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1.  World Congress Integrative Medicine & Health 2017: part two 
Ee, Carolyn | Thuraisingam, Sharmala | Pirotta, Marie | French, Simon | Xue, Charlie | Teede, Helena | Kristoffersen, Agnete E. | Sirois, Fuschia | Stub, Trine | Engler, Jennifer | Joos, Stefanie | Güthlin, Corina | Felenda, Jennifer | Beckmann, Christiane | Stintzing, Florian | Evans, Roni | Bronfort, Gert | Keefe, Daniel | Taberko, Anna | Hanson, Linda | Haley, Alex | Ma, Haiwei | Jolton, Joseph | Yarosh, Lana | Keefe, Francis | Nam, Jung | Evans, Roni | Ojala, Liwanag | Kreitzer, Mary J. | Hanson, Linda | Fink, Careen | Kraft, Karin | Flower, Andrew | Lewith, George | Harman, Kim | Stuart, Beth | Bishop, Felicity L. | Frawley, Jane | Füleki, Lilla | Kiss, Eva | Vancsik, Tamas | Krenacs, Tibor | Funabashi, Martha | Pohlman, Katherine A. | Mior, Silvano | Thiel, Haymo | Hill, Michael D. | Cassidy, David J. | Westaway, Michael | Yager, Jerome | Hurwitz, Eric | Kawchuk, Gregory N. | O’Beirne, Maeve | Vohra, Sunita | Gaboury, Isabelle | Morin, Chantal | Gaertner, Katharina | Torchetti, Loredana | Frei-Erb, Martin | Kundi, Michael | Frass, Michael | Gallo, Eugenia | Maggini, Valentina | Comite, Mattia | Sofi, Francesco | Baccetti, Sonia | Vannacci, Alfredo | Di Stefano, Mariella | Monechi, Maria V. | Gori, Luigi | Rossi, Elio | Firenzuoli, Fabio | Mediati, Rocco D. | Ballerini, Giovanna | Gardiner, Paula | Lestoquoy, Anna S. | Negash, Lily | Stillman, Sarah | Shah, Prachi | Liebschutz, Jane | Adelstein, Pamela | Farrell-Riley, Christine | Brackup, Ivy | Penti, Brian | Saper, Robert | Sampedro, Isabel Giralt | Carvajal, Gilda | Gleiss, Andreas | Gross, Marie M. | Brendlin, Dorothea | Röttger, Jonas | Stritter, Wiebke | Seifert, Georg | Grzanna, Noelle | Stange, Rainer | Guendling, Peter W. | Gu, Wen | Lu, Yan | Wang, Jie | Zhang, Chengcheng | Bai, Hua | He, Yuxi | Zhang, Xiaoxu | Zhang, Zhengju | Wang, Dali | Meng, Fengxian | Hagel, Alexander | Albrecht, Heinz | Vollbracht, Claudia | Dauth, Wolfgang | Hagel, Wolfgang | Vitali, Francesco | Ganzleben, Ingo | Schultis, Hans | Konturek, Peter | Stein, Jürgen | Neurath, Markus | Raithel, Martin | Hagel, Alexander | Vollbracht, Claudia | Raithel, Martin | Konturek, Peter | Krick, Bianka | Haller, Heidemarie | Klose, Petra | Dobos, Gustav | Kümmel, Sherko | Cramer, Holger | Haller, Heidemarie | Saha, Felix J. | Kowoll, Anna | Ebner, Barbara | Berger, Bettina | Dobos, Gustav | Choi, Kyung-Eun | He, Lisha | Wang, Han | He, X. | Gu, C. | Zhang, Y. | Zhao, Linhua | Tong, Xiaolin | He, Lisha | Wang, Han | He, Xinhui | Gu, Chengjuan | Zhang, Ying | Zhao, Linhua | Tong, Xiaolin | He, Lisha | Wang, Han | He, Xinhui | Gu, Chengjuan | Zhang, Ying | Zhao, Linhua | Tong, Xiaolin | Ho, Robin S. T. | Chung, Vincent C. H. | Wu, Xinyin | Wong, Charlene H. L. | Wu, Justin C. Y. | Wong, Samuel Y. S. | Lau, Alexander Y. L. | Sit, Regina W. S. | Wong, Wendy | Holmes, Michelle | Bishop, Felicity | Calman, Lynn | Holmes, Michelle | Bishop, Felicity | Lewith, George | Newell, Dave | Field, Jonathan | Htut, Win L. | Han, Dongwoon | Choi, Da I. | Choi, Soo J. | Kim, Ha Y. | Hwang, Jung H. | Huang, Ching W. | Jang, Bo H. | Chen, Fang P. | Ko, Seong G. | Huang, Wenjing | Jin, De | Lian, Fengmei | Jang, Soobin | Kim, Kyeong H. | Lee, Eun K. | Sun, Seung H. | Go, Ho Y. | Ko, Youme | Park, Sunju | Jang, Bo H. | Shin, Yong C. | Ko, Seong G. | Janik, Hubert | Greiffenhagen, Natalie | Bolte, Jürgen | Kraft, Karin | Jaworski, Mariusz | Adamus, Miroslawa | Dobrzynska, Aleksandra | Jeitler, Michael | Jaspers, Jessica | von Scheidt, Christel | Koch, Barbara | Michalsen, Andreas | Steckhan, Nico | Kessler, Christian | Jin, De | Huang, Wen-jing | Pang, Bing | Lian, Feng-Mei | Jong, Miek | Baars, Erik | Glockmann, Anja | Hamre, Harald | Kainuma, Mosaburo | Murakami, Aya | Kubota, Toshio | Kobayashi, Daisuke | Sumoto, Yasuhiro | Furusyo, Norihiro | Ando, Shin-Ichi | Shimazoe, Takao | Kelber, Olaf | Verjee, S. | Gorgus, Eva | Schrenk, Dieter | Kemper, Kathi | Hill, Ellie | Kemper, Kathi | Rao, Nisha | Gascon, Gregg | Mahan, John | Kienle, Gunver | Dietrich, Jörg | Schmoor, Claudia | Huber, Roman | Kim, Weon H. | Han, Dongwoon | Ahmed, Mansoor | He, Luzhu | Hwang, Jung Hye | Kiss, Eva | Vancsik, Tamas | Meggyeshazi, Nora | Kovago, Csaba | Krenacs, Tibor | Klaus, Anne K. | Zerm, Roland | Pranga, Danilo | Ostermann, Thomas | Reif, Marcus | von Laue, Hans Broder | Brinkhaus, Benno | Kröz, Matthias | Klaus, Anne K. | Zerm, Roland | Pranga, Danilo | Recchia, Daniela Rodrigues | Ostermann, Thomas | Reif, Marcus | von Laue, Hans B. | Brinkhaus, Benno | Kröz, Matthias | Klein-Laansma, Christien T. | Jong, Mats | von Hagens, Cornelia | Jansen, Jean P. | van Wietmarschen, Herman | Jong, Miek C. | Ko, Youme | Sun, Seung-Ho | Go, Ho-Yeon | Jeon, Chan-Yong | Song, Yun-Kyung | Ko, Seong-Gyu | Koch, Anna K. | Rabsilber, Sybille | Lauche, Romy | Kümmel, Sherko | Dobos, Gustav | Langhorst, Jost | Cramer, Holger | Koch, Anna K. | Trifunovic-Koenig, Milena | Klose, Petra | Cramer, Holger | Dobos, Gustav | Langhorst, Jost | Koster, Evi | Baars, Erik | Delnoij, Diana | Kroll, Lena | Weiss, Kathrin | Kubo, Ai | Hendlish, Sarah | Altschuler, Andrea | Connolly, Nancy | Avins, Andy | Lauche, Romy | Recchia, Daniela Rodrigues | Cramer, Holger | Wardle, Jon | Lee, David | Sibbritt, David | Adams, Jon | Ostermann, Thomas | Lauche, Romy | Sibbritt, David | Park, Crystal | Mishra, Gita | Adams, Jon | Cramer, Holger | Lechner, Johann | Lee, Inseon | Chae, Younbyoung | Lee, Jisu | Cho, Seung H. | Choi, Yujin | Lee, Jee Y. | Ryu, Han S. | Yoon, Sung S. | Oh, Hye K. | Hyun, Lyun K. | Kim, Jin O. | Yoon, Seong W. | Lee, Ju-Yeon | Shin, Sang-Hoon | Jang, Min | Müller, Indra | Park, So-Hyun Janson | Lestoquoy, Anna S. | Laird, Lance | Negash, Lily | Mitchell, Suzanne | Gardiner, Paula | Li, Xiaofei | Wang, Yunhui | Zhen, Jianhua | Yu, He | Liu, Tiegang | Gu, Xiaohong | Liu, Hui | Ma, Weiguo | Zhang, Chengcheng | Shang, Xuezheng | Bai, Yu | Meng, Fengxian | Liu, Wei | Rooney, Collin | Smith, Amos | Lopes, Shirlene | Demarzo, Marcelo | do Patrocínio Nunes, Maria | Lorenz, Peter | Gründemann, Carsten | Heinrich, Miriam | Garcia-Käufer, Manuel | Grunewald, Franziska | Messerschmidt, Silke | Herrick, Anja | Gruber, Kim | Beckmann, Christiane | Knödler, Matthias | Huber, Roman | Steinborn, Carmen | Stintzing, Florian | Lu, Taoying | Wang, Lixin | Wu, Darong | Luberto, Christina M | Hall, Daniel L. | Chad-Friedman, Emma | Lechner, Suzanne | Park, Elyse R. | Luberto, Christina M. | Park, Elyse | Goodman, Janice | Luer, Sonja | Heri, Matthias | von Ammon, Klaus | Frei-Erb, Martin | Ma, Weiguo | Meng, Fengxian | Maggini, Valentina | Gallo, Eugenia | Landini, Ida | Lapucci, Andrea | Nobili, Stefania | Mini, Enrico | Firenzuoli, Fabio | McDermott, Clare | Lewith, George | Richards, Selwyn | Cox, Diane | Frossell, Sarah | Leydon, Geraldine | Eyles, Caroline | Raphael, Hilly | Rogers, Rachael | Selby, Michelle | Adler, Charlotte | Allam, Jo | Meng, Fengxian | Gu, Wen | Zhang, Chengcheng | Bai, Hua | Zhang, Zhengju | Wang, Dali | Bu, Xiangwei | Zhang, Honghong | Zhang, Jianpeng | Liu, Hui | Mikolasek, Michael | Berg, Jonas | Witt, Claudia | Barth, Jürgen | Miskulin, Ivan | Lalic, Zdenka | Miskulin, Maja | Dumic, Albina | Sebo, Damir | Vcev, Aleksandar | Mohammed, Nasr A. A. | Han, Dongwoon | Ahmed, Mansoor | Choi, Soo Jeung | Im, Hyea Bin | Hwang, Jung Hye | Mukherjee, Anwesha | Kandhare, Amit | Bodhankar, Subhash | Mukherjee, Anwesha | Kandhare, Amit | Thakurdesai, Prasad | Bodhankar, Subhash | Munk, Niki | Evans, Erica | Froman, Amanda | Kline, Matthew | Bair, Matthew J. | Musial, Frauke | Kristoffersen, Agnete E. | Alræk, Terje | Hamre, Harald J. | Stub, Trine | Björkman, Lars | Fønnebø, Vinjar M. | Pang, Bing | Lian, Feng-mei | Ni, Qing | Tong, Xiao-lin | Li, Xin-long | Liu, Wen-ke | Feng, Shuo | Zhao, Xi-yan | Zheng, Yu-jiao | Zhao, Xue-min | Lin, Yi-qun | Pang, Bing | Lian, Feng-mei | Tong, Xiao-lin | Zhao, Tian-yu | Zhao, Xi-Yan | Phd, Hui Che | Zhang, Chen | Pang, Bing | Liu, Feng | Tong, Xiao-lin | Zhao, Lin-hua | Zhao, Xue-min | Ye, Ru | Gu, Cheng-juan | Pang, Bing | Ni, Qing | Tong, Xiao-lin | Lian, Feng-mei | Zhao, Xi-yan | Jin, De | Zhao, Xue-min | Zheng, Yu-jiao | Lin, Yi-qun | Peng, Wenbo | Lauche, Romy | Sibbritt, David | Adams, Jon | Peng, Wenbo | Wardle, Jon | Cramer, Holger | Mishra, Gita | Lauche, Romy | Pohlman, Katherine A. | Mior, Silvano | Funabashi, Martha | De Carvalho, Diana | El-Bayoumi, Mohamed | Haig, Bob | Kelly, Kimbalin | Wade, Darrell J. | O’Beirne, Maeve | Vohra, Sunita | Portalupi, Emanuela | Gobo, Giampietro | Bellavita, Luigi | Guglielmetti, Chiara | Raak, Christa | Teuber, Myriam | Molsberger, Friedrich | von Rath, Ulrich | Reichelt, Ulrike | Schwanebeck, Uta | Zeil, Sabine | Vogelberg, Christian | Veintimilla, Dolores Rodríguez | Vollbracht, Claudia | Mery, Guerrero Tapia | Villavicencio, Marisol Maldonado | Moran, Sandra Herrera | Sachse, Christian | Gündlin, Peter W | Stange, Rainer | Sahebkarkhorasani, Monirsadat | Azizi, Hoda | Schumann, Dania | Lauche, Romy | Sundberg, Tobias | Leach, Matthew J. | Cramer, Holger | Seca, Susana | Greten, Henry | Selliah, Sugir | Shakya, Anu | Han, Dongwoon | Kim, Ha Yun | Choi, Da I. | Im, Hyea B. | Choi, Soo J. | Sherbakova, Anna | Ulrich-Merzenich, Gudrun | Kelber, Olaf | Abdel-Aziz, Heba | Sibinga, Erica | Webb, Lindsey | Ellen, Jonathan | Skrautvol, Kari | Nåden, Dagfinn | Song, Rhayun | Grabowska, Weronika | Osypiuk, Kamila | Diaz, Gloria V. | Bonato, Paolo | Park, Moonkyoung | Hausdorff, Jeffrey | Fox, Michael | Sudarsky, Lewis R. | Tarsy, Daniel | Novakowski, James | Macklin, Eric A. | Wayne, Peter M. | Song, Rhayun | Hwang, Inok | Ahn, Sukhee | Lee, Myung-Ah | Wayne, Peter M. | Sohn, Min K. | Sorokin, Oleg | Steckhan, Nico | Heydeck, Dagmar | Borchert, Astrid | Hohmann, Christoph-Daniel | Kühn, Harmut | Michalsen, Andreas | Kessler, Christian | Steckhan, Nico | Hohmann, Christoph-Daniel | Cramer, Holger | Michalsen, Andreas | Dobos, Gustav | von Scheidt, Christel | Kirschbaum, Clemens | Stalder, Tobias | Stöckigt, Barbara | Teut, Michael | Suhr, Ralf | Sulmann, Daniela | Brinkhaus, Benno | Streeter, Chris | Gerbarg, Patrica | Silveri, Marisa | Brown, Richard | Jensen, John | Stritter, Wiebke | Rutert, Britta | Eggert, Angelika | Längler, Alfred | Seifert, Georg | Holmberg, Christine | Sun, Jin | Deng, Xin | Li, Wen-Yuan | Wen, Bin | Robinson, Nicola | Liu, Jian-Ping | Sung, Hyun K. | Yang, Narae | Go, Ho Y. | Shin, Seon M. | Jung, Hee | Kim, Young J. | Jung, Woo S. | Park, Tae Y. | Suzuki, Kiyoshi | Ito, Toshinori | Uchida, Seiya | Kamohara, Seika | Ono, Naoya | Takamura, Mitsuyuki | Yokochi, Ayumu | Maruyama, Kazuo | Tapia, Patricio | Thabaut, Katarzyna | Brinkhaus, Benno | Stöckigt, Barbara | Thronicke, Anja | Kröz, Matthias | Steele, Megan | Matthes, Harald | Herbstreit, Cornelia | Schad, Friedemann | Tian, Jiaxing | Lian, Fengmei | Yang, Libo | Tong, Xiaolin | Tian, Tian | Zhang, Hewei | Tian, Xia | Wang, CongCong | Chai, Qian Yun | Zhang, Lijuan | Xia, Ruyu | Huang, Na | Fei, Yutong | Liu, Jianpin | Trent, Natalie | Miraglia, Mindy | Dusek, Jeffrey | Pasalis, Edi | Khalsa, Sat B. | Trifunovic-König, Milena | Klose, Petra | Cramer, Holger | Lauche, Romy | Koch, Anna | Dobos, Gustav | Langhorst, Jost | Uebelacker, Lisa | Tremont, Geoffrey | Gillette, Lee | Epstein-Lubow, Gary | Strong, David | Abrantes, Ana | Tyrka, Audrey | Tran, Tanya | Gaudiano, Brandon | Miller, Ivan | Ullmann, Gerhild | Ullmann, Gerhild | Li, Yuhua | Vaidya, Sujata | Marathe, Vinod | Vale, Ana C. | Motta, Jacquelyne | Donadão, Fabíola | Valente, Angela C. | Valente, Luana C. Carvalho | Ghelman, Ricardo | Vesovic, Dusan | Jevdic, Dragan | Jevdic, Aleksandar | Jevdic, Katarina | Djacic, Mihael | Letic, Dragica | Bozic, Drago | Markovic, Marija | Dunjic, Slobodan | Vesovic, Dusan | Jevdic, Dragan | Jevdic, Aleksandar | Jevdic, Katarina | Djacic, Mihael | Letic, Dragica | Bozic, Drago | Markovic, Marija | Ruscuklic, Gordana | Baksa, Dezire | Dunjic, Slobodan | Vesovic, Dusan | Jevdic, Dragan | Jevdic, Aleksandar | Jevdic, Katarina | Djacic, Mihael | Letic, Dragica | Bozic, Drago | Markovic, Marija | Ruscuklic, Gordana | Baksa, Dezire | Dunjic, Slobodan | Vesovic, Dusan | Jevdic, Dragan | Jevdic, Aleksandar | Jevdic, Katarina | Djacic, Mihael | Letic, Dragica | Bozic, Drago | Markovic, Marija | Ruscuklic, Gordana | Baksa, Dezire | Dunjic, Slobodan | Vesovic, Dusan | Jevdic, Dragan | Jevdic, Aleksandar | Jevdic, Katarina | Djacic, Mihael | Letic, Dragica | Bozic, Drago | Markovic, Marija | Vrca, Kenan | Dunjic, Slobodan | Vincent, Ann | Wahner-Roedler, Dietlind | Whipple, Mary | Vogelius, Maria M. | Vollbracht, Claudia | Friesecke, Iris | Gündling, Peter W. | Wahner-Roedler, Dietlind | Mahapatra, Saswati | Hynes, Rebecca | Van Rooy, Kimberly | Looker, Sherry | Ghosh, Aditya | Bauer, Brent | Cutshall, Susanne | Walach, Harald | Flores, Ana Borges | Walach, Harald | Ofner, Michael | Kastner, Andreas | Schwarzl, Gerhard | Schwameder, Hermann | Alexander, Nathalie | Strutzenberger, Gerda | Wang, Jie | Lu, Yan | Gu, Wen | Zhang, Chengcheng | Bu, Xianwei | Zhang, Honghong | Zhang, Jianping | He, Yuxi | Zhang, Xiaoxu | Meng, Fengxian | Wang, Shang | Yu, He | Shi, Jinfeng | Hao, Yu | Liu, Tiegang | Wu, Jun | Qiu, Zeji | Gu, Xiaohong | Wang, Yuh-Hai | Lou, Chi-Jung | Watts, Sam | Wayne, Peter | Osypiuk, Kamila | Vergara-Diaz, Gloria | Bonato, Paolo | Gow, Brian | Hausdorff, Jeffrey | Miranda, Jose | Sudarsky, Lewis | Tarsy, Daniel | Fox, Michael | Macklin, Eric | Wode, Kathrin | Bergqvist, Jenny | Bernhardsson, Britt-Marie | Nordberg, Johanna Hök | Kienle, Gunver | Sharp, Lena | Henriksson, Roger | Woo, Yeonju | Hyun, Min K. | Wu, Hao | Wang, Tian-Fang | Zhao, Yan | Wei, Yu | Tian, Lei | He, Lei | Wang, Xue | Wu, Ruohan | Feng, Shuo | Han, Mei | Caldwell, Patrina H. Y. | Liu, Shigang | Zhang, Jing | Liu, Jianping | Xia, Ruyu | Chai, Qianyun | Fei, Yutong | Guo, Zhongning | Wang, Congcong | Liu, Zhijun | Li, Xun | Zhang, Ying | Liu, Jianping | Yang, I. J. | Lincha, V. Ruberio | Ahn, S. H. | Lee, D. U. | Shin, H. M. | Yang, Lu | Sibbritt, David | Peng, Wenbo | Adams, Jon | Yang, N. | Sung, H. | Shin, S. M. | Go, H. Y. | Jung, H. | Kim, Y. | Park, T. Y. | Yap, Angela | Kwan, Yu H. | Tan, Chuen S. | Ibrahim, Syed | Ang, Seng B. | Yayi, Alfred | Han, Dongwoon | Im, Hyea Bin | Hwang, Jung Hye | Choi, Soo Jeung | Yoo, Jeong E. | Yoo, Ho R. | Jang, Sae B. | Lee, Hye L. | Youssef, Ala’a | Ezzat, Shahira | Motaal, Amira Abdel | El-Askary, Hesham | Yu, Xiaotong | Cui, Yashan | Zhang, Ying | Lian, Fengmei | Yun, Younghee | Ko, Youme | Ahn, Jin-Hyang | Jang, Bo-Hyung | Kim, Kyu-Seok | Ko, Seong-Gyu | Choi, Inhwa | Zerm, Roland | Glinz, Augustina | Pranga, Danilo | Berger, Bettina | ten Brink, Fadime | Reif, Marcus | Büssing, Arnd | Gutenbrunner, Christoph | Kröz, Matthias | Zerm, Roland | Helbrecht, Bert | Pranga, Danilo | Brinkhaus, Benno | Michalsen, Andreas | Kröz, Matthias | Zhang, Honghong | Fang, Tiesheng | Wang, Jie | Zhang, Chengcheng | He, Yuxi | Zhang, Xiaoxu | Zhang, Zhengju | Wang, Dali | Meng, Fengxion | Zhang, Jianping | Zhang, Chengcheng | Bai, Hua | Shen, Zhiming | Ma, Weiguo | Liu, Hui | Bai, Yu | Shang, Xuezheng | Meng, Fengxian | Zhang, Ruixin | Wu, Fan | Li, Ming | Xuan, Xinyun | Shen, Xueyong | Ren, Ke | Berman, Brian | Zhen, Jianhua | Li, Xiaofei | Gu, Xiaohong | Yu, He | Zheng, Zian | Wan, Yuxiang | Wang, Yunhui | Ma, Xueyan | Dong, Fei | Liu, Tiegang | Zhen, Jianhua | Li, Xiaofei | Gu, Xiaohong | Yu, He | Zheng, Zian | Wan, Yuxiang | Wang, Yunhui | Ma, Xueyan | Dong, Fei | Liu, Tiegang | Zick, Suzie | Harris, Richard | Bae, Go E. | Kwon, Jung N. | Lee, Hye Y. | Nam, Jong K. | Lee, Sang D. | Lee, Dong H. | Han, Ji Y. | Yun, Young J. | Lee, Ji H. | Park, Hye L. | Park, Seong H. | Bocci, Chiara | Ivaldi, Giovanni B. | Vietti, Ilaria | Meaglia, Ilaria | Guffi, Marta | Ruggiero, Rubina | Gualea, Marita | Longa, Emanuela | Bonucci, Massimo | Croke, Sarah | Rodriguez, Lourdes Diaz | Caracuel-Martínez, Juan C. | Fajardo-Rodríguez, Manuel F. | Ariza-García, Angélica | la Fuente, Francisca García-De | Arroyo-Morales, Manuel | Estrems, Maria S. | Gómez, Vicente G. | Estrems, Maria S. | Sabater, Mónica Valero | Ferreri, Rosaria | Bernardini, Simonetta | Pulcri, Roberto | Cracolici, Franco | Rinaldi, Massimo | Porciani, Claudio | Firenzuoli, Fabio | Baccetti, Sonia | Di Stefano, Mariella | Monechi, Maria V. | Gallo, Eugenia | Maggini, Valentina | Gori, Luigi | Rossi, Elio | Fisher, Peter | Hughes, John | Mendoza, Ariadna | MacPherson, Hugh | Witt, Claudia | Filshie, Jacqueline | Lewith, George | Di Francesco, Antonia | Bernardini, Alberto | Messe, Monica | Primitivo, Vincenzo | Iasella, Piera A. | Ghelman, Ricardo | Taminato, Monica | Alcantara, Jaqueline Do Carmo | De Oliveira, Katia R. | Rodrigues, Debora C. De Azevedo | Mumme, Juliana R. Campana | Sunakozawa, Olga K. Matsumoto | Filho, Vicente Odone | Seifert, Georg | Goldenberg, Joshua | Day, Andrew | Sasagawa, Masa | Ward, Lesley | Cooley, Kieran | Gunnarsdottir, Thora | Hjaltadottir, Ingibjorg | Hajimonfarednejad, Mahdie
doi:10.1186/s12906-017-1783-3
PMCID: PMC5498867
2.  Arabidopsis thaliana FLA4 functions as a glycan‐stabilized soluble factor via its carboxy‐proximal Fasciclin 1 domain 
The Plant Journal  2017;91(4):613-630.
Summary
Fasciclin‐like arabinogalactan proteins (FLAs) are involved in numerous important functions in plants but the relevance of their complex structure to physiological function and cellular fate is unresolved. Using a fully functional fluorescent version of Arabidopsis thaliana FLA4 we show that this protein is localized at the plasma membrane as well as in endosomes and soluble in the apoplast. FLA4 is likely to be GPI‐anchored, is highly N‐glycosylated and carries two O‐glycan epitopes previously associated with arabinogalactan proteins. The activity of FLA4 was resistant against deletion of the amino‐proximal fasciclin 1 domain and was unaffected by removal of the GPI‐modification signal, a highly conserved N‐glycan or the deletion of predicted O‐glycosylation sites. Nonetheless these structural changes dramatically decreased endoplasmic reticulum (ER)‐exit and plasma membrane localization of FLA4, with N‐glycosylation acting at the level of ER‐exit and O‐glycosylation influencing post‐secretory fate. We show that FLA4 acts predominantly by molecular interactions involving its carboxy‐proximal fasciclin 1 domain and that its amino‐proximal fasciclin 1 domain is required for stabilization of plasma membrane localization. FLA4 functions as a soluble glycoprotein via its carboxy‐proximal Fas1 domain and its normal cellular trafficking depends on N‐ and O‐glycosylation.
Significance Statement
FLA4, a protein involved in root growth, salt tolerance and seed coat mucilage development consists of two fasciclin domains, multiple predicted glycosylation sites and a GPI‐anchoring motif. The functional significance of these features is elusive. Our structural functional dissection shows that the carboxy terminal fasciclin domain is crucial for FLA4 function while the amino‐terminal fasciclin domain, GPI‐anchoring N‐linked and O‐linked glycosylation are important for intracellular trafficking but not for function.
doi:10.1111/tpj.13591
PMCID: PMC5575511  PMID: 28482115
arabinogalactan protein; fasciclin; GPI‐anchor; N‐glycan; O‐glycan; Arabidopsis thaliana
3.  Synergistic Antitumour Properties of viscumTT in Alveolar Rhabdomyosarcoma 
Journal of Immunology Research  2017;2017:4874280.
Aqueous mistletoe extracts from the European mistletoe (Viscum album) contain mainly mistletoe lectins and viscotoxins as cytotoxic compounds. Lipophilic triterpene acids, which do not occur in conventional mistletoe preparations, were solubilised with β-cyclodextrins. The combination of an aqueous extract (viscum) and a triterpene-containing extract (TT) recreated a whole mistletoe extract (viscumTT). These extracts were tested on rhabdomyosarcoma in vitro, ex vivo, and in vivo with regard to anticancer effects. Viscum and viscumTT inhibited cell proliferation and induced apoptosis effectively in a dose-dependent manner in vitro and ex vivo, whereas TT showed only moderate inhibitory effects. viscumTT proved to be more effective than the single extracts and displayed a synergistic effect in vitro and a stronger effect in vivo. viscumTT induced apoptosis via the extrinsic and intrinsic pathways, evidenced by the loss of mitochondrial membrane potential and activation of CASP8 and CASP9. CASP10 inhibitor inhibited apoptosis effectively, emphasising the importance of CASP10 in viscumTT-induced apoptosis. Additionally, viscumTT changed the ratio of apoptosis-associated proteins by downregulation of antiapoptotic proteins such as XIAP and BIRC5, thus shifting the balance towards apoptosis. viscumTT effectively reduced tumour volume in patient-derived xenografts in vivo and may be considered a promising substance for rhabdomyosarcoma therapy.
doi:10.1155/2017/4874280
PMCID: PMC5534308
4.  World Congress Integrative Medicine & Health 2017: Part one 
Brinkhaus, Benno | Falkenberg, Torkel | Haramati, Aviad | Willich, Stefan N. | Briggs, Josephine P. | Willcox, Merlin | Linde, Klaus | Theorell, Töres | Wong, Lisa M. | Dusek, Jeffrey | Wu, Darong | Eisenberg, David | Haramati, Aviad | Berger, Bettina | Kemper, Kathi | Stock-Schröer, Beate | Sützl-Klein, Hedda | Ferreri, Rosaria | Kaplan, Gary | Matthes, Harald | Rotter, Gabriele | Schiff, Elad | Arnon, Zahi | Hahn, Eckhard | Luberto, Christina M. | Martin, David | Schwarz, Silke | Tauschel, Diethard | Flower, Andrew | Gramminger, Harsha | Gupta, Hedwig H. | Gupta, S. N. | Kerckhoff, Annette | Kessler, Christian S. | Michalsen, Andreas | Kessler, Christian S. | Kim, Eun S. | Jang, Eun H. | Kim, Rana | Jan, Sae B. | Mittwede, Martin | Mohme, Wiebke | Ben-Arye, Eran | Bonucci, Massimo | Saad, Bashar | Breitkreuz, Thomas | Rossi, Elio | Kebudi, Rejin | Daher, Michel | Razaq, Samaher | Gafer, Nahla | Nimri, Omar | Hablas, Mohamed | Kienle, Gunver Sophia | Samuels, Noah | Silbermann, Michael | Bandelin, Lena | Lang, Anna-Lena | Wartner, Eva | Holtermann, Christoph | Binstock, Maxwell | Riebau, Robert | Mujkanovic, Edin | Cramer, Holger | Lauche, Romy | Michalsen, Andres | Ward, Lesley | Cramer, Holger | Irnich, Dominik | Stör, Wolfram | Burnstock, Geoffrey | Schaible, Hans-Georg | Ots, Thomas | Langhorst, Jost | Lauche, Romy | Sundberg, Tobias | Falkenberg, Torkel | Amarell, Catherina | Amarell, Catherina | Anheyer, Melanie | Eckert, Marion | Eckert, Marion | Ogal, Mercedes | Eckert, Marion | Amarell, Catherina | Schönauer, Annette | Reisenberger, Birgit | Brand, Bernhard | Anheyer, Dennis | Dobos, Gustav | Kroez, Matthias | Martin, David | Matthes, Harald | Ammendola, Aldo | Mao, Jun J. | Witt, Claudia | Yang, Yufei | Dobos, Gustav | Oritz, Miriam | Horneber, Markus | Voiß, Petra | Reisenberger, Birgit | von Rosenstiel, Alexandra | Eckert, Marion | Ogal, Mercedes | Amarell, Catharina | Anheyer, Melanie | Schad, Friedemann | Schläppi, Marc | Kröz, Matthias | Büssing, Arndt | Bar-Sela, Gil | Matthes, Harald | Schiff, Elad | Ben-Arye, Eran | Arnon, Zahi | Avshalomov, David | Attias, Samuel | Schönauer, Annette | Haramati, Aviad | Witt, Claudia | Brinkhaus, Benno | Cotton, Sian | Jong, Miek | Jong, Mats | Scheffer, Christian | Haramati, Aviad | Tauschel, Diethard | Edelhäuser, Friedrich | AlBedah, Abdullah | Lee, Myeong Soo | Khalil, Mohamed | Ogawa, Keiko | Motoo, Yoshiharu | Arimitsu, Junsuke | Ogawa, Masao | Shimizu, Genki | Stange, Rainer | Kraft, Karin | Kuchta, Kenny | Watanabe, Kenji | Bonin, D | Büssing, Arndt | Gruber, Harald | Koch, Sabine | Gruber, Harald | Pohlmann, Urs | Caldwell, Christine | Krantz, Barbara | Kortum, Ria | Martin, Lily | Wieland, Lisa S. | Kligler, Ben | Gould-Fogerite, Susan | Zhang, Yuqing | Wieland, Lisa S. | Riva, John J. | Lumpkin, Michael | Ratner, Emily | Ping, Liu | Jian, Pei | Hamme, Gesa-Meyer | Mao, Xiaosong | Chouping, Han | Schröder, Sven | Hummelsberger, Josef | Wullinger, Michael | Brodzky, Marc | Zalpour, Christoff | Langley, Julia | Weber, Wendy | Mudd, Lanay M. | Wayne, Peter | Witt, Clauda | Weidenhammer, Wolfgang | Fønnebø, Vinjar | Boon, Heather | Steel, Amie | Bugarcic, Andrea | Rangitakatu, Melisa | Steel, Amie | Adams, Jon | Sibbritt, David | Wardle, Jon | Leach, Matthew | Schloss, Janet | Dieze, Helene | Boon, Heather | Ijaz, Nadine | Willcox, Merlin | Heinrich, Michael | Lewith, George | Flower, Andrew | Graz, Bertrand | Adam, Daniela | Grabenhenrich, Linus | Ortiz, Miriam | Binting, Sylvia | Reinhold, Thomas | Brinkhaus, Benno | Andermo, Susanne | Sundberg, Tobias | Falkenberg, Torkel | Nordberg, Johanna Hök | Arman, Maria | Bhasin, Manoj | Fan, Xueyi | Libermann, Towia | Fricchione, Gregory | Denninger, John | Benson, Herbert | Berger, Bettina | Stange, Rainer | Michalsen, Andreas | Martin, David D. | Boers, Inge | Vlieger, Arine | Jong, Miek | Brinkhaus, Benno | Teut, Michael | Ullmann, Alexander | Ortiz, Miriam | Rotter, Gabriele | Binting, Sylvia | Lotz, Fabian | Roll, Stephanie | Canella, Claudia | Mikolasek, Michael | Rostock, Matthias | Beyer, Jörg | Guckenberger, Matthias | Jenewein, Josef | Linka, Esther | Six, Claudia | Stoll, Sarah | Stupp, Roger | Witt, Claudia M. | Chuang, Elisabeth | Kligler, Ben | McKee, Melissa D. | Cramer, Holger | Lauche, Romy | Klose, Petra | Lange, Silke | Langhorst, Jost | Dobos, Gustav | Chung, Vincent C. H. | Wong, Hoi L. C. | Wu, Xin Y. | Wen, Grace Y. G. | Ho, Robin S. T. | Ching, Jessica Y. L. | Wu, Justin C. Y. | Coakley, Amanda | Flanagan, Jane | Annese, Christine | Empoliti, Joanne | Gao, Zishan | Liu, Xugang | Yu, Shuguang | Yan, Xianzhong | Liang, Fanrong | Hohmann, Christoph D. | Steckhan, Nico | Ostermann, Thomas | Paetow, Arion | Hoff, Evelyn | Michalsen, Andreas | Hu, Xiao-Yang | Wu, Ruo-Han | Logue, Martin | Blonde, Clara | Lai, Lily Y. | Stuart, Beth | Flower, Andrew | Fei, Yu-Tong | Moore, Michael | Liu, Jian-Ping | Lewith, George | Hu, Xiao-Yang | Wu, Ruo-Han | Logue, Martin | Blonde, Clara | Lai, Lily Y. | Stuart, Beth | Flower, Andrew | Fei, Yu-Tong | Moore, Michael | Liu, Jian-Ping | Lewith, George | Jeitler, Michael | Zillgen, Hannah | Högl, Manuel | Steckhan, Nico | Stöckigt, Barbara | Seifert, Georg | Michalsen, Andreas | Kessler, Christian | Khadivzadeh, Talat | Bashtian, Maryam Hassanzadeh | Aval, Shapour Badiee | Esmaily, Habibollah | Kim, Jihye | Kim, Keun H. | Klocke, Carina | Joos, Stefanie | Koshak, Abdulrahman | Wie, Li | Koshak, Emad | Wali, Siraj | Alamoudi, Omer | Demerdash, Abdulrahman | Qutub, Majdy | Pushparaj, Peter | Heinrich, Michael | Kruse, Sigrid | Fischer, Isabell | Tremel, Nadine | Rosenecker, Joseph | Leung, Brenda | Takeda, Wendy | Liang, Ning | Feng, Xue | Liu, Jian-ping | Cao, Hui-juan | Luberto, Christina M. | Shinday, Nina | Philpotts, Lisa | Park, Elyse | Fricchione, Gregory L. | Yeh, Gloria | Munk, Niki | Zakeresfahani, Arash | Foote, Trevor R. | Ralston, Rick | Boulanger, Karen | Özbe, Dominik | Gräßel, Elmar | Luttenberger, Katharina | Pendergrass, Anna | Pach, Daniel | Bellmann-Strobl, Judit | Chang, Yinhui | Pasura, Laura | Liu, Bin | Jäger, Sven F. | Loerch, Ronny | Jin, Li | Brinkhaus, Benno | Ortiz, Miriam | Reinhold, Thomas | Roll, Stephanie | Binting, Sylvia | Icke, Katja | Shi, Xuemin | Paul, Friedemann | Witt, Claudia M. | Rütz, Michaela | Lynen, Andreas | Schömitz, Meike | Vahle, Maik | Salomon, Nir | Lang, Alon | Lahat, Adi | Kopylov, Uri | Ben-Horin, Shomron | Har-Noi, Ofir | Avidan, Benjamin | Elyakim, Rami | Gamus, Dorit | NG, Siew | Chang, Jessica | Wu, Justin | Kaimiklotis, John | Schumann, Dania | Buttó, Ludovica | Langhorst, Jost | Dobos, Gustav | Haller, Dirk | Cramer, Holger | Smith, Caroline | de Lacey, Sheryl | Chapman, Michael | Ratcliffe, Julie | Johnson, Neil | Lyttleton, Jane | Boothroyd, Clare | Fahey, Paul | Tjaden, Bram | van Vliet, Marja | van Wietmarschen, Herman | Jong, Miek | Tröger, Wilfried | Vuolanto, Pia | Aarva, Paulina | Sorsa, Minna | Helin, Kaija | Wenzel, Claudia | Zoderer, Iris | Pammer, Patricia | Simon, Patrick | Tucek, Gerhard | Wode, Kathrin | Henriksson, Roger | Sharp, Lena | Stoltenberg, Anna | Nordberg, Johanna Hök | Xiao-ying, Yang | Wang, Li-qiong | Li, Jin-gen | Liang, Ning | Wang, Ying | Liu, Jian-ping | Balneaves, Lynda | Capler, Rielle | Bocci, Chiara | Guffi, Marta | Paolini, Marina | Meaglia, Ilaria | Porcu, Patrizia | Ivaldi, Giovanni B. | Dragan, Simona | Bucuras, Petru | Pah, Ana M. | Badalica-Petrescu, Marius | Buleu, Florina | Hogea-Stoichescu, Gheorghe | Christodorescu, Ruxandra | Kao, Lan | Cho, Yumin | Klafke, Nadja | Mahler, Cornelia | von Hagens, Cornelia | Uhlmann, Lorenz | Bentner, Martina | Schneeweiss, Andreas | Mueller, Andreas | Szecsenyi, Joachim | Joos, Stefanie | Neri, Isabella | Ortiz, Miriam | Schnabel, Katharina | Teut, Michael | Rotter, Gabriele | Binting, Sylvia | Cree, Margit | Lotz, Fabian | Suhr, Ralf | Brinkhaus, Benno | Rossi, Elio | Baccetti, Sonia | Firenzuoli, Fabio | Monechi, Maria V. | Di Stefano, Mariella | Amunni, Gianni | Wong, Wendy | Chen, Bingzhong | Wu, Justin | Amri, Hakima | Haramati, Aviad | Kotlyanskaya, Lucy | Anderson, Belinda | Evans, Roni | Kligler, Ben | Marantz, Paul | Bradley, Ryan | Booth-LaForce, Cathryn | Zwickey, Heather | Kligler, Benjamin | Brooks, Audrey | Kreitzer, Mary J. | Lebensohn, Patricia | Goldblatt, Elisabeth | Esmel-Esmel, Neus | Jiménez-Herrera, Maria | Ijaz, Nadine | Boon, Heather | Jocham, Alexandra | Stock-Schröer, Beate | Berberat, Pascal O. | Schneider, Antonius | Linde, Klaus | Masetti, Morgana | Murakozy, Henriette | Van Vliet, Marja | Jong, Mats | Jong, Miek | Agdal, Rita | Atarzadeh, Fatemeh | Jaladat, Amir M. | Hoseini, Leila | Amini, Fatemeh | Bai, Chen | Liu, Tiegang | Zheng, Zian | Wan, Yuxiang | Xu, Jingnan | Wang, Xuan | Yu, He | Gu, Xiaohong | Daneshfard, Babak | Nimrouzi, Majid | Tafazoli, Vahid | Alorizi, Seyed M. Emami | Saghebi, Seyed A. | Fattahi, Mohammad R. | Salehi, Alireza | Rezaeizadeh, Hossein | Zarshenas, Mohammad M. | Nimrouzi, Majid | Fox, Kealoha | Hughes, John | Kostanjsek, Nenad | Espinosa, Stéphane | Lewith, George | Fisher, Peter | Latif, Abdul | Lefeber, Donald | Paske, William | Öztürk, Ali Ö. | Öztürk, Gizemnur | Boers, Inge | Tissing, Wim | Naafs, Marianne | Busch, Martine | Jong, Miek | Daneshfard, Babak | Sanaye, Mohammad R. | Dräger, Kilian | Fisher, Peter | Kreitzer, Mary J. | Evans, Roni | Leininger, Brent | Shafto, Kate | Breen, Jenny | Sanaye, Mohammad R. | Daneshfard, Babak | Simões-Wüst, Ana P. | Moltó-Puigmartí, Carolina | van Dongen, Martien | Dagnelie, Pieter | Thijs, Carel | White, Shelley | Wiesener, Solveig | Salamonsen, Anita | Stub, Trine | Fønnebø, Vinjar | Abanades, Sergio | Blanco, Mar | Masllorens, Laia | Sala, Roser | Al-Ahnoumy, Shafekah | Han, Dongwoon | He, Luzhu | Kim, Ha Yun | In Choi, Da | Alræk, Terje | Stub, Trine | Kristoffersen, Agnete | von Sceidt, Christel | Michalsen, Andreas | Bruset, Stig | Musial, Frauke | Anheyer, Dennis | Cramer, Holger | Lauche, Romy | Saha, Felix J. | Dobos, Gustav | Anheyer, Dennis | Haller, Heidemarie | Lauche, Romy | Dobos, Gustav | Cramer, Holger | Azizi, Hoda | Khadem, Nayereh | Hassanzadeh, Malihe | Estiri, Nazanin | Azizi, Hamideh | Tavassoli, Fatemeh | Lotfalizadeh, Marzieh | Zabihi, Reza | Esmaily, Habibollah | Azizi, Hoda | Shabestari, Mahmoud Mohammadzadeh | Paeizi, Reza | Azari, Masoumeh Alvandi | Bahrami-Taghanaki, Hamidreza | Zabihi, Reza | Azizi, Hamideh | Esmaily, Habibollah | Baars, Erik | De Bruin, Anja | Ponstein, Anne | Baccetti, Sonia | Di Stefano, Mariella | Rossi, Elio | Firenzuoli, Fabio | Segantini, Sergio | Monechi, Maria Valeria | Voller, Fabio | Barth, Jürgen | Kern, Alexandra | Lüthi, Sebastian | Witt, Claudia | Barth, Jürgen | Zieger, Anja | Otto, Fabius | Witt, Claudia | Beccia, Ariel | Dunlap, Corina | Courneene, Brendan | Bedregal, Paula | Passi, Alvaro | Rodríguez, Alfredo | Chang, Mayling | Gutiérrez, Soledad | Beissner, Florian | Beissner, Florian | Preibisch, Christine | Schweizer-Arau, Annemarie | Popovici, Roxana | Meissner, Karin | Beljanski, Sylvie | Belland, Laura | Rivera-Reyes, Laura | Hwang, Ula | Berger, Bettina | Sethe, Dominik | Hilgard, Dörte | Heusser, Peter | Bishop, Felicity | Al-Abbadey, Miznah | Bradbury, Katherine | Carnes, Dawn | Dimitrov, Borislav | Fawkes, Carol | Foster, Jo | MacPherson, Hugh | Roberts, Lisa | Yardley, Lucy | Lewith, George | Bishop, Felicity | Al-Abbadey, Miznah | Bradbury, Katherine | Carnes, Dawn | Dimitrov, Borislav | Fawkes, Carol | Foster, Jo | MacPherson, Hugh | Roberts, Lisa | Yardley, Lucy | Lewith, George | Bishop, Felicity | Holmes, Michelle | Lewith, George | Yardley, Lucy | Little, Paul | Cooper, Cyrus | Bogani, Patrizia | Maggini, Valentina | Gallo, Eugenia | Miceli, Elisangela | Biffi, Sauro | Mengoni, Alessio | Fani, Renato | Firenzuoli, Fabio | Brands-Guendling, Nadine | Guendling, Peter W. | Bronfort, Gert | Evans, Roni | Haas, Mitch | Leininger, Brent | Schulz, Craig | Bu, Xiangwei | Wang, J. | Fang, T. | Shen, Z. | He, Y. | Zhang, X. | Zhang, Zhengju | Wang, Dali | Meng, Fengxian | Büssing, Arndt | Baumann, Klaus | Frick, Eckhard | Jacobs, Christoph | Büssing, Arndt | Grünther, Ralph-Achim | Lötzke, Désirée | Büssing, Arndt | Jung, Sonny | Lötzke, Désirée | Recchia, Daniela R. | Robens, Sibylle | Ostermann, Thomas | Berger, Bettina | Stankewitz, Josephin | Kröz, Matthias | Jeitler, Mika | Kessler, Christian | Michalsen, Andreas | Cheon, Chunhoo | Jang, Bo H. | Ko, Seong G. | Huang, Ching W. | Sasaki, Yui | Ko, Youme | Cheshire, Anna | Ridge, Damien | Hughes, John | Peters, David | Panagioti, Maria | Simon, Chantal | Lewith, George | Cho, Hyun J. | Han, Dongwoon | Choi, Soo J. | Jung, Young S. | Im, Hyea B | Cooley, Kieran | Tummon-Simmons, Laura | Cotton, Sian | Luberto, Christina M. | Wasson, Rachel | Kraemer, Kristen | Sears, Richard | Hueber, Carly | Derk, Gwendolyn | Lill, JR | An, Ruopeng | Steinberg, Lois | Rodriguez, Lourdes Diaz | la Fuente, Francisca García-de | De la Vega, Miguel | Vargas-Román, Keyla | Fernández-Ruiz, Jonatan | Cantarero-Villanueva, Irene | Rodriguez, Lourdes Diaz | García-De la Fuente, Francisca | Jiménez-Guerrero, Fanny | Vargas-Román, Keyla | Fernández-Ruiz, Jonatan | Galiano-Castillo, Noelia | Diaz-Saez, Gualberto | Torres-Jimenez, José I. | Garcia-Gomez, Olga | Hortal-Muñoz, Luis | Diaz-Diez, Camino | Dicen, Demijon | Diezel, Helene | Adams, Jon | Steel, Amie | Wardle, Jon | Diezel, Helene | Steel, Amie | Frawley, Jane | Wardle, Jon | Broom, Alex | Adams, Jon | Dong, Fei | Yu, He | Liu, Tiegang | Ma, Xueyan | Yan, Liyi | Wan, Yuxiang | Zheng, Zian | Gu, Xiaohong | Dong, Fei | Yu, He | Wu, Liqun | Liu, Tiegang | Ma, Xueyan | Ma, Jiaju | Yan, Liyi | Wan, Yuxiang | Zheng, Zian | Zhen, Jianhua | Gu, Xiaohong | Dubois, Julie | Rodondi, Pierre-Yves | Edelhäuser, Friedrich | Schwartze, Sophia | Trapp, Barbara | Cysarz, Dirk
doi:10.1186/s12906-017-1782-4
PMCID: PMC5498855
5.  World Congress Integrative Medicine & Health 2017: part three 
Ortiz, Miriam | Schnabel, Katharina | Teut, Michael | Rotter, Gabriele | Binting, Sylvia | Cree, Margit | Lotz, Fabian | Suhr, Ralf | Brinkhaus, Benno | Parvizi, Mohammad M. | Handjani, Farhad | Zarshenas, Mohammad M. | Moein, Mahmood R. | Nimrouzi, Majid | Hatam, Gholamreza | Hasanzadeh, Jafar | Hamidizadeh, Nasrin | Parvizi, Mohammad M. | Heydari, Mojtaba | Namazi, Mohammad R. | Parvizi, Zahra | Pasalar, Mehdi | Mosaffa-Jahromi, Maryam | Bagheri-Lankarani, Kamran | Afsharypuor, Suleiman | Tamaddon, Ali M. | Ostovar, Mohadeseh | Peloni, Giuseppe | Bolliger, Ingo | Faria, Rui M. Da Cunha | Quadri, Pierluigi | Sanzeni, Wilma | Zemp, Damiano | Risvoll, Hilde | Giverhaug, Trude | Halvorsen, Kjell H. | Waaseth, Marit | Musial, Frauke | Rossi, Elio | Baccetti, Sonia | Picchi, Marco | Conti, Tommaso | Firenzuoli, Fabio | Guido, Carmelo | Bosco, Filippo | Guido, Carmelo | Rossi, Elio | Panozzo, Marialessandra | Picchi, Marco | Cervino, Chiara | Nurra, Linda | Rossi, Elio | Picchi, Marco | Firenzuoli, Fabio | Traversi, Antonella | Vuono, Katia | Sabatini, Federica | Bellandi, Tommaso | Rutert, Britta | Eggert, Angelika | Seifert, Georg | Stritter, Wiebke | Holmberg, Christine | Längler, Alfred | Salamonsen, Anita | Wiesener, Solveig | Schad, Friedemann | Steele, Megan | Kröz, Matthias | Matthes, Harald | Herbstreit, Cornelia | Thronicke, Anja | Schlingensiepen, Irene | von Schoen-Angerer, Tido | Schneider, Romy | Waeber, Livia | Vagedes, Jan | Kaczala, Gregor | Pharisa, Cosette | Wildhaber, Johannes | Huber, Benedikt | Sidorov, Pavel | Sovershaeva, Evgeniya | Simões-Wüst, Ana P. | Nietlispach, Anna | Mennet, Mónica | Schnelle, Martin | von Mandach, Ursula | Wang, Xia | Woo, Hye L. | Lee, Jin M. | Wu, Yuhao | Cho, Yumin | Yun, Younghee | Kim, Hyunho | Jung, Wonmo | Jang, Bo-Hyung | Ziea, Eric | Hui, Henny | Li, Mia | Tsui, Dora | Lam, Christine | Hsieh, Joyce | Chan, Edith | Balneaves, Lynda | Burnside, Sandra | Doyle, Ethel | Dorazio, Shelley | Chan, Pak K. | Bhagra, Anjali | Chen, Po-Hsu | Chung, Vincent C. H. | Wu, Justin C. Y. | Lin, Zhi X. | Wong, Wendy | Wu, Xin Y. | Ho, Robin S. T. | Wong, Charlene H. L. | Chan, Lily | Ziea, Eric T. C. | Elder, William | Cardarelli, Roberto | Kaspar, Cornelia | Kempenich, Robert | Kopferschmitt, Jacques | Marinko, Zulj | Damir, Sebo | Vcev, Aleksandar | Monezi, Ricardo | Ruggerini, Eny Márcia | Fuchigami, Ivna M. | Mazini, Ana C. Moreno | Monezi, Ricardo | Oliveira, Maria Waldenez | Papuga, Petar | Schloss, Janet | Steel, Amie | Jacobsen, Márcia da Silva | Monezi, Ricardo | Jacobsen, Miranda Rodrigo | Mangini, Maria T. | Trapani, Gianfranco | Di Giampietro, Tiziana | Zanino, Luisella | Ciullo, Luigi | Lanaro, Diego | Cerritelli, Francesco | Macrì, Francesco | Tsai, Andre | Lin, Chin | Wu, Tu-Hsing | D’Alessandro, Eduardo | Watts, Sam | Zhang, Ying | Wu, Xufang | Li, Xun | Fei, Yutong | Liu, Jianping | Zhao, Nanqi | Jia, Liyan | Yan, Xiaoyi | Zhen, Fei | Liu, Zhaolan | Liu, Jianping | Ahn, Jinhyang | Yun, Younghee | AlEidi, Sulaiman | Mohamed, Ashry Gad | Al-Beda, Abdullah M. | Abutalib, Raid A. | Khalil, Mohemmed K. M. | Amri, Hakima | Badekila, Sathyanarayana | Behmanesh, Elham | Mozaffarpour, Seyyedali | Behmanesh, Elham | Mozaffarpour, Seyyedali | Behmanesh, Elham | Shirooye, Pantea | Meybodi, Razie N. | Mokaberinejad, Roshanak | Tansaz, Mojgan | Mozaffarpour, Seyyedali | Chung, Vincent C. H. | Wu, Xin Y. | Wu, Justin C. Y. | Daneshfard, Babak | Hosseinkhani, Ayda | Tafazoli, Vahid | Jaladat, Amir M. | Jaladat, Amir M. | Sadeghi, Hasan | Jia, Liyan | Zhao, Nanqi | Yan, Xiaoyi | Zhou, Li | Zhao, Meng | Li, Weiwei | Liu, Jianping | Liu, Zhaolan | Jia, Liyan | Zhao, Nanqi | Yan, Xiaoyi | Zhou, Li | Zhao, Meng | Li, Weiwei | Liu, Jianping | Liu, Zhaolan | Larsen, Anette L. | Salamonsen, Anita | Kristoffersen, Agnete E. | Hamran, Torunn | Evjen, Bjørg | Stub, Trine | Li, Meiling | Cai, Jianxiong | Lu, Taoying | Yin, Lingjia | Wu, Darong | Wang, Lixin | Liew, Siaw M. | Liu, Tiegang | Bai, Chen | Zheng, Zian | Wan, Yuxiang | Xu, Jingnan | Wang, Xuan | Yu, He | Gu, Xiaohong | Liu, Zhaolan | Yan, Xiaoyi | Jia, Liyan | Zhao, Nanqi | Yang, Guoyan | Liu, Jianping | Mozaffarpour, Seyyedali | Behmanesh, Elham | Nimrouzi, Majid | Tafazoli, Vahid | Daneshfard, Babak | Ostrowski, Deja | Fox, Kealoha | Pasalar, Mehdi | Tabatabei, Fatemeh | Amini, Fatemeh | Sathasivampillai, Saravanan | Rajamanoharan, Pholtan | Munday, Michael | Heinrich, Michael | Scherrer, Yvonne M. | Heinrich, Michael | Szuter, Carolyn | Amini, Fatemeh | Tabatabaei, Fatemeh | Tavakoli, Ali | Tavakoli, Fatemeh | Pasalar, Mehdi | rostami, Mahsa | Torri, Maria C. | Szuter, Carolyn | Walach, Harald | Warner, Faith | Majumdar, Anne | Serasingh, Palitha | Yan, Xiaoyi | Jia, Liyan | Zhao, Nanqi | Liu, Zhaolan | Liu, Jianping | Zhao, Nanqi | Zhen, Fei | Jia, Liyan | Yan, Xiaoyi | Liu, Zhaolan | Liu, Jianping | Abbing, Annemarie | Ponstein, Anne | Baars, Erik | Croke, Sarah | Hanser, Suzanne | Heckel, Viola | Krüerke, Daniel | Simões-Wüst, Ana P. | Weiss, Sebastian | Metzner, Susanne | Lee, Jang W. | Hyun, Min K. | Masetti, Morgana | Oepen, Renate | Gruber, Harald | Heusser, Peter | Pelz, Holger | Perlitz, Volker | Ponstein, Anne | Abbing, Annemarie | Baars, Erik | Robinson, Nicola | Ronan, Patricia | Mian, Awais | Madge, Su | Lorenc, Ava | Agent, Penny | Carr, Siobhan | Ronan, Patricia | Robinson, Nicola | Carr, Siobhan | Mian, Awais | Lorenc, Ava | Agent, Penny | Madge, Su | Winnubst, Monica E. | Monezi, Ricardo | Abolghasemi, Jafar | Heydari, Mojtaba | Baccetti, Sonia | Rossi, Elio | Fedi, Paolo | Di Stefano, Mariella | Belvedere, Katia | Baccetti, Sonia | Rossi, Elio | Firenzuoli, Fabio | Di Stefano, Mariella | Belvedere, Katia | Beaven, Katherine | Rose, Anita | Florschutz, Gerhard | Phil, Nicola Brough | Parsons, Helen | Stewart-Brown, Sarah | Burke, Katherine | Busch, Martine | Heyning, Fenna | Smit, Jan | Jeekel, Hans | de Goeij, Hans | Guido, Paulo Caceres | Barraza, Norma | Balbarrey, Ziomara | Ribas, Alejandra | Jimenez, Beatriz | Iachino, Claudia | Quattrone, Fabiana | Gaioli, Marisa | Dell’Orso, Marta | Villanueva, Silvia | Rocha, Carmen | Macchi, Adriana | Cai, Jianxiong | Chen, Lina | Wu, Darong | Wang, Sicheng | Choi, Eunji | Go, Namgyeong | Lee, Yongho | Dahal, Gokarna | Frauenknecht, Xaver | Gerhardt, Heike | Galanti, Mónica | Cerda, Carmen J. | Galanti, Mónica | Galanti, Mónica | Heckersdorf, Daniela Navarrete | Jorquera, Héctor | Saldivia, María L. Alcázar | Jakubonienė, Daiva | McEwen, Bradley | Melo, Francislete | Fontana, Fernanda Mulinari | Valle, Ana C. Viana | Neres, Maria T. Borges | Mohagheghzadeh, Abolali | Zohalinezhad, Mohammad E. | Njaradi, Olja | Dunjic, Momir | Njaradi, Olja | Dunjic, Momir | Ostrowski, Deja | Fox, Kealoha | Pokladnikova, Jitka | Selke-Krulichova, Iva | Seo, Jinsoon | Jang, Hyunchul | Simões-Wüst, Ana P. | Moltó-Puigmartí, Carolina | van Dongen, Martien | Dagnelie, Pieter | Thijs, Carel | Tihanyi, Eva | Hegyi, Gabriella | Zhang, Ying | Li, Xun | Fei, Yutong | Liu, Jianping | Zhang, Ying | Liu, Jianping | Tong, Xiaolin
doi:10.1186/s12906-017-1784-2
PMCID: PMC5499100
6.  ViscumTT induces apoptosis and alters IAP expression in osteosarcoma in vitro and has synergistic action when combined with different chemotherapeutic drugs 
Background
Osteosarcoma is the most common bone tumor and is associated with a poor prognosis. Conventional therapies, surgery and chemotherapy, are still the standard but soon reach their limits. New therapeutic approaches are therefore needed. Conventional aqueous mistletoe extracts from the European mistletoe (Viscum album L.) are used in complementary cancer treatment. These commercial extracts are water-based and do not include water-insoluble compounds such as triterpenic acids. However, both hydrophilic and hydrophobic triterpenic acids possess anti-cancer properties. In this study, a whole mistletoe extract viscumTT re-created by combining an aqueous extract (viscum) and a triterpene extract (TT) was tested for its anti-cancer potential in osteosarcoma.
Methods
Two osteosarcoma cell lines were treated with three different mistletoe extracts viscum, TT and viscumTT to compare their apoptotic potential. For this purpose, annexin/PI staining and caspase-3, −8 and −9 activity were investigated by flow cytometry. To determine the mechanism of action, alterations in expression of inhibitors of apoptosis (IAPs) were detected by western blot. Apoptosis induction by co-treatment of viscum, TT and viscumTT with doxorubicin, etoposide and ifosfamide was examined by flow cytometry.
Results
In vitro as well as ex vivo, the whole mistletoe extract viscumTT led to strong inhibition of proliferation and synergistic apoptosis induction in osteosarcoma cells. In the investigations of mechanism of action, inhibitors of apoptosis such as XIAP, BIRC5 and CLSPN showed a clear down-regulation after viscumTT treatment. In addition, co-treatment with doxorubicin, etoposide and ifosfamide further enhanced apoptosis induction, also synergistically.
Conclusion
ViscumTT treatment results in synergistic apoptosis induction in osteosarcoma cells in vitro and ex vivo. Additionally, conventional standard chemotherapeutic drugs such as doxorubicin, etoposide and ifosfamide were able to dramatically enhance apoptosis induction. These results promise a high potential of viscumTT as an additional adjuvant therapy approach for osteosarcoma.
Electronic supplementary material
The online version of this article (doi:10.1186/s12906-016-1545-7) contains supplementary material, which is available to authorized users.
doi:10.1186/s12906-016-1545-7
PMCID: PMC5219806  PMID: 28061770
Mistletoe; Viscum album L; Triterpenic acids; Osteosarcoma; Apoptosis; Chemotherapeutic drugs
7.  Multiple Active Compounds from Viscum album L. Synergistically Converge to Promote Apoptosis in Ewing Sarcoma 
PLoS ONE  2016;11(9):e0159749.
Ewing sarcoma is the second most common bone cancer in children and adolescents, with poor prognosis and outcome in ~70% of initial diagnoses and 10–15% of relapses. Hydrophobic triterpene acids and hydrophilic lectins and viscotoxins from European mistletoe (Viscum album L.) demonstrate anticancer properties, but have not yet been investigated for Ewing sarcoma. Commercial Viscum album L. extracts are aqueous, excluding the insoluble triterpenes. We recreated a total mistletoe effect by combining an aqueous extract (viscum) and a triterpene extract (TT) solubilized with cyclodextrins. Ewing sarcoma cells were treated with viscum, TT and viscumTT in vitro, ex vivo and in vivo. In vitro and ex vivo treatment of Ewing sarcoma cells with viscum inhibited proliferation and induced apoptosis in a dose-dependent fashion, while viscumTT combination treatment generated a synergistic effect. Apoptosis occurred via intrinsic and extrinsic apoptotic pathways, evidenced by activation of both CASP8 and CASP9. We show that viscumTT treatment shifts the balance of apoptotic regulatory proteins towards apoptosis, mainly via CLSPN, MCL1, BIRC5 and XIAP downregulation. ViscumTT also demonstrated strong antitumor activity in a cell line- and patient-derived mouse model, and may be considered an adjuvant therapy option for pediatric patients with Ewing sarcoma.
doi:10.1371/journal.pone.0159749
PMCID: PMC5010293  PMID: 27589063
8.  Regional hyperthermia combined with chemotherapy in paediatric, adolescent and young adult patients: current and future perspectives 
Here we evaluate the current status of clinical research on regional hyperthermia (RHT) in combination with chemotherapy or radiation therapy in paediatric oncology.
Data were identified in searches of MEDLINE, Current Contents, PubMed, and references from relevant articles using medical subject headings including hyperthermia, cancer, paediatric oncology, children, radiation therapy and chemotherapy. Currently, only two RHT centres exist in Europe which treat children. Clinical RHT research in paediatric oncology has as yet been limited to children with sarcomas and germ cell tumours that respond poorly to or recur after chemotherapy. RHT is a safe and effective treatment delivering local thermic effects, which may also stimulate immunological processes via heat-shock protein reactions. RHT is used chiefly in children and adolescents with sarcomas or germ cell tumours located in the abdomino-pelvic region, chest wall or extremities to improve operability or render the tumour operable. It could potentially be combined with radiation therapy in a post-operative R1 setting where more radical surgery is not possible or combined with chemotherapy instead of radiation therapy in cases where the necessary radiation dose is impossible to achieve or would have mutilating consequences. RHT might also be an option for chemotherapy intensification in the neoadjuvant first-line treatment setting for children and adolescents, as was recently reflected in the promising long-term outcome data in adults with high-risk soft tissue sarcomas (EORTC 62961/ESHO trial).
The limited data available indicate that combining RHT with chemotherapy is a promising option to treat germ cell tumours and, potentially, sarcomas. RHT may also be beneficial in first-line therapy in children, adolescents and young adults. The research should focus on optimising necessary technical demands and then initiate several clinical trials incorporating RHT into interdisciplinary treatment of children, adolescents and young adults that include translational research components exploring potential immunological mechanisms of action.
doi:10.1186/s13014-016-0639-1
PMCID: PMC4852447  PMID: 27138749
9.  Impact of Mistletoe Triterpene Acids on the Uptake of Mistletoe Lectin by Cultured Tumor Cells 
PLoS ONE  2016;11(4):e0153825.
Complementary treatment possibilities for the therapy of cancer are increasing in demand due to the severe side effects of the standard cytostatics used in the first-line therapy. A common approach as a complementary treatment is the use of aqueous extracts of Viscum album L. (Santalaceace). The therapeutic activity of these extracts is attributed to Mistletoe lectins which are Ribosome-inactivating proteins type II. Besides these main constituents the extract of Viscum album L. comprises also a mixture of lipophilic ingredients like triterpene acids of the oleanane, lupane and ursane type. However, these constituents are not contained in commercially available aqueous extracts due to their high lipophilicity and insolubility in aqueous extraction media. To understand the impact of the extract ingredients in cancer therapy, the intracellular uptake of the mistletoe lectin I (ML) by cultured tumor cells was investigated in relation to the mistletoe triterpene acids, mainly oleanolic acid. Firstly, these hydrophobic triterpene acids were solubilized using cyclodextrins (“TT” extract). Afterwards, the uptake of either single compounds (isolated ML and the aqueous “viscum” extract) or in combination with the TT extract (ML+TT, viscumTT), was analyzed. The uptake of ML was studied inTHP-1-, HL-60-, 143B- and Ewing TC-71-cells and determined after 30, 60 and 120 minutes by an enzyme linked immunosorbent assay which quantifies the A-chain of the hololectin. It could be shown that the intracellular uptake after 120 minutes amounted to 20% in all cell lines after incubation with viscumTT. The studies further revealed that the uptake in THP-1-, HL-60- and Ewing TC-71-cells was independent of the addition of TT extract. Interestingly, the uptake of ML by 143B-cells could only be measured after addition of triterpenes pointing to resistance to mistletoe lectin.
doi:10.1371/journal.pone.0153825
PMCID: PMC4835140  PMID: 27088729
10.  Post-Translational Modification and Secretion of Azelaic Acid Induced 1 (AZI1), a Hybrid Proline-Rich Protein from Arabidopsis 
Arabidopsis EARLI-type hybrid proline-rich proteins (HyPRPs) consist of a putative N-terminal secretion signal, a proline-rich domain (PRD), and a characteristic eight-cysteine-motif (8-CM). They have been implicated in biotic and abiotic stress responses. AZI1 is required for systemic acquired resistance and it has recently been identified as a target of the stress-induced mitogen-activated protein kinase MPK3. AZI1 gel migration properties strongly indicate AZI1 to undergo major post-translational modifications. These occur in a stress-independent manner and are unrelated to phosphorylation by MAPKs. As revealed by transient expression of AZI1 in Nicotiana benthamiana and Tropaeolum majus, the Arabidopsis protein is similarly modified in heterologous plant species. Proline-rich regions, resembling arabinogalactan proteins point to a possible proline hydroxylation and subsequent O-glycosylation of AZI1. Consistently, inhibition of prolyl hydroxylase reduces its apparent protein size. AZI1 secretion was examined using Arabidopsis protoplasts and seedling exudates. Employing Agrobacterium-mediated leaf infiltration of N. benthamiana, we attempted to assess long-distance movement of AZI1. In summary, the data point to AZI1 being a partially secreted protein and a likely new member of the group of hydroxyproline-rich glycoproteins. Its dual location suggests AZI1 to exert both intra- and extracellular functions.
doi:10.3390/ijms17010085
PMCID: PMC4730328  PMID: 26771603
hybrid proline-rich proteins (HyPRPs); glycosylation; AZI1; post-translational modification; arabino galactan proteins (AGPs)
11.  Dissecting Seed Mucilage Adherence Mediated by FEI2 and SOS5 
The plant cell wall is held together by the interactions between four major components: cellulose, pectin, hemicellulose, and proteins. Mucilage is a powerful model system to study the interactions between these components as it is formed of polysaccharides that are deposited in the apoplast of seed coat epidermal cells during seed development. When seeds are hydrated, these polysaccharides expand rapidly out of the apoplastic pocket, and form an adherent halo of mucilage around the seed. In Arabidopsis, mutations in multiple genes have similar loss of mucilage adherence phenotypes including CELLULOSE SYNTHASE 5 (CESA5)/MUCILAGE-MODIFIED 3 (MUM3), MUM5/MUCI21, SALT-OVERLY SENSITIVE 5 (SOS5), and FEI2. Here, we examine the interactions between these factors to better understand how they participate to control mucilage adherence. Double mutant phenotypes indicated that MUM5 and CESA5 function in a common mechanism that adheres pectin to the seed through the biosynthesis of cellulose and xylan, whereas SOS5 and FEI2, encoding a fasciclin-like arabinogalactan protein or a receptor-like kinase, respectively, function through an independent pathway. Cytological analyses of mucilage indicates that heteromannans are associated with cellulose, and not in the pathway involving SOS5 or FEI2. A SOS5 fluorescent protein fusion (SOS5-mCITRINE) was localized throughout the mucilage pocket, consistent with a structural role in pectin adhesion. The relationship between SOS5 and FEI2 mediated mucilage adherence was examined in more detail and while sos5 and fei2 mutants show similar phenotypes, key differences in the macromolecular characteristics and amounts of mucilage polymers were observed. FEI2 thus appears to have additional, as well as overlapping functions, with SOS5. Given that FEI2 is required for SOS5 function, we propose that FEI2 serves to localize SOS5 at the plasma membrane where it establishes interactions with mucilage polysaccharides, notably pectins, required for mucilage adherence prior to SOS5 being released into the apoplast.
doi:10.3389/fpls.2016.01073
PMCID: PMC4965450  PMID: 27524986
Arabidopsis; cell wall; mucilage; cellulose; arabinogalactan protein; receptor-like kinase; polysaccharides; genetics
12.  FASCICLIN LIKE ARABINOGALACTAN PROTEIN 4 and RESPIRATORY BURST OXIDASE HOMOLOG D and F independently modulate abscisic acid signaling 
Plant Signaling & Behavior  2015;10(2):e989064.
We previously suggested that At-FLA4 and ABA signaling act in synergy. Reactive oxygen species generated from the NADPH oxidases At-RBOHD and At-RBOHF play an important role in cell wall integrity control and ABA signaling and here we investigate their role for the At-FLA4 pathway. We find that in the At-fla4 At-rbohD At-rbohF triple mutant the root phenotype of At-fla4 is enhanced. Moreover, the abnormally high level of reactive oxygen species in At-fla4 mutant does not depend on AtRBOHD and -F. Likewise, suppression of the At-fla4 phenotype by ABA does not depend on the 2 oxidases. Consistent with their lack of effect on ROS level in At-fla4, transcript level of AtRBOHD and -F is reduced in the At-fla4 mutant background. Taken together, our findings suggest that neither At-RBOHD nor At-RBOHF is involved in the synergism between ABA and At-FLA4. Consistently, the oxidases and At-FLA4 act independently of each other in ROS control.
doi:10.4161/15592324.2014.989064
PMCID: PMC4622830  PMID: 25826261
ABA; At-FLA4; At-RBOHD; At-rbohF; ROS; qRT-PCR
13.  A Natural Combination Extract of Viscum album L. Containing Both Triterpene Acids and Lectins Is Highly Effective against AML In Vivo 
PLoS ONE  2015;10(8):e0133892.
Aqueous Viscum album L. extracts are widely used in complementary cancer medicine. Hydrophobic triterpene acids also possess anti-cancer properties, but due to their low solubility they do not occur in significant amounts in aqueous extracts. Using cyclodextrins we solubilised mistletoe triterpenes (mainly oleanolic acid) and investigated the effect of a mistletoe whole plant extract on human acute myeloid leukaemia cells in vitro, ex vivo and in vivo. Single Viscum album L. extracts containing only solubilised triterpene acids (TT) or lectins (viscum) inhibited cell proliferation and induced apoptosis in a dose-dependent manner in vitro and ex vivo. The combination of viscum and TT extracts (viscumTT) enhanced the induction of apoptosis synergistically. The experiments demonstrated that all three extracts are able to induce apoptosis via caspase-8 and -9 dependent pathways with down-regulation of members of the inhibitor of apoptosis and Bcl-2 families of proteins. Finally, the acute myeloid leukaemia mouse model experiment confirmed the therapeutic effectiveness of viscumTT-treatment resulting in significant tumour weight reduction, comparable to the effect in cytarabine-treated mice. These results suggest that the combination viscumTT may have a potential therapeutic value for the treatment AML.
doi:10.1371/journal.pone.0133892
PMCID: PMC4526680  PMID: 26244918
14.  Characterization of plants expressing the human β1,4-galactosyltrasferase gene 
Modification of the plant N-glycosylation pathway towards human type structures is an important strategy to implement plants as expression systems for therapeutic proteins. Nevertheless, relatively little is known about the overall impact of non-plant glycosylation enzymes in stable transformed plants. Here, we analyzed transgenic lines (Nicotiana benthamiana and Arabidopsis thaliana) that stably express a modified version of human β1,4-galactosyltransferase (STGalT). While some transgenic plants grew normally, other lines exhibited a severe phenotype associated with stunted growth and developmental retardation. The severity of the phenotype correlated with both increased STGalT mRNA and protein levels but no differences were observed between N-glycosylation profiles of plants with and without the phenotype. In contrast to non-transgenic plants, all STGalT expressing plants synthesized significant amounts of incompletely processed (largely depleted of core fucose) N-glycans with up to 40% terminally galactosylated structures. While transgenic plants showed no differences in nucleotide sugar composition and cell wall monosaccharide content, alterations in the reactivity of cell wall carbohydrate epitopes associated with arabinogalactan-proteins and pectic homogalacturonan were detected in STGalT expressing plants. Notably, plants with phenotypic alterations showed increased levels of hydrogen peroxide, most probably a consequence of hypersensitive reactions. Our data demonstrate that unfavorable phenotypical modifications may occur upon stable in planta expression of non-native glycosyltransferases. Such important issues need to be taken into consideration in respect to stable glycan engineering in plants.
Highlights
•Introduction of β1,4-galactosylation into plants.•Over-expression of human β1,4-galactosyltransferase may cause a phenotype in plants.•Plant proteins are poor substrates for β1,4-galactosylation.•Human antibodies are efficiently β1,4-galactosylated in plants.•Alteration of cell wall composition caused by the overexpression of β1,4-galactosyltransferase.
doi:10.1016/j.plaphy.2015.04.010
PMCID: PMC4451504  PMID: 25900423
β1,4-Galactosylation; Glyco-engineering; Nicotiana benthamiana; Transgenic plants; Developmental phenotype
15.  Heart Rate Variability Reflects the Natural History of Physiological Development in Healthy Children and Is Not Associated with Quality of Life 
PLoS ONE  2014;9(3):e91036.
Background
Quality of life (QoL), being the sum expression of diverse influencing factors, is not easy to determine. A clinically relevant option would be to identify and measure quality of life on the basis of physiological parameters which correlate plausibly and statistically with psychometrically measured QoL. Analysis of heart rate variability (HRV) offers readily measurable physiological parameters which could be of use here. A correlation of HRV with both course of disease and QoL has been reported in patients with chronic illness. Various psychometric instruments have been developed for use in paediatric oncology. The aim of this study was to obtain data on HRV and QoL and their correlations, initially in healthy children.
Methods
Holter ECG and quality of life were examined in 160 children and adolescents (72 male) aged between 8 and 18 years. QoL was determined with the established questionnaire PEDQoL. Standard parameters of HRV from the frequency domain were calculated and correlated with QoL domains using Spearman (nonparametric) correlation analysis.
Results
Minor but significant associations were revealed only with regard to the PEDQoL domain “autonomy” on the one hand and heart rate and HRV (e.g. MRR, MRRn, MRRd, HRV_ULF, SDNN) parameters which evidently reflect distinct physiological functions on the other.
Conclusions
In healthy children and adolescents we have a first indication that there is a correlation between parameters of HRV and QoL. However, to a greater extent, HRV reflects associated physiological processes of the autonomic nervous system. A higher correlation is more likely to be found in chronically ill children.
doi:10.1371/journal.pone.0091036
PMCID: PMC3953202  PMID: 24625571
16.  The Arabidopsis thaliana FASCICLIN LIKE ARABINOGALACTAN PROTEIN 4 gene acts synergistically with abscisic acid signalling to control root growth 
Annals of Botany  2014;114(6):1125-1133.
Background and Aims
The putative FASCICLIN-LIKE ARABINOGALACTAN PROTEIN 4 (At-FLA4) locus of Arabidopsis thaliana has previously been shown to be required for the normal growth of wild-type roots in response to moderately elevated salinity. However, the genetic and physiological pathway that connects At-FLA4 and normal root growth remains to be elucidated.
Methods
The radial swelling phenotype of At-fla4 was modulated with growth regulators and their inhibitors. The relationship of At-FLA4 to abscisic acid (ABA) signalling was analysed by probing marker gene expression and the observation of the At-fla4 phenotype in combination with ABA signalling mutants.
Key Results
Application of ABA suppresses the non-redundant role of At-FLA4 in the salt response. At-FLA4 positively regulates the response to low ABA concentration in roots and is required for the normal expression of ABA- and abiotic stress-induced genes. The At-fla4 phenotype is enhanced in the At-abi4 background, while two genetic suppressors of ABA-induced gene expression are required for salt oversensitivity of At-fla4. Salt oversensitivity in At-fla4 is suppressed by the CYP707A inhibitor abscinazole E2B, and salt oversensitivity in At-fla4 roots is phenocopied by chemical inhibition of ABA biosynthesis.
Conclusions
The predicted lipid-anchored glycoprotein At-FLA4 positively regulates cell wall biosynthesis and root growth by modulating ABA signalling.
doi:10.1093/aob/mcu010
PMCID: PMC4195540  PMID: 24603604
Fasciclin; arabinogalactan protein; root growth; cell wall; abscisic acid; plant cell wall signalling; Arabidopsis thaliana; At-FLA4
17.  Improvement of Circadian Rhythm of Heart Rate Variability by Eurythmy Therapy Training 
Background. Impairment of circadian rhythm is associated with various clinical problems. It not only has a negative impact on quality of life but can also be associated with a significantly poorer prognosis. Eurythmy therapy (EYT) is an anthroposophic movement therapy aimed at reducing fatigue symptoms and stress levels. Objective. This analysis of healthy subjects was conducted to examine whether the improvement in fatigue symptoms was accompanied by improvements in the circadian rhythm of heart rate variability (HRV). Design. Twenty-three women performed 10 hours of EYT over six weeks. Electrocardiograms (ECGs) were recorded before and after the EYT trial. HRV was quantified by parameters of the frequency and time domains and the nonlinear parameters of symbolic dynamics. Results. The day-night contrast with predominance of vagal activity at night becomes more pronounced after the EYT training, and with decreased Ultralow and very low frequencies, the HRV shows evidence of calmer sleep. During the night, the complexity of the HRV is significantly increased indicated by nonlinear parameters. Conclusion. The analysis of the circadian patterns of cardiophysiological parameters before and after EYT shows significant improvements in HRV in terms of greater day-night contrast caused by an increase of vagal activity and calmer and more complex HRV patterns during sleep.
doi:10.1155/2013/564340
PMCID: PMC3603202  PMID: 23533496
18.  Unexpected Course of Nonlinear Cardiac Interbeat Interval Dynamics during Childhood and Adolescence 
PLoS ONE  2011;6(5):e19400.
The fluctuations of the cardiac interbeat series contain rich information because they reflect variations of other functions on different time scales (e.g., respiration or blood pressure control). Nonlinear measures such as complexity and fractal scaling properties derived from 24 h heart rate dynamics of healthy subjects vary from childhood to old age. In this study, the age-related variations during childhood and adolescence were addressed. In particular, the cardiac interbeat interval series was quantified with respect to complexity and fractal scaling properties. The R-R interval series of 409 healthy children and adolescents (age range: 1 to 22 years, 220 females) was analyzed with respect to complexity (Approximate Entropy, ApEn) and fractal scaling properties on three time scales: long-term (slope β of the power spectrum, log power vs. log frequency, in the frequency range 10−4 to 10−2 Hz) intermediate-term (DFA, detrended fluctuation analysis, α2) and short-term (DFA α1). Unexpectedly, during age 7 to 13 years β and ApEn were higher compared to the age <7 years and age >13 years (β: −1.06 vs. −1.21; ApEn: 0.88 vs. 0.74). Hence, the heart rate dynamics were closer to a 1/f power law and most complex between 7 and 13 years. However, DFA α1 and α2 increased with progressing age similar to measures reflecting linear properties. In conclusion, the course of long-term fractal scaling properties and complexity of heart rate dynamics during childhood and adolescence indicates that these measures reflect complex changes possibly linked to hormonal changes during pre-puberty and puberty.
doi:10.1371/journal.pone.0019400
PMCID: PMC3098842  PMID: 21625487
19.  Use of Homeopathy in Pediatric Oncology in Germany 
Homeopathy is a frequently used complementary and alternative medicine (CAM) treatment. We present results comparing responses of homeopathy users (HUs) and users of other forms of CAM (NHUs) in pediatric oncology (PO) in Germany. Differences between these two groups (usage, associated demographic characteristics, previous experience with CAM) are investigated. 186 (45.2%) of the 367 CAM users were exposed to homeopathy. The treatment duration amounted to a median of 601 days for HUs and 282 days for NHUs. Parents with p (127; 76.5%) also used homeopathy for their child's cancer. Nonmedical practitioners played a considerably greater role as source of information than did treating physician. In the majority HUs received their prescriptions from nonmedical practitioners (56%; 29.4% of NHUs). HUs communicate more frequently with their physicians about the CAM-use (77.7% versus 65.2%) and recommend CAM more often than NHUs (94% versus 85.6%). Homeopathy is the most frequently used CAM treatment in PO in Germany. HUs sustain treatment and therapies considerably longer than NHUs. Most families who had used homeopathy before their child was diagnosed with cancer also used homeopathy for the treatment of their child's cancer. Compared to other CAM treatments, patient satisfaction with homeopathy appears to be very high.
doi:10.1155/2011/867151
PMCID: PMC2958565  PMID: 20981319
20.  Intraluminal instillation of urokinase and autologous plasma: a method to unblock occluded central venous ports 
BMC Cancer  2006;6:103.
Background
Therapeutic use and effective function of recombinant urokinase (r-UK) for occluded ports need the presence of plasminogen.
Methods
As a therapeutic proof of principle, we demonstrate that the use of r-UK and autologous plasma effectively reestablishes the function of occluded central venous ports (CVP) resistant to routine management of catheter occlusion. Five patients with occluded ports resistant to the routine management were treated.
Results
All patients were successfully treated with thrombolytic therapy using intraluminal instillation of r-UK and autologous plasma.
Conclusion
Instillation of r-UK and autologous plasma is a safe and effective method for management of CVP occlusion.
doi:10.1186/1471-2407-6-103
PMCID: PMC1501039  PMID: 16635269

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