK3 from Opuntia streptacantha

    Directory of Open Access Journals (Sweden)

    Itzell eHernandez

    2014-10-01

    Full Text Available Dehydrins belongs to a large group of highly hydrophilic proteins known as Late Embryogenesis Abundant (LEA proteins. It is well know that dehydrins are intrinsically disordered plant proteins that accumulate during the late stages of embryogenesis and in response to abiotic stresses; however, the molecular mechanisms by which their functions are carried out are still unclear. We have previously reported that transgenic Arabidopsis plants overexpressing an Opuntia streptacantha SK3 dehydrin (OpsDHN1 show enhanced tolerance to freezing stress. Herein, we show using a split-ubiquitin yeast two-hybrid system that OpsDHN1 dimerizes. We found that the deletion of regions containing K-segments and the histidine-rich region in the OpsDHN1 protein affects dimer formation. Not surprisingly, in silico protein sequence analysis suggests that OpsDHN1 is an intrinsically disordered protein, an observation that was confirmed by circular dichroism and gel filtration of the recombinantly expressed protein. The addition of zinc triggered the association of recombinantly expressed OpsDHN1 protein, likely through its histidine-rich motif. These data brings new insights about the molecular mechanism of the OpsDHN1 SK3-dehydrin

  6. Production and antioxidant activity of intracellular polysaccharide by Hypsizigus marmoreus SK-01

    Directory of Open Access Journals (Sweden)

    Honghong Liu

    2012-11-01

    Full Text Available The extraction parameters of intracellular polysaccharide (IPS from Hypsizigus marmoreus SK-01 mycelia were optimized, and the antioxidant activities of IPS were investigated. The optimum conditions of IPS extraction were predicted to be: an ultrasonic treatment time of 618.07 s, an extraction temperature of 84.53 °C, a pH of 7.57, and an IPS yield of ca. 6.84%. The in vitro inhibition effects of IPS on hydroxyl, superoxide anion, and 1,1-diphenyl-2-picrylhydrazyl (DPPH radicals were 52.63 ± 3.19%, 68.21 ± 5.09%, and 63.43 ± 5.27%, respectively, and the EC50 values of IPS were 0.85 ± 0.05 g/L, 0.47 ± 0.03 g/L, and 0.62 ± 0.04 g/L, respectively. The activities of glutathione peroxidase (GSH-Px, superoxide dismutase (SOD, and catalase (CAT in mice blood were 2.52 ± 0.02 U/mL, 453.19 ± 38.43 U/mL, and 118.59 ± 9.64 U/mL, respectively. The results provide a reference for large-scale extraction of IPS by H. marmoreus SK-01 in industrial fermentation, suggesting that IPS can be used as a potential antioxidant that enhances adaptive immune responses.

  7. FEM analysis of hot-pressing process of aspheric glass P-SK57 lens

    Science.gov (United States)

    Zhu, Yongjian; Na, Jingxin; Wang, Yu; Li, Anhu; Zhi, Yanan; Fan, Yufeng

    2013-09-01

    Lens molding has become the promising technique to conduct mass produce of aspheric glass lens. It overcomes some disadvantages of traditional grinding or turning methods, such as high cost, low efficiency, unstable accuracy, and so on. Up to now, the lens molding process has been looked on as one of the reliable methods in fabrication of aspheric glass lens. However, in real production, one has found that it's hard to control the molding parameters, e.g. molding temperature, molding period, molding speed and pressing pressure, etc. Therefore it's necessary to develop the specific molding processes for a certain glass material. In this paper, SCHOTT P-SK57 is adopted to carry out the lens molding analysis in order to achieve the relative processing parameters. The molding cases are analyzed based on three different temperatures of 510°C, 520°C, and 530°C, higher than transition point 493°C of P-SK57. Through continuous heating and pressing simulation, the results show that the best pressing temperature could be about 530°C, at which the residual stress is only 5.22MPa (with the molding speed of 0.1mm/s).

  8. SK channel modulation rescues striatal plasticity and control over habit in cannabinoid tolerance.

    Science.gov (United States)

    Nazzaro, Cristiano; Greco, Barbara; Cerovic, Milica; Baxter, Paul; Rubino, Tiziana; Trusel, Massimo; Parolaro, Daniela; Tkatch, Tatiana; Benfenati, Fabio; Pedarzani, Paola; Tonini, Raffaella

    2012-01-08

    Endocannabinoids (eCBs) regulate neuronal activity in the dorso-lateral striatum (DLS), a brain region that is involved in habitual behaviors. How synaptic eCB signaling contributes to habitual behaviors under physiological and pathological conditions remains unclear. Using a mouse model of cannabinoid tolerance, we found that persistent activation of the eCB pathway impaired eCB-mediated long-term depression (LTD) and synaptic depotentiation in the DLS. The loss of eCB LTD, occurring preferentially at cortical connections to striatopallidal neurons, was associated with a shift in behavioral control from goal-directed action to habitual responding. eCB LTD and behavioral alterations were rescued by in vivo modulation of small-conductance calcium activated potassium channel (SK channel) activity in the DLS, which potentiates eCB signaling. Our results reveal a direct relationship between drug tolerance and changes in control of instrumental performance by establishing a central role for eCB LTD in habit expression. In addition, SK channels emerge as molecular targets to fine tune the eCB pathway under pathological conditions.

  9. Progesterone and estradiol enhance lipid mediated transfection of Sk-Br-3 mammalian cancer cells.

    Science.gov (United States)

    Köster, Frank; Felberbaum, Ricardo; Finas, Dominique; Wünsch, Kurt; Schulz, Christiane; Diedrich, Klaus; Hauser, Charlotte

    2002-06-01

    Cyclodextrin encapsulated beta-estradiol and progesterone were used for enhancement of gene delivery using the breast cancer cell line Sk-Br-3. A non-toxic concentration of cyclodextrin encapsulated sex steroids (50 microM) added to lipid or liposomal transfection led to a 12-fold increase of reporter gene expression (luciferase) with progesterone and an 8-fold increase with estradiol using Lipofectamine Plus mediated transfection. Using the lipid formulation Fugene-6 the results were a 5.5-fold and a 4.5-fold increase respectively. This enhancement could only be observed if the sex steroids were added to the cells before application of the DNA-Fugene complex supporting the evidence that intracellular processes are responsible for the activity of the steroids. The strong differences between progesterone and estradiol in modifying Lipofectamine Plus transfection in Sk-Br-3 cells may to be explained by differences in the distribution of these receptors in the cellular compartments. These results seem to add evidence on the possibility of using sex steroids to increase the efficiency of non-viral vectors for transfection, and may ultimately prove to be relevant to gene therapy in the treatment of breast cancer as well as other solid tumors.

  10. Goniothalamin induces apoptosis associated with autophagy activation through MAPK signaling in SK-BR-3 cells.

    Science.gov (United States)

    Innajak, Sukanda; Mahabusrakum, Wilawan; Watanapokasin, Ramida

    2016-05-01

    Goniothalamin, a plant bioactive styrly-lactone, possesses many biological activities. In the present study, the anticancer effect of goniothalamin on human breast cancer cell line SK-BR-3 was investigated. The results showed that goniothalamin induced nuclear condensation, DNA fragmentation, apoptotic bodies and mitochondrial dysfunction as determined by JC-1 staining. Goniothalamin also increased the Bax/Bcl-2 ratio and expression of cleaved caspase-7, cleaved caspase-9 and cleaved PARP, but decreased Bcl-2 expression. In addition, goniothalamin induced apoptosis via p-JNK1/2 and p-p38 upregulation and inhibited cell survival via p-ERK1/2 and p-Akt downregulation. Notably, goniothalamin induced autophagy through upregulation of Atg7, Atg12-Atg5 conjugation and LC3II. The increased p-p38 and p-JNK1/2 and decreased p-Akt may lead to autophagy induction. Therefore, goniothalamin promoted apoptosis associated with autophagy induction in SK-BR-3 cells through p-p38 and p-JNK1/2 upregulation and p-Akt downregulation. The present study indicated that goniothalamin may be further used as a potential therapeutic candidate or may offer an alternative treatment for breast cancer.

  11. Resveratrol inhibits prostaglandin formation in IL-1β-stimulated SK-N-SH neuronal cells

    Directory of Open Access Journals (Sweden)

    Candelario-Jalil Eduardo

    2009-09-01

    Full Text Available Abstract Resveratrol, a polyphenol present in grapes and red wine, has been studied due to its vast pharmacological activity. It has been demonstrated that resveratrol inhibits production of inflammatory mediators in different in vitro and in vivo models. Our group recently demonstrated that resveratrol reduced the production of prostaglandin (PG E2 and 8-isoprostane in rat activated microglia. In a microglial-neuronal coculture, resveratrol reduced neuronal death induced by activated microglia. However, less is known about its direct roles in neurons. In the present study, we investigated the effects of resveratrol on interleukin (IL-1β stimulated SK-N-SH cells. Resveratrol (0.1-5 μM did not reduce the expression of cyclooxygenase (COX-2 and microsomal PGE2 synthase-1 (mPGES-1, although it drastically reduced PGE2 and PGD2 content in IL-1β-stimulated SK-N-SH cells. This effect was due, in part, to a reduction in COX enzymatic activity, mainly COX-2, at lower doses of resveratrol. The production of 8-iso-PGF2α, a marker of cellular free radical generation, was significantly reduced by resveratrol. The present work provides evidence that resveratrol reduces the formation of prostaglandins in neuroblastoma cells by reducing the enzymatic activity of inducible enzymes, such as COX-2, and not the transcription of the PG synthases, as demonstrated elsewhere.

  12. Global transcriptomic response of Anoxybacillus sp. SK 3-4 to aluminum exposure.

    Science.gov (United States)

    Lim, Jia Chun; Thevarajoo, Suganthi; Selvaratnam, Chitra; Goh, Kian Mau; Shamsir, Mohd Shahir; Ibrahim, Zaharah; Chong, Chun Shiong

    2017-02-01

    Anoxybacillus sp. SK 3-4 is a Gram-positive, rod-shaped bacterium and a member of family Bacillaceae. We had previously reported that the strain is an aluminum resistant thermophilic bacterium. This is the first report to provide a detailed analysis of the global transcriptional response of Anoxybacillus when the cells were exposed to 600 mg L(-1) of aluminum. The transcriptome was sequenced using Illumina MiSeq sequencer. Total of 708 genes were differentially expressed (fold change >2.00) with 316 genes were up-regulated while 347 genes were down-regulated, in comparing to control with no aluminum added in the culture. Based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the majority of genes encoding for cell metabolism such as glycolysis, sulfur metabolism, cysteine and methionine metabolism were up-regulated; while most of the gene associated with tricarboxylic acid cycle (TCA cycle) and valine, leucine and isoleucine metabolism were down-regulated. In addition, a significant number of the genes encoding ABC transporters, metal ions transporters, and some stress response proteins were also differentially expressed following aluminum exposure. The findings provide further insight and help us to understand on the resistance of Anoxybacillus sp. SK 3-4 toward aluminium. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Differential Cytokine Changes in Patients with Myasthenia Gravis with Antibodies against AChR and MuSK.

    Directory of Open Access Journals (Sweden)

    Vuslat Yilmaz

    Full Text Available Neuromuscular transmission failure in myasthenia gravis (MG is most commonly elicited by autoantibodies (ab to the acetylcholine receptor or the muscle-specific kinase, constituting AChR-MG and MuSK-MG. It is controversial whether these MG subtypes arise through different T helper (Th 1, Th2 or Th17 polarized immune reactions and how these reactions are blunted by immunosuppression. To address these questions, plasma levels of cytokines related to various Th subtypes were determined in patients with AChR-MG, MuSK-MG and healthy controls (CON. Peripheral blood mononuclear cells (PBMC were activated in vitro by anti-CD3, and cytokines were quantified in supernatants. In purified blood CD4+ T cells, RNA of various cytokines, Th subtype specific transcription factors and the co-stimulatory molecule, CD40L, were quantified by qRT-PCR. Plasma levels of Th1, Th2 and Th17 related cytokines were overall not significantly different between MG subtypes and CON. By contrast, in vitro stimulated PBMC from MuSK-MG but not AChR-MG patients showed significantly increased secretion of the Th1, Th17 and T follicular helper cell related cytokines, IFN-γ, IL-17A and IL-21. Stimulated expression of IL-4, IL-6, IL-10 and IL-13 was not significantly different. At the RNA level, expression of CD40L by CD4+ T cells was reduced in both AChR-MG and MuSK-MG patients while expression of Th subset related cytokines and transcription factors were normal. Immunosuppression treatment had two effects: First, it reduced levels of IL12p40 in the plasma of AChR-MG and MuSK-MG patients, leaving other cytokine levels unchanged; second, it reduced spontaneous secretion of IFN-γ and increased secretion of IL-6 and IL-10 by cultured PBMC from AChR-MG, but not MuSK-MG patients. We conclude that Th1 and Th17 immune reactions play a role in MuSK-MG. Immunosuppression attenuates the Th1 response in AChR-MG and MuSK-MG, but otherwise modulates immune responses in AChR-MG and MuSK

  14. [Maria Skłodowska-Curie--her chemistry at the centenary of the second Nobel Prize].

    Science.gov (United States)

    Zagórski, Zbigniew Paweł; Kornacka, Ewa Maria

    2012-01-01

    The article presents from the perspective of one hundred years the work of Maria Curie-Skłodowska, which in many cases was ahead of the state of knowledge of the time. It opened new horizons and for this reason we made many digressions. The fact of awarding her the Nobel Prize twice is a sensation enough to present the values of careful activity of the Nobel Prize Committee that emphasizes the importance of Maria's achievements. A significant element of Maria Skłodowska-Curie's achievements was still mysterious character of the radiation in her time, and only chemical approach made it possible to organise the phenomena and explain the origin of the radiation. The essence of the research was an arduous separation of components following the track of growing radiation of successive fractions of preparations. This research was a start of the technology of educement of dispersed elements in great mass of materials. We underline the paramount role of the chemical research Maria Skłodowska conducted while still in Warsaw in the laboratories of the Museum of Industry and Agriculture under the guidance of an excellent chemist Józef Jerzy Boguski. Her research in Paris was the origin of the semi-commercial scale in chemistry and setting aside a special shed outside the university building was the beginning of the institutes that now function beyond universities and are key element of scientific and technical progress. Technology of splitting developed by Maria Skłodowska-Curie was applied also by other radiochemists, e.g. By Otto Hahn. Lively movement in radiochemistry of her lifetime resulted in Maria's disputes with e.g. German chemist Marckwald, who questioned the originality of polonium. The scientific disputes like this one Maria won triumphantly although in several others she had to accept opponents' argument, as in the case of radon. Her experiments were planned with utmost rationality as it was with the rejection of the hypothesis saying that radioactivity was

  15. A novel role for MuSK and non-canonical Wnt signaling during segmental neural crest cell migration.

    Science.gov (United States)

    Banerjee, Santanu; Gordon, Laura; Donn, Thomas M; Berti, Caterina; Moens, Cecilia B; Burden, Steven J; Granato, Michael

    2011-08-01

    Trunk neural crest cells delaminate from the dorsal neural tube as an uninterrupted sheet; however, they convert into segmentally organized streams before migrating through the somitic territory. These neural crest cell streams join the segmental trajectories of pathfinding spinal motor axons, suggesting that interactions between these two cell types might be important for neural crest cell migration. Here, we show that in the zebrafish embryo migration of both neural crest cells and motor axons is temporally synchronized and spatially restricted to the center of the somite, but that motor axons are dispensable for segmental neural crest cell migration. Instead, we find that muscle-specific receptor kinase (MuSK) and its putative ligand Wnt11r are crucial for restricting neural crest cell migration to the center of each somite. Moreover, we find that blocking planar cell polarity (PCP) signaling in somitic muscle cells also results in non-segmental neural crest cell migration. Using an F-actin biosensor we show that in the absence of MuSK neural crest cells fail to retract non-productive leading edges, resulting in non-segmental migration. Finally, we show that MuSK knockout mice display similar neural crest cell migration defects, suggesting a novel, evolutionarily conserved role for MuSK in neural crest migration. We propose that a Wnt11r-MuSK dependent, PCP-like pathway restricts neural crest cells to their segmental path.

  16. Comparison of visual, refractive and topographic keratometry outcomes of intacs and intacs SK in mild to moderate keratoconus eyes

    Directory of Open Access Journals (Sweden)

    Abdulrahman Al Muammar

    2015-01-01

    Full Text Available Purpose: The purpose was to evaluate and compare the visual and refractive outcomes, topographic keratometry (K and complications of Intacs and Intacs SK for mild to moderate keratoconus. Methods: In this retrospective study, all mild to moderate keratoconus eyes that underwent implantation of Intacs (Intacs group or Intacs SK (Intacs SK group with minimum follow-up of 12 months were included. Preoperative and postoperative uncorrected distance visual acuity (UDVA, corrected distance visual acuity (CDVA, manifest refraction, manifest cylinder, spherical equivalent (SE, minimum topographic keratometry, maximum topographic keratometry, and average topographic keratometry were compared in both groups. Results: There were 16 eyes in the Intacs group and 18 eyes in the Intacs SK group. Preoperatively, both groups were comparable for most parameters except gender and minimum K and average K. At 6 months postoperatively there were statistically significant improvements in UDVA, CDVA, manifest sphere, SE, minimum K, maximum K, and average K (P 0.05. The outcomes remained stable with no statistically significant differences between the 6 and 12 months visits. There were no complications in both groups. Conclusion: Both models of Intacs significantly improved vision and refractive outcomes, and topographic keratometry in cases of mild to moderate keratoconus. Intacs SK provided better (not statistically significant results.

  17. „Gott samstarf heimilis og skóla skilar sér alltaf“ : einkenni farsæls samstarfs heimilis og skóla á yngsta stigi grunnskóla

    OpenAIRE

    Lára Ágústa Hjartardóttir 1988

    2014-01-01

    Verkefnið snýst um samstarf heimilis og skóla á yngsta stigi grunnskóla. Tilgangurinn með rannsókninni var að varpa ljósi á hvað einkennir farsælt samstarf á yngsta stigi grunnskólans, hver ber ábyrgð og hverjar eru skyldur hvers aðila þegar kemur að samstarfinu. Markmiðið var að öðlast öryggi og styrk í samskiptum við heimilin og kynnast fjölbreyttum leiðum til að hvetja foreldra til þátttöku í skólastarfi barna sinna. Auk þess var skoðað hvernig samstarf heimilis og skóla hefur þróast á und...

  18. 10-(6'-Plastoquinonyl)decyltriphenylphosphonium (SkQ1) Does Not Increase the Level of Cytochromes P450 in Rat Liver and Human Hepatocyte Cell Culture.

    Science.gov (United States)

    Myasoedova, K N; Silachev, D N; Petrov, A D

    2016-12-01

    Mitochondria-targeted antioxidant SkQ1 did not increase the content of cytochromes P450 in livers of rats that were given SkQ1 in drinking water for 5 days in a dose (2.5 µmol per kg body weight) that exceeded 10 times the SkQ1 therapeutic dose. SkQ1 did not affect the levels of cytochrome P450 forms CYP1A2, CYP2B6, and CYP3A4 in monolayer cultures of freshly isolated human hepatocytes, while specific inducers of these forms (omeprazole, phenobarbital, and rifampicin, respectively) significantly increased expression of the cytochromes P450 under the same conditions. We conclude that therapeutic doses of SkQ1 do not induce cytochromes P450 in liver, and the absence of the inducing effect cannot be explained by poor availability of hepatocytes to SkQ1 in vivo.

  19. Różnice indywidualne w skłonności do kupowania impulsywnego. Konstrukcja i walidacja skali pomiarowej

    OpenAIRE

    Gąsiorowska, Agata

    2013-01-01

    Dotychczasowe badania nad zakupami impulsywnymi sugerują istnienie indy- widualnych różnic w zakresie skłonności do takiego sposobu kupowania. Niniejszy artykuł prezentuje wyniki badań, których celem była konstrukcja i weryfikacja wielowymiarowej skali do pomiaru skłonności do kupowania impulsywnego (SKI). Skala ta składa się z pięciu podwymiarów, reprezentujących emocje zwią- zane z zakupami, poczucie nacisku podczas zakupów, przyjemność z nich czerpaną, odczuwanie żalu pozakupowego i brak r...

  20. Overexpression of YB1 C-terminal domain inhibits proliferation, angiogenesis and tumorigenicity in a SK-BR-3 breast cancer xenograft mouse model.

    Science.gov (United States)

    Shi, Jian-Hong; Cui, Nai-Peng; Wang, Shuo; Zhao, Ming-Zhi; Wang, Bing; Wang, Ya-Nan; Chen, Bao-Ping

    2016-01-01

    Y-box-binding protein 1 (YB1) is a multifunctional transcription factor with vital roles in proliferation, differentiation and apoptosis. In this study, we have examined the role of its C-terminal domain (YB1 CTD) in proliferation, angiogenesis and tumorigenicity in breast cancer. Breast cancer cell line SK-BR-3 was infected with GFP-tagged YB1 CTD adenovirus expression vector. An 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) proliferation assay showed that YB1 CTD decreased SK-BR-3 cell proliferation, and down-regulated cyclin B1 and up-regulated p21 levels in SK-BR-3 cells. YB1 CTD overexpression changed the cytoskeletal organization and slightly inhibited the migration of SK-BR-3 cells. YB1 CTD also inhibited secreted VEGF expression in SK-BR-3 cells, which decreased SK-BR-3-induced EA.hy926 endothelial cell angiogenesis in vitro. YB1 CTD overexpression attenuated the ability of SK-BR-3 cells to form tumours in nude mice, and decreased in vivo VEGF levels and angiogenesis in the xenografts in SK-BR-3 tumour-bearing mice. Taken together, our findings demonstrate the vital role of YB1 CTD overexpression in inhibiting proliferation, angiogenesis and tumorigenicity of breast cancer cell line SK-BR-3.

  1. Inhibition of SK4 Potassium Channels Suppresses Cell Proliferation, Migration and the Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer Cells.

    Science.gov (United States)

    Zhang, Panshi; Yang, Xiaowei; Yin, Qian; Yi, Jilin; Shen, Wenzhuang; Zhao, Lu; Zhu, Zhi; Liu, Jinwen

    2016-01-01

    Treatments for triple-negative breast cancer (TNBC) are limited; intermediate-conductance calcium-activated potassium (SK4) channels are closely involved in tumor progression, but little is known about these channels in TNBC. We aimed to investigate whether SK4 channels affect TNBC. First, by immunohistochemistry (IHC) and western blotting (WB), increased SK4 protein expression in breast tumor tissues was detected relative to that in non-tumor breast tissues, but there was no apparent expression difference between various subtypes of breast cancer (p>0.05). Next, functional SK4 channels were detected in the TNBC cell line MDA-MB-231 using WB, real-time PCR, immunofluorescence and patch-clamp recording. By employing SK4 specific siRNAs and blockers, including TRAM-34 and clotrimazole, in combination with an MTT assay, a colony-formation assay, flow cytometry and a cell motility assay, we found that the suppression of SK4 channels significantly inhibited cell proliferation and migration and promoted apoptosis in MDA-MB-231 cells (pMDA-MB-231 cells to undergo the epithelial-mesenchymal transition (EMT) and to show increased SK4 mRNA expression. In addition, the down-regulation of SK4 expression inhibited the EMT markers Vimentin and Snail1. Collectively, our findings suggest that SK4 channels are expressed in TNBC and are involved in the proliferation, apoptosis, migration and EMT processes of TNBC cells.

  2. Complete Sequences of Four Plasmids of Lactococcus lactis subsp. cremoris SK11 Reveal Extensive Adaptation to the Dairy Environment†

    Science.gov (United States)

    Siezen, Roland J.; Renckens, Bernadet; van Swam, Iris; Peters, Sander; van Kranenburg, Richard; Kleerebezem, Michiel; de Vos, Willem M.

    2005-01-01

    Lactococcus lactis strains are known to carry plasmids encoding industrially important traits. L. lactis subsp. cremoris SK11 is widely used by the dairy industry in cheese making. Its complete plasmid complement was sequenced and found to contain the plasmids pSK11A (10,372 bp), pSK11B (13,332 bp), pSK11L (47,165 bp), and pSK11P (75,814 bp). Six highly homologous repB-containing replicons were found, all belonging to the family of lactococcal theta-type replicons. Twenty-three complete insertion sequence elements segment the plasmids into numerous modules, many of which can be identified as functional units or containing functionally related genes. Plasmid-encoded functions previously known to reside on L. lactis SK11 plasmids were now mapped in detail, e.g., lactose utilization (lacR-lacABCDFEGX), the proteolytic system (prtM-prtP, pepO, pepF), and the oligopeptide permease system (oppDFBCA). Newly identified plasmid-encoded functions could facilitate the uptake of various cations, while the pabA and pabB genes could be essential for folate biosynthesis. A competitive advantage could be obtained by using the putative flavin adenine dinucleotide-dependent d-lactate dehydrogenase and oxalate:formate antiporter for enhanced ATP synthesis, while the activity of the predicted α-acetolactate decarboxylase may contribute to the formation of an additional electron sink. Various stress response proteins are plasmid encoded, which could enhance strain robustness. A substantial number of these “adaptation” genes have not been described before on L. lactis plasmids. Moreover, several genes were identified for the first time in L. lactis, possibly reflecting horizontal gene transfer. PMID:16332824

  3. The Making of the Gdańsk Metropolitan Region. Local Discourses of Identities, Powers, and Hopes

    Directory of Open Access Journals (Sweden)

    Czepczyński Mariusz

    2014-12-01

    Full Text Available The process of metropolitanisation of the Gdańsk area is facilitated by public discourse involving local and regional politicians, media, and inhabitants. The discussion is based upon historical narrations, but also local ambitions, hopes and emotions, as well as infrastructural projects and investment attractiveness. Foucault suggests that modern power is a dispersed set of micro-practices, many of which operate through the normalising gaze of surveillance regimes. Gdańsk metropolitan cooperation, competition and encounters make the core of the paper; local and regional unifying initiatives and processes are accompanied by examples of separatism, identity conflicts, and political disagreements

  4. Genetic Pd, Pt, Au, Ag, and Rh mineralogy in Noril'sk sulfide ores

    Science.gov (United States)

    Spiridonov, E. M.; Kulagov, E. A.; Serova, A. A.; Kulikova, I. M.; Korotaeva, N. N.; Sereda, E. V.; Tushentsova, I. N.; Belyakov, S. N.; Zhukov, N. N.

    2015-09-01

    The undeformed ore-bearing intrusions of the Noril'sk ore field (NOF) cut through volcanic rocks of the Late Permian-Early Triassic trap association folded in brachysynclines. Due to the nonuniform load on the roof of intrusive bodies, most sulfide melts were squeezed, up to the tops of ore-bearing intrusions; readily fusible Ni-Fe-Cu sulfide melts were almost completely squeezed. In our opinion, not only one but two stages of mineralization developed at the Noril'sk deposits: (i) syntrap magmatic and (ii) epigenetic post-trap metamorphic-hydrothermal. All platinum-group minerals (PGM) and minerals of gold are metasomatic in the Noril'sk ores. They replaced sulfide solid solutions and exsolution structures. All types of PGM and Au minerals occur in the ores, varying in composition from pyrrhotite to chalcopyrite, talnakhite, mooihoekite, and rich in galena; they are localized in the inner and outer contact zones and differ only in the quantitative proportions of ore minerals. The aureoles of PGM and Au-Ag minerals are wider than the contours of sulfide bodies and coincide with halos of fluid impact on orebodies and adjacent host rocks. The pneumatolytic PGM and Au-Ag minerals are correlated in abundance with the dimensions of sulfide bodies. Their amounts are maximal in veins of late fusible ore composed of eutectic PbS ss and iss intergrowths, as well as at their contacts. The Pd and Pt contents in eutectic sulfide ores of NOF are the world's highest. In the process of noble-metal mineral formation, the fluids supply Pd, Pt, Au, As, Sb, Sn, Bi, and a part of Te, whereas Fe, Ni, Cu, Pb, Ag, Rh, a part of Te and Pd are leached from the replaced sulfide minerals. The pneumatolytic PGM of the early stage comprises Pd and Pt intermetallic compounds enriched in Au along with Pd-Pt-Fe-Ni-Cu-Sn-Pb(As) and (Pd,Pt,Au)(Sn,Sb,Bi,Te,As) solid solutions. Pneumatolytic PGM and Au minerals of the middle stage are products of solid-phase transformation and recrystallization of

  5. Parrot SK400摩托车专用蓝牙套装

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    专门做手机无线接口设备的Parrot公司,近期发表了这款Parrot SK400摩托车专用蓝牙免持套件。配有FM无线电播放器和无线手机遥控器。“骑士们”可以自由选择听音乐、广播或接电话。多声器的语音辨识系统,可以辨识联络人姓名并可自动接打电话。特别是Text To Speech功能,可以透过耳机,

  6. Convergence of clock processes in random environments and ageing in the p-spin SK model

    CERN Document Server

    Bovier, Anton

    2010-01-01

    We derive a general criterion for the convergence of clock processes in random dynamics in random environments that is applicable in cases when correlations are not negligible, extending recent results by Gayrard [15,16], based on general criterion for convergence of sums of dependent random variables due to Durrett and Resnick [13]. We demonstrate the power of this criterion by applying it to the case of random hopping time dynamics of the p-spin SK model. We prove that on a wide range of time scales, the clock process converges to a stable subordinator almost surely with respect to the environment. We also show that a time-time correlation function converges to the arcsine law for this subordinator, almost surely. This improves recent results of Ben Arous et al. [1] that obtained similar convergence result in law with respect to the random environment.

  7. Comparison of different methods for DNA-free RNA isolation from SK-N-MC neuroblastoma

    Directory of Open Access Journals (Sweden)

    Ferreira Ricardo B

    2011-01-01

    Full Text Available Abstract Background RNA quality and quantity are important factors for ensuring the accuracy of gene expression analysis and other RNA-based downstream applications. Extraction of high quality nucleic acids is difficult from neuronal cells and brain tissues as they are particularly rich in lipids. In addition, most common RNA extraction methods are phenol-based, resulting in RNA that may be incompatible with downstream applications such as gene expression. Findings In this work, a comparative analysis of the RNA quality obtained from SK-N-MC cells was performed using six commonly used RNA isolation kits: two phenol-based kits and four non-phenol based kits. The non-phenol based kits tested AxyPrep Multisource Total RNA Miniprep, RNeasy® Mini, EasySpin and Ilustra RNAspin Mini RNA Isolation, all performed well and resulted in the isolation of high quality RNA, as evaluated by A260/A280. The RNA extracted with AxyPrep Multisource Total RNA Miniprep, RNeasy® Mini and EasySpin provided the highest RNA yields. In particular, the RNA isolated by AxyPrep Multisource Total RNA Miniprep Kit did not show any detectable genomic DNA contamination even without previous DNase treatment or after RNA direct PCR amplification using universal 18S primers. Conclusions The RNA extracted from SK-N-MC cells with AxyPrep Multisource Total RNA Miniprep Kit was superior with respect to the RNA quality and concentration. This kit does not use aggressive organic solvents and RNA free of genomic DNA was isolated without the need for DNase treatment.

  8. Human ortholog of a plant salicylic acid receptor found in SK-N-SH cell line.

    Science.gov (United States)

    Skubatz, Hanna; Howald, William N

    2013-12-01

    Our previous studies have described the purification and characterization of a novel plant NAD(P)-reductase like protein (RL) from the thermogenic appendix of the Sauromatum guttatum inflorescence. RL is mainly located in cytoplasm of thermogenic plants and it can act like a bistable switch. It adopts a compact conformation during heat-production and a more expanded conformation when heat is not generated. Addition of salicylic acid, a natural thermogenic inducer, at picomolar concentration to a solution of purified RL induced a discontinuous volume phase transition in which the volume of RL in the oligomeric form expanded and shrunk repeatedly every 4-5 min. In the present study using ESI-MS analysis we have demonstrated the existence of RL in the human SK-N-SH cell line and in mouse brain tissue. The molecular mass of human RL is in the same range as of its plant counterpart, 34,140 ± 34 Da. The charge state distribution of the human RL is identical to its plant counterpart from the Sauromatum appendix during heat-production. Human RL was present in the compact state when it was purified from the SK-N-SH cell line When these cells were treated with salicylic acid (10 μM) a shift to a much more compact conformation was observed. It seems that the potential of RL to respond to salicylic acid was conserved. These results may reveal the existence of a thermoregulation system that is evolutionarily conserved and is operating by conformational changes. This discovery may also represent an opportunity for a better understanding of some of the diverse functions of salicylic acid and aspirin in plants and humans.

  9. Antioxidant mechanism of mitochondria-targeted plastoquinone SkQ1 is suppressed in aglycemic HepG2 cells dependent on oxidative phosphorylation.

    Science.gov (United States)

    Ježek, Jan; Engstová, Hana; Ježek, Petr

    2017-09-01

    Previously suggested antioxidant mechanisms for mitochondria-targeted plastoquinone SkQ1 included: i) ion-pairing of cationic SkQ1(+) with free fatty acid anions resulting in uncoupling; ii) SkQ1H2 ability to interact with lipoperoxyl radical; iii) interference with electron flow at the inner ubiquinone (Q) binding site of Complex III (Qi), involving the reduction of SkQ1 to SkQ1H2 by ubiquinol. We elucidated SkQ1 antioxidant properties by confocal fluorescence semi-quantification of mitochondrial superoxide (Jm) and cytosolic H2O2 (Jc) release rates in HepG2 cells. Only in glycolytic cells, SkQ1 prevented the rotenone-induced enhancement of Jm and Jc but not basal releases without rotenone. The effect ceased in glutaminolytic aglycemic cells, in which the redox parameter NAD(P)H/FAD increased after rotenone in contrast to its decrease in glycolytic cells. Autofluorescence decay indicated decreased NADPH/NADH ratios with rotenone in both metabolic modes. SkQ1 did not increase cell respiration and diminished Jm established high by antimycin or myxothiazol but not by stigmatellin. The revealed SkQ1 antioxidant modes reflect its reduction to SkQ1H2 at Complex I IQ or Complex III Qi site. Both reductions diminish electron diversions to oxygen thus attenuating superoxide formation. Resulting SkQ1H2 oxidizes back to SkQ1at the second (flavin) Complex I site, previously indicated for MitoQ10. Regeneration proceeds only at lower NAD(P)H/FAD in glycolytic cells. In contrast, cyclic SkQ1 reduction/SkQ1H2 oxidation does not substantiate antioxidant activity in intact cells in the absence of oxidative stress (neither pro-oxidant activity, representing a great advantage). A targeted delivery to oxidative-stressed tissues is suggested for the effective antioxidant therapy based on SkQ1. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Effects of rhaponticin on proliferation of SK-BR-3 breast cancer cells%土大黄苷对乳腺癌细胞SK-BR-3增殖的影响

    Institute of Scientific and Technical Information of China (English)

    赵素容; 段海峰; 许尹; 卢兖伟; 蒋志文

    2010-01-01

    目的 观察土大黄苷对乳腺癌细胞SK-BR-3增殖的影响,并初步探讨其作用机制.方法 采用MTT法检测土大黄苷对SK-BR-3细胞的增殖抑制作用,倒置显微镜下观察细胞的形态学变化,Western印迹检测Akt及p-Akt蛋白的表达情况.结果 土大黄苷可抑制SK-BR-3细胞增殖,其作用具有浓度和时间依赖性,72 h的IC50为(181.3±11.4)μmol/L.200、400 μmol/L土大黄苷作用48 h后显示出明显的细胞毒作用,显微镜下可见细胞碎片增多、细胞密度减小.土大黄苷在100、200、400 μmol/L浓度时均可抑制p-Akt蛋白的表达.结论 土大黄苷可抑制SK-BR-3细胞的增殖,其机制可能与抑制p-Akt表达有关.

  11. Effect of morphine on L-calcium channel of SK-N-SH human neuroblastoma cells%吗啡对人神经母细胞瘤SK-N-SH细胞L-Ca2+ 通道的作用

    Institute of Scientific and Technical Information of China (English)

    雷洪伊; 徐世元; 张庆国; 叶小平

    2008-01-01

    Objective To study the effect of morphine on L-calcium channels of SK-N-SH human neuroblastoma cells.Metllods SK-N-SH human neuroblastoma cells were cultured in vitro. Electrical current and conductance of calcium channels of SK-N-SH cells were measured using cell-attached patch clamp technique in the presence of morphine with different concentrations(0.10-8 mol/L,10-7 mol/L,10-6 mol/L and 10-5 mol/L)preteated with or without naloxone(10-5 mol/L).Results Electrical current of L-calcium channels of SK-N-SH human neuroblastoma cells was concentration-dependently depressed by morphine(P <0.01 at concentrations of 10-7,10-6 and 10-5 mol/L).Pretreatment with naloxone eliminated the morphine-induced depression on electrical current of calcium channels. Electric conductance of calcium channels did not change in the presence or absence of morohine. Conclusions Morphine inhibits electric current of L-type calcium channels of SK-N-SH human neuroblastoma cells in a manner of concentration dependence,probably via blockade of μ-opioid receptor;but does not influence electric conductence ot L-type calcium channels.%目的 观察吗啡对人神经母细胞瘤SK-N-SH细胞L-Ca2+通道的影响.方法 培养人神经母细胞瘤SK-N-SH细胞,应用细胞贴附式膜片钳技术记录在不同浓度吗啡(0、10-8 mol/L、10-7 mol/L、10-6 mol/L、10-5 mol/L)作用下SK-N-SH细胞L-Ca2+通道电流和电导变化.预先加入10-5 mol/L纳洛酮后,再依次加入上述不同浓度吗啡,记录此通道电流和电导.结果 10-7 mol/L、10-6 mol/L、10-5 mol/L吗啡可抑制SK-N-SH细胞L-型Ca2+通道电流,吗啡浓度为10-6mol/L、10-5 mol/L时抑制作用更明显(P<0.01),具有浓度依赖性;各浓度吗啡对L-Ca2+通道电导无影响;预先加入纳络酮,可阻断吗啡对该通道的抑制作用.结论 吗啡可抑制SK-N-SH细胞上L-Ca2+通道电流,对该通道电导无作用.纳络酮可翻转吗啡的作用,其抑制作用可能通过μ阿片受体产生.

  12. THE EFFECT OF CASEIN HYDROLYSATES ON TRANSGLUTAMINASE PRODUCTION BY STRETOVERTICILLUM SK-2%酪蛋白水解物对轮枝链霉菌SK-1产谷氨酰胺转胺酶的影响

    Institute of Scientific and Technical Information of China (English)

    常中义; 江波; 王璋

    2001-01-01

    酪蛋白经胰酶水解后,可以被轮枝链霉菌SK-1所利用.采用pH-STAT法得到了DH=3、DH=6、DH=9、DH=12等4个水解度的酪蛋白水解物.当酪蛋白水解物作氮源时,其水解度(即肽相对分子质量的大小)对轮枝链霉菌SK-1产谷氨酰胺转胺酶酶影响很大,其中以DH=3的酪蛋白水解物效果最好,而且肽的浓度对轮枝链霉菌SK-1产谷胺酰胺转胺酶也有一定的影响,其中以4%的浓度最为合适.%After being hydrolyzing,casein was utilized by Stretoverticillium SK-2.Casein hydrolyzated (DH=3,DH=6,DH=9,DH=12)wer e obtained wit h pancreatin.When the casein hydrolyzates were used as a nitrogen source,the der gree of hydrolysis(the molecular weight of casein peptide)had a significant infl uence on the production of transglutaminae by Stretoverticillium SK- 2 and the op timum value was DH=3,The production of transglutaminase also depend on the c oncentration of casein peptide and,with 4% addition of DH=3 casein peptide,t he production of transglutaminase reached 3.89 u/mL.

  13. 熊果酸对乳腺癌SK-BR-3细胞增殖和凋亡的影响%Effects of Ursolic Acid on Proliferation and Apoptosis of SK-BR-3 Cells

    Institute of Scientific and Technical Information of China (English)

    徐新伟; 郭玲玲; 顾振纶; 蒋小岗; 周文轩; 郭次仪

    2009-01-01

    目的 探讨熊果酸(UA)对ER(-)、Her-2过表达的人乳腺癌SK-BR-3细胞增殖和凋亡的影响.方法 利用噻唑蓝(MTT)比色法观察UA对SK-BR-3细胞增殖的影响.用Hoechst 33258荧光染色及电子显微镜观察凋亡细胞核形态变化.流式细胞仪检测UA对细胞周期的影响;DNA琼脂糖凝胶电泳观察DNA片段的断裂.结果 UA明显抑制SK-BR-3细胞的增殖,差异有统计学意义(PSK-BR-3细胞阻滞在G0/G1期,差异有统计学意义(均P<0.05).DNA琼脂糖凝胶电泳显示DNA大片段的断裂.结论 UA在体外对SK-BR-3细胞具有抗增殖和诱导凋亡的作用.

  14. [Mitochondria-targeted antioxidant SkQR1 selectively protects MDR-negative cells against ionizing radiation].

    Science.gov (United States)

    Fetisova, E K; Antoshina, M M; Cherepanynets, V D; Izumov, D S; Kireev, I I; Kireev, R I; Lyamzaev, K G; Riabchenko, N I; Chernyak, B V; Skulachev, V P

    2014-01-01

    Radioprotection appeared to be an important problem of today due to atom energetic development and utilization of radiation material in the industry, science and medicine. It has been shown that mitochondrial targeted antioxidant SkQR1 could attenuate radiation injury of human erythroleukemia K562 cells. Pretreatment with SkQR1 before irradiation decreased DNA double strand breaks formation, diminished the number of chromosomal aberrations and suppressed delayed ROS production. Prevention of oxidative stress and normalization of mitochondrial function by mitochondria-targeted antioxidants may be a potential therapeutic strategy not only against immediate consequences of radiation, but, either against its late consequences such as genomic instability. SkQR1 did not protect against radiation-induced damage the K562 subline with high level of multidrug resistance (MDR) due to SkQR1 extrusion with Pgp 170 MDR pump. We suggest that mitochondria-targeted antioxidants might be used for selective protection of normal cells against radiation-induced damage without interference with radiotherapy of MDR-positive tumors.

  15. Transcription profiling of interactions between Lactococcus lactis subsp. cremoris SK11 and Lactobacillus paracasei ATCC 334 during Cheddar cheese simulation.

    Science.gov (United States)

    Desfossés-Foucault, Émilie; LaPointe, Gisèle; Roy, Denis

    2014-05-16

    The starter cultures (Lactococcus sp.) and non-starter lactic acid bacteria (mostly Lactobacillus spp.) are essential to flavor development of Cheddar cheese. The aim of this study was to elucidate the transcriptional interaction between Lactococcus lactis subsp. cremoris SK11 and Lactobacillus paracasei ATCC 334 in mixed cultures during simulated Cheddar cheese manufacture (Pearce activity test) and ripening (slurry). Reverse transcription quantitative PCR (RT-qPCR) was used to quantify the expression of 34 genes common to both bacteria and for eight genes specific to either L. lactis subsp. cremoris SK11 or L. paracasei ATCC 334. The multifactorial analysis (MFA) performed on fold change results for each gene revealed that the genes linked to stress, protein and peptide degradation as well as carbohydrate metabolism of L. paracasei ATCC 334 were especially overexpressed in mixed culture with L. lactis subsp. cremoris SK11 during the ripening simulation. For L. lactis subsp. cremoris SK11, genes coding for amino acid metabolism were more expressed during the cheese manufacture simulation, especially in single culture. These results show how complementary functions of starter and NSLAB contribute to activities useful for flavor development.

  16. Active uptake and extravesicular storage of m-iodobenzylguanidine in human neuroblastoma SK-N-SH cells

    Energy Technology Data Exchange (ETDEWEB)

    Smets, L.A.; Loesberg, C.; Janssen, M.; Metwally, E.A.; Huiskamp, R.

    1989-06-01

    Radioiodinated m-iodobenzylguanidine (MIBG), an analogue of the neurotransmitter norepinephrine (NE), is increasingly used in the diagnosis and treatment of neural crest tumors. Active uptake and subsequent retention of MIBG and NE was studied in human neuroblastoma SK-N-SH cells. Neuron-specific uptake of (125I)MIBG and (3H)NE saturated at extracellular concentration of 10(-6) M and exceeded by 20-30-fold that by passive diffusion alone. A minimum of 50% of accumulated MIBG remained permanently stored but the SK-N-SH cells were incapable of retaining recaptured (3H)NE. (125I)MIBG was displaced from intracellular binding sites by unlabeled MIBG with 10-fold higher potency than by unlabeled NE. MIBG stored in SK-N-SH cells was insensitive to depletion by the inhibitor of granular uptake reserpine (RSP) and was not precipitated in a granular fraction by differential centrifugation. Only few electron-dense granules were found in these cells by electron microscopy. In contrast, MIBG storage in PC-12 pheochromocytoma cells which contained many storage granules, was sensitive to RSP and part of accumulated drug was recovered in a granular fraction. Accordingly, storage of MIBG in the SK-N-SH neuroblastoma cells is predominantly extravesicular and thus essentially different from that of biogenic amines in normal adrenomedullary tissue or in pheochromocytoma tumors, while sharing with these tissues a common mechanism of active uptake.

  17. Production of coagulation factor VII in human cell lines Sk-Hep-1 and HKB-11.

    Science.gov (United States)

    Corrêa de Freitas, Marcela Cristina; Bomfim, Aline de Sousa; Mizukami, Amanda; Picanço-Castro, Virgínia; Swiech, Kamilla; Covas, Dimas Tadeu

    2017-09-01

    Recombinant factor VII (rFVII) is the main therapeutic choice for hemophilia patients who have developed inhibitory antibodies against conventional treatments (FVIII and FIX). Because of the post-translational modifications, rFVII needs to be produced in mammalian cell lines. In this study, for the first time, we have shown efficient rFVII production in HepG2, Sk-Hep-1, and HKB-11 cell lines. Experiments in static conditions for a period of 96 h showed that HepG2-FVII produced the highest amounts of rhFVII, with an average of 1843 ng/mL. Sk-hep-1-FVII cells reached a maximum protein production of 1432 ng/mL and HKB-11-FVII cells reached 1468 ng/mL. Sk-Hep-1-rFVII and HKB-11-rFVII were selected for the first step of scale-up. Over 10 days of spinner flask culture, HKB-11 and SK-Hep-1 cells showed a cumulative production of rFVII of 152 μg and 202.6 μg in 50 mL, respectively. Thus, these human cell lines can be used for an efficient production of recombinant FVII. With more investment in basic research, human cell lines can be optimized for the commercial production of different bio therapeutic proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. First record of fish microfossils from Ramsåsa, site C, Skåne, southern Sweden

    NARCIS (Netherlands)

    Vergoossen, J.M.J.

    2003-01-01

    Within the thelodont dominated fauna of Ramsåsa, site C, Skåne, southern Sweden (Ludlow, Whitcliffian), the scales of the Thelodus parvidens group outnumber those of the combined T. sculptilis-T. admirabilis groups, some specimens of which are indistinguishable. Scale forms that might belong to one

  19. Clinical fluctuations in MuSK myasthenia gravis are related to antigen-specific IgG4 instead of IgG1

    NARCIS (Netherlands)

    Niks, E H; van Leeuwen, Y; Leite, M I; Dekker, F W; Wintzen, A R; Wirtz, P W; Vincent, A; van Tol, M J D; Jol-van der Zijde, C M; Verschuuren, J J G M

    2008-01-01

    We studied the longitudinal relation between disease severity and titers of antigen-specific IgG subclasses in sera of patients with myasthenia gravis and antibodies to Muscle Specific Kinase (MuSK MG). Six patients were included of whom 55 samples had been collected during 2.5-13.4 years. Anti-MuSK

  20. Application program of CRUST-1 10km continental scientific drilling rig in SK-2 scientific drilling well

    Science.gov (United States)

    Sun, Youhong; Gao, Ke; Yu, Ping; Liu, Baochang; Guo, Wei; Ma, Yinlong; Yang, Yang

    2014-05-01

    SK-2 Well is located in DaQing city,where is site of the largest oil field in China,Heilongjiang province, north-east of China.The objective of SK-2 well is to obtain full cores of cretaceous formation in Song Liao basin,and to build the time tunnel of Cretaceous greenhouse climate change,and to clarify the causes,processes and results of the formations of DaQing oil field. This will ensure to achieve our ultimate goals,to test the CRUST-1 drilling rig and improve China's deep scientific drilling technology,to form the scientific drilling technology,method and system with independent intellectual property rights,and to provide technical knowledge and information for China's ten kilometers super-deep scientific drilling technical resources.SK-2 Well is at 6400 meter depth, where the drilling inclination is 90 degree and the continuous coring length is 3535 meter that from 2865 to 6400 meter,the recovery rate of the core is greater or equal to 95 percent with 100 millimeters core diameter and 3.9 degree per 100 meter geothermal gradient.The CRUST-1 rig is designated with special drilling equipment for continental scientific drilling combined to the oil drilling equipment ability with advanced geological drilling technology which is highly automatic and intelligent. CRUST-1 drilling ability is 10000 meter with the maximum hook load 700 tons, the total power is 4610 Kilowatt.CRUST-1 will be integrated with a complete set of automation equipment,including big torque hydraulic top drive,high accuracy automatic drilling rod feeding system, suspended automatic drill string discharge device,hydraulic intelligent iron roughneck,and hydraulic automatic catwalk to fully meet the drilling process requirements of SK-2.Designed with advanced drilling technique for 260 degree in the bottom of SK-2 well and hard rock,including the drilling tools of high temperature hydraulic hammer,high temperature resistance and high strength aluminum drill pipe,high temperature preparation of mud

  1. [Rhein lysinate induces apoptosis in breast cancer SK-Br-3 cells by inhibiting HER-2 signal pathway].

    Science.gov (United States)

    Lin, Ya-Jun; Huang, Yun-Hong; Zhen, Yong-Zhan; Liu, Xiu-Jun; Zhen, Yong-Su

    2008-11-01

    This study is to investigate the effect of rhein lysinate on inducing human breast cancer cell line SK-Br-3 apoptosis and the role of HER-2 signal pathway in the apoptosis. MTT assay was used to detect SK-Br-3 cell proliferation. Cell cycle and apoptosis were analyzed by flow cytometry. The protein expression and the protein phosphorylation of HER-2 signal pathway were detected by Western blotting. The level of HER-2 mRNA was detected by RT-PCR and the level of HER-2 expression was also detected by immunofluorescence cytochemical methods. The results showed that rhein lysinate remarkably inhibited breast cancer SK-Br-3 cell proliferation. The IC50 value for 48 h treatment was 85 micromol x L(-1). Apoptosis in SK-Br-3 cells was induced by rhein lysinate in a dose dependent manner. The protein expressions of HER-2, NF-KB, and the protein phosphorylation of HER-2 were downregulated, however the protein expression of p53 and p21 was upregulated after rhein lysinate treatment. The level of HER-2 mRNA decreased by using RT-PCR assay and the level of HER-2 expression was also decreased by using immunofluorescence cytochemical assay after rhein lysinate treatment. It can be concluded that rhein lysinate could inhibit SK-Br-3 cell proliferation and induce apoptosis. HER-2/NF-kappaB/p53/p21 signal pathway might be involved in this process. Rhein lysinate has a good prospect to be an adjuvant chemotherapeutic drug.

  2. 海兔素对人乳腺癌SK-BR-3细胞的抑制作用及机制研究%Effect of Aplysin on the Proliferation and Apoptosis in Human Breast Cancer SK-BR-3

    Institute of Scientific and Technical Information of China (English)

    马文龙; 梁惠; 刘颖

    2012-01-01

    本文阐述了海兔素(Aplysin)对人乳腺癌SK-BR-3细胞增殖和凋亡的影响,并探讨了其可能的作用机制.分别采用CCK-8法和流式细胞术Annexin V-FITC/PI双染法测定不同剂量海兔素对SK-BR-3细胞的增殖抑制和凋亡诱导作用,并以Western blot测定SK-BR-3细胞中EGFR、Akt及ERK表达水平和磷酸化水平.结果发现,20、30、40、45、50、55、60 mg/L海兔素处理SK-BR-3细胞24 h后,细胞的生长增殖明显受到抑制,呈量效依赖性,其IC25和IC50值为分别为29.4和33.7 mg/L; IC25和IC50剂量海兔素可明显诱导细胞凋亡,并下调SK-BR-3细胞EGFR、Akt及ERK的磷酸化蛋白表达水平,但是不影响总蛋白表达水平.表明海兔素对人乳腺癌SK-BR-3细胞具有抑制增殖和诱导凋亡的作用,其作用机制可能与海兔素抑制细胞中EGFR蛋白磷酸化,进而阻断下游效应分子Akt和ERK的活化有关.%The effects of aplysin, nature extract from Laurencia, on the proliferation and apoptosis on human breast cancer SK-BR-3 cells were investigated in this study. After treatment with aplysin at a serial of concentrations,cell proliferation was investigated by using Cell Counting Kit-8 and apoptosis was analyzed by Annexin V-FTTC/PI staining via flow cy-tometry.The total and phosphorylated proteins of EGFR.Akt,and ERK were detected by western blot. The results showed that aplysin was able to inhibit SK-BR-3 cell proliferation in a concentration dependent manner within the concentration range of 20,30,40,45,50,55,and 60 mg/L. Aplysin could induce significant apoptosis at the dose of IC25 and IC50. Phosphorylation levels of the receptor of EGFR and cytoplasmic protein of Akt and ERK were significantly down-regulated by aplysin at the dose of IC25 and IC50,while their total protein expression levels were not affected. The results indicated that aplysin could inhibit SK-BR-3 cell proliferation and induce apoptosis by blocking EGFR/Akt and EGFR/ERK signal pathways.

  3. The Inhibiting Effect of Wild Cactus Polysaccharide on Lung Squamous Carcinoma Cells (SK-MES-1)%野生仙人掌多糖对肺鳞癌细胞SK-MES-1生长的抑制作用

    Institute of Scientific and Technical Information of China (English)

    吴迪; 魏斌; 王双; 孙海霞; 辛毅; 张翠丽

    2012-01-01

    目的:探讨仙人掌多糖对体外肺鳞癌细胞(SK-MES-1)生长抑制作用.方法:体外培养SK-MES-1细胞,四甲基偶氮唑盐(MTT)法观察野生仙人掌多糖对其生长的抑制,计算最低抑制浓度及抑制率;观察不同浓度多糖对细胞形态的影响:SDS-PAGE凝胶电泳简析不同组别蛋白质表达的差异.结果:野生仙人掌多糖24 h和48 h对肿瘤细胞的最低抑制浓度和抑制率分别为0.0625 mg/ml.34.06%和0.0625 mg/ml 35.37%;不同组间蛋白质表达有差异.结论:野生仙人掌多糖对SK-MES-1肺鳞癌细胞有抑制作用.%Objective: To investigate the anti-tumor effect of wild Cactus polysaccharide on SK-MES-1 lung squamous carcinoma cells. Methods: SK-MES-1 cells were cultivated in vitro. MTT assay was used to detect the inhibition phenomena of wild Cactus polysaccharide on the growth of tumor cells, calculated the lowest inhibition concentration and tumor inhibitive ratio(IR). The influence of different concentrations of polysaccharide on cell shape was examined respectively. SDS-PAGE assay was used to estimate the difference of protein expression among each group. Results: The lowest inhibition concentration and IR of wild Cactus polysaccharide to SK-MES-1 for 24 h and 48h were 0.0625 mg/ml, 34.06% and 0.0625 mg/ml, 35.37%. The protein expression was different in each group. Conclusion: Wild Cactus polysaccharide had anti-tumor effect on lung squamous carcinoma cells.

  4. Microwave Accelerated Transglycosylation of Rutin by Cyclodextrin Glucanotransferase from Bacillus sp. SK13.002

    Directory of Open Access Journals (Sweden)

    Beilei Pan

    2011-06-01

    Full Text Available Rutin was subjected to intermolecular transglycosylation assisted with microwave irradiation using cyclodextrin glucanotransferase (CGTase produced from Bacillus sp. SK13.002. Compared with the conventional enzymatic method for rutin transglycosylation (without microwave irradiation, microwave-assisted reaction (MAR was much faster and thus more efficient. While the conventional reaction took dozens of hours to reach the highest conversion rate of rutin and yield of transglycosylated rutin, MAR of rutin transglycosylation completed within only 6 min providing almost the same conversion rate of rutin and yield of products consisting of mono-, di-, tri-, tetra-, penta-glucosylated rutins. The optimum transglycosylation conditions for microwave irradiation were 40 °C and 60 W with the reaction system consisting mainly of the mixture of 0.3 g rutin (0.49 mmol pre-dissolved in 15 mL methanol, 1.8 g maltodextrin in 15 mL of 0.2 M sodium acetate buffer (pH 5.5 and CGTase (900 U. Results from this study indicated that MAR could be a potentially useful and economical technique for a faster and more efficient transglycosylation of rutin.

  5. Morroniside protects SK-N-SH human neuroblastoma cells against H2O2-induced damage.

    Science.gov (United States)

    Zhang, Jing-Xing; Wang, Rui; Xi, Jin; Shen, Lin; Zhu, An-You; Qi, Qi; Wang, Qi-Yi; Zhang, Lun-Jun; Wang, Feng-Chao; Lü, He-Zuo; Hu, Jian-Guo

    2017-03-01

    Oxidative stress-induced cell injury has been linked to the pathogenesis of neurodegenerative disorders such as spinal cord injury, Parkinson's disease, and multiple sclerosis. Morroniside is an antioxidant derived from the Chinese herb Shan-Zhu-Yu. The present study investigated the neuroprotective effect of morroniside against hydrogen peroxide (H2O2)-induced cell death in SK-N-SH human neuroblastoma cells. H2O2 increased cell apoptosis, as determined by flow cytometry and Hoechst 33342 staining. This effect was reversed by pretreatment with morroniside at concentrations of 1-100 µM. The increase in intracellular reactive oxygen species (ROS) generation and lipid peroxidation induced by H2O2 was also abrogated by morroniside. H2O2 induced a reduction in mitochondrial membrane potential, increased caspase-3 activity, and caused downregulation of B cell lymphoma-2 (Bcl-2) and upregulation of Bcl-2-associated X protein (Bax) expression. These effects were blocked by morroniside pretreatment. Thus, morroniside protects human neuroblastoma cells against oxidative damage by inhibiting ROS production while suppressing Bax and stimulating Bcl-2 expression, thereby blocking mitochondrial-mediated apoptosis. These results indicate that morroniside has therapeutic potential for the prevention and treatment of neurodegenerative diseases.

  6. [Analytical chemistry in works of Maria Skłodowska-Curie].

    Science.gov (United States)

    Hulanicki, Adam

    2012-01-01

    Maria Skłodowska-Curie--a Nobel Prize winner in chemistry--the elements of learning of chemistry gained just by a dint of work of more than ten months in Warsaw in the Institute of Industry and Agriculture Museum. The Nobel Prize concerned a contribution to the progress of chemistry through the discovery of radium and polonium, separation of radium and study of properties of this amazing element. It was awarded for an extremely arduous work, during which the chemical reactions being the principles of analytical chemistry were realized. Unlike to a typical analytical procedure, an initial attempt here was the thousands of kilograms of uranium ore: pitchblende. The final effect was small amounts of new elements: polonium and radium. Both the knowledge and the intuition of the researcher let her have a triumph. The difficulties she experienced because the properties of the searched chemical elements could only be evaluated thanks to the knowledge on other chemical elements. A significant achievement was the determination of the samples by means of radioactivity measurement, which gave rise to radiochemical analytical methods. An extreme analytical precision was demanded in multiple processes of fractional crystallization and precipitation which finally led to the calculation of the atomic mass of radium.

  7. Operation of milling-cutter crushers in the Sukhodol'sk coal preparation plant

    Energy Technology Data Exchange (ETDEWEB)

    Lesikov, A.V.

    1984-04-01

    The Sukhodol'sk coal preparation plant, constructed in 1962 in the Donbass, and with a capacity 4,900 t/d, is equipped with 2 railroad car tippler systems. Coal is supplied in MPS cars. In winter, coal fines supplied to the plant freeze and form large blocks which do not pass through screens separating tipplers from coal hoppers. Breaking up coal blocks is time consuming. From 6 to 18 workers cut coal each day in winter. The Voroshilovgradugleobogashchenie developed the DFM-2 milling cutter for breaking up coal blocks in 1980. In 1982 the system was modified. The cutting drum which consists of 23 discs has a diameter of 750 mm and is 3850 mm wide, revolution rate is 245 rpm. The system is driven by AO2-92-6 and AO2-52-6 electric motors with a rated power of 7.5 kW. The complete milling cutter system consists of 2 units of DFM-2 cutters. The DFM-2 weighs 10.64 t, is 2.3 m long, 3.83 m wide and 1.28 m high. Cutting frozen coal blocks unloaded from a railroad car by means of the DFM-2 system does not take more than 1.5 min. Use of the system eliminates manual operations.

  8. Komposition som projekt i heterogena studentgrupper: Ett exempel från skådespelarutbildningen

    Directory of Open Access Journals (Sweden)

    Sven Bjerstedt

    2015-12-01

    Full Text Available En vanligt förekommande utmaning i högre utbildning är översiktskurser med snäva tidsramar och heterogena studentgrupper. Artikeln vill peka på den positiva potentialen i sådana omständigheter genom att presentera ett konkret exempel på ett arbetssätt som har visat sig framgångsrikt inom skådespelarutbildningens musikundervisning: tonsättningsuppgifter som konceptualiseras individuellt och realiseras gemensamt. I en intervjustudie visas detta arbetssätt ha positiv påverkan på studenternas individuella utveckling i flera avseenden. Bland de läranderesultat som förefaller särskilt intressanta och potentiellt överförbara till åtskilliga ämnesområden finns självförtroende, förmåga att kommunicera samt förmåga att gemensamt hantera en kreativ process.

  9. Developing translational medicine professionals: the Marie Skłodowska-Curie action model.

    Science.gov (United States)

    Petrelli, Alessandra; Prakken, Berent J; Rosenblum, Norman D

    2016-11-29

    End goal of translational medicine is to combine disciplines and expertise to eventually promote improvement of the global healthcare system by delivering effective therapies to individuals and society. Well-trained experts of the translational medicine process endowed with profound knowledge of biomedical technology, ethical and clinical issues, as well as leadership and teamwork abilities are essential for the effective development of tangible therapeutic products for patients. In this article we focus on education and, in particular, we discuss how programs providing training on the broad spectrum of the translational medicine continuum have still a limited degree of diffusion and do not provide professional support and mentorship in the long-term, resulting in the lack of well established professionals of translational medicine (TMPs) in the scientific community. Here, we describe the Marie Skłodowska-Curie Actions program ITN-EUtrain (EUropean Translational tRaining for Autoimmunity & Immune manipulation Network) where training on the Translational Medicine machinery was integrated with education on professional and personal skills, mentoring, and a long-lasting network of TMPs.

  10. Characterization of Probiotic Jelly Drinks with Addition of Lactobacillus plantarum (SK5 from Bekasam during Storage

    Directory of Open Access Journals (Sweden)

    Susi Merry Marini

    2017-02-01

    Full Text Available AbstractLactic acid bacteria from bekasam has potential as an antimicrobial and enzyme producer, as well as probiotics. The purpose of this study were to get the selected formula of the jelly drink with the addition of carrageenan by organoleptic and determine the effect of adding wet biomass (WB and dry biomass (DB Lactobacillus plantarum (SK5 from bekasam against chemical and microbiological parameters jelly beverage probiotics during storage. This study consisted of two phases where a preliminary study to determine the best carrageenan concentration and primary research to determine the chemical and microbiological characteristics jelly drink probiotics during storage. Concentrations of carrageenan used were 0.67%; 1% and 1.34%. The best concentration obtained from the preliminary study was 0.67%. The pH of WB during storage decreased to 2.29; total microbial 0.91 log cfu/g; BAL total of 0.2 log cfu/g; dietary fiber 1.26% and 0.53% total sugars. Dry biomass characterization during storage decreased to pH of 2.54; Microbial total of 3.13 log cfu/g; LAB total of 2.22 log cfu/g, while the increase of the dietary fiber of 2.13% and total sugars 1.96%.

  11. A novel subtilase with NaCl-activated and oxidant-stable activity from Virgibacillus sp. SK37

    Directory of Open Access Journals (Sweden)

    Yamabhai Montarop

    2011-06-01

    Full Text Available Abstract Background Microbial proteases are one of the most commercially valuable enzymes, of which the largest market share has been taken by subtilases or alkaline proteases of the Bacillus species. Despite a large amount of information on microbial proteases, a search for novel proteases with unique properties is still of interest for both basic and applied aspects of this highly complex class of enzymes. Oxidant stable proteases (OSPs have been shown to have a wide application in the detergent and bleaching industries and recently have become one of the most attractive enzymes in various biotechnological applications. Results A gene encoding a novel member of the subtilase superfamily was isolated from Virgibacillus sp. SK37, a protease-producing bacterium isolated from Thai fish sauce fermentation. The gene was cloned by an activity-based screening of a genomic DNA expression library on Luria-Bertani (LB agar plates containing 1 mM IPTG and 3% skim milk. Of the 100,000 clones screened, all six isolated positive clones comprised one overlapping open reading frame of 45% identity to the aprX gene from Bacillus species. This gene, designated aprX-sk37 was cloned into pET21d(+ and over-expressed in E. coli BL21(DE3. The enzyme product, designated AprX-SK37, was purified by an immobilized metal ion affinity chromatography to apparent homogeneity and characterized. The AprX-SK37 enzyme showed optimal catalytic conditions at pH 9.5 and 55°C, based on the azocasein assay containing 5 mM CaCl2. Maximum catalytic activity was found at 1 M NaCl with residual activity of 30% at 3 M NaCl. Thermal stability of the enzyme was also enhanced by 1 M NaCl. The enzyme was absolutely calcium-dependent, with optimal concentration of CaCl2 at 15 mM. Inhibitory effects by phenylmethanesulfonyl fluoride and ethylenediaminetetraacetic acid indicated that this enzyme is a metal-dependent serine protease. The enzyme activity was sensitive towards reducing agents

  12. Manumycin诱导细胞凋亡抑制乳腺癌细胞SK-BR-3活性%Manumycin inhibits the activity of breast cancer cell line SK-BR-3 via inducing apoptosis

    Institute of Scientific and Technical Information of China (English)

    陶祥; 杨惠玲; 杨林; 郑芹

    2004-01-01

    目的:研究manumycin对乳腺癌腹腔转移癌细胞株SK-BR-3的抑癌效应及其诱导凋亡.方法: 用MTT法检测manumycin对SK-BR-3细胞的抑癌作用.免疫印迹方法检测p38 MAPK蛋白表达.用caspase-3活性检测试剂盒定量检测manumycin诱导细胞凋亡的水平及评估特异性的p38 MAPK抑制剂SB203580对凋亡的影响.结果: 经6 μmol/L、18 μmol/L、54 μmol/L manumycin处理SK-BR-3细胞24 h时,其抑制率分别为(7.4±3.9)%、(21.0±4.4)%和(64.7±4.1)%,呈量效关系.其中后2者的细胞活性与对照组比有显著差异(P<0.01).用药24 h的IC50为42.5 μmol/L.同时此药物可明显增加caspase-3的活性,且这一效应可部分地被p38抑制剂SB203580阻断.免疫印迹结果显示manumycin促进p38的磷酸化.结论:manumycin可通过诱导SK-BR-3细胞凋亡而产生抑癌作用,p38 MAPK是manumycin诱导细胞凋亡的通路之一.

  13. A research on the equipment and use of hydraulic hammer on SK320-6%神钢SK320-6挖掘机液压锤的配置及使用

    Institute of Scientific and Technical Information of China (English)

    翁东玲; 曾利文

    2006-01-01

    系统论证神钢SK320-6履带式液压挖掘机与英格索兰(INGERSOLL-RAND)Ⅵ1200液压锤的配置合理性,分析改装和使用时需注意的事项,从而扩展液压挖掘机在工程实际中的用途.

  14. TaSK5, an abiotic stress-inducible GSK3/shaggy-like kinase from wheat, confers salt and drought tolerance in transgenic Arabidopsis.

    Science.gov (United States)

    Christov, Nikolai Kirilov; Christova, Petya Koeva; Kato, Hideki; Liu, Yuelin; Sasaki, Kentaro; Imai, Ryozo

    2014-11-01

    A novel cold-inducible GSK3/shaggy-like kinase, TaSK5, was isolated from winter wheat using a macroarray-based differential screening approach. TaSK5 showed high similarity to Arabidopsis subgroup I GSK3/shaggy-like kinases ASK-alpha, AtSK-gamma and ASK-epsilon. RNA gel blot analyses revealed TaSK5 induction by cold and NaCl treatments and to a lesser extent by drought treatment. TaSK5 functionally complemented the cold- and salt-sensitive phenotypes of a yeast GSK3/shaggy-like kinase mutant, △mck1. Transgenic Arabidopsis plants overexpressing TaSK5 cDNA showed enhanced tolerance to salt and drought stresses. By contrast, the tolerance of the transgenic plants to freezing stress was not altered. Microarray analysis revealed that a number of abiotic stress-inducible genes were constitutively induced in the transgenic Arabidopsis plants, suggesting that TaSK5 may function in a novel signal transduction pathway that appears to be unrelated to DREB1/CBF regulon and may involve crosstalk between abiotic and hormonal signals.

  15. Effects of SK-896, a new human motilin analogue ([Leu13]motilin-Hse), on postoperative ileus in dogs after laparotomy.

    Science.gov (United States)

    Furuta, Yoshiyuki; Takeda, Motohiro; Nakayama, Yukiharu; Ito, Mikio; Suzuki, Yoshio

    2002-08-01

    The effects of SK-896, a new human motilin analogue ([Leu13]motilin-Hse), on digestive tract motility in postoperative ileus were evaluated in a dog model of ileus after laparotomy. SK-896 was intravenously administered at 0.17, 0.33 and 0.67 microg/kg starting soon after operation and then at 6-h intervals, for a total of 9 times. SK-896 progressively, dose-dependently and significantly increased the duodenal motility from 1 h after operation. The recovery time of the gastrointestinal-interdigestive migrating complex (GI-IMC) activity, which is an indicator of normal gastrointestinal tract activity after laparotomy, was 56.5 +/- 5.0 h in the control group. SK-896 significantly shortened this recovery time. On the other hand, the plasma SK-896 concentrations declined diexponentially after administration, and can be described by a linear pharmacokinetic model within the dose range used. In addition, the pharmacokinetics of SK-896 did not change significantly at any postoperative time. There was no correlation between the plasma SK-896 concentrations and the intensity of duodenal motility, because the activity in the duodenum decreased transiently 13 h after laparotomy and increased with time thereafter. The changes in the activity are considered to reflect the progressive changes in the state of ileus. In conclusion, SK-896 increased the duodenal motility significantly, shortening the recovery time of GI-IMC-like activity in dogs with post-laparotomy ileus. Therefore, it is expected from these results that SK-896 would be useful and effective for the treatment of gastroparalysis after abdominal surgery.

  16. Inhibition of SK4 Potassium Channels Suppresses Cell Proliferation, Migration and the Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Panshi Zhang

    Full Text Available Treatments for triple-negative breast cancer (TNBC are limited; intermediate-conductance calcium-activated potassium (SK4 channels are closely involved in tumor progression, but little is known about these channels in TNBC. We aimed to investigate whether SK4 channels affect TNBC. First, by immunohistochemistry (IHC and western blotting (WB, increased SK4 protein expression in breast tumor tissues was detected relative to that in non-tumor breast tissues, but there was no apparent expression difference between various subtypes of breast cancer (p>0.05. Next, functional SK4 channels were detected in the TNBC cell line MDA-MB-231 using WB, real-time PCR, immunofluorescence and patch-clamp recording. By employing SK4 specific siRNAs and blockers, including TRAM-34 and clotrimazole, in combination with an MTT assay, a colony-formation assay, flow cytometry and a cell motility assay, we found that the suppression of SK4 channels significantly inhibited cell proliferation and migration and promoted apoptosis in MDA-MB-231 cells (p<0.05. Further investigation revealed that treatment with epidermal growth factor (EGF/basic fibroblast growth factor (bFGF caused MDA-MB-231 cells to undergo the epithelial-mesenchymal transition (EMT and to show increased SK4 mRNA expression. In addition, the down-regulation of SK4 expression inhibited the EMT markers Vimentin and Snail1. Collectively, our findings suggest that SK4 channels are expressed in TNBC and are involved in the proliferation, apoptosis, migration and EMT processes of TNBC cells.

  17. Very high weight ratios of S/K in individual haze particles over Kalimantan during the 1997 Indonesian forest fires

    Science.gov (United States)

    Ikegami, Miwako; Okada, Kikuo; Zaizen, Yuji; Makino, Yukio; Jensen, Jorgen B.; Gras, John L.; Harjanto, Hery

    The elemental composition of individual aerosol particles of 0.15-3 μm radius, collected over Kalimantan during the 1997 Indonesian forest fire event, was analyzed using a transmission electron microscope equipped with an energy-dispersive X-ray analyzer (EDX). Although 60-90% of the particles collected at altitudes of 1-5 km contained K, they exhibited high weight ratios of S/K with median values of 9-18 independent of particle size. These were much larger than those (median values of 2-4) obtained from the forest fires in northern Australia. The high weight ratios over Kalimantan are considered to be due to the heterogeneous growth of particles through the oxidation of SO 2. In addition to SO 2 from the combustion of forest biomass, SO 2 originating from the combustion of peat below the ground is believed to have been important in producing the high S/K ratios.

  18. Genome-wide analysis of KAP1, the 7SK snRNP complex, and RNA polymerase II

    Directory of Open Access Journals (Sweden)

    Ryan P. McNamara

    2016-03-01

    Full Text Available The transition of RNA polymerase II (Pol II from transcription initiation into productive elongation in eukaryotic cells is regulated by the P-TEFb kinase, which phosphorylates the C-terminal domain of paused Pol II at promoter-proximal regions. Our recent study found that P-TEFb (in an inhibited state bound to the 7SK snRNP complex interacts with the KAP1/TRIM28 transcriptional regulator, and that KAP1 and the 7SK snRNP co-occupy most gene promoters containing paused Pol II. Here we provide a detailed experimental description and analysis of the ChIP-seq datasets that have been deposited into Gene Expression Omnibus (GEO: GS72622, so that independent groups can replicate and expand upon these findings. We propose these datasets would provide valuable information for researchers studying mechanisms of transcriptional regulation including Pol II pausing and pause release.

  19. The anti-inflammatory effect of the SOCC blocker SK&F 96365 on mouse lymphocytes after stimulation by Con A or PMA/ionomycin.

    Science.gov (United States)

    Ye, Yanxia; Zhang, Yaxing; Lu, Xiaoyu; Huang, Xiuyan; Zeng, Xiangfeng; Lai, Xinqiang; Zeng, Yaoying

    2011-09-01

    SK&F 96365, 51-(beta-[3-(p-methoxyphenyl)-propyloxy]-p-methoxyphenethyl)-1H-imidazole hydrochloride, has emerged as a useful pharmacological tool in the study of store-operated Ca²⁺ entry (SOCE). But the precise molecular mechanism and effect of SK&F 96365 on mouse lymphocytes are still not well determined. This study investigated the pharmacological profile of SK&F 96365 on mouse lymphocytes stimulated by mitogen concanavalin A (Con A) or by a combination of a protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA) and a calcium ionophore, ionomycin in vitro. Our results showed that SK&F 96365 pre-treatment diminished the cytosolic calcium rise on lymphocytes induced by ionomycin, PMA/ionomycin, and thapsigargin (TG), respectively. CFDA-SE staining results showed that SK&F 96365 (5-20 μM) inhibited both Con A- and PMA/ionomycin-induced lymphocytes proliferation in a time- and dose-dependent manner. Upon the same stimulation, SK&F 96365 inhibited the expression of CD69 and CD25 on CD3⁺ T lymphocytes in a dose-dependent manner. The cell cycle analyzing results showed that SK&F 96365 caused a G0/G1 phase cell cycle arrest on both Con A- and PMA/ionomycin-activated lymphocytes in a dose-dependent manner. In addition, SK&F 96365 induced a decrease in mitochondrial membrane potential (ΔΨm) and promoted mitochondrial permeability transition (MPT) in both Con A- and PMA/ionomycin-activated lymphocytes. Furthermore, SK&F 96365 significantly inhibited the production of proinflammatory cytokines (interferon (IFN)-γ and tumor necrosis factor (TNF)), and the anti-inflammatory cytokine (IL-10) on both Con A- and PMA/ionomycin-activated lymphocytes. SK&F 96365 did not induce a statistically significant increase in levels of proinflammatory IL-6 and monocyte chemoattractant protein-1 (MCP-1) but of IL-12p70 upon the stimulation of Con A, whereas these three cytokines were markedly inhibited by it upon the stimulation of PMA/ionomycin. This finding

  20. Hafnium-neodymium constraints on source heterogeneity of the economic ultramafic-mafic Noril'sk-1 intrusion (Russia)

    Science.gov (United States)

    Malitch, K. N.; Belousova, E. A.; Griffin, W. L.; Badanina, I. Yu.

    2013-04-01

    The ultramafic-mafic Noril'sk-1 intrusion in Polar Siberia (Russia) hosts one of the world's major platinum-group-element (PGE)-Cusbnd Ni sulphide deposits. In situ Hf-isotope analyses of zircon and baddeleyite, combined with whole-rock Nd-isotope results, identify three distinct clusters of Hfsbnd Nd isotope values restricted to different lithological units (e.g., gabbro-diorite, unmineralised layered sequence gabbros, and mineralised portions, represented by ultramafic and taxitic-textured rocks). Hf-isotope signatures of zircon and baddeleyite from unmineralized mafic rocks (ɛHf from 7.3 ± 1.1 to 11.4 ± 0.3) reflect the dominant role of mantle-derived magmas and suggest that a juvenile mantle was one of the main sources for the ultramafic-mafic Noril'sk-1 intrusion. The less radiogenic Hf-isotope values for zircons from mineralised rocks (ɛHf from 4.9 ± 1.4 to 6.4 ± 1.2) and gabbro-diorite (ɛHf - 1.2 ± 1.9) are indicative of involvement of distinct source components, possibly equivalent to a subcontinental lithospheric mantle and a continental crust, respectively. The significant range in the initial 176Hf/177Hf values of unmineralised rocks and mineralised lithologies indicates interaction of distinct magma sources during formation of the Noril'sk-1 intrusion. Our new findings, in conjunction with whole-rock Nd-isotope results, imply that economic intrusions hosting PGE-Cusbnd Ni deposits of the Noril'sk area have a far more complex magmatic history than is commonly assumed.

  1. The first recorded bloom of Pseudochattonella farcimen (Dictyochophyceae, Heterokonta, (Riisberg I., 2008 in the Gulf of Gdańsk

    Directory of Open Access Journals (Sweden)

    Maria Łotocka

    2009-03-01

    Full Text Available In April 2001 a local bloom of the heterokont phytoflagellate Pseudochattonella farcimen (Riisberg I., 2008 (initially named Chattonella aff. verruculosa was observed for the first time in the southern part of the Gulf of Gdańsk.The species occurred in high cell densities: the count was 11.5 × 106 cells dm-3 and the biomass 927.5 µgC dm-3.

  2. METCAM/MUC18 augments migration, invasion, and tumorigenicity of human breast cancer SK-BR-3 cells.

    Science.gov (United States)

    Zeng, Guofang; Cai, Shaoxi; Liu, Yuan; Wu, Guang-Jer

    2012-01-15

    Previous research has identified METCAM/MUC18, an integral membrane cell adhesion molecule (CAM) in the Ig-like gene super-family, as a promoter or a suppressor in the development of human breast cancer by MCF7, MDA-MB-231, and MDA-MB-468. To resolve these conflicting results we have investigated the role of this CAM in the progression of the three aforementioned cell lines plus one additional human breast cancer cell line, SK-BR-3. We transfected the SK-BR-3 cells with human METCAM/MUC18 cDNA to obtain G418-resistant clones, which expressed different levels of the protein and which were used to test the effect of human METCAM/MUC18 expression on in vitro motility, invasiveness, anchorage-independent colony formation in soft agar, disorganized growth in a 3D basement membrane culture assay, and in vivo tumorigenesis in athymic nude mice. Enforced METCAM/MUC18 expression increased in vitro motility, invasiveness, and anchorage-independent colony formation of SK-BR-3 cells and favored disorganized growth of the cells in 3D basement membrane culture. Enforced expression also increased tumorigenicity and final tumor weights of SK-BR-3 clones/cells after subcutaneous injection of the cells under the left third nipple of female athymic nude mice. To understand the mechanisms, we also determined the expression of several downstream key effectors in the tumors. Tumor cells from METCAM/MUC18 expressing clones exhibited elevated expression of an anti-apoptotic and survival index (Bcl2), an aerobic glycolysis index (LDH-A), and pro-angiogenesis indexes (VEGF and VAGFR2). We concluded that human METCAM/MUC18 promotes the development of breast cancer cells by increasing an anti-apoptosis and survival pathway and augmenting aerobic glycolysis and angiogenesis.

  3. Enhanced internalization of ErbB2 in SK-BR-3 cells with multivalent forms of an artificial ligand.

    Science.gov (United States)

    Vaidyanath, Arun; Hashizume, Toshihiro; Nagaoka, Tadahiro; Takeyasu, Nao; Satoh, Hitomi; Chen, Ling; Wang, Jiyou; Kasai, Tomonari; Kudoh, Takayuki; Satoh, Ayano; Fu, Li; Seno, Masaharu

    2011-11-01

    Targeting and down-regulation of ErbB2, a member of EGF receptor family, is regarded as one of the key aspect for cancer treatment because it is often overexpressed in breast and ovarian cancer cells. Although natural ligands for ErbB2 have not been found, unlike other ErbB receptors, EC-1, a 20-amino acid circular peptide, has been shown to bind to ErbB2 as an artificial ligand. Previously we showed EC-1 peptide did not induce the internalization of ErbB2 in SK-BR-3 cells. In this report, we designed divalent and multivalent forms of EC-1 peptide with the Fc portion of the human IgG and bionanocapsule modified with ZZ-tag on its surface to improve the interaction with ErbB2. These forms showed higher affinity to ErbB2 than that of EC-1 monomer. Furthermore, prominent endosomal accumulation of ErbB2 occurred in SK-BR-3 cells when stimulated with EC-Fc ligand multivalently displayed on the surface of the bionanocapsule, whereas SK-BR-3 cells as themselves displayed stringent mechanism against ErbB2 internalization without stimulation. The multivalent form of EC-1 peptide appeared to internalize ErbB2 more efficiently than divalent form did. This internalization was unaffected by the inhibition of clathrin association, but inhibited when the cholesterol was depleted which explained either caveolar or GPI-AP-early endocytic compartment (GEEC) pathway. Because of the lack of caveolin-1 expression, caveolar machinery may be lost in SK-BR-3 cell line. Therefore, it is suggested that the multivalent form of EC-1 induces the internalization of ErbB2 through the GEEC pathway.

  4. Lycopene Inhibits Metastasis of Human Liver Adenocarcinoma SK-Hep-1 Cells by Downregulation of NADPH Oxidase 4 Protein Expression.

    Science.gov (United States)

    Jhou, Bo-Yi; Song, Tuzz-Ying; Lee, Inn; Hu, Miao-Lin; Yang, Nae-Cherng

    2017-08-16

    NADPH oxidase 4 (NOX4), with the sole function to produce reactive oxygen species (ROS), can be a molecular target for disrupting cancer metastasis. Several studies have indicated that lycopene exhibited anti-metastatic actions in vitro and in vivo. However, the role of NOX4 in the anti-metastatic action of lycopene remains unknown. Herein, we first confirmed the anti-metastatic effect of lycopene (0.1-5 μM) on human liver adenocarcinoma SK-Hep-1 cells. We showed that lycopene significantly inhibited NOX4 protein expression, with the strongest inhibition of 64.3 ± 10.2% (P Hep-1 cells. We then determined the effects of lycopene on transforming growth factor β (TGF-β)-induced metastasis. We found that TGF-β (5 ng/mL) significantly increased migration, invasion, and adhesion activity, the intracellular ROS level, matrix metalloproteinase 9 (MMP-9) and MMP-2 activities, the level of NOX4 protein expression, and NOX activity. All these TGF-β-induced effects were antagonized by the incubation of SK-Hep-1 cells with lycopene (2.5 μM). Using transient transfection of siRNA against NOX4, we found that the downregulation of NOX4 could mimic lycopene by inhibiting cell migration and the activities of MMP-9 and MMP-2 during the incubation with or without TGF-β on SK-Hep-1 cells. The results demonstrate that the downregulation of NOX4 plays a crucial role in the anti-metastatic action of lycopene in SK-Hep-1 cells.

  5. Lékařský software pro vyúčtování dokladů

    OpenAIRE

    Pohl, Ondřej

    2013-01-01

    Cílem práce je rozšíření lékařského softwaru OpenDositech.Rozšířením je implementace rozhraní pro elektronickou komunikaci s webovými portály zdravotních pojišťoven do programu OpenDositech. Nejprve je popsán dostupný lékařský software spolu s datovým rozhraním pro předávání lékařských dokladů zdravotním pojišťovnám. Práce se poté zabývá předáváním dokladů přes Portál zdravotních pojišťoven. V závěru práce je popsána implementace rozhraní do programu OpenDositech. The aim of this thesis is...

  6. Role of degassing of the Noril'sk nickel deposits in the Permian-Triassic mass extinction event.

    Science.gov (United States)

    Le Vaillant, Margaux; Barnes, Stephen J; Mungall, James E; Mungall, Emma L

    2017-03-07

    The largest mass extinction event in Earth's history marks the boundary between the Permian and Triassic Periods at circa 252 Ma and has been linked with the eruption of the basaltic Siberian Traps large igneous province (SLIP). One of the kill mechanisms that has been suggested is a biogenic methane burst triggered by the release of vast amounts of nickel into the atmosphere. A proposed Ni source lies within the huge Noril'sk nickel ore deposits, which formed in magmatic conduits widely believed to have fed the eruption of the SLIP basalts. However, nickel is a nonvolatile element, assumed to be largely sequestered at depth in dense sulfide liquids that formed the orebodies, preventing its release into the atmosphere and oceans. Flotation of sulfide liquid droplets by surface attachment to gas bubbles has been suggested as a mechanism to overcome this problem and allow introduction of Ni into the atmosphere during eruption of the SLIP lavas. Here we use 2D and 3D X-ray imagery on Noril'sk nickel sulfide, combined with simple thermodynamic models, to show that the Noril'sk ores were degassing while they were forming. Consequent "bubble riding" by sulfide droplets, followed by degassing of the shallow, sulfide-saturated, and exceptionally volatile and Cl-rich SLIP lavas, permitted a massive release of nickel-rich volcanic gas and subsequent global dispersal of nickel released from this gas as aerosol particles.

  7. Reflection seismic studies over the end-glacial Burträsk fault, Skellefteå, Sweden

    Directory of Open Access Journals (Sweden)

    C. Juhlin

    2011-01-01

    Full Text Available Reflection seismic data were acquired along a ca. 22 km long profile over the end-glacial Burträsk fault with a nominal receiver and source spacing of 20 m. A steeply dipping reflection can be correlated to the Burträsk fault, indicating that the fault dips at about 55° to the southeast near the surface. The reflection from the fault is rather poorly imaged, probably due to a lateral offset in the fault of about 1 km at this location and the crookedness of the seismic profile in the vicinity of the fault. A more pronounced steeply dipping reflection is observed about 4 km southeast of the Burträsk fault. Based on its correlation with a topographic low at the surface this reflection is interpreted to originate from a fracture zone. There are no signs of large displacements along this zone as the glacial ice receded, but earthquakes could be associated with it today. Other reflections on the processed seismic section may originate from changes in lithological variations in the supra-crustal rocks or from intrusions of more mafic rock. Constraints on the fault geometry provided by the reflection seismic data will help determine what stresses were required to activate the fault when the major rupture along it occurred ca. 9500 years ago.

  8. East Scandinavian and Noril'sk plume mafic large igneous provinces of Pd-Pt ores: Geological and metallogenic comparison

    Science.gov (United States)

    Mitrofanov, F. P.; Bayanova, T. B.; Korchagin, A. U.; Groshev, N. Yu.; Malitch, K. N.; Zhirov, D. V.; Mitrofanov, A. F.

    2013-09-01

    This paper compares the geological, geophysical, and isotopic geochemical data on the Paleoproterozoic East Scandinavian Pd-Pt province in the Baltic Shield and the Late Paleozoic Noril'sk Pd-Pt province in the Siberian Craton. Both provinces contain large magmatic PGE deposits: low-sulfide in the Baltic Shield and high-sulfide in the Siberian Craton. Multidisciplinary evidence shows that the East Scandinavian mafic large igneous province, which has a plume nature, is intracratonic and was not subjected to the crucial effect of subduction-related and other contamination processes, whereas the Noril'sk province is pericratonic with substantial crustal contamination of the intrusive processes. Low-sulfide Pd-Pt deposits dominate in the East Scandinavian province, while high-sulfide Ni-Cu-PGE deposits play the leading role in the Noril'sk province. The U-Pb, Sm-Nd, and Rb-Sr isotopic data indicate multistage and long-term (tens of millions of years) geological history of mafic large igneous provinces. The plume magmatism with specific geochemistry and metallogeny is probably related to lower mantle sources.

  9. Inhibitory Effects of Anti-sense PTTG on Malignant Phenotype of Human Ovarian Carcinoma Cell Line SK-OV-3

    Institute of Scientific and Technical Information of China (English)

    陈刚; 李静; 李辅军; 李箫; 周剑锋; 卢运萍; 马丁

    2004-01-01

    To construct eukaryotic expression vector expressing full length anti-sense pituitary tumor transforming gene (PTTG) mRNA and observe its blocking effect on the potential invasion of human ovarian carcinoma cell line SK-OV-3. PCR primers containing designed enzyme cut sites were used for cloning full-length PTTG gene fragment, and the resulting PCR product was inserted into the eukaryotic vector pcDNA3. 1 in the antisense direction. The recombinant vector was then transfected into SK-OV-3 by Lipofectamine. The positive cell clone was screened by G418, PTTG and bFGF at protein level expression were detected by Western blot. The biological behavior change of transfection positive cells was observed by colony formation in soft agar assay. Our results showed that SK-OV-3 clones stably expressing full-length recombinant pcDNA3. 1-PTTGas were obtained. The expressions of PTTG and bFGF protein in transfected cells were decreased by 61.5 % and 52.3%, respectively as compared with non-transfected ones. The number of colony formation was reduced significantly in transfected cells as compared with empty vector transfected and non-transfected cells. It is concluded that the recombinant vector pcDNA3. 1-PTTGas is a novel tool and provides an alternative anti-sense gene therapy targeted at PTTG in human carcinoma.

  10. Hepatotoxicity after liver irradiation in children and adolescents. Results from the RiSK

    Energy Technology Data Exchange (ETDEWEB)

    Roesler, Pascal; Christiansen, Hans [Medical School Hannover, Department of Radiotherapy and Special Oncology, Hannover (Germany); Kortmann, Rolf-Dieter [University of Leipzig, Department of Radiotherapy, Leipzig (Germany); Martini, Carmen [University Hospital of Freiburg, Department of Radiotherapy, Freiburg im Breisgau (Germany); Matuschek, Christiane [Heinrich-Heine University of Duesseldorf, Department of Radiotherapy, Medical Faculty, Duesseldorf (Germany); Meyer, Frank [Hospital Augsburg, Department of Radiotherapy, Augsburg (Germany); Ruebe, Christian [University Hospital of Homburg/Saar, Department of Radiotherapy, Homburg/Saar (Germany); Langer, Thorsten [University Hospital of Schleswig-Holstein, Department of Pediatrics, Pediatric Oncology, Campus Luebeck (Germany); Koch, Raphael [University of Muenster, Institute of Biostatistics and Clinical Research, Muenster (Germany); Eich, Hans Theodor; Willich, Normann [University Hospital of Muenster, Department of Radiotherapy, Muenster (Germany); Steinmann, Diana [Medical School Hannover, Department of Radiotherapy and Special Oncology, Hannover (Germany); University Hospital of Muenster, Department of Radiotherapy, Muenster (Germany)

    2015-05-01

    The aim of this study was to evaluate acute and late radiotherapy-associated hepatotoxicity in consideration of dose-volume effects and liver function in childhood and adolescence. Since 2001, irradiated children and adolescents in Germany have been prospectively documented in the ''Register of Treatment-Associated Late Effects After Radiotherapy of Malignant Diseases in Childhood and Adolescence (RiSK)'' using standardized forms. Toxicity was graded according to the Radiation Therapy Oncology Group (RTOG) criteria. Until April 2012, 1,392 children and adolescents from 62 radiotherapy centers were recruited. In all, 216 patients underwent irradiation of the liver (median age 9 years, range 1-18 years, 70 patients with total-body irradiation, TBI). For 75 % of patients without TBI, information on acute toxicity of the liver was available: 24 patients had acute toxicity of grade 1-4 (grade 1, 2, and 4, in 20, 3, and 1 patient, respectively), including five patients receiving simultaneous hepatotoxic chemotherapy. Information on late toxicity was documented in 465 forms from 216 patients, with a median follow-up of 2 years. A maximum grade of toxicity of ≥ 0 occurred in 18 patients over time (with grade 1, 2, and 3 toxicity occurring in 15, 2, and 1 patient, respectively), including three patients (17 %) with TBI. One of them received simultaneous hepatotoxic chemotherapy. In multivariable analysis, volume-dose correlations showed no statistically noticeable effect on acute or chronic toxicity. Only low hepatotoxicity developed in children after irradiation of various abdominal and thoracic tumors. Due to the low radiation doses to the liver (median liver dose = 5 Gy) and the low toxicities that were consecutively observed, dose-volume curves for liver toxicity could not be established. These findings reflect the cautious attitude of radiation oncologists in terms of attributable liver doses in the treatment of the investigated tumor entities. It

  11. Intracorneal Rings (INTACS SK) Might be Beneficial in Keratoconus; A Prospective Nonrandomized Study.

    Science.gov (United States)

    A Ibrahim, Tarek; Elmor, Osama

    2013-01-01

    In order to determine the effect of intracorneal rings (Intacs SK), when implanted in keratoconic patients, on corneal curvature, Uncorrected Visual Acuity (UCVA), Best Corrected Visual Acuity (BCVA) and on the progression of the cone through three years follow-up period. In this prospective nonrandomized study 114 eyes of 71 keratoconic patients (38 females and 33 males) were implanted with Intacs SK. Incisions were always made in the steep meridian. UCVA, BCVA, Corneal Topography (TMS) were measured pre and postoperatively and at intervals of 1, 3, 6 & 12 months then yearly for 3 consecutive years. Preoperative mean k-reading was 52.53 and 48.18, 49.56, 49.17, 48.51, 48.15 & 48.01 at 1, 3, 6, 12, 24 & 36 months postoperatively (P‹0.01). In terms of UCVA, 15.64% of patients gained more than 3 lines and 69.73% gained 1-3 lines with a total of 85.37% of patients gaining lines compared to their preoperative UCVA (P‹0.01) while 14.63% of cases did not gain any lines at 1 month postoperative. At three months postoperatively, 12.64% gained more than 3 lines, 71.15% gained 1-3 lines with a total of 83.79% while 16.21% did not gain any lines. Three years postoperative 11.82% of cases gained more than 3 lines, 73.23% gained 1-3 lines with a total of 85.05% while 14.95% did not gain any lines (P‹0.01). With regard to BCVA, 19.73% gained more than 3 lines, 68.26% gained 1-3 lines with a total of 87.99% of cases gaining lines compared to their preoperative BCVA (P‹0.01) while 12.01% did not gained any lines at 1 month postoperative. At three months postoperatively, 14.96% gained more than 3 lines, 70.19% gained 1-3 lines with a total of 85.15% while 14.85% did not gain any lines. Three years postoperative, 12.17% gained more than 3 lines, 71.78% gained 1-3 lines with a total of 83.95% (P‹0.01) while 16.05% did not gain any lines. No eyes lost any lines as it pertained to UCVA & BCVA. Despite the fluctuation of k-readings, UCVA and BCVA in the first 3 months, which

  12. [Maria Skłodowska-Curie and Piotr Curie an epoch-makingin year 1898].

    Science.gov (United States)

    Wielogórski, Zbigniew

    2012-01-01

    For many reasons the year 1898 was unusual for Maria Skłodowska-Curie and her husband. After defining the subject of the doctoral thesis and choosing Henri Becqerel as thesis supervisor, Maria started intensive experimental work. In the allotted room called storeroom, in conditions that were far too inadequate, they managed to put up a unique measuring equipment composed of instruments whose originator was Pierre Curie. In the ionization chamber and in the piezoelectric quartz charges formed, whose mutual neutralization was shown by the quadrant electrometer. Ionization current, which was measured quantitatively, was proportional to the radiation of the sample. Studying many elements, their compounds and minerals enabled Maria to state that uranium is not the only element endowed with the power of radiation; the second one turned out to be thorium. Anomaly detected in the radiation of uranium minerals made it possible for Maria to draw an extremely important conclusion: radioactive uranium and thorium are not the only elements endowed with such an attribute. Pitchblende, which was studied by the Curie couple, had to contain also other radioactive substances. Gustave Bémont also participated in the chemical analysis of the uranium ore and it is worth reminding that he was involved in the discovery of polonium and uranium. The phenomenon of radioactivity couldn't have been explained if it was not for the sources of strong radioactivity. Those sources undoubtedly could have been the discovered elements but their scanty content in the uranium ore made their isolation very difficult and laborious. Access to industrial remains after procession of pitchblende from Jachymov (Sankt Joachimstahl), obtained owing to the mediation of Eduard Suess, provided the source of this raw material. From it, in a shack also called le hangar, the Curie couple isolated the first samples of the radium salt. This element, later extracted by discoverers on a grand scale and handed over in a

  13. Bioelectrochemical Mn(II) leaching from manganese ore by Lactococcus lactis SK071115.

    Science.gov (United States)

    Jeon, Bo Young; Park, Doo Hyun

    2011-02-01

    L. lactis sk071115 has been shown to grow more actively and generate lower levels of lactate in glucose-defined medium with nitrate than in medium with Mn(IV). By adding Mn(IV) to a L. lactis culture, lactate production was relatively reduced in combination with Mn(II) production, but cell mass production levels did not increase. Both cell-free extract and intact L. lactis cells reacted electrochemically with Mn(IV) but did not react with Mn(II) upon cyclic voltammetry using neutral red (NR) as an electron mediator. A modified graphite felt cathode with NR (NR-cathode) was employed to induce electrochemical reducing equivalence for bacterial metabolism. Cell-free L. lactis extract catalyzed the reduction of Mn(IV) to Mn(II) under both control and electrochemical reduction conditions; however, the levels of Mn(II) generated under electrochemical reduction conditions were approximately 4 times those generated under control conditions. The levels of Mn(II) generated by the catalysis of L. lactis immobilized in the NR-cathode (L-NR-cathode) under electrochemical reduction conditions were more than 4 times that generated under control conditions. Mn(II) production levels were increased by approximately 2.5 and 4.5 times by the addition of citrate to the reactant under control and electrochemical reduction conditions, respectively. The cumulative Mn(II) produced from manganese ore by catalysis of the L-NR-cathode for 30 days reached levels of approximately 3,800 and 16,000 mg/l under control and electrochemical reduction conditions, respectively. In conclusion, the electrochemical reduction reaction generated by the NR-cathode activated the biochemical reduction of Mn(IV) to Mn(II) by L. lactis.

  14. Effect of rhaponticin on apoptosis in human breast cancer SK-BR-3 cells%土大黄苷对人乳腺癌细胞SK-BR-3凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    赵素容; 刘浩; 梁颖; 钱江华; 陈超; 蒋志文

    2012-01-01

    目的:观察土大黄苷对人乳腺癌细胞SK-BR-3凋亡的影响.方法:Annexin V-FITC/PI双标法检测100、200、400 μmol/L土大黄苷对SK-BR-3细胞凋亡的影响,Western blot法检测Bcl-2及Bax蛋白的表达情况,试剂盒检测caspase-3的活性变化.结果:土大黄苷可诱导SK-BR-3细胞出现明显的早期凋亡,并呈浓度依赖性(P<0.05~P<0.01).土大黄苷在100、200、400 μmol/L浓度时均可抑制Bcl-2蛋白的表达,且随着其浓度的增加,蛋白表达逐渐降低,并促进Bax蛋白的表达(P<0.01).土大黄苷对caspase-3具有激活作用,且随着土大黄苷浓度的增加,caspase-3的活化程度逐渐增强.结论:土大黄苷具有诱导乳腺癌细胞凋亡的作用,其机制可能与调节凋亡相关蛋白Bcl-2、Bax的表达及激活caspase-3有关(P<0.01).%Objective: To investigate the effect of rhaponticin on apoptosis in human breast cancer SK-BR-3 cells. Methods: SK-BR-3 cells were treated with rhaponticin at the concentrations of 100,200,and 400 ?mol/L. Apoptosis was examined with Annexin V-FITC Apoptosis Detection Kit by flow cytometry. The expressions of Bcl-2 and Bax protein were analyzed by Western blot, caspase-3 activity was detected by special kit. Results: Rhaponticin induced obvious early apoptosis in SK-BR-3 cells in a concentration-dependent manner( P < 0. 05 to P < 0. 01) . Western blot results showed that rhaponticin enhanced the expression of Bax protein, and inhibited the expression of Bcl-2 protein, which was gradually down-regulated following the increase of rhaponticin's concentration ( P < 0. 01 ). Meanwhile, rhaponticin induced the activation of caspase-3 , and caspase-3 activity was increased with its concentration ( P < 0. 01 ) . Conclusions: Rhaponticin can induce apoptosis in SK-BR-3 cells, which may be correlated to the down-regulation of Bcl-2, the up-regulation of Bax, and the activation of caspase-3.

  15. Direct Host Plasminogen Binding to Bacterial Surface M-protein in Pattern D Strains of Streptococcus pyogenes Is Required for Activation by Its Natural Coinherited SK2b Protein.

    Science.gov (United States)

    Chandrahas, Vishwanatha; Glinton, Kristofor; Liang, Zhong; Donahue, Deborah L; Ploplis, Victoria A; Castellino, Francis J

    2015-07-24

    Streptokinase (SK), secreted by Group A Streptococcus (GAS), is a single-chain ∼47-kDa protein containing three consecutive primary sequence regions that comprise its α, β, and γ modules. Phylogenetic analyses of the variable β-domain sequences from different GAS strains suggest that SKs can be arranged into two clusters, SK1 and SK2, with a subdivision of SK2 into SK2a and SK2b. SK2b is secreted by skin-tropic Pattern D M-protein strains that also express plasminogen (human Pg (hPg)) binding Group A streptococcal M-protein (PAM) as its major cell surface M-protein. SK2a-expressing strains are associated with nasopharynx tropicity, and many of these strains express human fibrinogen (hFg) binding Pattern A-C M-proteins, e.g. M1. PAM interacts with hPg directly, whereas M1 binds to hPg indirectly via M1-bound hFg. Subsequently, SK is secreted by GAS and activates hPg to plasmin (hPm), thus generating a proteolytic surface on GAS that enhances its dissemination. Due to these different modes of hPg/hPm recognition by GAS, full characterizations of the mechanisms of activation of hPg by SK2a and SK2b and their roles in GAS virulence are important topics. To more fully examine these subjects, isogenic chimeric SK- and M-protein-containing GAS strains were generated, and the virulence of these chimeric strains were analyzed in mice. We show that SK and M-protein alterations influenced the virulence of GAS and were associated with the different natures of hPg activation and hPm binding. These studies demonstrate that GAS virulence can be explained by disparate hPg activation by SK2a and SK2b coupled with the coinherited M-proteins of these strains.

  16. [Connection of magnetic antisense probe with SK-Br-3 oncocyte mRNA nucleotide detected by high resolution atomic force microscope].

    Science.gov (United States)

    Tan, Shude; Ouyang, Yu; Li, Xinyou; Wen, Ming; Li, Shaolin

    2011-06-01

    The present paper is aimed to detect superparamagnetic iron oxide labeled c-erbB2 oncogene antisense oligonucleotide probe (magnetic antisense probe) connected with SK-Br-3 oncocyte mRNA nucleotide by high resolution atomic force microscope (AFM). We transfected SK-Br-3 oncocyte with magnetic antisense probe, then observed the cells by AFM with high resolution and detected protein expression and magnetic resonance imagine (MRI). The high resolution AFM clearly showed the connection of the oligonucleotide remote end of magnetic antisense probe with the mRNA nucleotide of oncocyte. The expression of e-erbB2 protein in SK-Br3 cells were highly inhibited by using magnetic antisense probe. We then obtained the lowest signal to noise ratio (SNR) of SK-Br-3 oncocyte transfected with magnetic antisense probe by MRI (PSK-Br-3 mRNA of tumor cell nuclear.

  17. Pääsküla sõjaväeobjekti jääkreostus ning piirkonna edasise kasutamise perspektiivid / Triin Uudeväli, Anto Raukas

    Index Scriptorium Estoniae

    Uudeväli, Triin

    2004-01-01

    Pääskülas asunud NL-i raketijuhtimisekeskuse ja sideväeosa poolt tekitatud keskkonnareostuse hindamisest, likvideerimisest ning ettepanekutest territooriumi edasiseks kasutamiseks. Kaart. Skeem. Fotod

  18. Kit-negative fibroblast-like cells expressing SK3, a Ca2+-activated K+ channel, in the gut musculature in health and disease

    DEFF Research Database (Denmark)

    Vanderwinden, Jean-Marie; Rumessen, Jüri J; de Kerchove d'Exaerde, Alban;

    2002-01-01

    CD34-ir fibroblast-like cells adjacent to, but distinct from, the cells of Cajal remains elusive. The distribution of SK3 was studied by immunohistochemistry in the normal human gut, in motility disorders with a lack of cells of Cajal (infantile hypertrophic pyloric stenosis and Hirschsprung...... were lacking. These cells were CD34-ir fibroblast-like cells in the human gut and in the mouse stomach, while SK3-ir cells in the mouse intestine were CD34 negative. As SK channels are reportedly involved in inhibitory neurotransmission, our morphological observations suggest that SK3-ir interstitial...... cells, distinct from the Kit-ir interstitial cells of Cajal, may represent a novel cellular component in the control of excitability of the digestive musculature. Further studies will be required to directly address the function of these cells....

  19. The Mitochondria-Targeted Antioxidant SkQ1 Downregulates Aryl Hydrocarbon Receptor-Dependent Genes in the Retina of OXYS Rats with AMD-Like Retinopathy

    Directory of Open Access Journals (Sweden)

    M. L. Perepechaeva

    2014-01-01

    Full Text Available The mitochondria-targeted antioxidant SkQ1 is a novel drug thought to retard development of age-related diseases. It has been shown that SkQ1 reduces clinical signs of retinopathy in senescence-accelerated OXYS rats, which are a known animal model of human age-related macular degeneration (AMD. The aim of this work was to test whether SkQ1 affects transcriptional activity of AhR (aryl hydrocarbon receptor and Nrf2 (nuclear factor erythroid 2-related factor 2, which are considered as AMD-associated genes in the retina of OXYS and Wistar rats. Our results showed that only AhR and AhR-dependent genes were sensitive to SkQ1. Dietary supplementation with SkQ1 decreased the AhR mRNA level in both OXYS and Wistar rats. At baseline, the retinal Cyp1a1 mRNA level was lower in OXYS rats. SkQ1 supplementation decreased the Cyp1a1 mRNA level in Wistar rats, but this level remained unchanged in OXYS rats. Baseline Cyp1a2 and Cyp1b1 mRNA expression was stronger in OXYS than in Wistar rats. In the OXYS strain, Cyp1a2 and Cyp1b1 mRNA levels decreased as a result of SkQ1 supplementation. These data suggest that the Cyp1a2 and Cyp1b1 enzymes are involved in the pathogenesis of AMD-like retinopathy of OXYS rats and are possible therapeutic targets of SkQ1.

  20. Expression of the small conductance Ca²⁺-activated potassium channel subtype 3 (SK3 in rat uterus after stimulation with 17β-estradiol.

    Directory of Open Access Journals (Sweden)

    Mette Rahbek

    Full Text Available Preterm births accounts for roughly 9% of all births worldwide and can have detrimental or even lethal consequences for the infant. However to develop new treatment that will lower the rate of preterm births, more knowledge is required on the factors contributing to the contraction and relaxation of the myometrium. The small conductance Ca²⁺-activated potassium channel subtype 3 (SK3 has been identified in the myometrium of several species including humans, mice and rats, but with great inter species variation of the expression pattern and regulation. The aim of this study was to investigate the expression of SK3 in the uterus of rats stimulated with 17β-estradiol and progesterone in order to get an in depth understanding of the rat uterine SK3. Using immunohistochemistry SK3 was localized to the glandular and luminal endometrial lamina epitheliali. Furthermore, a weak signal was observed in the myometrium. Using Western blot the protein level of SK3 was found to increase in uteri from animals treated with 17β-estradiol, an effect that was not reflected at the mRNA level. The levels of mRNA for SK3 were significantly lower in the uterus of 17β-estradiol-treated animals than in the uterus of ovariectomized animals. We conclude that the SK channels are present in the endometrial epithelium, and possibly also in the myometrium of the rat uterus. Furthermore, the hormonal effect on SK3 caused by 17β-estradiol includes divergent regulation at mRNA and protein levels.

  1. Data on in vivo selection of SK-OV-3 Luc ovarian cancer cells and intraperitoneal tumor formation with low inoculation numbers

    Directory of Open Access Journals (Sweden)

    Elly De Vlieghere

    2016-03-01

    Full Text Available This data paper contains information about the in vivo model for peritoneal implants used in the paper “Tumor-environment biomimetics delay peritoneal metastasis formation by deceiving and redirecting disseminated cancer cells” (De Vlieghere et al., 2015 [1]. A double in vivo selection of SK-OV-3 Luc human ovarian cancer cell line was used to create SK-OV-3 Luc IP1 and SK-OV-3 Luc IP2 cell lines. This data paper shows functional activities of the three cell lines in vitro and in vivo. Phase-contrast images show the morphology of these cells, metabolic and luciferase activity has been determined. Survival data of mice peritoneally injected with SK-OV-3 Luc or SK-OV-3 Luc IP2 is available with H&E histology of the peritoneal implants. Tumor growth curves and bioluminescent images of mice inoculated with a different number of SK-OV-3 Luc IP2 cells are also included.

  2. Calcium-activated potassium channel SK1 is widely expressed in the peripheral nervous system and sensory organs of adult zebrafish.

    Science.gov (United States)

    Cabo, R; Zichichi, R; Viña, E; Guerrera, M C; Vázquez, G; García-Suárez, O; Vega, J A; Germanà, A

    2013-10-25

    Sensory cells contain ion channels involved in the organ-specific transduction mechanisms that convert different types of stimuli into electric energy. Here we focus on small-conductance calcium-activated potassium channel 1 (SK1) which plays an important role in all excitable cells acting as feedback regulators in after-hyperpolarization. This study was undertaken to analyze the pattern of expression of SK1 in the zebrafish peripheral nervous system and sensory organs using RT-PRC, Westernblot and immunohistochemistry. Expression of SK1 mRNA was observed at all developmental stages analyzed (from 10 to 100 days post fertilization, dpf), and the antibody used identified a protein with a molecular weight of 70kDa, at 100dpf (regarded to be adult). Cell expressing SK1 in adult animals were neurons of dorsal root and cranial nerve sensory ganglia, sympathetic neurons, sensory cells in neuromasts of the lateral line system and taste buds, crypt olfactory neurons and photoreceptors. Present results report for the first time the expression and the distribution of SK1 in the peripheral nervous system and sensory organs of adult zebrafish, and may contribute to set zebrafish as an interesting experimental model for calcium-activated potassium channels research. Moreover these findings are of potential interest because the potential role of SK as targets for the treatment of neurological diseases and sensory disorders.

  3. PAQR3增强乳腺癌细胞SK-BR-3的表柔比星敏感性%PAQR3 enhances chemosensitivity of breast cancer cell line SK-BR-3 to epirubicin

    Institute of Scientific and Technical Information of China (English)

    黄剑波; 罗鑫荣; 孔令泉; 向廷秀; 任国胜

    2013-01-01

    目的 探讨PAQR3增强乳腺癌细胞对表柔比星的敏感性.方法 采用Real-time PCR比较ER、PR及HER2受体不同的4株乳腺癌细胞(MDA-MB-231、MCF7、SK-BR-3及T47D)的PAQR3表达情况.在乳腺癌细胞SK-BR-3中转染人源性PAQR3全长表达质粒,设立对照组,观察比较转染PAQR3细胞组与空载质粒细胞组对表柔比星的敏感性,分别计算其所对应的IC50.通过细胞凋亡检测、Western blot探讨PAQR3增加表柔比星敏感性的机制.结果 在4株乳腺癌细胞中,受体三阴性细胞MDA-MB-231的PAQR3表达量最高,SK-BR-3与MCF7表达量相对较低;SK-BR-3过表达PAQR3后,其对表柔比星的化疗敏感性显著升高,IC50显著降低[(25.33±0.94) μg/mL vs(17.72±1.11) μg/mL,P<0.05];PAQR3本身并未促使SK-BR-3凋亡,实验组与对照组的凋亡率差异并无统计学意义(P>0.05).但在同等浓度表柔比星的作用下,PAQR3促使SK-BR-3表达凋亡相关蛋白Cleaved Caspase-7,从而导致表柔比星抑制率增加,对CleavedCaspase-3、Bcl-2、Bcl-xL表达则无影响.进一步分析发现,PAQR3可抑制乳腺癌化疗中表柔比星所致的ERK活化,因而促使乳腺癌细胞对表柔比星敏感.结论 PAQR3可提高乳腺癌细胞对表柔比星的化疗敏感性,PAQR3表达可能与乳腺癌对表柔比星的敏感性相关.

  4. Biological activity and binding of estradiol to SK-Mel 23 human melanoma cells

    Directory of Open Access Journals (Sweden)

    Sarti M.S.M.V.

    2004-01-01

    Full Text Available Patients expressing estradiol receptors in melanoma cells have been reported to have a better prognosis. We therefore decided to investigate the in vitro effects of ß-estradiol and tamoxifen on the growth and tyrosinase activity of SK-Mel 23 human melanoma cells. Twenty-four-hour treatment with 0.4 nM ß-estradiol inhibited cell proliferation in 30% (0.70 ± 0.03 x 10(5 cells and increased tyrosinase activity in 50% (7130.5 ± 376.5 cpm/10(5 cells, as compared to untreated cells (1.0 ± 0.05 x 10(5 cells and 4769 ± 25.5 cpm/10(5 cells, respectively. Both responses were completely (100% blocked by 1 µM tamoxifen. Higher concentrations (up to 1.6 nM or longer treatments (up to 72 h did not result in a larger effect of the hormone on proliferation or tyrosinase activity. Competition binding assays demonstrated the presence of binding sites to [2,4,6,7-³H]-ß-estradiol, and that the tritiated analogue was displaced by the unlabeled hormone (1 nM to 100 µM, Kd = 0.14 µM, maximal displacement of 93% or by 10 µM tamoxifen (displacement of 60%. ß-estradiol also increased the phosphorylated state of two proteins of 16 and 46 kDa, after 4-h treatment, as determined by Western blot. The absorbance of each band was 1.9- and 4-fold the controls, respectively, as determined with Image-Pro Plus software. Shorter incubation periods with ß-estradiol did not enhance phosporylation; after 6-h treatment with the hormone, the two proteins returned to the control phosphorylation levels. The growth inhibition promoted by estradiol may explain the better prognosis of melanoma-bearing women as compared to men, and open new perspectives for drug therapy.

  5. DJ1 Expression Downregulates in Neuroblastoma Cells (SK-N-MC Chronically Exposed to HIV-1 and Cocaine.

    Directory of Open Access Journals (Sweden)

    Upal eRoy

    2015-07-01

    Full Text Available Background: HIV-associated neurological disorder (HAND has long been recognized as a consequence of Human Immunodeficiency Virus (HIV infection in the brain. The pathology of HAND gets more complicated with the recreational drug use such as cocaine. Recent studies have suggested multiple genetic influences involved in the pathology of addiction and HAND but only a fraction of the entire genetic risk has been investigated so far. In this regard, role of DJ1 protein (a gene linked to autosomal recessive early-onset Parkinson’s disease in regulating dopamine transmission and reactive oxygen species (ROS production in neuronal cells will be worth investigating in HIV-1 and cocaine exposed microenvironment. Being a very abundant protein in the brain, DJ1 could serve as a potential marker for early detection of HIV-1 and/or cocaine related neurological disorder.Methods: In vitro analysis was done to observe the effect of HIV-1 and/or cocaine on DJ1 protein expression in neuroblastoma cells (SK-N-MC. Gene expression and protein analysis of DJ1 was done on the HIV infected and/or cocaine treated SK-N-MC and compared to untreated cells using real time PCR, Western Blot and flow cytometry.Results: Gene expression and protein analysis indicated that there was a significant decrease in DJ1 expression in SK-N-MC chronically exposed to HIV-1 and/or cocaine.Conclusion: This is the first study to establish that DJ1 expression level in the neuronal cells significantly decreased in presence of HIV-1and/or cocaine indicating oxidative stress level of dopamine neurons.

  6. Upregulation of SK3 and IK1 channels contributes to the enhanced endothelial calcium signaling and the preserved coronary relaxation in obese Zucker rats.

    Directory of Open Access Journals (Sweden)

    Belén Climent

    Full Text Available BACKGROUND AND AIMS: Endothelial small- and intermediate-conductance KCa channels, SK3 and IK1, are key mediators in the endothelium-derived hyperpolarization and relaxation of vascular smooth muscle and also in the modulation of endothelial Ca2+ signaling and nitric oxide (NO release. Obesity is associated with endothelial dysfunction and impaired relaxation, although how obesity influences endothelial SK3/IK1 function is unclear. Therefore we assessed whether the role of these channels in the coronary circulation is altered in obese animals. METHODS AND RESULTS: In coronary arteries mounted in microvascular myographs, selective blockade of SK3/IK1 channels unmasked an increased contribution of these channels to the ACh- and to the exogenous NO- induced relaxations in arteries of Obese Zucker Rats (OZR compared to Lean Zucker Rats (LZR. Relaxant responses induced by the SK3/IK1 channel activator NS309 were enhanced in OZR and NO- endothelium-dependent in LZR, whereas an additional endothelium-independent relaxant component was found in OZR. Fura2-AM fluorescence revealed a larger ACh-induced intracellular Ca2+ mobilization in the endothelium of coronary arteries from OZR, which was inhibited by blockade of SK3/IK1 channels in both LZR and OZR. Western blot analysis showed an increased expression of SK3/IK1 channels in coronary arteries of OZR and immunohistochemistry suggested that it takes place predominantly in the endothelial layer. CONCLUSIONS: Obesity may induce activation of adaptive vascular mechanisms to preserve the dilator function in coronary arteries. Increased function and expression of SK3/IK1 channels by influencing endothelial Ca2+ dynamics might contribute to the unaltered endothelium-dependent coronary relaxation in the early stages of obesity.

  7. P2X(7) receptor activation enhances SK3 channels- and cystein cathepsin-dependent cancer cells invasiveness.

    Science.gov (United States)

    Jelassi, B; Chantôme, A; Alcaraz-Pérez, F; Baroja-Mazo, A; Cayuela, M L; Pelegrin, P; Surprenant, A; Roger, S

    2011-05-05

    ATP-gated P2X(7) receptors (P2X(7)R) are unusual plasma membrane ion channels that have been extensively studied in immune cells. More recently, P2X(7)R have been described as potential cancer cell biomarkers. However, mechanistic links between P2X(7)R and cancer cell processes are unknown. Here, we show, in the highly aggressive human breast cancer cell line MDA-MB-435s, that P2X(7) receptor is highly expressed and fully functional. Its activation is responsible for the extension of neurite-like cellular prolongations, of the increase in cell migration by 35% and in cell invasion through extracellular matrix by 150%. The change in cancer cell morphology and the increased migration appeared to be due to the activation of Ca(2+)-activated SK3 potassium channels. The enhanced invasion through the extracellular matrix was related to the increase of mature forms of cysteine cathepsins in the extracellular medium, which was independent of SK3 channel activity and not associated with cell death. Pharmacological targeting of P2X(7)R in vivo was crucial for cell invasiveness in a zebrafish model of metastases. Our results demonstrate a novel mechanistic link between P2X(7)R functionality in cancer cells and invasiveness, a key parameter in tumour growth and in the development of metastases. They also suggest a potential therapeutic role for the newly developed P2X(7)R antagonists.

  8. The Effects of Boswellia Resin Extract on Dopaminergic Cell line, SK-N-SH, against MPP+-Induced Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Sareh Kazmi

    2011-10-01

    Full Text Available Introduction: Oxidative stress and neuroinflammation are involved in neurodegeneration procedure in Parkinson’s disease. Recently, neuroprotective potential of Boswellia resin has been demonstrated. Therefore, this study examined whether administration of Boswellia resin would attenuate MPP+- induced neuronal death in SK-N-SH- cell line, a human dopaminergic neurons- in vitro. Methods: Boswellia resin extract was added to culture medium (10μg/ml before and after exposure of SK-N-SH cell line to MPP+ (1000μM. Cell viability and apoptosis features were assessed using MTT and Hoechst staining, respectively. Results: Treatment with Boswellia resin 2 and 3h prior to MPP ° exposure and up to 60 minutes after MPP ° exposure significantly increased cell viability compare to untreated cells. Apoptotic features were also reduced significantly by Boswellia resin (10 μg/ml compare to that of control untreated cells. Discussion: Boswellia resin has neuroprotective effects on dopaminergic neurons which can be applicable in Parkinson’s disease.

  9. Spectral Knowledge (SK-UTALCA): Software for Exploratory Analysis of High-Resolution Spectral Reflectance Data on Plant Breeding

    Science.gov (United States)

    Lobos, Gustavo A.; Poblete-Echeverría, Carlos

    2017-01-01

    This article describes public, free software that provides efficient exploratory analysis of high-resolution spectral reflectance data. Spectral reflectance data can suffer from problems such as poor signal to noise ratios in various wavebands or invalid measurements due to changes in incoming solar radiation or operator fatigue leading to poor orientation of sensors. Thus, exploratory data analysis is essential to identify appropriate data for further analyses. This software overcomes the problem that analysis tools such as Excel are cumbersome to use for the high number of wavelengths and samples typically acquired in these studies. The software, Spectral Knowledge (SK-UTALCA), was initially developed for plant breeding, but it is also suitable for other studies such as precision agriculture, crop protection, ecophysiology plant nutrition, and soil fertility. Various spectral reflectance indices (SRIs) are often used to relate crop characteristics to spectral data and the software is loaded with 255 SRIs which can be applied quickly to the data. This article describes the architecture and functions of SK-UTALCA and the features of the data that led to the development of each of its modules. PMID:28119705

  10. Sedimentation from suspension and sediment accumulation rate in the River Vistula prodelta, Gulf of Gdańsk (Baltic Sea

    Directory of Open Access Journals (Sweden)

    Mateusz Damrat

    2013-11-01

    Full Text Available The River Vistula is one of the largest suppliers of fresh water and terrigenous matter to the Baltic Sea. The impact of this river on the Baltic coastal system and the fate of the sediment delivered to the Gulf of Gdańsk are not well understood. Spatial transport patterns, as well as the settling, deposition and accumulation of the sediments were studied at the Vistula prodelta in different seasons from January 2012 to January 2013. The concentration of suspended matter in the water column was measured with optical methods, the sedimentation rate was determined with sediment traps, and the sediment accumulation rate was estimated using 210Pb dating. Our data shows that the annual supply of sediment to the sediment-water interface exceeds the annual rate of sediment accumulation in the outer Vistula prodelta by a factor of three. Sediment trapping during rough weather showed that significant sediment redeposition was taking place, even at depths of 55 m. The dynamic sedimentary processes occurring in the Vistula prodelta mean that that more than two-thirds of the sediment mass can be remobilized and then redeposited in deeper parts of the Gdańsk Basin.

  11. Caffeine prevents transcription inhibition and P-TEFb/7SK dissociation following UV-induced DNA damage.

    Directory of Open Access Journals (Sweden)

    Giuliana Napolitano

    Full Text Available BACKGROUND: The mechanisms by which DNA damage triggers suppression of transcription of a large number of genes are poorly understood. DNA damage rapidly induces a release of the positive transcription elongation factor b (P-TEFb from the large inactive multisubunit 7SK snRNP complex. P-TEFb is required for transcription of most class II genes through stimulation of RNA polymerase II elongation and cotranscriptional pre-mRNA processing. METHODOLOGY/PRINCIPAL FINDINGS: We show here that caffeine prevents UV-induced dissociation of P-TEFb as well as transcription inhibition. The caffeine-effect does not involve PI3-kinase-related protein kinases, because inhibition of phosphatidylinositol 3-kinase family members (ATM, ATR and DNA-PK neither prevents P-TEFb dissociation nor transcription inhibition. Finally, caffeine prevention of transcription inhibition is independent from DNA damage. CONCLUSION/SIGNIFICANCE: Pharmacological prevention of P-TEFb/7SK snRNP dissociation and transcription inhibition following UV-induced DNA damage is correlated.

  12. In situ detection of alkB2 gene involved in Alcanivorax borkumensis SK2(T) hydrocarbon biodegradation.

    Science.gov (United States)

    Matturro, Bruna; Frascadore, Emanuela; Cappello, Simone; Genovese, Mariella; Rossetti, Simona

    2016-09-15

    This study aimed to develop a new assay based on the whole cell hybridization in order to monitor alkane hydroxylase genes (alkB system) of the marine bacterium Alcanivorax borkumensis SK2(T) commonly reported as the predominant microorganism responsible for the biodegradation of n-alkanes which are the major fraction of petroleum hydrocarbons. The assay based on the whole cell hybridization targeting alkB2 gene was successfully developed and calibrated on a pure culture of Alcanivorax borkumensis SK2(T) with a detection efficiency up to 80%. The approach was further successfully validated on hydrocarbon-contaminated seawater and provided cells abundance (6.74E+04alkB2-carryingcellsmL(-1)) higher of about one order of magnitude than those obtained by qPCR (4.96E+03alkB2genecopiesmL(-1)). This study highlights the validity of the assay for the detection at single cell level of key-functional genes involved in the biodegradation of n-alkanes.

  13. EFEKTIVITAS PERSYARATAN HYGIENE SANITASI TERHADAP USAHA RUMAH MAKAN DAN RESTORAN BERDASARKAN KEPMENKES RI NOMOR 1098/MENKES/SK/VII/2003

    Directory of Open Access Journals (Sweden)

    Gusti Ayu Dita Nomia Sari

    2016-09-01

    Full Text Available Tourists who visited tourism destination in addition to the cultural and natural environment, food and drinks being the main attraction. Lack of awareness of the restaurant business to maintain cleanliness and sanitation are not uncommon cause of food poisoning. Legal issues raised in this study are: a How obligation of entrepreneur restaurants and legal protection for consumers under the Consumer Protection Act; b how the effectiveness of sanitation hygiene is based on Kepmenkes No. 1098 / Menkes / SK / VII / 2003 against the restaurants in the Ubud area. This study uses empirical legal research . The data is processed by analyzing qualitative descriptive analytical. Wisatawan yang mengunjungi destinasi pariwisata selain budaya dan keindahan alam, makanan dan minuman menjadi daya tarik utama lainnya. Kurangnya kesadaran pengusaha restoran untuk menjaga kebersihan dan sanitasi yang tidak jarang menyebabkan terjadinya keracunan makanan. Isu hukum yang diangkat dalam penelitian ini adalah: a Bagaimana kewajiban pelaku usaha rumah makan dan restoran dan perlindungan hukum bagi konsumen menurut UU Perlindungan Konsumen; b bagaimana efektivitas hygiene sanitasi restoran berdasarkan Kepmenkes No. 1098 / Menkes / SK / VII / 2003 terhadap rumah makan dan restoran di kawasan ubud. Penelitian ini menggunakan penelitian hukum empiris . Data diolah dengan menganalisis deskriptif kualitatif analitis.

  14. In vitro detection of human breast cancer cells (SK-BR3) using herceptin-conjugated liquid crystal microdroplets as a sensing platform.

    Science.gov (United States)

    Ding, Wang; Gupta, Kailash Chandra; Park, Soo-Young; Kim, Young-Kyoo; Kang, Inn-Kyu

    2016-10-20

    The present study utilizes antibody-protein interactions to develop an LC microdroplet based biosensor for naked eye detection of SK-BR3 human breast cancer cells. The herceptin antibody-conjugated LC microdroplets were fabricated using 4-cyano-4'-pentyl biphenyl (5CB) as the liquid crystalline phase and sodium dodecyl sulfate (SDS) as the surfactant. The poly (styrene-b-acrylic acid) amphiphilic block copolymer (PS-b-PA) played a role as a modifier for the liquid crystalline interfaces. The 5CB molecules in the herceptin antibody-conjugated LC microdroplets have shown an orientation transition from radial to bipolar on selective interactions with targeted SK-BR3 breast cancer cells, which are over expressed by the human epidermal growth factor receptor 2-positive (HER2). The herceptin antibody-conjugated LC microdroplets are found to be highly selective in the detection of SK-BR3 cancer cells in the presence of control cells, such as KB cancer cells and fibroblast (FB), and also in the presence of 10% human blood plasma. The interaction forces of the SK-BR3 cancer cells were only effective in causing orientation transitions in 5CB molecules in the LC microdroplets, which clearly suggested that the herceptin antibody-conjugated LC microdroplets could be used as a selective biosensor for a real-time detection of SK-BR3 cancer cells in biological fluids.

  15. Transcription Factors Mediate the Enzymatic Disassembly of Promoter-Bound 7SK snRNP to Locally Recruit P-TEFb for Transcription Elongation

    Directory of Open Access Journals (Sweden)

    Ryan P. McNamara

    2013-12-01

    Full Text Available The transition from transcription initiation into elongation is controlled by transcription factors, which recruit positive transcription elongation factor b (P-TEFb to promoters to phosphorylate RNA polymerase II. A fraction of P-TEFb is recruited as part of the inhibitory 7SK small nuclear ribonucleoprotein particle (snRNP, which inactivates the kinase and prevents elongation. However, it is unclear how P-TEFb is captured from the promoter-bound 7SK snRNP to activate elongation. Here, we describe a mechanism by which transcription factors mediate the enzymatic release of P-TEFb from the 7SK snRNP at promoters to trigger activation in a gene-specific manner. We demonstrate that Tat recruits PPM1G/PP2Cγ to locally disassemble P-TEFb from the 7SK snRNP at the HIV promoter via dephosphorylation of the kinase T loop. Similar to Tat, nuclear factor (NF-κB recruits PPM1G in a stimulus-dependent manner to activate elongation at inflammatory-responsive genes. Recruitment of PPM1G to promoter-assembled 7SK snRNP provides a paradigm for rapid gene activation through transcriptional pause release.

  16. Epibionts and parasites on crustaceans (Copepoda, Cladocera, Cirripedia larvae inhabiting the Gulf of Gdańsk (Baltic Sea in very large numbers* This work was supported in part by grant No. BW/1320-5-0183-3 from the University of Gdańsk.

    Directory of Open Access Journals (Sweden)

    Luiza Bielecka

    2014-06-01

    Infestation by epibionts and parasites was not restricted to calanoid copepods: it was also detected in non-negligible numbers on other crustaceans, namely, Harpacticoida, Cladocera (Bosmina sp. and Cirripedia larvae (nauplii in the Gulf of Gdańsk.

  17. Study on meter-scale cycles of the Lower Cretaceous Quantou Formation in SK-1 well%SK-1井下白垩统泉头组米级旋回研究

    Institute of Scientific and Technical Information of China (English)

    郭娟娟; 吴欣松; 潘建国; 魏东涛; 付建伟

    2012-01-01

    Based on the data of core and well logging of SK-1 well,this paper carried out the sedimentary microfacies identification,and divided cycle into third-order,fourth-order,fifth-order and meter-scale cycles.According to the cyclic sequence,this paper carried out the Fischer graphic analysis,and established cyclic stratigraphic framework.The absolute age ofQuantou Formation in SongliaoBasin was obtained by usingwell logging spectral analysis,and the cycle times were estimated.The result shows that the fifth-order cycle is 112 ka and fourth-order cycle is 379 ka,which is separately corresponding toMilankovitch eccentricity short circle 85~140 ka and Milankovitch eccentricity long circle 350~400 ka.The results coincide with the result of logging.This further illustrates that the forming of cycle sequence formation is controlled byMilankovitch cycle,which provides scientific foundation for the test of influencing factors of climate change in Cretaceous period.%通过对SK-1井泉头组岩心的详细观察与描述,并结合测井曲线特征,开展了泉头组沉积微相的识别,并在此基础上,划分了Ⅲ级、Ⅳ级、Ⅴ级及米级旋回。通过对所划分的旋回地层进行Fischer图解分析,建立了反映泉头组地层叠置关系的旋回地层格架。利用测井谱分析,结合前人分析测试得到的松辽盆地泉头组的绝对年龄,对各级旋回进行周期计算,发现Ⅴ级旋回周期约为112ka,Ⅳ级旋回周期约为379ka,分别与米兰科维奇偏心率短周期85~140ka和长周期350~400ka相对应,从而表明SK-1井旋回地层的形成受米兰科维奇旋回的控制。此研究结果为早白垩世气候变化对旋回地层的影响研究提供了科学依据。

  18. Mechanism of TNFα Regulating KLF4 Expression in Breast Cancer Cells SK-BR-3%肿瘤坏死因子α调节乳腺癌SK-BR-3细胞中KLF4表达及其机制研究

    Institute of Scientific and Technical Information of China (English)

    刘彩云; 史建红; 周金飒; 赵明智; 王冰; 崔乃鹏; 陈保平

    2015-01-01

    目的 探讨肿瘤坏死因子α(TNFα)对乳腺癌SK-BR-3细胞中Krüppel样因子4(KLF4)表达的影响,明确KLF4在促进乳腺癌SK-BR-3细胞凋亡中的作用机制.方法 用不同浓度TNFα(0、1、5、10、20 ng/ml)刺激乳腺癌SK-BR-3细胞,采用Western blot法检测KLF4表达水平;用流式细胞术和DAPI染色法分析细胞凋亡情况.结果 随着刺激浓度的增高,KLF4表达水平呈剂量依赖性逐渐增多.流式细胞术和DAPI染色显示,TNFα可诱导乳腺癌SK-BR-3细胞凋亡.构建pAd-GFP和pAd-GFP-KLF4腺病毒表达载体,在乳腺癌SK-BR-3细胞中过表达GFP或GFP-KLF4,再给予TNFα刺激后,流式细胞术观察结果显示,KLF4过表达可促进乳腺癌SK-BR-3细胞凋亡.结论 TNFα可诱导乳腺癌SK-BR-3细胞中KLF4表达,KLF4参与了TNFα诱导的乳腺癌SK-BR-3细胞凋亡过程.

  19. Rapid agonist-induced loss of sup 125 I-. beta. -endorphin opioid receptor sites in NG108-15, but not SK-N-SH neuroblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Cone, R.I.; Lameh, J.; Sadee, W. (Univ. of California, San Francisco (United States))

    1991-01-01

    The authors have measured {mu} and {delta} opioid receptor sites on intact SK-N-SH and NG108-15 neuroblastoma cells, respectively, in culture. Use of {sup 125}I-{beta}-endorphin ({beta}E) as a tracer, together with {beta}E(6-31) to block high-affinity non-opioid binding in both cell lines, permitted the measurement of cell surface {mu} and {delta} opioid receptor sites. Labeling was at {delta} sites in NG108-15 cells and predominantly at {mu} sites in SK-N-SH cells. Pretreatment with the {mu} and {delta} agonist, DADLE, caused a rapid loss of cell surface {delta} receptor sites in NG108-15 cells, but failed to reduce significantly {mu} receptor density in SK-N-SH cells.

  20. Carcino-embryonic antigen in monitoring the growth of human colon adenocarcinoma tumour cells SK-CO-1 and HT-29 in vitro and in nude mice

    DEFF Research Database (Denmark)

    Sölétormos, G; Fogh, J M; Sehested-Hansen, B

    1997-01-01

    A set of experimental model systems were designed to investigate (a) the inter-relationship between growth of two human cancer cell lines (SK-CO-1, HT-29) and carcino-embryonic antigen (CEA) kinetics; and (b) whether neoplastic growth or CEA concentration is modulated by human growth hormone (h......GH). We found that increasing CEA concentration depended on tumour burden. SK-CO-1 cells had the lowest growth rates but the highest rates of CEA production. The rate of CEA increase exceeded the growth rate of both SK-CO-1 and HT-29. hGH modulated neither neoplastic growth nor CEA production....... In conclusion, our results suggest that experimental models may be useful for investigating the role of serological markers as monitors of increasing tumour burden. It will be of interest to investigate the performance of those model systems in examining the effect of cytotoxic agents in neoplastic growth....

  1. Krüppel-like factor 4 induces apoptosis and inhibits tumorigenic progression in SK-BR-3 breast cancer cells.

    Science.gov (United States)

    Wang, Bing; Zhao, Ming-Zhi; Cui, Nai-Peng; Lin, Dan-Dan; Zhang, An-Yi; Qin, Yan; Liu, Cai-Yun; Yan, Wei-Tao; Shi, Jian-Hong; Chen, Bao-Ping

    2015-01-01

    Krüppel-like factor 4 (KLF4) functions as either a tumor suppressor or an oncogene in different tissues by regulating the expression of various genes. The aim of this study was to reveal the functions of KLF4 in regulating breast cancer apoptosis, proliferation, and tumorigenic progression. KLF4 expression levels in breast cancer tissues and breast cancer cell lines were found to be much lower than those in nontumorous tissues and a nontransformed mammary epithelial cell line. KLF4 was upregulated in the tumor necrosis factor-α-induced SK-BR-3 breast cancer cell apoptotic process. Overexpression of KLF4 promoted SK-BR-3 breast cancer cell apoptosis and suppressed SK-BR-3 cell tumorigenicity in vivo.

  2. RuvBL2 is involved in histone deacetylase inhibitor PCI-24781-induced cell death in SK-N-DZ neuroblastoma cells.

    Directory of Open Access Journals (Sweden)

    Qinglei Zhan

    Full Text Available Neuroblastoma is the second most common solid tumor diagnosed during infancy. The survival rate among children with high-risk neuroblastoma is less than 40%, highlighting the urgent needs for new treatment strategies. PCI-24781 is a novel hydroxamic acid-based histone deacetylase (HDAC inhibitor that has high efficacy and safety for cancer treatment. However, the underlying mechanisms of PCI-24781 are not clearly elucidated in neuroblastoma cells. In the present study, we demonstrated that PCI-24781 treatment significantly inhibited tumor growth at very low doses in neuroblastoma cells SK-N-DZ, not in normal cell line HS-68. However, PCI-24781 caused the accumulation of acetylated histone H3 both in SK-N-DZ and HS-68 cell line. Treatment of SK-N-DZ with PCI-24781 also induced cell cycle arrest in G2/M phase and activated apoptosis signaling pathways via the up-regulation of DR4, p21, p53 and caspase 3. Further proteomic analysis revealed differential protein expression profiles between non-treated and PCI-24781 treated SK-N-DZ cells. Totally 42 differentially expressed proteins were identified by MALDI-TOF MS system. Western blotting confirmed the expression level of five candidate proteins including prohibitin, hHR23a, RuvBL2, TRAP1 and PDCD6IP. Selective knockdown of RuvBL2 rescued cells from PCI-24781-induced cell death, implying that RuvBL2 might play an important role in anti-tumor activity of PCI-24781 in SK-N-DZ cells. The present results provide a new insight into the potential mechanism of PCI-24781 in SK-N-DZ cell line.

  3. Slit2 and Robo1 induce opposing effects on metastasis of hepatocellular carcinoma Sk-hep-1 cells.

    Science.gov (United States)

    Yuan, Mingjing; Guo, Hui; Li, Jing; Sui, Chengzhi; Qin, Ying; Wang, Jingjing; Khan, Yasir Hayat; Ye, Liying; Xie, Fuan; Wang, Heng; Yuan, Li; Ye, Jun

    2016-07-01

    The neural guidance molecular, Slit2, and its cognate receptor, Robo1, play critical roles in the development of the nervous system, nevertheless, their functions are not limited to this system. Numerous studies have shown decreased Slit2 expression in a wide variety of cancers, highlighting its potential as a tumor suppressor. However, the Slit2/Robo1 signaling axis was reported to induce either suppressive or stimulatory effects on tumor growth and metastasis, depending on cellular context. There is a paucity of information on the effects of the Slit2/Robo1 signaling axis on the growth and metastasis of human hepatocellular carcinoma (HCC). Large-scale data mining of the Oncomine database has revealed heterogeneous expression of Slit2 in HCC. We screened the Sk-hep-1, a cell line showing a relatively high level of Slit2, and low level of Robo1 expression. After Slit2 knockdown and Robo1 overexpression in these cells, we found Slit2 and Robo1 exerted opposing effects on tumor growth and metastasis both in in vitro and in vivo models. Slit2 knockdown and Robo1 overexpression in Sk-hep-1 cells promoted tumor growth and metastasis, suggesting a negative and positive role for Slit2 and Robo1, respectively, in tumor progression. Robo1 overexpression upregulated matrix metalloproteinase (MMP)2, -9 and membrane-type1 MMP (MT1-MMP) expression, stimulated MMP2, but not MMP9 activation, and downregulated expression of TIMP1 and 2. The PI3K/Akt signaling pathway is of importance in regulating MMP2 expression in Sk-hep-1 cells, since Robo1 overexpression stimulated phosphorylation of Akt while the PI3K inhibitor LY294002, significantly inhibited the upregulation of MMP2 and also the enhanced cell invasion induced by Robo1 overexpression. We postulate that Robo1 promotes tumor invasion partly by the upregulation of MMP2 after activation of PI3K/Akt signaling pathway. Notably, Slit2 knockdown caused the upregulation of Robo1 expression both at the mRNA and protein levels

  4. Two-Particle Correlations in pp, $\\overline{p}\\overline{p}$ and $K^{0}_{s}K^{0}_{s}$ pairs from Hadronic Z decays

    CERN Document Server

    Schael, S; Brunelière, R; De Bonis, I; Décamp, D; Goy, C; Jézéquel, S; Lees, J P; Martin, F; Merle, E; Minard, M N; Pietrzyk, B; Trocmé, B; Bravo, S; Casado, M P; Chmeissani, M; Crespo, J M; Fernández, E; Fernández-Bosman, M; Garrido, L; Martínez, M; Pacheco, A; Ruiz, H; Colaleo, A; Creanza, D; De Filippis, N; De Palma, M; Iaselli, G; Maggi, G; Maggi, M; Nuzzo, S; Ranieri, A; Raso, G; Ruggieri, F; Selvaggi, G; Silvestris, L; Tempesta, P; Tricomi, A; Zito, G; Huang, X; Lin, J; Ouyang, Q; Wang, T; Xie, Y; Xu, R; Xue, S; Zhang, J; Zhang, L; Zhao, W; Abbaneo, D; Barklow, T; Buchmüller, O L; Cattaneo, M; Clerbaux, B; Drevermann, H; Forty, R W; Frank, M; Gianotti, F; Hansen, J B; Harvey, J; Hutchcroft, D E; Janot, P; Jost, B; Kado, M; Mato, P; Moutoussi, A; Ranjard, F; Rolandi, Luigi; Schlatter, W D; Sguazzoni, G; Teubert, F; Valassi, A; Videau, I; Badaud, F; Dessagne, S; Falvard, A; Fayolle, D; Gay, P; Jousset, J; Michel, B; Monteil, S; Pallin, D; Pascolo, J M; Perret, P; Hansen, J D; Hansen, J R; Hansen, P H; Kraan, A C; Nilsson, B S; Kyriakis, A; Markou, C; Simopoulou, E; Vayaki, A; Zachariadou, K; Blondel, A; Brient, J C; Machefert, F P; Rougé, A; Videau, H L; Ciulli, V; Focardi, E; Parrini, G; Antonelli, A; Antonelli, M; Bencivenni, G; Bossi, F; Capon, G; Cerutti, F; Chiarella, V; Laurelli, P; Mannocchi, G; Murtas, G P; Passalacqua, L; Kennedy, J; Lynch, J G; Negus, P; O'Shea, V; Thompson, A S; Wasserbaech, S R; Cavanaugh, R J; Dhamotharan, S; Geweniger, C; Hanke, P; Hepp, V; Kluge, E E; Putzer, A; Stenzel, H; Tittel, K; Wunsch, M; Beuselinck, R; Cameron, W; Davies, G; Dornan, P J; Girone, M; Marinelli, N; Nowell, J; Rutherford, S A; Sedgbeer, J K; Thompson, J C; White, R; Ghete, V M; Girtler, P; Kneringer, E; Kuhn, D; Rudolph, G; Bouhova-Thacker, E; Bowdery, C K; Clarke, D P; Ellis, G; Finch, A J; Foster, F; Hughes, G; Jones, R W L; Pearson, M R; Robertson, N A; Smizanska, M; van der Aa, O; Delaere, C; Leibenguth, G; Lemaître, V; Blumenschein, U; Hölldorfer, F; Jakobs, K; Kayser, F; Kleinknecht, K; Müller, A S; Renk, B; Sander, H G; Schmeling, S; Wachsmuth, H W; Zeitnitz, C; Ziegler, T; Bonissent, A; Coyle, P; Curtil, C; Ealet, A; Fouchez, D; Payre, P; Tilquin, A; Ragusa, F; David, A; Dietl, H; Ganis, G; Hüttmann, K; Lütjens, G; Männer, W; Moser, H G; Settles, R; Villegas, M; Wolf, G; Boucrot, J; Callot, O; Davier, M; Duflot, L; Grivaz, J F; Heusse, P; Jacholkowska, A; Serin, L; Veillet, J J; Azzurri, P; Bagliesi, G; Boccali, T; Foà, L; Giammanco, A; Giassi, A; Ligabue, F; Messineo, A; Palla, F; Sanguinetti, G; Sciabà, A; Spagnolo, P; Tenchini, R; Venturi, A; Verdini, P G; Awunor, O; Blair, G A; Cowan, G; García-Bellido, A; Green, M G; Medcalf, T; Misiejuk, A; Strong, J A; Teixeira-Dias, P; Clifft, R W; Edgecock, T R; Norton, P R; Tomalin, I R; Ward, J J; Bloch-Devaux, B; Boumediene, D E; Colas, P; Fabbro, B; Lançon, E; Lemaire, M C; Locci, E; Pérez, P; Rander, J; Tuchming, B; Vallage, B; Litke, A M; Taylor, G; Booth, C N; Cartwright, S; Combley, F; Hodgson, P N; Lehto, M H; Thompson, L F; Böhrer, A; Brandt, S; Grupen, C; Hess, J; Ngac, A; Prange, G; Borean, C; Giannini, G; He, H; Pütz, J; Rothberg, J E; Armstrong, S R; Berkelman, K; Cranmer, K; Ferguson, D P S; Gao, Y; González, S; Hayes, O J; Hu, H; Jin, S; Kile, J; McNamara, P A; Nielsen, J; Pan Yi Bin; Von Wimmersperg-Töller, J H; Wiedenmann, W; Wu, J; Wu Sau Lan; Wu, X; Zobernig, G; Dissertori, G

    2005-01-01

    Two-Particle correlations in pp, pbarpbar and K0sK0s pairs have been studied in hadronic Z decays recorded at LEP with the ALEPH detector. The correlations were measured as a function of the four-momentum difference Q of the pair. For pp, pbarpbar pairs a depletion of events is observed in the region Q < 3 GeV, and for K0sK0s pairs an enhancement of events is observed in the region Q < 0.5 GeV. These features are consistent with expectations from Fermi-Dirac and Bose-Einstein statistics, respectively.

  5. TIMP-1 overexpression does not affect sensitivity to HER2-targeting drugs in the HER2-gene-amplified SK-BR-3 human breast cancer cell line

    DEFF Research Database (Denmark)

    Deng, Xiaohong; Fogh, Louise; Lademann, Ulrik Axel

    2013-01-01

    affect sensitivity to the HER2-targeting drugs trastuzumab and lapatinib. SK-BR-3 human breast cancer cells were stably transfected with TIMP-1, characterized with regard to TIMP-1 protein expression, proliferation, and functionality of the secreted TIMP-1, and the sensitivity to trastuzumab...... and lapatinib was studied in five selected single-cell subclones expressing TIMP-1 protein at various levels plus the parental SK-BR-3 cell line. Both trastuzumab and lapatinib reduced cell viability, as determined by MTT assay, but the sensitivity to the drugs was not associated with the expression level...

  6. Egf binding to its receptor triggers a rapid tyrosine phosphorylation of the erbB-2 protein in the mammary tumor cell line SK-BR-3.

    OpenAIRE

    King, C. R.; Borrello, I; Bellot, F; Comoglio, P; Schlessinger, J

    1988-01-01

    The epidermal growth factor receptor (EGF-R) and the erbB-2 proto-oncogene product protein are closely related by their structural homology and their shared enzymatic activity as autophosphorylating tyrosine kinases. We show that in mammary tumor cells (SK-BR-3) EGF causes a rapid increase in tyrosine phosphorylation of the erbB-2 protein. Phosphorylation of erbB-2 does not occur in cells lacking the EGF-R (MDA-MB-453). Phosphorylation of erbB-2 in SK-BR-3 cells is blocked if EGF is prevented...

  7. The reconstruction of air pressure in Gdańsk in the period of instrumental observations, 1739-2012

    Science.gov (United States)

    Filipiak, Janusz

    2015-04-01

    The purpose of the paper is to characterise the details of reconstruction of air pressure in Gdańsk in the whole period of regular instrumental records spanning the period 1739-2012. Gdańsk pressure series has been reconstructed by joining air pressure observations of 15 local shorter series. The entire instrumental series can be divided into three sub-periods: the Early Observers period, lasting to 1806, the First Meteorological Networks, covering the years from 1807 to 1875 and Modern Measurements begun in 1876. During the first period, observations were made from two to four times per day, sometimes even at midnight. In the 19th century and up to 1945 thrice-daily barometer readings were a standard, in the last few decades the density of data is much denser. A serious gap in the original daily data exists for the period 1849-1875, where it appears that no original source of data have survived. Selected data are presented in the form of five-day or monthly averages. Numerous errors made probably during the re-writing of original observers' data by their assistants were discovered during digitalization. Despite this the quality of observations can be regarded as good. Data have been corrected to provide a monthly-mean measure of atmospheric pressure in the unit of hPa at standard conditions, i.e. standard gravity, 0 °C and at sea level. Some inconsistencies may still arise as the procedure of the homogenization of air temperature is not completed and in case of a few oldest series air temperature was estimated. Numerous breakpoints were identified in the homogenisation of the series and they cannot be always linked to known causes. A reasonably detailed station history has been compiled by incorporating metadata contained in various written sources. These metadata have facilitated the homogenisation of the data series. Mean annual atmospheric pressure in Gdańsk in period 1739-2012 calculated on the basis of homogenized series was 1014.9 hPa. Mean seasonal

  8. Analysis of PolSK based FSO system using wavelength and time diversity over strong atmospheric turbulence with pointing errors

    Science.gov (United States)

    Prabu, K.; Cheepalli, Shashidhar; Kumar, D. Sriram

    2014-08-01

    Free space optics (FSO) or wireless optical communication systems is an evolving alternative to the current radio frequency (RF) links due to its high and secure datarates, large license free bandwidth access, ease of installation, and lower cost for shorter range distances. These systems are largely influenced by atmospheric conditions due to wireless transmission; requirement of line of sight (LOS) propagation may lead to alignment problems in turn pointing errors. In this paper, we consider atmospheric turbulence and pointing errors are the major limitations. We tried to address these difficulties by considering polarization shift keying (PolSK) modulated FSO communication system with wavelength and time diversity. We derived the closed form expressions for estimation of the average bit error rate (BER) and outage probability, which are vital system performance metrics. Analytical results are shown considering different practical cases.

  9. 绝地大反攻击败SK NiP瑞典称霸王者再现

    Institute of Scientific and Technical Information of China (English)

    J.son

    2006-01-01

    <正> NiP 自2005年由 HeatoN 及 Potti 重组以来,仍然活跃在世界 CS 舞台,但却始终缺乏一种王者之气,即便是在瑞典国内,也未曾取得过令人瞩目的成绩。而 SK 虽然也几经重组,但仍然依靠着 Fisker 和 Spawn 等老将的稳定发挥保住了自己的霸主地位。但就在上个月,Spawn 突然由 SK 出走并进入了 NiP 的阵容,而且临时取代了 HeatoN 的位置。突如其来的变故使人们一下子关注起 NiP 来,毕竟 NiP 的阵容已经更趋向稳定和合理。两个豪门俱乐部的恩恩怨怨向来为世界 CS 爱好者们所津津乐道,如今新仇旧恨交织在一起的10个人将爆发出一场怎样的战争呢? NiP 自2005年由 HeatON 及 Potti 重组以来,仍然活跃在世界 CS 舞台,但却始终缺乏一种王者之气,即便是在瑞典国内,也未曾取得过令人瞩目的成绩。而 SK 虽然也几经重组,但仍然依靠着 Fisker 和 Spawn 等老将的稳定发挥保住了自己的霸主地位。但就在上个月,Spawn 突然由 SK 出走并进入了 NiP 的阵容,而且临时取代了 HeatON 的位置。突如其来的变故使人们一下子关注起 NiP 来,毕竟 NiP 的阵容已经更趋向稳定和合理。两个豪门俱乐部的恩恩怨怨向来为世界 CS 爱好者们所津津乐道,如今新仇旧恨交织在一起的10个人将爆发出一场怎样的战争呢?

  10. Polonium (210)Po activities in human blood of patients with ischaemic heart disease from Gdańsk in Poland.

    Science.gov (United States)

    Boryło, Alicja; Skwarzec, Bogdan; Romańczyk, Grzegorz; Siebert, Janusz

    The determination of polonium (210)Po in human blood samples is presented and discussed in this paper. The human blood samples were collected from patients of Medical University of Gdańsk with ischaemic heart disease (morbus ischaemicus cordis, MIC). The polonium concentrations in analyzed human blood samples are very differentiated. (210)Po is of particular interest in public health and although is present in the environment in extremely low amounts, it is easily bioaccumulated to the human body. The study shows that the amount of (210)Po that is incorporated into the human body depends on the food habits and some difference in its levels could be observed between smokers and non-smokers.

  11. COMPARATIVE ANALYSIS OF TRANSPORT ORGANIZATION AND FUNCTIONING OF WATER TRAMS IN GDAŃSK, BYDGOSZCZ AND KRAKÓW

    Directory of Open Access Journals (Sweden)

    Emilia Miszewska-Urbańsk

    2016-03-01

    Full Text Available The subject of this work is to identify and juxtapose solutions implemented in transport provided by water trams for the following cities: Gdańsk, Bydgoszcz and Kraków. As a result of the conducted analysis of transport factors, the degree of conformity of project objectives to the actual role of the water tram has been determined. It was found that the Kraków Water Tram (also known as Cracow Water Tram is characterized by the greatest degree of conformity with project objectives. The solutions adopted in the project can be used to develop organizational and functional standards for this type of transport in Poland, since the lack of system solutions and little experience in implementation of water trams resulted in different organizational and technical approaches in their functioning.

  12. Selegiline increases heme oxygenase-1 expression and the cytotoxicity produced by dopamine treatment of neuroblastoma SK-N-SH cells

    Directory of Open Access Journals (Sweden)

    Rieder C.R.M.

    2004-01-01

    Full Text Available Increased dopamine catabolism may be associated with oxidative stress and neuronal cell death in Parkinson's disease. The present study was carried out to examine the effect of dopamine on the expression of heme oxygenase-1 and -2 (HO-1 and HO-2 in human neuroblastomas (SK-N-SH cell line and the effects of selegiline and antioxidants on this expression. Cells were kept with close control of pH and were incubated with varying concentrations of dopamine (0.1-100 µM for 24 h. HO-1 and HO-2 cDNA probes were prepared by reverse transcription-polymerase chain reaction amplification. The mRNA expression of HO-1 and HO-2 was measured by Northern blot analysis. The levels of HO-1 mRNA increased after dopamine treatment, in a dose-dependent manner, in all cell lines studied, whereas levels of the two HO-2 transcripts did not. The HO-1 and HO-2 protein expression was analyzed by Western blotting. HO-1 protein was undetectable in untreated SK-N-SH cells and increased after treatment with dopamine. In contrast, the HO-2 protein (36 kDa was detected in untreated cells and the levels did not change as a result of treatment. alpha-Tocopherol (10-100 µM and ascorbic acid (100 µM did not attenuate the effects of dopamine. Selegiline (10 µM produced significant increase (P < 0.01 in the induction of HO-1 by dopamine (more than six times the control values. The increased expression of HO-1 following dopamine treatment indicates that dopamine produces oxidative stress in this cell line.

  13. Impact of image segmentation on high-content screening data quality for SK-BR-3 cells

    Directory of Open Access Journals (Sweden)

    Li Yizheng

    2007-09-01

    Full Text Available Abstract Background High content screening (HCS is a powerful method for the exploration of cellular signalling and morphology that is rapidly being adopted in cancer research. HCS uses automated microscopy to collect images of cultured cells. The images are subjected to segmentation algorithms to identify cellular structures and quantitate their morphology, for hundreds to millions of individual cells. However, image analysis may be imperfect, especially for "HCS-unfriendly" cell lines whose morphology is not well handled by current image segmentation algorithms. We asked if segmentation errors were common for a clinically relevant cell line, if such errors had measurable effects on the data, and if HCS data could be improved by automated identification of well-segmented cells. Results Cases of poor cell body segmentation occurred frequently for the SK-BR-3 cell line. We trained classifiers to identify SK-BR-3 cells that were well segmented. On an independent test set created by human review of cell images, our optimal support-vector machine classifier identified well-segmented cells with 81% accuracy. The dose responses of morphological features were measurably different in well- and poorly-segmented populations. Elimination of the poorly-segmented cell population increased the purity of DNA content distributions, while appropriately retaining biological heterogeneity, and simultaneously increasing our ability to resolve specific morphological changes in perturbed cells. Conclusion Image segmentation has a measurable impact on HCS data. The application of a multivariate shape-based filter to identify well-segmented cells improved HCS data quality for an HCS-unfriendly cell line, and could be a valuable post-processing step for some HCS datasets.

  14. Anthocyanins Protect SK-N-SH Cells Against Acrolein-Induced Toxicity by Preserving the Cellular Redox State.

    Science.gov (United States)

    Belkacemi, Abdenour; Ramassamy, Charles

    2016-01-01

    In Alzheimer's disease (AD) and in mild cognitive impairment (MCI) patients, by-products of lipid peroxidation such as acrolein accumulated in vulnerable regions of the brain. We have previously shown that acrolein is a highly reactive and neurotoxic aldehyde and its toxicity involves the alteration of several redox-sensitive pathways. Recently, protein-conjugated acrolein in cerebrospinal fluid has been proposed as a biomarker to distinguish between MCI and AD. With growing evidence of the early involvement of oxidative stress in AD etiology, one would expect that a successful therapy should prevent brain oxidative damage. In this regard, several studies have demonstrated that polyphenol-rich extracts exert beneficial effect on cognitive impairment and oxidative stress. We have recently demonstrated the efficacy of an anthocyanin formulation (MAF14001) against amyloid-β-induced oxidative stress. The aim of this study is to investigate the neuroprotective effect of MAF14001 as a mixture of anthocyanins, a particular class of polyphenols, against acrolein-induced oxidative damage in SK-N-SH neuronal cells. Our results demonstrated that MAF14001, from 5μM, was able to efficiently protect SK-N-SH cells against acrolein-induced cell death. MAF14001 was able to lower reactive oxygen species and protein carbonyl levels induced by acrolein. Moreover, MAF1401 prevented glutathione depletion and positively modulated, in the presence of acrolein, some oxidative stress-sensitive pathways including the transcription factors NF-κB and Nrf2, the proteins γ-GCS and GSK3β, and the protein adaptator p66Shc. Along with its proven protective effect against amyloid-β toxicity, these results demonstrate that MAF14001 could target multiple mechanisms and could be a promising agent for AD prevention.

  15. MULTICELLULAR-MEDIATED RESISTANCE TO CISPLATIN AND TAXOL IN HUMAN OVARIAN CANCER SK-OV-3IP1 MULTICELLULAR AGGREGATES

    Institute of Scientific and Technical Information of China (English)

    陈建利; 丰有吉; 张琴

    2002-01-01

    Objective: To investigate the chemosensitivity of ovarian cancer SK-OV-3ip1 multicellular aggregates (MCA) to cisplatin and taxol and to explore the possible mechanisms. Methods: Liquid overlay system was employed to obtain MCA. We detected the resistance using trypan blue exclusion testing, clonogenic assay, cell cycle profiles and apoptosis with flow cytometry (FCM). Results: After cisplatin exposure, MCA cells showed nearly equal cell viability with monolayer cells (P=0.05). After 40(M cisplatin exposure for 12 h, no clone ((50 cells) was formed, but more viable cells attached to the bottom of 24-well plate in MCA group than monolayer. Furthermore, apoptosis rate and cell cycle profiles with FCM had no significant change between MCA and monolayer cells. After taxol exposure, however, trypan blue exclusion testing demonstrated higher cell viability in MCA cells (P=0.003) and higher clone formation rate in 100-cell group than monolayer cells (0.01SK-OV-3ip1 cell line appear to be more resistant to taxol but not to cisplatin. Cell cycle redistribution and multicellular-mediated inhibition of apoptosis can partially account for the resistance.

  16. A High Molecular-Mass Anoxybacillus sp. SK3-4 Amylopullulanase: Characterization and Its Relationship in Carbohydrate Utilization

    Directory of Open Access Journals (Sweden)

    Kian Mau Goh

    2013-05-01

    Full Text Available An amylopullulanase of the thermophilic Anoxybacillus sp. SK3-4 (ApuASK was purified to homogeneity and characterized. Though amylopullulanases larger than 200 kDa are rare, the molecular mass of purified ApuASK appears to be approximately 225 kDa, on both SDS-PAGE analyses and native-PAGE analyses. ApuASK was stable between pH 6.0 and pH 8.0 and exhibited optimal activity at pH 7.5. The optimal temperature for ApuASK enzyme activity was 60 °C, and it retained 54% of its total activity for 240 min at 65 °C. ApuASK reacts with pullulan, starch, glycogen, and dextrin, yielding glucose, maltose, and maltotriose. Interestingly, most of the previously described amylopullulanases are unable to produce glucose and maltose from these substrates. Thus, ApuASK is a novel, high molecular-mass amylopullulanase able to produce glucose, maltose, and maltotriose from pullulan and starch. Based on whole genome sequencing data, ApuASK appeared to be the largest protein present in Anoxybacillus sp. SK3-4. The α-amylase catalytic domain present in all of the amylase superfamily members is present in ApuASK, located between the cyclodextrin (CD-pullulan-degrading N-terminus and the α-amylase catalytic C-terminus (amyC domains. In addition, the existence of a S-layer homology (SLH domain indicates that ApuASK might function as a cell-anchoring enzyme and be important for carbohydrate utilization in a streaming hot spring.

  17. Carcino-embryonic antigen in monitoring the growth of human colon adenocarcinoma tumour cells SK-CO-1 and HT-29 in vitro and in nude mice

    DEFF Research Database (Denmark)

    Sölétormos, G; Fogh, J M; Sehested-Hansen, B;

    1997-01-01

    A set of experimental model systems were designed to investigate (a) the inter-relationship between growth of two human cancer cell lines (SK-CO-1, HT-29) and carcino-embryonic antigen (CEA) kinetics; and (b) whether neoplastic growth or CEA concentration is modulated by human growth hormone (h...

  18. $K^{0}_{s}-K^{0}_{s}$ correlations in pp collisions at $\\sqrt{s}=7 TeV$ from the LHC ALICE experiment

    CERN Document Server

    Abelev, Betty; Adamova, Dagmar; Adare, Andrew Marshall; Aggarwal, Madan; Aglieri Rinella, Gianluca; Agocs, Andras Gabor; Agostinelli, Andrea; Aguilar Salazar, Saul; Ahammed, Zubayer; Ahmad, Arshad; Ahmad, Nazeer; Ahn, Sang Un; Akindinov, Alexander; Aleksandrov, Dmitry; Alessandro, Bruno; Alfaro Molina, Jose Ruben; Alici, Andrea; Alkin, Anton; Almaraz Avina, Erick Jonathan; Alme, Johan; Alt, Torsten; Altini, Valerio; Altinpinar, Sedat; Altsybeev, Igor; Andrei, Cristian; Andronic, Anton; Anguelov, Venelin; Anielski, Jonas; Anticic, Tome; Antinori, Federico; Antonioli, Pietro; Aphecetche, Laurent Bernard; Appelshauser, Harald; Arbor, Nicolas; Arcelli, Silvia; Armesto, Nestor; Arnaldi, Roberta; Aronsson, Tomas Robert; Arsene, Ionut Cristian; Arslandok, Mesut; Augustinus, Andre; Averbeck, Ralf Peter; Awes, Terry; Aysto, Juha Heikki; Azmi, Mohd Danish; Bach, Matthias Jakob; Badala, Angela; Baek, Yong Wook; Bailhache, Raphaelle Marie; Bala, Renu; Baldini Ferroli, Rinaldo; Baldisseri, Alberto; Baldit, Alain; Baltasar Dos Santos Pedrosa, Fernando; Ban, Jaroslav; Baral, Rama Chandra; Barbera, Roberto; Barile, Francesco; Barnafoldi, Gergely Gabor; Barnby, Lee Stuart; Barret, Valerie; Bartke, Jerzy Gustaw; Basile, Maurizio; Bastid, Nicole; Basu, Sumit; Bathen, Bastian; Batigne, Guillaume; Batyunya, Boris; Baumann, Christoph Heinrich; Bearden, Ian Gardner; Beck, Hans; Behera, Nirbhay Kumar; Belikov, Iouri; Bellini, Francesca; Bellwied, Rene; Belmont-Moreno, Ernesto; Bencedi, Gyula; Beole, Stefania; Berceanu, Ionela; Bercuci, Alexandru; Berdnikov, Yaroslav; Berenyi, Daniel; Bergognon, Anais Annick Erica; Berzano, Dario; Betev, Latchezar; Bhasin, Anju; Bhati, Ashok Kumar; Bhom, Jihyun; Bianchi, Livio; Bianchi, Nicola; Bianchin, Chiara; Bielcik, Jaroslav; Bielcikova, Jana; Bilandzic, Ante; Bjelogrlic, Sandro; Blanco, F; Blanco, Francesco; Blau, Dmitry; Blume, Christoph; Bock, Nicolas; Boettger, Stefan; Bogdanov, Alexey; Boggild, Hans; Bogolyubsky, Mikhail; Boldizsar, Laszlo; Bombara, Marek; Book, Julian; Borel, Herve; Borissov, Alexander; Bose, Suvendu Nath; Bossu, Francesco; Botje, Michiel; Boyer, Bruno Alexandre; Braidot, Ermes; Braun-Munzinger, Peter; Bregant, Marco; Breitner, Timo Gunther; Browning, Tyler Allen; Broz, Michal; Brun, Rene; Bruna, Elena; Bruno, Giuseppe Eugenio; Budnikov, Dmitry; Buesching, Henner; Bufalino, Stefania; Bugaiev, Kyrylo; Busch, Oliver; Buthelezi, Edith Zinhle; Caffarri, Davide; Cai, Xu; Caines, Helen Louise; Calvo Villar, Ernesto; Camerini, Paolo; Canoa Roman, Veronica; Cara Romeo, Giovanni; Carena, Francesco; Carena, Wisla; Carminati, Federico; Casanova Diaz, Amaya Ofelia; Castillo Castellanos, Javier Ernesto; Casula, Ester Anna Rita; Catanescu, Vasile; Cavicchioli, Costanza; Ceballos Sanchez, Cesar; Cepila, Jan; Cerello, Piergiorgio; Chang, Beomsu; Chapeland, Sylvain; Charvet, Jean-Luc Fernand; Chattopadhyay, Sukalyan; Chattopadhyay, Subhasis; Chawla, Isha; Cherney, Michael Gerard; Cheshkov, Cvetan; Cheynis, Brigitte; Chiavassa, Emilio; Chibante Barroso, Vasco Miguel; Chinellato, David; Chochula, Peter; Chojnacki, Marek; Choudhury, Subikash; Christakoglou, Panagiotis; Christensen, Christian Holm; Christiansen, Peter; Chujo, Tatsuya; Chung, Suh-Urk; Cicalo, Corrado; Cifarelli, Luisa; Cindolo, Federico; Cleymans, Jean Willy Andre; Coccetti, Fabrizio; Colamaria, Fabio; Colella, Domenico; Conesa Balbastre, Gustavo; Conesa del Valle, Zaida; Constantin, Paul; Contin, Giacomo; Contreras, Jesus Guillermo; Cormier, Thomas Michael; Corrales Morales, Yasser; Cortes Maldonado, Ismael; Cortese, Pietro; Cosentino, Mauro Rogerio; Costa, Filippo; Cotallo, Manuel Enrique; Crochet, Philippe; Cruz Alaniz, Emilia; Cuautle, Eleazar; Cunqueiro, Leticia; D'Erasmo, Ginevra; Dainese, Andrea; Dalsgaard, Hans Hjersing; Danu, Andrea; Das, Debasish; Das, Indranil; Das, Kushal; Dash, Ajay Kumar; Dash, Sadhana; De, Sudipan; de Barros, Gabriel; De Caro, Annalisa; de Cataldo, Giacinto; de Cuveland, Jan; De Falco, Alessandro; De Gruttola, Daniele; De Marco, Nora; De Pasquale, Salvatore; de Rooij, Raoul Stefan; Delagrange, Hugues; Deloff, Andrzej; Demanov, Vyacheslav; Denes, Ervin; Deppman, Airton; Di Bari, Domenico; Di Giglio, Carmelo; Di Liberto, Sergio; Di Mauro, Antonio; Di Nezza, Pasquale; Diaz Corchero, Miguel Angel; Dietel, Thomas; Divia, Roberto; Djuvsland, Oeystein; Dobrin, Alexandru Florin; Dobrowolski, Tadeusz Antoni; Dominguez, Isabel; Donigus, Benjamin; Dordic, Olja; Driga, Olga; Dubey, Anand Kumar; Ducroux, Laurent; Dupieux, Pascal; Dutta Majumdar, AK

    2013-07-16

    Identical neutral kaon pair correlations are measured in $\\sqrt{s}$=7 TeV pp collisions in the ALICE experiment. One-dimensional K$^{0}_{s}$-K$^{0}_{s}$ correlation functions in terms of the invariant momentum difference of kaon pairs are formed in two multiplicity and two transverse momentum ranges. The femtoscopic parameters for the radius and correlation strength of the kaon source are extracted. The fit includes quantum statistics and final-state interactions of the $a_0/f_0$ resonance. K$^{0}_{s}$-K$^{0}_{s}$ correlations show an increase in radius for increasing multiplicity and a slight decrease in radius for increasing transverse mass, $m_T$, as seen in pion-pion correlations in the pp system and in heavy-ion collisions. Transverse mass scaling is observed between the K$^{0}_{s}$-K$^{0}_{s}$ and pion-pion radii. Also, the first observation is made of the decay of the $f_{2}'$(1525) meson into the K$^{0}_{s}$-K$^{0}_{s}$ channel in pp collisions.

  19. Intracellular synthesis of glutamic acid in Bacillus methylotrophicus SK19.001, a glutamate-independent poly(γ-glutamic acid)-producing strain.

    Science.gov (United States)

    Peng, Yingyun; Zhang, Tao; Mu, Wanmeng; Miao, Ming; Jiang, Bo

    2016-01-15

    Bacillus methylotrophicus SK19.001 is a glutamate-independent strain that produces poly(γ-glutamic acid) (γ-PGA), a polymer of D- and L-glutamic acids that possesses applications in food, the environment, agriculture, etc. This study was undertaken to explore the synthetic pathway of intracellular L- and D-glutamic acid in SK19.001 by investigating the effects of tricarboxylic acid cycle intermediates and different amino acids as metabolic precursors on the production of γ-PGA and analyzing the activities of the enzymes involved in the synthesis of L- and D-glutamate. Tricarboxylic acid cycle intermediates and amino acids could participate in the synthesis of γ-PGA via independent pathways in SK19.001. L-Aspartate aminotransferase, L-glutaminase and L-glutamate synthase were the enzymatic sources of L-glutamate. Glutamate racemase was responsible for the formation of D-glutamate for the synthesis of γ-PGA, and the synthetase had stereoselectivity for glutamate substrate. The enzymatic sources of L-glutamate were investigated for the first time in the glutamate-independent γ-PGA-producing strain, and multiple enzymatic sources of L-glutamate were verified in SK19.001, which will benefit efforts to improve production of γ-PGA with metabolic engineering strategies. © 2015 Society of Chemical Industry.

  20. SK channels modulate the excitability and firing precision of projection neurons in the robust nucleus of the arcopallium in adult male zebra finches

    Institute of Scientific and Technical Information of China (English)

    Guo-Qiang Hou; Xuan Pan; Cong-Shu Liao; Song-Hua Wang; Dong-Feng Li

    2012-01-01

    [Objective] Motor control is encoded by neuronal activity.Small conductance Ca2+-activated Kˉ channels (SK channels) maintain the regularity and precision of firing by contributing to the afterhyperpolarization (AHP) of the action potential in mammals.However,it is not clear how SK channels regulate the output of the vocal motor system in songbirds.The premotor robust nucleus of the arcopallium (RA) in the zebra finch is responsible for the output of song information.The temporal pattern of spike bursts in RA projection neurons is associated with the timing of the acoustic features of birdsong.[Methods] The firing properties of RA projection neurons were analyzed using patch clamp wholecell and cell-attached recording techniques.[Results] SK channel blockade by apamin decreased the AHP amplitude and increased the evoked firing rate in RA projection neurons.It also caused reductions in the regularity and precision of firing.RA projection neurons displayed regular spontaneous action potentials,while apamin caused irregular spontaneous firing but had no effect on the firing rate.In the absence of synaptic inputs,RA projection neurons still had spontaneous firing,and apamin had an evident effect on the firing rate,but caused no significant change in the firing regularity,compared with apamin application in the presence of synaptic inputs.[Conclusion]SK channels contribute to the maintenance of firing regularity in RA projection neurons whichrequires synaptic activity,and consequently ensures the precision of song encoding.

  1. METCAM/MUC18 promoted tumorigenesis of human breast cancer SK-BR-3 cells in a dosage-specific manner

    Directory of Open Access Journals (Sweden)

    Chang-Yu Huang

    2016-04-01

    Conclusion: Transient suppression observed previously in the clone was caused by injection of a high cell number (2 × 106–5 × 106. METCAM/MUC18 positively promotes tumorigenesis of SK-BR-3 cells by increasing the survival and proliferation pathway.

  2. Effect of the SK/IK channel modulator 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591) on contractile force in rat, pig and human detrusor smooth muscle

    DEFF Research Database (Denmark)

    Nielsen, Jens Steen; Rode, Frederik; Rahbek, Mette

    2011-01-01

    • To investigate the importance of small (SK)- and intermediate (IK)-conductance Ca2(+) -activated K(+) channels on bladder function, by studying the effects of 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591), a new modulator of SK/IK channels, on contractions induced...

  3. Therapeutic action of the mitochondria-targeted antioxidant SkQ1 on retinopathy in OXYS rats linked with improvement of VEGF and PEDF gene expression.

    Directory of Open Access Journals (Sweden)

    Anton M Markovets

    Full Text Available UNLABELLED: The incidence of age-related macular degeneration (AMD, the main cause of blindness in older patients in the developed countries, is increasing with the ageing population. At present there is no effective treatment for the prevailing geographic atrophy, dry AMD, whereas antiangiogenic therapies successful used in managing the wet form of AMD. Recently we showed that mitochondria-targeted antioxidant plastoquinonyl-decyl-triphenylphosphonium (SkQ1 is able to prevent the development and moreover caused regression of pre-existing signs of the retinopathy in OXYS rats, an animal model of AMD. Here we examine the effects of SkQ1 on expression of key regulators of angiogenesis vascular endothelial growth factor A (VEGF and its antagonist pigment epithelium-derived factor (PEDF genes in the retina of OXYS rats as evidenced by real-time PCR and an ELISA test for VEGF using Wistar rats as control. Ophthalmoscopic examinations confirmed that SkQ1 supplementation (from 1.5 to 3 months of age, 250 nmol/kg prevented development while eye drops SkQ1 (250 nM, from 9 to 12 months caused some reduction of retinopathy signs in OXYS rats and did not reveal any negative effects on the control Wistar rat's retina. Prevention of premature retinopathy by SkQ1 was connected with an increase of VEGF mRNA and protein in OXYS rat's retina up to the levels corresponding to the Wistar rats, and did not involve changes in PEDF expression. In contrast the treatment with SkQ1 drops caused a decrease of VEGF mRNA and protein levels and an increase in the PEDF mRNA level in the middle-aged OXYS rats, but in Wistar rats the changes of gene expression were the opposite. CONCLUSIONS: The beneficial effects of SkQ1 on retinopathy connected with normalization of expression of VEGF and PEDF in the retina of OXYS rats and depended on age of the animals and the stage of retinopathy.

  4. A Long-Gap Peripheral Nerve Injury Therapy Using Human Skeletal Muscle-Derived Stem Cells (Sk-SCs): An Achievement of Significant Morphological, Numerical and Functional Recovery.

    Science.gov (United States)

    Tamaki, Tetsuro; Hirata, Maki; Nakajima, Nobuyuki; Saito, Kosuke; Hashimoto, Hiroyuki; Soeda, Shuichi; Uchiyama, Yoshiyasu; Watanabe, Masahiko

    2016-01-01

    Losses in vital functions of the somatic motor and sensory nervous system are induced by severe long-gap peripheral nerve transection injury. In such cases, autologous nerve grafts are the gold standard treatment, despite the unavoidable sacrifice of other healthy functions, whereas the prognosis is not always favorable. Here, we use human skeletal muscle-derived stem cells (Sk-SCs) to reconstitute the function after long nerve-gap injury. Muscles samples were obtained from the amputated legs from 9 patients following unforeseen accidents. The Sk-SCs were isolated using conditioned collagenase solution, and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN/29+) cells. Cells were separately cultured/expanded under optimal conditions for 2 weeks, then injected into the athymic nude mice sciatic nerve long-gap model (7-mm) bridging an acellular conduit. After 8-12 weeks, active cell engraftment was observed only in the Sk-34 cell transplanted group, showing preferential differentiation into Schwann cells and perineurial/endoneurial cells, as well as formation of the myelin sheath and perineurium/endoneurium surrounding regenerated axons, resulted in 87% of numerical recovery. Differentiation into vascular cell lineage (pericyte and endothelial cells) were also observed. A significant tetanic tension recovery (over 90%) of downstream muscles following electrical stimulation of the sciatic nerve (at upper portion of the gap) was also achieved. In contrast, Sk-DN/29+ cells were completely eliminated during the first 4 weeks, but relatively higher numerical (83% vs. 41% in axon) and functional (80% vs. 60% in tetanus) recovery than control were observed. Noteworthy, significant increase in the formation of vascular networks in the conduit during the early stage (first 2 weeks) of recovery was observed in both groups with the expression of key factors (mRNA and protein levels), suggesting the paracrine effects to angiogenesis. These results suggested that the human Sk

  5. Effects of magnetic c-erbB2 antisense probe on morphology and expression of SK-Br-3 cancer cell lines in vitro%磁性c-erbB2反义探针对SK-Br-3肿瘤细胞株形态及表达的影响

    Institute of Scientific and Technical Information of China (English)

    贺海容; 谭书德; 文明; 温志鹏; 刘海燕; 李少林

    2012-01-01

    目的:探讨磁性c-erbB2反义寡脱氧核苷酸探针对SK-Br-3肿瘤细胞株形态及表达的影响,阐明该探针是否同时具有诊断与治疗功能.方法:磁性c-erbB2反义探针转染高表达c-erbB2的SK Br 3肿瘤细胞作为实验组,磁性c-erbB2反义探针转染Fuda肿瘤细胞株、SPIO及ASODN转染SK-Br-3肿瘤细胞、未转染的SK-Br-3肿瘤细胞设置为4个对照组,普鲁士蓝染色光镜观察细胞内铁的分布,透射电镜观察其超微结构,并检测细胞cerbB2蛋白表达变化及铁含量,行体外MR成像.结果:光镜显示SK-Br-3肿瘤细胞胞浆内散在分布铁颗粒,透射电镜观察到SK-Br-3肿瘤细胞胞浆内铁颗粒、团状吞饮体,细胞出现胞膜空泡化、细胞固缩、核固缩及凋亡小体,而对照组细胞无上述改变;与对照组比较,实验组SK-Br3细胞蛋白的表达抑制率明显升高,细胞铁含量增加(P<0.01),MR扫描显示信号减低(P<0.05).结论:磁性c-erbB2反义探针能够顺利进入SK-Br-3肿瘤细胞,不仅能导致SK-Br-3细胞的凋亡,还能够被体外MR成像所检测,可能成为一种具有治疗与诊断意义的双功能探针.

  6. The activity of the nonsulfated sulfakinin Zopat-SK-1 in the neck-ligated larvae of the beetle Zophobas atratus.

    Science.gov (United States)

    Slocinska, M; Czubak, T; Marciniak, P; Jarmuszkiewicz, W; Rosinski, G

    2015-07-01

    Insect sulfakinins (SKs) are multifunctional neuropeptides structurally and functionally homologous to the mammalian gastrin/cholecystokinin (CCK). It has been proposed that SKs play a role in modulating energy management in insects by interacting with adipokinetic hormone (AKH), the principle hormone controlling insect intermediary metabolism. To exclude head factors (including AKH) that influence the activity of the nonsulfated sulfakinin Zopat-SK-1 in the larvae of the beetle Zophobas atratus, ligature and in vitro bioassays were used. Our study showed that in the neck-ligated larvae, Zopat-SK-1 evoked a much more pronounced glycogenolytic effect in fat body tissue and a significantly higher hypertrahelosemic effect in hemolymph than in larvae without ligation. We found that the concentration of the sugar trehalose increased under hormonal treatment but no changes in glucose levels were observed. Under in vitro conditions, the maximal glycogenolytic effect of Zopat-SK-1 in fat body was observed at 10 pmol of hormone. Ligature and in vitro bioassays indicated that Zopat-SK-1 activity in the Z. atratus larvae is modulated by head signals and/or factors from the gastrointestinal tract. Our data indicate the existence of a brain-gastrointestinal axis that has a role in controlling of energy (carbohydrate) metabolism in the insect body. Moreover, these results, together with immunological evidence of a cholecystokinin-like (sulfakinin) receptor in the Z. atratus fat body, help us to better understand the SK signaling pathways and its physiological role in insect biology. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Thrombin/Matrix Metalloproteinase-9-Dependent SK-N-SH Cell Migration is Mediated Through a PLC/PKC/MAPKs/NF-κB Cascade.

    Science.gov (United States)

    Yang, Chien-Chung; Lin, Chih-Chung; Chien, Peter Tzu-Yu; Hsiao, Li-Der; Yang, Chuen-Mao

    2016-11-01

    Thrombin has been known to activate inflammatory genes including matrix metalloproteinases (MMPs). The elevated expression of MMP-9 has been observed in patients with neuroinflammatory diseases and may contribute to the pathology of brain diseases. However, the mechanisms underlying thrombin-induced MMP-9 expression in SK-N-SH cells remain unknown. The effects of thrombin on MMP-9 expression were examined in SK-N-SH cells by gelatin zymography, Western blot, real-time PCR, promoter activity assay, and cell migration assay. The detailed mechanisms were analyzed by using pharmacological inhibitors and small intefering RNA (siRNA) transfection. Here, we demonstrated that thrombin induced the expression of proform MMP-9 and migration of SK-N-SH cells, which were attenuated by pretreatment with the inhibitor of thrombin (PPACK), Gq (GPA2A), PC-PLC (D609), PI-PLC (ET-18-OCH3), nonselective protien kinase C (PKC, GF109203X), PKCα/βII (Gö6983), PKCδ (Rottlerin), p38 mitogen-activated protein kinases (MAPK) (SB202190), JNK1/2 (SP600125), or NF-κB (Bay11-7082 or Helenalin) and transfection with siRNA of Gq, PKCα, PKCβ, PKCδ, p38, JNK1/2, IKKα, IKKβ, or p65. Moreover, thrombin-stimulated PKCα/βII, PKCδ, p38 MAPK, JNK1/2, or p65 phosphorylation was abrogated by their respective inhibitor of PPACK, GPA2A, D609, ET-18-OCH3, Gö6983, Rottlerin, SB202190, SP600125, Bay11-7082, or Helenalin. Pretreatment with these inhibitors or transfection with MMP-9 siRNA also blocked thrombin-induced SK-N-SH cell migration. Our results show that thrombin stimulates a Gq/PLC/PKCs/p38 MAPK and JNK1/2 cascade, which in turn triggers NF-κB activation and ultimately induces MMP-9 expression and cell migration in SK-N-SH cells.

  8. KLF5在 TNFα诱导的 SK-BR-3乳腺癌细胞凋亡中的作用%Roles of KLF5 in inhibition TNFα-induced SK-BR-3 breast cancer cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    史建红; 刘彩云; 张安易; 崔乃鹏; 王冰; 陈保平; 马振峰

    2014-01-01

    目的探讨肿瘤坏死因子α( TNFα)对 SK-BR-3乳腺癌细胞中 Krüppel 样因子5(KLF5)表达的影响,明确KLF5在TNFα诱导SK-BR-3乳腺癌细胞凋亡中的作用。方法用不同浓度TNFα(0、1、5、10、20μg/L)刺激SK-BR-3乳腺癌细胞不同时间(0、6、12、24、36 h),采用Western印迹方法检测KLF5表达水平;用实时定量PCR( qRT-PCR)检测TNFα刺激对SK-BR-3乳腺癌细胞凋亡基因表达的影响, qRT-PCR和流式细胞术观察过表达KLF5对SK-BR-3乳腺癌凋亡的影响。结果TNFα刺激SK-BR-3乳腺癌细胞后,随着刺激浓度的增高,KLF5表达水平呈剂量和时间依赖性逐渐降低。 qRT-PCR结果显示,TNFα可上调SK-BR-3乳腺癌细胞凋亡基因cascpase3、caspase9和bax表达,并下调bcl-2表达水平。构建pAd-GFP和pAd-GFP-KLF5腺病毒表达载体,在SK-BR-3乳腺癌细胞中过表达GFP或GFP-KLF5,再给予TNFα刺激,qRT-PCR和流式细胞术观察结果显示,过表达外源性KLF5可抑制TNFα诱导的SK-BR-3乳腺癌细胞凋亡。结论 TNFα可抑制SK-BR-3乳腺癌细胞中KLF5表达,KLF5参与了TNFα诱导的SK-BR-3乳腺癌细胞凋亡过程。%Objective To explore the expression levels and roles of Kr üpple-like factor 5 ( KLF5 ) in tumor necrosis factor α( TNFα)-induced SK-BR-3 breast cancer cells.Methods SK-BR-3 breast cancer cells were stimulated by TNFαat different concentrations (0, 1, 5, 10, 20 μg/L) for specified durations (0, 6, 12, 24, 36 h).Western blot was performed to detect KLF 5 protein levels.Then Western blot and quantitative real-time PCR ( qRT-PCR) were used to detect the expression levels of apoptosis genes.Flow cytometry and qRT-PCR were used to observe the effects of exogenous KLF 5 on TNFα-induced apoptosis of SK-BR-3 breast cancer cell.Results KLF5 expression levels significantly decreased in TNFα-stimulated SK-BR-3 breast cancer cells in a concentration-and time-dependent manner.Quantitative RT

  9. 苦参碱对人肾母细胞瘤SK-NEP-1细胞趋化因子受体4表达的影响%The effect of matrine on CXCR4 expression in SK-NEP-1 cells

    Institute of Scientific and Technical Information of China (English)

    毛玲; 薛天阳; 许伟

    2014-01-01

    Objectives To investigate the effects of matrine on the proliferation and apoptosis of SK-NEP-1 cells in vitro, and its possible mechanism. Methods Trials were divided into following groups:control group, 0.5, 1.0 and 1.5mg/ml of ma-trine intervention groups. The inhibition rate of SK-NEP-1 cells treated with different concentration of Matrine was detected by MTT colorimetric assay. Apoptosis rate was detected by flow cytometry (FCM). RT-PCR analysis was employed to measure the PDCD4 mRNA expression. Results Matrine (final concentrations=0.5, 1.0 and 1.5mg/ml) could induce apoptosis and inhibit the growth of SK-NEP-1 cells. Compared with the controls without matrine treatment (8.81±3.71)%, the inhibition rates of SK-NEP-1 cells were (20.79 ± 6.20)%, (31.25 ± 5.07)%, and (51.15 ± 12.70)%, respectively;the apoptotic rates of SK-NEP-1 cells treated with different concentration of matrine were (13.67±0.78)%,(17.43±1.65)%and (20.80±1.54)%, respectively. Significant difference in the inhibition and apoptotic rates of SK-NEP-1 cells between each drug group and control group was observed(P<0.05), and the inhibition and apoptotic rates of SK-NEP-1 cells increased gradually with increased matrine concentration, thus exhibiting a dose-dependent effect(P<0.05). To the expression of CXCR4 mRNA,the grey levels of SK-NEP-1 cells treated with matrine intervention group (final concentrations=0.5, 1.0 and 1.5 mg/ml) were (0.720 ± 0.058), (0.540 ± 0.095) and (0.307 ± 0.050), respectively. The mRNA expression of CXCR4 was seen in SK-NEP-1 cells. Compared with control group, the expres-sion of CXCR4 mRNA was decreased significantly in matrine intervention group (P<0.01).There were significant difference in CXCR4 mRNA level among the SK-NEP-1 cells treated with 0.5,1.0,1.5mg/mL of matrine (P<0.01). Conclusions Matrine could induce apoptosis and inhibit the growth of SK-NEP-1 cells in a dose-dependent way which may be associated with the down-regulated CXCR4 expression in SK

  10. Inhibition of beta-site amyloid precursor protein-cleaving enzyme and beta-amyloid precursor protein genes in SK-N-SH cells

    Institute of Scientific and Technical Information of China (English)

    Suqin Gao; Lin Sun; Enji Han; Hongshun Qi; Jinbo Feng; Shunliang Xu; Wen Xia

    2009-01-01

    BACKGROUND:Previous studies have demonstrated that Piper futokadsura stem selectively inhibits expression of amyloid precursor protein (APP) at the mRNA level.In addition,the piperlonguminine (A) and dihydropiperlonguminine (B) components (1:0.8),which can be separated from Futokadsura stem,selectively inhibit expression of the APP at mRNA and protein levels.OBJECTIVE:Based on previous findings,the present study investigated the effects of β-site amyloid precursor protein cleaving enzyme (BACE1) and APP genes on the production of β-amyloid peptide 42 (Aβ42) in human neuroblastoma cells (SK-N-SH cells) using small interfering RNAs (siRNAs) and A/B components separated from Futokadsura stem,respectively.DESIGN,TIME AND SETTING:A gene interference-based randomized,controlled,in vitro experiment was performed at the Key Laboratory of Cardiovascular Remodeling and Function Research,Ministries of Education and Public Health,and Institute of Pharmacologic Research,School of Pharmaceutical Science & Department of Biochemistry,School of Medicine,Shandong University between July 2006 and December 2007.MATERIALS:SK-N-SH cells were provided by Shanghai Institutes of Biological Sciences,Chinese Academy of Sciences,Shanghai,China;mouse anti-human BACE1 monoclonal antibody was purchased from R&D Systems,USA;mouse anti-human APP monoclonal antibody was purchased from Cell Signaling Technology,USA;and horseradish peroxidase (HRP)-conjugated goat anti-mouse IgG was provided by Sigma,USA.METHODS:The human BACE1 cDNA sequence was obtained from NCBI website (www.ncbi.nlm.nih.gov/sites/entrez).Three pairs of siRNAs,specific to human BACE1 gene,were synthesized through the use of Silencer? pre-designed siRNA specification,and were transfected into SK-N-SH cells with siPORT NeoFX transfection agent to compare the effects of different concentrations of siRNAs (10-50 nmol/L) on SK-N-SH cells.Futokadsura stem was separated and purified with chemical methods,and the crystal was composed of

  11. 噬菌体肽库筛选与SK-BR-3细胞表面HER2特异性结合的活性短肽%Screening Short Active Peptide Combinded with HER2 on SK-BR-3 by Phage Display Peptide Library

    Institute of Scientific and Technical Information of China (English)

    汪静; 高晓娟; 吴秀丽

    2015-01-01

    目的 利用噬菌体展示肽库技术筛选与人乳腺癌细胞表面HER2特异性结合的活性短肽.方法 以过表达HER2的人乳腺癌细胞SK-BR-3为靶细胞,Herceptin(R)作为竞争性洗脱剂,采用竞争结合实验,经四轮亲和筛选,获得阳性噬菌体富集;通过ELISA评价与SK-BR-3细胞高特异性结合的阳性噬菌体克隆;分析DNA测序结果并推导短肽序列;采用MTT法比较筛选短肽与Herceptin(R)对SK-BR-3细胞生长的抑制率.结果 随机挑选的16个克隆对SK-BR-3细胞具有特异性结合力,其中S-1阳性克隆与靶细胞特异结合活性最强,且其短肽序列对SK-BR-3细胞生长具有一定的抑制作用.结论 通过噬菌体展示肽库对过表达HER2乳腺癌细胞进行筛选,获得与SK-BR-3细胞高特异性结合的活性短肽序列,为设计乳腺癌靶向药物与导向治疗提供参考数据.

  12. Definitive Endoderm Formation from Plucked Human Hair-Derived Induced Pluripotent Stem Cells and SK Channel Regulation

    Directory of Open Access Journals (Sweden)

    Anett Illing

    2013-01-01

    Full Text Available Pluripotent stem cells present an extraordinary powerful tool to investigate embryonic development in humans. Essentially, they provide a unique platform for dissecting the distinct mechanisms underlying pluripotency and subsequent lineage commitment. Modest information currently exists about the expression and the role of ion channels during human embryogenesis, organ development, and cell fate determination. Of note, small and intermediate conductance, calcium-activated potassium channels have been reported to modify stem cell behaviour and differentiation. These channels are broadly expressed throughout human tissues and are involved in various cellular processes, such as the after-hyperpolarization in excitable cells, and also in differentiation processes. To this end, human induced pluripotent stem cells (hiPSCs generated from plucked human hair keratinocytes have been exploited in vitro to recapitulate endoderm formation and, concomitantly, used to map the expression of the SK channel (SKCa subtypes over time. Thus, we report the successful generation of definitive endoderm from hiPSCs of ectodermal origin using a highly reproducible and robust differentiation system. Furthermore, we provide the first evidence that SKCas subtypes are dynamically regulated in the transition from a pluripotent stem cell to a more lineage restricted, endodermal progeny.

  13. Sprawozdanie z polityki rachunkowości jako odrębny składnik sprawozdania finansowego

    Directory of Open Access Journals (Sweden)

    Ewa Walińska

    2016-07-01

    Full Text Available Niniejszy artykuł poświęcono rozważaniom na temat polityki rachunkowości z perspektywy użytkownika sprawozdania finansowego. Jego celem jest prezentacja nowej formuły ujawnień informacji dotyczącej polityki rachunkowości, która zdaniem autorki podnosiłaby rangę i znaczenie tego elementu systemu rachunkowości. W artykule przedstawiono istotę i miejsce polityki rachunkowości w sprawozdaniu finansowym w świetle obowiązującego prawa bilansowego i praktyki największych spółek publicznych notowanych na Giełdzie Papierów Wartościowych w Warszawie. Podsumowaniem rozważań jest propo- zycja ujawniania polityki rachunkowości jako odrębnego składnika sprawozdania finansowego – spra- wozdania z polityki rachunkowości.

  14. From laboratory to pilot plant: the solid-state process development of a highly potent cathepsin S/K inhibitor.

    Science.gov (United States)

    Feth, Martin Philipp; Heyse, Winfried; Baumgartner, Bruno; Nagel, Norbert; Tappertzhofen, Christoph; Olpp, Thomas; Jurascheck, Jörg; Ulrich, Joachim; Helmdach, Lydia; Petzoldt, Christine

    2013-04-01

    The solid-state development for the low dose drug molecule SAR114137, a selective and reversible inhibitor of cysteine cathepsin S/K, is reported. Six polymorphic forms as well as various solvate phases were discovered by an extensive polymorphism screening. The solid phase characterizations revealed that phase 1, from which a single crystal structure could be obtained, is the thermodynamically most stable form and therefore it was chosen for pharmaceutical development. The successful scale-up from development laboratory into pilot plant for the crystallization and drying processes is presented. Testing of different drying techniques, like agitated drying in conical or filter dryers as well as spray drying, proved them to be very promising alternatives to the conventional tray drying process and might be used during the industrialization phase of the project. The use of online analytical tools (e.g., Raman spectroscopy) for a better process understanding and as tools for process optimization is shown. Furthermore, wet milling by ultrasound was performed on laboratory scale and discussed as potential option to reach the desired particle size distribution necessary for a good content uniformity of the API in an oral formulation.

  15. Emissions from the copper-nickel industry on the Kola Peninsula and at Noril'sk, Russia

    Science.gov (United States)

    Boyd, Ron; Barnes, S.-J.; De Caritat, P.; Chekushin, V.A.; Melezhik, V.A.; Reimann, C.; Zientek, M.L.

    2009-01-01

    Published estimates for base metal emissions from the copper-nickel industry on the Kola Peninsula are re-examined in the light of (a) chemical data on the composition of the ores; (b) official emission figures for 1994; and (c) modelled emissions based on dry and wet deposition estimates derived from data for snow and rain samples collected in 1994. The modelled emissions, official emission figures and chemical data are mutually compatible for Ni, Cu and Co and show that previously published figures underestimated the emissions of the major elements, Ni and Cu (though within the same order of magnitude) and overestimated the emissions of As, Pb, Sb and Zn by up to several orders of magnitude, in some cases exceeding the calculated total input to the plants. Published estimates have neglected information on the nature and chemistry of the ores processed in metallurgical industries in the Noril'sk area of Siberia and the Urals. Revised emission estimates for 1994, using knowledge of the chemistry of the ores, are proposed: taken with published information on total emissions up to 2000 these data give an indication of emission levels in more recent years. ?? 2008 Elsevier Ltd. All rights reserved.

  16. Spectroscopic and Gas Chromatographic Studies of Pigments and Binders in Gdańsk Paintings of the 17th Century

    Directory of Open Access Journals (Sweden)

    Justyna Olszewska-Świetlik

    2013-01-01

    Full Text Available This work presents spectroscopic (optical microscopy, OM; micro-Raman, Raman; and Fourier-transform adsorption infrared, FT-IR and gas chromatographic studies of two famous panel paintings from the Gdańsk artists of the 17th century Golden Age, “Servilius Appius” by Isaac van den Blocke and “Allegory of Wealth” probably by Anton Möller. Application of the aforementioned methods allowed us to identify pigments and binders used in the panel paintings. In particular, it was determined that the yellow pigment used by both artists is lead-tin yellow type I (2PbO·SnO2, the white pigment is lead (II carbonate hydroxide (2PbCO3·Pb(OH2, and the ground layer material consist of chalk (CaCO3. The analysis showed also that in the case of “Allegory of Wealth,” the red layer consists not only of cinnabar (HgS but also of lead-tin yellow type I.

  17. Contamination of Runoff Water at Gdańsk Airport (Poland by Polycyclic Aromatic Hydrocarbons (PAHs and Polychlorinated Biphenyls (PCBs

    Directory of Open Access Journals (Sweden)

    Jacek Namieśnik

    2011-12-01

    Full Text Available Airport runoff can contain high concentrations of various pollutants, in particular polycyclic aromatic hydrocarbons (PAHs and polychlorinated biphenyls (PCBs, the environmental levels of which have to be monitored. Airport runoff water samples, collected at the Gdańsk-Rębiechowo Airport from 2008 to 2009, were analysed for PAHs and PCBs by gas chromatography. The aromatic fractions were separated by liquid-liquid extraction and analysed by GC/MS. Total PAH concentrations were 295–6,758 ng/L in 2008 and 180–1,924 ng/L in 2009, while total PCB levels in 2008 ranged from 0.14 to 0.44 µg/L and in 2009 from 0.06 to 0.23 µg/L. The PAH and PCB compositions in airport runoff waters were examined over a range of spatial and temporal scales to determine distributions, trends and possible sources. This pollution is mainly pyrolytic and related to anthropogenic activity. There were significant differences between the samples collected in the two seasons. An understanding of the magnitude of contamination due to airport runoff water is important for the effective management of airport infrastructure.

  18. Immobilization of α-Amylase from Anoxybacillus sp. SK3-4 on ReliZyme and Immobead Supports

    Directory of Open Access Journals (Sweden)

    Ummirul Mukminin Kahar

    2016-09-01

    Full Text Available α-Amylase from Anoxybacillus sp. SK3-4 (ASKA is a thermostable enzyme that produces a high level of maltose from starches. A truncated ASKA (TASKA variant with improved expression and purification efficiency was characterized in an earlier study. In this work, TASKA was purified and immobilized through covalent attachment on three epoxide (ReliZyme EP403/M, Immobead IB-150P, and Immobead IB-150A and an amino-epoxide (ReliZyme HFA403/M activated supports. Several parameters affecting immobilization were analyzed, including the pH, temperature, and quantity (mg of enzyme added per gram of support. The influence of the carrier surface properties, pore sizes, and lengths of spacer arms (functional groups on biocatalyst performances were studied. Free and immobilized TASKAs were stable at pH 6.0–9.0 and active at pH 8.0. The enzyme showed optimal activity and considerable stability at 60 °C. Immobilized TASKA retained 50% of its initial activity after 5–12 cycles of reuse. Upon degradation of starches and amylose, only immobilized TASKA on ReliZyme HFA403/M has comparable hydrolytic ability with the free enzyme. To the best of our knowledge, this is the first report of an immobilization study of an α-amylase from Anoxybacillus spp. and the first report of α-amylase immobilization using ReliZyme and Immobeads as supports.

  19. Reproduktorová skříň pro laboratorní měření impedance reproduktoru

    OpenAIRE

    Nevole, Tomáš

    2009-01-01

    V této práci je řešena problematika návrhu a konstrukce univerzální modulární reproduktorové skříně- ozvučnice, která by měla sloužit pro laboratorní měření impedance širokopásmového elektromagnetického reproduktoru. Toto měření má prokázat, jak se mění elektrické parametry reproduktoru vlivem změny vlastností akustického prostředí, do nějž vyzařuje. V první části je nejprve vysvětlena potřebná teorie ke zvládnutí problému, jako způsob šíření zvukového vlnění látkovým prostředím, vlastnosti a...

  20. Neuroprotective effects of KR-62980, a new PPARγ agonist, against chemical ischemia-reperfusion in SK-N-SH cells.

    Science.gov (United States)

    Kim, Ki Young; Cho, Hyun Sill; Lee, Su Hee; Ahn, Jin Hee; Cheon, Hyae Gyeong

    2011-02-01

    PPARγ agonists exert neuroprotective effects against various types of brain injuries. In the present study, we investigated the effects of KR-62980, a new PPARγ agonist, and rosiglitazone on the neuronal cell death induced by chemical ischemia-reperfusion in SK-N-SH cells and their underlying molecular mechanisms. Both agonists inhibited chemical ischemia-reperfusion-induced cell death, and the effects were associated with anti-apoptotic action. KR-62980 and rosiglitazone suppressed NO and ROS formation, and N-acetyl-N-acetoxy-4-chlorobenzenesulfonamide, an NO generator, reversed the protective effects of the agonists on cell viability. In the agonist-induced anti-apoptotic process, PTEN expression was suppressed in parallel with increased Akt and ERK phosphorylation, whereas PD98059 (an ERK inhibitor) or wortmannin (a PI-3K inhibitor) abolished the cell survival by KR-62980 and rosiglitazone. All of the effects of KR-62980 and rosiglitazone appeared to be PPARγ-dependent because the effects were reversed by bisphenol A diglycidyl ether, a PPARγ antagonist, or by PPARγ knockdown. Our results demonstrate that two PPARγ agonists, KR-62980 and rosiglitazone, inhibited chemical ischemia-reperfusion-induced neuronal cell death by PPARγ-mediated anti-apoptotic and anti-oxidant mechanisms related to PTEN suppression and ERK phosphorylation.

  1. A synergistic antiproliferation effect of curcumin and docosahexaenoic acid in SK-BR-3 breast cancer cells: unique signaling not explained by the effects of either compound alone

    Directory of Open Access Journals (Sweden)

    Jo Davisson V

    2011-04-01

    Full Text Available Abstract Background Breast cancer is a collection of diseases in which molecular phenotypes can act as both indicators and mediators of therapeutic strategy. Therefore, candidate therapeutics must be assessed in the context of multiple cell lines with known molecular phenotypes. Docosahexaenoic acid (DHA and curcumin (CCM are dietary compounds known to antagonize breast cancer cell proliferation. We report that these compounds in combination exert a variable antiproliferative effect across multiple breast cell lines, which is synergistic in SK-BR-3 cells and triggers cell signaling events not predicted by the activity of either compound alone. Methods Dose response curves for CCM and DHA were generated for five breast cell lines. Effects of the DHA+ CCM combination on cell proliferation were evaluated using varying concentrations, at a fixed ratio, of CCM and DHA based on their individual ED50. Detection of synergy was performed using nonlinear regression of a sigmoid dose response model and Combination Index approaches. Cell molecular network responses were investigated through whole genome microarray analysis of transcript level changes. Gene expression results were validated by RT-PCR, and western blot analysis was performed for potential signaling mediators. Cellular curcumin uptake, with and without DHA, was analyzed via flow cytometry and HPLC. Results CCM+DHA had an antiproliferative effect in SK-BR-3, MDA-MB-231, MDA-MB-361, MCF7 and MCF10AT cells. The effect was synergistic for SK-BR-3 (ER- PR- Her2+ relative to the two compounds individually. A whole genome microarray approach was used to investigate changes in gene expression for the synergistic effects of CCM+DHA in SK-BR-3 cells lines. CCM+DHA triggered transcript-level responses, in disease-relevant functional categories, that were largely non-overlapping with changes caused by CCM or DHA individually. Genes involved in cell cycle arrest, apoptosis, inhibition of metastasis, and

  2. Study on geometric approach of SVM algorithm SK algorithm analysis and study%SVM的几何方法——SK类思路的研究

    Institute of Scientific and Technical Information of China (English)

    常振华; 陈伯成; 李英杰; 刘文煌; 闫学为

    2011-01-01

    The geometric approach of the Support Vector Machine(SVM) is a kind of geometric way to find the solution to the problem of the SVM algorithm. Based on its geometric characters,the SK(Schlesinger-Kozinec) algorithm is studied intuitively. It briefly sums up the two convex hulls,based on their relative positions, into five categories,and makes sure their optimizing position got in each computing is mostly at the hull vertices or boundary,it can get to the boundary(the optimization place of the computing) at the first computation.The manual single-step simulation results show that the projection is not always successful for such kind of algorithms in many cases,though it can't affect the computing result,but can weaken the algorithm efficiency. Based on the analysis,it demonstrates two improving ways for the soft SK algorithm(Backward-SK and Forward-SK methods),and makes some simulation for comparing. The simulation results show that the improved method computing results are almost same as the SK and soft SK ones,but the computing process of improved one is more intuitive.%支持向量机(Support Vector Machine,SVM)的几何方法是一种基于SVM计算过程中几何意义出发的求解方法.利用其几何特点,比较直观地对其基本算法的构建过程进行了分析.两凸包相对位置可以简要地归纳成5类,且在该类算法迭代过程最优点多在顶点和边界上,该类算法在第一次迭代就可能达到边界(最优点);该类算法的手动单步模拟计结果揭示:很多情况下,该类算法迭代过程的投影并不成功,虽不影响解法的最终结果,但会影响迭代效率:基于几何的分析,给出软SK软算法的两种改进思路(Backward-SK和Forward-SK思路),并进行了仿真比较计算.实验表明,该方法计算效果与原思路相似,但是计算过程理解更加直观.

  3. Connection of Magnetic Antisense Probe with SK-Br-3 Oncocyte mRNA Nucleotide Detected by High Resolution Atomic Force Microscope%高精度原子力显微镜显示磁性反义探针与SK-Br-3肿瘤细胞mRNA核苷酸连接

    Institute of Scientific and Technical Information of China (English)

    谭书德; 欧阳羽; 李信友; 文明; 李少林

    2011-01-01

    为了将高精度原子力显微镜(AFM)用于显示超顺磁性氧化铁标记的c-erbB2癌基因反义寡脱氧核苷酸探针(磁性反义探针)与SK-Br-3肿瘤细胞mRNA核苷酸的连接,我们在磁性反义探针转染SK-Br-3肿瘤细胞基础上,用AFM对转染后的肿瘤细胞进行观察,并同时对转染后的肿瘤细胞进行蛋白表达检测及MRI成像,以进一步证实AFM的观察结果.从AFM显示的磁性反义探针转染SK-Br-3肿瘤细胞后单个细胞的全貌图及局部放大图发现,探针中反义寡脱氧核苷酸中的脱氧胞嘧啶核苷酸闭环与肿瘤细胞mRNA嘌呤核苷酸环相连接;此外,磁性反义探针能特异性抑制SK-Br3细胞c-erbB2的蛋白表达,MRI显示磁性反义探针转染SK-Br-3肿瘤细胞的信号强度最低(P<0.05).实验表明,AFM可以清楚显示磁性反义探针与SK-Br-3肿瘤细胞核mRNA核苷酸的连接.%The present paper is aimed to detect superparamagnetic iron oxide labeled c-erbB2 oncogene antisense oli-gonucleotide probe (magnetic antisense probe) connected with SK-Br-3 oncocyte mRNA nucleotide by high resolution atomic force microscope (AFM). We transfected SK-Br-3 oncocyte with magnetic antisense probe, then observed the cells by AFM with high resolution and detected protein expression and magnetic resonance imagine ( MRI). The high resolution AFM clearly showed the connection of the oligonucleotide remote end of magnetic antisense probe with the mRNA nucleotide of oncocyte. The expression of c-erbB2 protein in SK-Br3 cells were highly inhibited by using magnetic antisense probe. We then obtained the lowest signal to noise ratio (SNR) of SK-Br-3 oncocyte transfected with magnetic antisense probe by MRI (P<0. 05). These experiments demonstrated that the high resolution AFM could be used to show the binding of magnetic antisense probe and SK-Br-3 mRNA of tumor cell nuclear.

  4. Antiarrhythmic effect of the Ca(2+)-activated K(+) (SK) channel inhibitor ICA combined with either amiodarone or dofetilide in an isolated heart model of atrial fibrillation

    DEFF Research Database (Denmark)

    Kirchhoff, Jeppe Egedal; Diness, Jonas Goldin; Abildgaard, Lea;

    2016-01-01

    whether a combination of the SK channel blocker N-(pyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (ICA) together with either dofetilide or amiodarone provided a synergistic effect. The duration of AF was reduced with otherwise subefficacious concentrations of either dofetilide or amiodarone when combined......Dose is an important parameter in terms of both efficacy and adverse effects in pharmacological treatment of atrial fibrillation (AF). Both of the class III antiarrhythmics dofetilide and amiodarone have documented anti-AF effects. While dofetilide has dose-related ventricular side effects......, amiodarone primarily has adverse non-cardiac effects. Pharmacological inhibition of small conductance Ca(2+)-activated K(+) (SK) channels has recently been reported to be antiarrhythmic in a number of animal AF models. In a Langendorff model of acutely induced AF on guinea pig hearts, it was investigated...

  5. Pharmacologic inhibition of small-conductance calcium-activated potassium (SK) channels by NS8593 reveals atrial antiarrhythmic potential in horses

    DEFF Research Database (Denmark)

    Haugaard, Maria Mathilde; Hesselkilde, Eva Zander; Pehrson, Steen Michael

    2015-01-01

    . The electrophysiologic and anti-AF effects of the relative selective SK channel inhibitor NS8593 (5 mg/kg IV) were evaluated in anesthetized horses, focusing on the potential of NS8593 to terminate acute pacing-induced AF, drug-induced changes in atrial effective refractory period, AF duration and vulnerability....... NS8593 terminated all induced AF episodes (duration ≥15 minutes), caused pronounced prolongation of atrial effective refractory period, and reduced AF duration and vulnerability. QRS duration and QTc interval were not affected by treatment. CONCLUSION: SK channels are widely distributed in atrial...... and ventricular cardiomyocytes and contribute to atrial repolarization. Inhibition by NS8593 terminates pacing-induced AF of short duration and decreases AF duration and vulnerability without affecting ventricular conduction and repolarization. Thus, inhibition by NS8593 demonstrates clear atrial antiarrhythmic...

  6. The Skælskør structure in eastern Denmark – wrench-related anticline or primary Late Cretaceous sea-floor topography?

    DEFF Research Database (Denmark)

    Surlyk, Finn; Boldreel, Lars Ole; Lykke-Andersen, Holger;

    2010-01-01

    Sorgenfrei (1951) identified a number of NW–SE oriented highs in the Upper Cretaceous – Danian Chalk Group in eastern Denmark, including the Skælskør structure and interpreted them as anticlinal folds formed by wrenching along what today is known as the Ringkøbing-Fyn High. Recent reflection...... seismic studies of the Chalk Group in Øresund and Kattegat have shown that similar highs actually represent topographic highs on the Late Cretaceous – Danian seafloor formed by strong contourparallel bottom currents. Reflection seismic data collected over the Skælskør structure in order to test...... the hypothesis of Sorgenfrei show that the Base Chalk reflection is relatively flat with only very minor changes in inclination and cut by only a few minor faults. The structure is situated along the northern margin of a high with roots in a narrow basement block, projecting towards the northwest from...

  7. Współistnienie linijnej IgA dermatozy pęcherzowej z atopowym zapaleniem skóry. Trudności diagnostyczne. Opis przypadku

    Directory of Open Access Journals (Sweden)

    Marcin Zakrzewski

    2011-12-01

    Full Text Available Wprowadzenie: Linijna IgA dermatoza pęcherzowa (ang. linear IgAbullous dermatosis – LABD jest przewlekłą autoimmunologiczną chorobąpęcherzową skóry, która niezwykle rzadko współistnieje z innymischorzeniami. Cel pracy: Przedstawienie wyjątkowo rzadkiego współistnienia LABDz atopowym zapaleniem skóry (AZS. Opis przypadku: Kobieta, lat 28, zgłosiła się do poradni dermatologicznejz powodu rozsianych na skórze całego ciała, układających sięobrączkowato zmian pęcherzowych na rumieniowym podłożu oraznadżerek w obrębie błon śluzowych jamy ustnej. Poza tym na skórzetwarzy, nadgarstków oraz w zgięciach łokciowych stwierdzano zmianytypowe dla AZS. Pacjentka od wczesnego dzieciństwa choruje naAZS, idiopatyczną nadpłytkowość oraz obecnie na bezobjawowewrzodziejące zapalenie jelita grubego. U matki kobiety rozpoznanostwardnienie rozsiane. W badaniu immunofluorescencyjnym bezpośrednimwycinka skóry wykazano obecność linijnych złogów IgA nagranicy skórno-naskórkowej, za pomocą badania immunofluorescencyjnegopośredniego nie stwierdzono obecności przeciwciał reagującychz błoną podstawną, a metodą ELISA przeciwciał anty-NC16A. Napodstawie obrazu klinicznego oraz wykonanych badań rozpoznanoLABD, co dodatkowo potwierdzono badaniem wycinka skóry metodąmikroskopii konfokalnej. Ze względu na nadpłytkowość pacjentkabyła konsultowana hematologicznie i miała wykonaną biopsję szpiku.Rozpoznano u niej nadpłytkowość idiopatyczną. Pomimo zaburzeńhematologicznych podjęto leczenie prednizonem w dawkach zmniejszającychsię (od 40 mg/dobę oraz enoksaparyną. Podczas terapiiobserwowano systematyczną poprawę kliniczną, pęcherze wchłonęłysię, pozostawiając pozapalne przebarwienia. Przy redukcji dawki prednizonuobserwowano stopniowe pogarszanie się zmian skórnych typowychdla AZS, zwłaszcza w obrębie twarzy i kończyn górnych. Z tegowzględu włączono leczenie cyklosporyną A. Wnioski

  8. Epibionts and parasites on crustaceans (Copepoda, Cladocera, Cirripedia larvae inhabiting the Gulf of Gdańsk (Baltic Sea in very large numbers

    Directory of Open Access Journals (Sweden)

    Luiza Bielecka

    2014-06-01

    Full Text Available The occurrence of epizoic filter-feeding Protozoa (Vorticella and Zoothamnium and parasitic Protozoa (Ellobiopsis on Calanoida was noticed in the Gulf of Gdańsk in 1998, 1999 and 2006. The relatively high (4-16% of all calanoids level of infestation varied depending on the type of infestation (0.1-13% of the population of particular taxa. The dominant copepods – Acartia spp., Temora longicornis and Centropages hamatus - were attacked the most frequently (from 10.5% to 54% of all infested calanoids. Epibiosis and parasitism were observed on all copepod developmental stages (adults, juveniles and nauplii. Epibionts and parasites were located on different parts of the body, but mainly on the prosome. Infestation by epibionts and parasites was not restricted to calanoid copepods: it was also detected in non-negligible numbers on other crustaceans, namely, Harpacticoida, Cladocera (Bosmina sp. and Cirripedia larvae (nauplii in the Gulf of Gdańsk.

  9. En dag med vin och historia : Utveckling av en ny produkt för Finlands Skärgårdsbokning

    OpenAIRE

    Salminen, Helen

    2013-01-01

    Dagens resenärer är allt mera intresserade av lokal producerad vin och mat. Under 1990-talet växte enoturismen fram som en nisch och efter alkohollagförändringen 1995 kunde enoturismen också slå rot i Finland. Idag finns det 25 vingårdar runtom i Finland, majoriteten av dessa ligger i södra Finland. Syftet med detta examensarbete är att genom tjänsteutveckling skapa en ny produkt för Finlands Skärgårdsbokning där jag sammanbinder Åbolands Skärgård och enoturismen. För att kunna utveckla denna...

  10. Measuring the CP asymmetry in the decay $D^0 \\rightarrow K^0_SK^0_S$ using Run II data at LHCb.

    CERN Document Server

    Fischer, Kamil Leszek

    2017-01-01

    A sensitivity study for the measurement of $CP$ asymmetry in the decay $D^0 \\rightarrow K^0_{S}K^0_{S}$ has been performed using $pp$ collision data collected by the LHCb experiment during Run II at center-of-mass energy $\\sqrt{s} =13 \\ TeV$. The results indicate that an improvement of a factor of at least three in efficiency is necessary to achieve a world's best precision on $\\mathcal{A}_{CP}$. A proposed set of changes to the trigger selection for this channel is presented. If implemented these changes would increase the signal yield per unit of integrated luminosity by a factor of six, and therefore place LHCb in the position to perform the world's most precise measurement of $\\mathcal{A}_{CP}$($D^0 \\rightarrow K^0_{S}K^0_{S}$).

  11. Synergistic antiarrhythmic effect of combining inhibition of Ca(2+)-activated K(+) (SK) channels and voltage-gated Na(+) channels in an isolated heart model of atrial fibrillation

    DEFF Research Database (Denmark)

    Kirchhoff, Jeppe Egedal; Goldin Diness, Jonas; Sheykhzade, Majid

    2015-01-01

    be subefficacious as monotherapy, may prevent atrial fibrillation (AF) and have reduced proarrhythmic potential in the ventricles. METHODS: Subefficacious concentrations of ranolazine, flecainide, and lidocaine were tested alone or in combination with the SK channel blocker N-(pyridin-2-yl)-4-(pyridin-2-yl...... of the adverse effect profile could be an additional advantage if compound concentrations could be reduced. OBJECTIVE: The purpose of this study was to test the hypothesis that combined inhibition of Ca(2+)-activated K(+) channels (SK channels) and voltage-gated Na(+) channels, in concentrations that would......)thiazol-2-amine (ICA) in a Langendorff-perfused guinea pig heart model in which AF was induced after acetylcholine application and burst pacing. RESULTS: AF duration was reduced when both flecainide and ranolazine were combined with ICA in doses that did not reduce AF as monotherapy. At higher...

  12. Antiarrhythmic effect of the Ca(2+)-activated K(+) (SK) channel inhibitor ICA combined with either amiodarone or dofetilide in an isolated heart model of atrial fibrillation

    DEFF Research Database (Denmark)

    Kirchhoff, Jeppe Egedal; Diness, Jonas Goldin; Abildgaard, Lea;

    2016-01-01

    Dose is an important parameter in terms of both efficacy and adverse effects in pharmacological treatment of atrial fibrillation (AF). Both of the class III antiarrhythmics dofetilide and amiodarone have documented anti-AF effects. While dofetilide has dose-related ventricular side effects...... that combination of subefficacious concentrations of an SK channel blocker and either dofetilide or amiodarone can maintain anti-AF properties, while the risk of ventricular arrhythmias is reduced....

  13. [Oxidative stress and autophagy in SK-N-SH cells induced by manganese chloride or 1-methyl-4-phenylpyridinium: a comparative analysis].

    Science.gov (United States)

    Liu, W L; Dou, C S; Wang, Y; Zhao, P; Fu, J L; Yao, B Y; Zhou, Z C

    2017-02-20

    Objective: To investigate the effect of manganese chloride (MnCl(2)) or 1-methyl-4-phenylpyridinium (MPP (+)) on oxidative stress and autophagy in human neuroblastomaSK-N-SH cells and the mechanism of the neurotoxicity of manganese. Methods: SK-N-SH cells were treated with MnCl(2) or MPP(+) at doses of 0.062 5, 0.125, 0.25, 0.5, 1.0, and 2.0 mmol/L for 24 hours, and MTT assay was used to measure cell viability. The cells weretreated with MnCl(2) or MPP(+) at doses of 0.125, 0.25, and 0.5 mmol/L for 24 hours, and flow cytometry was used to measure the content of reactive oxygen species (ROS) in cells, a laser scanning confocal microscope was used to observe autophagosome in cells, and Western blot was used to measure the expression of autophagy-related proteins P62 and LC3-II/LC3-I. Results: Compared with the control group, the 0.0625-2.0 mmol/L MnCl(2) and 0.125-2.0 mmol/L MPP (+) treatment groups had significant reductions in the viability of SK-N-SH cells, and the 0.25-2.0 mmol/L MnCl(2) treatment groups had significantly lower viability than the groups treated with the same doses of MPP(+) (all PN-SH cells, and MPP(+) has a significantly greater inductive effect on autophagy of SK-N-SH cells than MnCl(2).

  14. Bromodomain and extra-terminal (BET) bromodomain inhibition activate transcription via transient release of positive transcription elongation factor b (P-TEFb) from 7SK small nuclear ribonucleoprotein.

    Science.gov (United States)

    Bartholomeeusen, Koen; Xiang, Yanhui; Fujinaga, Koh; Peterlin, B Matija

    2012-10-19

    By phosphorylating elongation factors and the C-terminal domain of RNA polymerase II, the positive transcription elongation factor b (P-TEFb) is the critical kinase for transcription elongation and co-transcriptional processing of eukaryotic genes. It exists in inactive small nuclear ribonucleoprotein (7SK snRNP) and active (free P-TEFb) complexes in cells. The P-TEFb equilibrium determines the state of cellular activation, proliferation, and differentiation. Free P-TEFb, which is required for growth, can be recruited to RNA polymerase II via transcription factors, BRD4, or the super elongation complex (SEC). UV light, various signaling cascades, transcriptional blockade, or compounds such as hexamethylene bisacetamide (HMBA), suberoylanilide hydroxamic acid (SAHA), and other histone deacetylase inhibitors lead to a rapid release of free P-TEFb, followed by its reassembly into the 7SK snRNP. As a consequence, transcription of HEXIM1, a critical 7SK snRNP subunit, and HIV is induced. In this study, we found that a bromodomain and extra-terminal (BET) bromodomain inhibitor, JQ1, which inhibits BRD4 by blocking its association with chromatin, also leads to the rapid release of free P-TEFb from the 7SK snRNP. Indeed, JQ1 transiently increased levels of free P-TEFb and BRD4·P-TEFb and SEC·P-TEFb complexes in cells. As a consequence, the levels of HEXIM1 and HIV proteins rose. Importantly, the knockdown of ELL2, a subunit of the SEC, blocked the ability of JQ1 to increase HIV transcription. Finally, the effects of JQ1 and HMBA or SAHA on the P-TEFb equilibrium were cooperative. We conclude that HMBA, SAHA, and JQ1 affect transcription elongation by a similar and convergent mechanism.

  15. THE INFLUENCE OF HYDROLOGICAL DATA QUALITY ON ESTIMATING THE RUNOFF FROM CITY CATCHMENT ON THE EXAMPLE OF STRZYŻA STEAM IN GDAŃSK

    Directory of Open Access Journals (Sweden)

    Michał Szydłowski

    2015-10-01

    Full Text Available Channel flow control and prediction of waterbodies reaction on heavy rainfalls or rapid snowmelt become critical when forecasting the flood risk in urban catchments. A very good example of both problematic and carrying a real threat to urban infrastructure is the Strzyża Creek in Gdańsk. In years 2011–2013 undertook the implementation of storm water monitoring system in the Strzyża Creek basin in Gdańsk. Since that time, it has become possible to collect valuable hydrological data on rainfall and flows in the strongly diversified urbanized districts of the city. Currently, the work is underway to extend the Strzyża Creek monitoring system. The ongoing research project is being realized again in years 2015–2017. The main aims of a project are: development of the methods of flood control, expansion of the existing rainfall-runoff and storage monitoring system in the basin and integrated water quantity and quality analysis, since the Strzyża Creek is one of the main stormwater collectors in Gdańsk. The article presents an example of using continuous data collected by the hydrological monitoring system to determine the annual runoff coefficient. The results were compared with the same parameter estimated on the basis of monthly instantaneous flow measurements and rainfall observations from the precipitation gauge localized in the vicinity of the analyzed catchment.

  16. Phenolic phytochemicals derived from red pine (Pinus densiflora) inhibit the invasion and migration of SK-Hep-1 human hepatocellular carcinoma cells.

    Science.gov (United States)

    Lee, Sang Jun; Lee, Ki Won; Hur, Haeng Jeon; Chun, Ji Young; Kim, Seo Young; Lee, Hyong Joo

    2007-01-01

    Considerable attention has recently been focused on identifying chemopreventive phytochemicals derived from medicinal plants. Here, we analyzed phenolic phytochemicals from red pine (RP) leaves and found epigallocatechin gallate (EGCG) and epigallocatechin (EGC), and catechin gallate (CG) as their major phenolic phytochemicals. This article also investigated whether RP leaf extract and its phenolic phytochemicals inhibit the invasion of SK-Hep-1 human hepatocellular carcinoma cells (SK-Hep-1 cells). RP suppressed the invasion and the migration of SK-Hep-1 cells. EGCG and CG also inhibited the invasion and migration, with EGC exhibiting a lower efficacy. Matrix metalloproteinases (MMPs), particularly gelatinase-A (MMP-2) and gelatinase-B (MMP-9), degrade components of the basement membrane and are strongly implicated in invasion and metastasis formation of malignant tumors. RP suppressed both MMP-2 and MMP-9 activities. EGCG and CG reduced the activities of MMP-9 and MMP-2 in a dose-dependent manner, with EGC exhibiting a lower efficacy on both MMPs. Our results suggest that RP inhibits tumor invasion and migration, which may be attributed to the effects of EGCG and CG. In particular, EGCG plays a key role in the efficacy of RP against hepatocarcinogenesis.

  17. Stjórnvald eða silkihúfa. Um hlutverk skólanefnda í íslenskum framhaldsskólum

    Directory of Open Access Journals (Sweden)

    Magnús Ingvarsson

    2008-12-01

    Full Text Available Þessi grein er byggð á rannsókn sem gerð var á starfsemi skólanefnda í íslenskum framhaldsskólum og var hún lokaverkefni til meistaraprófs í opinberri stjórnsýslu við Háskóla Íslands vorið 2008. Í greininni eru dregin saman helstu atriðin í rannsókninni. Þess ber þó að geta að síðan rannsóknin var gerð voru ný framhaldsskólalög samþykkt, en samkvæmt nýju lögunum breytist starfsemi skólanefnda lítillega og þau færast aðeins nær því að endurspegla raunveruleg störf nefndanna.

  18. Macrophage inhibitory cytokine-1 transactivates ErbB family receptors via the activation of Src in SK-BR-3 human breast cancer cells.

    Science.gov (United States)

    Park, Yun Jung; Lee, Hansoo; Lee, Jeong-Hyung

    2010-02-01

    The function of macrophage inhibitory cytokine-1 (MIC-1) in cancer remains controversial, and its signaling pathways remain poorly understood. In this study, we demonstrate that MIC-1 induces the transactivation of EGFR, ErbB2, and ErbB3 through the activation of c-Src in SK-BR-3 breast cells. MIC-1 induced significant phosphorylation of EGFR at Tyr845, ErbB2 at Tyr877, and ErbB3 at Tyr1289 as well as Akt and p38, Erk1/2, and JNK mitogen-activated protein kinases (MAPKs). Treatment of SK-BR-3 cells with MIC-1 increased the phosphorylation level of Src at Tyr416, and induced invasiveness of those cells. Inhibition of c-Src activity resulted in the complete abolition of MIC-1-induced phosphorylation of the EGFR, ErbB2, and ErbB3, as well as invasiveness and matrix metalloproteinase (MMP)-9 expression in SK-BR-3 cells. Collectively, these results show that MIC-1 may participate in the malignant progression of certain cancer cells through the activation of c-Src, which in turn may transactivate ErbB-family receptors.

  19. The Apoptotic Effect of Ursolic Acid on SK-Hep-1 Cells is Regulated by the PI3K/Akt, p38 and JNK MAPK Signaling Pathways.

    Science.gov (United States)

    Chuang, Wan-Ling; Lin, Ping-Yi; Lin, Hui-Chuan; Chen, Yao-Li

    2016-01-01

    Ursolic acid (UA) is a pentacyclic triterpene acid that is present in a wide variety of medicinal herbs and edible plants. This study investigated the effect of UA on apoptosis and proliferation of hepatocellular carcinoma SK-Hep-1 cells. After treatment of SK-Hep-1 cells with different concentrations of UA, we observed that cell viability was reduced in a dose- and time-dependent manner. Furthermore, there was a dose-dependent increase in the percentage of cells in the sub-G1 and G2/M phases, with cells treated with 60 μM showing the highest percentages of cells in those phases. UA-induced chromatin condensation of nuclei was observed by using DAPI staining. The western blot results revealed that exposure to UA was associated with decreased expression of the anti-apoptotic proteins Mcl-1, Bcl-xL, Bcl-2, and TCTP and increased expression of apoptosis-related proteins TNF-α, Fas, FADD, Bax, cleaved caspase-3, caspase-8, caspase-9, and PARP. Immunocytochemistry staining showed that treatment with UA resulted in increased expression of caspase-3. Moreover, exposure to UA resulted in the inhibition of the PI3K/Akt and p38 MAPK signaling pathways. These findings suggest that UA inhibits the proliferation of SK-Hep-1 cells and induces apoptosis.

  20. Choroby oraz pielęgnacja skóry głowy i włosów

    OpenAIRE

    Szklarczyk, Małgorzata; Goździalska, Anna; Jaśkiewicz, Jerzy

    2012-01-01

    Praca recenzowana / peer-reviewed paper Skóra głowy może być wrażliwa z natury lub może stać się taka w wyniku niekorzystnie działających czynników zewnętrznych, które prowadzą do osłabienia naturalnej bariery ochronnej skóry. Mieszek włosowy, z którego wyrasta włos jest bardzo wrażliwy. Zmiany w jego obrębie powodują wyraźne wahania w rozwoju włosa, w tym prowadząc do jego utraty. Problemy związane ze skórą głowy i włosów wymagają natychmiastowej reakcji, gdyż są wskaźnikiem nieprawidł...

  1. Loss of function mutation in LARP7, chaperone of 7SK ncRNA, causes a syndrome of facial dysmorphism, intellectual disability, and primordial dwarfism.

    Science.gov (United States)

    Alazami, Anas M; Al-Owain, Mohammad; Alzahrani, Fatema; Shuaib, Taghreed; Al-Shamrani, Hussain; Al-Falki, Yahya H; Al-Qahtani, Saleh M; Alsheddi, Tarfa; Colak, Dilek; Alkuraya, Fowzan S

    2012-10-01

    Primordial dwarfism (PD) is a clinically and genetically heterogeneous condition. Various molecular mechanisms are known to underlie the disease including impaired mitotic mechanics, abnormal IGF2 expression, perturbed DNA damage response, defective spliceosomal machinery, and abnormal replication licensing. Here, we describe a syndromic form of PD associated with severe intellectual disability and distinct facial features in a large multiplex Saudi family. Analysis reveals a novel underlying mechanism for PD involving depletion of 7SK, an abundant cellular noncoding RNA (ncRNA), due to mutation of its chaperone LARP7. We show that 7SK levels are tightly linked to LARP7 expression across cell lines, and that this chaperone is ubiquitously expressed in the mouse embryo. The 7SK is known to influence the expression of a wide array of genes through its inhibitory effect on the positive transcription elongation factor b (P-TEFb) as well as its competing role in HMGA1-mediated transcriptional regulation. This study documents a critical role played by ncRNA in human development and adds to the growing list of molecular mechanisms that, when perturbed, converge on the PD phenotype. © 2012 Wiley Periodicals, Inc.

  2. The effect of VMP35 supplement ingredients encapsulated in a novel Phospholipid Prodosome SK713 SLP nutrient delivery technology on properties of live human blood.

    Directory of Open Access Journals (Sweden)

    Kenneth Blum

    2015-09-01

    Full Text Available Background: In North America digestive malfunction in terms of disintegration, dissolution, and absorption of food and nutrients, is a widespread malady. Malabsorption is also an exacerbating factor in most chronic degenerative diseases that might benefit from dietary supplementation. The purpose of this experiment was to determine, as shown by changes in properties of live blood, whether, a novel soy-lecithin-phospholipid-nutrient encapsulation technology could promote rapid bioavailability and bioactivity of a VMP35 nutraceutical formulation encapsulated within its clustoidal multilamellar Soy Lecithin Phospholipid (SLP liquid SK713 SLP structures. Method: Changes in peripheral blood smears from 38 subjects were measured utilizing peripheral live blood cell imaging (LBCI with phase contrast microscopy. Results: Compared to baseline and control, consistently and reproducibly, the SK713 SLP technology effected positive changes in the blood as demonstrated by observable morphological, hematological and rheological changes five minutes from intake and sustained for at least 30 minutes post intake. Conclusions: These results showed that the SK713 SLP system makes an important contribution by increasing the potential benefits of dietary supplementation to those patients with compromised digestive processes. We encourage additional research on this novel delivery system believing that it has potential impact on future therapy.

  3. Morphology and Hydraulics of Nine Sand-bed Fluvial Bifurcations from the Mossy Delta, SK: Implications for Their Stability

    Science.gov (United States)

    Slingerland, R.; Klein, F. E.; Edmonds, D. A.; Best, J. L.; Parsons, D. R.; Bridge, J. S.; Janesko, D.; Smith, N. D.

    2007-12-01

    The distributary channel network of the Mossy Delta, SK consists of ~25 presently-active bifurcations created by channel splitting around river mouth bars during a 70 year history of delta growth. Detailed morphologic and hydraulic data from nine bifurcations are analyzed here to define the processes that determine their stability. Processes considered include bedload steering by adverse bed slopes, sediment and flow steering by secondary circulation, flow steering by inherited channel planform, and gradient advantage due to external boundary conditions. Stability of the bifurcations was determined from serial aerial photo analysis. Results indicate that the net topology and planforms of the bifurcations were set early during deposition of river mouth bars. Inherited alignment of a bifurcate channel thalweg with the main stem does not play a large role in subsequent bifurcation evolution; today roughly half of the side-channels take a greater proportion of the flow. After creation, bifurcate channels decreased in width by c. 15 %, with most of the reduction occurring in the first decade through bank accretion of scroll bars. Modern bifurcate channel depths and widths follow a hydraulic geometry scaling law (although they are wider and shallower than typical river channels), indicating a morphodynamically stable channel network. Most active bifurcations today are asymmetric; the average proportion of discharge through subordinate channels is 37 % with variation from 20 to 50 %. Local water surface slopes are flat approaching a bifurcation and steepen down the bifurcate arms, with the steeper slope in the shallower channel. All subordinate bifurcate channels possess morphologic ramps from the main channel with adverse bed slopes of 3-5 %. Although this suggests topographic steering of bedload is an important process in maintaining stability, it is not the only controlling process, because the subordinate ramp is shallower in c. 30 % of the cases.

  4. siRNA干扰人BMP9重组腺病毒载体的构建及其促进乳腺癌SK-BR-3细胞增殖%Construction of recombinant adenovirus vector interfering the expression of human BMP9 and promoting the proliferation of breast cancer SK-BR-3 cells

    Institute of Scientific and Technical Information of China (English)

    刘月红; 王科; 孙笑笑; 万绍恒; 王维; 陈莹莹; 张彦

    2013-01-01

    目的 筛选特异性干扰人BMP9基因的siRNA序列并制备重组腺病毒AdsiBMP9,探讨RNAi人BMP9基因后对乳腺癌SK-BR-3细胞增殖能力的影响.方法 设计制备3对干扰人BMP9的双链DNA序列,亚克隆至Pses-Hus质粒中获得Pses-Hus-siBMP9质粒,脂质体转染乳腺上皮细胞HBL-100筛选有效干扰质粒,构建重组腺病毒并感染SK-BR-3细胞,RT-PCR,Western blot检测BMP9表达,MTT检测细胞增殖能力.结果 成功构建并筛选出针对人BMP9基因的有效干扰质粒并包装成腺病毒,病毒滴度为1×1010IU/mL,感染SK-BR-3细胞显示BMP9在转录水平和翻译水平表达量显著低于对照组和空白组(P<0.05),第5天AdsiBMP9组细胞的增殖率显著高于AdsiNC组(P<0.05).结论 成功构建特异性沉默人BMP9基因的siRNA腺病毒载体,可有效抑制SK-BR-3细胞中BMP9基因的表达从而促进该细胞增殖.%Objective To screen specific small interfering RNA(siRNA) target human BMP9 gene and to prepare recombinant adenovirus vector AdsiBMP9 for investigation of its effects on the proliferation of breast cancer SK-BR-3 cells. Methods Three pairs of double-stranded DNA fragments for silencing human BMP9 were designed and synthesized, then subcloned into the shuttle plasmid Pses-Hus. The recombinant plasmids Pses-Hus-siBMP9 were transfected into the breast epithelial cells HBL-100 by lipofectamine transfection reagent, screened the effective interfering plasmid, constructed AdsiBMP9 and infected SK-BR-3 cells. The expression level of BMP9 mRNA and protein were detected by RT-PCR and western blot. The proliferation of SK-BR-3 cells were observed with MTT assay. Results The recombinant plasmid Pses-Hus-siBMP9 and recombinant adenovirus AdsiBMP9 were successfully constructed and its titer was 1 × 1010 IU/mL. Compared to the negative and non-infected controls, the expres- sion of BMP9 gene was significantly inhibited after the SK-BR-3 cells were infected by AdsiBMP9. SK-BR-3 cells infected with

  5. SK-ⅡFallout

    Institute of Scientific and Technical Information of China (English)

    MATT; YOUNG

    2006-01-01

    How the fallen product line in China will affect P&G... Everyone knows Crest cleans your teeth, Pantene shines your hair and Pampers comforts your baby's bottom. And Procter & Gamble Co.'s P&G label, for branding purposes, is almost everywhere these products are, helping to build one of China's most trusted names in advertising and manufacturing.

  6. PS1-12sk IS A PECULIAR SUPERNOVA FROM A He-RICH PROGENITOR SYSTEM IN A BRIGHTEST CLUSTER GALAXY ENVIRONMENT

    Energy Technology Data Exchange (ETDEWEB)

    Sanders, N. E.; Soderberg, A. M.; Foley, R. J.; Chornock, R.; Milisavljevic, D.; Margutti, R.; Drout, M. R.; Moe, M.; Berger, E.; Brown, W. R.; Lunnan, R. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Smartt, S. J.; Fraser, M.; Kotak, R.; Magill, L.; Smith, K. W.; Wright, D. [Astrophysics Research Centre, School of Maths and Physics, Queens University, Belfast BT7 1NN (United Kingdom); Huang, K. [Academia Sinica Institute of Astronomy and Astrophysics, Taipei 106, Taiwan (China); Urata, Y. [Institute of Astronomy, National Central University, Chung-Li 32054, Taiwan (China); Mulchaey, J. S., E-mail: nsanders@cfa.harvard.edu [Carnegie Observatories, 813 Santa Barbara Street, Pasadena, CA 91101 (United States); and others

    2013-05-20

    We report on our discovery and observations of the Pan-STARRS1 supernova (SN) PS1-12sk, a transient with properties that indicate atypical star formation in its host galaxy cluster or pose a challenge to popular progenitor system models for this class of explosion. The optical spectra of PS1-12sk classify it as a Type Ibn SN (SN Ibn; cf. SN 2006jc), dominated by intermediate-width (3 Multiplication-Sign 10{sup 3} km s{sup -1}) and time variable He I emission. Our multi-wavelength monitoring establishes the rise time dt {approx} 9-23 days and shows an NUV-NIR spectral energy distribution with temperature {approx}> 17 Multiplication-Sign 10{sup 3} K and a peak magnitude of M{sub z} = -18.88 {+-} 0.02 mag. SN Ibn spectroscopic properties are commonly interpreted as the signature of a massive star (17-100 M{sub Sun }) explosion within an He-enriched circumstellar medium. However, unlike previous SNe Ibn, PS1-12sk is associated with an elliptical brightest cluster galaxy, CGCG 208-042 (z = 0.054) in cluster RXC J0844.9+4258. The expected probability of an event like PS1-12sk in such environments is low given the measured infrequency of core-collapse SNe in red-sequence galaxies compounded by the low volumetric rate of SN Ibn. Furthermore, we find no evidence of star formation at the explosion site to sensitive limits ({Sigma}{sub H{alpha}} {approx}< 2 Multiplication-Sign 10{sup -3} M{sub Sun} yr{sup -1} kpc{sup -2}). We therefore discuss white dwarf binary systems as a possible progenitor channel for SNe Ibn. We conclude that PS1-12sk represents either a fortuitous and statistically unlikely discovery, evidence for a top-heavy initial mass function in galaxy cluster cooling flow filaments, or the first clue suggesting an alternate progenitor channel for SNe Ibn.

  7. Pro-inflammatory cytokines derived from West Nile virus (WNV-infected SK-N-SH cells mediate neuroinflammatory markers and neuronal death

    Directory of Open Access Journals (Sweden)

    Nerurkar Vivek R

    2010-10-01

    Full Text Available Abstract Background WNV-associated encephalitis (WNVE is characterized by increased production of pro-inflammatory mediators, glial cells activation and eventual loss of neurons. WNV infection of neurons is rapidly progressive and destructive whereas infection of non-neuronal brain cells is limited. However, the role of neurons and pathological consequences of pro-inflammatory cytokines released as a result of WNV infection is unclear. Therefore, the objective of this study was to examine the role of key cytokines secreted by WNV-infected neurons in mediating neuroinflammatory markers and neuronal death. Methods A transformed human neuroblastoma cell line, SK-N-SH, was infected with WNV at multiplicity of infection (MOI-1 and -5, and WNV replication kinetics and expression profile of key pro-inflammatory cytokines were analyzed by plaque assay, qRT-PCR, and ELISA. Cell death was measured in SK-N-SH cell line in the presence and absence of neutralizing antibodies against key pro-inflammatory cytokines using cell viability assay, TUNEL and flow cytometry. Further, naïve primary astrocytes were treated with UV-inactivated supernatant from mock- and WNV-infected SK-N-SH cell line and the activation of astrocytes was measured using flow cytometry and ELISA. Results WNV-infected SK-N-SH cells induced the expression of IL-1β, -6, -8, and TNF-α in a dose- and time-dependent manner, which coincided with increase in virus-induced cell death. Treatment of cells with anti-IL-1β or -TNF-α resulted in significant reduction of the neurotoxic effects of WNV. Furthermore treatment of naïve astrocytes with UV-inactivated supernatant from WNV-infected SK-N-SH cell line increased expression of glial fibrillary acidic protein and key inflammatory cytokines. Conclusion Our results for the first time suggest that neurons are one of the potential sources of pro-inflammatory cytokines in WNV-infected brain and these neuron-derived cytokines contribute to WNV

  8. Effect of antisense oligodeoxyribonucleotides targeting at HER-2 mRNA on Caspase-3 protein expression in SK-BR-3 breast cancer cells%靶向HER-2 mRNA反义寡核苷酸对SK-BR-3乳腺癌细胞Caspase-3蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    杨栓平; 宋海峰; 宋三泰; 郑晓玲; 张凤霞

    2003-01-01

    目的检测HER-2特异性的反义寡核苷酸HA824对SK-BR-3乳腺癌细胞Caspase-3蛋白表达的影响.方法选用HER-2 高表达的SK-BR-3乳腺癌细胞株作为试验的细胞株.HA824合成如前所述,HA4为已报道的阳性序列,Scramble设定为随机对照序列.上述药物分别以浓度为200 nmol*L-1孵育SK-BR-3细胞8 h和36 h,之后采用逆转录PCR法与免疫细胞化学技术检测SK-BR-3细胞HER-2 mRNA 及Caspase-3蛋白表达水平.结果与Scramble对照序列相比,HA824、HA4能抑制HER-2 mRNA的表达,HA824作用更强;与Scramble 相比,HA824、HA4对Caspase-3蛋白表达水平则无影响.结论 HA824、HA4这两种靶向HER-2 mRNA反义药物对SK-BR-3乳腺癌细胞株增殖的抑制作用可能与激活Caspase-3蛋白无关.

  9. Development of cell-based bioassay with Sf9 cells expressing TcSKR1 and TcSKR2 and differential activation by sulfated and non-sulfated SK peptides.

    Science.gov (United States)

    Yu, Na; Swevers, Luc; Nachman, Ronald J; Smagghe, Guy

    2014-03-01

    Insect sulfakinin receptors (SKRs) are G-protein-coupled receptors (GPCRs) that interact with sulfakinins (SKs) to modulate diverse biological processes. One of the indispensable roles of SKs is in the regulation of food intake in insects. In this project we report on the development of a cell-based receptor assay system with insect Sf9 cells, expressing TcSKR1 and TcSKR2 from the red flour beetle Tribolium castaneum, a model and important pest insect in agriculture. In this system, a stable presence of the two TcSKRs was supported by Western blotting. The expressed TcSKRs were coupled to Gαs-protein upon activation and stimulated cAMP accumulation in Sf9 cells. Exposure of the transfected cell lines to sulfated SK (sSK) activated TcSKR1 at 1 nM; the EC50 of sSK to obtain 50% of receptor activation was similar for both receptors. In contrast, μM concentrations of non-sulfated SK were necessary to activate both TcSKRs. In conclusion, this cell-based TcSKR assay system is useful to screen SK-related peptides and mimetics and to better document ligand-receptor structure-activity relationships. Given the importance of SK signaling system in insects, the present study may provide new insights on the development of new methods to control pest insects.

  10. Osmotic Stress Confers Enhanced Cell Integrity to Hydrostatic Pressure but Impairs Growth in Alcanivorax borkumensis SK2

    Science.gov (United States)

    Scoma, Alberto; Boon, Nico

    2016-01-01

    Alcanivorax is a hydrocarbonoclastic genus dominating oil spills worldwide. While its presence has been detected in oil-polluted seawaters, marine sediment and salt marshes under ambient pressure, its presence in deep-sea oil-contaminated environments is negligible. Recent laboratory studies highlighted the piezosensitive nature of some Alcanivorax species, whose growth yields are highly impacted by mild hydrostatic pressures (HPs). In the present study, osmotic stress was used as a tool to increase HP resistance in the type strain Alcanivorax borkumensis SK2. Control cultures grown under standard conditions of salinity and osmotic pressure with respect to seawater (35.6 ppt or 1136 mOsm kg-1, respectively) were compared with cultures subjected to hypo- and hyperosmosis (330 and 1720 mOsm kg-1, or 18 and 62 ppt in salinity, equivalent to brackish and brine waters, respectively), under atmospheric or increased HP (0.1 and 10 MPa). Osmotic stress had a remarkably positive impact on cell metabolic activity in terms of CO2 production (thus, oil bioremediation) and O2 respiration under hyperosmosis, as acclimation to high salinity enhanced cell activity under 10 MPa by a factor of 10. Both osmotic shocks significantly enhanced cell protection by reducing membrane damage under HP, with cell integrities close to 100% under hyposmosis. The latter was likely due to intracellular water-reclamation as no trace of the piezolyte ectoine was found, contrary to hyperosmosis. Notably, ectoine production was equivalent at 0.1 MPa in hyperosmosis-acclimated cells and at 10 MPa under isosmotic conditions. While stimulating cell metabolism and enhancing cell integrity, osmotic stress had always a negative impact on culture growth and performance. No net growth was observed during 4-days incubation tests, and CO2:O2 ratios and pH values indicated that culture performance in terms of hydrocarbon degradation was lowered by the effects of osmotic stress alone or combined with increased HP

  11. Is assimilation of country rocks in camera of crystallization an important factor for origin of the Noril'sk ores?

    Science.gov (United States)

    Krivolutskaya, Nadezhda; Kryazhev, Sergey; Svirskaya, Natalia

    2013-04-01

    In origin of the unique PGE-Cu Noril'sk deposits a great significance is attached to assimilation of country rocks by mafic melts in camera of crystallization for formation large-scale sulfide ore bodies. The main argument in favor of widespread assimilation is the enrichment of ore sulfides in the heavy sulfur isotope due to the participation of anhydrite from country rocks (Godlevsky, Grinenko, 1963). But real data demonstrated this process are almost absent in literature. We have studied geochemistry rocks of some sections from surrounding rocks to intrusive ones with sulfide ores. Two of them were done at the Southern Maslovsky deposit located in basalts and one was considered at Talnakh deposit (SW branch) that is situated among carbonate-terrigenouse rocks with evaporates (salt, anhydrite, gypsum). Ores at the Maslovsky deposit are characterized by δ34S = 6-11‰ while the host basalts of the Nadezhdinsky Formation have δ34S country basalts on composition of intrusive rocks is not detected at all and revealed in a narrow zone (country rocks by magma must be reflected in change of chemical and modal composition of intrusive rocks, especially in contact zones of intrusions, but this effect is noted established. Line of component variations have sharp profile from sedimentary rocks to gabbro-dolerites without intermediate values. It shows an absent of contamination in situ. Data on Nd, Sr, and Pb isotopic compositions of anydrite from the Devonian rocks demonstrate that the initial 87Sr/86Sr ratio (0.708637-0.708949, 251 Ma) in anhydrite is lower than in the Nadezhdinsky basalt, where this ratio attains 0.709171 (Wooden et al., 1993), The studied samples are characterized by anomalous enrichment in radiogenic lead (206Pb/204Pb attains 24.53). It would be expressed in isotopic composition of contaminated igneous rocks, but this is not the case. Thus, anhydrite cannot be a contaminant for igneous rocks and assimilation of country rocks in intrusive chambers was

  12. Osmotic stress confers enhanced cell integrity to hydrostatic pressure but impairs growth in Alcanivorax borkumensis SK2

    Directory of Open Access Journals (Sweden)

    Alberto eScoma

    2016-05-01

    Full Text Available Alcanivorax is a hydrocarbonoclastic genus dominating oil spills worldwide. While its presence has been detected in oil-polluted seawaters, marine sediment and salt marshes under ambient pressure, its presence in deep-sea contaminated environments is negligible. Recent laboratory evidences highlighted the piezosensitive nature of some Alcanivorax species, whose growth yields are highly impacted by mild hydrostatic pressures (HPs. In the present study, osmotic stress was used as a tool to increase HP resistance in the type strain A. borkumensis SK2. Control cultures grown under standard conditions of salinity and osmotic pressure with respect to seawater (35.6 ppt or 1136 mOsm kg-1, respectively were compared with cultures subjected to hypo- and hyperosmosis (330 and 1720 mOsm kg-1, or 18 and 62 ppt in salinity, equivalent to brackish and brine waters, respectively, under atmospheric or increased HP (0.1 and 10MPa. Osmotic stress had a remarkably positive impact on cell metabolic activity in terms of CO2 production (thus, oil bioremediation and O2 respiration under hyperosmosis, as acclimation to high salinity enhanced cell activity under 10MPa by a factor of 10. Both osmotic shocks significantly enhanced cell protection by reducing membrane damage under HP, with cell integrities close to 100% under hyposmosis. The latter was likely due to intracellular water-reclamation as no trace of the piezolyte ectoine was found, contrary to hyperosmosis. Notably, ectoine production was equivalent at 0.1MPa in hyperosmosis-acclimated cells and at 10MPa under isosmotic conditions, supporting the hypothesis that ectoine synthesis may be primarily triggered by HP rather than osmotic stress. While stimulating cell metabolism and enhancing cell integrity, osmotic stress had always a negative impact on culture growth and performance. No net growth was observed during 4-day incubation tests, and CO2:O2 ratios and pH values indicated that culture performance in

  13. 不同质量浓度磁性c-erbB-2反义探针对SK-Br-3肿瘤细胞株形态及表达的影响%Effects of Magnetic c-erbB-2 Antisense Probe of Different Concentrations on Morphology and Expression of SK-Br-3 Cancer Cell Lines in vitro

    Institute of Scientific and Technical Information of China (English)

    刘海燕; 温志鹏; 文明; 贺海容; 谭书德; 李少林

    2013-01-01

    目的 探讨不同质量浓度磁性c-erbB-2反义探针转染乳腺癌SK-Br-3细胞株后,对其形态及表达的影响.方法将反义探针含铁质量浓度分别定为5、10、25、50、100 mg/L,转染乳腺癌SK-Br-3细胞24 h.采用普鲁士蓝染色并在光学显微镜及透射电镜下直接观察细胞铁颗粒,原子吸收光谱法测定细胞内铁含量,台盼蓝排除实验、CCK-8试剂盒观察细胞活性,Western blot法检测蛋白质表达,磁共振成像研究信号强度的变化.结果 SK-Br-3细胞对反义探针在一定质量浓度范围内(5、10、25 mg/L)呈依赖式摄取.当探针质量浓度为25 mg/L时,细胞内铁含量为(18.38±0.28) pg,细胞活力、存活率及细胞内c-erbB-2蛋白表达量明显降低(P均<0.05),磁共振扫描图像显示该组细胞T2值出现明显降低(P<0.05).50及100 mg/L组各项结果与25 mg/L组比较差异无统计学意义(P均>0.05).结论 当磁性c-erbB-2反义探针质量浓度为25 mg/L时,可有效转染并特异性抑制SK-Br-3细胞株的表达,并被磁共振成像所检测.%Objective To explore the effects of the magnetic c-erbB-2 antisense probe of different concentrations on the morphology and expression of SK-Br-3 cancer cells in vitro. Methods Breast cancer SK-Br-3 cells were transfected for 24 h by antisense probe at an iron concentration of 5, 10, 25, 50, and 100 mg/L, respectively. The distribution and content of iron particles in SK-Br-3 cells was determined by Prussian blue staining, electron microscopy, and atomic absorption spectrometry. Cell viability was observed by trypan-blue exclusion and CCK-8 test. The protein expression of c-erbB-2 was assessed by the Western blot analysis. The changes of the signal strength were considered by magnetic resonance imaging ( MRI). Results c-erbB-2 anti-sense probe was uptake by SK-Br-3 cells in a concentration-dependence manner within a certain range (5 , 10,25 mg/L). When the probe concentration was 25 mg/L, iron content in

  14. RNAi silencing of HER2 gene induces apoptosis and antiproliferative effect of SK-BR-3 cell line%HER2基因RNA干扰质粒对SK-BR-3细胞增殖及凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    韩冬; 徐煌; 李文浩; 张成文

    2011-01-01

    Objective To examine thebiologic effects of HER 2 gene silencing on SKBR 3 eels through the transfection of HER2-specific shRNA expression vector. Methods SK-BR-3 breast cancer cells overexpressing the HER2 gene were transfected with HER2-shRNA2 vector using Lipofectan ine2000 .After transfection the antiproliferative effect of HER2-shRNA2 was detected by MTT assay and apoptosis percentage was detected by flow cytom etry .The expressbns of proliferating cell nuclear antigen (PCNA ) were e-valuated by W estem bbtanalysis .Results After tramsfection with HER2-shRNA2,inhibitory ratio of HER2-shARNA2 group was 16 . 53% (48h),39.03% (72 h),or65.47% (96 h) .After Seventy-two hours ,apoptosis percentage of SK-BR-3 cells of transfected w ith HER2-shARNA2 was increased to 10 .29% compared to that in negative control and blank control groups .Conclusbn Silencing of H ER2 gene by shRNA can inhisit proliferation and induce apoptosis in SK-BR-3 cells .These prom ising results suggest that shRNA tergeted against hum anHER2maybe valuable tools as antiproferative agents against neoplastic cells .%目的 探讨HER2基因高效RNA干扰质粒转染到SK-BR-3乳腺癌细胞后,对细胞的增殖及其凋亡的影响.方法 采用脂质体转染法将针对HER2基因的高效RNA干扰质粒转染至乳腺癌细胞SK-BR-3中,通过细胞计数、MTT比色法、流式细胞术和Western blot检测PCNA增殖细胞核抗原,分析检测其对SK-BR-3细胞增殖、凋亡的影响.结果 MTT比色测定显示, HER2-shRNA2干扰质粒转染到SK-BR-3细胞后在48 h后现抑制,与空白对照组比抑制率分别为48 h 16.53%、72h 39.03%、96h 65.47%.流式细胞分析HER2-shRNA组细胞在96 h凋亡率达17.36%,明显高于阴性对照组的1.41%和空白对照组的1.25%(P<0.05).结论 将RNA干扰质粒HER2-shRNA2转染至SK-BR-3细胞中,可特异性地抑制SK-BR-3细胞的增殖并诱导其凋亡,为乳腺癌的靶向治疗奠定了基础.

  15. 人参皂苷Rb1、Re对Aβ25-35诱导SK-N-SH细胞损伤的保护作用%Protective effects of ginsenoside Rbl and Re on SK-N-SH cells injured by Aβ25-35

    Institute of Scientific and Technical Information of China (English)

    贾立云; 潘晓华; 刘晶; 崔行; 王墨林

    2011-01-01

    Objective To investigate protective effects of ginsenoside Rbl and Re against injury of SK-N-SH cells induced by Aβ25-35 and the possible mechanism. Methods Aβ25-35 was added to the medium for cell culture to make a cell model of Alzheimer disease, and ginsenoside Rb1 or Re were used to treat the injured cells. Cell survival rates were determined by the MTr assay, intracellular ROS levels were determined by fluorescence probes, and expressions of phosphorylated tau and active glycogen synthase kinase 3β(GSK-3β) were determined by Western blot. Results The survival ratio of SK-N-SH cells were significantly decreased after exposure to Aβ25-35, and treatment with ginsenoside Rbl or Re significantly increased the survival ratio and decreased the cellular ROS level. Ginsenoside Rbl and Re decreased expressions of phosphorylated tau and active GSK-3β, respectively. Conclusion Ginsenoside Rbl and Re may exert a neuroprotective effect on SH-N-SH neural cells induced by neurotoxic Aβ25-35.%目的 观察人参皂苷Rb1和Re对Aβ25-35诱导损伤SK-N-SH细胞的保护作用进而研究其内在机制.方法 用Aβ25-35处理人神经母细胞瘤细胞(SK-N-SH细胞),模拟阿尔茨海默病的神经元损伤,并以适当浓度人参皂苷Rb1或Re处理.采用MTT法测定细胞存活率,荧光探针法检测细胞内ROS水平变化,Western blot法检测tau蛋白磷酸化水平及活性GSK-3β蛋白表达.结果 培养基中添加Aβ25-35后SK-N-SH细胞存活率明显下降,而人参皂苷Rb1和Re均能显著提高损伤细胞的存活率,降低细胞内ROS水平,降低活性GSK-3β的表达,造成tau蛋白396位点的磷酸化程度下降,缓解tau蛋白的过度磷酸化.结论 人参皂苷Rb1和Re对Aβ25-35诱导损伤的SK-N-SH细胞具有一定的保护作用.

  16. Response of the diatom flora in the Gdańsk Basin (southern Baltic Sea) to eutrophication in the last century

    Science.gov (United States)

    Witak, Małgorzata

    2016-04-01

    The diatom flora in six short cores (length of 10-20 cm) taken from Gdańsk Basin, southern Baltic Sea, was analyzed in order to response of diatoms to environmental changes over the past 100 years. This study is a part of CLISED project (Climate Change Impact on Ecosystem Health - Marine Sediments Indicators) funded from Norway Grants in the Polish-Norwegian Research Programme. Three cores P116, M1 and P1 were retrieved from the Gdańsk Deep region, whereas P104, BMPK10 and P110 were drilled from the shallower part - Gulf of Gdańsk. The sediment cores were dated by 210Pb and represented time interval of AD 1895-2015. In this period an artificial mouth of the Vistula River near Świbno was excavated and riverine waters flowed directly to the Gulf of Gdańsk. Urbanization, progressive industrialization and an increase in the inflow of waste water had a strong influence on ecosystem in the last 120 years. The transport of large amounts of nutrients, organic matter and pollutants by the rivers resulted in environmental degradation of the Gdańsk Basin and its progressive eutrophication in particular. Diatoms, being the major component of algal assemblages, are excellent bioindicators for assessing the state of basin ecosystems. They are usually abundant in marine sediments, diverse and sensitive to numerous environmental variables, including physical (e.g. light, temperature, water transparency) and chemical (e.g. pH, alkalinity, nutrient availability) factors. Changes in nutrients concentrations may lead to substantial transformations in the structure of diatom assemblages. Samples for diatom analyses (ca. 0.3-2.0 g dry sediment) were prepared following the standard procedure for diatom observation under light microscope (Battarbee, 1986). To estimate the concentration of siliceous microfossils per unit weight of dry sediment (absolute abundance), a random settling technique was used (Bodén, 1991). Permanent diatom preparations were mounted in Naphrax® (refractive

  17. German register for detection of late sequelae after radiotherapy for children and adolescents (RiSK): present status and first results

    Energy Technology Data Exchange (ETDEWEB)

    Boelling, T.; Schuck, A.; Willich, N. [Dept. of Radiotherapy of the Univ. Hospital Muenster (Germany); Pape, H. [Dept. of Radiotherapy of the Univ. Hospital Duesseldorf (Germany); Ruebe, C. [Dept. of Radiotherapy of the Univ. Saarland, Homburg/Saar (Germany); Meyer, F.M. [Dept. of Radiotherapy of the Clinic of Augsburg (Germany); Martini, C. [Dept. of Radiotherapy of the Univ. Hospitals Freiburg (Germany); Timmermann, B. [Paul Scherrer Inst., Villigen (Switzerland); Asadpour, B. [Dept. of Radiotherapy of the Univ. Hospital Aachen (Germany); Kortmann, R.D. [Dept. of Radiotherapy of the Univ. Hospital Leipzig (Germany); Beck, J.D.; Langer, T.; Paulides, M. [LESS Center, Univ. Children' s Hospital Erlangen (Germany)

    2007-12-15

    Undoubtedly, radiotherapy is an important treatment strategy for many malignancies in paediatric oncology. However, sufficient data about late side effects do not exist. There is a lack of information about radiation dose-effect relationships in view of late side effects in childhood and adolescence. Late effects after radiotherapy in childhood and adolescence have mainly been characterized retrospectively with small patient numbers. Many of these analyses are limited due to little information about organ dose levels and older radiation techniques in some cases. Therefore the German Group of Paediatric Radiation Oncology (APRO) established the 'Register for the evaluation of late side effects after radiation in childhood and adolescence (RiSK)'. Aim of this prospective multicentric register study is to evaluate irradiation dose effect relationships of organs and part of organs with respect to late effects. The feasibility of RiSK has already been shown and first results have recently been published. The characterization of late effects after cancer therapy in childhood is of rising interest. In Germany, several study groups like the 'Late Effects Surveillance System' (LESS) or the working group 'Quality of life' examine different aspects of late effects. In the United States of America, the 'Childhood Cancer Survivor Study' has been established to characterize retrospectively the health status of 5-year-survivors of childhood cancer. In these studies, more than 12,000 patients were evaluated by questionnaires regarding their health status. For radiotherapy, this study is not able to give detailed information about late side effects due to rare data about radiation doses and organ dose levels. To our knowledge, 'RiSK' is the only multicentric study that evaluates radiation associated side effects prospectively with detailed information about organ dose levels. (orig.)

  18. The presence of c-erbB-2 gene product-related protein in culture medium conditioned by breast cancer cell line SK-BR-3

    Energy Technology Data Exchange (ETDEWEB)

    Alper, O.; Yamaguchi, K.; Hitomi, J.; Honda, S.; Matsushima, T.; Abe, K. (National Cancer Center Research Institute, Tokyo (Japan))

    1990-12-01

    The Mr 185,000 glycoprotein encoded by human c-erbB-2/neu/HER2 gene, termed c-erbB-2 gene product, shows a close structural similarity with epidermal growth factor receptor and is now regarded to be a growth factor receptor for an as yet unidentified ligand. Abundant c-erbB-2 mRNA was demonstrated by Northern blot studies in the human breast cancer cell line SK-BR-3. Cellular radiolabeling experiments followed by immunoprecipitation with three different anti-c-erbB-2 gene product antibodies, recognizing extracellular domain, kinase domain, and carboxyl-terminal portion, respectively, demonstrated the production of a large amount of c-erbB-2 gene product which had the capacity to be phosphorylated. Immunization of mice with concentrated culture medium conditioned by SK-BR-3 cells always generated antibodies against c-erbB-2 gene product, demonstrating that this culture medium contained substance(s) immunologically indistinguishable from c-erbB-2 gene product. This observation was supported by the successful development of a monoclonal antibody against c-erbB-2 gene product, GFD-OA-p185-1, by immunizing mice with this culture medium. The biochemical nature of the substance(s) present in the culture medium was further characterized. When the culture medium conditioned by (35S)cysteine-labeled SK-BR-3 cells was immunoprecipitated by three different anti-c-erbB-2 gene product antibodies, only the antibody recognizing extracellular domain precipitated the (35S)-labeled protein with a molecular weight of 110,000, namely p110. The newly developed monoclonal antibody also immunoprecipitated this protein.

  19. Release of positive transcription elongation factor b (P-TEFb) from 7SK small nuclear ribonucleoprotein (snRNP) activates hexamethylene bisacetamide-inducible protein (HEXIM1) transcription.

    Science.gov (United States)

    Liu, Pingyang; Xiang, Yanhui; Fujinaga, Koh; Bartholomeeusen, Koen; Nilson, Kyle A; Price, David H; Peterlin, B Matija

    2014-04-04

    By phosphorylating negative elongation factors and the C-terminal domain of RNA polymerase II (RNAPII), positive transcription elongation factor b (P-TEFb), which is composed of CycT1 or CycT2 and CDK9, activates eukaryotic transcription elongation. In growing cells, it is found in active and inactive forms. In the former, free P-TEFb is a potent transcriptional coactivator. In the latter, it is inhibited by HEXIM1 or HEXIM2 in the 7SK small nuclear ribonucleoprotein (snRNP), which contains, additionally, 7SK snRNA, methyl phosphate-capping enzyme (MePCE), and La-related protein 7 (LARP7). This P-TEFb equilibrium determines the state of growth and proliferation of the cell. In this study, the release of P-TEFb from the 7SK snRNP led to increased synthesis of HEXIM1 but not HEXIM2 in HeLa cells, and this occurred only from an unannotated, proximal promoter. ChIP with sequencing revealed P-TEFb-sensitive poised RNA polymerase II at this proximal but not the previously annotated distal HEXIM1 promoter. Its immediate upstream sequences were fused to luciferase reporters and were found to be responsive to many P-TEFb-releasing compounds. The superelongation complex subunits AF4/FMR2 family member 4 (AFF4) and elongation factor RNA polymerase II 2 (ELL2) were recruited to this proximal promoter after P-TEFb release and were required for its transcriptional effects. Thus, P-TEFb regulates its own equilibrium in cells, most likely to maintain optimal cellular homeostasis.

  20. Seed oil composition of Acacia nilotica (L. Delile from Iran / Skład oleju z nasion Acacia nilotica (L. Delile rosnącej w Iranie

    Directory of Open Access Journals (Sweden)

    Abbasian Karim

    2016-03-01

    Full Text Available Wstęp: Acacia nilotica (L. Delile należy do rodziny Fabaceae, podrodziny Mimosoideae; otrzymuje się z niej gumę arabską. W południowym Iranie są spożywane pieczone młode strąki i nasiona tej rośliny Cel: Badano skład oleju z dojrzałych nasion A. nilotica zebranych z naturalnych stanowisk na południu Iranu w celu określenia jego przydatności do spożycia przez ludzi i zwierzęta. Metody: Wyekstrahowany olej analizowano metodą chromatografii gazowej sprzężonej ze spektrometrią mas (GC/MS. Wyniki: Zawartość oleju w jadalnych nasionach wynosiła 3.4% (v/w świeżej masy. Olej zawierał rzadko spotykany fitosterol, sześć kwasów tłuszczowych, dziewięć węgolwodorów i jeden diterpenoid; związki te stanowiły łącznie około 83.5% oleju. Głównymi składnikami oleju były: fitosterol, 26-ethylcholesta-5,25(Z-dien-3.β-ol (20.8% oraz nasycone i nienasycone kwasy tłuszczowe. Zawartość pozostałych składników nie przekroczyła 5%. Wniosek: Olej z nasion omawianego gatunku może być nowym naturalnym środkiem odżywczym dla ludzi.

  1. 使用SK算法构造组合凸线性感知器%Construction of Multiconlitron Using SK Algorithm

    Institute of Scientific and Technical Information of China (English)

    冷强奎; 李玉鑑

    2013-01-01

    组合凸线性感知器(multiconlitron)是用来构造分片线性分类器的一个通用理论框架.基于此框架,引入一种典型的凸包间最近点求解方法——Schlesinger-Kozinec (SK)算法,来计算线性可分样本间的分类超平面;然后构造可处理凸可分数据的凸线性感知器和处理叠可分数据的组合凸线性感知器.在人工合成数据集和标准数据集上的实验说明,所构造的感知器具有良好的分类性能,与其他典型分片线性分类器的对比也说明了该方法的有效性.%Multiconlitron is a general framework for constructing piecewise linear classifiers.This paper introduces a typical nearest point method,i.e.Schlesinger-Kozinec (SK) algorithm to compute the separating hyperplane between two convex polytopes for linearly separable data sets.By using SK algorithm,this paper constructs conlitron and multiconlitron to solve convexly separable and commonly separable problems,respectively.Experiments on both synthetic and real data sets show that the presented method has a good classification performance.Comparing with some other piecewise linear classifiers verifies the effectiveness of the presented method.

  2. 10Be exposure age chronology of the last glaciation of the Roháčská Valley in the Western Tatra Mountains, central Europe

    Science.gov (United States)

    Engel, Zbyněk; Mentlík, Pavel; Braucher, Régis; Křížek, Marek; Pluháčková, Markéta; Arnold, Maurice; Aumaître, Georges; Bourlès, Didier; Keddadouche, Karim

    2017-09-01

    10Be exposure ages from moraines and bedrock sites in the Roháčská Valley provide chronology of the last glaciation in the largest valley of the Western Tatra Mts., the Western Carpathians. The minimum apparent exposure age of 19.4 ± 2.1 ka obtained for the oldest sampled boulder and the mean age of 18.0 ± 0.8 ka calculated for the terminal moraine indicate that the oldest preserved moraine was probably deposited at the time of the global Last Glacial Maximum (LGM). The age of this moraine coincides with the termination of the maximum glacier expansion in other central European ranges, including the adjacent High Tatra Mts. and the Alps. The equilibrium line altitude (ELA) of the LGM glacier in the Roháčská Valley, estimated at 1400-1410 m a.s.l., was 50-80 m lower than in the eastern part of the range, indicating a positive ELA gradient from west to east among the north-facing glaciers in the Tatra Mts. Lateglacial glacier expansion occurred no later than 13.4 ± 0.5 ka and 11.9 ± 0.5 ka, as indicated by the mean exposure ages calculated for re-advance moraines. This timing is consistent with the exposure age chronology of the last Lateglacial re-advance in the High Tatra Mts., Alps and lower mountain ranges in central Europe. The ELA in the Roháčská Valley estimated at 1690-1770 m a.s.l. in this period was located 130-300 m lower than in the north-facing valleys in the High Tatra Mts. 10Be exposure ages obtained for a rock glacier constrains the timing of this landform stabilization in the Salatínska Valley and provides the first chronological evidence for the Lateglacial activity of rock glaciers in the Carpathians.

  3. Role of an S4-S5 linker lysine in the trafficking of the Ca(2+)-activated K(+) channels IK1 and SK3.

    Science.gov (United States)

    Jones, Heather M; Hamilton, Kirk L; Devor, Daniel C

    2005-11-04

    We have investigated the role of the S4-S5 linker in the trafficking of the intermediate (human (h) IK1) and small (rat SK3) conductance K(+) channels using a combination of patch-clamp, protein biochemical, and immunofluorescence-based techniques. We demonstrate that a lysine residue (Lys(197)) located on the intracellular loop between the S4 and S5 domains is necessary for the correct trafficking of hIK1 to the plasma membrane. Mutation of this residue to either alanine or methionine precluded trafficking of the channel to the membrane, whereas the charge-conserving arginine mutation had no effect on channel localization or function. Immunofluorescence localization demonstrated that the K197A mutation resulted in a channel that was primarily retained in the endoplasmic reticulum, and this could not be rescued by incubation at 27 degrees C. Furthermore, immunoblot analysis revealed that the K197A mutation was overexpressed compared with wild-type hIK1 and that this was due to a greatly diminished rate of channel degradation. Co-immunoprecipitation studies demonstrated that the K197A mutation did not preclude multimer formation. Indeed, the K197A mutation dramatically suppressed expression of wild-type hIK1 at the cell surface. Finally, mutation of this conserved lysine in rat SK3 similarly resulted in a channel that failed to correctly traffic to the plasma membrane. These results are the first to demonstrate a critical role for the S4-S5 linker in the trafficking and/or function of IK and SK channels.

  4. Valproic acid-mediated transcriptional regulation of human GM3 synthase (hST3Gal V) in SK-N-BE(2)-C human neuroblastoma cells

    Institute of Scientific and Technical Information of China (English)

    Haw-young KWON; Nam-young KANG; Hyun-mi DAE; Kyoung-sook KIM; Cheorl-ho KIM; Su-il DO; Young-choon LEE

    2008-01-01

    Aim:To investigate whether valproic acid (VPA) modulates human GM3 syn-thase (hST3Gal V) mRNA expression, as a part of ganglioside GM3 biosynthe-sis, in human neuroblastoma cells. Methods: Using RT-PCR and immunofluo-rescent confocal microscopy, we examined hST3Gal V mRNA and GM3 levels during VPA-induced differentiation of human neuroblastoma SK-N-BE(2)-C cells. We characterized the VPA-inducible promoter region within the hST3-Gal V gene using luciferase constructs carrying 5'-deletions of the hST3Gal V promoter. Results: RT-PCR indicated that VPA-mediated hST3Gal V induction is transcriptionally regulated. Functional analysis of the 5'-flanking region of the hST3Gal V gene demonstrated that the -177 to -83 region, which contains a cAMP-responsive element (CRE) at -143, functions as the VPA-inducible promoter by actively binding CRE binding protein (CREB). In addition, site-directed mutagenesis and electrophoretic mobility shift assay indicated that the CRE at -143 is crucial for the VPA-induced expression of hST3Gal V in SK-N-BE(2)-C cells. Conclusion: Our results isolated the core promoter region in the hST3Gal V promoter, a CRE at -143, and demonstrated that it is essential for transcriptional activation of hST3Gal V in VPA-induced SK-N-BE(2)-C cells. Subsequent CREB binding to this CRE mediates VPA-dependent upregulation of hST3Gal V gene expression.

  5. Effect of 3-bromopyruvate on mitochondrial membrane potential and apoptosis of human breast carcinoma SK-BR-3 cells%3-溴丙酮酸诱导人乳腺癌SK-BR-3细胞凋亡及对细胞线粒体膜电位的影响

    Institute of Scientific and Technical Information of China (English)

    张媛媛; 刘哲; 张倩雯; 晁振华; 张配; 夏飞; 蒋琛琛; 刘浩; 蒋志文

    2013-01-01

    目的探讨糖酵解抑制剂3-溴丙酮酸(3-BrPA)诱导乳腺癌细胞SK-BR-3凋亡的作用及其可能相关机制。方法MTT法检测3-BrPA对乳腺癌细胞SK-BR-3增殖的抑制作用;碘化丙啶(PI)单染流式细胞术检测细胞凋亡;ATP检测试剂盒检测细胞内ATP水平;DHE荧光探针标记法检测细胞内超氧阴离子水平;线粒体膜电位检测试剂盒(JC-1)检测细胞线粒体膜电位。结果MTT结果显示,3-BrPA可抑制SK-BR-3细胞的增殖活性,且呈浓度和时间依赖性。80、160、320μmol·L-1的3-BrPA诱导SK-BR-3细胞24 h的凋亡率分别为6.7%、22.3%、79.6%。80、160、320μmol·L-13-BrPA作用于SK-BR-3细胞5 h后,细胞内ATP水平与对照组相比分别为87.7%、60.6%、23.7%。160μmol·L-1的3-BrPA增加SK-BR-3细胞中活性氧的生成,同时使细胞线粒体膜电位降低。结论3-BrPA可以抑制乳腺癌细胞SK-BR-3的增殖活性,引起线粒体膜电位降低,并且诱导其凋亡,机制可能与抑制肿瘤细胞的糖酵解从而减少ATP的产生并升高细胞内活性氧的水平有关。%Objective To study the effect of glycolysis inhibitor 3-bromopyruvate (3-BrPA) in inducing apoptosis of human breast carcinoma cells SK-BR-3 and the possible mechanism. Methods MTT assay was used to detect the growth inhibition induced by 3-BrPA in breast cancer cells SK-BR-3. The apoptotic cells were detected by flow cytometry with propidium iodide (PI). ATP levels in the cells were detected by ATP assay kit, and DHE fluorescent probe technique was used to determine superoxide anion levels; the mitochondrial membrane potential was assessed using JC-1 staining assay. Results MTT assay showed that the proliferation of SK-BR-3 cells was inhibited by 3-BrPA in a time- and concentration-dependent manner. Exposure to 80, 160, and 320μmol·L-1 3-BrPA for 24 h resulted in cell apoptosis rates of 6.7%, 22.3%, and 79.6%, respectively, and the intracellular ATP levels of SK

  6. RNA干扰下调HE4基因表达对人卵巢癌SK-OV-3细胞增殖和侵袭的影响%Effect of HE4 gene silenced by siRNA on the proliferation and invasiveness of ovarian cancer cell SK-OV-3

    Institute of Scientific and Technical Information of China (English)

    房青; 王在; 游嘉; 詹雪梅; 杨爱莲; 魏继红; 房昭

    2014-01-01

    目的应用 RNA 干扰技术下调人附睾蛋白 HE4基因表达水平,观察 HE4对人卵巢癌 SK-OV-3细胞增殖和侵袭能力的影响。  方法化学合成3对 HE4特异性小分子干扰 RNA ( siRNA ),脂质体法转染人卵巢癌细胞系 SK-OV-3( HE4-siRNA 组),同时以非特异序列 siRNA 转染的SK-OV-3细胞(阴性对照组)和正常培养的 SK-OV-3细胞(正常对照组)为对照,于转染后48 h,采用实时荧光定量 PCR 技术(RT-qPCR)和 Western blot 方法分别检测HE4 mRNA 及蛋白表达水平。采用 CCK8试剂盒检测卵巢癌细胞增殖活性的变化,穿膜小室模型测定 HE4对细胞侵袭能力的影响。  结果与正常对照组相比,HE4-siRNA 转染卵巢癌SK-OV-3细胞48 h 后,HE4 mRNA 的表达水平显著下降,仅为正常对照组的12.7%(P0.05)。HE4-siRNA 下调卵巢癌 SK-OV-3细胞 HE4表达后,细胞增殖受到明显抑制,细胞增殖活性仅为正常对照组的60%,阴性对照组细胞增殖未见明显变化。体外侵袭实验显示,HE4-siRNA 组穿膜细胞数为每视野(21.8±2.86)个,显著低于正常对照组(187.4±11.17)个(P 0.05)。  结论 HE4特异性 siRNA 能成功下调 SK-OV-3细胞中HE4基因的表达,显著降低卵巢癌细胞增殖和侵袭能力, HE4有可能成为人卵巢癌侵袭转移防治的重要靶点。%Objective To investigate the effect of HE4 gene knocked down by small interfering RNA (siRNA) on proliferation and invasiveness of ovarian cancer cell SK-OV-3. Methods 3 pairs of synthetic siRNAs targeted HE4 gene were transiently transfected into SK-OV-3 cells by liposomal method (HE4-siRNA group), siRNA of scrambled sequence were transfected at the same time as a negative control, and normal cultured SK-OV-3 without any transfection were used as normal control. HE4 expression level in SK-OV-3 cells was determined using real-time quantitative PCR method and Western blot. CCK8 assay was

  7. 苦参碱联合顺铂对人肾母细胞瘤SK-NEP-1细胞PDCD4表达的影响%Effect of matrine combined with cisplatin on survival and apoptosis of SK-NEP-1 cells

    Institute of Scientific and Technical Information of China (English)

    毛玲; 薛天阳; 许伟

    2014-01-01

    Objective Objective To explore the effects of matrine and cisplatin on survival and apoptosis of nephroblastoma cell line SK-NEP-1 , and its potential mechanism. Methods SK-NEP-1 cells were treated with different concentration of Matrine and cisplatin individually or in combination.Trials were divided into following groups:control group,cisplatin intervention group, matrine intervention group,and matrine combined with cisplatin intervention group.The survival rate of SK-NEP-1 cells treated with different concentration of Matrine and cisplatin was detected by MTT colorimetric assay.Apoptosis rate of them by flow cytometry(FCM).RT-PCR analysis was employed to measure the PDCD4 mRNA expression.Results There was significant difference in survival and apoptosis of SK-NEP-1 cells between each group and control group (P<0.05 ),The survival rate and apoptosis of SK-NEP-1 cells was statistically significant between Matrine group and Matrine combined with cisplation group (P <0.05 );and also between the Matrine joint cisplation group and cisplation intervention group(P <0.05 ).Compared with control group ,the expression of PDCD4 mRNA was increased significantly in matrine intervention group,cisplatin intervention group,and matrine combined with cisplatin intervention group (P <0.05 ).Combined with matrine and cisplation individual drug group,the expression of PDCD4 mRNA was increased significantly in matrine combined with cisplatin intervention group.Conclusion Matrine could induce apoptosis and inhibit the growth of SK-NEP-1 cells in a does-dependent way .Matrine could increase the sensibility of chemotherapy of cisplatin and this effect is correlated to increase expression of PDCD4.%目的:探讨苦参碱及苦参碱联合顺铂对人肾母细胞瘤SK-NEP-1细胞存活及凋亡的影响,以及可能的作用机制。方法苦参碱、顺铂单独及联合作用SK-NEP-1细胞,实验分对照组、顺铂干预组、苦参碱干预组、苦参碱联合顺铂干预组

  8. Etteheited räsivad pidu / Henri Reeder, Ly Rääsk, Heli Jürgenson ... [jt.] ; intervjueerinud Anneli Aasmäe

    Index Scriptorium Estoniae

    2009-01-01

    Küsimustele tänavusele üldlaulu- ja üldtantsupeole minekust ja peo repertuaari raskusest vastavad Aruküla noortekoori laulja Henri Reeder, Äksi segakoori dirigent Ly Rääsk, üldlaulupeo segakooride liigijuht Heli Jürgenson, Laulu- ja Tantsupeo SA muusikatoimetaja Ave Sopp, Laulu- ja Tantsupeo SA tantsutoimetaja Kadri Tiis , Lüganuse segakoori dirigent Priit-Andres Pärtna ja kolme tantsurühma juhendaja Vändrast Kädi Pärnoja

  9. Etteheited räsivad pidu / Henri Reeder, Ly Rääsk, Heli Jürgenson ... [jt.] ; intervjueerinud Anneli Aasmäe

    Index Scriptorium Estoniae

    2009-01-01

    Küsimustele tänavusele üldlaulu- ja üldtantsupeole minekust ja peo repertuaari raskusest vastavad Aruküla noortekoori laulja Henri Reeder, Äksi segakoori dirigent Ly Rääsk, üldlaulupeo segakooride liigijuht Heli Jürgenson, Laulu- ja Tantsupeo SA muusikatoimetaja Ave Sopp, Laulu- ja Tantsupeo SA tantsutoimetaja Kadri Tiis , Lüganuse segakoori dirigent Priit-Andres Pärtna ja kolme tantsurühma juhendaja Vändrast Kädi Pärnoja

  10. Expression of the Small Conductance Ca(2+)-Activated Potassium Channel Subtype 3 (SK3) in Rat Uterus after Stimulation with 17β-Estradiol

    DEFF Research Database (Denmark)

    Rahbek, Mette; Nazemi, Sasan; Odum, Lars

    2014-01-01

    Preterm births accounts for roughly 9% of all births worldwide and can have detrimental or even lethal consequences for the infant. However to develop new treatment that will lower the rate of preterm births, more knowledge is required on the factors contributing to the contraction and relaxation...... of the myometrium. The small conductance Ca(2+)-activated potassium channel subtype 3 (SK3) has been identified in the myometrium of several species including humans, mice and rats, but with great inter species variation of the expression pattern and regulation. The aim of this study was to investigate...

  11. Effects of Down-regulating BMP9 on Proliferation and Migration of Human Breast Cancer SK-BR-3 Cells and Its Possible Mechanism in Simulated Bone Microenvironment in vitro%在体外模拟的骨微环境中下调BMP9对人乳腺癌SK-BR-3细胞增殖、迁移的影响及其可能机制

    Institute of Scientific and Technical Information of China (English)

    陈莹莹; 王维; 刘月红; 万绍恒; 张志慧; 王婷; 王晋蜀; 张彦

    2013-01-01

    探讨在体外模拟的乳腺癌骨转移微环境中,采用RNAi技术下调骨形态发生蛋白9(bone morphogenetic protein 9,BMP9)基因对人乳腺癌SK-BR-3细胞增殖、迁移的影响及可能机制.用Transwell小室将空白组SK-BR-3细胞、感染腺病毒AdRFP的对照组SK-BR-3/RFP细胞、感染腺病毒AdsiBMP9的实验组SK-BR-3/siBMP9细胞分别与人骨髓基质HS-5细胞间接共培养后,MTT增殖实验、划痕愈合实验、Transwell迁移实验分别检测下调BMP9对SK-BR-3细胞增殖、迁移的影响;RT-PCR和Western blot法检测相关因子的变化.结果显示,在共培养体系中,SK-BR-3/siBMP9组的BMP9显著低于对照组(P<0.05);下调BMP9可有效促进SK-BR-3/siBMP9细胞增殖P<0.05),SK-BR-3/siBMP9细胞的划痕愈合率、穿膜细胞数也明显升高(P<0.05); SK-BR-3/siBMP9组血管内皮细胞生长因子(VEGF)、结缔组织生长因子(CTGF) mRNA和蛋白表达均显著上调(P<0.05),且Western blot结果显示p-AKT显著上调(P<0.05).综上,在骨转移微环境中,干扰BMP9表达可促进人乳腺癌SK-BR-3细胞增殖及迁移,其作用机制可能与上调VEGF、CTGF表达有关,且这个过程可能涉及PI3K/AKT通路的激活.

  12. BMP9 inhibits proliferation and metastasis of HER2-positive SK-BR-3 breast cancer cells through ERK1/2 and PI3K/AKT pathways.

    Directory of Open Access Journals (Sweden)

    Wei Ren

    Full Text Available Bone morphogenetic protein 9 (BMP9, a member of TGF-β superfamily, is reported to inhibit the growth and migration of prostate cancer, osteosarcoma and triple-negative MDA-MB-231 breast cancer cells. However, little is known about the effect of on the biological behaviors of HER2-positive SK-BR-3 breast cancer cells and the underlying mechanisms. This study aimed to investigate the effects of BMP9 on the proliferation and metastasis of SK-BR-3 cells with BMP9 over-expression or BMP9 down-regulated expression. Results indicated that exogenously expressed BMP9 inhibited the proliferation and metastasis of SK-BR-3 cells while decreased endogenous BMP9 expression in SK-BR-3 cells promoted the proliferation and migration of breast cancer cells in vitro and in vivo. In SK-BR-3 cells with BMP9 over-expression, the phosphorylation of HER2, ERK1/2 and AKT was markedly suppressed and the HER2 expression decreased at both mRNA and protein levels, while opposite results were observed in SK-BR-3 cells with BMP9 knock down. When the phosphorylation of ERK1/2 and PI3K/AKT was inhibited by PD98059 and LY294002, respectively, the decreased proliferation and invasion induced by BMP9 knock down were eliminated. These findings suggest that BMP9 can inhibit the proliferation and metastasis of SK-BR-3 cells via inactivating ERK1/2 and PI3K/AKT signaling pathways. Thus, BMP9 may serve as a useful agent in the treatment of HER-2 positive breast cancer.

  13. BMP9 inhibits proliferation and metastasis of HER2-positive SK-BR-3 breast cancer cells through ERK1/2 and PI3K/AKT pathways.

    Science.gov (United States)

    Ren, Wei; Liu, Yuehong; Wan, Shaoheng; Fei, Chang; Wang, Wei; Chen, Yingying; Zhang, Zhihui; Wang, Ting; Wang, Jinshu; Zhou, Lan; Weng, Yaguang; He, Tongchuan; Zhang, Yan

    2014-01-01

    Bone morphogenetic protein 9 (BMP9), a member of TGF-β superfamily, is reported to inhibit the growth and migration of prostate cancer, osteosarcoma and triple-negative MDA-MB-231 breast cancer cells. However, little is known about the effect of on the biological behaviors of HER2-positive SK-BR-3 breast cancer cells and the underlying mechanisms. This study aimed to investigate the effects of BMP9 on the proliferation and metastasis of SK-BR-3 cells with BMP9 over-expression or BMP9 down-regulated expression. Results indicated that exogenously expressed BMP9 inhibited the proliferation and metastasis of SK-BR-3 cells while decreased endogenous BMP9 expression in SK-BR-3 cells promoted the proliferation and migration of breast cancer cells in vitro and in vivo. In SK-BR-3 cells with BMP9 over-expression, the phosphorylation of HER2, ERK1/2 and AKT was markedly suppressed and the HER2 expression decreased at both mRNA and protein levels, while opposite results were observed in SK-BR-3 cells with BMP9 knock down. When the phosphorylation of ERK1/2 and PI3K/AKT was inhibited by PD98059 and LY294002, respectively, the decreased proliferation and invasion induced by BMP9 knock down were eliminated. These findings suggest that BMP9 can inhibit the proliferation and metastasis of SK-BR-3 cells via inactivating ERK1/2 and PI3K/AKT signaling pathways. Thus, BMP9 may serve as a useful agent in the treatment of HER-2 positive breast cancer.

  14. Składniki tworzyw sztucznych zaburzające funkcje układu nerwowego

    Directory of Open Access Journals (Sweden)

    Konrad Andrzej Szychowski

    2013-05-01

    Full Text Available Rozwój przemysłu chemicznego spowodował opracowywanie nowych związków chemicznych niewystępujących w środowisku naturalnym. Substancje te spełniają różnorodne funkcje, takie jak obniżenie palności, zwiększenie plastyczności czy poprawienie rozpuszczalności innych substancji. Wiele związków wchodzących w skład tworzyw sztucznych, kosmetyków nowej generacji, aparatury medycznej, opakowań spożywczych oraz innych produktów codziennego użytku, z łatwością uwalniają się do środowiska naturalnego. Liczne badania wykazały, że substancje, takie jak: ftalany, BPA, TBBPA oraz PCB charakteryzują się znaczną lipofilnością dzięki czemu w łatwy sposób wnikają do żywych komórek oraz akumulują się w tkankach i narządach. Niesie to za sobą zagrożenie dla zdrowia ludzi i zwierząt. Wymienione związki, ze względu na swoją budowę chemiczną, są zdolne do naśladowania endogennych hormonów np. estradiolu, zaburzając hormonalną homeostazę organizmu. Co więcej substancje te z łatwością pokonują barierę łożyskową oraz barierę krew-mózg i dlatego, jak wykazały liczne badania, zaburzają prawidłowe działanie układu nerwowego już od najwcześniejszych chwil życia. Udowodniono, że związki te wpływają na proces neurogenezy oraz transmisję synaptyczną, a w konsekwencji zaburzają proces kształtowania się płci mózgu, a także procesy uczenia, pamięci, zachowania. Ponadto ich cytotoksyczne i proapoptotyczne działanie może być przyczyną powstawania chorób neurodegeneracyjnych. Praca przedstawia aktualny stan wiedzy na temat oddziaływania ftalanów, BPA, TBBPA, oraz PCB na układ nerwowy.

  15. Contribution of SK and BK channels in the control of catecholamine release by electrical stimulation of the cat adrenal gland.

    Science.gov (United States)

    Montiel, C; López, M G; Sánchez-García, P; Maroto, R; Zapater, P; García, A G

    1995-07-15

    on catecholamine release induced by electrical stimulation was observed at low but not at high [Ca2+]o. 6. Simultaneous release of acetylcholine and catecholamines upon electrical stimulation was achieved in glands in which the endogenous acetylcholine stores in the splanchnic nerve terminals had been prelabelled by perfusion with [3H]choline. While apamin enhanced more than 2-fold the postsynaptic release of catecholamines, the presynaptic release of acetylcholine remained unaffected. 7. The results are compatible with the hypothesis that, under physiological conditions, Ca(2+)-activated SK channels present in chromaffin cells control the firing patterns of action potentials induced by the acetylcholine released from splanchnic nerves during stress.(ABSTRACT TRUNCATED AT 400 WORDS)

  16. Contribution of SK and BK channels in the control of catecholamine release by electrical stimulation of the cat adrenal gland.

    Science.gov (United States)

    Montiel, C; López, M G; Sánchez-García, P; Maroto, R; Zapater, P; García, A G

    1995-01-01

    on catecholamine release induced by electrical stimulation was observed at low but not at high [Ca2+]o. 6. Simultaneous release of acetylcholine and catecholamines upon electrical stimulation was achieved in glands in which the endogenous acetylcholine stores in the splanchnic nerve terminals had been prelabelled by perfusion with [3H]choline. While apamin enhanced more than 2-fold the postsynaptic release of catecholamines, the presynaptic release of acetylcholine remained unaffected. 7. The results are compatible with the hypothesis that, under physiological conditions, Ca(2+)-activated SK channels present in chromaffin cells control the firing patterns of action potentials induced by the acetylcholine released from splanchnic nerves during stress.(ABSTRACT TRUNCATED AT 400 WORDS) Images Figure 3 Figure 4 Figure 6 PMID:7473208

  17. Inhibitory effect of c-erbB2 antisense oligodeoxynucleotide combined with taxol on proliferation of SK-Br-3 cells%c-erbB2反义寡脱氧核苷酸联合紫杉醇对乳腺癌细胞SK-Br-3的抑制作用

    Institute of Scientific and Technical Information of China (English)

    彭志平; 蒋明东; 王树斌; 尹晓玲; 张清华; 李少林

    2009-01-01

    目的:探讨以c-erbB2 mRNA为靶点的反义寡脱氧核苷酸(ASODN)联合紫杉醇对乳腺癌SK-Br-3细胞的抑制作用.方法:实验分为7组:ASODN组,紫杉醇组,赫赛汀组,表阿霉素组,ASODN+紫杉醇组,赫赛汀+紫杉醇组,表阿霉素+紫杉醇组.分别处理乳腺癌SK-Br-3细胞72 h,MTT法测定细胞抑制率,中效原理判定药物联合应用的效果,WesternBlot检测细胞c-erbB2,Bcl-2蛋白表达水平.结果:各组中SK-Br-3细胞的抑制率均随药物浓度的增加而增大;紫杉醇的中效浓度紫杉醇组为0.14 umol/L;ASODN+紫杉醇组为0.07umol/L,其合用指数(CI)<1,为协同作用.ASODN+紫杉醇组c-erbB2,Bcl-2蛋白表达明显低于紫杉醇组,两组相比较,差异具有统计学意义(P<0.05).结论:ASODN可明显增强紫杉醇对乳腺癌SK-Br-3细胞的抑制效应,可明显降低紫杉醇的用药量.

  18. Influence of adenovirus vector-mediated RNAi on expression of c-Met in SK-BR-3 cells%腺病毒载体介导的RNAi对SK-BR-3细胞c-Met表达的影响

    Institute of Scientific and Technical Information of China (English)

    赵慧; 陈东; 袁振华; 王忠山; 吴小兵

    2006-01-01

    目的:通过腺病毒载体介导的RNA干扰技术抑制乳腺癌细胞HGF受体c-Met的表达,抑制乳腺癌细胞增殖、诱导细胞凋亡.方法:PCR法获得人U6启动子及带有c-Met反向互补靶序列的片段HU6shmet;利用腺病毒载体将其传递至SK-BR-3细胞;RNA狭缝杂交检测SK-BR-3细胞c-Met mRNA水平,Western印迹检测c-Met蛋白水平.结果:获得了带有人U6启动子及c-Met反向互补靶序列的重组腺病毒载体rAdUshmet1和rAdUshmet2.转导了重组腺病毒的SK-BR-3细胞的c-Met mRNA和蛋白相对表达量均有所下降.结论:腺病毒载体rAdUshmet通过抑制HGF受体c-Met表达,能在一定程度上阻断HGF-c-Met信号转导通路,有可能成为对乳腺癌进行基因治疗的有效载体.

  19. Study on the effect of PDGF-D shRNA on proliferation and invasion of breast cancer SK-BR-3 cells%PDGF-D 稳定沉默后对乳腺癌细胞 SK-BR-3生物学功能的影响

    Institute of Scientific and Technical Information of China (English)

    李红昌; 冯雯; 陈亚峰; 梅怡; 蔡含; 蒋一鸣; 陈腾; 殷佩浩; 奉典旭

    2016-01-01

    目的:通过慢病毒载体沉默乳腺癌细胞系 SK - BR -3中血小板衍生生长因子 D(PDGF - D)基因的表达,探讨 PDGF - D 基因沉默后对乳腺癌细胞增殖、凋亡及迁移的调控作用。方法应用 RT - PCR 及蛋白质印迹方法检测5种乳腺癌细胞系中 PDGF - D 的表达状况;设计人 PDGF - D 基因的 shRNA 慢病毒载体,在293T 细胞中包装病毒并感染 PDGF - D 高表达的乳腺癌细胞系,运用蛋白质免疫印迹的方法鉴定其对 PDGF - D 基因的沉默效果;PDGF - D基因沉默后通过细胞增殖实验和软琼脂克隆形成实验检测其对细胞增殖能力的影响,并应用流式细胞技术检测细胞凋亡;运用 Transwell 迁移实验检测细胞的体外侵袭迁移能力。结果 PDGF - D 在5种细胞系中存在差异性表达,其中具有低转移潜能的 HT -29和 SK - BR -3细胞与具有高转移潜能的 LOVO、RKO 和 SW620细胞相比,具有更高的 PDGF -D 表达水平( t =3.880,P <0.05)。选取低转移细胞株中 PDGF - D 表达相对较高的 SK - BR -3作为研究对象,构建PDGF - D shRNA 慢病毒载体沉默 SK - BR -3细胞中 PDGF - D 的表达,蛋白质免疫印迹结果提示,PDGF - D 稳定沉默的 SK - BR -3细胞系构建成功;在稳定沉默 PDGF - D 基因后,MTT 细胞增殖实验和软琼脂克隆形成实验表明 SK - BR-3细胞增殖能力增强( F =75.23,P <0.001);流式细胞技术检测显示 PDGF - D 基因沉默后可抑制 SK - BR -3细胞凋亡( F =84.44,P <0.001);细胞小室实验结果显示,PDGF - D 沉默后 SK - BR -3迁移能力增强( F =155.9,P <0.001)。结论 PDGF - D 基因可能与乳腺癌的细胞增殖、凋亡与转移有关,进而参与了乳腺癌的发生、发展。%Objective The shRNA lentiviral vector was constructed to silence PDGF - D expression in BrCa cells,in order to explore the role of PDGF - D in proliferation,apoptosis and migration

  20. siRNA抑制人乳腺癌SK-BR-3细胞株VEGF基因表达的实验研究%Inhibition of siRNA on VEGF expression in SK-BR-3 cells:An experimental study

    Institute of Scientific and Technical Information of China (English)

    李霞; 王宏伟; 李伟; 孙志军; 秦迎

    2010-01-01

    目的 研究siRNA(small interfering,RNA)对乳腺癌细胞SK-BR-3的VEGF基因表达的抑制作用,为RNAi技术在肿瘤生物治疗中的应用提供实验基础.方法 体外合成一条针对VEGF基因的siRNA,使用脂质体转染的方法导入细胞,观察转染后乳腺癌细胞SK-BR-3的增殖变化,MTT法检测细胞存活率,RT-PCR检测转染后VEGF mRNA表达水平的变化,ELISA检测蛋白表达的下降效果.结果 所设计的siRNA能有效抑制乳腺癌细胞的生长;降低了 VEGF mRNA的表达;蛋白表达水平也显著降低.作为阴性对照的错义序列组siRNA则没有这种效果,不起作用.结论 siRNA可以有效抑制细胞株SK-BR-3中VEGF的表达,从而抑制细胞生长.应用RNA干扰技术可以有效抑制肿瘤细胞的增殖.

  1. Y 盒结合蛋白1在 SK-BR-3乳腺癌细胞增殖中的作用%Roles of Y box-binding protein 1 in SK-BR-3 breast cancer proliferation

    Institute of Scientific and Technical Information of China (English)

    史建红; 吕心瑞; 王冰; 林丹丹; 王亚婻; 步玉辉; 马振峰

    2014-01-01

    Objective To explore the roles of Y box-binding protein 1 (YB-1) in breast cancer cell proliferation.Methods Twenty cases of surgical removal of breast cancer tissue ( diagnosed with invasive ductal carcinoma , stage Ⅱ, by postoperative paraffin pathology ) and normal breast tissues adjacent to carcinoma were collected during June 2013 to August 2013.Quantitative real-time PCR ( qRT-PCR ) was performed to detect the YB1 mRNA levels.Cultured mammary epithelial cells (HBL-100) and breast cancer cells (MCF7, MDA-MB-231 &SK-BR-3 cells) were harvested and qRT-PCR was performed to detect the YB1 mRNA levels.SK-BR-3 cells were stimulated with various concentrations of PDGF-BB and YB1 expression levels were detected by qRT-PCR.Down-regulation or over-expression of YB1 by si-YB1 or Ad-GFP-YB1 was detected in SK-BR-3 cells.And MTS cell proliferation assay kit was used to detect cell proliferation.Results YB1 mRNA levels were significantly higher in breast cancer tissues and MDA-MB-231 and SK-BR-3 breast cancer cell lines than that in adjacent normal breast tissues and HBL -100 mammary epithelial cells respectively ( P<0.05 ).YB1 expression levels increased in PDGF-BB stimulated SK-BR-3 cells in a dose-dependent manner.Conclusion A down-regulation of endogenous YB 1 decreases and an over-expression of exogenous YB 1 promotes the proliferation activity in SK-BR-3 cells.%目的:探讨Y盒结合蛋白1(YB1)在乳腺癌细胞增殖中的作用。方法收集河北大学附属医院2013年6-8月的乳腺浸润性导管癌及癌旁正常乳腺组织标本,实时定量PCR( qRT-PCR)分析YB1基因的mRNA水平;培养乳腺上皮细胞HBL-100和乳腺癌细胞MCF-7、MDA-MB-231和SK-BR-3,qRT-PCR 观察 YB1的表达水平, MTS 法分析细胞增殖活力;血小板源性生长因子 BB ( PDGF-BB)刺激SK-BR-3细胞,观察YB1的表达水平;应用特异性小干扰RNA敲低内源性YB1或应用GFP-YB1腺病毒载体过表达外源性GFP-YB1,MTS

  2. Influence and Significance of Herceptin on the Notch-1 Signaling Pathway in Breast Cancer SK-BR3 Cells%赫赛汀对乳腺癌SK-BR3细胞Notch-1信号通路的影响及意义

    Institute of Scientific and Technical Information of China (English)

    韩铭; 邓华瑜; 隆玲; 姜蓉

    2011-01-01

    Objective: To investigate the effects and mechanism of action of herceptin on Notch-1 protein in breast cancer SK-BR3 cells, and to explore the significance of Notch-1 signaling pathway in breast cancer cell resistance to herceptin.Methods: The breast cancer cells SK-BR3 with HER2 overexpression and MDA-MB-231 overexpression with HER2 non-overexpression were selected.Immunocytochemistry and Western-blot analysis were used to detect the expression of Notch-1 protein and activate Notch-1 ( Notch-1IC ) in the SK-BR3 and MDA-MB-231 cells, respectively.SK-BR3 cells were treated with herceptin.Western blot analysis was used to detect the expression of Notch-1IC and HER2 proteins.Reverse transcriptase polymerase chain reaction was used to assay HES-1 mRNA expression.Co-immunoprecipitation detected the interaction between HER2 and Notch-1 proteins in the SK-BR3 cells.Results: The level of Notch-1IC nucleic localization and the expression of Notch-1IC protein in SK-BR3 cells ( 9.37 ± 0.64 ) were significantly lower than in the MDA-MB-231 cells ( 21.665 ± 1.11 ) ( P < 0.01 ).SK-BR3 cells were treated with herceptin.Compared with the controls, the expression of Notch-1IC protein and HES-1 mRNA was significantly increased ( P < 0.01 ).There was no apparent change in HER2 protein expression after herceptin treatment ( F = 0.973, P > 0.05 ).Co-immunoprecipitation showed coprecipitation between the Notch-1 and HER2 proteins.Conclusion: The activity of Notch-1 protein was decreased in the breast cancer cells with HER2 overexpression.HER2 could combine with Notch-1, thereby negatively regulating Notch-1 activity.Herceptin could increase the activity of Notch-1, which could be associated with the cell resistance.%目的:探讨赫赛汀对乳腺癌SK-BR3细胞Notch-1蛋白的影响及其作用机制,认识Notch-1信号通路在乳腺癌细胞形成赫赛汀耐药中的意义.方法:选用HER-2过表达乳腺癌SK-BR3细胞及HER-2非过表达乳腺癌MDA-MB-231细

  3. Identification of Max binding protein as a novel binding protein of Nck1 and characterization of its role in inhibiting human liver cancer SK-HEP-1 cells

    Institute of Scientific and Technical Information of China (English)

    ZHOU Qi; HUANG Tao; WANG Ya-feng; ZHANG Kun-sun; CHEN Dong; PENG Bao-gang

    2012-01-01

    Background The tendency of tumor cells to disperse throughout the liver is a distinct feature of hepatocellular carcinoma (HCC).Nck family adaptor proteins function to regulate actin cytoskeletal reorganization that leads to cell motility.We previously found that Max binding protein (MNT) was differentially expressed in HCC,and interacted with Nck1 by 2-DE.MNT is a protein member of the Myc/Max/Mad network which plays roles in cell proliferation,differentiation,and death.We investigated the effects of MNT on migration of human liver cancer SK-HEP-1 cells to study the migration regulatory role of MNT in HCC cells.Methods Interaction between MNT and Nck1 was further validated in hepatoma cells by GST-pull down assay and immunoprecipitation,siRNAs specific to MNT (MNT siRNA) were used to knockdown MNT expression.Western blotting,transwell assay were used to determine the migration potential of cells.Results Interaction between MNT and Nck1 was validated in hepatoma cells.MNT knockdown promoted the migration of human liver cancer SK-HEP-1 cells (P <0.01 ).Conclusion The results suggest that MNT,via interaction with Nck1,inhibits hepatoma cell migration.

  4. Toxic Nodularia spumigena blooms in the coastal waters of the Gulf of Gdańsk: a ten-year survey

    Directory of Open Access Journals (Sweden)

    Hanna Mazur-Marzec

    2006-06-01

    Full Text Available In the Baltic Sea, summer blooms of the filamentous, nitrogen-fixingcyanobacterium Nodularia spumigena are favoured by high P concentrationsat low N:P ratios and a salinity range of 5-13 PSU. The bloomsare initiated by calm and sunny weather, an elevated surfacewater temperature and thermal stratification. The mass occurrenceof N. spumigena in coastal waters is a matter of special concern,as the cyanobacterium produces nodularin, a potent pentapeptidehepatotoxin. In the Gulf of Gdansk, the large-scale occurrenceof N. spumigena was recorded for the first time in 1994. Bloomsof a similar intensity occurred in 2001, 2003 and 2004. Nodularinconcentrations in freeze-dried bloom samples varied from 0.01to 4.01 mg g-1 d.w. In the coastal waters of the Gulf of Gdańsk,cell-bound nodularin concentrations in 2004 and 2005 attainedmaxima of 25852 ± 107 µg dm-3 and3964 ± 125 µg dm-3, respectively. Microscopic analysis revealedthe presence of diverse N. spumigena forms, with the dominance of curvedfilaments in bloom samples. The results of in situ studies and remotesensing measurements indicate a high frequency and intensity of cyanobacterialblooms in the Gulf of Gdańsk in the last ten years.

  5. Lycopene inhibits reactive oxygen species production in SK-Hep-1 cells and attenuates acetaminophen-induced liver injury in C57BL/6 mice.

    Science.gov (United States)

    Bandeira, Ana Carla Balthar; da Silva, Talita Prato; de Araujo, Glaucy Rodrigues; Araujo, Carolina Morais; da Silva, Rafaella Cecília; Lima, Wanderson Geraldo; Bezerra, Frank Silva; Costa, Daniela Caldeira

    2017-02-01

    Our aim was to investigate the antioxidant potential of lycopene in different experimental liver models: in vitro, to evaluate the influence of lycopene on reactive oxygen species (ROS) production mediated by the PKC pathway and in vivo, to evaluate the protective effects of lycopene in an experimental model of hepatotoxicity. The in vitro study assessed the lycopene antioxidant potential by the quantification of ROS production in SK-Hep-1 cells unstimulated or stimulated by an activator of the PKC pathway. The role of NADPH oxidase was evaluated by measuring its inhibition potential using an inhibitor of this enzyme. In the in vivo study, male C57BL/6 mice received lycopene (10 or 100 mg/kg by oral gavage) and 1 h later, acetaminophen (APAP) (500 mg/kg) was administrated. Lycopene decreased ROS production in SK-Hep-1 cells through inhibition of NADPH oxidase, brought about in the PKC pathway. Lycopene improved hepatotoxicity acting as an antioxidant, reduced GSSG and regulated tGSH and CAT levels, reduced oxidative damage primarily by decreasing protein carbonylation, promoted the downregulation of MMP-2 and reduced areas of necrosis improving the general appearance of the lesion in C57BL/6 mice. Lycopene is a natural compound that was able to inhibit the production of ROS in vitro and mitigate the damage caused by APAP overdose in vivo.

  6. Preparation of Ginsenoside Rg3 and Protection against H2O2-Induced Oxidative Stress in Human Neuroblastoma SK-N-SH Cells

    Directory of Open Access Journals (Sweden)

    Gang Li

    2014-01-01

    Full Text Available The aim of this study is to evaluate the protection of ginsenoside Rg3 against oxidative stress in human neuroblastoma SK-N-SH cells. 20(R-ginsenoside Rg3 (20(R-Rg3 and 20(S-ginsenoside Rg3 (20(S-Rg3 were prepared by the method of chemical degradation and column chromatography, and the structure of the two compounds was characterized by 1H-NMR and 13C-NMR spectroscopy. MTT assay and LDH leakage assay were used to determine the cell viability and the oxidative stress cellular model was established by means of H2O2 (600 μM for 4 h. We also investigated the changes of intracellular MDA content, SOD activity, and ROS formation after the treatment of ginsenoside Rg3 for 20 h. The results indicated that both 20 (R-Rg3 and 20 (S-Rg3 had obvious protection against H2O2-induced oxidative stress in SK-N-SH cells. Moreover, 20(R-Rg3 exhibited better antioxidant activity than 20(S-Rg3 in vitro. These findings are expected to provide some implication for further research and application of ginsenoside Rg3 in neuroprotection.

  7. A Model for Spheroid versus Monolayer Response of SK-N-SH Neuroblastoma Cells to Treatment with 15-Deoxy-PGJ2

    Directory of Open Access Journals (Sweden)

    Dorothy I. Wallace

    2016-01-01

    Full Text Available Researchers have observed that response of tumor cells to treatment varies depending on whether the cells are grown in monolayer, as in vitro spheroids or in vivo. This study uses data from the literature on monolayer treatment of SK-N-SH neuroblastoma cells with 15-deoxy-PGJ2 and couples it with data on growth rates for untreated SK-N-SH neuroblastoma cells grown as multicellular spheroids. A linear model is constructed for untreated and treated monolayer data sets, which is tuned to growth, death, and cell cycle data for the monolayer case for both control and treatment with 15-deoxy-PGJ2. The monolayer model is extended to a five-dimensional nonlinear model of in vitro tumor spheroid growth and treatment that includes compartments of the cell cycle (G1,S,G2/M as well as quiescent (Q and necrotic (N cells. Monolayer treatment data for 15-deoxy-PGJ2 is used to derive a prediction of spheroid response under similar treatments. For short periods of treatment, spheroid response is less pronounced than monolayer response. The simulations suggest that the difference in response to treatment of monolayer versus spheroid cultures observed in laboratory studies is a natural consequence of tumor spheroid physiology rather than any special resistance to treatment.

  8. EGF stimulates Pit-1 independent transcription of the human prolactin pituitary promoter in human breast cancer SK-BR-3 cells through its proximal AP-1 response element.

    Science.gov (United States)

    Manfroid, Isabelle; Van de Weerdt, Cécile; Baudhuin, Ariane; Martial, Joseph A; Muller, Marc

    2005-01-14

    Normal and neoplastic human mammary gland cells are targets for the proliferative action of prolactin. These cells also synthesize prolactin, thereby inducing an autocrine/paracrine proliferative loop. We present the first extensive analysis of the transcriptional regulation of the human prolactin gene (hPRL) in human mammary tumor cells, SK-BR-3. We show that the pituitary promoter is functional in these cells in the absence of the pituitary-specific factor Pit-1. Expression of exogenous Pit-1 or epidermal growth factor (EGF) treatment stimulates the transfected hPRL pituitary promoter and the endogenous hPRL expression. EGF stimulation is mediated by increased synthesis of c-fos and c-jun, resulting in AP-1 binding to the proximal hPRL pituitary promoter. This regulation involves the EGF receptor, possibly ErbB2 that is highly expressed in SK-BR-3 cells, and a PI3K/JNK pathway. The stimulation of hPRL gene transcription by EGF in mammary cells may include hPRL in a complex regulatory network controlling growth of human mammary cells.

  9. TIMP-1 overexpression does not affect sensitivity to HER2-targeting drugs in the HER2-gene-amplified SK-BR-3 human breast cancer cell line.

    Science.gov (United States)

    Deng, Xiaohong; Fogh, Louise; Lademann, Ulrik; Jensen, Vibeke; Stenvang, Jan; Yang, Huanming; Brünner, Nils; Schrohl, Anne-Sofie

    2013-04-01

    Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been suggested as a marker of prognosis and response to treatment in breast cancer. In vitro, TIMP-1 can regulate shedding of the extracellular domain of HER2 and signalling via the Akt pathway, and we hypothesize that TIMP-1 therefore can affect sensitivity to the HER2-targeting drugs trastuzumab and lapatinib. SK-BR-3 human breast cancer cells were stably transfected with TIMP-1, characterized with regard to TIMP-1 protein expression, proliferation, and functionality of the secreted TIMP-1, and the sensitivity to trastuzumab and lapatinib was studied in five selected single-cell subclones expressing TIMP-1 protein at various levels plus the parental SK-BR-3 cell line. Both trastuzumab and lapatinib reduced cell viability, as determined by MTT assay, but the sensitivity to the drugs was not associated with the expression level of TIMP-1 protein. Western blotting showed that the activation of Akt, PTEN, and HER2 as well as ADAM10 was similar in all clones. In conclusion, in this model, TIMP-1 overexpression does not affect HER2 cleavage by ADAM10 or signalling via the Akt pathway, and TIMP-1 does not influence sensitivity to trastuzumab and lapatinib.

  10. Application of geochemical logging for palaeoenvironmental research in the Late Cretaceous Qingshankou Formation from the Chinese Continental Scientific Drilling Project-SK-2e, Songliao Basin, NE China

    Science.gov (United States)

    Peng, Cheng; Zou, Changchun; Pan, Li; Niu, Yixiong

    2017-08-01

    The Chinese Continental Scientific Drilling Project of the Cretaceous Songliao Basin (CCSD-SK) provides an excellent opportunity to understand the response of terrestrial environments to greenhouse climate change in the Cretaceous. We conducted a palaeoenvironmental study of the Late Cretaceous Qingshankou Formation (K2qn) based on geochemical log data from the SK-2 east borehole. According to the characteristic of Ti mainly from terrigenous minerals, the content of authigenic elements was calculated. Correlation space was proposed to study the variation of the correlation between two log curves along the depth. Palaeoenvironmental proxies were selected from log data to study the evolution of the climate and lake, productivity of the paleolake, and organic matter deposition. The results demonstrate that the productivity of the paleolake was driven by chemical weathering in K2qn, in which the first section of the Qingshankou Formation (K2qn1) has higher productivity than the second and third sections of the Qingshankou Formation (K2qn2+3). The high content of pyrite in several thin layers reveals lake water of high sulfate concentration. This may have been caused by acid rain related to large volcanic activity. In K2qn2+3, several periods of high productivity without the formation of source rocks and high organic matter content were identified. This may show that organic matter deposition was limited by low accommodation space or oxidation environment. Therefore, the preservation condition is suggested as the main controlling factor of organic matter deposition in K2qn.

  11. Model metrik potravinářské firmy a jeho ověření v nástroji Business Intelligence

    OpenAIRE

    Klapal, David

    2007-01-01

    Diplomová práce se zabývá problematikou strategického měření výkonnosti podniků. Konkrétně je zacílena na měření výkonnosti potravinářské firmy působící na trhu výroby a prodeje surovin pro pekaře, cukráře a gastronomii. Řeší především důležitost sledování výkonnosti podniku, ukazuje možné moderní koncepty měření výkonnosti, zabývá se metrikami a odhaluje podstatu multidimenzionálního přístupu. Za pomoci získaných teoretických znalostí je následně vytvořen model metrik potravinářské firmy. Pr...

  12. İstanbul Tasavvuf Kültüründe Bedeviyyenin Yeri ve Üsküdar Bedeviyye Tekkeleri

    OpenAIRE

    Kadir ÖZKÖSE

    2012-01-01

    Bedeviyye Tarîkatı on sekizinciyüzyıldan itibaren İstanbul’da teşkilatlanmasını sürdürmüş, özelde Üsküdargenelde ise İstanbul tasavvuf kültürüne önemli katkılarda bulunmuş birtarîkattır. Kurulan tekkelerin işlevselliği, görevli meşayihin etkinliği,gerçekleştirilen ayinlerin yankıları ile tarîkat İstanbul’da ilgi odağıolmuştur. İstanbul ile Mısır ve Ortadoğu halkları arasında sağlanan ilişkilerde tarîkatın bir diğer katkısıdır. Üsküdar Bedeviyye meşayıhının siyasî,kültürel ve dinî kişilikleri ...

  13. 赖氨大黄酸通过抑制HER-2信号通路诱导乳腺癌SK-Br-3细胞凋亡%Rhein lysinate induces apoptosis in breast cancer SK-Br-3 cells by inhibiting HER-2 signal pathway

    Institute of Scientific and Technical Information of China (English)

    林雅军; 黄云虹; 甄永占; 刘秀均; 甄永苏

    2008-01-01

    为研究赖氨大黄酸(rhein lysinate,RHL)对人乳腺癌细胞株SK-Br-3细胞增殖、凋亡的影响及HER-2信号通路在其中的作用.应用MTT法检测赖氨大黄酸对SK-Br-3细胞增殖的影响;应用流式细胞仪检测细胞周期变化及细胞凋亡;应用Western blotting检测HER-2信号通路蛋白表达水平及蛋白磷酸化水平;应用RT-PCR和免疫化学方法分别检测HER-2 mRNA和蛋白表达水平.结果显示,赖氨大黄酸能有效抑制乳腺癌SK-Br-3细胞增殖,作用48 h的IC50值为85 μmol·L-1,并能诱导其凋亡,随药物浓度的增加,细胞凋亡率也逐渐升高;Western blotting结果显示,赖氨大黄酸抑制HER-2蛋白表达和蛋白磷酸化,抑制NF-κB蛋白表达,升高p53和p21蛋白表达;RT-PCR和免疫化学结果表明,赖氨大黄酸能抑制HER-2 mRNA的转录水平,从而抑制其蛋白表达.因此,赖氨大黄酸能有效抑制SK-Br-3细胞增殖,并诱导其凋亡,HER-2/NF-κB/p53/p21参与了赖氨大黄酸诱导SK-Br-3细胞凋亡的过程.赖氨大黄酸解决了大黄酸不溶于水的难题,并且能够通过HER-2信号通路诱导细胞凋亡,有望成为临床肿瘤辅助化疗药物.

  14. SK变频器在平弯钢化玻璃设备上的应用%Application of SK Frequency Invertor in the Bending Section of Tempering Glass Equipment

    Institute of Scientific and Technical Information of China (English)

    宁波

    2012-01-01

    The SK diver from control techniques are playing an important role at the tempering glass equipment from Luoyang North Glass Co. Ltd. The paper introduces that how the SK drive control the motor in the bending section area, and SK dirver offers the switch function between the speed control and the torque control in the production engineering.%本文讲述了艾默生CT的SK变频器在洛阳北方玻璃技术股份有限公司生产的平弯玻璃钢化设备中的具体应用.详细讲解了SK变频器在该设备的弯风栅段对变弧电机的控制功能,并重点介绍了SK变频器在该工艺中特有的速度控制和转矩控制的切换功能.

  15. Functional analysis of a recombinant PIII-SVMP, GST-acocostatin; an apoptotic inducer of HUVEC and HeLa, but not SK-Mel-28 cells.

    Science.gov (United States)

    Teklemariam, Takele; Seoane, Agustin I; Ramos, Carla J; Sanchez, Elda E; Lucena, Sara E; Perez, John C; Mandal, Stephanie A; Soto, Julio G

    2011-04-01

    Disintegrins and disintegrin-like peptides interact with integrins and interfere with cell-cell and cell-matrix interactions. A disintegrin-like snake venom gene, Acocostatin was cloned from the venom gland mRNA of Agkistrodon contortrix contortrix. Acocostatin belongs to the PIII-SVMP subfamily of disintegrin-like peptides. The recombinant acocostatin peptide was produced and purified as GST-fusion. The GST-acocostatin peptide, at 44 μg/mL, inhibited platelet aggregation by 30% in PRP and 18% in whole blood. In addition GST-acocostatin, at 220 μg/mL, inhibited SK-Mel-28 cell migration by 48%, but did not inhibit T24 cell migration. The GST-acocostatin peptide ability to induce apoptosis on HUVEC, HeLa, and SK-Mel-28 cells was determined using Annexin V-FITC and chromatin fragmentation assays after 24 h of treatment. At 5 μM GST-acocostatin peptide, 19.68%+/- 3.09 of treated HUVEC, and 35.86% +/- 2.05 of treated HeLa cells were in early apoptosis. The GST-acocostatin peptide also caused chromatin fragmentation of HUVEC and HeLa cells as determined by fluorescent microscopy and Hoechst staining. The GST-acocostatin peptide failed to induce apoptosis of SK-Mel-28 cells. We characterized the HUVEC, HeLa, and T24 integrin expression by flow cytometry, as the first step in determining GST-acocostatin binding specificity. Our results indicate that HUVEC express αv, αvβ3, αvβ5, α6, β1, and β3 integrin receptors. HeLa cells express α1, α2, α6, αv, αvβ5, and β1 integrin receptors. T24 cells express α1, α3, α6, αv, αvβ3, αvβ5, β1, β3, and β6 integrin receptors.

  16. Survivin knockdown increased anti-cancer effects of (-)-epigallocatechin-3-gallate in human malignant neuroblastoma SK-N-BE2 and SH-SY5Y cells

    Energy Technology Data Exchange (ETDEWEB)

    Hossain, Md. Motarab [Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC (United States); Banik, Naren L. [Department of Neurosciences, Medical University of South Carolina, Charleston, SC (United States); Ray, Swapan K., E-mail: swapan.ray@uscmed.sc.edu [Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC (United States)

    2012-08-01

    Neuroblastoma is a solid tumor that mostly occurs in children. Malignant neuroblastomas have poor prognosis because conventional chemotherapeutic agents are hardly effective. Survivin, which is highly expressed in some malignant neuroblastomas, plays a significant role in inhibiting differentiation and apoptosis and promoting cell proliferation, invasion, and angiogenesis. We examined consequences of survivin knockdown by survivin short hairpin RNA (shRNA) plasmid and then treatment with (-)-epigallocatechin-3-gallate (EGCG), a green tea flavonoid, in malignant neuroblastoma cells. Our Western blotting and laser scanning confocal immunofluorescence microscopy showed that survivin was highly expressed in malignant neuroblastoma SK-N-BE2 and SH-SY5Y cell lines and slightly in SK-N-DZ cell line. Expression of survivin was very faint in malignant neuroblastoma IMR32 cell line. We transfected SK-N-BE2 and SH-SY-5Y cells with survivin shRNA, treated with EGCG, and confirmed knockdown of survivin at mRNA and protein levels. Survivin knockdown induced morphological features of neuronal differentiation, as we observed following in situ methylene blue staining. Combination of survivin shRNA and EGCG promoted neuronal differentiation biochemically by increases in the expression of NFP, NSE, and e-cadherin and also decreases in the expression of Notch-1, ID2, hTERT, and PCNA. Our in situ Wright staining and Annexin V-FITC/PI staining showed that combination therapy was highly effective in inducing, respectively, morphological and biochemical features of apoptosis. Apoptosis occurred with activation of caspase-8 and cleavage of Bid to tBid, increase in Bax:Bcl-2 ratio, mitochondrial release of cytochrome c, and increases in the expression and activity of calpain and caspase-3. Combination therapy decreased migration of cells through matrigel and inhibited proliferative (p-Akt and NF-{kappa}B), invasive (MMP-2 and MMP-9), and angiogenic (VEGF and b-FGF) factors. Also, in vitro

  17. Involvement of soluble guanylate cyclase alpha(1) and alpha(2), and SK(Ca) channels in NANC relaxation of mouse distal colon.

    Science.gov (United States)

    Dhaese, Ingeborg; Vanneste, Gwen; Sips, Patrick; Buys, Emmanuel; Brouckaert, Peter; Lefebvre, Romain A

    2008-07-28

    In distal colon, both nitric oxide (NO) and ATP are involved in non-adrenergic non-cholinergic (NANC) inhibitory neurotransmission. The role of the soluble guanylate cyclase (sGC) isoforms alpha(1)beta(1) and alpha(2)beta(1), and of the small conductance Ca(2+)-dependent K(+) channels (SK(Ca) channels) in the relaxation of distal colon by exogenous NO and by NANC nerve stimulation was investigated, comparing wild type (WT) and sGCalpha(1) knockout (KO) mice. In WT strips, the relaxation induced by electrical field stimulation (EFS) at 1 Hz but not at 2-8 Hz was significantly reduced by the NO-synthase inhibitor L-NAME or the sGC inhibitor ODQ. In sGCalpha(1) KO strips, the EFS-induced relaxation at 1 Hz was significantly reduced and no longer influenced by L-NAME or ODQ. The SK(Ca) channel blocker apamin alone had no inhibitory effect on EFS-induced relaxation, but combined with ODQ or L-NAME, apamin inhibited the relaxation induced by EFS at 2-8 Hz in WT strips and at 8 Hz in sGCalpha(1) KO strips. Relaxation by exogenous NO was significantly attenuated in sGCalpha(1) KO strips, but could still be reduced further by ODQ. Basal cGMP levels were lower in sGCalpha(1) KO strips but NO still significantly increased cGMP levels versus basal. In conclusion, in the absence of sGCalpha(1)beta(1), exogenous NO is able to partially act through sGCalpha(2)beta(1). NO, acting via sGCalpha(1)beta(1), is the principal neurotransmitter in EFS-evoked responses at 1 Hz. At higher stimulation frequencies, NO, acting at sGCalpha(1)beta(1) and/or sGCalpha(2)beta(1), functions together with another transmitter, probably ATP acting via SK(Ca) channels, with some degree of redundancy.

  18. BMP9 Inhibits Proliferation and Metastasis of HER2-Positive SK-BR-3 Breast Cancer Cells through ERK1/2 and PI3K/AKT Pathways

    OpenAIRE

    Wei Ren; Yuehong Liu; Shaoheng Wan; Chang Fei; Wei Wang; Yingying Chen; Zhihui Zhang; Ting Wang; Jinshu Wang; Lan Zhou; Yaguang Weng; Tongchuan He; Yan Zhang

    2014-01-01

    Bone morphogenetic protein 9 (BMP9), a member of TGF-β superfamily, is reported to inhibit the growth and migration of prostate cancer, osteosarcoma and triple-negative MDA-MB-231 breast cancer cells. However, little is known about the effect of on the biological behaviors of HER2-positive SK-BR-3 breast cancer cells and the underlying mechanisms. This study aimed to investigate the effects of BMP9 on the proliferation and metastasis of SK-BR-3 cells with BMP9 over-expression or BMP9 down-reg...

  19. Upsilon(1S)->gamma+f2'(1525); f2'(1525)->K0sK0s decays

    CERN Document Server

    Besson, D; Pedlar, T K; Cronin-Hennessy, D; Hietala, J; Zweber, P; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A; Xiao, T; Brisbane, S; Martin, L; Powell, A; Spradlin, P; Wilkinson, G; Mendez, H; Ge, J Y; Miller, D H; Shipsey, I P J; Xin, B; Adams, G S; Hu, D; Moziak, B; Napolitano, J; Ecklund, K M; Insler, J; Muramatsu, H; Park, C S; Pearson, L J; Thorndike, E H; Yang, F; Ricciardi, S; Thomas, C; Artuso, M; Blusk, S; Mountain, R; Skwarnicki, T; Stone, S; Wang, J C; Zhang, L M; Bonvicini, G; Cinabro, D; Lincoln, A; Smith, M J; Zhou, P; Zhu, J; Naik, P; Rademacker, J; Asner, D M; Edwards, K W; Randrianarivony, K; Tatishvili, G; Briere, R A; Vogel, H; Onyisi, P U E; Rosner, J L; Alexander, J P; Cassel, D G; Das, S; Ehrlich, R; Fields, L; Gibbons, L; Gray, S W; Hartill, D L; Heltsley, B K; Kreinick, D L; Kuznetsov, V E; Patterson, J R; Peterson, D; Riley, D; Ryd, A; Sadoff, A J; Shi, X; Sun, W M; Yelton, J; Rubin, P; Lowrey, N; Mehrabyan, S; Selen, M; Wiss, J; Libby, J; Kornicer, M; Mitchell, R E; Tarbert, C M

    2011-01-01

    We report on a study of exclusive radiative decays of the Upsilon(1S) resonance into a final state consisting of a photon and two K0s candidates. We find evidence for a signal for Upsilon(1S)->gamma f_2'(1525); f_2'(1525)->K0sK0s, at a rate (4.0+/-1.3+/-0.6)x10^{-5}, consistent with previous observations of Upsilon(1S)->gamma f_2'(1525); f_2'(1525)->K+K-, and isospin. Combining this branching fraction with existing branching fraction measurements of Upsilon(1S)->gamma f_2'(1525) and J/psi->gamma f_2'(1525), we obtain the ratio of branching fractions: B(Upsilon(1S)->gamma f_2'(1525))/B(J/psi->gamma f_2'(1525))=0.09+/-0.02, approximately consistent with expectations based on soft collinear effective theory.

  20. MiR-200a enhances the migrations of A549 and SK-MES-1 cells by regulating the expression of TSPAN1

    Indian Academy of Sciences (India)

    Yaqing Chen; Wei Peng; Yixiang Lu; Jianxin Chen; York Yuanyuan Zhu; Tao Xi

    2013-09-01

    MicroRNA-200a (miR-200a) has been reported to regulate tumour progression in several tumours; however, little is known about its role in non-small cell lung cancer cells (NSCLCs). Here, we found that miR-200a was up-regulated in A549 and SK-MES-1 cells compared with normal lung cells HELF. By a series of gain-of-function and loss-offunction studies, over-expression of miR-200a was indicated to enhance cells migration, and its knock-down inhibited migration of cells in NSCLC cell lines. Furthermore, miR-200a was identified to induce TSPAN1 expression which was related to migration. TSPAN1 was proved to induce migration, and so up-regulation of TSPAN1 by miR-200a may explain why over-expressing miR-200a promotes NSCLC cells migration.

  1. Non-native crab Rhithropanopeus harrisii (Gould, 1984 - a new component of the benthic communities in the Gulf of Gdańsk (southern Baltic Sea

    Directory of Open Access Journals (Sweden)

    Joanna Hegele-Drywa

    2014-01-01

    Full Text Available The aim of this study was to determine the occurrence, spatial distribution and abundance pattern of the Harris mud crab Rhithropanopeus harrisii in the Gulf of Gdańsk (southern Baltic Sea. Between 2006 and 2010, this species was found at 69 out of 129 sampling stations, at depths from 0 to 20 m. Two main aggregations of the Harris mud crab were established: (1 in Puck Bay (max. density 19 indiv. 100 m-2 and (2 in the Gdynia and Sopot area (max. density 5 indiv. 100 m-2. 920 specimens were collected during the whole sampling period: 150 juveniles, 370 females and 400 males. The minimum measured carapace width was 1.96 mm, the maximum 21.40 mm (mean 9.03 ±4.11 mm.

  2. Využití biomasy pro získávání elektřiny v ostrovních provozech

    OpenAIRE

    Roule, Jaroslav

    2013-01-01

    Diplomová práce pojednává o využití biomasy pro získávání elektřiny v ostrovních provozech. V první kapitole je vysvětlen pojem biomasa a její rozdělení. Dále je zde uveden potenciál a dostupnost biomasy. Ve druhé kapitole jsou popsány transformace biomasy do vhodné podoby paliva. Třetí až pátá kapitola popisuje přeměnu biomasy jako paliva na elektrickou energii pomocí spalovacího, Stirlingova a parního motoru. V těchto kapitolách jsou dále uvedeny parametry a ceny těchto motorů a také jednof...

  3. ‘Close to the city centre, close to the university’. Are there symptoms of studentification in Gdańsk, Poland?

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    Grabkowska Maja

    2016-06-01

    Full Text Available Students are increasingly recognised as important actors of urban change in contemporary cities. The article presents an analysis of incipient studentification processes in Gdańsk. Its general aim is to reveal patterns of students’ presence and activity which translate into spatial and socio-economic transformations of a post-socialist city at the level of neighbourhoods. The study consists of a survey on students’ residential behaviour, complemented by field and desk research. According to the results, due to the fact that Polish students’ housing and lifestyle choices are limited by their low purchasing power, student-dedicated services have a rather negative impact on the quality of urban space. Furthermore, under these conditions studentification may not be regarded as a stimulus to the gentrification process, which is rather driven by hipsters and affluent foreign students.

  4. Associations between cognitive abilities and life satisfaction in the oldest-old. Results from the longitudinal population study Good Aging in Skåne

    Directory of Open Access Journals (Sweden)

    Enkvist Å

    2013-07-01

    Full Text Available Åsa Enkvist, Henrik Ekström, Sölve Elmståhl Department of Health Sciences, Division of Geriatric Medicine, Lund University, Skåne University Hospital, Malmö, Sweden Introduction: Studies on the associations between cognitive abilities and life satisfaction (LS in the oldest-old are few. The aim of this study was to explore whether abilities in six different cognitive domains could predict LS in the oldest-old 3 years later. Methods: The study population consisted of 681 individuals aged 78–98 years, drawn from the longitudinal population study “Good Aging in Skåne,” which is part of a national survey (The Swedish National Study on Aging and Care. Scores on 13 cognitive tests were related to scores on Neugartens’ LS index A (LSI-A 3 years later. The cognitive tests were added into six different cognitive domains. A multiple regression analysis was constructed for each cognitive domain separately, with scores on the LSI-A as the dependent variable. The model was adjusted stepwise for sex, age, education, functional capacity, and depressive mood. Results: Significant correlations were found between digit cancellation, word recall, verbal fluency (VF A, VF animals, VF occupations, and mental rotations at baseline, as well as LSI-A at follow-up. The domains of spatial abilities (B = 0.453, P = 0.014 and processing speed (B = 0.118, P = 0.020 remained significantly associated with LSI-A 3 years later after adjustment. Conclusion: The cognitive domains of spatial abilities and processing speed predicted LS 3 years later in the oldest-old. Clinical implications are discussed. Keywords: oldest-old, life satisfaction, longitudinal, crystallized and fluid intelligence, cognition

  5. MULTICELLULAR-MEDIATED EXPRESSION OF P-GP AND MRP AND RELATIONSHIP WITH CELL CYCLE PROFILES IN HUMAN OVARIAN CANCER SK-OV-3ip1 MULTICELLULAR AGGREGATES

    Institute of Scientific and Technical Information of China (English)

    陈建利; 丰有吉; 张琴

    2001-01-01

    To investigate the expression of P-glycoprotein (P-gp) and multidrug resistance- associated protein (MRP) and the relationship with cell cycle profiles in ovarian cancer SK-OV-3ip1 multicellular aggregates. Methods: Liquid overlay system was employed to obtain multicellular aggregates. Expression of P-gp and MRP was detected with flow cytometry (FCM). Outer, intermediate and inner cells from multicellular aggregates were collected by layer-trypsinized method. Cell cycle profiles were also analyzed by FCM. Results: Compared with control cells, no expression of P-gp and MRP was detected in monolyer cells (P=0.128 and P=0.604), but expression of P-gp and MRP in aggregate cells was significantly elevated (P<0.01). P-gp expression in every layer cells was also obviously increased (P<0.01). Furthermore, P-gp expression in every layer cells was also obviously increased (P=0.071). Tendency to increased G0-G1 phase and reduced S phase cells existed from outer through intermediate to inner layers in multicellular aggregates but with no statistical difference. Cell percentages in G2-M phase also had no difference. However, compared with monolayer cells, cells in G0-G1 phase increased and cells in S and G2-M phases lowered significantly in every layer and in the whole multicellular aggregates. Expression elevation of P-gp and MRP was consistent with increased G0-G1 percentage in aggregate cells. Conclusion: Expression of P-gp and MRP increases in cells of SK-OV-3ip1 multicellular aggregates and is consistent with increased G0-G1 percentage, which implies the possible relationship between them and the possible role in multicellular-mediated drug resistance.

  6. S-K Equations of Calculating Formatiom Water Density%计算地层水密度的S-K方程

    Institute of Scientific and Technical Information of China (English)

    康志勇; 谢开宁

    2012-01-01

    通过对现有地层水密度确定方法的分析对比,结合渤海湾地区已有地层水高压物性分析成果,证实Schowalter诺谟图能客观地反映地层水密度的变化规律.提出影响地层水密度变化的五大因素:地层温度、地层压力、地层水矿化度、气水比及盐与水的质量比.系统建立了求取地层水密度通用方程(简称S-K方程),改变了依靠查图版求地层水密度的传统方法,并为利用压汞资料确定原始含油饱和度奠定了基础.%Now known methods of determining formation water density have been compared and analysed, density vary property of formation water is approved by Schowaller' s Nomograph and Bohai Gulf area' s PVT analysis data of formation water to determine density of formation water at subsurface conditions. At the same time, put forward five influence factors for density of formation water,they are temperature and pressure and mineralization and GWR and mass concentration of salts. The equations calculating density of formation water have been established, for short S-K equations. It changed the tradition method to determine density of formation water depending on Nomograph, and laid a foundation for S-K equations to determine original oil saleralion by mercury injection curve.

  7. 慢病毒介导下干涉酪氨酸激酶B表达对乳腺癌SK-BR-3细胞增殖的影响%Impact of lentivirus-mediated knockdown of tyrosine kinase B on proliferation of breast cancer cell line SK-BR-3

    Institute of Scientific and Technical Information of China (English)

    赵庆丽; 赵易; 秦芬武; 马骥; 乔如丽; 任晖; 蔡黔

    2015-01-01

    Objective To explore the impact of lentivirus-mediated knockdown of tyrosine kinase B (TrkB) on the proliferation of breast cancer cell line SK-BR-3 and its the mechanisms.Methods TrkB expression in 4 breast cancer cell lines including MCF-7,BCAP-37,SK-BR-3 and MDA-MB231 were measured and the cell line with relatively high TrkB expression was selected for interference of TrkB using lentivirus infection.The Lv-sh-TrkB cell line with stable interference of TrkB was confirmed by Western blot assay detection; in addition,the Lv-scramble cell line was also built.The four methyl tetrazolium (MTT) method and flow cytometry assays detection were used to assess the proliferation and cell cycle changes.Results Expression level of TrkB in SK-BR-3 cell line was higher than that of other cell lines,and it was used to construct the Lv-sh-TrkB cell line with stable interference of TrkB.Western blot assay showed that TrkB of Lv-sh-TrkB was significantly reduced compared with that of control and Lv-scramble cell line.MTT assay showed that the cell proliferation of Lv-sh-TrkB cell line was significantly slower than that of control and Lv-scramble cell line (P < 0.05).Flow cytometry assays showed that G1 phase arrest occurred in Lv-sh-TrkB cell line (Lv-sh-TrkB cell line G1 phase 78%,control cell line G1 phase 61%,Lv-scramble cell line G1 phase 62%).Conclusion The proliferation of breast cancer cell SK-BR-3 is significantly inhibited and the cell cycle G1 phase arrest is induced by interference of TrkB gene.%目的 探讨慢病毒介导下干涉酪氨酸激酶B(TrkB)表达对乳腺癌细胞SK-BR-3增殖的影响及其作用机制.方法 对MCF-7、BCAP-37、SK-BR-3和MDA-MB231乳腺癌细胞进行筛选,选取TrkB表达水平相对较高的细胞进行慢病毒感染以干涉TrkB表达,构建稳定干涉TrkB的乳腺癌细胞系Lv-sh-TrkB,通过蛋白质印迹(Western blot)实验检测TrkB干涉效果,同时构建乱序干涉细胞系Lv-scramble.采用噻唑蓝方法、流

  8. Kaempferol induces autophagy through AMPK and AKT signaling molecules and causes G2/M arrest via downregulation of CDK1/cyclin B in SK-HEP-1 human hepatic cancer cells.

    Science.gov (United States)

    Huang, Wen-Wen; Tsai, Shih-Chang; Peng, Shu-Fen; Lin, Meng-Wei; Chiang, Jo-Hua; Chiu, Yu-Jen; Fushiya, Shinji; Tseng, Michael T; Yang, Jai-Sing

    2013-06-01

    Kaempferol belongs to the flavonoid family and has been used in traditional folk medicine. Here, we investigated the antitumor effects of kaempferol on cell cycle arrest and autophagic cell death in SK-HEP-1 human hepatic cancer cells. Kaempferol decreased cell viability as determined by MTT assays and induced a G2/M phase cell cycle arrest in a concentration-dependent manner. Kaempferol did not induce DNA fragmentation, apoptotic bodies or caspase-3 activity in SK-HEP-1 cells as determined by DNA gel electrophoresis, DAPI staining and caspase-3 activity assays, respectively. In contrast, kaempferol is involved in the autophagic process. Double-membrane vacuoles, lysosomal compartments, acidic vesicular organelles and cleavage of microtubule-associated protein 1 light chain 3 (LC3) were observed by transmission electron microscopy, LysoΤracker red staining, GFP-fluorescent LC3 assays and acridine orange staining, respectively. In SK-HEP-1 cells, kaempferol increased the protein levels of p-AMPK, LC3-II, Atg 5, Atg 7, Atg 12 and beclin 1 as well as inhibited the protein levels of CDK1, cyclin B, p-AKT and p-mTOR. Taken together, CDK1/cyclin B expression and the AMPK and AKT signaling pathways contributed to kaempferol-induced G2/M cell cycle arrest and autophagic cell death in SK-HEP-1 human hepatic cancer cells. These results suggest that kaempferol may be useful for long-term cancer prevention.

  9. Zircon and baddeleyite from the economic ultramafic-mafic Noril'sk-1 intrusion (Russia): Hf-isotope constraints on source composition

    Science.gov (United States)

    Malitch, K. N.; Belousova, E. A.; Badanina, I. Yu.; Griffin, W. L.

    2012-04-01

    The ultramafic-mafic Noril'sk-1 intrusion in the northwestern part of the Siberian Craton (Russia) represents one of three known Noril'sk-type, ore-bearing intrusions, which host one of the world's major economic sulphide platinum-group-element (PGE)-Cu-Ni deposits. Zircon and baddeleyite dated previously both by SHRIMP (i.e. 248.0 ± 3.7 Ma, Campbell et al. 1992) and ID-TIMS (251.1 ± 3.6 Ma, Kamo et al. 1996) have been restricted to one lithology (e.g. leucogabbro) of the Noril'sk-1 intrusion. To better constrain the age of igneous event and sources involved in its generation our multi-technique study utilized ten rock samples characteristic of unmineralized and mineralized lithologies. The rocks investigated comprise (from top to bottom) gabbro-diorite (sample N1-1), leucogabbro (N1-3), olivine-free gabbro (N1-2 and N1-4), olivine-bearing gabbro (N1-5), olivine gabbro (N1-6), plagiowehrlite and plagiodunite (N1-7), taxitic-textured rocks comprising melanotroctolite, olivine gabbro with relics of ultramafic rocks (N1-8, N1-9) and contact fine-grained gabbro (N1-10). Sulphide PGE-Cu-Ni ores occur in ultramafic (N1-7) and taxitic-textured rocks (N1-8 and N1-9), which have thickness of about 17 m, whereas the low-sulphide horizon of about 1 m thick occurs in the upper part of intrusion (N1-3). In situ U-Pb analyses of zircon from these rocks, combined with detailed study of crystal morphology and internal structure, identify four zircon populations (Malitch et al. 2012). The U-Pb ages of baddeleyite and the defined zircon populations cover a significant time span, from Late Paleozoic to Early Mesozoic (e.g., 290 ± 2.8; 261.3 ± 1.6; 245.7 ± 1.1; 236.5 ± 1.8 and 226.7 ± 0.9 Ma). The established distribution of U-Pb ages implies that crystallization of baddeleyite and zircon corresponds to several stages of protracted evolution of ultramafic-mafic magmas at deep-seated staging chambers and/or probably characterizes interaction of distinct magmas during formation

  10. Influence of MTDH gene down regulation on proliferation and apoptosis of human breast cancer SK-BR 3 cells%转移粘附基因下调对乳腺癌SK-BR-3细胞增殖和凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    杜成; 刘兆喆; 丁震宇; 郭放; 马东初; 谢晓冬

    2013-01-01

    Objective To investigate if down regulation of MTDH could inhibit proliferation and induce apoptosis in breast cancer SK-BR-3 cells.Methods RNA interference was employed to reduce MTDH expression in human breast cancer SK-BR-3 cells.Western blot assay was applied to measure the down regulation of MTDH.MTT assay was performed to assess the proliferation of SK-BR-3 cell.Flow cytometry was employed to detect cell cycle and apoptosis.Western blot assay was applied to detect the molecular alterations that was associated with cell proliferation,cell cycle and apoptosis.Results MTDH down regulation significantly inhibited cell proliferation.48 hours and 72 hours after trasnfection,the absorbance value(A value)in blank control,negative control and treatment group was (2.0 ± 0.1) vs (1.9 ± 0.3) vs (0.9 ± 0.1) (P =0.02) and (2.7 ± 0.2) vs (2.5 ± 0.4) vs (1.3 ± 0.2) (P =0.008).MTDH down regulation resulted in accumulation of the G0/G1 phase cells and reduction of S and G2/M phase cells.Moreover,MTDH down regulation significantly induced cell apoptosis.The cell apoptosis rate in blank control,negative control and trial group was (1.3 ± 0.2) %,(1.4 ± 0.3) % and (19.6 ± 2.7) % (P =0.012).MTDH down regulation resulted in a decreased expression of cyclinD1 and Bcl-2,an increased expression of P21 and the activation of caspase-3.Conclusions Reduced MTDH expression in SKBR-3 cells can inhibit proliferation and induce apoptosis,which may be associated with decreased expression of cyclinD1 and Bcl-2,an increased expression of P21 and the activation of caspase-3.%目的 探讨转移粘附基因(metadherin,MTDH)表达下调对乳腺癌SK-BR-3细胞增殖和凋亡的影响及可能的机制.方法 采用RNA干扰技术,下调乳腺癌SK-BR-3细胞MTDH基因的表达,Western blot实验验证MTDH表达下调.四甲基偶氮唑盐比色法(methyl thiazolyl tetrazolium,MTT)实验检测MTDH下调对SK-BR-3细胞增殖的影响,流式细胞术检测细

  11. Antagonism by 8-hydroxy-2(di-n-propylamino)tetraline and other serotonin agonists of muscarinic M1-type receptors coupled to inositol phospholipid breakdown in human IMR-32 and SK-N-MC neuroblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, C.J. (Astra Research Centre AB, Soedertaelje (Sweden) Karolinska Institutet (Sweden)); Ahlgren, P.C. (Karolinska Institutet (Sweden)); O' Neill, C. (Huddinge Univ. Hospital (Sweden))

    1991-01-01

    IMR-32 and SK-N-MC cells were found to contain ({sup 3}H)quinuclidinyl benzilate specific binding sites inhibited by pirenzepine in a manner suggesting the presence of both M1-type and M2-type muscarinic receptor recognition sites. Neither cell had detectable ({sup 3}H)8-OH-DPAT binding sites. Carbachol stimulated the rate of inositol phospholipid breakdown in IMR-32 and SK-N-MC human neuroblastoma cells with an EC{sub 50} value of about 50 {mu}M in both cases. Pirenzepine inhibited the carbachol stimulated inositol phospholipid breakdown in both cells with Hill slopes of unity and IC{sub 50} values of 15 nM (IMR-32) and 12 nM (SK-N-MC). The 5-HT{sub 1A} receptor agonist 8-OH-DPAT competitively inhibited carbachol-stimulated inositol phospholipid breakdown with pA{sub 2} values of 5.78 (IMR-32) and 5.61 (SK-N-MC). The 5-HT agonists 5-MeODMT and buspirone at micromolar concentrations inhibited carbachol-stimulated breakdown in IMR-32 cells. The inhibition by 8-OH-DPAT and 5-MeODMT was not affected by preincubation with (-)alprenolol. 5-HT was without effect on either basal or carbachol-stimulated breakdown. It is concluded that IMR-32 and SK-N-MC neuroblastoma cells express muscarinic M1-type but not serotoninergic receptors coupled to phosphoinositide-specific phospholipase C. 8-OH-DPAT acts as a weak antagonist at these muscarinic receptors.

  12. Biological functions of the nude mice subcutaneous tumor established by MDA-MB-468 and SK-BR-3 breast cancer cells%MDA-MB-468和SK-BR-3乳腺癌细胞建立裸鼠皮下种植瘤的生物学功能

    Institute of Scientific and Technical Information of China (English)

    赵期康; 吴颖; 莫雪丽; 熊兵红

    2015-01-01

    目的 建立SK-BR-3和MDA-MB-468裸鼠皮下种植瘤模型,观察两种乳腺癌细胞株在建立裸鼠皮下移植瘤中的成瘤性和生物学与形态学特征.探讨阿霉素缓释剂对两种乳腺癌细胞裸鼠皮下种植瘤的生物学功能的影响.方法 将80只裸小鼠随机分为MDA-MB-468组和SK-BR-3组,MDA-MB-468组小鼠皮下注射乳腺癌MDA-MB-468细胞株,SK-BR-3组小鼠皮下注射乳腺癌SK-BR-3细胞株,每组40只.选取一半数量的小鼠,采用皮下注射法将细胞种植在裸鼠右侧腹股沟区,每天注射1次,连续注射4周后处死裸鼠,剥离瘤体,计算两组裸鼠皮下肿瘤的体积抑瘤率,取出两组小鼠模型中另一半小鼠,将阿霉素缓制剂注入两组小鼠模型皮下肿瘤旁,4周后处死两组小鼠,剥离瘤体,测量肿瘤大小.采用原位缺口末端标记法(TUNEL)法检测两组小鼠瘤体组织中肿瘤细胞的凋亡指数,观察阿霉素对两组乳腺癌细胞周期和凋亡的影响.结果 (1)肿瘤生长:至第8周时,两组小鼠肿瘤的体积分别为(3.212±0.151)和(2.924 ±0.316) cm3,两组间差异有统计学意义(t=2.758,P<0.05).(2)注射阿霉素后肿瘤体积抑制率结果:两组乳腺癌小鼠模型注射阿霉素缓释剂后,皮下瘤体停止生长并逐渐缩小,两组肿瘤体积差异有统计学意义(x2=2.53,P<0.05).(3)阿霉素对两组细胞周期和凋亡的影响:阿霉素使两组细胞生长阻滞在G0/G1期.阿霉素可显著引起MDA-MB-468细胞凋亡,最大凋亡率达62.5%.阿霉素处理SK-BR-3细胞后,亦可引起较明显的细胞凋亡,最大凋亡率可达53.8%.结论 成功制备两种乳腺癌转移瘤小鼠模型,同时制备阿霉素缓释剂,证实了其在乳腺癌转移瘤小鼠模型中抑制肿瘤生长的良好疗效.%Objective To establish the tumor models of SK-BR-3 and MDA-MB-468 in subcutaneous xenograft,observe the two breast cancer cell lines in the establishment of tumor and the biological and morphological

  13. Cultural Identity of Citizens of Gdańsk from an Ethnolinguistic Perspective on the Basis of Chosen Texts of the Free City of Danzig

    Directory of Open Access Journals (Sweden)

    Izabela Olszewska

    2015-06-01

    Full Text Available Cultural Identity of Citizens of Gdańsk from an Ethnolinguistic Perspective on the Basis of Chosen Texts of the Free City of Danzig As a consequence of the First World War and in the wake of the Treaty of Versailles the Free City of Danzig was established. The image of Danzig identity was created, first of all, by the following ethnic groups: German, Polish and Jewish. Was the Free City of Danzig multicultural or was it German with Polish and Jewish minorities? Did those nationalities live beside each other, did they together, as citizens of Danzig, create a common reality? Is it possible to talk about a uniform culture/identity of Danzig? The aim of this article is an analysis of linguistic image of the world of the citizens of the Free City of Danzig, which has been carried out on the basis of characteristics of the image of relations and cultural differences in the interpretation of Polish community. Yet, the whole image of identity consists of a mosaic of smaller interpretations which, only after being reduced to the lowest common denominator, may give the holistic image of Danzig identity as an image of a common multiple subjectivity. Mutual perception of nationalities inhabiting the area of the Free City of Danzig is the starting point for the discussion on their identity and an attempt to answer the question: did the citizens of Danzig see themselves as one community – exactly the one of Danzig? The analysed research material consists of chosen texts of the local press (in Polish and occasionally in German concerning socio-cultural and political and informative issues. The Polish "Gazeta Gdańska" had been published since 1891 as the first Polish Danzig newspaper in Polish. Its first aim was to integrate Polish circles and to defend the rights of the Polish. "Danziger Neuesten Nachrichten", published since 1894, was the biggest Danzig conservative newspaper in German which influenced public opinion. In the analysis of the linguistic

  14. Morphological alterations and G0/G1 cell cycle arrest induced by curcumin in human SK-MEL-37 melanoma cells

    Directory of Open Access Journals (Sweden)

    Marcella Lemos Brettas Carneiro

    2010-04-01

    Full Text Available The aim of this work was to study the effect of curcumin on cell cycle in the human SK-MEL-37 melanoma cell line. In addition, morphological and structural analyses were also performed. Flow cytometric analysis showed a G0/G1 arrest at 5 µM after 24 h exposure and a concentration-dependent increase in the proportion of sub-G0 hypodiploid cells. Typical apoptotic events were also observed by the fluorescence microscopy, transmission and scanning electronic microscopy. Loss of mitochondrial membrane potential was not detected. Results suggested that curcumin could arrest human melanoma cells at G0/G1 phase and induce a mitochondrial-independent apoptotic pathway.O melanoma é um tipo agressivo de câncer cujo tratamento culmina com o estabelecimento de resistência aos quimioterápicos empregados. Portanto, é importante o desenvolvimento de novos agentes farmacológicos que sejam menos tóxicos e que não provoquem quimiorresistência. As inúmeras propriedades terapêuticas da curcumina vêm sendo confirmadas através de estudos sobre o seu mecanismo de ação em células cultivadas. No presente estudo, empregamos células de melanoma humano da linhagem SK-MEL-37, que desenvolveram resistência in vitro à doxorubicina e cisplatina, drogas normalmente utilizadas na clínica. Investigamos o efeito da curcumina sobre o ciclo celular através de citometria de fluxo. Além disso, análises morfológicas e estruturais também foram realizadas. Os resultados demonstraram que o tratamento com uma concentração de 5 ?M de curcumina provocou uma parada na subfase G0/G1. Além disso, observou-se um aumento dose-dependente na proporção de células hipodiplóides em sub-G0. Eventos apoptóticos típicos foram observados por microscopia de fluorescência, microscopia eletrônica de transmissão e microscopia eletrônica de varredura. Não foi detectada alteração no potencial de membrana mitocondrial. Os resultados indicam que futuros estudos poder

  15. Orthostatic intolerance predicts mild cognitive impairment: incidence of mild cognitive impairment and dementia from the Swedish general population cohort Good Aging in Skåne

    Directory of Open Access Journals (Sweden)

    Elmståhl S

    2014-11-01

    Full Text Available Sölve Elmståhl, Elisabet Widerström Division of Geriatric Medicine, Department of Health Sciences, Lund University, Skåne University Hospital, Malmö, Sweden Introduction: Contradictory results have been reported on the relationship between orthostatic hypotension (OH and mild cognitive impairment (MCI. Objective: To study the incidence of MCI and dementia and their relationship to OH and subclinical OH with orthostatic symptoms (orthostatic intolerance.Study design and setting: This study used a prospective general population cohort design and was based on data from the Swedish Good Aging in Skåne study (GÅS-SNAC, they were studied 6 years after baseline of the present study, with the same study protocol at baseline and at follow-up. The study sample comprised 1,480 randomly invited subjects aged 60 to 93 years, and had a participation rate of 82% at follow-up. OH test included assessment of blood pressure and symptoms of OH. Results: The 6-year incidence of MCI was 8%, increasing from 12.1 to 40.5 per 1,000 person-years for men and 6.9 to 16.9 per 1,000 person-years for women aged 60 to >80 years. The corresponding 6-year incidence of dementia was 8%. Orthostatic intolerance during uprising was related to risk for MCI at follow-up (odds ratio [OR] =1.84 [1.20–2.80][95% CI], adjusted for age and education independently of blood pressure during testing. After stratification for hypertension (HT, the corresponding age-adjusted OR for MCI in the non-HT group was 1.71 (1.10–2.31 and 1.76 (1.11–2.13 in the HT group. Among controls, the proportion of those with OH was 16%; those with MCI 24%; and those with dementia 31% (age-adjusted OR 1.93 [1.19–3.14]. Conclusion: Not only OH, but also symptoms of OH, seem to be a risk factor for cognitive decline and should be considered in the management of blood pressure among the elderly population. Keywords: orthostatic blood pressure, epidemiology, elderly

  16. Między brakiem a nadmiarem. Z Ireną Grudzińską-Gross rozmawia Joanna Tokarska-Bakir

    Directory of Open Access Journals (Sweden)

    Joanna Tokarska-Bakir

    2012-12-01

    Full Text Available Between overabundance and scarcity. Joanna Tokarska-Bakir in an interview with Irena Grudzińska Gross This conversation with Irena Grudzińska-Gross starts a series of interviews in “Studia Litteraria et Historica”, which motto is the title of the essay of Jan Stanisław Bystroń “On subjects I was advised not to pursue”. Among these subjects that Irena Grudzińska-Gross names are: war, family history, women.  Grudzińska-Gross tells also about the reactions to “Złote Żniwa” - a book that she wrote together with Jan Tomasz Gross, and about academic work of people of Eastern Europe living in the United States. One part of the interview concerns also a “collective hypnosis”, that Americans underwent after the 9/11 World Trade Center Attack and the price, that Susan Sontag had to pay for being critical about American militarism.   Między brakiem a nadmiarem. Z Ireną Grudzińską-Gross rozmawia Joanna Tokarska-Bakir Rozmowa z Ireną Grudzińską-Gross otwiera cykl wywiadów “Studia Litteraria et Historica”, których mottem jest tytuł eseju Jana Stanisława Bystronia: “Tematy, które mi odradzano”. Wśród “odradzanych” tematów, które wymienia Irena Grudzińska-Gross są między innymi: wojna, historia rodzinna, kobiety. Grudzińska-Gross opowiada także o reakcjach na książkę “Złote żniwa”, którą napisała wraz z Janem Tomaszem Grossem oraz o pracy akademickiej osób z Europy Wschodniej w Stanach Zjednoczonych. Część rozmowy dotyczy także “zbiorowej hipnozy”, której ulegli mieszkańcy USA po ataku 11 września 2001 na World Trade Center i ceny, jaką musiała zapłacić Susan Sontag za krytykę amerykańskiego militaryzmu.

  17. Decreased expression of BRCA1 in SK-BR-3 cells is the result of aberrant activation of the GABP Beta promoter by an NRF-1-containing complex

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    MacDonald Gwen

    2011-05-01

    Full Text Available Abstract Background BRCA1 has recently been identified as a potential regulator of mammary stem/progenitor cell differentiation, and this function may explain the high prevalence of breast cancer in BRCA1 mutation carriers, as well as the downregulation of BRCA1 in a large proportion of sporadic breast cancers. That is, loss of BRCA1 function results in blocked differentiation with expansion of the mammary stem/progenitor cells. Because BRCA1 also maintains genomic integrity, its loss could produce a pool of genetically unstable stem/progenitor cells that are prime targets for further transforming events. Thus, elucidating the regulatory mechanisms of BRCA1 expression is important to our understanding of normal and malignant breast differentiation. Results Loss of BRCA1 expression in the ErbB2-amplified SK-BR-3 cell line was found to be the result of loss of activity of the ets transcription factor GABP, a previously characterized regulator of BRCA1 transcription. The expression of the non-DNA binding GABPβ subunit was shown to be deficient, while the DNA binding subunit, GABPα was rendered unstable by the absence of GABPβ. Deletion analysis of the GABPβ proximal promoter identified a potential NRF-1 binding site as being critical for expression. Supershift analysis, the binding of recombinant protein and chromatin immunoprecipitation confirmed the role of NRF-1 in regulating the expression of GABPβ. The siRNA knockdown of NRF-1 resulted in decreased GABPβ and BRCA1 expression in MCF-7 cells indicating that they form a transcriptional network. NRF-1 levels and activity did not differ between SK-BR-3 and MCF-7 cells, however the NRF-1 containing complex on the GABPβ promoter differed between the two lines and appears to be the result of altered coactivator binding. Conclusions Both NRF-1 and GABP have been linked to the regulation of nuclear-encoded mitochondrial proteins, and the results of this study suggest their expression is

  18. Seasonal dynamics of Pseudocalanus minutus elongatus and Acartia spp. in the southern Baltic Sea (Gdańsk Deep – numerical simulations

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    L. Dzierzbicka-Głowacka

    2006-01-01

    Full Text Available A population dynamics model for copepods is presented, describing the seasonal dynamics of Pseudocalanus minutus elongatus and Acartia spp. in the southern Baltic Sea (Gdańsk Deep. The copepod model was coupled with a one-dimensional physical and biological upper layer model for nutrients (total inorganic nitrogen, phosphate, phytoplankton, microzooplankton, and an early juvenile of herring as a predator. In this model, mesozooplankton (herbivorous copepods has been introduced as an animal having definite patterns of growth in successive stages, reproduction and mortality. The populations are represented by 6 cohorts in different developmental stages, thus assuming that recruitment of the next generation occurs after a fixed period of adult life. The copepod model links trophic processes and population dynamics, and simulates individual growth within cohorts and the changes in biomass between cohorts. The simulations of annual cycles of copepods contain one complete generation of Pseudocalanus and two generations of Acartia in the whole column water, and indicate the importance of growth in the older stages of 6 cohorts of each species, to arrive at a total population biomass. The peaks of copepods' biomass are larger at the turn of June and July for Pseudocalanus and smaller in July for Acartia, lagging that of phytoplankton by ca. two mouths, due to the growth of cohorts in successive stages and egg production by females. The numerical results show that the investigated species could not be the main factor limiting the spring phytoplankton bloom in the Gdańsk Deep, because the initial development was slow for Acartia and faster for Pseudocalanus, but the main development formed after the bloom, in both cases. The phytoplankton bloom is very important in the diet of the adults of the copepods, but it is not particularly important for the youngest part of new generation (early nauplii. However, the simulated microzooplankton biomass was

  19. Activation of retinoic acid receptor alpha is sufficient for full induction of retinoid responses in SK-BR-3 and T47D human breast cancer cells.

    Science.gov (United States)

    Schneider, S M; Offterdinger, M; Huber, H; Grunt, T W

    2000-10-01

    Retinoid signaling via retinoic acid (RA) and retinoid X receptors (RARs and RXRs) regulates mammary epithelial cell growth and differentiation. Loss of RAR-beta might represent an early event during breast carcinogenesis. Higher differentiated, estrogen-dependent, estrogen receptor (ER)-positive (ER+) mammary carcinoma cells have been found to contain relatively high levels of RAR-alpha and to be responsive to retinoids, whereas most undifferentiated, estrogen-independent, ER-negative (ER-) cells are characterized by low RAR-alpha expression and by retinoid resistance. In contrast, RAR-gamma is detectable at equal levels in both ER+ and ER- cells. In the present investigation, we directly examined the relative contribution of the distinct retinoid receptors to the retinoid response of breast cancer cells by comparing the effects of low concentrations of specific retinoids, which selectively activate individual receptor subtypes, on growth, cell cycle distribution, apoptosis, and on the autoregulation of RAR-alpha and RAR-gamma in ER- SK-BR-3 and ER+ T47D breast cancer cells. In vitro growth activity was determined by using a colorimetric cell viability assay and analysis of cell cycle distribution, and apoptosis was performed by flow cytometry of propidium iodide-stained or fluorescent Annexin V-labeled cells, respectively, whereas expression of RAR-alpha and RAR-gamma was determined by Northern blotting. Both cell lines are retinoid sensitive and express high amounts of RAR-alpha, RAR-gamma, and RXR-alpha. RAR-alpha-selective compounds (AM80 and AM580) inhibit cell growth, induce G1 arrest, stimulate apoptosis, and up-regulate RAR-alpha and RAR-gamma mRNA as efficiently as RAR/RXR-pan-reactive (9-cis RA) and RAR-pan-reactive retinoids (all-trans RA, TTNPB). Remarkably, an RAR-alpha antagonist (Ro 41-5253) not only blocks the RAR-alpha-selective agonists but also the pan-reactive compounds. In contrast, RAR-13-selective (CD417), RAR-gamma-selective (CD437/AHPN

  20. Neuroprotection via RNA-binding protein RBM3 expression is regulated by hypothermia but not by hypoxia in human SK-N-SH neurons

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    Rosenthal LM

    2017-05-01

    Full Text Available Lisa-Maria Rosenthal,1 Giang Tong,1 Christoph Walker,1 Sylvia J Wowro,1 Jana Krech,1 Constanze Pfitzer,1,2 Georgia Justus,1 Felix Berger,1,3 Katharina Rose Luise Schmitt1 1Department of Congenital Heart Disease/Pediatric Cardiology, German Heart Institute Berlin, 2Berlin Institute of Health (BIH, 3Department of Pediatric Cardiology, Charité – University Medical Center, Berlin, Germany Objective: Therapeutic hypothermia is an established treatment for perinatal asphyxia. Yet, many term infants continue to die or suffer from neurodevelopmental disability. Several experimental studies have demonstrated a beneficial effect of mild-to-moderate hypothermia after hypoxic injury, but the understanding of hypothermia-induced neuroprotection remains incomplete. In general, global protein synthesis is attenuated by hypothermia, but a small group of RNA-binding proteins including the RNA-binding motif 3 (RBM3 is upregulated in response to cooling. The aim of this study was to establish an in vitro model to investigate the effects of hypoxia and hypothermia on neuronal cell survival, as well as to examine the kinetics of concurrent cold-shock protein RBM3 gene expression. Methods: Experiments were performed by using human SK-N-SH neurons exposed to different oxygen concentrations (21%, 8%, or 0.2% O2 for 24 hours followed by moderate hypothermia (33.5°C or normothermia for 24, 48, or 72 hours. Cell death was determined by quantification of lactate dehydrogenase and neuron-specific enolase releases into the cell cultured medium, and cell morphology was assessed by using immunofluorescence staining. The regulation of RBM3 gene expression was assessed by reverse transcriptase-quantitative polymerase chain reaction and Western blot analysis.Results: Exposure to hypoxia (0.2% O2 for 24 hours resulted in significantly increased cell death in SK-N-SH neurons, whereas exposure to 8% O2 had no significant impact on cell viability. Post-hypoxia treatment with

  1. A correlation study between CTG repeats in SK3 gene and clinical symptoms for schizophrenic patients%精神分裂症患者SK3基因内CTG重复扩展突变与临床症状的相关研究

    Institute of Scientific and Technical Information of China (English)

    杨甫德; 吉中孚; 付卫红; 王国相; 顾卫红; 白京生

    2003-01-01

    目的探讨精神分裂症患者的弱传导钙激活钾通道蛋白(SK3)基因内CTG重复数目及其与临床症状的关系.方法采用聚合酶链反应(PCR)扩增技术,对30例高发家系的精神分裂症患者,30例散发精神分裂症患者以及5个高发家系的10例同病者和17名未患病的一级亲属进行SK3基因内CTG重复数目检测,同时对70例精神分裂症患者进行下列评定:阳性症状评定量表(SAPS)、阴性症状评定量表(SANS)和治疗副反应量表(TESS);韦氏智力量表(WAIS-R)、韦氏记忆量表(WMS)、威斯康星卡片分类测验(WCST)、连线测验A(Trial-A)及语言流利性测验(LFT).结果高发和散发精神分裂症患者的CTG重复数目明显高于正常对照者,差异有非常显著性(X±SD分别为8.8±1.2,7.9±0.7,6.2±0.6,P<0.01),尤以高发家系最为明显.CTG重复数目与阴性症状呈显著正相关(r=0.769,P=0.000),而与认知功能呈显著负相关(r=-0.350-0.690,P均<0.05).结论精神分裂症SK3基因内CTG重复多态性变化可能是该病的一个生物学致病因素.

  2. 高精度刚架梁式SK-1应变计参数测定装置的结构和精度评定%Structure and Accuracy of SK- 1 High Accurate Strain Gauge Parameters Testing Apparatus Bused on a Rigid Framed Beam

    Institute of Scientific and Technical Information of China (English)

    邓足斌; 张振洲

    2001-01-01

    The SK- i strain gauge parameters testing apparatus presented in this paper is based on the rigid frame bean principle. It is different from those commonly used internationally based on simply spported beams of pure bending moments or cantilever beams of equal strength. According to the two newly proposed concepts, i. e., the shape error of the cylindric surface of the calibration beam and the measurement error of the calibration beam deflection, this paper carries out the error analysis and accuracy evaluation of the apparatus to illustriate the justification of its choice of scheme, and design of structure. It is proven that the SK -1 apparatus is a high accuracy standard apparatus for the implementation of interna- tional Recommendation No. 62 of OIML“The Performance aracteristics of Metallic Resistance Strain Gauges”, and Chi- nese National Standards of Resistance Strain Gauges, GB/T 13992 - 92. Its relative expanded uncertainty has been achieved Ur = 0.11%.%文中提出的SK-1刚架梁式应变计参数测定装置,同目前国际上一般采用简支纯弯矩梁和等强度悬臂梁原理制成的这类装置不一样,沈阳仪器仪表工艺研究所是采用刚架梁原理研制而成的,并按新提出的标定梁园柱面形状误差和标定梁挠度误差两概念[3],对其进行误差分析和不确定度评定。从而说明该装置的方案,设计思路和精度检定的合理性。为我国电阻应变计(GB/T 13992-92)国家标准和国际电阻应变计行业贯彻实施[OIML]国际建议62号“金属电阻应变计工作特性”提供一种高精度应变计参数的标准装置。它的相对展伸不确定度已达0.1%。

  3. Effects of NRP-1 Overexpression on Biological Behaviors of Breast Cancer Cell Lines MDA-MB-231 and SK-BR-3%NRP-1过表达对乳腺癌细胞MDA-MB-231、SK-BR-3生物学行为的影响

    Institute of Scientific and Technical Information of China (English)

    张梦瑾; 徐杰; 王红梅; 杜秀平; 韩正祥

    2016-01-01

    目的 通过上调乳腺癌细胞MDA-MB-231、SK-BR-3中NRP-1的表达,观察NRP-1对细胞增殖、凋亡、迁移及侵袭能力的影响.方法 构建pcDNA3.1-NRP-1表达载体,脂质体介导NRP-1表达质粒转染MDA-MB-231、SK-BR-3细胞,用G418筛选出稳定转染的乳腺癌细胞株.利用RT-qPCR、Western blot法分别检测NRP-1基因mRNA及其蛋白表达;CCK-8法、AnnexinⅤ-APC/7-AAD法、Transwell小室分别检测转染细胞增殖率、凋亡率及侵袭、迁移能力.结果 成功构建pcDNA3.1-NRP-1表达载体,转染MDA-MB-231、SK-BR-3细胞并筛选稳定表达系.与对照组相比,过表达组细胞的NRP-1 mRNA及蛋白表达水平明显升高(均P<0.05);NRP-1过表达组的细胞较对照组增殖率增加、凋亡率降低、侵袭及迁移能力增强(均P<0.05).结论 NRP-1在乳腺癌发展、浸润、转移中起着一定的作用,它可促进乳腺癌细胞增殖、迁移和侵袭,抑制其凋亡.

  4. Using clinical symptoms to predict adverse maternal and perinatal outcomes in women with preeclampsia: data from the PIERS (Pre-eclampsia Integrated Estimate of RiSk) study.

    Science.gov (United States)

    Yen, Tin-Wing; Payne, Beth; Qu, Ziguang; Hutcheon, Jennifer A; Lee, Tang; Magee, Laura A; Walters, Barry N; von Dadelszen, Peter

    2011-08-01

    Preeclampsia is a leading cause of maternal morbidity. The clinical challenge lies in predicting which women with preeclampsia will suffer adverse outcomes and would benefit from treatment, while minimizing potentially harmful interventions. Our aim was to determine the ability of maternal symptoms (i.e., severe nausea or vomiting, headache, visual disturbance, right upper quadrant pain or epigastric pain, abdominal pain or vaginal bleeding, and chest pain or dyspnea) to predict adverse maternal or perinatal outcomes. We used data from the PIERS (Pre-eclampsia Integrated Estimate of RiSk) study, a multicentre, prospective cohort study designed to investigate the maternal risks associated with preeclampsia. Relative risks and receiver operating characteristic (ROC) curves were assessed for each preeclampsia symptom and outcome pair. Of 2023 women who underwent assessment, 52% experienced at least one preeclampsia symptom, with 5.2% and 5.3% respectively experiencing an adverse maternal or perinatal outcome. No symptom and outcome pair, in either of the maternal or perinatal groups, achieved an area under the ROC curve value > 0.7, which would be necessary to demonstrate a discriminatory predictive value. Maternal symptoms of preeclampsia are not independently valid predictors of maternal adverse outcome. Caution should be used when making clinical decisions on the basis of symptoms alone in the preeclamptic patient.

  5. Hydrolysis of triglyceride by the whole cell of Pseudomonas putida 3SK in two-phase batch and continuous reactors systems.

    Science.gov (United States)

    Lee, S Y; Rhee, J S

    1994-08-05

    Batch and continuous hydrolysis of olive oil in an organic-aqueous two-phase system using the live whole cell of Pseudomonas putida 3SK as a source of a lipase is investigated. The strain was not only fully viable and grown well, but also produced extracellular lipase simultaneously. The degree of hydrolysis, depending on olive oil concentration in the solvents, was maximal at 13.5% (w/v) and decreased with the increase of the substrate concentration. At the optimal condition, a degree of hydrolysis higher than 95% was achieved with 24 h at 30 degrees C when the reaction was carried out in a two-phase batch stirred reactor. For long-term operation a continuous stirred reactor was designed. When the reaction was carried out in a continuous stirred reactor, the degree was hydrolysis reached 86% at a dilution rate of 0.2 h(-1). Satisfactory performance of a two-phase bioreactor was obtained in a long-term continous operation, which lasted for at least 30 days by feeding organic solvent containing olive oil and aqueous media separately. (c) 1994 John Wiley & Sons, Inc.

  6. Associations between functional ability and life satisfaction in the oldest old: results from the longitudinal population study Good Aging in Skåne

    Directory of Open Access Journals (Sweden)

    Enkvist Å

    2012-08-01

    Full Text Available Åsa Enkvist, Henrik Ekström, Sölve ElmståhlDepartment of Health Sciences, Lund University, Malmö University Hospital, Malmö, SwedenObjectives: To describe change in functional ability in the oldest-old population during 3 years and examine its relation to life satisfaction (LS. A total of 681 individuals aged 78 and older from the population-based study Good Aging in Skåne took part.Methods: Functional ability was assessed using Sonn and Åsberg's Activities of Daily Living (ADL scale and related to LS assessed by Neugarten et al's Life Satisfaction Index A (LSI-A.Results: Fifty-one percent of 87–93-year-olds reported ADL decline during 3 years. Individuals reporting impaired ADL had a mean LSI-A value of 23.0 compared to 26.4 in those unchanged. ADL decline had a stronger negative effect on LS in the younger group (78–84 years, r = 0.207, P < 0.001. In a multiple regression model, one score's decline in ADL capacity corresponded to 1.5 scores lower LS (P < 0.001.Discussion: Effort put into keeping the oldest old on a high level of functional ability has the potential to maintain the LS of this population.Keywords: life satisfaction, functional ability, longitudinal, oldest old

  7. Návrh predikčního modelu prodeje vybraných potravinářských komodit

    OpenAIRE

    Řešetková, Dagmar

    2015-01-01

    Disertační práce se obecně zaměřuje na využití nástrojů umělé inteligence v praxi a s ohledem na zaměření studia v oboru Řízení a ekonomika podniku na využití nástrojů umělé inteligence v praxi firemní, jako nástroje pro podporu rozhodování na operativní a taktické úrovni řízení. V užším pojetí se práce zabývá návrhem predikčního modelu prodeje vybraných potravinářských komodit. Navržený model má posloužit jako substitut lidského experta při podpoře v rozhodovacím procesu nákupu vybraných kom...

  8. Apigenin modulates the expression levels of pro-inflammatory mediators to reduce the human insulin amyloid-induced oxidant damages in SK-N-MC cells.

    Science.gov (United States)

    Amini, R; Yazdanparast, R; Ghaffari, S H

    2015-06-01

    Amyloid depositions of proteins play crucial roles in a wide variety of degenerative disorders called amyloidosis. Although the exact mechanisms involved in amyloid-mediated cytotoxicity remain unknown, increased formation of reactive oxygen species (ROS) and nitrogen species and overproduction of pro-inflammatory cytokines are believed to play key roles in the process. In that regard, we investigated the effect of apigenin, a common dietary flavonoid with high antioxidant and anti-inflammatory properties on potential factors involved in cytotoxicity of human insulin amyloids. Pretreatment of SK-N-MC neuroblastoma cells with apigenin increased cell viability and reduced the apoptosis induced by insulin fibrils. In addition, apigenin attenuated insulin fibril-induced ROS production and lipid peroxidation. Our result also demonstrated that pretreatment of the fibril-affected cells with apigenin caused an increase in catalase activity and the intracellular glutathione content along with reduction in nitric oxide production and nuclear factor κB, tumor necrosis factor α, and interleukin 6 gene expression based on real-time polymerase chain reaction evaluation. In accordance with these results, apigenin could be a promising candidate in the design of natural-based drugs for treatment or prevention of amyloid-related disorders.

  9. Cellular uptake and retention measurements of alkylphosphocholines in the SK-BR-3 breast cancer and Molt-4 leukemia cell line using capillary gas chromatography.

    Science.gov (United States)

    Brochez, V; Van Heuverswyn, D; Diniz, J A; De Potter, C R; Van den Eeckhout, E G

    1999-05-01

    The determination of cellular content of octadecylphosphocholine (D-19391) and hexadecylphosphocholine (HePC, D-18506), two anticancer agents of the alkylphosphocholine group, using capillary gas chromatography is described. The compounds' cytotoxicity was first determined by the MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium] assay, being indicative for the concentration used in the uptake and retention measurements. D-19391 was added to the SK-BR-3 breast cancer cell line and HePC to the Molt-4 leukemia cell line in concentrations of, respectively, 18.6 and 15.0 microM, during a 36-h incubation period at 37 degrees C, 5% CO2. HePC uptake in the leukemia cells was followed by a 24-h reversibility test in drug-free medium. Subsequently, sample clean-up was performed on a weak cation-exchange column. For the quantitative analysis, HePC was used as internal standard for the D-19391 measurements and vice versa. Derivatization of the samples with trimethylsilylbromide was followed by capillary gas chromatographic analysis. From these data we conclude that our uptake results are quite similar with those of a previous study of HePC cellular uptake in the more resistant Caco-2T colon cancer cell line. Without having investigated the mechanism that underlies the cellular uptake results obtained, our study points to no direct correlation between the compounds' cellular uptake and their cytotoxic effects.

  10. Characterization of an organic solvent-tolerant thermostable glucoamylase from a halophilic isolate, Halolactibacillus sp. SK71 and its application in raw starch hydrolysis for bioethanol production.

    Science.gov (United States)

    Yu, Hui-Ying; Li, Xin

    2014-01-01

    A halophilic bacterium Halolactibacillus sp. SK71 producing extracellular glucoamylase was isolated from saline soil of Yuncheng Salt Lake, China. Enzyme production was strongly influenced by the salinity of growth medium with maximum in the presence of 5% NaCl. The glucoamylase was purified to homogeneity with a molecular mass of 78.5 kDa. It showed broad substrate specificity and raw starch hydrolyzing activity. Analysis of hydrolysis products from soluble starch by thin-layer chromatography revealed that glucose was the sole end-product, indicating the enzyme was a true glucoamylase. Optimal enzyme activity was found to be at 70°C, pH 8.0, and 7.5% NaCl. In addition, it was highly active and stable over broad ranges of temperature (0-100°C), pH (7.0-12.0), and NaCl concentration (0-20%), showing excellent thermostable, alkali stable, and halotolerant properties. Furthermore, it displayed high stability in the presence of hydrophobic organic solvents. The purified glucoamylase was applied for raw corn starch hydrolysis and subsequent bioethanol production using Saccharomyces cerevisiae. The yield in terms of grams of ethanol produced per gram of sugar consumed was 0.365 g/g, with 71.6% of theoretical yield from raw corn starch. This study demonstrated the feasibility of using enzymes from halophiles for further application in bioenergy production.

  11. Performance Analysis of Heterodyne-Detected OCDMA Systems Using PolSK Modulation over a Free-Space Optical Turbulence Channel

    Directory of Open Access Journals (Sweden)

    Fan Bai

    2015-10-01

    Full Text Available This paper presents a novel model of heterodyne-detected optical code-division multiple-access (OCDMA systems employing polarization shift keying (PolSK modulation over a free-space optical (FSO turbulence channel. In this article, a new transceiver configuration and detailed analytical model for the proposed system are provided and discussed, taking into consideration the potential of heterodyne detection on mitigating the impact of turbulence-induced irradiance fluctuation on the performance of the proposed system under the gamma-gamma turbulence channel. Furthermore, we derived the closed-form expressions for the system error probability and outage probability, respectively. We determine the advantages of the proposed modeling by performing a comparison with a direct detection scheme obtained from an evaluation of link performance under the same environment conditions. The presented work also shows the most significant impact factor that degrades the performance of the proposed system and indicates that the proposed approach offers an optimum link performance compared to conventional cases.

  12. What is the diet of Palaemon elegans Rathke, 1837 (Crustacea, Decapoda, a non-indigenous species in the Gulf of Gdańsk (southern Baltic Sea?

    Directory of Open Access Journals (Sweden)

    Urszula Janas

    2008-06-01

    Full Text Available Palaemon elegans, a new component of the Gulf of Gdańsk macrozoobenthos,colonised the southern Baltic coastal zone in the late 20th and early 21stcentury. Analysis of the stomach contents of P. elegans revealed 16plant and animal taxa that these prawns had fed on. The principal dietarycomponent was detritus, with a mean frequency of occurrence in stomachs of > 80%.The most frequently occurring plant components in the diet were algaefrom the genus Cladophora and the family Ectocarpaceae, while the mostsignificant animal components were Harpacticoida, Chironomidae, Ostracoda andGammarus spp. The results of the study show that the dietary composition ofP. elegans differed significantly between stations and months. The foraging area consisted of two distinctive regions - the Inner Puck Bay, and the Outer Puck Bay together with the Dead Vistula River; two of the stations - Gdynia and Sopot - were distinctfrom all the others. However, no obvious seasonality in the food compositioncould be demonstrated.

  13. Postavení OPEC v mezinárodních hospodářských vztazích

    OpenAIRE

    Košteková, Eva

    2008-01-01

    Bakalárska práca sa týka Organizácie krajín vyvážajúcich ropu.Cieľom práce je zhodnotiť postavenie OPEC od jeho vzniku, charakterizovať význam tejto organizácie a popísať zapojenie OPEC vo svetovej ekonomike.V prvej časti práce je základná charakteristika OPEC. Druhá časť práce skúma vývoj postavenia OPEC od jeho vzniku v roku 1960 do roku 2000 so zameraním na ropné šoky. Tretia časť práce sa zaoberá postavením OPEC v treťom miléniu, vzťahmi s EÚ a obnoviteľnými zdrojmi energie....

  14. Activation of ATP-sensitive potassium channels enhances DMT1-mediated iron uptake in SK-N-SH cells in vitro

    Science.gov (United States)

    Du, Xixun; Xu, Huamin; Shi, Limin; Jiang, Zhifeng; Song, Ning; Jiang, Hong; Xie, Junxia

    2016-01-01

    Iron importer divalent metal transporter 1 (DMT1) plays a crucial role in the nigal iron accumulation in Parkinson’s disease (PD). Membrane hyperpolarization is one of the factors that could affect its iron transport function. Besides iron, selective activation of the ATP-sensitive potassium (KATP) channels also contributes to the vulnerability of dopaminergic neurons in PD. Interestingly, activation of KATP channels could induce membrane hyperpolarization. Therefore, it is of vital importance to study the effects of activation of KATP channels on DMT1-mediated iron uptake function. In the present study, activation of KATP channels by diazoxide resulted in the hyperpolarization of the membrane potential and increased DMT1-mediated iron uptake in SK-N-SH cells. This led to an increase in intracellular iron levels and a subsequent decrease in the mitochondrial membrane potential and an increase in ROS production. Delayed inactivation of the Fe2+-evoked currents by diazoxide was recorded by patch clamp in HEK293 cells, which demonstrated that diazoxide could prolonged DMT1-facilitated iron transport. While inhibition of KATP channels by glibenclamide could block ferrous iron influx and the subsequent cell damage. Overexpression of Kir6.2/SUR1 resulted in an increase in iron influx and intracellular iron levels, which was markedly increased after diazoxide treatment. PMID:27646472

  15. Sportovní hala se zázemím a restaurací, Valašské Klobouky

    OpenAIRE

    Naiser, Jaromír

    2013-01-01

    Diplomová práce se týká novostavby samostatně stojící sportovní haly se zázemím a restaurací ve Vlašských Kloboukách. Sportovní hala má jedno podlaží částečně zapuštěné pod terénem, obsahuje tribunu pro 340 diváků. Druhá část, tj. zázemí sportovní haly je v podzemním podlaží, v nadzemním podlaží je restaurace s kuchyní. Objekt je navržen v půdorysném tvaru dvou obdélníků. Střecha je sedlová a pultová. Obvodové konstrukce u haly jsou provětrávané, část se zázemím a restaurací je kontaktně zate...

  16. A Natural Product from Polygonum cuspidatum Sieb. Et Zucc. Promotes Tat-Dependent HIV Latency Reversal through Triggering P-TEFb's Release from 7SK snRNP.

    Directory of Open Access Journals (Sweden)

    Cong Wang

    Full Text Available The latent reservoirs of HIV represent a major impediment to eradication of HIV/AIDS. To overcome this problem, agents that can activate latent HIV proviruses have been actively sought after, as they can potentially be used in combination with the highly active antiretroviral therapy (HAART to eliminate the latent reservoirs. Although several chemical compounds have been shown to activate latency, they are of limited use due to high toxicity and poor clinical outcomes. In an attempt to identify natural products as effective latency activators from traditional Chinese medicinal herbs that have long been widely used in human population, we have isolated procyanidin C-13,3',3"-tri-O-gallate (named as REJ-C1G3 from Polygonum cuspidatum Sieb. et Zucc., that can activate HIV in latently infected Jurkat T cells. REJ-C1G3 preferentially stimulates HIV transcription in a process that depends on the viral encoded Tat protein and acts synergistically with prostratin (an activator of the NF-κB pathway or JQ1 (an inhibitor of Brd4 to activate HIV latency. Our mechanistic analyses further show that REJ-C1G3 accomplishes these tasks by inducing the release of P-TEFb, a host cofactor essential for Tat-activation of HIV transcription, from the cellular P-TEFb reservoir 7SK snRNP.

  17. Anionic surfactant linear alkylbenzene sulfonates (LAS) in sediments from the Gulf of Gdańsk (southern Baltic Sea, Poland) and its environmental implications.

    Science.gov (United States)

    Hampel, Miriam; Mauffret, Aourell; Pazdro, Ksenia; Blasco, Julian

    2012-10-01

    Linear alkylbenzene sulfonate (LAS) is a group of anionic surfactants employed in the formulation of laundry and cleaning products, with a global production rate of 4 million metric tons. Sediments from the Polish coast of the southern Baltic Sea were collected at ten stations. Total LAS concentrations, measured by high-performance liquid chromatography, were between 0.04 and 0.72 mg LAS·kg(-1) dry weight. Highest LAS concentrations were found in suspended matter collected from the Vistula River, sediment collected close to the Vistula River mouth and from the Gdańsk Deep, known as the depositional area. With the obtained environmental LAS concentrations, a risk assessment for this surfactant has been carried out, based on publicly available acute and chronic toxicity data in target organisms. The results indicated that LAS could pose a low risk for the existing benthic community applying worst case scenario assessment. This is the first time that levels of LAS have been measured in environmental samples of the southern Baltic Sea.

  18. Extract of Monascus purpureus CWT715 Fermented from Sorghum Liquor Biowaste Inhibits Migration and Invasion of SK-Hep-1 Human Hepatocarcinoma Cells

    Directory of Open Access Journals (Sweden)

    Wen-Teish Chang

    2016-12-01

    Full Text Available Liver cancer is the most endemic cancer in a large region of the world. This study investigated the anti-metastatic effects of an extract of Monascus purpureus CWT715 (MP fermented from sorghum liquor biowaste and its mechanisms of action in highly metastatic human hepatocarcinoma SK-Hep-1 cells. Kinmen sorghum liquor waste was used as the primary nutrient source to produce metabolites (including pigments of MP. In the presence of 10 µg/mL MP-fermented broth (MFB, the anti-invasive activity increased with increasing fermentation time reaching a maximum at six days of fermentation. Interestingly, MFB also produced maximal pigment content at six days. Treatment for 24 h with MFB (10–100 µg/mL obtained from fermentation for six days significantly inhibited cell migration and invasion, and these effects were concentration-dependent. MFB also significantly enhanced nm23-H1 protein expression in a concentration-dependent manner, which was highly correlated with migration and invasion. These results suggest that MFB has significant anti-migration and anti-invasion activities and that these effects are associated with the induction of nm23-H1 protein expression.

  19. siRNA INHIBITS Her2/neu EXPRESSION AND CELL PROLIFERATION IN SK-BR-3 CELL LINE%siRNA抑制SK-BR-3细胞株Her2/neu的表达及细胞增殖

    Institute of Scientific and Technical Information of China (English)

    蒋磊; 倪吴花; 吴建波; 李继承

    2005-01-01

    目的研究siRNA(small interfering RNA)对乳腺癌SK-BR-3细胞株Her2/neu基因表达的抑制作用,为RNAi技术在肿瘤生物治疗中的应用提供实验基础.方法体外合成两条针对Her2/neu基因的siRNA,转染SKBR-3细胞株;分别应用逆转录聚合酶连反应(RT-PCR)法和流式细胞仪测定Her2/neu基因和蛋白的表达,并用MTT比色法测定细胞的增殖活性,Annexin V检测细胞凋亡. 结果两条siRNA分别使Her2/neu基因表达降低了42.88%、49.27%,蛋白表达降低了25.03%、56.59%.同时转染siRNA后细胞生长受到抑制,并发生细胞凋亡,凋亡率分别为28.51%、42.81%.结论siRNA可以有效抑制SK-BR-3细胞株中Her2/neu的表达,从而抑制细胞生长,并导致细胞凋亡.

  20. Study of the process $e^+ e^- \\to K^0_{S}K^0_{L}$ in the center-of-mass energy range 1004--1060 MeV with the CMD-3 detector at the VEPP-2000 $e^+ e^-$ collider

    CERN Document Server

    Kozyrev, E A

    2016-01-01

    The $e^+ e^- \\to K^0_{S}K^0_{L}$ cross section has been measured in the center-of-mass energy range 1004--1060 MeV at 25 energy points using $6.1 \\times 10^5$ events with $K^0_{S}\\to \\pi^+\\pi^-$ decay. The analysis is based on 5.9 pb$^{-1}$ of an integrated luminosity collected with the CMD-3 detector at the VEPP-2000 $e^+ e^-$ collider. To obtain $\\phi(1020)$ meson parameters the measured cross section is approximated according to the Vector Meson Dominance model as a sum of the $\\rho, \\omega, \\phi$-like amplitudes and their excitations. This is the most precise measurement of the $e^+ e^- \\to K^0_{S}K^0_{L}$ cross section with a 1.8\\% systematic uncertainty.

  1. Efficacy and safety of oral SK3530 for the treatment of erectile dysfunction in Korean men: a multicenter, randomized, double- blind, placebo-controlled, fixed dose, parallel group clinical trial

    Institute of Scientific and Technical Information of China (English)

    Jae-Seung Paick; Kwanjin Park; Hyonggi Jung; Nam-Cheol Park; Hyung-Ki Choi; Sae-Chul Kim; Tai-Young Ahn; Je-Jong Kim; Jong-Kwan Park; Kwang-Sung Park; Sung-Won Lee; Sae-Woong Kim

    2008-01-01

    Aim: To evaluate the efficacy and safety of SK3530, a newly developed type 5 phosphodiesterase inhibitor (PDE5I), in Korean men with erectile dysfunction (ED). Methods: A total of 119 patients were randomized at 10 centers in Korea to receive either SK3530 (50, 100, or 150 mg; n = 89) or placebo (n = 30) taken 1 h before anticipated sexual activity for an 8-week period. The patients were evaluated at baseline and 4 and 8 weeks after beginning therapy. Efficacy was assessed using the International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP), and the Global Assessment Question (GAQ). Safety was analyzed by adverse events, laboratory values and vital signs. Results: At the end of the study, all the primary and secondary efficacy end-points were statistically significantly improved by SK3530 compared with placebo (P < 0.05). Of the 89 patients in the treatment arm, 36 (42.3 %) achieved normal erectile mfunction after treatment, including six patients with severe ED. Treatment-related adverse events occurred in 32 patients.The most common adverse events were flushing, headache, dizziness and eye redness (10.9%, 7.6%, 2.5% and 2.5%, respectively), and most were mild. Only two patients discontinued treatment during the study period because of adverse events. Conclusion: The results of our phase Ⅱ study have confirmed the efficacy and safety of SK3530 in a broad population of men with ED of various etiologies and severity. The optimal doses in terms of efficacy and safety were determined to be 50 mg and 100 mg, respectively.

  2. [Roman Czaja. Die Anfänge preussischer Hansestädte im Lichte der historischen und archäologischen quellen : Danzig/Gdańsk, Elbing/Elbląg, Thorn/Toruń] / Dennis Hormuth

    Index Scriptorium Estoniae

    Hormuth, Dennis

    2013-01-01

    Arvustus : Roman Czaja. Die Anfänge preussischer Hansestädte im Lichte der historischen und archäologischen quellen : Danzig/Gdańsk, Elbing/Elbląg, Thorn/Toruń. In: Stadtgründung und Stadterweiterung. Beiträge von Archäologie und Stadtgeschichtsforschung. (=Beiträge zur Geschichte der Städte Mitteleuropas XXII). LInz, 2011. S. 59-74

  3. [Roman Czaja. Die Anfänge preussischer Hansestädte im Lichte der historischen und archäologischen quellen : Danzig/Gdańsk, Elbing/Elbląg, Thorn/Toruń] / Dennis Hormuth

    Index Scriptorium Estoniae

    Hormuth, Dennis

    2013-01-01

    Arvustus : Roman Czaja. Die Anfänge preussischer Hansestädte im Lichte der historischen und archäologischen quellen : Danzig/Gdańsk, Elbing/Elbląg, Thorn/Toruń. In: Stadtgründung und Stadterweiterung. Beiträge von Archäologie und Stadtgeschichtsforschung. (=Beiträge zur Geschichte der Städte Mitteleuropas XXII). LInz, 2011. S. 59-74

  4. Gildi stúdentsprófseinkunnar og hugrænnar getu í forspá um árangur í háskólanámi

    OpenAIRE

    Ásta Bjarnadóttir 1988

    2005-01-01

    Gerð var athugun á forspárgildi stúdentsprófseinkunna og prófs sem mælir almenna hugræna getu (Wonderlic Personnel Test) fyrir árangur nemenda í grunnnámi í háskóla. Niðurstöður fylgniathugana með langtímagögnum frá 85 háskólanemum í viðskipta- og tölvunarfræði benda til að almenn hugræn geta spái betur en stúdentsprófseinkunnir fyrir um einkunnir í háskólanámi (r=0,39 á móti r=0,29). Fylgnin á milli forspárþáttanna tveggja innbyrðis er það lítil (r=0,16) að notkun hugrænnar getu til viðbó...

  5. SK-N-MC cell death occurs by distinct molecular mechanisms in response to hydrogen peroxide and superoxide anions: involvements of JAK2-STAT3, JNK, and p38 MAP kinases pathways.

    Science.gov (United States)

    Moslehi, Maryam; Yazdanparast, Razieh

    2013-07-01

    Oxidative stress plays a vital role in the pathogenesis of neurodegenerative diseases. Nerve cells are incessantly exposed to environmental stresses leading to overproduction of some harmful species like reactive oxygen species (ROS). ROS including hydrogen peroxide and superoxide anion are potent inducers of various signaling pathways encompassing MAPKs and JAK-STAT pathways. In the current study, we scrutinized the effects of hydrogen peroxide and/or menadione (superoxide anion generator) on JNK/p38-MAPKs and JAK2-STAT3 pathways to elucidate the mechanism(s) by which each oxidant modulated the above-mentioned pathways leading to SK-N-MC cell death. Our results delineated that hydrogen peroxide and superoxide anion radical induced distinct responses as we showed that STAT3 and p38 were activated in response to hydrogen peroxide, but not superoxide anion radicals indicating the specificity in ROS-induced signaling pathways activations and behaviors. We also observed that menadione induced JNK-dependent p53 expression and apoptotic death in SK-N-MC cells while H2O2-induced JNK activation was p53 independent. Thus, we declare that ROS type has a key role in selective instigation of JNK/p38-MAPKs and JAK2-STAT3 pathways in SK-N-MC cells. Identifying these differential behaviors and mechanisms of hydrogen peroxide and superoxide anion functions illuminates the possible therapeutic targets in the prevention or treatment of ROS-induced neurodegenerative diseases such as Alzheimer's disease.

  6. Application of ZnO/graphene and S6 aptamers for sensitive photoelectrochemical detection of SK-BR-3 breast cancer cells based on a disposable indium tin oxide device.

    Science.gov (United States)

    Liu, Fang; Zhang, Yan; Yu, Jinghua; Wang, Shaowei; Ge, Shenguang; Song, Xianrang

    2014-01-15

    ZnO/graphene (ZnO/G) composite and S6 aptamer were employed to sensitive photoelectrochemical (PEC) strategy for the specific detection of SK-BR-3 cancer cells based on a portable indium tin oxide microdevice. ZnO/G composite was synthesized using a facile ultrasonic method, and then applied to improve the PEC performance due to the unique hollow structure of ZnO naospheres and the superior properties of graphene. Subsequently, S6 aptamer was applied to this specific detection of SK-BR-3 cancer cells. And the concentration of SK-BR-3 cells was measured with a low detection limit of 58 cells mL(-1) and a wide linear range of 1×10(2)-1×10(6) cells mL(-1), through the decrease in photocurrent intensity resulting from the increase in steric hindrances when specifically recognized with S6 aptamers. Excellent discrimination against target and analogous cells was demonstrated, indicating the high selectivity of the proposed cell sensor. Our work also demonstrated a sensitive, stable and low cytotoxicity approach for early and accurate detection of cancer cells.

  7. Notexin upregulates Fas and FasL protein expression of human neuroblastoma SK-N-SH cells through p38 MAPK/ATF-2 and JNK/c-Jun pathways.

    Science.gov (United States)

    Chen, Ku-Chung; Chang, Long-Sen

    2010-04-01

    Notechis scutatus scutatus notexin induced an increase in Fas and FasL protein expression of human neuroblastoma SK-N-SH cells in a dose- and time-dependent manner. Moreover, notexin treatment upregulated transcription of Fas/FasL mRNA. Downregulation of FADD blocked notexin-induced procaspase-8 degradation and cleavage of Bid and rescued viability of notexin-treated cells. Upon exposure to notexin, activation of JNK and p38 MAPK was observed in SK-N-SH cells. Notexin-induced upregulation of Fas and FasL was suppressed by SB202190 (p38 MAPK inhibitor) and S600125 (JNK inhibitor). Downregulation of p38alpha MAPK and JNK1 by siRNA proved that upregulation of Fas/FasL was related to p38alpha MAPK and JNK1 activation. Notexin treatment evoked p38alpha MAPK-mediated ATF-2 phosphorylation and JNK1-mediated c-Jun phosphorylation. Knockdown of c-Jun and ATF-2 by siRNA or overexpression of dominant-negative c-Jun and ATF-2 revealed that both c-Jun and ATF-2 were crucial for Fas/FasL upregulation. Taken together, our data indicate that notexin-induced upregulation of Fas and FasL is triggered by p38 MAPK/ATF-2 and JNK/c-Jun signaling pathways in SK-N-SH cells. Copyright 2009 Elsevier Ltd. All rights reserved.

  8. High glucose upregulates BACE1-mediated Aβ production through ROS-dependent HIF-1α and LXRα/ABCA1-regulated lipid raft reorganization in SK-N-MC cells.

    Science.gov (United States)

    Lee, Hyun Jik; Ryu, Jung Min; Jung, Young Hyun; Lee, Sei-Jung; Kim, Jeong Yeon; Lee, Sang Hun; Hwang, In Koo; Seong, Je Kyung; Han, Ho Jae

    2016-11-10

    There is an accumulation of evidence indicating that the risk of Alzheimer's disease is associated with diabetes mellitus, an indicator of high glucose concentrations in blood plasma. This study investigated the effect of high glucose on BACE1 expression and amyloidogenesis in vivo, and we present details of the mechanism associated with those effects. Our results, using ZLC and ZDF rat models, showed that ZDF rats have high levels of amyloid-beta (Aβ), phosphorylated tau, BACE1, and APP-C99. In vitro result with mouse hippocampal neuron and SK-N-MC, high glucose stimulated Aβ secretion and apoptosis in a dose-dependent manner. In addition, high glucose increased BACE1 and APP-C99 expressions, which were reversed by a reactive oxygen species (ROS) scavenger. Indeed, high glucose increased intracellular ROS levels and HIF-1α expression, associated with regulation of BACE1 and Liver X Receptor α (LXRα). In addition, high glucose induced ATP-binding cassette transporter A1 (ABCA1) down-regulation, was associated with LXR-induced lipid raft reorganization and BACE1 localization on the lipid raft. Furthermore, silencing of BACE1 expression was shown to regulate Aβ secretion and apoptosis of SK-N-MC. In conclusion, high glucose upregulates BACE1 expression and activity through HIF-1α and LXRα/ABCA1-regulated lipid raft reorganization, leading to Aβ production and apoptosis of SK-N-MC.

  9. Sá veit gjörst hvar skórinn kreppir að sem hefur hann á fætinum

    Directory of Open Access Journals (Sweden)

    Bragi Guðbrandsson

    2006-06-01

    Full Text Available Hér er á ferðinni þriðja athugun Rauða kross Íslands á þessu viðfangsefni, sú fyrsta frá 1994, önnur frá 1999 og svo sú sem hér er til umræðu. Eftir lestur skýrslunnar verð ég að telja það athyglisverðast, og standa raunar algjörlega upp úr, að þeir þjóðfélagshópar sem allar skýrslurnar fjalla um eru að stærstum hluta þeir sömu þótt þær spanni rúmlega áratug: bótaþegar (öryrkjar, einkum geðfatlaðir, aldraðir, hópar lágtekjufólks (einstæðar mæður, einstæðingar og börn sem glíma við erfiðleika. Sagt með öðrum orðum: séu viðteknir mælikvarðar fátæktar, einangrunar og mismununar lagðir til grundvallar hefur - að bestu manna yfirsýn - nánast engin teljandi breyting orðið á samsetningu þess hóps meðbræðra okkar sem höllum fæti standa í samfélaginu á heilum áratug. Eina markverða undantekningin á þessu er sú að í fyrstu könnuninni beindust sjónir manna m.a. að þeim sem voru atvinnulausir en nú eru innflytjendur komnir til sögunnar í þeirra stað. Ástæðan er augljós: uppgangur í efnahagslífinu hefur nánast eytt atvinnuleysinu en þess í stað skapað eftirspurn eftir vinnuafli sem ekki hefur verið unnt að mæta öðru vísi en með því að leita út fyrir landsteinana eftir erlendu verkafólki.

  10. Neuroprotective effects of the Phellinus linteus ethyl acetate extract against H2O2-induced apoptotic cell death of SK-N-MC cells.

    Science.gov (United States)

    Choi, Doo Jin; Cho, Sarang; Seo, Jeong Yeon; Lee, Hyang Burm; Park, Yong Il

    2016-01-01

    Numerous studies have suggested that neuronal cells are protected against oxidative stress-induced cell damage by antioxidants, such as polyphenolic compounds. Phellinus linteus (PL) has traditionally been used to treat various symptoms in East Asian countries. In the present study, we prepared an ethyl acetate extract from the fruiting bodies of PL (PLEA) using hot water extraction, ethanol precipitation, and ethyl acetate extraction. The PLEA contained polyphenols as its major chemical component, and thus, we predicted that it may exhibit antioxidant and neuroprotective effects against oxidative stress. The results showed that the pretreatment of human brain neuroblastoma SK-N-MC cells with the PLEA (0.1-5 μg/mL) significantly and dose-dependently reduced the cytotoxicity of H2O2 and the intracellular ROS levels and enhanced the expression of HO-1 (heme oxygenase-1) and antioxidant enzymes, such as CAT (catalase), GPx-1 (glutathione peroxidase-1), and SOD-1 and -2 (superoxide dismutase-1 and -2). The PLEA also directly scavenged free radicals. PLEA pretreatment also significantly attenuated DNA fragmentation and suppressed the mRNA expression and activation of mitogen-activated protein kinases extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 kinase, which are induced by oxidative stress and lead to cell death. PLEA pretreatment inhibited the activation of the apoptosis-related proteins caspase-3 and poly (ADP-ribose) polymerase. These results demonstrate that the PLEA has neuroprotective effects against oxidative stress (H2O2)-induced neuronal cell death via its antioxidant and anti-apoptotic properties. PLEA should be investigated in an in vivo model on its potential to prevent or ameliorate neurodegenerative disease.

  11. Comparison of the neurotoxicities between volatile organic compounds and fragrant organic compounds on human neuroblastoma SK-N-SH cells and primary cultured rat neurons

    Directory of Open Access Journals (Sweden)

    Yasue Yamada

    2015-01-01

    Full Text Available These are many volatile organic compounds (VOCs that are synthesized, produced from petroleum or derived from natural compounds, mostly plants. Fragrant and volatile organic compounds from plants have been used as food additives, medicines and aromatherapy. Several clinical and pathological studies have shown that chronic abuse of VOCs, mainly toluene, causes several neuropsychiatric disorders. Little is known about the mechanisms of neurotoxicity of the solvents. n-Octanal, nonanal, and 2-ethyl-1-hexanol, which are used catalyzers or intermediates of chemical reactions, are released into the environment. Essential oils have the functions of self-defense, sterilization, and antibiosis in plants. When volatile organic compounds enter the body, there is the possibility that they will pass through the blood–brain barrier (BBB and affect the central nervous system (CNS. However, the direct effects of volatile organic compounds on neural function and their toxicities are still unclear. We compared the toxicities of n-octanal, nonanal and 2-ethyl-1-hexanol with those of five naturally derived fragrant organic compounds (FOCs, linalool, cis-3-hexen-1-ol, isoamyl alcohol, n-propyl alcohol and n-phenethyl alcohol. MTT assay of human neuroblastoma SK-N-SH cells showed that the IC50 values of linalool, cis-3-hexen-1-ol, isoamyl alcohol, n-propyl alcohol and phenethyl alcohol were 1.33, 2.3, >5, >5, and 2.39 mM, respectively, and the IC50 values of toluene, n-octanal, nonanal and 2-ethyl-1-hexanol were 850, 37.2, 8.31 and 15.1 μM, respectively. FOCs showed lower toxicities than those of VOCs. These results indicate that FOCs are safer than other compounds.

  12. Acyclic Cucurbit[n]uril-Type Molecular Container Enables Systemic Delivery of Effective Doses of Albendazole for Treatment of SK-OV-3 Xenograft Tumors.

    Science.gov (United States)

    Hettiarachchi, Gaya; Samanta, Soumen K; Falcinelli, Shane; Zhang, Ben; Moncelet, Damien; Isaacs, Lyle; Briken, Volker

    2016-03-07

    Approximately, 40-70% of active pharmaceutical ingredients (API) are severely limited by their extremely poor aqueous solubility, and consequently, there is a high demand for excipients that can be used to formulate clinically relevant doses of these drug candidates. Here, proof-of-concept studies demonstrate the potential of our recently discovered acyclic cucurbit[n]uril-type molecular container Motor1 (M1) as a solubilizing agent for insoluble drugs. M1 did not induce significant rates of mutations in various Salmonella typhimurium test strains during the Ames test, suggesting low genotoxicity. M1 also has low risk of causing cardiac toxicity in humans since it did not inhibit the human Ether-à-go-go-Related Gene channel as tested on transfected CHO cell lines via patch clamp analysis. Albendazole (ABZ) is a widely used antihelminthic agent but that has also shown promising efficacy against cancerous cells in vitro. However, due to its low aqueous solubility (2.7 μM) and poor pharmacokinetics, ABZ is clinically limited as an anticancer agent. Here we investigated the potential of M1 as a solubilizing excipient for ABZ formulation. A pharmacokinetic study indicated that ABZ escapes the peritoneal cavity resulting in 78% absolute bioavailability, while its active intermediate metabolite, albendazole sulfoxide, achieved 43% absolute bioavailability. The daily dosing of 681 mg/kg M1 complexed with 3.2 mg/kg of ABZ for 14 days did not result in significant weight loss or pathology in Swiss Webster mice. In vivo efficacy studies using this M1·ABZ inclusion complex showed significant decreases in tumor growth rates and increases in survival of mice bearing SK-OV-3 xenograft tumors. In conclusion, we provide substantial new evidence demonstrating that M1 is a safe and efficient excipient that enables in vivo parenteral delivery of poorly water-soluble APIs.

  13. Pleiotropic Anti-Angiogenic and Anti-Oncogenic Activities of the Novel Mithralog Demycarosyl-3D-ß-D-Digitoxosyl-Mithramycin SK (EC-8042.

    Directory of Open Access Journals (Sweden)

    Azahara Fernández-Guizán

    Full Text Available Demycarosyl-3D-ß-D-digitoxosyl-mithramycin SK (DIG-MSK is a recently isolated analogue of mithramycin A (MTA that showed differences with MTA in the DNA binding strength and selectivity. These differences correlated with a better therapeutic index and less toxicity in animal studies. Herein, we show that DIG-MSK displays a potent anti-tumor activity against different types of cancer cell lines, ovarian tumor cells being particularly sensitive to this drug. Of relevance, DIG-MSK exerts low toxicity on fibroblasts and peripheral blood mononuclear cells, this toxicity being significantly lower than that of MTA. In correlation with its antitumor activity, DIG-MSK strongly inhibited Sp1-mediated transcription and endogenous Sp1 mRNA expression, which correlated with the inhibition of the expression of key Sp1-regulated genes involved in tumorigenesis, including VEGFA, BCL2L1 (Bcl-XL, hTERT, BRCA2, MYC and SRC in several ovarian cells. Significantly, DIG-MSK was a stronger inhibitor of VEGFA expression than MTA. Accordingly, DIG-MSK also exhibited potent anti-angiogenic activity on microvascular endothelial cells. Likewise, it significantly inhibited the gene expression of VEGFR1, VEGFR2, FGFR, PDGFB and PDGFRA and, additionally, it induced the expression of the anti-angiogenic factors angiostatin and tunstatin. These effects correlated with a pro-apoptotic effect on proliferating microvascular endothelial cells and the inhibition of the formation of endothelial capillary structures. Overall, the pleiotropic activity of DIG-MSK in inhibiting key oncogenic and angiogenic pathways, together with its low toxicity profile, highlight the therapeutic potential of this new drug.

  14. HLXB9 gene expression, and nuclear location during in vitro neuronal differentiation in the SK-N-BE neuroblastoma cell line.

    Directory of Open Access Journals (Sweden)

    Claudia Giovanna Leotta

    Full Text Available Different parts of the genome occupy specific compartments of the cell nucleus based on the gene content and the transcriptional activity. An example of this is the altered nuclear positioning of the HLXB9 gene in leukaemia cells observed in association with its over-expression. This phenomenon was attributed to the presence of a chromosomal translocation with breakpoint proximal to the HLXB9 gene. Before becoming an interesting gene in cancer biology, HLXB9 was studied as a developmental gene. This homeobox gene is also known as MNX1 (motor neuron and pancreas homeobox 1 and it is relevant for both motor neuronal and pancreatic beta cells development. A spectrum of mutations in this gene are causative of sacral agenesis and more broadly, of what is known as the Currarino Syndrome, a constitutional autosomal dominant disorder. Experimental work on animal models has shown that HLXB9 has an essential role in motor neuronal differentiation. Here we present data to show that, upon treatment with retinoic acid, the HLXB9 gene becomes over-expressed during the early stages of neuronal differentiation and that this corresponds to a reposition of the gene in the nucleus. More precisely, we used the SK-N-BE human neuroblastoma cell line as an in vitro model and we demonstrated a transient transcription of HLXB9 at the 4th and 5th days of differentiation that corresponded to the presence, predominantly in the cell nuclei, of the encoded protein HB9. The nuclear positioning of the HLXB9 gene was monitored at different stages: a peripheral location was noted in the proliferating cells whereas a more internal position was noted during differentiation, that is while HLXB9 was transcriptionally active. Our findings suggest that HLXB9 can be considered a marker of early neuronal differentiation, possibly involving chromatin remodeling pathways.

  15. Et skæg

    DEFF Research Database (Denmark)

    Rytter, Mikkel

    2014-01-01

    I islam er profeten Muhammad en refleksion af Guds vilje, og han har følgelig status som “det perfekte menneske’. Profeten er således et ideal og eksempel til efterfølgelse for muslimer verden over. Dette kapitel diskuterer, hvordan danske sufi-muslimer an- lægger sig signifikante fuldskæg – selvom...

  16. The change on expression level of Alzheimer disease related genes in APP transfected SK-N-SH cells%APP基因转染SK-N-SH细胞中阿尔兹海默病相关基因表达水平的变化

    Institute of Scientific and Technical Information of China (English)

    侯亚萍; 罗涛; 李声; 申秀银; 周跃; 周令麒; 汪华侨

    2015-01-01

    目的 探讨淀粉样前体蛋白(APP)表达对AD相关基因表达水平的影响.方法 构建APP基因的真核表达质粒,并转染人神经母细胞瘤细胞株SK-N-SH细胞,实时定量PCR法检测转染细胞中SIRT1、Tau、PS1、PS2及ApoE4的表达水平变化.结果 成功构建了APP基因的真核表达载体,相对于空载体转染组,转染24、48 h时APP基因的过表达对SK-N-SH中SIRT1基因的表达具有明显的抑制作用(P<0.01、P<0.05);对ApoE4的表达水平有一定的上调作用(P<0.001).转染24、48h时,PS2基因的表达水平均有一定的上调,但均未发现差异有统计学意义(P>0.05).转染24h时,对PS1有上调趋势,但差异无统计学意义(P>0.05),转染48h时,则有下调作用(P<0.05).对Tau,转染24h时有明显的上调作用(P< 0.001),但转染48h时,则有下调趋势,差异无统计学意义(P>0.05).相对于空载体转染组,APP基因转染组的细胞活力显著降低.结论 APP基因的过表达对SK-N-SH细胞中SIRT1基因的表达具有明显的抑制作用;对ApoE4、PS2的表达水平有一定的上调作用,对Tau、PS1的表达水平有上调和下调作用不一,表明这些基因之间存在密切关系和对AD病理机制影响的复杂性,这为揭示不同AD相关基因之间的相互影响及调控机制提供一定的实验证据.

  17. The Jurassic of Denmark and Greenland: An offshore transgressive–regressive mudstone-dominated succession from the Sinemurian of Skåne, Sweden

    Directory of Open Access Journals (Sweden)

    Surlyk, Finn

    2003-10-01

    Full Text Available A Sinemurian mudstone-dominated succession was exposed until recently in the Gantofta quarry in Skåne, southern Sweden. The deposits are placed in the Döshult and Pankarp Members of the Sinemurian–Aalenian Rya Formation. Similar facies of the same age are widespread in the Danish Basin where they constitute the F-Ib unit (F-I member of the Fjerritslev Formation. The Gantofta succession thus represents the easternmost extension of the environment characteristic of the Fjerritslev Formation and is essentially the only locality where it has been possible tostudy the facies of this formation in outcrop. Sedimentation seems to have taken place under relatively quiet tectonic conditions except for the possible fault-control of the basin margin. Thelower part of the Gantofta section is of Early and early Late Sinemurian age. It represents the upper part of the Döshult Member and consists of muddy, lower shoreface sandstones, abruptlyoverlain by dark, bioturbated, fossiliferous mudstones with thin storm siltstones and sandstones. They are overlain by the Upper Sinemurian Pankarp Member which comprises red-brown, restricted marine calcareous mudstones with an upwards increasing number of storm siltstones and sandstones reflecting general shallowing and shoreline progradation.The succession spans the greater part of two simple sequences with a distal sequence boundary located at the boundary between the Döshult Member and the Pankarp Member. The exposed part of the lower sequence includes a thick transgressive systems tract and a very thin highstand systems tract. The upper sequence is represented by an undifferentiated transgressive and highstand systems tract. An Early Sinemurian sea-level rise, a late Early Sinemurian highstand, an early Late Sinemurian fall and a Late Sinemurian minor rise and a major fall are recognised. Nearby boreholes show evidence for an end-Sinemurian – Early Pliensbachian major rise. This evolution corresponds well with

  18. [Spa types and antibiotic resistance of Staphylococcus aureus bloodstream isolates obtained form patients of the University Clinical Center in Gdańsk].

    Science.gov (United States)

    Wiśniewska, Katarzyna; Kasprzyk, Joanna; Piechowicz, Lidia; Bronk, Marek; Swieć, Krystyna

    2013-01-01

    Staphylococcus aureus is a leading cause of bloodstream infections. For epidemiological investigations of this bacteria spa genotyping is used as the method which has a high discriminatory power and gives results that can be easily compared between laboratories. In contrast to methicillin-resistant S.aureus (MRSA), relatively little is known about spa types among methicillin-susceptible strains (MSSA). We used spa typing and antibiotic resistance patterns analysis for retrospective study of S.aureus bloodstream isolates population from the University Clinical Centre (UCC) in Gdańsk. The study was performed on 53 isolates from patients of 19 different units/ departments of the UCC. The isolates were tested for the susceptibility to antimicrobial agents. Spa typing was performed on the basis of the sequence analysis of the polymorphic X region of the protein A gene (spa) amplified form the isolates. Spa types were determined by Ridom Staph Type software and were clustered into spa-CCs (clonal complexes) using the algorithm BURP-based upon repeat pattern. MLST (Multilocus Sequence Typing) clonal complexes were predicted from BURP analysis by the Ridom SpaServer database. In MRSA the staphylococcal chromosomal casette (SCC) mec was determined, Spa-typing yielded 26 types. Six spa-CC and seven singletons were identified. The most frequent was spa-CC021involving 38% of isolates. The CC021 consisted of 7 spa types and the most common was t021 corresponding with MLST-CC30. The second frequent was singleton, related to MLST-CC1, with only one type t127. There were 3 MRSA isolates in the population. The MRSA strains were identified as different spa types: t003/ SCCmecII, t008/SCCmecIV and clonally related to MSSA t032/SCCmecIV. No one MRSA strains belonged to spa-CC021. The spa clonal cluster corresponding with widely distributed among invasive S.aureus strains in Europe MLST-CC30 was found as the most frequent among S.aureus bloodstream isolates from the UCC. Occurrence of

  19. Wybrane problemy wyceny składnikówaktywów i ich ujęcie w sprawozdaniachfinansowych banków

    Directory of Open Access Journals (Sweden)

    Joanna Wielgórska-Leszczyńska

    2010-05-01

    Full Text Available Rachunkowość udostępnia szczegółową i wszechstronną informację o działalności banku. Dla odbiorców najważniejsze są dane o należnościach i depozytach, gdyż to one decydują o kondycji finansowej i płynności banku. Z analizy sprawozdań finan-sowych dwunastu banków, których akcje są notowane na Giełdzie Papierów Warto-ściowych w Warszawie, wynika że nie zawsze są ujawniane wystarczające dane o polityce rachunkowości i zbyt mało miejsca poświęca się należnościom od klien-tów, które stanowią od 30% do 86,8% aktywów. Także nie wskazuje się na fakt, że tylko od 5% do 13,4% aktywów jest finansowanych kapitałami własnymi. Badanie pokazało rozbieżności między bankami w zakresie ujawniania informacji, zastoso-wanych metod wyceny, prezentacji danych w raportach finansowych pod względem ilości i jakości. W najbliższych latach rachunkowość w bankach będzie zmieniała się i rozwijała wraz ze zmianami, jakie są wprowadzane w systemie bankowym. Rozwój ten powinien też iść w kierunku lepszej prezentacji tych składników, które mają zasadniczy wpływ na kondycję i bezpieczeństwo banku. Udostępniane dane powinny być wiarygodne, porównywalne i aktualne oraz podane w sposób syntetyczny (skoncentrowany.

  20. 粪肠球菌SK32.001精氨酸脱亚胺酶的分离纯化及酶学性质研究%Purification and characterization of an arginine deiminase from Enterococcus faecalis SK32.001 producing citrulline

    Institute of Scientific and Technical Information of China (English)

    刘昕; 帅玉英; 张涛; 江波; 缪铭; 沐万孟

    2015-01-01

    对Enterococcus faecalis SK32.001所产的精氨酸脱亚胺酶(ADI)进行分离纯化并对其酶学性质进行研究.实验结果表明,通过细胞破碎,硫酸铵沉淀,HiPrep Q FF 16/10阴离子交换层析,Sephadex G-75等纯化方法获得电泳纯精氨酸脱亚胺酶,分子量约为42ku,催化最适温度和pH分别为50℃和6.5,在30~40℃和pH5.5~7.5时较稳定.不同浓度的Zn2+对酶活性影响较大.1 mmol/L的Zn2+和10mmol/L的Co2+、Ca2+、Mg2+对酶活有较大的促进作用,10mmol/L的Cu2+对酶的抑制作用最强.精氨酸脱亚胺酶在最适反应条件测定其米氏常数为1.33mmol/L,最大反应速度为2.41 μmol/min.

  1. Mechanizmy regulacji odpowiedzi immunologicznej w zwierzęcym modelu alergicznego kontaktowego zapalenia skóry [Mechanisms involved in the regulation of immune response in animal model of allergic contact dermatitis

    Directory of Open Access Journals (Sweden)

    Anna Strzępa

    2014-09-01

    Full Text Available Streszczenie Alergiczne kontaktowe zapalenie skóry jest klasycznym przykładem późnej reakcji nadwrażliwości typu IV, którą mediują limfocyty efektorowe CD4+ Th1. Rozwój alergicznego kontaktowego zapalenia skóry (ACD jest następstwem ekspozycji na działanie małocząsteczkowych substancji (hapteny. Obecnie ACD jest jedną z najczęstszych chorób zawodowych. Występowanie alergii kontaktowej na co najmniej jeden czynnik w krajach Europy Zachodniej i Ameryki Północnej dochodzi do 19,5% dla różnych grup wiekowych. Klasyczna egzematyczna postać ACD manifestuje się jako rumień, naciek, nadmierne rogowacenie, obrzęk i pęcherze, którym towarzyszy świąd. Modelem zwierzęcym ACD jest reakcja nadwrażliwości kontaktowej (CS. Składa się ona z dwóch następujących po sobie etapów: indukcja (faza aferentna i wywołanie (faza eferentna. W trakcie pierwszego kontaktu z haptenem powstają swoiste limfocyty efektorowe (Tef, które są rekrutowane do miejsca ponownej ekspozycji na hapten. W tym artykule przedstawiono mechanizmy immunologiczne leżące u podstaw ACD, opierając się na modelu CS.

  2. Ion Fluxes through KCa2 (SK) and Cav1 (L-type) Channels Contribute to Chronoselectivity of Adenosine A1 Receptor-Mediated Actions in Spontaneously Beating Rat Atria

    Science.gov (United States)

    Bragança, Bruno; Oliveira-Monteiro, Nádia; Ferreirinha, Fátima; Lima, Pedro A.; Faria, Miguel; Fontes-Sousa, Ana P.; Correia-de-Sá, Paulo

    2016-01-01

    Impulse generation in supraventricular tissue is inhibited by adenosine and acetylcholine via the activation of A1 and M2 receptors coupled to inwardly rectifying GIRK/KIR3.1/3.4 channels, respectively. Unlike M2 receptors, bradycardia produced by A1 receptors activation predominates over negative inotropy. Such difference suggests that other ion currents may contribute to adenosine chronoselectivity. In isolated spontaneously beating rat atria, blockade of KCa2/SK channels with apamin and Cav1 (L-type) channels with nifedipine or verapamil, sensitized atria to the negative inotropic action of the A1 agonist, R-PIA, without affecting the nucleoside negative chronotropy. Patch-clamp experiments in the whole-cell configuration mode demonstrate that adenosine, via A1 receptors, activates the inwardly-rectifying GIRK/KIR3.1/KIR3.4 current resulting in hyperpolarization of atrial cardiomyocytes, which may slow down heart rate. Conversely, the nucleoside inactivates a small conductance Ca2+-activated KCa2/SK outward current, which eventually reduces the repolarizing force and thereby prolong action potentials duration and Ca2+ influx into cardiomyocytes. Immunolocalization studies showed that differences in A1 receptors distribution between the sinoatrial node and surrounding cardiomyocytes do not afford a rationale for adenosine chronoselectivity. Immunolabelling of KIR3.1, KCa2.2, KCa2.3, and Cav1 was also observed throughout the right atrium. Functional data indicate that while both A1 and M2 receptors favor the opening of GIRK/KIR3.1/3.4 channels modulating atrial chronotropy, A1 receptors may additionally restrain KCa2/SK activation thereby compensating atrial inotropic depression by increasing the time available for Ca2+ influx through Cav1 (L-type) channels. PMID:27014060

  3. Interferencje składniowe w gwarach wyspowych (na przykładzie rosyjskiej gwary staroobrzędowców z regionu suwalsko-augustowskiego i polskiej gwary mieszkańców Wierszyny na Syberii

    Directory of Open Access Journals (Sweden)

    Dorota Angelika Paśko-Koneczniak

    2015-12-01

    Full Text Available Syntactic interferences in isolated dialects (on the basis of the Russian dialect of the Suwałki–Augustów region Old Believers and the Polish dialect of the inhabitants of Vershina in Siberia The aim of the article is to discuss Polish syntactic interferences in the Russian dialect used by the Old Believers and, by analogy, Russian interferences in the Polish dialect of the inhabitants of Vershina. The dialects of the Old Believers living in the Suwałki-Augustów region and the inhabitants of Vershina are island dialects and are subject to the interferences caused by the languages surrounding them, especially on lexical and syntactic levels. In both dialects, in the case of syntactic interferences, we can observe loan translations of many structures, for instance, changes in terms of government, the ways of expressing age, structures with such cardinal numbers as one, two, three and four, the ways of expressing nominal predicates and the temporal relation signifying frequency and repeatability. Such structures do not contribute towards enriching the lexicon of the dialects with new lexemes, yet they indicate the dynamics of changes in them.   Interferencje składniowe w gwarach wyspowych (na przykładzie rosyjskiej gwary staroobrzędowców z regionu suwalsko-augustowskiego i polskiej gwary mieszkańców Wierszyny na Syberii Celem niniejszego artykułu jest zaprezentowanie polskich interferencji składnio­wych w rosyjskiej gwarze staroobrzędowców i analogicznych rosyjskich interferencji w polskiej gwarze wierszynian. Rosyjska gwara staroobrzędowców z regionu suwal­sko-augustowskiego i polska gwara mieszkańców Wierszyny na Syberii są gwarami wyspowymi i podlegają interferencji ze strony języków otoczenia szczególnie na poziomie leksykalnym i składniowym. W gwarach staroobrzędowców i mieszkańców Wierszyny w przypadku interferencji składniowych możemy zauważyć kalkowanie wielu struktur, np. zmiany w zakresie związku rz

  4. Synthesis of carbon-11 labeled 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinolinium derivatives as new potential PET SK{sub Ca} channel imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Gao Mingzhang; Wang Min [Department of Radiology, Indiana University School of Medicine, 1345 West 16th Street, L-3 Room 202, Indianapolis, IN 46202 (United States); Zheng Qihuang [Department of Radiology, Indiana University School of Medicine, 1345 West 16th Street, L-3 Room 202, Indianapolis, IN 46202 (United States)], E-mail: qzheng@iupui.edu

    2008-02-15

    Small conductance Ca{sup 2+}-activated K{sup +} (SK{sub Ca}) channels play an important role in many functions such as neuronal communication and behavioral plasticity, secretion, and cell proliferation. SK{sub Ca} channel modulation is associated with various brain, heart, and cancer diseases. N-methyl-laudanosine and its structurally related derivatives, substituted 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums, are reversible and selective SK{sub Ca} channel blockers. Carbon-11 labeled N-methyl-laudanosine and its tetrahydroisoquinolinium derivatives may serve as new probes for positron emission tomography (PET) to image SK{sub Ca} channels in the brain, heart, and cancer. The key intermediates, substituted isoquinolines (3a-c), were synthesized using a modification of the Pomeranz-Fritsch procedure. The precursors, substituted 1-(3,4-dimethoxybenzyl)-2-methyl-1,2,3,4-tetrahydroisoquinolines (8a-c), and their corresponding reference standards, substituted 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums (9a-c), were synthesized from compounds 3a-c with 3,4-dimethoxybenzyl chloride (2) in multiple steps with moderate to excellent chemical yields. The precursor 6,7-dimethoxy-1-(3,4-dimethoxybenzyl)-2-methyl-1,2,3, 4-tetrahydroisoquinoline (10) was commercially available, and the methylation of compound 10 with methyl iodide provided N-methyl-laudanosine (11). The target quaternary ammonium tracers, carbon-11 labeled 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums ([{sup 11}C]9a-c and [{sup 11}C]11), were prepared by N-[{sup 11}C]methylation of the tertiary amine precursors (8a-c and 10) with [{sup 11}C]methyl triflate and isolated by a simplified solid-phase extraction (SPE) purification using a SiO{sub 2} or cation-exchange CM Sep-Pak cartridge in 40-65% radiochemical yields.

  5. Inhibition of glucose regulated protein 78 in sensitizing adriamycin-induced apoptosis of human breast cancer cells%抑制葡萄糖调节蛋白78表达对阿霉素诱导人乳腺癌SK-BR-3细胞凋亡的增敏作用

    Institute of Scientific and Technical Information of China (English)

    刘宏莉; 龚萍; 刘浩; 张旭东; 蒋志文

    2010-01-01

    目的:探讨特异性下调葡萄糖调节蛋白78(GRP78)对阿霉素(adriamycin,ADR)诱导人乳腺癌SK-BR-3细胞凋亡的影响,以期为乳腺癌化疗提供新的靶点.方法:培养人乳腺癌SK-BR-3细胞,用ADR(1 mg/L)处理人乳腺癌SK-BR-3细胞0、6、12、24、36 h,Western blot检测GRP78的表达;ADR处理SK-BR-3细胞48 h后,用溴化丙啶染色测定细胞凋亡率;用小分子干扰RNA siRNA预处理SK-BR-3细胞,再予ADR同上处理,检测细胞凋亡率,比较siRNA作用前后细胞凋亡率的变化.结果:ADR可诱导内质网应激,上调GRP78的表达,SK-BR-3细胞对ADR诱导的细胞凋亡率<30%;siRNA可明显阻断GRP78的表达,显著增加ADR诱导的细胞凋亡作用,凋亡率达到(62.30±0.88)%(P<0.01).结论:抑制GRP78的表达可增强人乳腺癌SK-BR-3细胞对ADR经内质网应激途径诱导细胞凋亡的敏感性,促进肿瘤细胞的凋亡,增强其抗肿瘤作用.

  6. Bufalin inhibits migration and invasion in human hepatocellular carcinoma SK-Hep1 cells through the inhibitions of NF-kB and matrix metalloproteinase-2/-9-signaling pathways.

    Science.gov (United States)

    Chen, Ya-Yin; Lu, Hsu-Feng; Hsu, Shu-Chun; Kuo, Chao-Lin; Chang, Shu-Jen; Lin, Jen-Jyh; Wu, Ping-Ping; Liu, Jia-You; Lee, Ching-Hsiao; Chung, Jing-Gung; Chang, Jin-Biou

    2015-01-01

    Metastasis plays an important role in mortality of cancer patients. Migration and invasion are the major characteristics of tumor metastasis. The induction of matrix metalloproteinases (MMPs) such as MMP-2 and -9 are particularly important for the invasiveness of various cancer cells. Bufalin, a class of toxic steroids, was purified from the skin glands of Bufo gargarizans or Bufo melanostictus; it is known to inhibit proliferation of human cancer cells. In this study, we investigated the antiinvasive mechanisms of bufalin in the human hepatocellular cancer cell line SK-Hep1. Bufalin significantly reduced serum-induced cell invasion and migration. Furthermore, bufalin markedly inhibited MMP-2 and -9 activity, mRNA expression and protein levels in SK-Hep1 cells. Bufalin attenuated phosphoinisitide-3-kinase (PI3K) and phosphorylation of AKT which was associated with reduced levels of nuclear factor kappa B (NF-κB). Bufalin also suppressed protein levels of FAK and Rho A, VEGF, MEKK3, MKK7, and uPA and it diminished NF-κB translocation. Based on these observations, we propose that bufalin is acts as an antiinvasive agent by inhibiting MMP-2 and -9 and involving PI3K/AKT and NF-κB pathways. Bufalin is a potential therapeutic agent that may have efficacy in preventing the invasion and metastasis of malignant liver tumors.

  7. Influence of SkQ1 on Expression of Nrf2 Gene, ARE-Controlled Genes of Antioxidant Enzymes and Their Activity in Rat Blood Leukocytes under Oxidative Stress.

    Science.gov (United States)

    Vnukov, V V; Gutsenko, O I; Milutina, N P; Kornienko, I V; Ananyan, A A; Danilenko, A O; Panina, S B; Plotnikov, A A; Makarenko, M S

    2015-12-01

    The study demonstrated that oxidative stress induced by hyperoxia (0.5 MPa for 90 min) resulted in reduction of mRNA levels of transcription factor Nrf2 and Nrf2-induced genes encoding antioxidant enzymes (SOD1, CAT, GPx4) in peripheral blood leukocytes of rats. The changes in gene expression profiles under hyperoxia were accompanied by disbalance of activity of antioxidant enzymes in the leukocytes, namely activation of superoxide dismutase and inhibition of catalase, glutathione peroxidase, and glutathione-S-transferase. Pretreatment of rats with SkQ1 (50 nmol/kg for five days) significantly increased mRNA levels of transcription factor Nrf2 and Nrf2-induced genes encoding antioxidant enzymes SOD2 and GPx4 and normalized the transcriptional activity of the SOD1 and CAT genes in the leukocytes in hyperoxia-induced oxidative stress. At the same time, the activity of catalase and glutathione peroxidase was increased, and the activity of superoxide dismutase and glutathione-S-transferase returned to the control level. It is hypothesized that protective effect of SkQ1 in hyperoxia-induced oxidative stress can be realized via a direct antioxidant property and the stimulation of the Keap1/Nrf2 redox-sensitive signaling system.

  8. 两种培养方法用于乳腺癌SK-BR-3细胞克隆形成实验的对比研究

    Institute of Scientific and Technical Information of China (English)

    张迎; 袁胜利; 姜鹏飞; 邢世超

    2010-01-01

    目的 观察平板克隆形成实验(PCF)和软琼脂克隆形成实验(SACF)用于乳腺癌SK-BR-3细胞学研究的价值.方法 接种1×103~6×104个细胞于12.5 cm2培养瓶(设4个平行样本),分别利用PCF和SACF培养,计数形成克隆数、计算克隆形成率.结果 PCF克隆形成率为0.50%~10.64%,其中接种密度≥1.6×103/cm2者细胞间迅速汇合、难以分辨形成的克隆;SACF克隆形成率为0%~0.33%,接种密度<6.4×102/cm2者无克隆形成.PCF克隆形成率显著高于SACF(P<0.05).结论 检测SK-BR-3细胞对药物或其他治疗方式的敏感性时采用PCF优于SACF.

  9. SK hand scraping polyurea sealing construction for expansion joints of Dahuofang diversion tunnel%大伙房输水隧洞伸缩缝SK手刮聚脲止水施工

    Institute of Scientific and Technical Information of China (English)

    陈浩

    2014-01-01

    In view of the special tunnel construction conditions of the 2nd-stage Dahuofang diversion project, at the expansion joints, superfine cement grouting was conducted first for the internal side of sealing strip, then SK hand scraping polyurea was applied to close the joint. The tunnel was inspected after it was put into operation for more than one year. The results of inspection show good closing of expansion joints. The adhesive strength between SK hand scraping polyurea and concrete exceeds 2.5MPa up to expected effects.%针对大伙房水库输水(二期)工程隧洞施工的特殊条件,伸缩缝处理采取先对伸缩缝止水带内侧进行超细水泥接缝灌浆,再采用SK手刮聚脲进行封闭的方案施工。经1年多的运行后检测,伸缩缝封闭情况良好,SK手刮聚脲与混凝土之间的粘接强度大于2.5 MPa,达到了预期效果。

  10. TRAIL Activates a Caspase 9/7-Dependent Pathway in Caspase 8/10-Defective SK-N-SH Neuroblastoma Cells with Two Functional End Points: Induction of Apoptosis and PGE2 Release

    Directory of Open Access Journals (Sweden)

    Giorgio Zauli

    2003-09-01

    Full Text Available Most neuroblastoma cell lines do not express apical caspases 8 and 10, which play a key role in mediating tumor necrosis factor-related apoptosis-inducing ligand (TRAIL cytotoxicity in a variety of malignant cell types. In this study, we demonstrated that TRAIL induced a moderate but significant increase of apoptosis in the caspase 8/10-deficient SK-N-SH neuroblastoma cell line, through activation of a novel caspase 9/7 pathway. Concomitant to the induction of apoptosis, TRAIL also promoted a significant increase of prostaglandin E2 (PGE2 release by SKN-SH cells. Moreover, coadministration of TRAIL plus indomethacin, a pharmacological inhibitor of cyclooxygenase (COX, showed an additive effect on SKN-SH cell death. In spite of the ability of TRAIL to promote the phosphorylation of both ERKi/2 and p38/MAPK, which have been involved in the control of COX expression/activity, neither PD98059 nor SB203580, pharmacological inhibitors of the ERKi/2 and p38/MAPK pathways, respectively, affected either PGE2 production or apoptosis induced by TRAIL. Finally, both induction of apoptosis and PGE2 release were completely abrogated by the broad caspase inhibitor z-VAD4mk, suggesting that both biologic end points were regulated in SK-N-SH cells through a caspase 9/7-dependent pathway.

  11. Estradiol regulates the expression of small conductance Ca2+ activated K+ channel 3 in rat colonic smooth muscle cells in an estrogen receptor α-dependent manner%α受体依赖的雌二醇对大鼠结肠平滑肌细胞SK3表达的影响

    Institute of Scientific and Technical Information of China (English)

    杨微微; 汤玉蓉; 王云; 李平; 王庆娥; 林琳

    2013-01-01

    目的 探讨17β-雌二醇对大鼠结肠平滑肌细胞(SMC)表达小电导钙激活钾通道3(SK3)的影响及其机制.方法 酶解法分离SD雄性成年大鼠结肠SMC,进行原代培养.细胞免疫荧光双标观察SK3与α-肌动蛋白共表达.取2~3代SMC,不同浓度和不同时间17β-雌二醇刺激后、以反转录实时荧光定量(qRT)-PCR、Western印迹检测SMC表达SK3情况;观察雌激素受体阻断剂ICI182780在17β-雌二醇影响SK3表达中的作用及牛血清白蛋白结合的17β-雌二醇(BSA-E2)、α受体激动剂PPT及β受体激动剂DPN对SK3表达的影响.结果 细胞免疫荧光双标法发现大鼠结肠SMC存在SK3与α-肌动蛋白共表达.不同浓度17β-雌二醇(10、50 nmol/L)刺激结肠SMC后SK3蛋白和mRNA表达量均显著高于溶剂对照组(0.217±0.030、0.321±0.077比0.103±0.063,1.872±0.606、2.967±0.659比0.813±0.202,均P<0.05),50 nmol/L为体外最大有效浓度;SK3表达的高峰时间为第12和24小时(蛋白表达量分别是0h组的2.91、3.30倍,mRNA表达量分别为3.46、3.37倍,均P <0.05).予ICI 182780预处理后加17β-雌二醇,SK3蛋白表达低于17β-雌二醇组(0.111±0.050比0.351±0.084,P<0.05),而与对照组差异无统计学意义;BSA-E2对SK3的表达无影响.α受体激动剂PPT组SK3蛋白表达与17β-雌二醇组均显著高于对照组(0.270±0.071、0.309±0.052比0.087±0.018,均P<0.05);β受体激动剂DPN对SK3蛋白表达无影响.结论 大鼠结肠SMC上存在SK3,17β-雌二醇可促进SK3表达,该作用由α受体介导.%Objective To explore the effects and possible mechanism of 17β-estradiol on the expression of small conductance Ca2+ activated K + channel 3 (SK3) in rat colonic smooth muscle cells (SMC).Methods The SMC isolated from male SD rats by enzymolysis were cultured.And double immunofluorescence staining was used to detect the co-expression of SK3 and α-actin.Colonic SMC were cultured with different concentrations of 17

  12. The Issue of Income from Operating Ukraine Coal Deep Mines/ Problematika Hospodářského Výsledku Hlubinných Uhelných Dolů Ukrajiny

    Directory of Open Access Journals (Sweden)

    Dvořáček Jaroslavav

    2012-12-01

    Full Text Available Příspěvek se zabývá hledáním faktorů, které ovlivňují dosažení kladného nebo záporného hospodářského výsledku hlubinných uhelných dolů Ukrajiny. Je použitá metoda diskriminační analýzy. Dochází se k závěru, že nejvýznamnější příčinou jsou důlně-geologické podmínky, v menší míře pak vliv lidského činitele.

  13. Modular anti-EGFR and anti-Her2 targeting of SK-BR-3 and BT474 breast cancer cell lines in the presence of ErbB receptor-specific growth factors.

    Science.gov (United States)

    Diermeier-Daucher, Simone; Breindl, Stefanie; Buchholz, Stefan; Ortmann, Olaf; Brockhoff, Gero

    2011-09-01

    Over the last decade, a number of monoclonal antibodies and small molecule inhibitors emerged as potent therapeutic agents in the treatment of Her2/neu overexpressing breast cancer. Numerous patients, however, do not adequately respond to anti-epidermal growth factor receptor (EGFR)/Her2 receptor targeting. Receptor- and, in turn, growth-stimulating effects, which potentially hamper antiproliferative cell treatment, have barely been investigated. BT474 and SK-BR-3 breast cancer cell lines were treated with Trastuzumab, Pertuzumab, and Lapatinib alone using different combinations and concentrations. Moreover, epidermal growth factor (EGF) or heregulin (HRG) was added to reveal potential growth factor-mediated compensatory effects. Receptor and intracellular signaling were analyzed as a function of cell treatment. Read-out parameters were cell proliferation and apoptosis. BT474 cells were efficiently driven into quiescence by Trastuzumab, but not by Pertuzumab treatment. Simultaneous EGF or HRG administration, however, restored the BT474 cell proliferation capacity. In contrast, neither therapeutic antibody treatment caused a profound inhibition of SK-BR-3 cell-cycle progress. Lapatinib turned out to be the most potent cell-cycle inhibitor in both cell lines even though its impact was significantly abrogated in the presence of EGF and HRG. The compensatory effect of EGF on Lapatinib-induced cell-cycle inhibition was reversed by Trastuzumab as well as by Pertuzumab treatment. Most importantly, HRG-caused compensation of Lapatinib-induced cell-cycle exit was reversed by Pertuzumab but not by Trastuzumab. Apparently, multiple anti-EGFR/Her2 targeting by using Trastuzumab, Pertuzumab, and Lapatinib more efficiently affects receptor function (interaction and activation) and consequently enhances their antiproliferative capacity. Growth inhibition by anticancer drugs targeted to Her/ErbB receptors, however, can be significantly undermined in the presence of EGF and in

  14. Expression, purification, and analysis of three recombinant ECD disintegrins (r-colombistatins) from P-III class snake venom metalloproteinases affecting platelet aggregation and SK-MEL-28 cell adhesion.

    Science.gov (United States)

    Suntravat, Montamas; Helmke, Thomas J; Atphaisit, Chairat; Cuevas, Esteban; Lucena, Sara E; Uzcátegui, Nestor L; Sánchez, Elda E; Rodriguez-Acosta, Alexis

    2016-11-01

    Crotalid venoms are rich sources of components that affect the hemostatic system. Snake venom metalloproteinases are zinc-dependent enzymes responsible for hemorrhage that also interfere with hemostasis. The disintegrin domain is a part of snake venom metalloproteinases, which involves the binding of integrin receptors. Integrins play an essential role in cancer survival and invasion, and they have been major targets for drug development and design. Both native and recombinant disintegrins have been widely investigated for their anti-cancer activities in biological systems as well as in vitro and in vivo systems. Here, three new cDNAs encoding ECD disintegrin-like domains of metalloproteinase precursor sequences obtained from a Venezuelan mapanare (Bothrops colombiensis) venom gland cDNA library have been cloned. Three different N- and C-terminal truncated ECD disintegrin-like domains of metalloproteinases named colombistatins 2, 3, and 4 were amplified by PCR, cloned into a pGEX-4T-1 vector, expressed in Escherichia coli BL21, and tested for inhibition of platelet aggregation and inhibition of adhesion of human skin melanoma (SK-Mel-28) cancer cell lines on collagen I. Purified recombinant colombistatins 2, 3, and 4 were able to inhibit ristocetin- and collagen-induced platelet aggregation. r-Colombistatins 2 showed the most potent inhibiting SK-Mel-28 cancer cells adhesion to collagen. These results suggest that colombistatins may have utility in the development of therapeutic tools in the treatment of melanoma cancers and also thrombotic diseases. Copyright © 2016. Published by Elsevier Ltd.

  15. Both deterioration and improvement in activities of daily living are related to falls: a 6-year follow-up of the general elderly population study Good Aging in Skåne

    Directory of Open Access Journals (Sweden)

    Stenhagen M

    2014-10-01

    Full Text Available Magnus Stenhagen, Henrik Ekström, Eva Nordell, Sölve Elmståhl Department of Health Sciences, Division of Geriatric Medicine, Lund University, Skåne University Hospital, Malmö, Sweden Objectives: To determine the relationship between long-term change in activities of daily living (ADL and falls in the elderly and to identify characteristics of groups at risk for falls.Methods: This was a 6-year, prospective cohort study using data from the Good Aging in Skåne study in southern Sweden, involving 1,540 elderly subjects, including the oldest-old (age, 60–93 years. The subjects were recruited from the general population. ADL was measured at a baseline and follow-up assessment, using Sonn and Åsberg’s revised scale and the ADL staircase. Falls were recorded in a period of 6 months before the follow-up assessment. The association between falls and change in ADL was calculated using adjusted, multiple logistic regression analysis and presented in odds ratios (ORs.Results: Thirteen percent of the study population reported one or several falls in the measured period. Over the course of 6 years, one in four participants changed their ADL status, and parts of this category had an increased risk for falls compared with those who stayed independent in ADL or who had no change in the ADL staircase. Groups with different characteristics had a prominent risk for falls: those with a reduction of two to eight steps in the ADL staircase (OR, 4.05; 95% confidence interval [CI], 1.62–10.11 and those becoming independent from dependency in instrumental ADL (OR, 4.13; 95% CI, 1.89–9.00. The former group had advanced age with a greater burden of cognitive impairment, gait disability, arrhythmia, and fall risk medications. The latter group had a higher prevalence of ischemic heart disease and low walking speed. Conclusion: Both deterioration and improvement in ADL over the course of 6 years increased the risk for falls in a general elderly population

  16. Skłonność do unikania i uchylania się od opodatkowania w świetle teorii moralnego rozwoju Kohlberga – zagadnienia etyczne w praktyce rachunkowości

    Directory of Open Access Journals (Sweden)

    Sabina Kołodziej

    2016-04-01

    Full Text Available Współczesne służby rachunkowości mają w swoich rękach narzędzia nie tylko umożliwiające ewidencjonowanie operacji gospodarczych w księgach rachunkowych, ale również mogące służyć zarówno do zniekształcania obrazu sytuacji finansowej podmiotu, jak i manipulowania rozliczeniami podatkowymi. Dlatego profesjonaliści w rachunkowości muszą posiąść określoną wiedzę, ale także powinni stać na straży standardów etycznych, co gwarantuje prawidłowość rozliczeń podatkowych oraz sporządzanie informacji wiarygodnej w systemie informacyjnym rachunkowości. Celem artykułu jest przedstawienie wyników badań analizujących częstość wyboru przez księgowych działań zmierzających do redukcji obciążenia podatkowego, będących skutkiem złamania norm etycznych lub prawnych. Ponadto analizowano związek skłonności do podjęcia decyzji prowadzącej do unikania lub uchylania się od opodatkowania z przedstawioną zgodnie z teorią rozwoju moralnego Kohlberga argumentacją takich działań. Wyniki badań wskazują na większą częstość decyzji obniżających zobowiązania podatkowe w wyniku złamania normy etycznej niż etycznej i prawnej. Stwierdzono również, że skłonność do podejmowania działań nieetycznych (i niezgodnych z prawem jest związana z niższymi poziomami wnioskowania moralnego, co potwierdza ważność postulatu uzupełnienia edukacji księgowych o zagadnienia świadomości i odpowiedzialności etycznej przedstawicieli tego zawodu.

  17. LC-MS/MS profiling of a mastic leaf phenol enriched extract and its effects on H2O2 and Aβ(25-35) oxidative injury in SK-B-NE(C)-2 cells.

    Science.gov (United States)

    Pacifico, Severina; Piccolella, Simona; Marciano, Sabina; Galasso, Silvia; Nocera, Paola; Piscopo, Vincenzo; Fiorentino, Antonio; Monaco, Pietro

    2014-12-10

    The development of polyphenol neuroprotective nutraceuticals useful for functional foods could be a valuable strategy for counteracting oxidative stress relative diseases as Alzheimer's Disease (AD). Oxidative stress is one of the AD earliest event and seems to play a central role in Aβ generation, neuroinflammation, and neuronal apoptosis. In order to counteract AD neurodegeneration, the inhibition of the vicious cycle of Aβ generation and oxidation is an attractive therapeutic strategy, and antiamyloidogenic and antioxidant plant drugs could represent an alternative and valid approach. In this context, an alcoholic extract (Pl-M) from deterpenated Pistacia lentiscus L. leaves was investigated for its phenol composition through LC-ESI-MS/MS analysis. Besides the identified metabolites, ten compounds were reported for the first time as constituents of Pistacia lentiscus leaves. Through DPPH, ABTS, and ORAC methods, the antioxidant potential of the extract was initially investigated. In order to evaluate the preparation of a safe and no toxic extract, MTT, SRB, and LDH assays toward SH-5YSY, and SK-N-BE(2)-C human neuronal cell lines, as well as on C6 mouse glial cell line, were performed. Evaluating the protective effects from oxidant injury in SK-N-BE(2)-C cells cotreated with the plant complex and H2O2, or Aβ(25-35) fragment, it was observed that Pl-M extract exerted a significant cytoprotective response in both the oxidized cell systems. In particular, Pl-M extract was able to reduce by nearly 50% the Aβ(25-35) induced toxicity at 25.0 μg/mL dose level, whereas it counteracted almost completely the cytotoxic action at 100.0 μg/mL. Data obtained allow us to hypothesize the use of Pistacia lentiscus leaves, a broadly available and renewable source, as an alternative strategy for the enrichment of food matrices with polyphenol bioactives. The present study put the basis for bioavailability and preclinical studies, able to define Pl-M extract safety and

  18. Myndmennt í íslensku skólakerfi : ætti hún að vera skyldunámsgrein í gegnum allan grunnskólann eða breytast í valgrein á efsta stigi?

    OpenAIRE

    2015-01-01

    Í þessari ritgerð verður fjallað um og lögð fram rök fyrir því af hverju myndmennt ætti að vera skyldunám í grunnskóla á öllum stigum. Eins og staðan er í dag er vægi myndmenntar metið hátt á yngsta stigi en eftir því sem börnin eldast dvínar það og tímafjöldinn sem áætlaður er fyrir list- og verkgreinar í skólum minnkar almennt. Til þess að gefa umræðunni fræðilegan vinkil er horft til fræðimannanna Elliot W. Eisners, Howard Gardners og Lev Vygotskys. Kenningar Eisners eru lagðar til gru...

  19. Induction of Mitochondrial Changes Associated with Oxidative Stress on Very Long Chain Fatty Acids (C22:0, C24:0, or C26:0-Treated Human Neuronal Cells (SK-NB-E

    Directory of Open Access Journals (Sweden)

    Amira Zarrouk

    2012-01-01

    Full Text Available In Alzheimer's disease, lipid alterations point towards peroxisomal dysfunctions. Indeed, a cortical accumulation of saturated very long chain fatty acids (VLCFAs: C22:0, C24:0, C26:0, substrates for peroxisomal β-oxidation, has been found in Alzheimer patients. This study was realized to investigate the effects of VLCFAs at the mitochondrial level since mitochondrial dysfunctions play crucial roles in neurodegeneration. On human neuronal SK-NB-E cells treated with C22:0, C24:0, or C26:0 (0.1–20 μM; 48 h, an inhibition of cell growth and mitochondrial dysfunctions were observed by cell counting with trypan blue, MTT assay, and measurement of mitochondrial transmembrane potential (Δψm with DiOC6(3. A stimulation of oxidative stress was observed with DHE and MitoSOX used to quantify superoxide anion production on whole cells and at the mitochondrial level, respectively. With C24:0 and C26:0, by Western blotting, lower levels of mitochondrial complexes III and IV were detected. After staining with MitoTracker and by transmission electron microscopy used to study mitochondrial topography, mass and morphology, major changes were detected in VLCFAs treated-cells: modification of the cytoplasmic distribution of mitochondria, presence of large mitochondria, enhancement of the mitochondrial mass. Thus, VLCFAs can be potential risk factors contributing to neurodegeneration by inducing neuronal damages via mitochondrial dysfunctions.

  20. Akt/Nrf2 activated upregulation of heme oxygenase-1 involves in the role of Rg1 against ferrous iron-induced neurotoxicity in SK-N-SH cells.

    Science.gov (United States)

    Du, Xixun; Xu, Huamin; Jiang, Hong; Xie, Junxia

    2013-07-01

    Iron accumulation is considered to be involved in the pathogenesis of Parkinson's disease (PD). Our previous studies have observed that Rg1, a major pharmacologically active ingredient from Ginseng, could protect dopaminergic neurons by reducing nigral iron levels through regulating the expression of iron transporters in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice. The aim of this study is to investigate other mechanism involved in the cytoprotection of Rg1 against iron-induced neurotoxicity in human neuroblastoma SK-N-SH cells. Significant rescue of Rg1 on cell viability against 100 μM ferrous iron-induced neurotoxicity was observed. Upregulation of heme oxygenase-1 (HO-1) and Cu-Zn superoxide dismutase (Cu/Zn SOD) were observed in Rg1 pretreated group. Moreover, Rg1 pretreatment induces Nrf2 nuclear translocation, which is upstream of HO-1 expression, and activated PI3K/Akt pathway was also observed in Rg1 pretreated group. This could antagonize iron-induced increase in intracellular reactive oxygen species and decrease in mitochondrial transmembrane potential. These results suggest that the neuroprotective effects of Rg1 against iron toxicity are attributed to the anti-oxidative properties by activating Akt/Nrf2 pathway and increasing Nrf2-induced expression of HO-1 and Cu/Zn SOD.

  1. Study of the $K^{0}_{S}K^{0}_{S}$ Final State and the $K^{0}_{S}$ Inclusive Production in Two-Photon Collisions with the L3 Detector at LEP

    CERN Document Server

    Braccini, S

    2001-01-01

    The K$^0_s$K$^0_s$ final state in two-photon collisions is studied with the L3 detector at LEP using data collected at centre of mass energies from 91 GeV to 202 GeV. The mass spectrum is dominated by the formation of the f$'_2$(1525) tensor meson in helicity two state. Clear evidence for destructive f$_2$-a$_2$ interference is observed. The first study of the f$_J$(1710) in two-photon collisions is presented. No signal has been observed in the region around 2.2 GeV and an upper limit for the two-photon partial width of the $\\xi$(2220) glueball candidate is derived. In the reaction $\\epem\\rightarrow\\epem$hadrons the inclusive production of $\\kos$ mesons is studied using data collected by the L3 detector at LEP centre of mass energies from 189 to 202 GeV. The differential production cross sections as a function of the transverse momentum and of the pseudorapidity are measured and a reasonable agreement is found between our measurement and the Next-to-Leading order QCD predictions.

  2. Description of Cretaceous Sedimentary Sequence of the Second and Third Member of the Qingshankou Formation Recovered by CCSD-SK-Is Borehole in Songliao Basin: Lithostratigraphy, Sedimentary Facies and Cyclic Stratigraphy

    Science.gov (United States)

    Wang, Pujun; Gao, Youfeng; Cheng, Rihui; Wang, Guodong; Wu, Heyong; Wan, Xiaoqiao; Yang, Gansheng; Wang, Zhongxing

    The second and third member of the Qingshankou Formation recovered by CCSD-SK-Is borehole (China Cretaceous Continental Scientific Drilling-SongkeI-the south borehole) is 415.61 m long and 100% of cores recovery. The age of the member corresponds approximately to the Coniacian. The sequence and process of lithology-lithofacies and cyclic stratigraphy were revealed by a detailed core description. 12 rock types and 2 kinds of sedimentary subfacies including semi-deep lake and shallow lake were recognized from the drilling core of the second and third member of the Qingshankou Formation. 10 sedimentary microfacies are present, including dolomite, marl, limestone, oil shale, semi-deep lake turbidite, volcanic ash, seismite, semi-deep lake mudstone, shallow lake mudstone, and shallow lake turbidite microfacies. The second and third member of the Qingshankou Formation represents 422 meter-scale cycles (sixth-order cycle), 130 fifth-order cycles, 21 fourth-order cycles, and one third-order cycles. The special lithologies, such as mudstone, seismite, dolomite, volcanic ash, and so on are important to researches on source rocks and lacustrine event sediments.

  3. Curcumin Suppresses Phthalate-Induced Metastasis and the Proportion of Cancer Stem Cell (CSC)-like Cells via the Inhibition of AhR/ERK/SK1 Signaling in Hepatocellular Carcinoma.

    Science.gov (United States)

    Tsai, Cheng-Fang; Hsieh, Tsung-Hua; Lee, Jau-Nan; Hsu, Chia-Yi; Wang, Yu-Chih; Kuo, Kung-Kai; Wu, Hua-Lin; Chiu, Chien-Chih; Tsai, Eing-Mei; Kuo, Po-Lin

    2015-12-09

    Recent evidence indicating that phthalates promote cancer development, including cell proliferation, migration, and invasion, has raised public health concerns. Here, we show that bis(2-ethylhexyl) phthalate promotes the migration, invasion, and epithelial-mesenchymal transition of hepatocellular carcinoma cells. In addition, bis(2-ethylhexyl) phthalate increased the proportion of cancer stem cell (CSC)-like cells and stemness maintenance in vitro as well as tumor growth and metastasis in vivo. The various activities of curcumin, including anticancer, anti-inflammation, antioxidation, and immunomodulation, have been investigated extensively. Curcumin suppressed phthalate-induced cell migration, invasion, and epithelial-mesenchymal transition, decreased the proportion of CSC-like cells in hepatocellular carcinoma cell lines in vitro, and inhibited tumor growth and metastasis in vivo. We also reveal that curcumin suppressed phthalate-induced migration, invasion, and CSC-like cell maintenance through inhibition of the aryl hydrocarbon receptor/ERK/SK1/S1P3 signaling pathway. Our results suggest that curcumin may be a potential antidote for phthalate-induced cancer progression.

  4. An apolar Pistacia lentiscus L. leaf extract: GC-MS metabolic profiling and evaluation of cytotoxicity and apoptosis inducing effects on SH-SY5Y and SK-N-BE(2)C cell lines.

    Science.gov (United States)

    Piccolella, Simona; Nocera, Paola; Carillo, Petronia; Woodrow, Pasqualina; Greco, Vincenza; Manti, Lorenzo; Fiorentino, Antonio; Pacifico, Severina

    2016-09-01

    In the course of a cytotoxicity screening of Mediterranean plants vs. neuroblastoma cells, Pistacia lentiscus was of interest. Pl-C extract, prepared from dried leaves by ultrasound assisted maceration (UAM) in chloroform, was profiled through using GC-MS techniques. To evaluate Pl-C cytotoxicity towards SH-SY5Y and SK-N-BE(2)-C cell lines, MTT, SRB and LDH assays were performed. The caspase-3 activation, DNA fragmentation, as well as micronucleation, were also evaluated. The Pl-C oxidant/antioxidant ability was estimated using different methods. The extract, rich in pentacyclic triterpenes, inhibited mitochondrial redox activity and cell viability of the tested cell lines. LDH assay established that Pl-C did not affect the cell membrane integrity. Indeed, it was able to activate caspase-3 and to cause a ladder pattern of DNA. Western blotting analysis showed that Pl-C processed caspase-3 providing two cleavage products of approximately 20 and 17-kDa, whose densitometric evaluation highlighted that Pl-C was more effective than vinblastine by 3-fold. The pro-apoptotic effect could be related to a disturbance in cell redox balance. In fact, it increased intracellular ROS production, GSSG/GSH ratio and the formation of lipoperoxidation products. The data obtained prompted to further investigate and assess the in vivo efficacy of Pl-C to prevent and/or treat neuroblastoma.

  5. Research of Financing Technological Equipment in Process of Loading and Transportation of Sand and Gravel/ Výzkum Financování Technologických Zařízení V Procesu Nakládání A Dopravy Štěrkopísků

    Directory of Open Access Journals (Sweden)

    Kučerová Lucie

    2012-12-01

    Full Text Available Příspěvek se zabývá problematikou financování technologických investic. Konkrétně jde o proces nakládání a dopravy štěrkopísků. Výzkum byl proveden formou dotazníkového šetření. Hlavním cílem příspěvku je zjistit, z jakých zdrojů je financován proces nakládání a dopravy štěrkopísků ve vybraných podnicích. Dalším cílem bylo vyhodnotit, zda vybrané průmyslové podniky outsourcují proces nakládání a dopravy. Pokud ano, pak bylo zapotřebí zjistit, jaký je nejčastější důvod takového rozhodnutí. Problematika financování technologických procesů při nakládání a dopravě štěrkopísků představuje zajímavou oblast, která doposud nebyla zmapována.

  6. HER-2/neu·siRNA表达载体的构建及对人乳腺癌细胞株的影响%Vector construction and silencing effects of siRNA to HER-2/neu gene of human breast cancer cell line SK-BR-3

    Institute of Scientific and Technical Information of China (English)

    万光霞; 林辉; 刘浔阳

    2010-01-01

    目的:探讨siRNA 对人乳腺癌细胞株SK-BR-3 的HER-2/neu基因表达的影响.方法:以HER-2/neu mRNA 序列为模板设计合成2对siRNA 序列,构建pGenesil-1-HER-2/neu siRNA 重组质粒,转化感受态的大肠杆菌,质粒酶切、测序鉴定.转染SK-BR-3 细胞48 h后,提取RNA 进行RT-PCR,采用方差分析(ANOVA),分析RNA 干扰效应.结果:成功构建了pGenesil-1-HER-2/neu siRNA 重组质粒,成功转染SK-BR-3 细胞.重组质粒抑制HER-2/neu基因的表达接近54.45 %( P =0.000).结论: HER-2/neu siRNA 重组质粒明显下调HER-2/neu 基因在乳腺癌细胞中的表达.

  7. Hypothyroidism After Head-and-Neck Radiotherapy in Children and Adolescents: Preliminary Results of the 'Registry for the Evaluation of Side Effects After Radiotherapy in Childhood and Adolescence' (RiSK)

    Energy Technology Data Exchange (ETDEWEB)

    Boelling, Tobias, E-mail: Tobias.Boelling@uni-muenster.de [Department of Radiotherapy, University Hospital of Muenster, Muenster (Germany); Department of Radiotherapy, Paracelsus Clinic Osnabrueck, Osnabrueck (Germany); Geisenheiser, Alina [Department of Radiotherapy, University Hospital of Muenster, Muenster (Germany); Pape, Hildegard [Department of Radiotherapy, University Hospital of Duesseldorf, Duesseldorf (Germany); Martini, Carmen [Department of Radiotherapy, University Hospital of Freiburg, Freiburg (Germany); Ruebe, Christian [Department of Radiotherapy, University Hospital of Homburg/Saar, Homburg/Saar (Germany); Timmermann, Beate [Center for Proton Radiation Therapy, Paul-Scherrer-Institute, Villigen (Switzerland); Fischedick, Karin [Department of Radiotherapy, University of Aachen, Aachen (Germany); Kortmann, Rolf-Dieter [Department of Radiotherapy, University of Leipzig, Leipzig (Germany); Gerss, Joachim; Koch, Raphael [Department of Medical Informatics and Biomathematics, University of Muenster, Muenster (Germany); Center for Clinical Trials, University Hospital of Muenster, Muenster (Germany); Willich, Normann [Department of Radiotherapy, University Hospital of Muenster, Muenster (Germany)

    2011-12-01

    Purpose: The 'Registry for the Evaluation of Side Effects After Radiotherapy in Childhood and Adolescence' (RiSK) has been established to prospectively characterize dose-volume effects of radiation in terms of side effects. The aim of this analysis was to characterize the function of the thyroid gland after radiotherapy to the head-and-neck region in children and adolescents. Methods and Materials: Detailed information regarding radiation doses to at-risk organs has been collected across Germany since 2001. Thyroid function was evaluated by blood value examinations of thyroid-stimulating hormone, triiodothyronine, and thyroxine. Information regarding thyroid hormone substitution was requested from the treating physicians. Results: Until May 2009, 1,086 patients from 62 centers were recruited, including 404 patients (median age, 10.9 years) who had received radiotherapy to the thyroid gland and/or hypophysis. Follow-up information was available for 264 patients (60.9%; median follow-up, 40 months), with 60 patients (22.7%) showing pathologic values. In comparison to patients treated with prophylactic cranial irradiation (median dose, 12 Gy), patients with radiation doses of 15 to 25 Gy to the thyroid gland had a hazard ratio of 3.072 (p = 0.002) for the development of pathologic thyroid blood values. Patients with greater than 25 Gy to the thyroid gland and patients who underwent craniospinal irradiation had hazard ratios of 3.768 (p = 0.009) and 5.674 (p < 0.001), respectively. The cumulative incidence of thyroid hormone substitution therapy did not differ between defined subgroups. Conclusions: Radiation-induced thyroid function impairment, including damage to the thyroid gland and/or hypophysis, can frequently be observed after radiotherapy in children. A structured follow-up examination is advised.

  8. Silencing of CerS6 increases the invasion and glycolysis of melanoma WM35, WM451 and SK28 cell lines via increased GLUT1-induced downregulation of WNT5A.

    Science.gov (United States)

    Tang, Yuanyuan; Cao, Ke; Wang, Qi; Chen, Jia; Liu, Rui; Wang, Shaohua; Zhou, Jianda; Xie, Huiqing

    2016-05-01

    Ceramide synthases (CerSs) have been shown to regulate numerous aspects of cancer development. CerS6 has been suggested to be involved in cancer etiology. However, little is known concerning the exact effect of CerS6 on the malignant behavior of melanoma, including glycolysis, proliferation and invasion. In the present study, we found that the expression of CerS6 was low in the melanoma cell lines, including WM35, WM451 and SK-28, and the expression level was related to the malignanct behavior of the melanoma cell lines. We constructed overexpression and silencing models of CerS6 in three melanoma cell lines and found that silencing of CerS6 promoted the ability of proliferation and invasion in the melanoma cell lines. Additionally, downregulation of CerS6 upregulated the activity of glycolysis-related enzyme, and enhanced the expression of glycolysis-related genes, including GLUT1 and MCT1. Furthermore, we identified the genes whose expression levels were changed after silencing of CerS6 by gene microarray. The expression of glycolysis-related gene SLC2A1 (also known as GLUT1) was found to be upregulated, while notably WNT5A was downregulated. The altered expression of GLUT1 and WNT5A was verified by qPCR and western blotting. Furthermore, silencing of GLUT1 in the melanoma cells resulted in the increased expression of WNT5A and the decreased ability of invasion and proliferation in the melanoma cells. Collectively, silencing of CerS6 induced the increased expression of GLUT1, which downregulated the expression of WNT5A and enhanced the invasion and proliferation of melanoma cells. Thus, CerS6 may provide a novel therapeutic target for melanoma treatment.

  9. Apigenin causes G(2)/M arrest associated with the modulation of p21(Cip1) and Cdc2 and activates p53-dependent apoptosis pathway in human breast cancer SK-BR-3 cells.

    Science.gov (United States)

    Choi, Eun Jeong; Kim, Gun-Hee

    2009-04-01

    We studied the effects of apigenin on the cell cycle distribution and apoptosis of human breast cancer cells and explored the mechanisms underlying these effects. We first investigated the antiproliferative effects in SK-BR-3 cells exposed to between 1 and 100 microM apigenin for 24, 48 and 72 h. Apigenin significantly inhibited cell proliferation at concentrations over 50 microM, regardless of exposure time (P<.05), and resulted in significant cell cycle arrest in the G(2)/M phase after 48 h of treatment at high concentrations (50 and 100 microM; P<.05). To investigate the regulatory proteins of cell cycle arrest affected by apigenin, we treated cells with 50 and 100 microM apigenin for 72 h. Apigenin caused a slight decrease in cyclin D and cyclin E expression, with no change in CDK2 and CDK4. In addition, the apigenin-induced accumulation of the cell population in the G(2)/M phase resulted in a decrease in CDK1 together with cyclin A and cyclin B. In an additional study, apigenin also increased the accumulation of p53 and further enhanced the level of p21(Cip1), with no change in p27(Kip1). The expression of Bax and cytochrome c of p53 downstream target was increased markedly at high concentration treatment over 50 microM apigenin. Based on our findings, the mechanism by which apigenin causes cell cycle arrest via the regulation of CDK1 and p21(Cip1) and induction of apoptosis seems to be involved in the p53-dependent pathway.

  10. The use of spa and phage typing for characterization of clinical isolates of methicillin-resistant Staphylococcus aureus in the University Clinical Center in Gdańsk, Poland.

    Science.gov (United States)

    Wiśniewska, Katarzyna; Szewczyk, Anna; Piechowicz, Lidia; Bronk, Marek; Samet, Alfred; Swieć, Krystyna

    2012-05-01

    The emergence of spa types and spa-clonal complexes (CC) among clinical methicillin-resistant Staphylococcus aureus isolates collected from the University Clinical Center in Gdańsk between 2008 and 2009 were investigated. Phage typing was used as the initial screening in the study. The basic set of phages and the additional set of phages were used. Most of the isolates (56 %) belonged to the phage group III. With the additional set of phages, eight types were found, with predominant one MR8 (50 %). Sixteen distinct spa types were observed. The most frequent were t003 (22 %), t151 (16 %), and t008 (12 %). The spa types were clustered into two spa-CC and eight singletons. The predominant CC010 (50 %) consisted of six types, with the most common t003 (36.7 %) and t151(26.7 %), and in 80 % was identified as staphylococcal chromosomal casette mec (SCCmec) type II. The second cluster has no founder (12 %) with only two spa types: t037 belonging to SCCmec type III and t029. In the most frequent singleton, spa type t008 alone was clustered in 12 % of the isolates. All singletons correspond to SCCmec type IV. The CC010 was distributed in most of the hospital wards, corresponded to Multilocus sequence typing type ST5/ST225 and was constantly present throughout the observed period. The isolates of CC010 generally belonged to the phage group III, and most of them (53.3 %) were resistant to erythromycin, clindamycin, and ciprofloxacin. The concordance between spa-clone and phage type was very high, but the same phage type MR8 was observed within different spa types of the predominant clone.

  11. Skønlitteraturen som opposition

    DEFF Research Database (Denmark)

    Larsen, Pelle Oliver

    2011-01-01

    Troels Troels-Lund er kendt som foregangsmanden i den første kulturhistoriske bølge i Danmark fra omkring 1880. Hans form for kulturhistorie vandt imidlertid aldrig for alvor faghistorikernes anerkendelse, og Troels-Lund blev udgrænset. Denne artikel går tilbage til 1870’erne og indeholder en ana...

  12. Fra SK 4b til MH 17

    DEFF Research Database (Denmark)

    Stræde, Therkel

    2015-01-01

    Om den nazistiske besættelsespolitik i Sydøstukraine og Sonderkommando 4b's udryddelse af jøder på den egn, hvor Malaysian Airlines MH 17 styrtede ned den 17. juli 2014......Om den nazistiske besættelsespolitik i Sydøstukraine og Sonderkommando 4b's udryddelse af jøder på den egn, hvor Malaysian Airlines MH 17 styrtede ned den 17. juli 2014...

  13. Skærmlæsning

    DEFF Research Database (Denmark)

    Bundsgaard, Jeppe

    2009-01-01

    Faglig læsning har fået en stadig større plads i læseundervisningen i de senere år. Denne artikel handler om de læseformer som er nødvendige ved det man kan kalde surfesøgning på internettet. I artiklen præsenteres også undervisningskonceptet Dynamitbogen, som elever kan bruge til at skrive til h...

  14. Skærpet bevidsthed om supervision

    DEFF Research Database (Denmark)

    Pedersen, Inge Nygaard

    2002-01-01

    This article presents a historical survey of the initiatives which have taken place in european music therapy towards developing a deeper consciousness about supervision. Supervision as a disciplin in music therapy training, as a maintenance of music therapy profession and as a postgraduate...... training for examined music therapists. Definitions are presented and methods developed by working groups in european music therapy supervision are presented....

  15. Nordlyset og skæbnen

    DEFF Research Database (Denmark)

    Pedersen, Jens Olaf Pepke

    2012-01-01

    Sophus Tromholt. Udforskningen af nordlyset blev hans livsopgave, men han var langt forud for sin tid, og i dag er hans indsats stort set ukendt. Det rådes der nu bod på.......Sophus Tromholt. Udforskningen af nordlyset blev hans livsopgave, men han var langt forud for sin tid, og i dag er hans indsats stort set ukendt. Det rådes der nu bod på....

  16. Fra SK 4b til MH 17

    DEFF Research Database (Denmark)

    Stræde, Therkel

    2015-01-01

    Om den nazistiske besættelsespolitik i Sydøstukraine og Sonderkommando 4b's udryddelse af jøder på den egn, hvor Malaysian Airlines MH 17 styrtede ned den 17. juli 2014......Om den nazistiske besættelsespolitik i Sydøstukraine og Sonderkommando 4b's udryddelse af jøder på den egn, hvor Malaysian Airlines MH 17 styrtede ned den 17. juli 2014...

  17. Brig SK Mazumdar and INMAS : A Profile

    Directory of Open Access Journals (Sweden)

    A. Nagaratnam

    1990-10-01

    Full Text Available As a warm human personality that Brig. Mazumdar is remembered by his colleagues, friends and patients. He was basically an agnostic but was extremely understanding of and respectful to differing points of view. He thought deeply about the role of the physician in tomorrow's world, He felt that valid connections have to be established between culture, religion, morality, environment and scientific humanism. The ultimate goal of the physician is not mere delivery of medical skill but to bring man into tune with his environment. He was not merely a nuclear medicine specialist, but an outstanding endocrinologist, cardiologist and neurologist. In fact, he viewed the disease p-rocess in its totality and never forgot the human element.

  18. Rideudstyr og skøjter

    DEFF Research Database (Denmark)

    2014-01-01

    Finds from Aggersborg: snaffle-bit, buckles, strap-slides, strap-mounts, iron loop, strap-pendants, bell, enamelled roundel, spurs, animal-head - fragment of a spur?, calkin, ice-skates......Finds from Aggersborg: snaffle-bit, buckles, strap-slides, strap-mounts, iron loop, strap-pendants, bell, enamelled roundel, spurs, animal-head - fragment of a spur?, calkin, ice-skates...

  19. Humboldt SK pilot biodigester receives funding

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    2005-09-30

    The Canada-Saskatchewan Western Economic Partnership Agreement (WEPA) will provide funding for Canada's first pilot-scale biodigester to be built in Humboldt, Saskatchewan. The $208,138 pilot facility will use household garbage as well as agricultural waste such as manure and livestock operations, abattoirs and food processing to create heat or power and fertilizer. Support for this bio-energy facility, which could also reduce greenhouse gases, will come from the Prairie Agricultural Machinery Institute which has received $186,138 from Canada and Saskatchewan in the form of cost-shared federal-provincial funding. The pilot plant will test different combinations of waste material feedstocks and the characteristics of the resulting gas end products. The pilot facility will also provide design information for full-scale biodigester manufacturers in Canada. It is expected that 25 full-scale biodigesters will be constructed in Canada in the near future.

  20. 发酵产菊糖果糖转移酶的培养基设计及菌体生长动力学研究%Optimization of Inulin Fructotransferase-producing Medium and Determination of Cell Growth Kinetic Parameter for Arthrobacter ureafaciens SK-8.001

    Institute of Scientific and Technical Information of China (English)

    卢峥嵘; 赵萌; 沐万孟; 张涛; 江波

    2009-01-01

    In this paper,the optimal inulin fructotransferase-producing medium and fermentation kinetic parameters of Arthrobacter ureafaciens SK -8.001 were studied. The recipes of optimal media included 2. 5% inulin,0. 3% NaN0_3,0. 1% yeast extract,0. 01% MgSO_4,0. 04% KH_2P0_4,0. 001% FeSO_4·7H_2O. The maximum enzyme activity reached 19. 85 U/mL,which was 2. 04 fold higher than in initial media. The study on the fermentation process in the optimal media suggested the right time to add inducers into the media was 12 h or 66th hours during the fermentation. The cell growth kinetic model for SK-8.001 in batch fermentation was X (t) = 9. 356 05/ [1 + exp~((4.4222-0.1102l)) ].%对1株产菊糖果糖转移酶(inulin fructotransferase)的金黄色节杆菌(Arthrobacter ureafaciens)SK-8.001的产酶培养基进行了优化,同时对其在分批发酵过程中培养基组分变化和菌体生长动力学进行了研究.所得到的改进型产酶培养基配方为25 g/L菊糖,3 g/L NaNO_3,1g/L酵母膏,0.1 g/L MgSO_4,0.4g/L KH_2PO_4,0.01g/LFeSO_4·7H_2O.在此培养基中的最高酶活达到19.85 U/mL,较初始培养基提高了2.04倍.对在此培养基中Sk-8.001的发酵过程研究发现发酵12 h和66 h是较为理想的诱导物添加时刻.得到SK-8.001在优化培养基中分批培养的菌体生长动力学模型为:X(t)=9.356 05/[1+exp~((4.4222-0.1102:))].

  1. 壳聚糖纳米粒介导人表皮生长因子受体2小干扰RNA抑制乳腺癌细胞迁移%Inhibitory effect of chitosan nanoparticles-mediated HER-2 siRNA on migration of breast cancer cell line SK-BR-3

    Institute of Scientific and Technical Information of China (English)

    张永成; 武晓英; 陈晓兰

    2011-01-01

    目的 以壳聚糖纳米粒作为人类表皮生长因子受体2小干扰RNA(HER-2 siRNA)的载体转染人乳腺癌细胞SK-BR-3,观察HER-2沉默对其体外迁移能力的影响.方法 采用离子凝胶法制备壳聚糖-HER-2 siRNA纳米粒,原子力显微镜观察纳米粒的形态.分4组进行转染,分别加入转染试剂壳聚糖-HER-2 siRNA纳米粒(实验组)、LipofectamineTM 2000和HER-2 siRNA(阳性对照组)、壳聚糖-阴性对照siRNA纳米粒(阴性对照组)和空白壳聚糖纳米粒(空白组).一步法逆转录-聚合酶链反应(RT-PCR)和Western blot鉴定HER-2在SK-BR-3细胞中的表达变化.Transwell小室法检测HER-2 siRNA对细胞体外迁移能力的影响.统计分析采用单因素方差分析、K-W H秩和检验.结果 成功制备了壳聚糖-siRNA纳米粒,呈球形,大小约100 nm.实验组能有效抑制HER-2 mRNA和蛋白的表达以及SK-BR-3细胞的体外迁移能力,与阴性对照组和空白组相比差异有显著的统计学意义(P均=0.000).结论 壳聚糖纳米粒介导的HER-2 siRNA能有效抑制人乳腺癌细胞SK-BR-3中HER-2的表达及其体外迁移能力.%Objective To investigate the effect of chitosan nanoparticles loaded with small interference RNA ( siRNA ) of HER-2( human epidermal growth factor receptor 2 )on in vitro migratory activity of SK-BR-3 cells from a human breast carcinoma cell line. Methods Chitosan-siRNA nanoparticle targeting HER-2 Mrna was prepared by ionic gelation using tripolyphosphate, and the morphology of the nanoparticles was observed with atomic force microscope. The transfected SK-BR-3 cells were divided into 4 groups: the experimental group, which was transfected with chitosan-HER-2 siRNA nanoparticle, the positive control group, which was transfected with HER-2 siRNA by Lipofectamine? 2000, the negative control group, which was transfected with chitosan-negative control siRNA nanoparticle, and the blank group, which was transfected with blank chitosan-nanoparticle. The

  2. A risk prediction model for the assessment and triage of women with hypertensive disorders of pregnancy in low-resourced settings: the miniPIERS (Pre-eclampsia Integrated Estimate of RiSk multi-country prospective cohort study.

    Directory of Open Access Journals (Sweden)

    Beth A Payne

    2014-01-01

    Full Text Available Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs. We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications.From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous; gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC of 0.768 (95% CI 0.735-0.801 with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.658-0.768. A predicted probability ≥25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability.The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive disorders of pregnancy. It could be

  3. Stýrinet: Nýsköpun innan Stjórnarráðsins. Nýtt verklag í samstarfi milli stjórnsýslustiga

    Directory of Open Access Journals (Sweden)

    Héðinn Unnsteinsson

    2012-06-01

    Full Text Available Í þessari grein er vakin athygli á nýju samskiptaformi sem er að ryðja sér til rúms innan stjórnsýslunnar með tilkomu stefnumörkunarinnar Ísland 2020. Stýrinet (e. governance network er hugtak sem æ fleiri fræðimenn og embættismenn hafa skoðað síðastliðin tíu ár sem mögulegan valkost við stigveldisstjórnsýslu og útvistaða stjórnsýslu, sem varð vinsæl í lok tíunda áratugarins með tilkomu nýsköpunar í ríkisrekstri (New Public Management. Samstarf þvert á ráðuneyti eru ekki ný af nálinni en með stefnuskjalinu Ísland 2020 eru sett fram verkefni sem krefjast annars konar vinnubragða en tíðkast hafa áður innan stjórnsýslunnar. Ísland 2020 hefur ýtt bæði undir samhentari stjórnsýslu með auknu samstarfi en krefst þess jafnframt að starfshópar starfi í anda stýrineta svo að sem mestur árangur megi verða af starfi þeirra. Í greininni er stýrinetskerfi, sem sett var upp innan Stjórnarráðsins og landshlutasamtaka í tengslum við sóknaráætlanir landshluta, skoðað. Tilraun er gerð til að meta hvort stýrinet séu betur til þess fallin en annars konar samstarf til að skila markvissari árangri við lausn verkefna.

  4. Sjá roðann í austri. Efnahagsleg og pólitísk umskipti í Póllandi og víðar í Mið- og Austur-Evrópu

    Directory of Open Access Journals (Sweden)

    Kjartan Emil Sigurðsson

    2007-06-01

    Full Text Available Teljandi kaflaskipti urðu í eftirstríðsárasögu Evrópu 4. júní árið 1989 þegar fyrstu hálf-frjálsu kosningarnar fóru fram í Póllandi. Landið skyldi að endingu verða hefðbundið ríki og "snúa aftur í faðm Evrópuríkja" (the Return to Europe. Hér er fjallað um árin sem á eftir fylgdu í Póllandi og víðar í Mið- og Austur-Evrópu. Sjónum er beint að svokölluðum "upphafsskilyrðum" (initial conditions Póllands. Pólland tók á sínum tíma af skarið og leiddi byltingu sem síðan varð að veruleika um alla Mið- og Austur-Evrópu. Tvö hugtök settu mjög svip sinn á umskiptin miklu í Póllandi, þ.e. "umbætur í einum rykk" og "extraordinary politics", en þau verða skýrð og skilgreind í öðrum kafla. Einnig er fjallað um hin Visegrad-löndin, en þau eru auk Póllands, Slóvakía, Ungverjaland og Tékkland. Í þriðja kafla verður nokkrum orðum eytt í almenn skilyrði fyrir alþjóðafyrirtæki í Mið- og Austur-Evrópu, m.a. rætt um hvernig bílaiðnaðurinn var "drepin úr dróma" sem og um nokkrar gangtruflanir meðan á umskiptunum stóð, bæði í Tékklandi og Slóvakíu. Markmiðið er að skrifa stutta yfirlitsgrein um "transition"-fræði eða "transitology".

  5. Heterologous expression of an SK2-type dehydrin gene (MrDHN3)from Medicago ruthenica enhances Escherichia coli tolerance under salt and high temperature stress%扁蓿豆 SK2型脱水素基因 MrDHN3的异源表达提高大肠杆菌对盐和高温胁迫的抗性

    Institute of Scientific and Technical Information of China (English)

    沈迎芳; 马超; 吴小培; 张业猛; 王海庆

    2016-01-01

    扁蓿豆为高原高寒地区优质豆科牧草,具有极强的抗旱、耐寒、抗盐碱的能力。脱水素(DHNs)是参与植物逆境应答的一类蛋白。根据前期 RNA-seq 的结果,从扁蓿豆幼苗中克隆到一个编码脱水素的基因 MrDHN3。序列分析显示该基因含666 bp 的开放阅读框,编码221个氨基酸,为一个 SK2型酸性脱水蛋白。氨基酸序列比对结果表明,MrDHN3与豆科植物白三叶和蒺藜苜蓿相似性最高,达83%。实时荧光定量 PCR 结果显示,MrDHN3基因受脱水、低温、高盐和脱落酸处理诱导表达,表明 MrDHN3参与了扁蓿豆的非生物胁迫响应。通过构建原核表达载体,在大肠杆菌中过表达 MrDHN3蛋白,检测重组菌在盐和高温胁迫处理下的生长存活情况。结果发现,在0.5 mol/L NaCl 和0.5 mol/L KCl 高盐胁迫条件下,重组大肠杆菌的存活率明显高于对照菌株;在55℃高温胁迫条件下,转化大肠杆菌的生长状态明显优于对照。表明 MrDHN3对盐和高温引起的细胞损伤具有保护作用。为今后作物抗逆性遗传改良的研究提供了有用信息。%Medicago ruthenica ,is an excellent legume in highland and cold regions,and is highly resistant to drought,cold and high salinity.Dehydrins (DHNs)are stress proteins involved in plant protective reactions a-gainst environmental stress.According to our previous RNA-sequence data,a DHN gene,MrDHN3,was cloned from young seedlings of M.ruthenica.Sequence analyses showed that the MrDHN3 gene contained a 666 bp open reading frame,putatively translated to 221 amino acids,and was an SK2-type acidic DHN.Amino acid sequence alignment showed that MrDHN3 shared the highest similarity (83%)with TrDHN3 and Mt-DHN3.Quantitative RT-PCR analysis showed that the expression of MrDHN3 was induced by dehydration, cold,high salinity stress and abscisic acid (ABA),which suggests that MrDHN3 is involved in abiotic stress responses

  6. Ocena częstości występowania składowych zespołu metabolicznego w grupie pacjentów ze stabilną dusznicą bolesną kwalifikowanych do planowej koronarografii = Assessment of frequency of components of metabolic syndrome in patients with stable angina qualified for planning angiography

    OpenAIRE

    Sawicka, Katarzyna; Kapłon, Marta; Łuczyk, Robert; Wawryniuk, Agnieszka

    2016-01-01

    Sawicka Katarzyna, Kapłon Marta, Łuczyk Robert, Wawryniuk Agnieszka. Ocena częstości występowania składowych zespołu metabolicznego w grupie pacjentów ze stabilną dusznicą bolesną kwalifikowanych do planowej koronarografii = Assessment of frequency of components of metabolic syndrome in patients with stable angina qualified for planning angiography. Journal of Education, Health and Sport. 2016;6(9):391-421. eISSN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.62069 http://ojs.ukw....

  7. Korelace mezi délkou lyžařské tratě a rychlostí vrcholových slalomářů Correlation between the length of the ski track and the velocity of top slalom skiers

    Directory of Open Access Journals (Sweden)

    Blaž Lešnik

    2007-02-01

    Full Text Available Teoreticky je nejlepší co nejkratší lyžařská dráha (lyžařská trať. V praxi je to však těžko proveditelné a kromě toho je to velmi riskantní. Může se proto stát pouze součástí taktiky těch nejlepších soutěžících. Pomocí kinematické analýzy byly stanoveny rozdíly mezi volbou lyžařské dráhy u jednotlivých soutěžících, a to na základě vzorku vrcholových soutěžících ve světovém poháru v Kranjske Gore. Snažili jsme se zjistit, zda soutěžící dosahovali na takové lyžařské dráze vyšší rychlosti, tedy zda dosahovali rychlejšího pohybu mezi slalomovými brankami a tudíž v konečném důsledku i lep ších časových výsledků. V první části našeho výzkumu bylo prokázáno, že žádný ze soutěžících neměl v prvních dvou po sobě následujících obratech extrémně krátkou lyžařskou dráhu. Bylo rovněž zjištěno, že soutěžící s nejkratšími lyžařskými drahami v prvním obratu měli zpravidla nejdelší lyžařské dráhy v obratu druhém a naopak. Na základě těchto zjištění bylo možno tvrdit, že za současných podmínek je mimořádně obtížné, a snad dokonce nemožné, lyžovat tak, aby lyžařský oblouk byl v několika po sobě následujících obratech velmi krátký. Druhá část našeho výzkumu se zaměřila na zjišťování korelace mezi trajektorií lyží a rychlostí lyžování. Výpočty korelací prokázaly statisticky významnou korelaci mezi průměrnou rychlostí lyžování a průměrnou vzdáleností délky lyžařské dráhy od osy y v celém měřeném úseku. Bylo zjištěno, že měřený prostor překonávali soutěžící s kratší, tedy přímější, lyžařskou dráhou rychleji. Theoretically, the shortest possible line of skiing (ski track is the best one. But in practice it is very difficult to carry this out and besides it is very risky. It can therefore be only a part of the tactics of the best competitors. With

  8. 双酚A及玉米赤霉烯酮对神经母细胞瘤细胞周期蛋白表达的影响%Effect of bisphenol A and zearalenone on the expression of cell cycle protein in SK-N-SH human neuroblastoma cells

    Institute of Scientific and Technical Information of China (English)

    郑继翠; 马阳阳; 刘江斌; 肖现民

    2011-01-01

    目的 探讨两种环境内分泌干扰物双酚A(bisphenol A,BPA)与玉米赤霉烯酮(zearalenone,ZEA)对人神经母细胞瘤SK-N-SH细胞细胞周期素CyclinD1、CDK4、p21表达的影响.方法 SK-N-SH细胞经培养扩增后分为7组:组1,无干预(对照组);组2,加17β-雌二醇(E2);组3,加BPA;组4,加ZEA;组5,同时加E2和ICI 182,780;组6,同时加BPA和ICI 182,780;组7,同时加ZEA和ICI 182,780.在72 h用免疫细胞化学染色及Western blot分析法检测细胞周期蛋白CyclinD1、CDK4、p21的蛋白表达.结果 72 h时免疫组化和Western blot检测发现,组2、3、4中CyclinD1、CDK4的表达明显高于对照组和5、6、7组(P0.05).结论 BPA与ZEA可能通过调节细胞周期蛋白而影响SK-N-SH细胞的周期变化,从而促进其增殖.%Objective To investigate the effect of environmental endocrine disruptors, bisphenol A (BPA) and zearalenone (ZEA), on the expression of CyclinD1, CDK4 and p21 in SK-N-SH human neuroblastoma (NB) cells in vitro.Methods NB cells were cultured in estrogen free improved minimum essential medium and divided into 7 groups based on different treatments: group 1, no treatment; group 2, treated with 17β-estradiol (E2) ; group 3, treated with BPA; group 4, treated with zearalenone (ZEA); group 5, treated with both E2 and ICI 182,780; group 6, treated with both BPA and ICI 182,780; group 7, treated with both ZEA and ICI 182,780.Western blot analysis and immunol cytochemistry were employed to monitor the expression of CyclinD1, CDK4 and p21.Results At 72 hours, the expression of CyclinD1 and CDK4 was abundant in 2, 3 and 4 group, but was little in control and 5, 6, 7 group (P>0.05).There was no difference on expression of p21 among the groups (P>0.05).Conclusions Disrupting cell cycle may be involved in the process of growth of SK-N-SH cells, which is directed by BPA and ZEA.

  9. Construction of recombinant plasmid pEGFP-N2-GPC3 and effects of GPC3 gene on the growth promotion of growth factors in GPC3-SK-Hep-1%重组质粒pEGFP-N2-GPC3的构建及GPC3对生长因子FGF2、IGF2促进细胞增殖的影响

    Institute of Scientific and Technical Information of China (English)

    王冰; 林山; 王烈

    2008-01-01

    目的 构建GPC3基因真核表达重组质粒,观察GPC3对生长因子FGF2、IGF2促进肝癌细胞增殖的影响.方法 自行设计引物从GPC3原核扩增重组质粒pDNR-LIB.GPC3中获得编码GPC3的基因片段.应用基因重组技术,将GPC3基因片段克隆到真核表达载体pEGFP-N2中,然后经脂质体介导转染SK-Hep-1,并通过C418(600 mg/L)筛选出抗性克隆,应用荧光显微镜及逆转录-聚合酶链反应(RT-PER)法对转染细胞内pEGFP-GPC3的表达进行鉴定,采用噻唑蓝(MTT)比色法研究GPC3对生长因子FGF2、IGF2促细胞增殖效应的影响.结果 限制性内切酶酶切分析、重组质粒测序鉴定表明为正确重组子,荧光显微镜下可见转染的SK-Hep-1胞膜区发出强绿色荧光,RT-PCR表明GPC3在SK-Hep-1中成功表达,生长因子实验中,GPC3明显抑制FGF2促细胞增殖效应,与空质粒转染组比较差异有统计学意义(P0.05).结论 测序表明,编码的氨基酸序列与人GPC3完全一致;构建完成真核表达重组质粒pEGFP-N2-GPC3;GPC3基因在SK-Hep-1中成功表达;GPC3在FGF2信号通路中可能发挥负性调控因子的作用.%Objective To construct a eukaryotic expression recombinant plasmid named pEGFP-N2-GPC3, and study the effects of GPC3 gene on the growth promotion of growth factors in GPC3-SK-Hep-1. Methods Human GPC3 full-length eDNA was obtained from pDNR-LIB-GPC3 prokaryotic amplified recombinant plasmid by PCR. The target gene GPC3 was inserted into the eukaryotic expression vector pEGFP-N2. The recombinant plasmid was transfected into the SK-Hep-1 human hepatoma carcinoma cells via Lipofeetin transfection. Transfected SK-Hep-1 cells were selectively screened with G418 (600 mg/L).The expression of GPC3 gene in transfected SK-Hep-1 was detected by fluorescence microscopy and RT-PCR. Effects of GPC3 gene on the growth promotion of growth factors in GPC3-SK-Hep-1 were assayed by MTL Results The recombinant plasmid was identified to be right for ORF by

  10. An analysis of Finnish skiing school students' academic education and athletic success [Analýza akademického vzdělání a sportovních úspěchů studentů finských lyžařských škol

    Directory of Open Access Journals (Sweden)

    Jan-Erik Romar

    2012-03-01

    Full Text Available BACKGROUND: Skiing boarding schools provide an opportunity to combine academic education and an athletic career. Many athletes select to go to a boarding school at an age of 16 because they have poor local training possibilities; however, this physical move away from home providesmany challenges. OBJECTIVE: The purpose of this study was to analyze academic education and athletic success of skiing school students in Finland. METHODS: The participants were 49 students (15 girls and 34 boys with an average age of 17 years. They came from three skiing boarding schools, two cross-country and one alpine school. Sixty percent of the alpine skiers were members of the junior national team while only six percent of the cross-country skiers. All participants completed a survey about study success and athletic performance. RESULTS: The results showed that 80% of the students extended their high school studies from three to four years. About 50% of all students were satisfied with their academic success. Fifty-four percent of alpine skiers and 15% of cross-country skiers indicated that their best athletic success were in international competitions. Almost all students perceived that skiing school helped by combining sport and school. However, only 40% of the alpine skiers and 62% of the cross-country skiers were satisfied with their present athletic success. Seventy-three percent of the alpine skiers felt that sport participation affected negatively their success in school. Success in sport, good training possibilities, skilled coaches and caring friends were reason for enjoying life in skiing boarding schools. CONCLUSIONS: These findings support the concept of skiing schools and suggest that there are many things to consider when combining education and an athletic career.[VÝCHODISKA: Lyžařské internátní školy nabízejí možnost spojit akademické vzdělání a sportovní kariéru. Mnozí sportovci odcházejí ve věku 16 let na internátní

  11. Seafare or Sovereignty? Explaining Iceland's particular position amongst the Nordics in European Integration Fiskurinn eða fullveldið? Hvað skýrir ólík tengsl Íslands og hinna Norðurlandanna við Evrópusamrunann?

    Directory of Open Access Journals (Sweden)

    Eiríkur Bergmann

    2006-06-01

    Full Text Available Abstract in English is unavailable.Þrátt fyrir að Norðurlöndin fimm hafi verið heldur treg í taumi í Evrópusamvinnunni hafa þau öll kosið að taka virkan þátt í Evrópusamrunanum, þótt með æði ólíkum hætti sé. Fræðikonan Cristine Ingebritsen heldur því fram að það séu hagsmunir ríkjandi atvinnugreina í hverju ríkja Norðurlandanna sem á endanum ráði tengslunum við Evrópusamrunann. Samkvæmt henni eru það hagsmunir sjávarútvegsins sem komi í veg fyrir ESB-aðild Íslands. Það veikir hins vegar kenningu Ingebritsen að aldrei hefur verið látið reyna á hvort mögulegt sé að finna ásættanlega lausn fyrir íslenskan sjávarútveg í aðildarviðræðum. Sú staðreynd bendir til að það sé eitthvað annað en sjávarútvegurinn sem raunverulega hindri ESB-aðild Íslands. Fræðimenn hafa verið ósammála um hvort hagsmunir eða hugmyndir skipti meiru við að skýra tengsl ríkja við Evrópusamrunann. Í þessari grein er sýnt fram á að öfugt við kenningu Ingebritsen er skýringanna ekki síður að leita í hugmyndum, svo sem í skilningi þjóðanna á fullveldi og þjóðerni. Í því ljósi er sú spurning áhugaverð hvort hugmyndir Íslendinga um formlegt fullveldi komi í veg fyrir fulla aðild að ESB en að innan ramma þeirra heimilist það raunverulega framsal ákvarðanatöku sem þegar fellst í EES-aðildinni.

  12. The ruthenium complex cis-(dichloro)tetraammineruthenium(III) chloride presents selective cytotoxicity against murine B cell lymphoma (A-20), murine ascitic sarcoma 180 (S-180), human breast adenocarcinoma (SK-BR-3), and human T cell leukemia (Jurkat) tumor cell lines.

    Science.gov (United States)

    Silveira-Lacerda, Elisângela de Paula; Vilanova-Costa, Cesar Augusto Sam Tiago; Hamaguchi, Amélia; Pavanin, Luiz Alfredo; Goulart, Luiz Ricardo; Homsi-Brandenburgo, Maria Inês; Dos Santos, Wagner Batista; Soares, Andreimar Martins; Nomizo, Auro

    2010-06-01

    The aim of present study was to verify the in vitro antitumor activity of a ruthenium complex, cis-(dichloro)tetraammineruthenium(III) chloride (cis-[RuCl(2)(NH(3))(4)]Cl) toward different tumor cell lines. The antitumor studies showed that ruthenium(III) complex presents a relevant cytotoxic activity against murine B cell lymphoma (A-20), murine ascitic sarcoma 180 (S-180), human breast adenocarcinoma (SK-BR-3), and human T cell leukemia (Jurkat) cell lines and a very low cytotoxicity toward human peripheral blood mononuclear cells. The ruthenium(III) complex decreased the fraction of tumor cells in G0/G1 and/or G2-M phases, indicating that this compound may act on resting/early entering G0/G1 cells and/or precycling G2-M cells. The cytotoxic activity of a high concentration (2 mg mL(-1)) of cis-[RuCl(2)(NH(3))(4)]Cl toward Jurkat cells correlated with an increased number of annexin V-positive cells and also the presence of DNA fragmentation, suggesting that this compound induces apoptosis in tumor cells. The development of new antineoplastic medications demands adequate knowledge in order to avoid inefficient or toxic treatments. Thus, a mechanistic understanding of how metal complexes achieve their activities is crucial to their clinical success and to the rational design of new compounds with improved potency.

  13. Analýza užívaných citačních stylů v publikacích autorů z lékařských, sportovních a přírodovědných oborů na Masarykově univerzitě

    OpenAIRE

    Kratochvíl Jiří

    2014-01-01

    Příspěvek představuje výsledky analýzy citačních stylů, podle kterých citovali autoři z vybraných fakult Masarykovy univerzity. Autoři z lékařské fakulty citovali nejčastěji podle stylu Vancouver/NLM (32, 42 % případů) nebo ISO 690 (12, 71 %), autoři z fakulty sportovních studií podle stylu APA (38,24 %), ISO 690 (6,86 %) nebo Vancouver/NLM (5,39 %) a autoři z přírodovědecké fakulty podle vlastního stylu časopisu (46,60 %). Některý z obecně známých stylů následovali jen autoři z oboru astrofy...

  14. Detection significance of AchR antibody,Titin antibody and MuSK antibody in myasthenia gravis combined with thymic lesion%重症肌无力合并胸腺病变患者血清乙酰胆碱受体抗体、肌联蛋白抗体和肌肉特异性酪氨酸激酶抗体的检测意义

    Institute of Scientific and Technical Information of China (English)

    刘岚剑; 杨文娟

    2016-01-01

    目的:探究对重症肌无力合并胸腺病变的患者血清中乙酰胆碱受体(acetylcholine receptors,AchR)抗体、肌联蛋白(Titin)抗体和肌肉特异性酪氨酸激酶(muscle specific tyrosine kinase,MuSK)抗体的检测意义。方法选取我院收治的80例重症肌无力患者,根据是否存在胸腺病变分为胸腺病变组48例和非胸腺病变组32例,另取80例健康个体作为对照组,通过免疫酶联吸附试验对3组成员血清中 AchR 抗体、Titin 抗体和 MuSK 抗体进行检测并比较。结果重症肌无力患者血清 AchR 抗体和 Titin 抗体阳性率(76.3%,52.5%)均明显高于对照组(11.3%,5.0%)(P <0.05);重症肌无力组及对照组患者血清 MuSK 抗体阳性率均为0,但前者血清中 MuSK 抗体水平明显高于后者(P <0.05);AchR,Titin 两种抗体联合检测可明显提高检测重症肌无力的灵敏度;AchR 和 Titin 抗体在胸腺病变组中的阳性率明显高于非胸腺病变组(P <0.05);全身型重症肌无力患者的血清 AchR 抗体和 Titin 抗体阳性率明显高于眼肌型(P <0.05)。结论 AchR 抗体和 Titin 抗体的阳性率与重症肌无力患者的病情相关,病情严重或合并胸腺病变可明显提高两者的阳性率,此外两者联合检测可提高诊断的灵敏度。而 MuSK 抗体在我国重症肌无力患者中的阳性率较低。%ABSTRACT:Objective To explore the significance of AchR antibody,Titin antibody and MuSK antibody in myasthenia gravis patients combined with thymic lesion.Methods A total 80 cases of myasthenia gravis patients treated in our hospital were selected.They were divided into thymic lesion group(n =48)and no-thymic lesion group (n = 32 ).Another 80 cases of healthy individuals were selected as control group.The positive rates of AchR antibody,Titin antibody and MuSK antibody were compared among three groups and different Osserman types. Results The positive rates of AchR antibody and Titin antibody of myasthenia gravis

  15. 晶体外延生长模式的完备理论描述与“后S-K异质兼容生长模式”的预言%Novel Comprehensive Theoretical Description of Epitaxial Crystal-Growth Modes and the Prediction of“Post S-K Compatible-Heterogeneous-Growth Mode”

    Institute of Scientific and Technical Information of China (English)

    任晓敏; 王琦

    2014-01-01

    指出了晶体外延生长模式现有理论描述的若干问题,包括:①弗兰克-范·德·默夫模式被描述为仅存在于衬底表面能优势度为正值的情形中,这和晶格失配度足够小的2种材料能够以该模式交替生长的实验事实不符;②对于不同的衬底表面能优势度,弗兰克-范·德·默夫模式与斯特兰斯基-克拉斯塔诺夫( S-K)模式之间的转换被描述为发生在某一固定的晶格失配度上,这显然是不合理的;③由弗兰克-范·德·默夫模式似可直接转换为沃尔默-韦伯模式,反之亦然,这一描述值得质疑。针对这些问题,提出了改进的、更加完备的理论描述,其中引入了“准弗兰克-范·德·默夫模式”的概念。在此基础上,提出了“后S-K异质兼容生长模式”的概念,并探讨了基于该模式实现高质量异质兼容体材料生长的可能性。%Some problems are found in currently-available theoretical description of epitaxial crystal-growth mods, including that①Frank-van der Merve mode is described as it only exists for positive domi-nance-level of the substrate surface energy and this is not in agreement with the experimental fact that a pair of materials with small enough lattice mismatch between them can grow alternately both in the Frank-van der Merve mode;②the transition between Frank-van der Merve mode and Stranski-Krastanow ( S-K) mode is regarded as it happens at a fixed lattice mismatch for different dominance-levels of the substrate surface energy and this description seems obviously unreasonable;③the direct transitions from Frank-van der Merve mode to Volmer-Weber mode and vice versa are supposed possible and the truthfulness of this understanding might be seriously suspected. Taking these problems into consideration, a modified and more comprehensive theoretical description is proposed and the concept of quasi-Frank-van der Merve mode is introduced in it. Based upon the

  16. The comparison of efficiency of Fenton and photo-Fenton treatment of stabilised landfill leachate / Porównanie efektywności oczyszczania odcieków z ustabilizowanego składowiska odpadów komunalnych w procesie Fentona i foto-Fentona

    Directory of Open Access Journals (Sweden)

    Kwarciak-Kozłowska Anna

    2015-09-01

    Full Text Available W pracy porównano efektywność oczyszczania odcieków pochodzących ze „starego” składowiska odpadów komunalnych w procesie Fentona i foto-Fentona. Podczas wszystkich etapów badań stosunek masowy ChZT:H2O2 był stały (1:2. Dawki reagentów (stosunek siarczan żelaza/nadtlenek wodoru zmieniano w zakresie od 0.1 do 0.5. Efektywność obu procesów oceniano w oparciu o stopień obniżenia BZT5 (biochemicznego zaporzebowania tlenu, ChZT (chemicznego zapotrzebowania tlenu, OWO (ogólnego węgla organicznego, azotu amonowego i zmiany wskaźnika BZT5/ChZT. Podczas oczyszczania odcieków z odczynnikiem Fentona wyznaczono najkorzystniejsze parametry prowadzenia procesu tj. temperatura (25ºC, początkowy odczyn odcieków (pH=3.0 . Czas trwania reakcji ustalono na 60 min. Stwierdzono, że dla tego rodzaju wód odpadowych najkorzystniejsza dawka reagentów to 0.25. Zauważono, że obecność dodatkowego czynnika (UV przy każdej przebadanej dawce reagentów skutkowało średnio 14% wyższym stopniem usunięcia ChZT i OWO z badanych odcieków

  17. Preliminary results of the monumental tree monitoring based on terrestrial laser scanning - a case study of the Oak Bartek in Zagnańsk (Poland). (Polish Title: Wstepne wyniki monitorowania drzewa pomnikowego - Debu Bartek w Zagnansku z wykorzystaniem chmur punktow naziemnego skanowania laserowego)

    Science.gov (United States)

    Wężyk, P.; Szostak, M.; Zięba, K.; Rysiak, P.; Hawryło, P.; Ratajczak, M.

    2015-12-01

    In April 2013, the Laboratory of Geomatics launched the project under the acronym "Bartek 3D" in cooperation with the Research Section of Students from the AGH in Krakow, Pedagogical University and the Jagiellonian University as well. The main aim of the project is to monitor the biggest and probably one of the oldest trees in Poland - Oak Bartek in Zagnańsk (N 50o59'14"; E 20o38'59"), based on multi-temporal Terrestrial Laser Scanning (TLS) technology. One of the results of the project should be a 3D model of Oak Bartek and detection of the changes in the shape of the tree. Terrestrial Laser Scanning and the traditional forest inventory measurements were performed during the Leaf-OFF season in April 2013 and April 2014 and repeated in Leaf-ON period in July 2013 and October 2014 with using scanners: FARO FOCUS 3D, RIEGL VZ-400, LEICA C10 and RevScan (HandyScan). The results based on TLS technology showed some differences comparing to existing data obtained by traditional measurements for forestry inventory: Height (H) of the tree: altimeter Vertex (Haglˆf) H = 29.31 m; HTLS = 28.49 m; Trunk circumference (L) measured with stretched tape: LST = 9.80 m; adjacent along the shape of bark: LT = 13.70 m; TLS measurments: LTLS1/4 = 9.97 m oraz LRevScan = 13.54 m, The average diameter at breast height (DBH130cm) calculated on the basis of 3D basal area of stem DBHTLS1/4 = 3.03 m (DBHT = 3.12 m).

  18. I skæret fra Stella Nova

    DEFF Research Database (Denmark)

    Nørgaard-Nielsen, Hans Ulrik; Brandt, Søren Kristian

    2009-01-01

    Tyske og japanske astronomer har for nylig observeret reflekteret lys fra den supernova, som Tycho Brahe observerede i 1572. Observationerne åbner et fascinerende vindue til fortiden, og minder os om, hvorfor 2009 er internationalt astronomi-år.......Tyske og japanske astronomer har for nylig observeret reflekteret lys fra den supernova, som Tycho Brahe observerede i 1572. Observationerne åbner et fascinerende vindue til fortiden, og minder os om, hvorfor 2009 er internationalt astronomi-år....

  19. Podnikateľský plán

    OpenAIRE

    Pilát, Roman

    2011-01-01

    Goal of the graduation thesis is elaboration of business plan which is aimed at production and distribution of formula cars. The thesis is divided into two parts. First part is devoted to theoretical base about entrepreneurship, entrepreneurs and enterprises followed by decomposed structure of business plan. In second, practical part, specific business plan of author is compiled with all of its requirements including analysis of micro and macro environment and production, marketing and financ...

  20. Hatten af for Cohens skønheder og skyggesider

    DEFF Research Database (Denmark)

    Mortensen, Lise Majgaard

    2011-01-01

    Der er højt til loftet i Aarhus Teaters nye teaterkoncert, som behandler selveste Leonard Cohens lyriske univers. Det er svært at lade være med at sammenligne forestillingen her med Nick Cave Teaterkoncerten, der gik sin sejrsgang i 2007 og 2008. Men det skal man ikke. Instruktøren er den samme....... Men hvor ’Nick Cave’ var rå, grim, provokerende og uanstændig, er ’Leonard Cohen’ en skrøbelig gentleman med en skyggeside....

  1. En skåltale for det tyske demokrati?

    DEFF Research Database (Denmark)

    Peters, Rikke

    2009-01-01

      The essay introduces and discusses Kurt Sontheimer's article: "The Continuity in German antidemocratic Thought. From the Weimar Republic to the Federal Republic" published in the anthology: Gessenharter & Pfeiffer (eds): Die Neue Rechte - eine Gefahr für die Demokratie?, Wiesbaden 2004. Kurt So...... of intellectuals are attempting to make nationalism acceptable to the political centre. Sontheimer's warning against the revival of a new nationalism may therefore very well be appreciated when celebrating the 60s anniversary of The Federal Republic of Germany in 2009....

  2. El complejo Billingehus-Skövde – Suecia

    Directory of Open Access Journals (Sweden)

    Heineman, Hans Erland

    1972-06-01

    Full Text Available The Billingehus was designed with the idea of bringing the people of the town into contact with cultural and sporting activities developed in natural surroundings. With this aim, a very wooded area enclosed by mountains was chosen, which also had a small lake nearby which would make fishing possible. In this place was built a complex, which houses in its central nucleus a series of cafes, restaurants, halls for social functions, a small hotel, and even a private church, with several swimming-pools, multi-purpose sports fields and car-park in the immediate vicinity. Advantage was taken of the nearby mountains to build ski-runs, which are equipped with ski-lifts.El Billingehus se realizó con la idea de facilitar el contacto de la gente del pueblo con las actividades culturales y deportivas desarrolladas en plena naturaleza. Con este fin se eligió una zona de gran arbolado, enclavada entre montañas y que cuenta asimismo con la proximidad de un pequeño lago, que daría la posibilidad de practicar el deporte de la pesca. En este lugar se construyó un complejo, que alberga en su núcleo central una serie de cafeterias, restaurantes, salas de tipo social, un pequeño hotel y hasta una iglesia particular, y situando en sus inmediaciones varias piscinas, pistas polideportivas y la zona de aparcamientos. Se aprovechó una de las montañas cercanas para la construcción de pistas de esquí, servidas por dos elevadores.

  3. Klassifikation og indeksering af skønlitteratur

    DEFF Research Database (Denmark)

    Eriksson, Rune

    diskuteres nogle bredere problemstillinger.  I forhold til folkebibliotekernes barndom er spørgsmålet, om der er en sammenhæng mellem DDC, de alternative systemer, disse systemers nederlag i ALA og den flere årtier lange debat om fiktion, som i USA og Storbritannien kaldes the Great Fiction Question. Og i...

  4. KIILANG SK AT AA (Haida Reading Book: Learning Your Language).

    Science.gov (United States)

    Lawrence, Erma

    One in a series introducing students to Southeast Alaska Native languages, this booklet presents simple dialogues in Haida with English translations following. The eight dialogues, consisting of three or four questions with replies, provide practice with a variety of basic sentence patterns. Dialogues include social greetings and questions about…

  5. Skal vi skærme børnene?

    DEFF Research Database (Denmark)

    Mehlsen, Camilla

    2012-01-01

    iPads, digitalkameraer og ny touch-teknologi rykker ind i skolen, ud i vuggestuens sandkasse og med børnehaven på tur. Er digitale medier nødvendige redskaber i det pædagogiske arbejde, eller er det bare hype? Bliver børn smartere af smart teknologi – eller dummere?...

  6. Podnikateľský plán

    OpenAIRE

    2010-01-01

    The subject of the processed work on theme business plan was to elaborate a business plan for the development of English exercise books. In the theoretical part, in addition to the instructions for writing a business plan, work investigates the level of special preparations done by beginning businessmen. The practical part consists of the actual business plan. The business plan includes surveys, market analysis and customer analysis, product description and financial plan. The final part is d...

  7. I skæret fra Stella Nova

    DEFF Research Database (Denmark)

    Nørgaard-Nielsen, Hans Ulrik; Brandt, Søren Kristian

    2009-01-01

    Tyske og japanske astronomer har for nylig observeret reflekteret lys fra den supernova, som Tycho Brahe observerede i 1572. Observationerne åbner et fascinerende vindue til fortiden, og minder os om, hvorfor 2009 er internationalt astronomi-år.......Tyske og japanske astronomer har for nylig observeret reflekteret lys fra den supernova, som Tycho Brahe observerede i 1572. Observationerne åbner et fascinerende vindue til fortiden, og minder os om, hvorfor 2009 er internationalt astronomi-år....

  8. A labVIEW Code for PolSK encoding

    CERN Document Server

    Soorat, Ram; Vudayagiri, Ashok

    2015-01-01

    We have developed an integrated software module for use in free space Optical communication using Polarization Shift Keying. The module provides options to read the data to be transmitted from a file, convert this data to on/off code for laser diodes as well as measure the state of polarization of the received optical pulses. The Software bundle consists of separate transmitter and receiver components. The entire protocol involves handshaking commands, data transmission as well as an error correction based on post-processing Hamming 7,4 code. The module is developed using \\lv, a proprietary software development IDE from National Instruments Inc. USA

  9. S-K Smartphone Barcode Reader for the Blind.

    Science.gov (United States)

    Tekin, Ender; Vásquez, David; Coughlan, James M

    We describe a new smartphone app called BLaDE (Barcode Localization and Decoding Engine), designed to enable a blind or visually impaired user find and read product barcodes. Developed at The Smith-Kettlewell Eye Research Institute, the BLaDE Android app has been released as open source software, which can be used for free or modified for commercial or non-commercial use. Unlike popular commercial smartphone apps, BLaDE provides real-time audio feedback to help visually impaired users locate a barcode, which is a prerequisite to being able to read it. We describe experiments performed with five blind/visually impaired volunteer participants demonstrating that BLaDE is usable and that the audio feedback is key to its usability.

  10. Skær ind til benet, men hurtigt!

    DEFF Research Database (Denmark)

    Meyer, Ion

    2010-01-01

    Før introduktion af anæstesi og antiseptik var kirurgiske indgreb yderst smertefulde og oftest livstruende. Amputationer blev udført, men i begtrænset omfang og kun ved alvorlige indikationer. Artiklen giver en kort gennemgang af udviklingen fra de tidligste amputationer over cirkelsnittets...

  11. Diglossi i moderne arabisk skønlitteratur

    DEFF Research Database (Denmark)

    Moestrup, Elisabeth A.

    2009-01-01

    Artiklen ser nærmere på to forfatteres brug af dialekt i litteraturen, dvs. på fænomenet diglossi i arabisk. De to forfatteres tilgang til dilemmaet holdes op i mod dels Dan Diners bog om den arabisk verdens tilbageståenhed som han bla. ser diglossien som et symptom, dels Sidney Pollock artikel o...

  12. Study of $B \\to \\psi (2S)K$ and $B \\to \\psi (2S)K^{*}$(892) Decays

    CERN Document Server

    Richichi, S; Skubic, P L; Undrus, A; Chen, S; Fast, J; Hinson, J W; Lee, J; Miller, D H; Shibata, E I; Shipsey, I P J; Pavlunin, V; Cronin-Hennessy, D; Lyon, A L; Thorndike, E H; Jessop, C P; Marsiske, H; Perl, Martin Lewis; Savinov, V; Zhou, X; Coan, T E; Fadeev, V; Maravin, Y; Narsky, I; Stroynowski, R; Ye, J; Wlodek, T; Artuso, M; Ayad, R; Boulahouache, C; Bukin, K; Dambasuren, E; Karamov, S; Majumder, G; Moneti, G C; Mountain, R; Schuh, S; Skwarnicki, T; Stone, S; Viehhauser, G; Wang, J C; Wolf, A; Wu, J; Kopp, S E; Mahmood, A H; Csorna, S E; Danko, I; McLean, K W; Marka, S; Xu, Z; Godang, R; Kinoshita, K; Lai, I C; Schrenk, S; Bonvicini, G; Cinabro, D; McGee, S; Perera, L P; Zhou, G J; Lipeles, E; Pappas, S P; Schmidtler, M; Shapiro, A; Sun, W M; Weinstein, A J; Würthwein, F; Jaffe, D E; Masek, G E; Paar, H P; Potter, E M; Prell, S; Sharma, V; Asner, D M; Eppich, A; Hill, T S; Morrison, R J; Nelson, H N; Briere, R A; Chen, G P; Behrens, B H; Ford, W T; Gritsan, A; Roy, J D; Smith, J G; Alexander, J P; Baker, R; Bebek, C; Berger, B E; Berkelman, K; Blanc, F; Boisvert, V; Cassel, David G; Dickson, M; Drell, P S; Ecklund, K M; Ehrlich, R; Foland, A D; Gaidarev, P B; Gibbons, L K; Gittelman, B; Gray, S W; Hartill, D L; Heltsley, B K; Hopman, P I; Jones, C D; Kreinick, D L; Lohner, M; Magerkurth, A; Meyer, T O; Mistry, N B; Nordberg, E; Patterson, J R; Peterson, D; Riley, D; Thayer, J G; Urner, D; Valant-Spaight, B L; Warburton, A; Avery, P; Prescott, C; Rubiera, A I; Yelton, J; Zheng, J; Brandenburg, G; Ershov, A; Gao, Y S; Kim, D Y J; Wilson, R; Browder, T E; Li, Y; Rodríguez, J L; Yamamoto, H; Bergfeld, T; Eisenstein, B I; Ernst, J; Gladding, G E; Gollin, G D; Hans, R M; Johnson, E; Karliner, I; Marsh, M A; Palmer, M; Plager, C; Sedlack, C; Selen, M; Thaler, J J; Williams, J; Edwards, K W; Janicek, R; Patel, P M; Sadoff, A J; Ammar, R; Bean, A; Besson, D; Davis, R; Kwak, N; Zhao, X; Anderson, S; Frolov, V V; Kubota, Y; Lee, S J; Mahapatra, R; O'Neill, J J; Poling, R A; Riehle, T; Smith, A; Stepaniak, C J; Urheim, J; Ahmed, S; Alam, M S; Athar, S B; Jian, L; Ling, L; Saleem, M; Timm, S; Wappler, F; Anastassov, A; Duboscq, J E; Eckhart, E; Gan, K K; Gwon, C; Hart, T; Honscheid, K; Hufnagel, D; Kagan, H; Kass, R; Pedlar, T K; Schwarthoff, H; Thayer, J B; Von Törne, E; Zoeller, M M

    2001-01-01

    Color-suppressed decays of $B$ mesons to final states with $\\psi(2S)$ mesons have been observed with the CLEO detector. The branching fractions for the decays $B^+ \\to \\psi(2S) K^+$, $B^+ \\to \\psi(2S) K^*(892)^+$, $B^0 \\to \\psi(2S) K^0$, and $B^0 \\to \\psi(2S) K^*(892)^0$ are measured to be (7.8 +- 0.7 +- 0.9) 10^{-4}$, (9.2 +- 1.9 +- 1.2) 10^{-4}$, (5.0 +- 1.1 +- 0.6) 10^{-4}$, and (7.6 +- 1.1 +- 1.0) 10^{-4}$, respectively, where the first uncertainty is statistical and the second is systematic. The first measurement of the longitudinal polarization fraction is extracted from the angular analysis of the $B \\to \\psi(2S) K^*(892)$ candidates: $\\Gamma_L / \\Gamma = 0.45 +- 0.11 +- 0.04 $. Our measurements of the decays $B^0 \\to \\psi(2S) K^0$ and $B^+ \\to \\psi(2S) K^*(892)^+$ are first observations.

  13. TRAKYA BÖLGESİ’NDEKİ ÜNİVERSİTELERDE GÖREV YAPAN ÖĞRETİM ELEMANLARININ ONLİNE ALIŞVERİŞTEN ALGILADIKLARI RİSK VE FAYDA ÜZERİNE BİR ARAŞTIRMA

    Directory of Open Access Journals (Sweden)

    Nevin ALTUĞ

    2012-07-01

    Full Text Available TRAKYA BÖLGESİ’NDEKİ ÜNİVERSİTELERDE GÖREV YAPAN ÖĞRETİM ELEMANLARININ ONLINE ALIŞVERİŞTEN ALGILADIKLARI RİSK VE FAYDA ÜZERİNE BİR ARAŞTIRMAÖzet: İnternetin gelişmesiyle birlikte, giderek artan sayıda tüketici internet üzerinden çeşitli ürün veya hizmetler hakkında bilgi toplamakta ve satın almaktadır. Online alışveriş fiziksel alışveriş faaliyetleri yapmayı gerektirmemesi, mesafe ve zaman engelini ortadan kaldırması vb. nedenlerle tüketiciler tarafından faydalı; bunun yanında güvenlik ve gizlilik vb. açılardan da riskli bulunmaktadır. Bu çerçevede araştırmanın amacı, internet üzerinden gerçekleştirilen online satın alma davranışı ile öğretim elemanlarının bu satın alma davranışına yönelik risk ve fayda algılamaları arasındaki ilişkilerin belirlenmesi ve incelenmesidir. Çalışma sonucunda, online alışveriş sıklığı ve online alışverişte yapılan harcama tutarının risk ve fayda algılamaları üzerinde etkili olduğu görülmüştür. Ayrıca, online alışveriş yapmayan katılımcıların online alışveriş yapan katılımcılara göre online alışverişi daha riskli olarak algıladığı saptanmıştır.A STUDY AMONG ACADEMIC STAFF AT UNIVERSITIES IN THE REGION OF THRACE ON PERCEIVED RISKS AND BENEFITS OF ONLINE SHOPPINGAbstract: With the development of the Internet; a growing number of consumers collects information about a variety of goods or services, and purchases over the internet. Online shopping is useful on aspects of removing physical shopping activities, distance and time but in addition, there are risks such as security and privacy. In this context, the aim of the research is to determine and analyze online buying behavior over the internet and the relationship between risk and benefit perceptions of teaching staffs’ buying behavior. As a result of the research, it is displayed that the frequency of online shopping and amount of online

  14. Různé věkové kategorie ve vztahu k objemu a intenzitě širokého spektra cyklických pohybů hráčů mužské házené Various age category – related differences in the volume and intensity of the large-scale cyclic movements of male players in team handball

    Directory of Open Access Journals (Sweden)

    Maja Dolenec

    2005-02-01

    Full Text Available Cílem této studie bylo identifikovatrozdílyvsílea intenzitě cyklických pohybů ve velkém měřítku vykonávaných hráči házené ve třech věkových kategoriích – kadeti (chlapci ve věku mezi 15 a 17 lety, junioři (muži ve věku 17 až 20 let a senioři (ve věku 20 let a více. Pro tento účel bylo analyzováno šest experimentálních modelových zápasů (2 × 20 minut, odehraných slovinskými mužskými házenkářskými družstvy. Vzorek sestával z 84 hráčů ve dvanácti týmech (průměrný věk 20,26 let ± 4,28 let; průměrná výška 182,51 cm ± 6,59 cm; průměrná tělesná hmotnost 80,61 kg ± 10,37 kg a byl rozdělen do tří dalších podskupin podle věku (kadet, junior a senior. Soubor údajů širokého spektra cyklických pohybů v zápase házené byl získán metodou SAGIT (Ljubljana, Slovinsko, založenou na počítačovém zobrazování. Takto získané údaje byly zpracovány vybranými deskriptivními statistickými metodami. Zjistili jsme statisticky významné rozdíly mezi různými věkovými kategoriemi v objemu celkové vzdálenosti, kterou ušli a uběhli během zápasů. Největší vzdálenost byla dosažena skupinou seniorů, následně juniory a poslední byli kadeti. Ve všech analyzovaných kategoriích byly celkové vzdálenosti větší v první polovině zápasu než ve druhé polovině. Statisticky významné rozdíly se rovněž objevily v průměrném podílu času zaznamenaném ve všech rychlostních třídách, kromě druhé rychlostní třídy. V první rychlostní třídě byly některé statisticky významné rozdíly spatřeny mezi kadety a seniory a rovněž mezi kadety a juniory, zatímco mezi juniory a seniory nebyly zaznamenány žádné rozdíly. Ve třetí rychlostní třídě se objevily statisticky významné rozdíly mezi všemi analyzovanými věkovými kategoriemi. Podobně jako v první rychlostní třídě byly i ve čtvrté rychlostní třídě zaznamen

  15. CyPPA, a Positive SK3/SK2 Modulator, Reduces Activity of Dopaminergic Neurons, Inhibits Dopamine Release, and Counteracts Hyperdopaminergic Behaviors Induced by Methylphenidate

    DEFF Research Database (Denmark)

    Herrik, Kjartan F; Redrobe, John P; Holst, Dorte

    2012-01-01

    Dopamine (DA) containing midbrain neurons play critical roles in several psychiatric and neurological diseases, including schizophrenia and attention deficit hyperactivity disorder, and the substantia nigra pars compacta neurons selectively degenerate in Parkinson's disease. Pharmacological...... modulation of DA receptors and transporters are well established approaches for treatment of DA-related disorders. Direct modulation of the DA system by influencing the discharge pattern of these autonomously firing neurons has yet to be exploited as a potential therapeutic strategy. Small conductance Ca(2...... mouse and rat midbrain slices. Using an immunocytochemically and pharmacologically validated DA release assay employing cultured DA neurons from rats, we show that CyPPA repressed DA release in a concentration-dependent manner with a maximal effect equal to the D2 receptor agonist quinpirole. In vivo...

  16. Att skåda och skärskåda : konstnärlig forskning med avstamp i Swedenborgs drömmar

    OpenAIRE

    Aleman, Madeleine

    2012-01-01

    In this artistic research Swedenborg´s world of dreams is investigated. The aim of the project is to observe and reflect upon dreams potential and impact on the practical artmaking. Several tools were used for this purpose: I Ching, a Tarot deck, a selfmade Dream deck, Oblique Strategies and C.G Jungs method Active Imagination. The final outcome is a performance in Swedenborg´s Summerhouse in Stockholm. The idea emanates from the story that Swedenborg served meals to the spirits in his summer...

  17. Potreba skúmania podnikateľských stretégií v postindustriálnej ére podnikania

    OpenAIRE

    Zagorsek, Branislav

    2010-01-01

    The purpose of this article is to find out if there is a necessity of doing research in business strategies due to differences between businesses in industrial and postindustrial era. Business strategies are a key factor of success. Only a company with a good strategy can beat others in hard competition. There are some rational reasons to think that the strategies used in industrial era are not sufficient enough to by appropriate to be used in postindustrial era. The idea is that the share of...

  18. Skøjteskader. En undersøgelse of skademønstret i en dansk kommunal skøjtehal

    DEFF Research Database (Denmark)

    Johannsen, H G; Mikkelsen, J.B.; Fricke, A

    1997-01-01

    A review is presented of injuries sustained at an ice rink and treated at the emergency room, Odense University Hospital in Denmark, during 1993. Of the 105 patients treated, 67 (64 per cent) were 10-19 years of age. Most patients had been injured during a fall, no other participant being involved....... About 25 per cent of the injuries were lesions the face or head. In seven cases the patient had been cut on the hand by the blade of another participant's skate, two patients had tendon lesions and in 16 cases the patient had sustained a fracture of the forearm or hand as the result of a fall. Many...

  19. Superconformal index with surface defects for class ${\\cal S}_k$

    CERN Document Server

    Ito, Yuto

    2016-01-01

    We study surface defects in 4d $\\mathcal{N}=1$ $SU(N)$ superconformal gauge theories of class $\\mathcal{S}_k$ obtained from the 6d (1,0) theories of type $A_{N-1}$, which are worldvolume theories on $N$ M5-branes at $\\mathbb{C}^2/\\mathbb{Z}_k$ singularities, compactified on Riemann surfaces with punctures. First we apply a method based on Riemann surface description and obtain the superconformal index of the theories in the presence of surface defects labelled by arbitrary symmetric representations of $su(N)$. Then we propose another description for the same surface defects, which involves 4d-2d coupled systems, by identifying which 2d $\\mathcal{N}=(0,2)$ theories should be coupled. We compute the index of the 4d-2d systems and reproduce the results obtained from the first method. Finally we study the 2d TQFT structure of the index for class $\\mathcal{S}_{k}$ theories by obtaining several eigenfunctions and eigenvalues of the difference operators that capture the surface defects and checking their relation.

  20. Nodularia spumigena blooms and the occurrence of hepatotoxin in the Gulf of Gdańsk

    Directory of Open Access Journals (Sweden)

    Hanna Mazur

    2003-06-01

    Full Text Available Nodularia spumigena forms extensive summer blooms in the Baltic Sea. The occurrence of the blooms is determined by water temperature, light intensity and nutrient concentration; levels of nitrogen and phosphorus in particular are critical. The time of the seasonal maximum and intensity of the Nodularia bloomin the Gulf of Gdansk vary significantly from year to year. In2001 a rapid and massive proliferation of N. spumigenawas observed in late June - early July. The concentration ofnodularin in water ranged from 90 to 18135 µg dm-3and in lyophilised phytoplankton samples from 3000 to 3520µg g-1 d.w. (dry weight.Such a high concentration of toxin in the recreational watersof the Gulf of Gdansk constitutes a health risk for users ofbathing areas. In 2002, the N. spumigena bloom wasless dense, but lasted longer, with a maximum in late July- early August. In 2002 the concentration of nodularin did notexceed 12.6 µg dm-3 in water and 919 µg g-1d.w. in lyophilised phytoplankton samples. Other cyanobacterial toxins- microcystins and anatoxin-a - were also detected in the coastal waters ofthe Gulf of Gdansk.

  1. Zmiany skórne w przebiegu ostrej białaczki szpikowej – opis przypadku

    Directory of Open Access Journals (Sweden)

    Waldemar Placek

    2011-08-01

    Full Text Available Introduction. Acute myeloid leukaemia is a malignant neoplastic diseaseof white blood cells. About 80% of acute leukaemias in adult arediagnosed as myeloid leukaemias. The presence of transformed cellclones in bone marrow and blood, which originate from very earlystages of myelopoiesis, is characteristic. Beside systemic symptoms(anaemia, thrombocytopenia there are infiltrations in other organs,including skin. Skin lesions are most frequently non-specific (pruritus,skin spots, erythema multiforme, bullous pemphigoid but can be alsospecific (skin tumours. Cases of diffuse xanthomatoses and myeloidsarcoma have also been found in patients with acute myeloidleukaemia. Skin lesions are present more often in lymphocytic thanmyeloid leukaemias. They may precede the disease or its relapse, occurconcomitantly or after systemic symptoms, and sometimes may be ofprognostic value.Objective. To present the case of a patient in whom skin lesions werethe cause of detailed examinations, which revealed acute myeloidleukaemia.Case report. We present a case of a 61-year old patient with purplebrownnodular lesions 1-3 cm in diameter on the face, scalp skin, trunk,limbs and the oral cavity’s mucous membranes with coexistent intensepruritus and generalized lymphadenopathy. The first skin lesionsoccurred three months earlier. During hospitalization in the Departmentof Dermatology the renewal of blasts in the circulatory blood wasobserved and skin biopsy revealed a large amount of mononuclearcells. The patient was directed to the haematological ward, where thediagnosis of acute myeloid leukaemia was established.Conclusions. Our case indicates that the presence of skin lesions andthorough diagnostic procedures may contribute to the diagnosis ofmalignant neoplastic diseases of white blood cells.

  2. 火车上的瑞典德比 SK vs Begrip

    Institute of Scientific and Technical Information of China (English)

    Byron

    2006-01-01

    SK和Begrip之间的对决无疑是05冬季CPL中盘的重头戏,当然这并不仅仅是瑞典内战的缘故,拥有IsKall、dsn等名将的Begrip,拿下了WEGII的冠军和夏季CPL第四,相比而言,SK和NiP在05年都缺乏一个有说服力的战绩。在瑞典三强里面,NiP是最有人气的,SK是最令人期待的,而Begrip仿佛是隐隐中呼声最高的。本场比赛是胜者组第五轮的较量,在de_train上,双方都打出了很耐人寻味的攻防,Begrip的外场前压式防守,SK的双AWP摸点,部显示顶尖战队在当代CS的理解将在战术上更有针对性;而在残局处理中,Begrilp采用的是方式在两炸点之间的连接处进行移动,实战中也效果颇佳,这主要是由于他们出众的远枪能力,而SK的打法则更为灵活,更注重对对方心理的把握。这两支队伍的特点比较相近,发挥稳定,teamwork出色,我们除了在胜者角度寻找答案之外,在败者角度分析其失利原因,则可知得失矣。

  3. Lejringsbetingede skæve hoveder hos spædbørn kan forebygges

    DEFF Research Database (Denmark)

    Knudsen, Birgit; Christensen, Karen; Baagøe, Susanne;

    2011-01-01

    The prevalence of positional plagiocephaly is increasing. A systematic database search (Cochrane, MEDLINE, Embase, Cinahl and PEDro), critical appraisal and systematic evaluation of the quality of 14 selected studies show that the following are certain risk factors for the development of position...

  4. Marine bioearosol in the area of Gdańsk Bay

    Directory of Open Access Journals (Sweden)

    Małgorzata Michalska

    2011-03-01

    Full Text Available Formation of bioaerosol is an important process of mass and energy exchange between sea and atmosphere by means of droplets of marine dust. Studies on aerosol activity of the sea was developed in the last decades of the 20 th century. Those studies revealed that concentrations of bacteria in aerosol droplets were hundreds times higher than their concentrations in superficial parts of seawater. The research also proved that aerosol activity of the sea can influence the sanitary condition of the air, especially at the seacoast areas. Surveys of air structure in coastal regions were performed on the Tricity beaches as well as in Sobieszewo and Komary. Atmospheric air sampling stations in the marine zone were located on the Gulf of Gdansk at the Vistula river mouth. Air samples were collected from the front platform on the ship R/V Baltica at 4m above the sea surface. The air samples were collected by filtration method using Sartorius apparatus. Airborne microbes were deposited onto sterile gelatine Sartorius filters. All filters were exposed directly towards the oncoming wind. After sampling, the exposed filters were placed onto the agar media on Petri plates and incubated. All measurement results were depicted in (CFU/m3 i.e. colony forming units in 1 m3 of the examined air. Meteorological measurements included: temperature, humidity, wind speed and direction. The obtained results revealed that statistically significant trends were observed between the total number of bacteria or moulds and a season of sampling. The greatest number of microorganisms was noted in spring and autumn. Correlation analysis showed that statistically significant relationship exists between microbial abundance and the wind direction or speed and location of sampling site. Large quantities of fungal spores was detected in the areas of Gdynia and Gdansk - Brzeêno when south-west winds were blowing from the land. The highest number of bacteria were observed at the sampling stations located closest to the Vistula river mouth (Sobieszewo and Komary.

  5. Developing translational medicine professionals : The Marie Skłodowska-Curie action model

    NARCIS (Netherlands)

    Petrelli, Alessandra; Prakken, Berent J.|info:eu-repo/dai/nl/156714183; Rosenblum, Norman D.

    2016-01-01

    End goal of translational medicine is to combine disciplines and expertise to eventually promote improvement of the global healthcare system by delivering effective therapies to individuals and society. Well-trained experts of the translational medicine process endowed with profound knowledge of

  6. Kroměřížská architektura 19. století

    OpenAIRE

    Zatloukal, Pavel

    2012-01-01

    Change of the Chateau Garden and the renovation of the Church of St Maurice became the essential events for Kroměříž architecture of the late 18th century and the first half of the 19th century. Between the years 1790 and 1800 the original baroque look of the garden was changed into a late Enlightenment park in the jardin pittoresque style, covering twice as large area as the original garden. During the 30s and 40s of the 19th century, architect Anton Arche has carried out a manifold enlargem...

  7. Begær, forførelse og kvindelig skønhed

    DEFF Research Database (Denmark)

    Hansen-Hansen, Erik

    2008-01-01

    på mere end £ 2 millarder og ejet af luksuskorporationen LVMH der er globalt børsnoteret. Afhandlingens hovedformål er at analysere og forklare, hvordan dette nye luksusmodesystem fungerer, herunder, hvordan det afspejler en ny fase i modens historie. For at lave den analyse udvikles der en teoretisk...

  8. Poslech hudby v mateřské škole

    OpenAIRE

    KOLINGEROVÁ, Aneta

    2016-01-01

    Pre-school children are full of motivation to broaden their knowledge and discover the wor