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6. Abstracts

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Derlon J. M., Petit-taboué M. C., Dauphin F., Courtheoux P., Chapon F., Creissard P., Darcel F., Houtteville J. P., Kaschten, B., Sadzot, B., Stevenaert, A., Tjuvajev, Juri G., Macapinlac, Homer A., Daghighian, Farhad, Ginos, James Z., Finn, Ronald D., Jiaju Zhang, M. S., Beattie, Bradley, Graham, Martin, Larson, Steven M., Blasberg, Ronald G., Levivier, M., Goldman, S., Pirotte, B., Brucher, J. M., Balériaux, D., Luxen, A., Hildebrand, J., Brotchi, J., Go K. G., Kamman R. L., Mooyaart E. L., Heesters M. A. A. M., Sijens, P. E., Oudksrk, M., van Dijk, P., Levendag, P. C., Vecht, Ch. J., Metz, R. J., Kennedy, D. N., Rosen, B. R., Hochberg, F. H., Fishman, A. J., Filipek, P. A., Caviness, V. S., Gross, M. W., Weinzierl, F. X., Trappe, A. E., Goebel, W. E., Frank, A. M., Becker, Georg, Krone, Andreas, Schmidt, Karsten, Hofmann, Erich, Bogdahn, Ulrich, Bencsch, H., Fclber, S., Finkenstedt, G., Kremser, C., Sfockhammer, G., Aichner, F., Bogdahn U., Fröhlich T., Becker G., Krone A., Schlief R., Schürmann J., Jachimczak P., Hofmann E., Roggendorf W., Roosen K., Carapella, C. M., Carpinelli, G., Passalacqua, R., Raus, L., Giannini, M., Mastrostefano, R., Podo, F., Tofani, A., Maslrostefano, R., Mottoles, M., Ferraironi, A., Scelsa, M. G., Oppido, P., Riccio, A., Maini, C. L., Collombier, L., Taillandier, L., Dcbouverie, M., Laurens, M. H., Thouvenot, P., Weber, M., Bertrand, A., Cruickshank G. S., Patterson J., Hadley D., De Witte, Olivier, Hildebrand, Jerzy, Luxen, André, Goldman, Serge, Ernestus, R. -I., Bockhorst, K., Eis, M., Els, T., Hoehn-Berlage, M., Gliese, M., Fründ, R., Geissler, A., Woertgen, C., Holzschuh, M., Goldman, Serge, Levivier, M., Pirotte, B., Brucher, J. M., Luxen, A., Brotchi, J., Hildebrand, J., Hausmann, O., Merlo, A., Jerrnann, E., Uirich, J., Chiquet-Ehrismann, R., Müller, J., Mäcke, H., Gratzl, O., Herholz, K., Ghaemi, M., Würker, M., Pietrzyk, U., Heiss, W. -D., Kotitschke, K., Brandl, M., Tonn, J. C., Haase, A., Bogdahn, U., Kotitschke, K., Muigg, S., Felber, S., Aichner, F., Haase, A., Bogdahn, U., Krone A., Becker G., Woydt M., Roggendorf W., Hofmann E., Bogdahn U., Roosen K., Lanfermann, Heinrich, Heindel, Walter, Kugel, Harald, Erneslus, Ralf -Ingo, Röhn, Gabricle, Lackner, Klaus, Metz, R. J., Kennedy, D. N., Pardo, F. S., Kutke, S., Sorensen, A. G., Hochberg, F. H., Fishman, A. J., Filipek, P. A., Rosen, B. R., Caviness, V. S., Mechtler, L. L., Withiam-Lench, S., Shin, K., Klnkel, W. R., Patel, M., Truax, B., Kinkel, P., Shin, K., Mechtler, L., Ricci M., Pantano P., Maleci A., Pierallini S., Di Stefano D., Bozzao L., Cantore G. P., Röhn, Gabriele, Els, T., Schröder, R., Hoehn-Berlage, M., Ernestus, R. -I., Ruda, R., Mocellini, C., Soffietti, R., Campana, M., Ropolo, R., Riva, A., de Filippi, P. G., Schiffer, D., Salgado D., Rodrigues M., Salgado L., Fonseca A. T., Vieira M. R., Bravo Marques J. M., Satoh, H., Uozumi, T., Kiya, K., Kurisu, K., Arita, K., Sumida, M., Ikawa, F., Tzuk-Shina, Tz., Gomori, J. M., Rubinstein, R., Lossos, A., Siegal, T., Vaalburg, W., Paans, A. M. J., Willemsen, A. T. M., van Waarde, A., Pruim, J., Visser, G. M., Go, K. G., Valentini, S., Ting, Y. L. T., De Rose, R., Chidichimo, G., Corricro, G., van Lcycn-Pilgram, Karin, Erncslus, Ralf -Ingo, Klug, Norfried, van Leyen-Pilgram, K., Ernestus, R. -I., Schröder, R., Klug, N., Woydt M., Krone A., Tonn J. C., Becker G., Neumann U., Roggendorf W., Roosen K., Plate, Karl H., Breier, Georg, Millaucr, Birgit, Weich, Herbert A., Ullrich, Axel, Risau, Werner, Roosen N., Chopra R. K., Mikkelsen T., Rosenblum S. D., Yan P. S., Knight R., Windham J., Rosenblum M. L., Schiffer, D., Attanasio, A., Cavalla, P., Chio, A., Giordana, M. T., Migheli, A., Amberger, V., Hensel, T., Schwab, M. E., Cervoni, Luigi, Celli, Paolo, Tarantino, Roberto, Huettner, C., Tonn, J. C., Berweiler, U., Roggendorf, W., Salmon, I., Rorive, S., Rombaut, K., Pirotte, B., Haot, J., Brotchi, J., Kiss, R., Maugard-Louboutin C., Charrier J., Fayet G., Sagan C., Cuillioere P., Ricolleau G., Martin S., Menegalli-Bogeelli D., Lajat Y., Resche F., Molnàr, Péter, Bárdos, Helga, Ádány, Róza, Rogers, J. P., Pilkington, G. J., Pollo, B., Giaccone, G., Allegranza, A., Bugiani, O., Prim, J., Badia, J., Ribas, E., Coello, F., Shezen, E., Lossos, A., Abramsky, O., Siegal, T., Scerrati M., Roselli R., Iacoangeli M., Pompucci A., Rossi G. F., Deeb, Saleh M. Al., Koreich, Osama, Yaqub, Basim, Moutaery, Khalaf R. Al., Giordana, M. T., Cavalla, P., Chio, A., Marino, S., Vigliani, M. C., Schiffer, D., Deburghgraeve, V., Darcel, F., Gedouin, D., Hassel, M. Ben, Guegan, Y., Jeremic, B., Grujicic, D., Antunovic, V., Matovic, M., Shibamoto, Y., Kallio, Merja, Huhmar, Helena, Kudoh, Ch., Detta, A., Sugiura, K., Hitchcock, E. R., Mastrostefano, R., Di Russo, R., Cipriani§, M., Occhipinti, E. M., Conti, E. M. S., Clowegeser A., Ortler M., Seiwald M., Kostron H., Rajan B., Ross G., Lim C., Ashlcy S., Goode D., Traish D., Brada M., Sanden, G. A. C. vd, Schouten, L. J., Coebergh, J. W. W., Razenberg, P. P. A., Twijnstra, A., Snilders-Keilholz, A., Voormolen, J. H. C., Hermans, J., Leer, J. W. H., Taillandier, L., Baylac, F., Dcbouvcrie, M., Anxionnal, R., Bracard, S., Vignand, J. M., Duprcz, A., Weber, M., Winking, M., Böker, D. K., Simmet, T., Rothbart, David, Strugar, John, Balledux, Jeroen, Criscuolo, Gregory R., Jachimczak, Piotr, Blesch, Armin, Heβdörfer, Birgit, Bogdahn, Ulrich, Ernestus, Ralf -Ingo, Schröder, Roland, Klug, Norfrid, Krouwer, H. G. J., Duinen, S. G. v., Algra, A., Zentner, J., Wolf, H. K., Ostertun, B., Hufnagel, A., Campos, M. G., Solymosi, L., Schramm, J., Newlands, E. S., O'Reilly, S. M., Brampton, M., Soffietti, R., Chio, A., Mocellini, C., Ruda, R., Vigliani, M. C., Schiffer, D., Sciolla, R., Seliak, D., Henriksson, R., Bergenheim, A. T., Björk, P., Gunnarsson, P. -O., Hariz, Ml., Grant, R., Collie, D., Gregor A., Ebmeier K. P., Jarvis G., Lander F., Cull A., Sellar R., Brada, M., Thomas, C., Elyan, S., Hines, F., Ashley, S., Stenning, S., Bernstein J. J., Goldberg W. J., Roelcke U., Von Ammon K., Hausmann O., Radu E. W., Kaech D., Leenders K. L., Fitzek, II, M. M., Aronen J. Efird, Hochberg, F., Gruber, M., Schmidt, E., Rosen, B., Flschman, A., Pardo, P., Afra U. M. U., Sipos, L., Slouik, F., Boiardi A., Salmaggi A., Pozzi A., Farinotti L., Fariselli L., Silvani A., Brandes, A., Scelzi, E., Rigon, A., Zampieri, P., Pignataro, M., Amanzo, P. D'., Amista, P., Rotilio, A., Fiorentino, M. V., Thomas, R., Brazil, L., O'Connor, A. M., Ashley, S., Brada, M., Salvati, Maurizio, Cervoni, Luigi, Puzzilli, Fabrizio, Cervoni, Luigi, Salvati, Maurizio, Raguso, Michele, Cruickshank G. S., Duckworth R., Rumpling R., Rottuci M., Fariselli L., Boiardi A., Broggi G., Plrint, N. G., Sabattini, E., Manetto, V., Gambacorta, H., Poggi, S., Pileri, S., Ferracini, R., Grant, R., Plev D. V., Hopf N. J., Knosp E., Bohl J., Perncczky A., Kiss, R., Salmon, I., Catnby, I., Dewitte, O., Brotchi, J., Pasteels, J. L., Camby, I., Salmon, I., Darro, F., Danguy, A., Brotchi, J., Pasteels, J. L., Kiss, R., Kiu, M. C., Lai, G. M., Yang, T. S., Ng, K. T., Chen, J. S., Chang, C. N., Leung, W. M., Ho, Y. S., Rychter, M. Deblec, Klimek, A., Liberski, P. P., Karpinaka, A., Krauseneck P., Schöffel V., Müller B., Kreth, F. W., Faist, M., Warnke, P. C., Ostertag, C. B., Nielen, K. M. B. v., Visscr, M. C., Lebrun C., Lonjon M., Desjardin T., Michiels J. F., Chanalet Sa. Lagrange J. L., Roche J. L., Chatel M., Mastronardi L., Puzzilli F., Osman Farah J., Lunardi P., Matsutani, M., Ushio, Y., Takakura, K., Menten, Johan, Hamers, Han, Ribot, Jacques, Dom, René, Tcepen, Hans, Müller B., Weidner N., Krauseneck P., Naujocks, G., van Roost, D., Wiestler, O. D., Kuncz, A., Nieder, C., Setzel-Sesterhein, M., Niewald, M., Schnabel, I., O'Neill, K. S., Kitchen, N. D., Wilkins, P. R., Marsh, H. T., Pierce, E., Doshi, R., Deane, R., Previtali, S., Quattrini, A., Nemni, R., Ducati, A., Wrabetz, L., Canal, N., Punt, C. J. A., Stamatakis, L., Giroux, B., Rutten, E., Quigley, Matthew R., Beth Sargent P. A. -C., Flores, Nicholas, Simon, Sheryl, Maroon, Joseph C., Quigley, Matthew R., Beth Sargent P. A. -C., Flores, Nicholas, Maroon, Joseph C., Rocca A. A., Gervasoni C., Castagna A., Picozzi P., Giugni E., Rocca A. A., Tonnarelli G. P., Ducati A., Mangili F., Truci G., Canal N., Giovanelli M., Roelcke U., Von Ammon K., Radu E. W., Leenders K. L., Sachsenheimer, W., Bimmler, T., Seiwald M., Eiter H. Rhomberg W., Ortler M., Obwegesser A., Kostron H., Steilen H., Henn W., Moringlane J. R., Kolles H., Feiden W., Zang K. D., Sleudel W. I., Steinbrecher, Andreas, Schabet, Martin, Heb, Clemens, Bamberg, Michael, Dichgans, Johannes, Stragliotto, G., Delattre, J. Y., Poisson, M., Zampieri, P., Brandes, A., Rigon, A., Tosatto, L., D'Amanzo, P., Menicucci, N., Rotilio, A., Mingrino, S., Steudel, W. I., Feld, R., Henn, W., Zang, K. D., Maire, J. Ph., Caudry, M., Guerin, J., Celerier, D., Salem, N., Demeaux, H., Fahregat, J. F., Kusak, M. E., Bucno, A., Albisua, J., Jerez, P., Sarasa, J. L., Garefa, R., de Campos, J. M., Kusak, M. E., de Campos, J. M., Bueno, A., García-Delgado, R., Sarasa, J. L., García-Sola, R., Lantsov A. A., Shustova T. I., Lcnartz, D., Wellenreuther, R., von Deirnling, A., Köning, W., Menzel, J., Scarpa, S., Manna, A., Reale, M. G., Oppido, P. A., Carapella, C. M., Frati, L., Valery, C. A., Ichen, M., Foncin, J. P., Soubrane, C., Khayat, D., Philippon, J., Vaz, R., Cruz, C., Weis S., Protopapa D., März R., Winkler P. A., Reulen H. J., Bise K., Beuls E., Berg J., Deinsberger, W., Böker, D. K., Samii, M., Caudry, M., Darrouzet, V., Guérin, J., Trouette, R., Causse, N., Bébéar, J. P., Parker, F., Vallee, J. N., Carlier, R., Zerah, M., Lacroix-Jousselin, C., Piepmeier, Joseph M., Kveton, John, Czibulka, Agnes, Tigliev G. S., Chernov M. P., Maslova L. N., Valdueza, José M., Jänisch, Werner, Bock, Alexander, Harms, Lutz, Bessell, E. M., Graus, F., Punt, J., Firth, J., Hope, T., Koriech, Osama, Al Deeb, Saleh, Al Moutaery, Khalaf, Yaqub, B., Silvani A., Salmaggi A., Pozzi A., Franzini A., Boiardi A., Goldbrunner, R., Warmuth-Metz, M., Paulus, W., Tonn, J. -Ch., Roosen, K., Strik I. I., Müller B., Markert C., Pflughaupt K. -W., Krauseneck P., O'Neill, B. P., Dinapoli, R. P., Voges, J., Sturm, V., Deuß, U., Traud, C., Treuer, H., Lehrke, R., Kim, D. G., Müller, R. P., Alexandrov Yu. S., Moutaery, K., Aabed, M., Koreich, O., Ross, G. M., Rajan, B., Traish, D., Ashley, S., Ford, D., Brada, M., Schmeets, I. L. O., Jager, J. J., Pannebakker, M. A. G., de Jong, J. M. A., van Lindert, E., Knosp, E., Kitz, K., Blond, S., Dubois, F., Assaker, R., Baranzelli, M. C., Sleiman, M., Pruvo, J. P., Coche-Dequeant, B., Matsutani M., Takakura K., Sano K., PetriČ-Grabnar, G., Jereb, B., Župančič, N., Koršič, M., Rainov N. G., Burkert W., Ushio, Yukitaka, Kochi, Masato, Itoyama, Youichi, de Campos, J. M., Kusak, M. E., Sarasa, J. L., García, R., Bueno, A., Ferrando, L., Hoang-Xuan, K., Sanson, M., Merel, P., Delattre, J. Y., Poisson, M., Delattre, O., Thomas, G., Hoang-Xuan, K., Delattre, J. Y., Poisson, M., Thomas, G., Haritz, D., Obersen, B., Grochulla, F., Gabel, D., Haselsberger K., Radner H., Pendl G., Brada, M., Laing, R. W., Warrington, A. P., Nowak, P. J. C. M., Kolkman-Deurloo, I. K. K., Visser, A. G., Berge, Hv. d., Niël, C. G. J. H., Levendag, P. C., Bergström P., Hariz M., Löfroth P. -O., Bergenheim T., Henriksson R., Blond, S., Assaker, R., Cortet-rudelli, C., Dewailly, D., Coche-dequeant, B., Castelain, B., Dinapoli, R., Shaw, E., Coffey, R., Earle, J., Foote, R., Schomberg, P., Gorman, D., Girard N., Courel M. N., Delpech B., Haselsberger K., Friehs G. M., Schröttner O., Pendl G., Pötter, R., hawliczek, R., Sperveslage, P., Prott, F. J., Wachter, S., Dieckmann, K., Würker, M., Herholz, K., Pietrzyk, U., Voges, J., Treuer, H., Sturm, V., Bauer, B., Heiss, W. -D., Jund, R., Zimmermann, F., Feldmann, H. J., Gross, M. W., Kneschaurek, P., Molls, M., Lederman, G., Lowry, J., Wertheim, S., Voulsinas, L., Fine, M., Lederman, G., Lowry, J., Wertheim, S., Fine, M., Voutsinas, I., Qian, G., Rashid, H., Lederman, G., Lowry, J., Wertheim, S., Fine, M., Voulsinas, L., Qian, G., Rashid, H., Moutaery, K., Aabed, M., Koreich, O., Scerrati M., Montemaggi P., Iacoangeli M., Pompucci A., Roselli R., Trignani R., Rossi G. F., Shin, K., Mechtler, L., West, C., Grand, W., Shin, K., Sibata, C., West, C., Mechtler, L., Grand, W., Thomas, R., Guerrero, D., James, N., Ashley, S., Gregor, A., Brada, M., Voges, J., Sturm, V., Bramer, R., Pahlke, H., Lehrke, R., Treuer, H., Banik, N., Kim, D. G., Hövels, M., Bernsen H. J. J. A., Rijken P. F. J. W., Van der Sanden B. P. J., Hagemeier N. E. M., Van der Kogel A. J., Koehler P. J., Verbiest H., Jager J., Vecht Ch. J., Ross G. M., McIlwrath A., Brown R., Mottolesb, C., Pierre'Kahn, A., Croux, M., Roche, J. L., Marchai, J., Delhemes, P., Tremoulet, M., Stilhart, B., Chazai, J., Caillaud, P., Ravon, R., Passacha, J., Bouffet, E., Dirven C. M. F., Mooy J. J. A., Molenaar W. M., Lewandowicz, G. M., Grant, N., Harkness, W., Hayward, R., Thomas, D. G. T., Darling, J. L., Delepine, N., Subovici I. I., Cornille B., Markowska S., Alkallaf JC. Desbois, KühI, J., Niethammer, D., Spaar, H. J., Gnekow, A., Havers, W., Berthold, F., Graf, N., Lampert, F., Maass, E., Mertens, R., Schöck, V., Aguzzi, A., Boukhny, A., Smirtukov, S., Prityko, A., Hoiodov, B., Geludkova, O., Nikanorov, A., Levin, P., Rothbart, David, Balledux, Jeroen, Criscuolo, Gregory R., D'haen, B., Van Calenbergh, F., Casaer, P., Dom, R., Menten, J., Goffin, J., Plets, C., Hertel, A., Hernaiz, P., Seipp, C., Siegler, K., Baum, R. P., Maul, F. D., Schwabe, D., Jacobi, G., Kornhuber, B., Hör, G., Menten, J., Casaer, P., Pilkington, G. J., Merzak, A., Rooprai, H. K., Bullock, P., van Domburg P. H. M. F., Wesseling P., Thijssen H. O. M., Wolff, J. E. A., Boos, J., Krähling, K. H., Gressner-Brocks, V., Jürgens, H., Schlegel, J., Scherthan, H., Arens, N., Stumm, Gabi, Kiessling, Marika, Merzak, A., Koochekpour, S., Pilkington, G. J., Reifenberger, G., Reifenberger, J., Liu, L., James, C. D., Wechsler, W., Collins, V. P., Fabel-Schulte, Klaus, Jachimczak, Plotr, Heßdörfer, Birgitt, Baur, Inge, Schlingensiepen, Karl -Hermann, Brysch, Wolgang, Bogdahn, Ulrich, Blesch A., Bosserhoff A. K., Apfel R., Lottspeich F., Jachimczak P., Büttner R., Bogdahn U., Cece, R., Barajon, I., Tazzari, S., Cavaletti, G., Torri-Tarelli, L., Tredici, G., Hecht, B., Turc-Carel, C., Atllas, R., Chatel, M., Gaudray, P., Gioanni, J., Hecht, F., Balledux, Jeroen, Rothbart, David, Criscuolo, Gregory R., de Campos, J. M., Kusak, M. E., Rey, J. A., Bello, M. J., Sarasa, J. L., Dubois, F., Blond, S., Parent, M., Assaker, R., Gosselin, P., Christiaens, J. L., Feld, R., Moringlane, J. R., Steudel, W. I., Schaudies, J. R., Janka M., Tonn J. C., Fischer U., Meese E., Roosen K., Remmelink, M., Salmon, I., Cras, P., Pasteels, J. L., Brotchi, J., Kiss, R., Bensadoun R. J., Frenay M., Formento J. L., Milano G., Lagrange J. L., Grellier P., Lee, J. -Y., Ernestus, R. -I., Riese, H. -H., Cervós-Navarro, J., Reutter, W., Lippitz, B., Scheitinger, C., Scholz, M., Weis, J., Gilsbach, J. M., Füzesi, L., Koochekpour, S., Merzak, A., Pilkington, G. J., Sanson, M., Li, Y. J., Hoang-Xuan, K., Delattre, J. Y., Poisson, M., Hamelin, R., Van de Kelft, Erik, Dams, Erna, Martin, Jean -Jacques, Willems, Patrick, Lehrke R., Voges J., Treuer H., Erdmann J., Müller R. P., Sturm V., Wurm R. E., Warrington A. P., Laing R. W., Sardell S., Hines F., Graham J. D., Brada M., Ushio, Yukitaka, Kuratsu, Jun -ichi, Kochi, Masato, Kitz K., Aichholzer M., Rössler K., Alesch F., Ertl A., Sorensen, P. S., Helweg-Larsen, S., Mourldsen, H., Hansen, H. H., El Sharoum, S. Y., Berfelo, M. W., Theunissen, P. H. M. H., Jager, J. J., de Jong, J. M. A., Fedorcsák, I., Nyáry, I., Osztie, É., Horvath, Á., Kontra, G., Frenay M., Burgoni-chuzel J., Paquis P., Lagrange J. L., Helweg-Larsen, S., Hansen, SW., Sørensen, PS., Salmon, I., Kiss, R., Krauseneck P., Müller B., Morche M., Tonn J. C., Lagerwaard, F. J., Levendag, P. C., Eijkenboom, W. M. H., Schmilz, P. I. M., Lentzsch S., Weber F., Franke J., Dörken B., Lunardi P., Schettini G., Osman Farah J., Qasho R., Mocellini, C., Ruda, R., Soffietti, R., Garabello, D., Sales, S., De Lucchi, R., Vasario, E., Schiffer, D., Muracciole, X., Régis, J., Manera, L., Peragut, J. C., Juin, P., Sedan, R., Nieder, C., Niewald, M., Walter, K., Schnabel, K., Nieder, C., Niewald, N., Nestle, U., Schnabel, K., Berberich, W., Oschmann, P., Theißen R. D., Reuner K. H., Kaps M., Dorndorf W., Martin, K. K., Akinwunmi, J., Rooprai, H. K., Kennedy, A., Linke, A., Ognjenovic, N., Pilkington, G. J., Svadovsky A. I., Peresedov V. V., Bulakov A. A., Butyalko M. Y., Zhirnova I. G., Labunsky D. A., Gnazdizky V. V., Gannushkina I. V., Taphoorn, M. J. B., Potman, R., Barkhof, F., Weerts, J. G., Karim, A. B. M. F., Heimans, J. J., van de Pol, M., van Aalst, V. C., Wilmink, J. T., Twijnstra, A., van der Sande, J. J., Boogerd, W., Kröger, R., Jäger A., Wismeth C., Dekant A., Brysch W., Schlingensiepen K. H., Jachimczak P., Bogdahn U., Pirolte, B., Cool, V., Gérard, C., Levivier, M., Dargent, J. L., Goldman, S., Brotchi, J., Hildebrand, J., Velu, T., Herrlinger, U., Schabet, M., Ohneseit, P., Buchholz, R., Zhu, Jianhong, Reszka, Regina, Weber, Friedrich, Walther, Wolfgang, Zhang, L. I., Brock, Mario, Roosen N., Rock J. P., Zeng H., Feng J., Fenstermacher J. D., Rosenblum M. L., Siegal, T., Gabizon, A., Beljanski M., Crochet S., Bergenheim, A. T., Zackrisson, B., Elfverson, J., Bergström, P., Henriksson, R., Butti, G., Baetta, R., Magrassi, L., De Renzis, M. R., Soma, M. R., Davegna, C., Pezzotta, S., Paoletti, R., Fumagalli, R., Infuso, L., Sankar, A. A., Darling, J. L., Thomas, D. G. T., Defer, G. -L., Brugières, P., Gray, F., Chomienne, C., Poirier, J., Degos, L., Degos, J. D., Colombo, Bruno M., DiDonato, Stefano, Finocchiaro, Gaetano, Hebeda, K. M., Sterenborg, H. J. C. M., Saarnak, A. E., Wolbers, J. G., van Gemert, M. J. C., Kaaijk P., Troost D., Leenstra S., Das P. K., Bosch D. A., Kostron H., Hochleitner B. W., Obwegeser A., Ortler M., Seiwald M., Vooys, W., Krouwer, H. G. J., de Gast, G. C., Marx, J. J. M., Osman Farah J., Lunardi P., Puzzilli F., Menovsky, T., Beek, J. F., Wolbers, J. G., van Gemert, M. J. C., Naujocks, G., Wiestler, O. D., Schirrmacher, V., Schramm, J., Schmitz, A., Eis-Hübinger, A. M., Piepmeier, p. h., Pedersen, Patricia, Greer, Charles, Quigley, Matthew R., Shih, Tommy, Elrifal, Amr, Rothfus, William, Maroon, Joseph C., Rohertson, L., Rampling, R., Whoteley, T. L., Piumb, J. A., Kerr, D. J., Falina, P. A., Crossan, I. M., Roosen N., Rock J. P., Feng J., Zeng H., Ho K. L., Fenstermacher J. D., Rosenblum M. L., Ruchoux, M. M., Vincent, S., Jonca, F., Plouet, J., Lecomte, M., Samid, D., Thibault, A., Ram, Z., Oldfield, E. H., Myers, C. E., Reed, E., Schabet, M., Herrlinger, U., Buchholz, R., Shoshan, Y., Siegal, T., Siegal, T., Shezen, E., Siegal, Tz., Stockhammer, G., Rosenblum, M., Samid, D., Lieberman, F., Terzis, A. J. A., Bjerkvig, R., Laerum, O. D., Arnold, H., Thibault, A., Samid, D., Figg, W. D., Myers, C. E., Reed, E., Thomas, R., Flux, G., Chittenden, S., Doshi, P., Brazil, L., Thomas, D. G. T., Bignor, D., Zalutsky, M., Brada, M., Tjuvajev, Juri, Kaplitt, Michael, Desai, Revathi, Bradley, M. S., Bettie B. S., Gansbacher, Bernd, Blasberg, Ronald, Haugland, H. K., Saraste, J., Rooseni, K., Laerum, O. D., Vincent, A. J. P. E., Avezaat, C. J. J., Bout, A., Noteboom, J. L., Vecht, C. h., Valerio, D., Hoogerbrugge, P. M., Weber, F., Reszka, R., Zhu, J., Walther, W., List, J., Schulz, W., Wolbers, J. G., Sterenborg, I. I. J. C. M., Kamphorst, W., van Gemert, M. J. C., van Alplien, H. A. M., Salander P., Bergenheim T., Henriksson R., Grant, R., Brazil, L., Thomas, R., Guerrero, D., Laing, R., Ashley, S., Brada, M., Schmidt B., Bauer B., Grau G., Bohnstedt, T., Frydrych A., Franz K., Lorenz R., Brandes, A., Amanzo, P. D'., Zampieri, P., Rigon, A., Scelzi, E., Rotilio, A., Berti, F., Paccagnella, A., Fiorentino, M. V., Müller B., Krauseneck P., van Deventer, P. L., Dellemijn, P. L. I., van den Bent, M. J., Vecht, Ch. J., Kansen, P. J., Tredici, G., Petruccioli, N. G., Cavaletti, G., Cavalletti, E., Kiburg, B., Müller, L. J., Moorer-van Delft, C. M., Heimans, J. J., Boer, H. H., Pace A., Bove L., Pietrangeli A., Innocenti P., Aloe A., Nardi M., Jandolo B., Kellie S. J., De Graaf S. S. N., Bloemhof H., Roebuck D., Dalla Pozza L., Uges D. D. R., Johnston I., Besser M., Chaseling R. A., Koeppen, S., Gründemann, S., Lossos, A., Siegal, T., Nitschke M., Vieregge P., Reusche E., Rob P., Kömpf D., Postma, T. J., Vermorken, J. B., Heimans, J. J., Rampling R. P., Dunlop D. J., Steward M. S., Campbell S. M., Roy S., Hilkens, P. H. E., Verweij, J., van Putten, W. L. J., Vecht, Ch. J., van den Bent, M. J., Hilkens, P. H. E., Moll, J. W. B., van der Burg, M. E. L., Planting, A. S. T., van Putten, W. L. J., Vecht, Ch. J., van den Bent, M. J., Wondrusch E., Zifko U., Drlicek M., Liszka U., Grisold W., Zifko U., Fazeny B., Dittrich Ch., Wondrusch E., Grisold W., Verschuuren, Jan J., Meneses, Patricio I., Rosenfeld, Myrna R., Kaplitt, Michael G., Posner, Jerome B., Dalmau, Josep, Sillevis Smitt P. A. E., Manley G., Posner J. B., Cavaletti, G., Bogliun, G., Margorati, L., Bianchi, G., Drlicek, M., Liska, U., Casati, B., Kolig, C., Grisold, H., Graus, F., Reñe, R., Uchuya, M., Valldeoriola, F., Delattre, J. Y., Benedetti de Cosentiro C., Ortale D., Martinez R., Lambre J., Cagnolati S., Vinai C., Salmaggi A., Nemni R., Silvani A., Forno M. G., Luksch R., Confalonieri P., Boiardi A., Nitschke M., Scholz J., Vieregge P., Kömpf D., Hochberg F. H., Pfeiffer, G., Netzer, J., Hansen, Ch., Eggers, Ch., Hagel Ch., Kunze, K., Verschuuren, Jan J., Rosenblum, Marc K., Lieberman, Frank S., Posner, Jerome B., and Dalmau, Josep

Published
1994
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10. Oberschenkelbrüche (31:33) Operative Konzepte — Methoden — Implantatwahl

Author

Scherbel, U., primary, Lefering, R., additional, Troidl, H., additional, Tiling, Th., additional, Euler, E., additional, Huber, St., additional, Heining, S., additional, Schweiberer, L., additional, Kecskés, S., additional, Thümmler, J., additional, Yasar, H. I., additional, Friedl, W., additional, Herrmann, H., additional, Dorow, C., additional, Markgraf, E., additional, Bonnaire, F., additional, Hönninger, A., additional, Kuner, E. H., additional, Einert, A., additional, Moser, E., additional, Frenyo, S., additional, Manninger, J., additional, Kazár, G., additional, Cserháti, P., additional, Lowatscheff, Th., additional, Verheyden, P., additional, Beck, J., additional, Weise, K., additional, Sandner, K., additional, Mayer, E., additional, Voggenreiter, G., additional, Assenmacher, St., additional, Klaes, W., additional, Schmit-Neuerburg, K. P., additional, Degreif, J., additional, Rudig, L., additional, Runkel, M., additional, Rommens, P. M., additional, Volkmann, R., additional, Eingartner, Ch., additional, Pütz, M., additional, Weller, S., additional, Prinz, S., additional, Letsch, R., additional, Büscher, D., additional, Müller, K.-H., additional, Kempf, I., additional, Taglang, G., additional, Favreul, E., additional, Grosse, A., additional, Holmenschlager, F., additional, Schilling, Th., additional, Redlich, U., additional, Winkler, St., additional, Schroeder, L., additional, Schulz, R., additional, Elenz, St., additional, Hoffmann, R., additional, Südkamp, P., additional, Tralles, D., additional, Schwarz, E., additional, Paraskevas, S., additional, Louverdis, D., additional, Kontos, P., additional, Strouboulas, G., additional, Krettek, Ch., additional, Schandelmaier, P., additional, Bertram, R., additional, Tscherne, H., additional, Köck, E., additional, Ketterl, R., additional, Dávid, A., additional, Hüfner, T., additional, Richter, J., additional, Ullrich, P., additional, Walther, K., additional, Gellner, H., additional, Wessel, L., additional, Seyfriedt, C.-S., additional, Holland-Cunz, St., additional, Sommer, A., additional, Klein, W., additional, Rieger, H., additional, Neuman, H.-S., additional, Fühner, J., additional, Obertacke, U., additional, Neudeck, F., additional, Olivier, L. C., additional, Schmit-Neuerburg, K.-P., additional, Abdussalam, K., additional, Schlickewei, W., additional, Kuner, E., additional, Braun, W., additional, Markmiller, M., additional, Rüter, A., additional, Heini, P., additional, Höntzsch, D., additional, Kundel, K., additional, Haas, N., additional, Schwab, E., additional, Bretschneider, C., additional, Wenda, K., additional, Könemann, B., additional, Rudolf, J., additional, Leitner, A., additional, Blome, G., additional, Köstler, W., additional, Schmidtmann, U., additional, Knopp, W., additional, Stürmer, K. M., additional, Aufmkolk, M., additional, Mai, P., additional, Kotter, A., additional, von Salis-Soglio, U., additional, Naumann, St., additional, Sander, K., additional, Hochstein, P., additional, Pfrengle, St., additional, Winkler, H., additional, Wentzensen, A., additional, Marzi, I., additional, Weber, St., additional, Fries, W., additional, Mutschler, W., additional, Kolbeck, St., additional, Schütz, M., additional, Südkamp, N., additional, Sander, D., additional, Breyer, H.-G., additional, Teiser, R., additional, Laudy, F., additional, Beisse, R., additional, Gonschorek, O., additional, Schupfner, B., additional, Bühren, V., additional, Pommer, A., additional, Pape, D., additional, Muhr, G., additional, Kettrukat, M., additional, Pröbstel, M., additional, Börner, M., additional, Holbein, O., additional, Bauer, G., additional, Kinzl, L., additional, Feil, R., additional, Josten, Ch., additional, Ekkernkamp, A., additional, Gössung, Th., additional, Wagner, R., additional, Weckbach, A., additional, Mella, C., additional, Eggers, Ch., additional, Lungershausen, W., additional, Schumann, M., additional, Ostermann, P., additional, Hahn, M. P., additional, Janzing, H. M. J., additional, Stockman, B., additional, Van Damme, G., additional, Broos, P., additional, Laun, R. A., additional, Ostermann, P. A. W., additional, Menth-Chiari, W. A., additional, Wozasek, G. E., additional, Vécsei, V., additional, Vichard, Ph., additional, Garbuio, P., additional, Elias, B. E., additional, and Gagneux, E., additional

Published
1996
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29. Substanzen

Author

Martinius, J., primary, Nissen, G., additional, and Eggers, Ch., additional

Published
1984
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42. Kognitive Funktionsstörungen bei Kindern und Jugendlichen mit akuten Psychosen und solchen mit Schizophrenierisiko

Author

Bunk, D. and Eggers, Ch.

Subjects
Cognitive Impairment, Psychose Schizoaffektive, Perceptual Style, Susceptibility (Disorders), Kind, Anfälligkeit (Krankheiten), Childhood Psychosis, Kognitive Störung, Wahrnehmungsstil, Perceptual Disturbances, Kindheitspsychosen, Cognitive Ability, Psychose, Imagination, Kognitive Fähigkeiten, Kognitive Beeinträchtigung, Wahrnehmungsstörung
Abstract

Die Arbeit geht aus von der ätiologischen Bedeutung perzeptiv-kognitiver Dysfunktionen für psychotische Erkrankungen des Kindes- und Jugendalters. Es wird der Frage nachgegangen, ob sich drei verschiedene psychiatrische Patientengruppen hinsichtlich der allgemeinen Intelligenz, der visuellen Figur-Hintergrunddifferenzierung und anderer cerebraler Funktionsstörungen unterscheiden. Die abhängigen Variablen wurden mit herkömmlichen Testverfahren gemessen (Wechsler-IQ, Embedded-Figures-Test, Testbatterie kognitiver Operationen, Gottinger Formenreproduktionstest). Die Versuchspersonen (Vpn) waren 9-20 Jahre alt. 4 waren akut psychotisch, 4 waren high-risk-Kinder (schizophrene Mutter), 14 zeigten neurotische Störungen (Kontrollgruppe). Die quantitative und qualitative Analyse der Untersuchungsergebnisse zeigt, daß sich psychotische und high-risk-Kinder in ihrem visuellen Wahrnehmungsstil und den Intelligenztestleistungen von der Kontrollgruppe (neurotische Patienten) unterscheiden. Neben vermehrten Anzeichen leichter cerebraler Dysfunktionen fand sich bei ihnen ein höheres Potential perzeptiv-kognitiver Funktionsstörungen. Ihr Test-Antwortverhalten wird in Begriffen einer Informationsverarbeitungs-Theorie diskutiert und mit Annahmen über ein gestörtes Zusammenspiel cerebraler Subsysteme in Verbindung gebracht. Daraus werden Hypothesen über möglicherweise spezifische Dysregulationen des Problemlöseprozesses abgeleitet. Ausgehend von der Hypothese eines Zusammenhangs zwischen der Lebhaftigkeit des Phantasie- und Assoziationsverhaltens und einer Prädisposition für psychotische Störungen, untersuchten wir die Gesamtstichprobe mit einer durch uns übertragenen und für Kinder adaptierten Form des QMI (Questionnaire upon mental imagery, Sheehan 1967). Hier fanden sich keine systematischen Gruppendifferenzen. Korrelative Zusammenhänge zwischen QMI-Werten, den Phantasieeinschätzungen unabhängiger Rater und kognitiver Variablen wurden nicht beobachtet.

Published
1987

43. Antibodies to myelin oligodendrocyte glycoprotein in HIV-1 associated neurocognitive disorder: a cross-sectional cohort study

Author

Berger Thomas, Morandell Maria, Reindl Markus, Kuenz Bettina, Lackner Peter, Schmutzhard Erich, and Eggers Christian

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Neuroinflammation and demyelination have been suggested as mechanisms causing HIV-1 associated neurocognitive disorder (HAND). This cross-sectional cohort study explores the potential role of antibodies to myelin oligodendrocyte glycoprotein (MOG), a putative autoantigen in multiple sclerosis, in the pathogenesis of HAND. Methods IgG antibodies against MOG were measured by ELISA in sera and cerebrospinal fluid (CSF) of 65 HIV-positive patients with HAND (n = 14), cerebral opportunistic infections (HIVOI, n = 25), primary HIV infection (HIVM, n = 5) and asymptomatic patients (HIVasy, n = 21). As control group HIV-negative patients with bacterial or viral CNS infections (OIND, n = 18) and other neurological diseases (OND, n = 22) were included. In a subset of HAND patients MOG antibodies were determined before and during antiviral therapy. Results In serum, significantly higher MOG antibody titers were observed in HAND compared to OND patients. In CSF, significantly higher antibody titers were observed in HAND and HIVOI patients compared to HIVasy and OND patients and in OIND compared to OND patients. CSF anti-MOG antibodies showed a high sensitivity and specificity (85.7% and 76.2%) for discriminating patients with active HAND from asymptomatic HIV patients. MOG immunopositive HAND patients performed significantly worse on the HIV dementia scale and showed higher viral load in CSF. In longitudinally studied HAND patients, sustained antibody response was noted despite successful clearance of viral RNA. Conclusions Persistence of MOG antibodies despite viral clearance in a high percentage of HAND patients suggests ongoing neuroinflammation, possibly preventing recovery from HAND.

Published
2010
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44. Phage-Mediated Genetic Manipulation of the Lyme Disease Spirochete Borrelia burgdorferi.

Author

Eggers CH

Subjects
Humans, Genetic Vectors genetics, DNA, Anti-Bacterial Agents pharmacology, Borrelia burgdorferi genetics, Bacteriophages genetics, Lyme Disease diagnosis
Abstract

Introducing foreign DNA into the spirochete Borrelia burgdorferi has been almost exclusively accomplished by transformation using electroporation. This process has notably lower efficiencies in the Lyme disease spirochete relative to other, better-characterized Gram-negative bacteria. The rate of success of transformation is highly dependent upon having concentrated amounts of high-quality DNA from specific backgrounds and is subject to significant strain-to-strain variability. Alternative means for introducing foreign DNA (i.e., shuttle vectors, fluorescent reporters, and antibiotic-resistance markers) into B. burgdorferi could be an important addition to the armamentarium of useful tools for the genetic manipulation of the Lyme disease spirochete. Bacteriophage have been well-recognized as natural mechanisms for the movement of DNA among bacteria in a process called transduction. In this study, a method has been developed for using the ubiquitous borrelial phage φBB-1 to transduce DNA between B. burgdorferi cells of both the same and different genetic backgrounds. The transduced DNA includes both borrelial DNA and heterologous DNA in the form of small shuttle vectors. This demonstration suggests a potential use of phage-mediated transduction as a complement to electroporation for the genetic manipulation of the Lyme disease spirochete. This report describes methods for the induction and purification of phage φBB-1 from B. burgdorferi, the use of this phage in transduction assays, and the selection and screening of potential transductants.

Published
2022
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45. Multipartite Genome of Lyme Disease Borrelia : Structure, Variation and Prophages.

Author

Schwartz I, Margos G, Casjens SR, Qiu WG, and Eggers CH

Subjects
Borrelia classification, Borrelia virology, Disease Susceptibility, Gene Expression Regulation, Bacterial, Host-Pathogen Interactions, Humans, Lyme Disease epidemiology, Lyme Disease transmission, Molecular Typing, Plasmids genetics, Prophages genetics, Whole Genome Sequencing, Borrelia genetics, Genome, Bacterial, Genomics methods, Lyme Disease microbiology
Abstract

All members of the Borrelia genus that have been examined harbour a linear chromosome that is about 900 kbp in length, as well as a plethora of both linear and circular plasmids in the 5-220 kbp size range. Genome sequences for 27 Lyme disease Borrelia isolates have been determined since the elucidation of the B. burgdorferi B31 genome sequence in 1997. The chromosomes, which carry the vast majority of the housekeeping genes, appear to be very constant in gene content and organization across all Lyme disease Borrelia species. The content of the plasmids, which carry most of the genes that encode the differentially expressed surface proteins that interact with the spirochete's arthropod and vertebrate hosts, is much more variable. Lyme disease Borrelia isolates carry between 7-21 different plasmids, ranging in size from 5-84 kbp. All strains analyzed to date harbor three plasmids, cp26, lp54 and lp17. The plasmids are unusual, as compared to most bacterial plasmids, in that they contain many paralogous sequences, a large number of pseudogenes, and, in some cases, essential genes. In addition, a number of the plasmids have features indicating that they are prophages. Numerous methods have been developed for Lyme disease Borrelia strain typing. These have proven valuable for clinical and epidemiological studies, as well as phylogenomic and population genetic analyses. Increasingly, these approaches have been displaced by whole genome sequencing techniques. Some correlations between genome content and pathogenicity have been deduced, and comparative whole genome analyses promise future progress in this arena.

Published
2021
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46. Phage-mediated horizontal gene transfer of both prophage and heterologous DNA by ϕBB-1, a bacteriophage of Borrelia burgdorferi.

Author

Eggers CH, Gray CM, Preisig AM, Glenn DM, Pereira J, Ayers RW, Alshahrani M, Acabbo C, Becker MR, Bruenn KN, Cheung T, Jendras TM, Shepley AB, and Moeller JT

Subjects
Anti-Bacterial Agents pharmacology, Bacteriophages drug effects, Borrelia burgdorferi drug effects, DNA, Bacterial, Ethanol pharmacology, Humans, Lyme Disease microbiology, Microbial Sensitivity Tests, Bacteriophages physiology, Borrelia burgdorferi genetics, Borrelia burgdorferi virology, DNA, Gene Transfer, Horizontal
Abstract

Horizontal gene transfer (HGT) in Borrelia burgdorferi, the Lyme disease agent, is likely mediated by bacteriophage. Studies of the B. burgdorferi phage, ϕBB-1 and its role in HGT have been hindered by the lack of an assay for readily characterizing phage-mediated DNA movement (transduction). Here we describe an in vitro assay in which a clone of B. burgdorferi strain CA-11.2A encoding kanamycin resistance on a ϕBB-1 prophage is co-cultured with different clones encoding gentamicin resistance on a shuttle vector; transduction is monitored by enumerating colonies selected in the presence of both kanamycin and gentamicin. When both clones used in the assay were derived from CA-11.2A, the frequency of transduction was 1.23 × 10 -6 transductants per cell, and could be increased 5-fold by exposing the phage-producing strain to 5% ethanol. Transduction was also demonstrated between the CA-11.2A clone and clones of both high-passage B. burgdorferi strain B31 and low-passage, virulent B. burgdorferi strain 297, although with lower transduction frequencies. The transductant in the 297 background produced phage capable of transducing another B. burgdorferi clone: this is the first experimental demonstration of transduction from a clone of a virulent strain. In addition to prophage DNA, small Escherichia coli-derived shuttle vectors were also transduced between co-cultured B. burgdorferi strains, suggesting both a broad role for the phage in the HGT of heterologous DNA and a potential use of the phage as a molecular tool. These results enhance our understanding of phage-mediated transduction as a mechanism of HGT in the Lyme disease spirochetes. Furthermore, the reagents and techniques developed herein will facilitate future studies of phage-mediated HGT, especially within the tick vector and vertebrate host., (© FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2016
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47. Oxford-style debates in a microbiology course for majors: a method for delivering content and engaging critical thinking skills.

Author

Boucaud DW, Nabel M, and Eggers CH

Abstract

Developing scientific expertise in the classroom involves promoting higher-order cognitive skills as well as content mastery. Effective use of constructivism can facilitate these outcomes. However this is often difficult to accomplish when delivery of content is paramount. Utilizing many of the tenets of constructivist pedagogy, we have designed an Oxford-style debate assignment to be used in an introductory microbiology course. Two teams of students were assigned a debatable topic within microbiology. Over a five-week period students completed an informative web page consisting of three parts: background on the topic, data-based positions for each side of the argument, and a data-based persuasive argument to support their assigned position. This was followed by an in-class presentation and debate. Analysis of student performance on knowledge-based questions shows that students retain debate-derived content acquired primarily outside of lectures significantly better than content delivered during a normal lecture. Importantly, students who performed poorly on the lecture-derived questions did as well on debate-derived questions as other students. Students also performed well on questions requiring higher-order cognitive skills and in synthesizing data-driven arguments in support of a position during the debate. Student perceptions of their knowledge-base in areas covered by the debate and their skills in using scientific databases and analyzing primary literature showed a significant increase in pre- and postassignment comparisons. Our data demonstrate that an Oxford-style debate can be used effectively to deliver relevant content, increase higher-order cognitive skills, and increase self-efficacy in science-specific skills, all contributing to developing expertise in the field.

Published
2013
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48. Borrelia burgdorferi requires the alternative sigma factor RpoS for dissemination within the vector during tick-to-mammal transmission.

Author

Dunham-Ems SM, Caimano MJ, Eggers CH, and Radolf JD

Subjects
Animals, Bacterial Proteins metabolism, Borrelia burgdorferi metabolism, Disease Vectors, Ixodes, Microscopy, Confocal, Microscopy, Electron, Transmission, Reverse Transcriptase Polymerase Chain Reaction, Sigma Factor metabolism, Bacterial Proteins genetics, Borrelia burgdorferi genetics, Lyme Disease genetics, Lyme Disease transmission, Sigma Factor genetics
Abstract

While the roles of rpoS(Bb) and RpoS-dependent genes have been studied extensively within the mammal, the contribution of the RpoS regulon to the tick-phase of the Borrelia burgdorferi enzootic cycle has not been examined. Herein, we demonstrate that RpoS-dependent gene expression is prerequisite for the transmission of spirochetes by feeding nymphs. RpoS-deficient organisms are confined to the midgut lumen where they transform into an unusual morphotype (round bodies) during the later stages of the blood meal. We show that round body formation is rapidly reversible, and in vitro appears to be attributable, in part, to reduced levels of Coenzyme A disulfide reductase, which among other functions, provides NAD+ for glycolysis. Our data suggest that spirochetes default to an RpoS-independent program for round body formation upon sensing that the energetics for transmission are unfavorable.

Published
2012
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49. Genetics of Borrelia burgdorferi.

Author

Brisson D, Drecktrah D, Eggers CH, and Samuels DS

Subjects
Alleles, Animals, Antigenic Variation, Antigens, Bacterial genetics, Antigens, Bacterial immunology, Antigens, Bacterial metabolism, Bacterial Outer Membrane Proteins genetics, Bacterial Outer Membrane Proteins metabolism, Bacterial Proteins genetics, Bacterial Proteins immunology, Bacterial Proteins metabolism, Bacteriophages genetics, Bacteriophages metabolism, Bacteriophages pathogenicity, Borrelia burgdorferi immunology, Borrelia burgdorferi pathogenicity, Borrelia burgdorferi virology, DNA, Bacterial metabolism, Electroporation, Evolution, Molecular, Genetic Variation, Humans, Ixodes microbiology, Linkage Disequilibrium, Lipoproteins genetics, Lipoproteins immunology, Lipoproteins metabolism, Lyme Disease microbiology, Plasmids genetics, Plasmids metabolism, Prophages genetics, Recombination, Genetic, Selection, Genetic, Species Specificity, Transduction, Genetic, Transformation, Genetic, Borrelia burgdorferi genetics, DNA, Bacterial genetics, Genes, Bacterial, Prophages metabolism
Abstract

The spirochetes in the Borrelia burgdorferi sensu lato genospecies group cycle in nature between tick vectors and vertebrate hosts. The current assemblage of B. burgdorferi sensu lato, of which three species cause Lyme disease in humans, originated from a rapid species radiation that occurred near the origin of the clade. All of these species share a unique genome structure that is highly segmented and predominantly composed of linear replicons. One of the circular plasmids is a prophage that exists as several isoforms in each cell and can be transduced to other cells, likely contributing to an otherwise relatively anemic level of horizontal gene transfer, which nevertheless appears to be adequate to permit strong natural selection and adaptation in populations of B. burgdorferi. Although the molecular genetic toolbox is meager, several antibiotic-resistant mutants have been isolated, and the resistance alleles, as well as some exogenous genes, have been fashioned into markers to dissect gene function. Genetic studies have probed the role of the outer membrane lipoprotein OspC, which is maintained in nature by multiple niche polymorphisms and negative frequency-dependent selection. One of the most intriguing genetic systems in B. burgdorferi is vls recombination, which generates antigenic variation during infection of mammalian hosts.

Published
2012
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50. The transition from closed to open conformation of Treponema pallidum outer membrane-associated lipoprotein TP0453 involves membrane sensing and integration by two amphipathic helices.

Author

Luthra A, Zhu G, Desrosiers DC, Eggers CH, Mulay V, Anand A, McArthur FA, Romano FB, Caimano MJ, Heuck AP, Malkowski MG, and Radolf JD

Subjects
Animals, Bacterial Outer Membrane Proteins genetics, Bacterial Outer Membrane Proteins metabolism, Cell Membrane genetics, Cell Membrane metabolism, Crystallography, X-Ray, Hydrophobic and Hydrophilic Interactions, Liposomes chemistry, Liposomes metabolism, Protein Structure, Quaternary, Protein Structure, Secondary, Rabbits, Syphilis genetics, Syphilis metabolism, Treponema pallidum genetics, Treponema pallidum metabolism, Bacterial Outer Membrane Proteins chemistry, Cell Membrane chemistry, Cell Membrane Permeability, Protein Multimerization, Treponema pallidum chemistry
Abstract

The molecular architecture and composition of the outer membrane (OM) of Treponema pallidum (Tp), the noncultivable agent of venereal syphilis, differ considerably from those of typical Gram-negative bacteria. Several years ago we described TP0453, the only lipoprotein associated with the inner leaflet of the Tp OM. Whereas polypeptides of other treponemal lipoproteins are hydrophilic, non-lipidated TP0453 can integrate into membranes, a property attributed to its multiple amphipathic helices (AHs). Furthermore, membrane integration of the TP0453 polypeptide was found to increase membrane permeability, suggesting the molecule functions in a porin-like manner. To better understand the mechanism of membrane integration of TP0453 and its physiological role in Tp OM biogenesis, we solved its crystal structure and used mutagenesis to identify membrane insertion elements. The crystal structure of TP0453 consists of an α/β/α-fold and includes five stably folded AHs. In high concentrations of detergent, TP0453 transitions from a closed to open conformation by lateral movement of two groups of AHs, exposing a large hydrophobic cavity. Triton X-114 phase partitioning, liposome floatation assay, and bis-1-anilino-8-naphthalenesulfonate binding revealed that two adjacent AHs are critical for membrane sensing/integration. Using terbium-dipicolinic acid complex-loaded large unilamellar vesicles, we found that TP0453 increased efflux of fluorophore only at acidic pH. Gel filtration and cross-linking experiments demonstrated that one AH critical for membrane sensing/insertion also forms a dimeric interface. Based on structural dynamics and comparison with Mycobacterium tuberculosis lipoproteins LprG and LppX, we propose that TP0453 functions as a carrier of lipids, glycolipids, and/or derivatives during OM biogenesis.

Published
2011
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