Author: "Barth, R." / Publication Year Range: Last 3 years - Searchworks@Jio Institute Digital Library Search Results

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44 results on '"Barth, R."'

1. Rare HCV subtypes and retreatment outcomes in a cohort of European DAA-experienced patients

Author: Antoni, C., Teufel, A., Vogelmann, R., Ebert, M., Balavoine, J., Giostra, E., Berning, M., Hampe, J., Boettler, T., Neumann-Haefelin, C., Thimme, R., De Gottardi, A., Rauch, A., Semmo, N., Ellenrieder, V., Gress, M., Herrmann, A., Stallmach, A., Hoffmann, D., Protzer, U., Kodal, A., Löbermann, M., Götze, T., Keitel-Anselmino, V., Lange, C.M., Zachoval, R., Mayerle, J., Maieron, A., Michl, P., Merle, U., Moradpour, D., Chave, J.-P., Muche, M., Epple, H.-J., Müller-Schilling, M., Kocheise, F., Müller, T., Tacke, F., Roeb, E., Rissland, J., Krawczyk, M., Schulze, P., Semela, D., Spengler, U., Rockstroh, J., Strassburg, C.P., Siebler, J., Schulze zur Wiesch, J., Piecha, F., von Felden, J., Jordan, S., Lohse, A., Sprinzl, M., Galle, P., Stauber, R., Strey, B., Steckstor, W., Schmiegel, W., Brockmeyer, N.H., Canbay, A., Trautwein, C., Uschner, F., Trebicka, J., Weber, T., Wedemeyer, H., Cornberg, M., Manns, M., Wietzke-Braun, P., Günther, R., Willuweit, K., Hilgard, G., Schmidt, H., Zizer, E., Backhus, J., Seufferlein, T., Al-Taie, O., Angeli, W., Beckebaum, S., Erhardt, A., Garrido-Lüneburg, A., Gattringer, H., Genné, D., Gschwantler, M., Gundling, F., Hametner, S., Schöfl, R., Haag, S., Heinzow, H., Heyer, T., Hirschi, C., Jussios, A., Kanzler, S., Kordecki, N., Kraus, M., Kullig, U., Wollschläger, S., Magenta, L., Beretta-Piccoli, B. Terziroli, Menges, M., Mohr, L., Muehlenberg, K., Niederau, C., Paulweber, B., Petrides, A., Pinkernell, M., Piso, R., Rambach, W., Reinhardt, L., Reiser, M., Riecken, B., Rieke, A., Roth, J., Schelling, M., Schlee, P., Schneider, A., Scholz, D., Schott, E., Schuchmann, M., Schulten-Baumer, U., Seelhoff, A., Stich, A., Stickel, F., Ungemach, J., Walter, E., Weber, A., Wege, H., Winzer, T., Abels, W., Adler, M., Audebert, F., Baermann, C., Bästlein, E., Barth, R., Barthel, K., Becker, W., Behrends, J., Benninger, J., Berger, F., Berzow, D., Beyer, T., Bierbaum, M., Blaukat, O., Bodtländer, A., Böhm, G., Börner, N., Bohr, U., Bokemeyer, B., Bruch, H.R., Bucholz, D., Buggisch, P., Matschenz, K., Petersen, J., Burkhard, O., Busch, N., Chirca, C., Delker, R., Diedrich, J., Frank, M., Diehl, M., Tal, A.O., Schneider, M., Dienethal, A., Dietel, P., Dikopoulos, N., Dreck, M., Dreher, F., Drude, L., Ende, K., Ehrle, U., Baumgartl, K., Emke, F., Glosemeyer, R., Felten, G., Hüppe, D., Fischer, J., Fischer, U., Frederking, D., Frick, B., Friese, G., Gantke, B., Geyer, P., Schwind, H.R., Glas, M., Glaunsinger, T., Goebel, F., Göbel, U., Görlitz, B., Graf, R., Gruber, H., Hartmann, C., Klag, C., Härter, G., Herder, M., Heuchel, T., Heuer, S., Hinrichsen, H., Seegers, B., Höffl, K.-H., Hörster, H., Sonne, J.-U., Hofmann, W.P., Holst, F., Hunstiger, M., Hurst, A., Jägel-Guedes, E., John, C., Jung, M., Kallinowski, B., Kapzan, B., Kerzel, W., Khaykin, P., Klarhof, M., Klüppelberg, U., Wolfratshausen, Klugewitz, K., Knapp, B., Knevels, U., Kochsiek, T., Körfer, A., Köster, A., Kuhn, M., Langekamp, A., Künzig, B., Link, R., Littman, M., Löhr, H., Lutz, T., Gute, P., Knecht, G., Lutz, U., Mainz, D., Mahle, I., Maurer, P., Mauss, S., Mayer, C., Möller, H., Heyne, R., Moritzen, D., Mroß, M., Mundlos, M., Naumann, U., Nehls, O., K, Ningel, R., Oelmann, A., Olejnik, H., Gadow, K., Pascher, E., Philipp, A., Pichler, M., Polzien, F., Raddant, R., Riedel, M., Rietzler, S., Rössle, M., Rufle, W., Rump, A., Schewe, C., Hoffmann, C., Schleehauf, D., Schmidt, W., Schmidt-Heinevetter, G., Fabris, J. Schmidtler-von, Schneider, L., Schober, A., Niehaus-Hahn, S., Schwenzer, J., Seidel, T., Seitel, G., Sick, C., Simon, K., Stähler, D., Stenschke, F., Steffens, H., Stein, K., Steinmüller, M., Sternfeld, T., Svensson, K., Tacke, W., Teuber, G., Teubner, K., Thieringer, J., Tomesch, A., Trappe, U., Ullrich, J., Urban, G., Usadel, S., von Lucadou, A., Weinberger, F., Werheid-Dobers, M., Werner, P., Winter, T., Zehnter, E., Zipf, A., Dietz, Julia, Graf, Christiana, Berg, Christoph P., Port, Kerstin, Deterding, Katja, Buggisch, Peter, Peiffer, Kai-Henrik, Vermehren, Johannes, Dultz, Georg, Geier, Andreas, Reiter, Florian P., Bruns, Tony, Schattenberg, Jörn M., Durmashkina, Elena, Gustot, Thierry, Moreno, Christophe, Trauth, Janina, Discher, Thomas, Fischer, Janett, Berg, Thomas, Kremer, Andreas E., Müllhaupt, Beat, Zeuzem, Stefan, and Sarrazin, Christoph
Published: 2024
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2. Trends in mortality in people with HIV from 1999 to 2020: a multi-cohort collaboration

Author: Tusch, E, Ryom, L, Pelchen-Matthews, A, Mocroft, A, Elbirt, D, Oprea, C, Günthard, H, Staehelin, C, Zangerle, R, Suarez, I, Vehreschild, J, Wit, F, Menozzi, M, d'Arminio Monforte, A, Spagnuolo, V, Pradier, C, Carlander, C, Suanzes, P, Wasmuth, J, Carr, A, Petoumenos, K, Borgans, F, Bonnet, F, De Wit, S, El-Sadr, W, Neesgaard, B, Jaschinski, N, Greenberg, L, Hosein, S, Gallant, J, Vannappagari, V, Young, L, Sabin, C, Lundgren, J, Peters, L, Reekie, J, Calvo, G, Dabis, F, Kirk, O, Law, M, Monforte, A, Morfeldt, L, Reiss, P, Weber, R, Lind-Thomsen, A, Brandt, R, Hillebreght, M, Zaheri, S, Scherrer, A, Schöni-Affolter, F, Rickenbach, M, Tavelli, A, Fanti, I, Leleux, O, Mourali, J, Marec, F, Boerg, E, Thulin, E, Sundström, A, Bartsch, G, Thompsen, G, Necsoi, C, Delforge, M, Fontas, E, Caissotti, C, Dollet, K, Mateu, S, Torres, F, Blance, A, Huang, R, Puhr, R, Laut, K, Kristensen, D, Phillips, A, Kamara, D, Smith, C, Hatleberg, C, Raben, D, Matthews, C, Bojesen, A, Grevsen, A, Powderly, B, Shortman, N, Moecklinghoff, C, Reilly, G, Franquet, X, Smit, C, Ross, M, Fux, C, Morlat, P, Friis-Møller, N, Kowalska, J, Bohlius, J, Bower, M, Fätkenheuer, G, Grulich, A, Sjøl, A, Meidahl, P, Iversen, J, Reiss, C, Hillebregt, M, Prins, J, Kuijpers, T, Scherpbier, H, van der Meer, J, Godfried, M, van der Poll, T, Nellen, F, Geerlings, S, van Vugt, M, Pajkrt, D, Bos, J, Wiersinga, W, van der Valk, M, Goorhuis, A, Hovius, J, van Eden, J, Henderiks, A, van Hes, A, Mutschelknauss, M, Nobel, H, Pijnappel, F, Jurriaans, S, Back, N, Zaaijer, H, Berkhout, B, Cornelissen, M, Schinkel, C, Thomas, X, Ziekenhuis, A, van den Berge, M, Stegeman, A, Baas, S, de Looff, L, Versteeg, D, Ziekenhuis, C, Pronk, M, Ammerlaan, H, De Munnik, E, Jansz, A, Tjhie, J, Wegdam, M, Deiman, B, Scharnhorst, V, van der Plas, A, Weijsenfeld, A, van der Ende, M, De Vries-Sluijs, T, van Gorp, E, Schurink, C, Nouwen, J, Verbon, A, Rijnders, B, Bax, H, van der Feltz, M, Bassant, N, van Beek, J, Vriesde, M, van Zonneveld, L, de Oude-Lubbers, A, van den Berg-Cameron, H, Bruinsma-Broekman, F, de Groot, J, de Man, M, Boucher, C, Koopmans, M, van Kampen, J, Pas, S, Mc–sophia, E, Driessen, G, van Rossum, A, van der Knaap, L, Visser, E, Branger, J, Rijkeboer-Mes, A, de Ven, C, Ziekenhuis, H, Schippers, E, van Nieuwkoop, C, van IJperen, J, Geilings, J, van der Hut, G, Franck, P, van Eeden, A, Brokking, W, Groot, M, Elsenburg, L, Damen, M, Kwa, I, Groeneveld, P, Bouwhuis, J, van den Berg, J, van Hulzen, A, van der Bliek, G, Bor, P, Bloembergen, P, Wolfhagen, M, Ruijs, G, Kroon, F, de Boer, M, Bauer, M, Jolink, H, Vollaard, A, Dorama, W, van Holten, N, Claas, E, Wessels, E, den Hollander, J, Pogany, K, Roukens, A, Kastelijns, M, Smit, J, Smit, E, Struik-Kalkman, D, Tearno, C, Bezemer, M, van Niekerk, T, Pontesilli, O, Lowe, S, Lashof, A, Posthouwer, D, Ackens, R, Schippers, J, Vergoossen, R, Weijenberg-Maes, B, van Loo, I, Havenith, T, Leyten, E, Gelinck, L, van Hartingsveld, A, Meerkerk, C, Wildenbeest, G, Mutsaers, J, Jansen, C, Mulder, J, Vrouenraets, S, Lauw, F, van Broekhuizen, M, Paap, H, Vlasblom, D, Smits, P, Zuiderzee, M, Weijer, S, El Moussaoui, R, Bosma, A, van Vonderen, M, van Houte, D, Kampschreur, L, Dijkstra, K, Faber, S, Weel, J, Kootstra, G, Delsing, C, van der Burg-van de Plas, M, Heins, H, Lucas, E, Kortmann, W, van Twillert, G, Stuart, J, Diederen, B, Pronk, D, van Truijen-Oud, F, van der Reijden, W, Jansen, R, Brinkman, K, van den Berk, G, Blok, W, Frissen, P, Lettinga, K, Schouten, W, Veenstra, J, Brouwer, C, Geerders, G, Hoeksema, K, Kleene, M, van der Meché, I, Spelbrink, M, Sulman, H, Toonen, A, Wijnands, S, Kwa, D, Witte, E, Koopmans, P, Keuter, M, van der Ven, A, ter Hofstede, H, Dofferhoff, A, van Crevel, R, Albers, M, Bosch, M, Grintjes-Huisman, K, Zomer, B, Stelma, F, Rahamat-Langendoen, J, Burger, D, Richter, C, Gisolf, E, Hassing, R, ter Beest, G, van Bentum, P, Langebeek, N, Tiemessen, R, Swanink, C, van Lelyveld, S, Soetekouw, R, Hulshoff, N, van der Prijt, L, van der Swaluw, J, Bermon, N, Herpers, B, Veenendaal, D, Verhagen, D, van Wijk, M, Ziekenhuis, S, van Kasteren, M, Brouwer, A, de Wiel, B, Kuipers, M, Santegoets, R, van der Ven, B, Marcelis, J, Buiting, A, Kabel, P, Bierman, W, Scholvinck, H, Wilting, K, Stienstra, Y, Jonge, H, van der Meulen, P, de Weerd, D, Ludwig-Roukema, J, Niesters, H, Riezebos-Brilman, A, van Leer-Buter, C, Knoester, M, Hoepelman, A, Mudrikova, T, Ellerbroek, P, Oosterheert, J, Arends, J, Barth, R, Wassenberg, M, Schadd, E, van Elst-Laurijssen, D, van Oers-Hazelzet, E, Vervoort, S, van Berkel, M, Schuurman, R, Verduyn-Lunel, F, Wensing, A, Peters, E, van Agtmael, M, Bomers, M, de Vocht, J, Heitmuller, M, Laan, L, Pettersson, A, Vandenbroucke-Grauls, C, Ang, C, Kinderziekenhuis, W, Geelen, S, Wolfs, T, Bont, L, Nauta, N, Bezemer, D, van Sighem, A, Boender, T, de Jong, A, Bergsma, D, Hoekstra, P, de Lang, A, Grivell, S, Jansen, A, Rademaker, M, Raethke, M, Meijering, R, Schnörr, S, de Groot, L, van den Akker, M, Bakker, Y, Claessen, E, El Berkaoui, A, Koops, J, Kruijne, E, Lodewijk, C, Munjishvili, L, Peeck, B, Ree, C, Regtop, R, Ruijs, Y, Rutkens, T, van de Sande, L, Schoorl, M, Timmerman, A, Tuijn, E, Veenenberg, L, van der Vliet, S, Wisse, A, Woudstra, T, Tuk, B, Dupon, M, Gaborieau, V, Lacoste, D, Malvy, D, Mercié, P, Neau, D, Pellegrin, J, Tchamgoué, S, Lazaro, E, Cazanave, C, Vandenhende, M, Vareil, M, Gérard, Y, Blanco, P, Bouchet, S, Breilh, D, Fleury, H, Pellegrin, I, Chêne, G, Thiébaut, R, Wittkop, L, Lawson-Ayayi, S, Gimbert, A, Desjardin, S, Lacaze-Buzy, L, Petrov-Sanchez, V, André, K, Bernard, N, Caubet, O, Caunegre, L, Chossat, I, Courtault, C, Dauchy, F, De Witte, S, Dondia, D, Duffau, P, Dutronc, H, Farbos, S, Faure, I, Ferrand, H, Gerard, Y, Greib, C, Hessamfar, M, Imbert, Y, Lataste, P, Marie, J, Mechain, M, Monlun, E, Ochoa, A, Pistone, T, Raymond, I, Receveur, M, Rispal, P, Sorin, L, Valette, C, Viallard, J, Wille, H, Wirth, G, Lafon, M, Trimoulet, P, Bellecave, P, Tumiotto, C, Haramburu, F, Miremeont-Salamé, G, Blaizeau, M, Decoin, M, Hannapier, C, Lenaud, E, Pougetoux, A, Delveaux, S, D’Ivernois, C, Diarra, F, Uwamaliya-Nziyumvira, B, Palmer, G, Conte, V, Sapparrart, V, Law, C, Moore, R, Edwards, S, Hoy, J, Watson, K, Roth, N, Lau, H, Bloch, M, Baker, D, Cooper, D, O’Sullivan, M, Nolan, D, Guelfi, G, Calvo, C, Domingo, P, Sambeat, M, Gatell, J, Del Cacho, E, Cadafalch, J, Fuster, M, Codina, C, Sirera, G, Vaqué, A, Clumeck, N, Gennotte, A, Gerard, M, Kabeya, K, Konopnicki, D, Libois, A, Martin, C, Payen, M, Semaille, P, Van Laethem, Y, Neaton, C, Krum, E, Thompson, G, Wentworth, D, Luskin-Hawk, R, Telzak, E, Abrams, D, Cohn, D, Markowitz, N, Arduino, R, Mushatt, D, Friedland, G, Perez, G, Tedaldi, E, Fisher, E, Gordin, F, Crane, L, Sampson, J, Baxter, J, Gazzard, B, Horban, A, Karpov, I, Losso, M, Pedersen, C, Ristola, M, Rockstroh, J, Fischer, A, Larsen, J, Podlekareva, D, Cozzi-Lepri, A, Shepherd, L, Schultze, A, Amele, S, Kundro, M, Schmied, B, Wien, P, Vassilenko, A, Mitsura, V, Paduto, D, Florence, E, Vandekerckhove, L, Hadziosmanovic, V, Begovac, J, Machala, L, Jilich, D, Sedlacek, D, Kronborg, G, Benfield, T, Gerstoft, J, Katzenstein, T, Møller, N, Ostergaard, L, Wiese, L, Nielsen, L, Zilmer, K, Smidt, J, Siseklinik, N, Aho, I, Viard, J, Duvivier, C, Schmidt, R, Degen, O, Stellbrink, H, Stefan, C, Goethe, J, Bogner, J, Chkhartishvili, N, Gargalianos, P, Xylomenos, G, Armenis, K, Sambatakou, H, Szlávik, J, Gottfredsson, M, Mulcahy, F, Yust, I, Turner, D, Burke, M, Shahar, E, Hassoun, G, Elinav, H, Haouzi, M, Sthoeger, Z, Esposito, R, Mazeu, I, Mussini, C, Mazzotta, F, Gabbuti, A, Annunziata, O, Vullo, V, Lichtner, M, Zaccarelli, M, Antinori, A, Acinapura, R, Plazzi, M, Lazzarin, A, Castagna, A, Gianotti, N, Galli, M, Ridolfo, A, Rozentale, B, Uzdaviniene, V, Matulionyte, R, Staub, T, Hemmer, R, Ormaasen, V, Maeland, A, Bruun, J, Knysz, B, Gasiorowski, J, Inglot, M, Bakowska, E, Flisiak, R, Grzeszczuk, A, Parczewski, M, Maciejewska, K, Aksak-Was, B, Beniowski, M, Mularska, E, Smiatacz, T, Gensing, M, Jablonowska, E, Malolepsza, E, Wojcik, K, Mozer-Lisewska, I, Caldeira, L, Mansinho, K, Maltez, F, Radoi, R, Panteleev, A, Panteleev, O, Yakovlev, A, Trofimora, T, Khromova, I, Kuzovatova, E, Blokhina, I, Novogrod, N, Borodulina, E, Vdoushkina, E, Jevtovic, D, Tomazic, J, Miró, J, Moreno, S, Rodriguez, J, Clotet, B, Jou, A, Paredes, R, Tural, C, Puig, J, Bravo, I, Gutierrez, M, Mateo, G, Laporte, J, Sonnerborg, A, Brännström, I, Flamholc, L, Cavassini, M, Calmy, A, Furrer, H, Battegay, M, Schmid, P, Kuznetsova, A, Kyselyova, G, Sluzhynska, M, Johnson, A, Simons, E, Johnson, M, Orkin, C, Weber, J, Scullard, G, Clarke, A, Leen, C, Morfeldt, C, Thulin, G, Åkerlund, B, Koppel, K, Karlsson, A, Håkangård, C, Castelli, F, Cauda, R, Perri, G, Iardino, R, Ippolito, G, Marchetti, G, Perno, C, von Schloesser, F, Viale, P, Ceccherini-Silberstein, F, Girardi, E, Caputo, S, Puoti, M, Andreoni, M, Ammassari, A, Balotta, C, Bandera, A, Bonfanti, P, Bonora, S, Borderi, M, Calcagno, A, Calza, L, Capobianchi, M, Cingolani, A, Cinque, P, De Luca, A, Biagio, A, Gori, A, Guaraldi, G, Lapadula, G, Madeddu, G, Maggiolo, F, Marcotullio, S, Monno, L, Nozza, S, Roldan, E, Rossotti, R, Rusconi, S, Santoro, M, Saracino, A, Galli, L, Lorenzini, P, Rodano, A, Shanyinde, M, Carletti, F, Carrara, S, Caro, A, Graziano, S, Petrone, F, Prota, G, Quartu, S, Truffa, S, Giacometti, A, Costantini, A, Barocci, V, Angarano, G, Santoro, C, Suardi, C, Donati, V, Verucchi, G, Minardi, C, Quirino, T, Abeli, C, Manconi, P, Piano, P, Cacopardo, B, Celesia, B, Vecchiet, J, Falasca, K, Pan, A, Lorenzotti, S, Sighinolfi, L, Segala, D, Vichi, F, Cassola, G, Viscoli, C, Alessandrini, A, Bobbio, N, Mazzarello, G, Mastroianni, C, Belvisi, V, Caramma, I, Chiodera, A, Milini, P, Rizzardini, G, Moioli, M, Piolini, R, Salpietro, S, Tincati, C, Puzzolante, C, Abrescia, N, Chirianni, A, Borgia, G, Orlando, R, Bonadies, G, Martino, F, Gentile, I, Maddaloni, L, Cattelan, A, Marinello, S, Cascio, A, Colomba, C, Baldelli, F, Schiaroli, E, Parruti, G, Sozio, F, Magnani, G, Ursitti, M, Cristaudo, A, Baldin, G, Capozzi, M, Cicalini, S, Sulekova, L, Iaiani, G, Latini, A, Mastrorosa, I, Savinelli, S, Vergori, A, Cecchetto, M, Viviani, F, Bagella, P, Rossetti, B, Franco, A, Del Vecchio, R, Francisci, D, Giuli, C, Caramello, P, Orofino, G, Sciandra, M, Bassetti, M, Londero, A, Pellizzer, G, Manfrin, V, Starnini, G, Ialungo, A, Central, C, Dellamonica, P, Bernard, E, Courjon, J, Cua, E, De Salvador-Guillouet, F, Durant, J, Etienne, C, Ferrando, S, Mondain-Miton, V, Naqvi, A, Perbost, I, Pillet, S, Prouvost-Keller, B, Pugliese, P, Rio, V, Risso, K, Roger, P, Aubert, V, Bernasconi, E, Böni, J, Braun, D, Bucher, H, Ciuffi, A, Dollenmaier, G, Egger, M, Elzi, L, Fehr, J, Fellay, J, Haerry, D, Hasse, B, Hirsch, H, Hoffmann, M, Hösli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kouyos, R, Kovari, H, Ledergerber, B, Martinetti, G, de Tejada, B, Marzolini, C, Metzner, K, Müller, N, Nicca, D, Pantaleo, G, Paioni, P, Rauch, A, Rudin, C, Speck, R, Stöckle, M, Tarr, P, Trkola, A, Vernazza, P, Wandeler, G, Yerly, S, Valk, M, Hutchinson, J, Rupasinghe, D, Han, W, Appoyer, H, Vera, J, Broster, B, Barbour, L, Carney, D, Greenland, L, Coughlan, R, Saint-Pierre, C, Stephan, C, Bucht, M, Chokoshvili, O, Borghi, V, Casabona, J, Miro, J, Lampe, F, Burns, F, Chaloner, C, Muccini, C, Lolatto, R, Sönnerborg, A, Nowak, P, Vesterbacka, J, Mattsson, L, Carrick, D, Stigsäter, K, Kusejko, K, Schulze, N, Franke, B, Rooney, J, Mcnicholl, I, Garges, H, Campo, R, Volny-Anne, A, Dedes, N, Williams, E, Bruguera, A, Volny-Anne, R, Mendão, L, Timiryasova, A, Fursa, O, Jakobsen, M, Kraef, C, Gardizi, M, Andersen, K, Kumar, L, Elsing, T, Shahi, S, Valdenmaiier, O, Bansi-Matharu, L, Byonanebye, D, Bannister, W, Roen, A, Null, N, Tusch, Erich, Ryom, Lene, Pelchen-Matthews, Annegret, Mocroft, Amanda, Elbirt, Daniel, Oprea, Cristiana, Günthard, Huldrych F, Staehelin, Cornelia, Zangerle, Robert, Suarez, Isabelle, Vehreschild, Jörg Janne, Wit, Ferdinand, Menozzi, Marianna, d'Arminio Monforte, Antonella, Spagnuolo, Vincenzo, Pradier, Christian, Carlander, Christina, Suanzes, Paula, Wasmuth, Jan-Christian, Carr, Andrew, Petoumenos, Kathy, Borgans, Frauke, Bonnet, Fabrice, De Wit, Stephane, El-Sadr, Wafaa, Neesgaard, Bastian, Jaschinski, Nadine, Greenberg, Lauren, Hosein, Sean R, Gallant, Joel, Vannappagari, Vani, Young, Lital, Sabin, Caroline, Lundgren, Jens, Peters, Lars, Reekie, Joanne, Monforte, A d’Arminio, Brandt, R Salbøl, Wit, F W N M, Marec, F Le, Laut, K Grønborg, Sabin, C A, Phillips, A N, Kamara, D A, Smith, C J, Hatleberg, C I, Brandt, R S, Grevsen, A L, Lundgren, J D, Fux, C A, Monforte, A d'Arminio, Iversen, J S, Reiss, Central P, Prins, J M, Kuijpers, T W, Scherpbier, H J, van der Meer, J T M, Godfried, M H, Nellen, F J B, Geerlings, S E, Bos, J C, Wiersinga, W J, Hovius, J W, 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Tejada, B, Marzolini, C, Metzner, K, Müller, N, Nicca, D, Pantaleo, G, Paioni, P, Rauch, A, Rudin, C, Speck, R, Stöckle, M, Tarr, P, Trkola, A, Vernazza, P, Wandeler, G, Yerly, S, Valk, M, Hutchinson, J, Rupasinghe, D, Han, W, Appoyer, H, Vera, J, Broster, B, Barbour, L, Carney, D, Greenland, L, Coughlan, R, Saint-Pierre, C, Stephan, C, Bucht, M, Chokoshvili, O, Borghi, V, Casabona, J, Miro, J, Lampe, F, Burns, F, Chaloner, C, Muccini, C, Lolatto, R, Sönnerborg, A, Nowak, P, Vesterbacka, J, Mattsson, L, Carrick, D, Stigsäter, K, Kusejko, K, Schulze, N, Franke, B, Rooney, J, Mcnicholl, I, Garges, H, Campo, R, Volny-Anne, A, Dedes, N, Williams, E, Bruguera, A, Volny-Anne, R, Mendão, L, Timiryasova, A, Fursa, O, Jakobsen, M, Kraef, C, Gardizi, M, Andersen, K, Kumar, L, Elsing, T, Shahi, S, Valdenmaiier, O, Bansi-Matharu, L, Byonanebye, D, Bannister, W, Roen, A, Null, N, Tusch, Erich, Ryom, Lene, Pelchen-Matthews, Annegret, Mocroft, Amanda, Elbirt, Daniel, Oprea, Cristiana, Günthard, Huldrych F, Staehelin, Cornelia, Zangerle, Robert, Suarez, Isabelle, Vehreschild, Jörg Janne, Wit, Ferdinand, Menozzi, Marianna, d'Arminio Monforte, Antonella, Spagnuolo, Vincenzo, Pradier, Christian, Carlander, Christina, Suanzes, Paula, Wasmuth, Jan-Christian, Carr, Andrew, Petoumenos, Kathy, Borgans, Frauke, Bonnet, Fabrice, De Wit, Stephane, El-Sadr, Wafaa, Neesgaard, Bastian, Jaschinski, Nadine, Greenberg, Lauren, Hosein, Sean R, Gallant, Joel, Vannappagari, Vani, Young, Lital, Sabin, Caroline, Lundgren, Jens, Peters, Lars, Reekie, Joanne, Monforte, A d’Arminio, Brandt, R Salbøl, Wit, F W N M, Marec, F Le, Laut, K Grønborg, Sabin, C A, Phillips, A N, Kamara, D A, Smith, C J, Hatleberg, C I, Brandt, R S, Grevsen, A L, Lundgren, J D, Fux, C A, Monforte, A d'Arminio, Iversen, J S, Reiss, Central P, Prins, J M, Kuijpers, T W, Scherpbier, H J, van der Meer, J T M, Godfried, M H, Nellen, F J B, Geerlings, S E, Bos, J C, Wiersinga, W J, Hovius, J W, van Hes, A M H, Nobel, H E, Pijnappel, F J J, Back, N K T, Zaaijer, H L, Cornelissen, M T E, Schinkel, C J, Thomas, X V, Ziekenhuis, Admiraal De Ruyter, de Looff, L Hage, Ziekenhuis, Catharina, Pronk, M J H, Ammerlaan, H S M, De Munnik, E S, Jansz, A R, Wegdam, M C A, Weijsenfeld, A M, van der Ende, M E, De Vries-Sluijs, T E M S, van Gorp, E C M, Schurink, C A M, Nouwen, J L, Rijnders, B J A, Bax, H I, van Beek, J E A, van Zonneveld, L M, van den Berg-Cameron, H J, Bruinsma-Broekman, F B, de Man, M de Zeeuw, Boucher, C A B, Koopmans, M P G, van Kampen, J J A, Pas, S D, MC–Sophia, Erasmus, Driessen, G J A, van Rossum, A M C, van der Knaap, L C, de Ven, C J H M Duijf-van, Ziekenhuis, Haga, Schippers, E F, van IJperen, J M, Franck, P F H, Elsenburg, L J M, Kwa, I S, Groeneveld, P H P, Bouwhuis, J W, van den Berg, J F, van Hulzen, A G W, van der Bliek, G L, Bor, P C J, Wolfhagen, M J H M, Ruijs, G J H M, Kroon, F P, de Boer, M G J, Bauer, M P, Vollaard, A M, Claas, E C J, den Hollander, J G, Smit, J V, Lowe, S H, Lashof, A M L Oude, Ackens, R P, van Loo, I H M, Havenith, T R A, Leyten, E M S, Gelinck, L B S, Wildenbeest, G S, Mutsaers, J A E M, Jansen, C L, Mulder, J W, Vrouenraets, S M E, Lauw, F N, van Broekhuizen, M C, Vlasblom, D J, Smits, P H M, Zuiderzee, M C, Bosma, A S, van Vonderen, M G A, van Houte, D P F, Kampschreur, L M, Kootstra, G J, Delsing, C E, Stuart, J W T Cohen, Diederen, B M W, van Truijen-Oud, F A, van der Reijden, W A, van den Berk, G E L, Blok, W L, Frissen, P H J, Lettinga, K D, Schouten, W E M, Brouwer, C J, Geerders, G F, Kleene, M J, van der Meché, I B, Toonen, A J M, Koopmans, P P, van der Ven, A J A M, ter Hofstede, H J M, Dofferhoff, A S M, Bosch, M E W, Grintjes-Huisman, K J T, Zomer, B J, Stelma, F F, Gisolf, E H, Hassing, R J, van Bentum, P H M, Swanink, C M A, van Lelyveld, S F L, van der Prijt, L M M, Herpers, B L, Verhagen, D W M, Ziekenhuis, St Elisabeth, van Kasteren, M E E, Brouwer, A E, de Wiel, B A F M de Kruijf-van, Santegoets, R M W J, Marcelis, J H, Buiting, A G M, Kabel, P J, Bierman, W F W, Wilting, K R, Jonge, H de Groot-de, van der Meulen, P A, de Weerd, D A, Niesters, H G M, van Leer-Buter, C C, Hoepelman, A I M, Ellerbroek, P M, Oosterheert, J J, Arends, J E, Barth, R E, Wassenberg, M W M, Schadd, E M, van Elst-Laurijssen, D H M, van Oers-Hazelzet, E E B, Wensing, A M J, Peters, E J G, van Agtmael, M A, Laan, L M, Pettersson, A M, Vandenbroucke-Grauls, C M J E, Ang, C W, Kinderziekenhuis, Wilhelmina, Geelen, S P M, Wolfs, T F W, Bont, L J, Bezemer, D O, van Sighem, A I, Boender, T S, Rademaker, M J, Pellegrin, J L, Vareil, M O, Dauchy, F A, Receveur, M C, Vandenhende, M A, Viallard, J F, Lafon, Me, Blaizeau, M J, Boerg, Eloïse, Law, Central M, Calvo, Central G, Sambeat, M A, Gennotte, A F, Payen, M C, Neaton, Central J, El-Sadr, W M, Abrams, D I, Crane, L R, Fischer, A H, Larsen, J F, Wien, Pulmologisches Zentrum der Stadt, Mitsura, V M, Møller, N F, Nielsen, L N, Smidt, Jelena, Siseklinik, Nakkusosakond, Viard, J-P, Stellbrink, H J, Goethe, J W, Sthoeger, Z M, Monforte, A D’Arminio, Annunziata, Ospedale S Maria, Blokhina, I N, Novogrod, Nizhny, Gatell, J M, Miró, J M, Rodriguez, J M, Laporte, J M, Johnson, A M, Johnson, M A, Morfeldt, Central L, Perri, G Di, Marchetti, G C, Perno, C F, Caputo, S Lo, Capobianchi, M R, Biagio, A Di, Roldan, E Quiros, Santoro, M M, Caro, A Di, Manconi, P E, Moioli, M C, Ridolfo, A L, Martino, F Di, Cattelan, A M, Ursitti, M A, Sulekova, L Fontanelli, Plazzi, M M, Del Vecchio, R Fontana, Giuli, C Di, Orofino, G C, Roger, P M, Braun, D L, Bucher, H C, Günthard, H F, Hirsch, H H, Kouyos, R D, de Tejada, B Martinez, Metzner, K J, Scherrer, A U, Valk, Marc vd, Han, W Min, Saint-Pierre, C H U, Miro, J M, Wasmuth, J C, Vehreschild, J J, McNicholl, I, Williams, E D, Volny-Anne, R Campo Alain, Dedes, Nikos, Mendão, Luis, Jakobsen, M L, Kumar, L Ramesh, Elsing, T W, and null, null
Abstract: Background: Mortality among people with HIV declined with the introduction of combination antiretroviral therapy. We investigated trends over time in all-cause and cause-specific mortality in people with HIV from 1999-2020. Methods: Data were collected from the D:A:D cohort from 1999 through January 2015 and RESPOND from October 2017 through 2020. Age-standardized all-cause and cause-specific mortality rates, classified using Coding Causes of Death in HIV (CoDe), were calculated. Poisson regression models were used to assess mortality trends over time. Results: Among 55716 participants followed for a median of 6 years (IQR 3-11), 5263 participants died (crude mortality rate [MR] 13.7/1000 PYFU; 95%CI 13.4-14.1). Changing patterns of mortality were observed with AIDS as the most common cause of death between 1999- 2009 (n = 952, MR 4.2/1000 PYFU; 95%CI 4.0-4.5) and non-AIDS defining malignancy (NADM) from 2010 -2020 (n = 444, MR 2.8/1000 PYFU; 95%CI 2.5-3.1). In multivariable analysis, all-cause mortality declined over time (adjusted mortality rate ratio [aMRR] 0.97 per year; 95%CI 0.96, 0.98), mostly from 1999 through 2010 (aMRR 0.96 per year; 95%CI 0.95-0.97), and with no decline shown from 2011 through 2020 (aMRR 1·00 per year; 95%CI 0·96-1·05). Mortality due all known causes except NADM also declined over the entire follow-up period. Conclusion: Mortality among people with HIV in the D:A:D and/or RESPOND cohorts decreased between 1999 and 2009 and was stable over the period from 2010 through 2020. The decline in mortality rates was not fully explained by improvements in immunologic-virologic status or other risk factors.
Published: 2024

3. Long-term persistence of HCV resistance-associated substitutions after DAA treatment failure

Author: Balavoine, J., Giostra, E., Berning, M., Hampe, J., Canbay, A., Steckstor, W., Schmiegel, W., Brockmeyer, N.H., De Gottardi, A., Rauch, A., Semmo, N., Fischer, J., Gress, M., Heinzow, H., Hilgard, G., Schmidt, H., Herrmann, A., Stallmach, A., Hoffmann, D., Protzer, U., Klinker, H., Schulze, P., Kodal, A., Kremer, A., Siebler, J., Löbermann, M., Götze, T., Weigt, J., Lohse, A., Von Felden, J., Jordan, S., Lange, C.M., Zachoval, R., Mayerle, J., Maieron, A., Moradpour, D., Chave, J.-P., Moreno, C., Muche, M., Epple, H.-J., Müller-Schilling, M., Kocheise, F., Müllhaupt, B., Port, K., Deterding, K., Wedemeyer, H., Cornberg, M., Manns, M., Reinhardt, L., Ellenrieder, V., Rissland, J., Semela, D., Spengler, U., Rockstroh, J., Roeb, E., Sprinzl, M., Galle, P., Stauber, R., Stremmel, W., Strey, B., Thimme, R., Boettler, T., Tacke, F., Teufel, A., Vogelmann, R., Ebert, M., Tomasiewicz, K., Trautwein, C., Koenen, T., Weber, T., Wietzke-Braun, P., Günther, R., Zizer, E., Backhus, J., Seufferlein, T., Angeli, W., Beckebaum, S., Doberauer, C., Durmashkina, E., Hackelsberger, A., Erhardt, A., Garrido-Lüneburg, A., Gattringer, H., Genné, D., Gschwantler, M., Gundling, F., Hametner, S., Schöfl, R., Hartmann, C., Heyer, T., Hirschi, C., Jussios, A., Kanzler, S., Kordecki, N., Kraus, M., Kullig, U., Wollschläger, S., Magenta, L., Terziroli Beretta-Piccoli, B., Menges, M., Mohr, L., Muehlenberg, K., Niederau, C., Paulweber, B., Petrides, A., Pinkernell, M., Piso, R., Rambach, W., Reiser, M., Riecken, B., Rieke, A., Roth, J., Schelling, M., Schlee, P., Schneider, A., Scholz, D., Schott, E., Schuchmann, M., Schulten-Baumer, U., Seelhoff, A., Stich, A., Stickel, F., Ungemach, J., Walter, E., Weber, A., Winzer, T., Abels, W., Adler, M., Audebert, F., Baermann, C., Bästlein, E., Barth, R., Barthel, K., Becker, W., Behrends, J., Benninger, J., Berger, F., Berzow, D., Beyer, T., Bierbaum, M., Blaukat, O., Bodtländer, A., Böhm, G., Börner, N., Bohr, U., Bokemeyer, B., Bruch, H.R., Bucholz, D., Burkhard, O., Busch, N., Chirca, C., Delker, R., Diedrich, J., Frank, M., Diehl, M., Dienethal, A., Dietel, P., Dikopoulos, N., Dreck, M., Dreher, F., Drude, L., Ende, K., Ehrle, U., Baumgartl, K., Emke, F., Glosemeyer, R., Felten, G., Hüppe, D., Fischer, U., Frederking, D., Frick, B., Friese, G., Gantke, B., Geyer, P., Schwind, H.R., Glas, M., Glaunsinger, T., Goebel, F., Göbel, U., Görlitz, B., Graf, R., Gruber, H., Härter, G., Herder, M., Heuchel, T., Heuer, S., Höffl, K.-H., Hörster, H., Sonne, J.-U., Hofmann, W.P., Holst, F., Hunstiger, M., Hurst, A., Jägel-Guedes, E., John, C., Jung, M., Kallinowski, B., Kapzan, B., Kerzel, W., Khaykin, P., Klarhof, M., Klüppelberg, U., Wolfratshausen, Klugewitz, K., Knapp, B., Knevels, U., Kochsiek, T., Körfer, A., Köster, A., Kuhn, M., Langekamp, A., Künzig, B., Link, R., Littman, M., Löhr, H., Lutz, T., Knecht, G., Lutz, U., Mainz, D., Mahle, I., Maurer, P., Mayer, C., Meister, V., Möller, H., Heyne, R., Moritzen, D., Mroß, M., Mundlos, M., Naumann, U., Nehls, O., Ningel, K.R., Oelmann, A., Olejnik, H., Gadow, K., Pascher, E., Petersen, J., Philipp, A., Pichler, M., Polzien, F., Raddant, R., Riedel, M., Rietzler, S., Rössle, M., Rufle, W., Rump, A., Schewe, C., Hoffmann, C., Schleehauf, D., Schmidt, W., Schmidt-Heinevetter, G., Schmidtler-von Fabris, J., Schneider, L., Schober, A., Niehaus-Hahn, S., Schwenzer, J., Seegers, B., Seidel, T., Seitel, G., Sick, C., Simon, K., Stähler, D., Stenschke, F., Steffens, H., Stein, K., Steinmüller, M., Sternfeld, T., Svensson, K., Tacke, W., Teuber, G., Teubner, K., Thieringer, J., Tomesch, A., Trappe, U., Ullrich, J., Urban, G., Usadel, S., Von Lucadou, A., Weinberger, F., Werheid-Dobers, M., Werner, P., Winter, T., Zehnter, E., Zipf, A., Dietz, Julia, Müllhaupt, Beat, Buggisch, Peter, Graf, Christiana, Peiffer, Kai-Henrik, Matschenz, Katrin, Schattenberg, Jörn M., Antoni, Christoph, Mauss, Stefan, Niederau, Claus, Discher, Thomas, Trauth, Janina, Dultz, Georg, Schulze zur Wiesch, Julian, Piecha, Felix, Klinker, Hartwig, Müller, Tobias, Berg, Thomas, Neumann-Haefelin, Christoph, Berg, Christoph P., Zeuzem, Stefan, and Sarrazin, Christoph
Published: 2023
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4. CSi—a joint industry project into CPTUs in silty soils

Author: Augustesen, A.H., primary, Carotenuto, P., additional, Bilici, C., additional, Lunne, T., additional, Lindeboom, R.C.J., additional, Krogh, L., additional, van den Bosch, J., additional, Barth, R., additional, Erbrich, C., additional, Ingarfield, S., additional, Giretti, D., additional, Fioravante, V., additional, Dias, H., additional, Sougle, M-C, additional, Barwise, A., additional, de Wit, S., additional, Burbury, D., additional, and Adams, N., additional
Published: 2022
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5. Single-molecule visualization of twin-supercoiled domains generated during transcription

Author: Janissen, R. (author), Barth, R. (author), Polinder, M.L. (author), van der Torre, J. (author), Dekker, C. (author), Janissen, R. (author), Barth, R. (author), Polinder, M.L. (author), van der Torre, J. (author), and Dekker, C. (author)
Abstract: Transcription-coupled supercoiling of DNA is a key factor in chromosome compaction and the regulation of genetic processes in all domains of life. It has become common knowledge that, during transcription, the DNA-dependent RNA polymerase (RNAP) induces positive supercoiling ahead of it (downstream) and negative supercoils in its wake (upstream), as rotation of RNAP around the DNA axis upon tracking its helical groove gets constrained due to drag on its RNA transcript. Here, we experimentally validate this so-called twin-supercoiled-domain model with in vitro real-time visualization at the single-molecule scale. Upon binding to the promoter site on a supercoiled DNA molecule, RNAP merges all DNA supercoils into one large pinned plectoneme with RNAP residing at its apex. Transcription by RNAP in real time demonstrates that up- and downstream supercoils are generated simultaneously and in equal portions, in agreement with the twin-supercoiled-domain model. Experiments carried out in the presence of RNases A and H, revealed that an additional viscous drag of the RNA transcript is not necessary for the RNAP to induce supercoils. The latter results contrast the current consensus and simulations on the origin of the twin-supercoiled domains, pointing at an additional mechanistic cause underlying supercoil generation by RNAP in transcription., BN/Bionanoscience, BN/Cees Dekker Lab
Published: 2024
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6. Dynamic ParB–DNA interactions initiate and maintain a partition condensate for bacterial chromosome segregation

Author: Tišma, M. (author), Janissen, R. (author), Antar, Hammam (author), Martin Gonzalez, A. (author), Barth, R. (author), Beekman, T.G.T. (author), van der Torre, J. (author), Michieletto, Davide (author), Gruber, Stephan (author), Dekker, C. (author), Tišma, M. (author), Janissen, R. (author), Antar, Hammam (author), Martin Gonzalez, A. (author), Barth, R. (author), Beekman, T.G.T. (author), van der Torre, J. (author), Michieletto, Davide (author), Gruber, Stephan (author), and Dekker, C. (author)
Abstract: In most bacteria, chromosome segregation is driven by the ParABS system where the CTPase protein ParB loads at the parS site to trigger the formation of a large partition complex. Here, we present in vitro studies of the partition complex for Bacillus subtilis ParB, using single-molecule fluorescence microscopy and AFM imaging to show that transient ParB–ParB bridges are essential for forming DNA condensates. Molecular Dynamics simulations confirm that condensation occurs abruptly at a critical concentration of ParB and show that multimerization is a prerequisite for forming the partition complex. Magnetic tweezer force spectroscopy on mutant ParB proteins demonstrates that CTP hydrolysis at the N-terminal domain is essential for DNA condensation. Finally, we show that transcribing RNA polymerases can steadily traverse the ParB–DNA partition complex. These findings uncover how ParB forms a stable yet dynamic partition complex for chromosome segregation that induces DNA condensation and segregation while enabling replication and transcription., BN/Cees Dekker Lab, BN/Bionanoscience
Published: 2023
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7. Looping the Genome with SMC Complexes

Author: Kim, Eugene (author), Barth, R. (author), Dekker, C. (author), Kim, Eugene (author), Barth, R. (author), and Dekker, C. (author)
Abstract: SMC (structural maintenance of chromosomes) protein complexes are an evolutionarily conserved family of motor proteins that hold sister chromatids together and fold genomes throughout the cell cycle by DNA loop extrusion. These complexes play a key role in a variety of functions in the packaging and regulation of chromosomes, and they have been intensely studied in recent years. Despite their importance, the detailed molecular mechanism for DNA loop extrusion by SMC complexes remains unresolved. Here, we describe the roles of SMCs in chromosome biology and particularly review in vitro single-molecule studies that have recently advanced our understanding of SMC proteins. We describe the mechanistic biophysical aspects of loop extrusion that govern genome organization and its consequences., BN/Cees Dekker Lab
Published: 2023
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8. Testing pseudotopological and nontopological models for SMC-driven DNA loop extrusion against roadblock-traversal experiments

Author: Barth, R. (author), Pradhan, B. (author), Kim, E. (author), Davidson, Iain F. (author), van der Torre, J. (author), Peters, Jan Michael (author), Dekker, C. (author), Barth, R. (author), Pradhan, B. (author), Kim, E. (author), Davidson, Iain F. (author), van der Torre, J. (author), Peters, Jan Michael (author), and Dekker, C. (author)
Abstract: DNA loop extrusion by structural-maintenance-of-chromosome (SMC) complexes has emerged as a primary organizing principle for chromosomes. The mechanism by which SMC motor proteins extrude DNA loops is still unresolved and much debated. The ring-like structure of SMC complexes prompted multiple models where the extruded DNA is topologically or pseudotopologically entrapped within the ring during loop extrusion. However, recent experiments showed the passage of roadblocks much bigger than the SMC ring size, suggesting a nontopological mechanism. Recently, attempts were made to reconcile the observed passage of large roadblocks with a pseudotopological mechanism. Here we examine the predictions of these pseudotopological models and find that they are not consistent with new experimental data on SMC roadblock encounters. Particularly, these models predict the formation of two loops and that roadblocks will reside near the stem of the loop upon encounter—both in contrast to experimental observations. Overall, the experimental data reinforce the notion of a nontopological mechanism for extrusion of DNA., BN/Cees Dekker Lab
Published: 2023
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9. Author Correction: Testing pseudotopological and nontopological models for SMC-driven DNA loop extrusion against roadblock-traversal experiments (Scientific Reports, (2023), 13, 1, (8100), 10.1038/s41598-023-35359-2)

Author: Barth, R. (author), Pradhan, B. (author), Kim, E. (author), Davidson, Iain F. (author), van der Torre, J. (author), Peters, Jan‑Michael ‑M (author), Dekker, C. (author), Barth, R. (author), Pradhan, B. (author), Kim, E. (author), Davidson, Iain F. (author), van der Torre, J. (author), Peters, Jan‑Michael ‑M (author), and Dekker, C. (author)
Abstract: Correction to: Scientific Reports, published online 19 May 2023 The original version of this Article contained an error in Figure 1b-1, where the fore- and background order of the strands “DNA” (in black) and “Brn1 Kleisin” (in green), were switched. The original Figure 1 and accompanying legend appear below. (Figure presented.) Description of the mechanism postulated by Shaltiel et al. for roadblock passage into an extruded loop on the DNA and a potential nontopological model. (a) The steps through the proposed DNA loop extrusion cycle are commented in more detail in steps 1–6 within the figure. Adapted from Ref.11. (b) Potential nontopological model which is closely analogous to the pseudotopological model, but with a slight variation in the DNA-SMC topology which allows particle bypass. The original Article has been corrected., author correction DOI 10.1038/s41598-023-35359-2, BN/Cees Dekker Lab
Published: 2023
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10. CTCF is a DNA-tension-dependent barrier to cohesin-mediated loop extrusion

Author: Davidson, Iain F. (author), Barth, R. (author), Zaczek, Maciej (author), van der Torre, J. (author), Tang, Wen (author), Nagasaka, Kota (author), Janissen, R. (author), Kerssemakers, J.W.J. (author), Wutz, Gordana (author), Dekker, C. (author), Peters, Jan Michael (author), Davidson, Iain F. (author), Barth, R. (author), Zaczek, Maciej (author), van der Torre, J. (author), Tang, Wen (author), Nagasaka, Kota (author), Janissen, R. (author), Kerssemakers, J.W.J. (author), Wutz, Gordana (author), Dekker, C. (author), and Peters, Jan Michael (author)
Abstract: In eukaryotes, genomic DNA is extruded into loops by cohesin1. By restraining this process, the DNA-binding protein CCCTC-binding factor (CTCF) generates topologically associating domains (TADs)2,3 that have important roles in gene regulation and recombination during development and disease1,4–7. How CTCF establishes TAD boundaries and to what extent these are permeable to cohesin is unclear8. Here, to address these questions, we visualize interactions of single CTCF and cohesin molecules on DNA in vitro. We show that CTCF is sufficient to block diffusing cohesin, possibly reflecting how cohesive cohesin accumulates at TAD boundaries, and is also sufficient to block loop-extruding cohesin, reflecting how CTCF establishes TAD boundaries. CTCF functions asymmetrically, as predicted; however, CTCF is dependent on DNA tension. Moreover, CTCF regulates cohesin’s loop-extrusion activity by changing its direction and by inducing loop shrinkage. Our data indicate that CTCF is not, as previously assumed, simply a barrier to cohesin-mediated loop extrusion but is an active regulator of this process, whereby the permeability of TAD boundaries can be modulated by DNA tension. These results reveal mechanistic principles of how CTCF controls loop extrusion and genome architecture., BN/Cees Dekker Lab, BN/Bionanoscience
Published: 2023
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11. Dynamin A as a one-component division machinery for synthetic cells

Author: De Franceschi, N. (author), Barth, R. (author), Meindlhumer, S. (author), Fragasso, A. (author), Dekker, C. (author), De Franceschi, N. (author), Barth, R. (author), Meindlhumer, S. (author), Fragasso, A. (author), and Dekker, C. (author)
Abstract: Membrane abscission, the final cut of the last connection between emerging daughter cells, is an indispensable event in the last stage of cell division and in other cellular processes such as endocytosis, virus release or bacterial sporulation. However, its mechanism remains poorly understood, impeding its application as a cell-division machinery for synthetic cells. Here we use fluorescence microscopy and fluorescence recovery after photobleaching measurements to study the in vitro reconstitution of the bacterial protein dynamin A inside liposomes. Upon external reshaping of the liposomes into dumbbells, dynamin A self-assembles at the membrane neck, resulting in membrane hemi-scission and even full scission. Dynamin A proteins constitute a simple one-component division machinery capable of splitting dumbbell-shaped liposomes, marking an important step towards building a synthetic cell., Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., BN/Cees Dekker Lab
Published: 2023
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12. A highly virulent variant of HIV-1 circulating in the Netherlands

Author: Wymant, Chris, Bezemer, Daniela, Blanquart, François, Ferretti, Luca, Gall, Astrid, Hall, Matthew, Golubchik, Tanya, Bakker, Margreet, Ong, Swee Hoe, Zhao, Lele, Bonsall, David, de Cesare, Mariateresa, MacIntyre-Cockett, George, Abeler-Dörner, Lucie, Albert, Jan, Bannert, Norbert, Fellay, Jacques, Grabowski, M Kate, Gunsenheimer-Bartmeyer, Barbara, Günthard, Huldrych F, Kivelä, Pia, Kouyos, Roger D, Laeyendecker, Oliver, Meyer, Laurence, Porter, Kholoud, Ristola, Matti, van Sighem, Ard, Berkhout, Ben, Kellam, Paul, Cornelissen, Marion, Reiss, Peter, Fraser, Christophe, Aubert, V, Battegay, M, Bernasconi, E, Böni, J, Braun, D L, Bucher, H C, Burton-Jeangros, C, Calmy, A, Cavassini, M, Dollenmaier, G, Egger, M, Elzi, L, Fehr, J, Fellay, J, Furrer, H, Fux, C A, Gorgievski, M, Günthard, H, Haerry, D, Hasse, B, Hirsch, H H, Hoffmann, M, Hösli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kouyos, R, Kovari, H, Ledergerber, B, Martinetti, G, de Tejada, B Martinez, Marzolini, C, Metzner, K, Müller, N, Nadal, D, Nicca, D, Pantaleo, G, Rauch, A, Regenass, S, Rudin, C, Schöni-Affolter, F, Schmid, P, Speck, R, Stöckle, M, Tarr, P, Trkola, A, Vernazza, P, Weber, R, Yerly, S, van der Valk, M, Geerlings, S E, Goorhuis, A, Hovius, J W, Lempkes, B, Nellen, F J B, van der Poll, T, Prins, J M, Reiss, P, van Vugt, M, Wiersinga, W J, Wit, F W M N, van Duinen, M, van Eden, J, Hazenberg, A, van Hes, A M H, Pijnappel, F J J, Smalhout, S Y, Weijsenfeld, A M, Jurriaans, S, Back, N K T, Zaaijer, H L, Berkhout, B, Cornelissen, M T E, Schinkel, C J, Wolthers, K C, Peters, E J G, van Agtmael, M A, Autar, R S, Bomers, M, Sigaloff, K C E, Heitmuller, M, Laan, L M, Ang, C W, van Houdt, R, Jonges, M, Kuijpers, T W, Pajkrt, D, Scherpbier, H J, de Boer, C, van der Plas, A, van den Berge, M, Stegeman, A, Baas, S, Hage de Looff, L, Buiting, A, Reuwer, A, Veenemans, J, Wintermans, B, Pronk, M J H, Ammerlaan, H S M, van den Bersselaar, D N J, de Munnik, E S, Deiman, B, Jansz, A R, Scharnhorst, V, Tjhie, J, Wegdam, M C A, van Eeden, A, Nellen, J, Brokking, W, Elsenburg, L J M, Nobel, H, van Kasteren, M E E, Berrevoets, M A H, Brouwer, A E, Adams, A, van Erve, R, de Kruijf-van de Wiel, B A F M, Keelan-Phaf, S, van der Ven, B, Buiting, A G M, Murck, J L, de Vries-Sluijs, T E M S, Bax, H I, van Gorp, E C M, de Jong-Peltenburg, N C, de Mendonç A Melo, M, van Nood, E, Nouwen, J L, Rijnders, B J A, Rokx, C, Schurink, C A M, Slobbe, L, Verbon, A, Bassant, N, van Beek, J E A, Vriesde, M, van Zonneveld, L M, de Groot, J, Boucher, C A B, Koopmans, M P G, van Kampen, J J A, Fraaij, P L A, van Rossum, A M C, Vermont, C L, van der Knaap, L C, Visser, E, Branger, J, Douma, R A, Cents-Bosma, A S, Duijf-van de Ven, C J H M, Schippers, E F, van Nieuwkoop, C, van Ijperen, J M, Geilings, J, van der Hut, G, van Burgel, N D, Leyten, E M S, Gelinck, L B S, Mollema, F, Davids-Veldhuis, S, Tearno, C, Wildenbeest, G S, Heikens, E, Groeneveld, P H P, Bouwhuis, J W, Lammers, A J J, Kraan, S, van Hulzen, A G W, Kruiper, M S M, van der Bliek, G L, Bor, P C J, Debast, S B, Wagenvoort, G H J, Kroon, F P, de Boer, M G J, Jolink, H, Lambregts, M M C, Roukens, A H E, Scheper, H, Dorama, W, van Holten, N, Claas, E C J, Wessels, E, den Hollander, J G, El Moussaoui, R, Pogany, K, Smit, J V, Struik-Kalkman, D, van Niekerk, T, Pontesilli, O, Lowe, S H, Oude Lashof, A M L, Posthouwer, D, van Wolfswinkel, M E, Ackens, R P, Burgers, K, Schippers, J, Weijenberg-Maes, B, van Loo, I H M, Havenith, T R A, van Vonderen, M G A, Kampschreur, L M, Faber, S, Steeman-Bouma, R, Al Moujahid, A, Kootstra, G J, Delsing, C E, van der Burg-van de Plas, M, Scheiberlich, L, Kortmann, W, van Twillert, G, Renckens, R, Ruiter-Pronk, D, van Truijen-Oud, F A, Cohen Stuart, J W T, Jansen, E R, Hoogewerf, M, Rozemeijer, W, van der Reijden, W A, Sinnige, J C, Brinkman, K, van den Berk, G E L, Blok, W L, Lettinga, K D, de Regt, M, Schouten, W E M, Stalenhoef, J E, Veenstra, J, Vrouenraets, S M E, Blaauw, H, Geerders, G F, Kleene, M J, Kok, M, Knapen, M, van der Meché, I B, Mulder-Seeleman, E, Toonen, A J M, Wijnands, S, Wttewaal, E, Kwa, D, van Crevel, R, van Aerde, K, Dofferhoff, A S M, Henriet, S S V, Ter Hofstede, H J M, Hoogerwerf, J, Keuter, M, Richel, O, Albers, M, Grintjes-Huisman, K J T, de Haan, M, Marneef, M, Strik-Albers, R, Rahamat-Langendoen, J, Stelma, F F, Burger, D, Gisolf, E H, Hassing, R J, Claassen, M, Ter Beest, G, van Bentum, P H M, Langebeek, N, Tiemessen, R, Swanink, C M A, van Lelyveld, S F L, Soetekouw, R, van der Prijt, L M M, van der Swaluw, J, Bermon, N, Jansen, R, Herpers, B L, Veenendaal, D, Verhagen, D W M, Lauw, F N, van Broekhuizen, M C, van Wijk, M, Bierman, W F W, Bakker, M, Kleinnijenhuis, J, Kloeze, E, Middel, A, Postma, D F, Schölvinck, E H, Stienstra, Y, Verhage, A R, Wouthuyzen-Bakker, M, Boonstra, A, de Groot-de Jonge, H, van der Meulen, P A, de Weerd, D A, Niesters, H G M, van Leer-Buter, C C, Knoester, M, Hoepelman, A I M, Arends, J E, Barth, R 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Chiarello, Pierre, Godinot, Mathieu, Brunel-Dalmas, Florence, Gibert, Sylvie, Trepo, Christian, Peyramond, Dominique, Miailhes, Patrick, Koffi, Joseph, Thoirain, Valérie, Brochier, Corinne, Baudry, Thomas, Pailhes, Sylvie, Lafeuillade, Alain, Philip, Gisèle, Hittinger, Gilles, Assi, Assi, Lambry, Véronique, Rosenthal, Eric, Naqvi, Alissa, Dunais, Brigitte, Cua, Eric, Pradier, Christian, Durant, Jacques, Joulie, Aline, Quinsat, Denis, Tempesta, Serge, Ravaux, Isabelle, Martin, Isabelle Poizot, Faucher, Olivia, Cloarec, Nicolas, Champagne, Hélène, Pichancourt, Gilles, Morlat, Philippe, Pistone, Thierry, Bonnet, Fabrice, Mercie, Patrick, Faure, Isabelle, Hessamfar, Mojgan, Malvy, Denis, Lacoste, Denis, Pertusa, Marie-Carmen, Vandenhende, Marie-Anne, Bernard, Noëlle, Paccalin, François, Martell, Cédric, Roger-Schmelz, Julien, Receveur, Marie-Catherine, Duffau, Pierre, Dondia, Denis, Ribeiro, Emmanuel, Caltado, Sabrina, Neau, Didier, Dupont, Michel, Dutronc, Hervé, Dauchy, Frédéric, Cazanave, Charles, Vareil, Marc-Olivier, Wirth, Gaétane, Le Puil, Séverine, Pellegrin, Jean-Luc, Raymond, Isabelle, Viallard, Jean-François, Chaigne de Lalande, Severin, Garipuy, Daniel, Delobel, Pierre, Obadia, Martine, Cuzin, Lise, Alvarez, Muriel, Biezunski, Noemie, Porte, Lydie, Massip, Patrice, Debard, Alexa, Balsarin, Florence, Lagarrigue, Myriam, Prevoteau du Clary, François, Aquilina, Christian, Reynes, Jacques, Baillat, Vincent, Merle, Corinne, Lemoing, Vincent, Atoui, Nadine, Makinson, Alain, Jacquet, Jean Marc, Psomas, Christina, Tramoni, Christine, Aumaitre, Hugues, Saada, Mathieu, Medus, Marie, Malet, Martine, Eden, Aurélia, Neuville, Ségolène, Ferreyra, Milagros, Sotto, Albert, Barbuat, Claudine, Rouanet, Isabelle, Leureillard, Didier, Mauboussin, Jean-Marc, Lechiche, Catherine, Donsesco, Régine, Cabie, André, Abel, Sylvie, Pierre-Francois, Sandrine, Batala, Anne-Sophie, Cerland, Christophe, Rangom, Camille, Theresine, Nadine, Hoen, Bruno, Lamaury, Isabelle, Fabre, Isabelle, Schepers, Kinda, Curlier, Elodie, Ouissa, Rachida, Gaud, Catherine, Ricaud, Carole, Rodet, Roland, Wartel, Guillaume, Sautron, Carmele, Beck-Wirth, Geneviève, Michel, Catherine, Beck, Charles, Halna, Jean-Michel, Kowalczyk, Jakub, Benomar, Meryem, Drobacheff-Thiebaut, Christine, Chirouze, Catherine, Faucher, Jean-François, Parcelier, François, Foltzer, Adeline, Haffner-Mauvais, Cécile, Hustache Mathieu, Mathieu, Proust, Aurélie, Piroth, Lionel, Chavanet, Pascal, Duong, Michel, Buisson, Marielle, Waldner, Anne, Mahy, Sophie, Gohier, Sandrine, Croisier, Delphine, May, Thierry, Delestan, Mikael, Andre, Marie, Zadeh, Mahsa Mohseni, Martinot, Martin, Rosolen, Béatrice, Pachart, Anne, Martha, Benoît, Jeunet, Noëlle, Rey, David, Cheneau, Christine, Partisani, Maria, Priester, Michèle, Bernard-Henry, Claudine, Batard, Marie-Laure, Fischer, Patricia, Berger, Jean-Luc, Kmiec, Isabelle, Robineau, Olivier, Huleux, Thomas, Ajana, Faïza, Alcaraz, Isabelle, Allienne, Christophe, Baclet, Véronique, Meybeck, Agnès, Valette, Michel, Viget, Nathalie, Aissi, Emmanuelle, Biekre, Raphael, Cornavin, Pauline, Merrien, Dominique, Seghezzi, Jean-Christophe, Machado, Moise, Diab, Georges, Raffi, François, Bonnet, Bénédicte, Allavena, Clotilde, Grossi, Olivier, Reliquet, Véronique, Billaud, Eric, Brunet, Cecile, Bouchez, Sabelline, Morineau-Le Houssine, Pascale, Sauser, Fabienne, Boutoille, David, Besnier, Michel, Hue, Hervé, Hall, Nolwenn, Brosseau, Delphine, Souala, Faouzi, Michelet, Christian, Tattevin, Pierre, Arvieux, Cédric, Revest, Matthieu, Leroy, Helene, Chapplain, Jean-Marc, Dupont, Matthieu, Fily, Fabien, Patra-Delo, Solène, Lefeuvre, Céline, Bernard, Louis, Bastides, Frédéric, Nau, Pascale, Verdon, Renaud, de la Blanchardiere, Arnaud, Martin, Anne, Feret, Philippe, Geffray, Loïk, Daniel, Corinne, Rohan, Jennifer, Fialaire, Pascale, Chennebault, Jean Marie, Rabier, Valérie, Abgueguen, Pierre, Rehaiem, Sami, Luycx, Odile, Niault, Mathilde, Moreau, Philippe, Poinsignon, Yves, Goussef, Marie, Mouton-Rioux, Virginie, Houlbert, Dominique, Alvarez-Huve, Sandrine, Barbe, Frédérique, Haret, Sophie, Perre, Philippe, Leantez-Nainville, Sophie, Esnault, Jean-Luc, Guimard, Thomas, Suaud, Isabelle, Girard, Jean-Jacques, Simonet, Véronique, Debab, Yasmine, Schmit, Jean-Luc, Jacomet, Christine, Weinberck, Pierre, Genet, Claire, Pinet, Pauline, Ducroix, Sophie, Durox, Hélène, Denes, Éric, Abraham, Bruno, Gourdon, Florence, Antoniotti, Odile, Molina, Jean-Michel, Ferret, Samuel, Lascoux-Combe, Caroline, Lafaurie, Matthieu, Colin de Verdiere, Nathalie, Ponscarme, Diane, De Castro, Nathalie, Aslan, Alexandre, Rozenbaum, Willy, Pintado, Claire, Clavel, François, Taulera, Olivier, Gatey, Caroline, Munier, Anne-Lise, Gazaigne, Sandrine, Penot, Pauline, Conort, Guillaume, Lerolle, Nathalie, Leplatois, Anne, Balausine, Stéphanie, Delgado, Jeannine, Timsit, Julie, Tabet, Magda, Gerard, Laurence, Girard, Pierre-Marie, Picard, Odile, Tredup, Jürgen, Bollens, Diane, Valin, Nadia, Campa, Pauline, Bottero, Julie, Lefebvre, Benedicte, Tourneur, Muriel, Fonquernie, Laurent, Wemmert, Charlotte, Lagneau, Jean-Luc, Yazdanpanah, Yazdan, Phung, Bao, Pinto, Adriana, Vallois, Dorothée, Cabras, Ornella, Louni, Françoise, Pialoux, Gilles, Lyavanc, Thomas, Berrebi, Valérie, Chas, Julie, Lenagat, Sophie, Rami, Agathe, Diemer, Myriam, Parrinello, Maguy, Depond, Audrey, Salmon, Dominique, Guillevin, Loïc, Tahi, Tassadit, Belarbi, Linda, Loulergue, Pierre, Zak Dit Zbar, Olivier, Launay, Odile, Silbermann, Benjamin, Leport, Catherine, Alagna, Laura, Pietri, Marie-Pierre, Simon, Anne, Bonmarchand, Manuela, Amirat, Naouel, Pichon, François, Kirstetter, Myriam, Katlama, Christine, Valantin, Marc Antoine, Tubiana, Roland, Caby, Fabienne, Schneider, Luminita, Ktorza, Nadine, Calin, Ruxandra, Merlet, Audrey, Ben Abdallah, Saadia, Weiss, Laurence, Buisson, Martin, Batisse, Dominique, Karmochine, Marina, Pavie, Juliette, Minozzi, Catherine, Jayle, Didier, Castel, Philippe, Derouineau, Jean, Kousignan, Pascale, Eliazevitch, Murielle, Pierre, Isabelle, Collias, Lio, Viard, Jean-Paul, Gilquin, Jacques, Sobel, Alain, Slama, Laurence, Ghosn, Jade, Hadacek, Blanka, Thu-Huyn, Nugyen, Nait-Ighil, Lella, Cros, Agnes, Maignan, Aline, Duvivier, Claudine, Consigny, Paul Henri, Lanternier, Fanny, Shoai-Tehrani, Michka, Touam, Fatima, Jerbi, Saadia, Bodard, Loïc, Jung, Corinne, Goujard, Cécile, Quertainmont, Yann, Duracinsky, Martin, Segeral, Olivier, Blanc, Arnaud, Peretti, Delphine, Cheret, Antoine, Chantalat, Christelle, Dulucq, Marie Josée, Levy, Yves, Lelievre, Jean Daniel, Lascaux, Anne Sophie, Dumont, Cécile, Boue, François, Chambrin, Véronique, Abgrall, Sophie, Kansau, Imad, Raho-Moussa, Mariem, De Truchis, Pierre, Dinh, Aurélien, Davido, Benjamin, Marigot, Dhiba, Berthe, Huguette, Devidas, Alain, Chevojon, Pierre, Chabrol, Amélie, Agher, Nouara, Lemercier, Yvon, Chaix, Fabrice, Turpault, Isabelle, Bouchaud, Olivier, Honore, Patricia, Rouveix, Elisabeth, Reimann, Evelyne, Belan, Alix Greder, Godin Collet, Claire, Souak, Safia, Mortier, Emmanuel, Bloch, Martine, Simonpoli, Anne-Marie, Manceron, Véronique, Cahitte, Isabelle, Hiraux, Emmanuel, Lafon, Erik, Cordonnier, François, Zeng, Ai-Feng, Zucman, David, Majerholc, Catherine, Bornarel, Dominique, Uludag, Agnès, Gellen-Dautremer, Justine, Lefort, Agnès, Bazin, Christine, Daneluzzi, Vincent, Gerbe, Juliette, Jeantils, Vincent, Coupard, Mélissa, Patey, Olivier, Bantsimba, Jonas, Delllion, Sophie, Paz, Pauline Caraux, Cazenave, Benoit, Richier, Laurent, Garrait, Valérie, Delacroix, Isabelle, Elharrar, Brigitte, Vittecoq, Daniel, Bolliot, Claudine, Lepretre, Annie, Genet, Philippe, Masse, Virginie, Perrone, Véronique, Boussard, Jean-Luc, Chardon, Patricia, Froguel, Eric, Simon, Philippe, Tassi, Sylvie, Avettand Fenoel, Véronique, Barin, Francis, Bourgeois, Christine, Cardon, Fanny, Chaix, Marie-Laure, Delfraissy, Jean François, Essat, Asma, Fischer, Hugues, Lecuroux, Camille, Petrov-Sanchez, Ventzislava, Rouzioux, Christine, Saez-Cirion, Asier, Seng, Rémonie, Kuldanek, Kristin, Mullaney, Scott, Young, Carmel, Zucchetti, Antonella, Bevan, Margaret-Ann, McKernan, Sinead, Wandolo, Emily, Richardson, Celia, Youssef, Elaney, Green, Pippa, Faulkner, Sue, Faville, Rebecca, Herman, Sandra, Care, Christine, Blackman, Helen, Bellenger, Katharine, Fairbrother, Keith, Phillips, Andrew, Babiker, Abdel, Delpech, Valerie, Fidler, S, Clarke, Mindy, Fox, Julie, Gilson, R, Goldberg, David, Hawkins, David, Johnson, Anne, Johnson, Margaret, McLean, Ken, Nastouli, Eleni, Post, Frank, Kennedy, N, Pritchard, J, Andrady, U, Rajda, N, Donnelly, C, McKernan, S, Drake, S, Gilleran, G, White, D, Ross, J, Harding, J, Faville, R, Sweeney, J, Flegg, P, Toomer, S, Wilding, H, Woodward, R, Dean, G, Richardson, C, Perry, N, Gompels, M, Jennings, L, Bansaal, D, Browing, M, Connolly, L, Stanley, B, Estreich, S, Magdy, A, O'Mahony, C, Fraser, P, Jebakumar, S P R, David, L, Mette, R, Summerfield, H, Evans, M, White, C, Robertson, R, Lean, C, Morris, S, Winter, A, Faulkner, S, Goorney, B, Howard, L, Fairley, I, Stemp, C, Short, L, Gomez, M, Young, F, Roberts, M, Green, S, Sivakumar, K, Minton, J, Siminoni, A, Calderwood, J, Greenhough, D, DeSouza, C, Muthern, Lisa, Orkin, C, Murphy, S, Truvedi, M, McLean, K, Hawkins, D, Higgs, C, Moyes, A, Antonucci, S, McCormack, S, Lynn, W, Bevan, M, Fox, J, Teague, A, Anderson, J, Mguni, S, Post, F, Campbell, L, Mazhude, C, Russell, H, Carrick, G, Ainsworth, J, Waters, A, Byrne, P, Johnson, M, Kuldanek, K, Mullaney, S, Lawlor, V, Melville, R, Sukthankar, A, Thorpe, S, Murphy, C, Wilkins, E, Ahmad, S, Green, P, Tayal, S, Ong, E, Meaden, J, Riddell, L, Loay, D, Peacock, K, Blackman, H, Harindra, V, Saeed, A M, Allen, S, Natarajan, U, Williams, O, Lacey, H, Care, C, Bowman, C, Herman, S, Devendra, S V, Wither, J, Bridgwood, A, Singh, G, Bushby, S, Kellock, D, Young, S, Rooney, G, Snart, B, Currie, J, Fitzgerald, M, Arumainayyagam, J, Chandramani, S, Rajamanoharan, S, Robinson, T, Taylor, B, Brewer, C, Mayr, Christoph, Schmidt, Wolfgang, Speidel, Andrea, Strohbach, Frank, Arastéh, Keikawus, Cordes, Christiane, Stündel, Manfred, Claus, Jörg, Baumgarten, Axel, Carganico, Andreas, Ingiliz, Patrick, Dupke, Stephan, Freiwald, Matthias, Rausch, Michael, Moll, Arend, Schleehauf, Dorothea, Hintsche, Bettina, Klausen, Gerd, Jessen, Heiko, Jessen, Arne, Köppe, Siegfried, Kreckel, Peter, Schranz, Dietmar, Fischer, Klaus, Schulbin, Hubert, Speer, Miriam, Glaunsinger, Tobias, Wicke, Thomas, Bieniek, Bernhard, Hillenbrand, Heribert, Schlote, Frank, Lauenroth-Mai, Elke, Schuler, Christoph, Schürmann, Dirk, Wesselmann, Hans, Brockmeyer, Norbert, Gehring, Peter, Schmalöer, Dirk, Hower, Martin, Spornraft-Ragaller, Petra, Häussinger, Dieter, Reuter, Stefan, Esser, Stefan, Markus, Rudolf, Kreft, Burkhard, Berzow, Dirk, Christl, Andreas, Meyer, Andreas, Plettenberg, Andreas, Stoehr, Albrecht, Graefe, Katrin, Lorenzen, Thore, Adam, Axel, Schewe, Knut, Weitner, Lutwin, Fenske, Stefan, Hansen, Stefan, Stellbrink, Hans-Jürgen, Wiemer, Dorothea, Hertling, Sandra, Schmidt, Reinhold, Arbter, Peter, Claus, Bernd, Galle, Peter, Jäger, Hans, Jä Gel-Guedes, Eva, Postel, Nils, Fröschl, Monika, Spinner, Christoph, Bogner, Johannes, Salzberger, Bernd, Schölmerich, Jürgen, Audebert, Franz, Marquardt, Ties, Schaffert, Andreas, Schnaitmann, Eiko, Trein, Andreas, Frietsch, Bernhard, Müller, Marcus, Ulmer, Albrecht, Detering-Hübner, Barbara, Kern, Peter, Schubert, Franz, Dehn, Günther, Schreiber, Maria, Güler, Cengiz, Schmidt, Daniel, Meixenberger, Karolin, Medical Microbiology & Infectious Diseases, Internal Medicine, Virology, Pediatrics, Medical Microbiology and Infection Prevention, AII - Infectious diseases, Global Health, Infectious diseases, APH - Aging & Later Life, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Internal medicine, VU University medical center, Surgery, AMS - Rehabilitation & Development, APH - Quality of Care, Psychiatry, Pediatric surgery, Neurology, Public and occupational health, APH - Mental Health, Pathology, Cardiology, ACS - Heart failure & arrhythmias, Anesthesiology, IOO, Rehabilitation medicine, Obstetrics and gynaecology, General practice, Gastroenterology and hepatology, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Medical oncology laboratory, Hematology, Epidemiology and Data Science, Physiology, Microbes in Health and Disease (MHD), University of Oxford, Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Amsterdam UMC - Amsterdam University Medical Center, The Wellcome Trust Sanger Institute [Cambridge], Karolinska Institutet [Stockholm], Robert Koch Institute [Berlin] (RKI), Ecole Polytechnique Fédérale de Lausanne (EPFL), Johns Hopkins University (JHU), Universität Zürich [Zürich] = University of Zurich (UZH), Helsinki University Hospital [Helsinki, Finlande], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University College of London [London] (UCL), Kymab Ltd, Cambridge, England, Institut Pasteur [Paris] (IP), This study was funded by ERC Advanced Grant PBDR-339251 and a Li Ka Shing Foundation grant, both awarded to C.F. The ATHENA Cohort is managed by Stichting HIV Monitoring and supported by a grant from the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment., We thank K. Fransen and G. Vanham for help with the Belgian data, O. Ratmann for help in identifying the Dutch clusters, K. Kusejko for testing for additional VB individuals in the SHCS, B. Foley for help with genome sharing, B. Dearlove and L. Thomson for help with software, and J. Herbeck and three other reviewers for helpful suggestions., Contributors and affiliations are listed in the supplementary materials., Department of Medicine, University of Helsinki, Infektiosairauksien yksikkö, HUS Inflammation Center, and Clinicum
Subjects: Adult, Male, HIV-1/genetics, Genotype, Anti-HIV Agents, Evolution, [SDV]Life Sciences [q-bio], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], HIV Infections/drug therapy, selection, HIV Infections, Genome, Viral, heritability, epidemic, human-immunodeficiency-virus, Evolution, Molecular, SDG 3 - Good Health and Well-being, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Viral, Phylogeny, Netherlands, Multidisciplinary, Genome, model, Virulence, transmission, Molecular, setpoint viral load, reverse-transcriptase, dynamics, Viral Load, CD4 Lymphocyte Count, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], 3121 General medicine, internal medicine and other clinical medicine, Anti-HIV Agents/therapeutic use, Mutation, HIV-1, Female, progression
Abstract: Comment in Does HIV-1 virulence matter in the ART era? Lewitus E, Rolland M. Med (N Y). 2022 Apr 8;3(4):217-219. doi: 10.1016/j.medj.2022.03.003. PMID: 35590149; International audience; We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log 10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV—CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences—is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.
Published: 2022

13. ParB proteins can bypass DNA-bound roadblocks via dimer-dimer recruitment

Author: Tišma, M. (author), Panoukidou, Maria (author), Antar, Hammam (author), Soh, Young Min (author), Barth, R. (author), Pradhan, B. (author), Barth, A. (author), van der Torre, J. (author), Dekker, C. (author), Tišma, M. (author), Panoukidou, Maria (author), Antar, Hammam (author), Soh, Young Min (author), Barth, R. (author), Pradhan, B. (author), Barth, A. (author), van der Torre, J. (author), and Dekker, C. (author)
Abstract: The ParABS system is essential for prokaryotic chromosome segregation. After loading at parS on the genome, ParB (partition protein B) proteins rapidly redistribute to distances of ~15 kilobases from the loading site. It has remained puzzling how this large-distance spreading can occur along DNA loaded with hundreds of proteins. Using in vitro single-molecule fluorescence imaging, we show that ParB from Bacillus subtilis can load onto DNA distantly of parS, as loaded ParB molecules themselves are found to be able to recruit additional ParB proteins from bulk. Notably, this recruitment can occur in cis but also in trans, where, at low tensions within the DNA, newly recruited ParB can bypass roadblocks as it gets loaded to spatially proximal but genomically distant DNA regions. The data are supported by molecular dynamics simulations, which show that cooperative ParB-ParB recruitment can enhance spreading. ParS-independent recruitment explains how ParB can cover substantial genomic distance during chromosome segregation, which is vital for the bacterial cell cycle., BN/Cees Dekker Lab
Published: 2022
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14. SMC complexes can traverse physical roadblocks bigger than their ring size

Author: Pradhan, B. (author), Barth, R. (author), Kim, E. (author), van Laar, T. (author), Yang, W.W.W. (author), Ryu, J.K. (author), van der Torre, J. (author), Peters, Jan Michael (author), Dekker, C. (author), Pradhan, B. (author), Barth, R. (author), Kim, E. (author), van Laar, T. (author), Yang, W.W.W. (author), Ryu, J.K. (author), van der Torre, J. (author), Peters, Jan Michael (author), and Dekker, C. (author)
Abstract: Ring-shaped structural maintenance of chromosomes (SMC) complexes like condensin and cohesin extrude loops of DNA. It remains, however, unclear how they can extrude DNA loops in chromatin that is bound with proteins. Here, we use in vitro single-molecule visualization to show that nucleosomes, RNA polymerase, and dCas9 pose virtually no barrier to loop extrusion by yeast condensin. We find that even DNA-bound nanoparticles as large as 200 nm, much bigger than the SMC ring size, also translocate into DNA loops during extrusion by condensin and cohesin. This even occurs for a single-chain version of cohesin in which the ring-forming subunits are covalently linked and cannot open to entrap DNA. The data show that SMC-driven loop extrusion has surprisingly little difficulty in accommodating large roadblocks into the loop. The findings also show that the extruded DNA does not pass through the SMC ring (pseudo)topologically, hence pointing to a nontopological mechanism for DNA loop extrusion., BN/Cees Dekker Lab, BN/Bionanoscience, BN/Nynke Dekker Lab
Published: 2022
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15. Bureau voor Archeologie Rapport 927. Tuinbouwweg 1D, Haarsteeg, gemeente Heusden: een bureau- en inventariserend veldonderzoek in de vorm van boringen in de verkennende fase

Author: Barth, R. and Bureau voor Archeologie
Subjects: Archaeology
Published: 2022
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16. Bureau voor Archeologie Rapport 915. West-Vlisterdijk 8, Vlist, gemeente Krimpenerwaard: een bureau- en inventariserend veldonderzoek in de vorm van boringen in de verkennende en karterende fase

Author: Barth, R. and Bureau voor Archeologie
Subjects: Archaeology
Published: 2022
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17. CSi - a joint industry project into CPTUs in silty soils

Author: Augustesen, A.H., Carotenuto, Pasquale, Bilici, Cagdas, Lunne, Tom, Lindeboom, R.C.J., Krogh, L., van den Bosch, J., Barth, R., Erbrich, C., Ingarfield, S., Giretti, D., Fioravante, V., Dias, H., Sougle, M.-C., Barwise, A., de Wit, S., Burbury, D., and Adams, N.
Published: 2022

18. Bureau voor Archeologie Rapport 933. Carolus Simplexplein 3, Netersel, gemeente Bladel: een bureau- en inventariserend veldonderzoek in de vorm van boringen in de verkennende fase

Author: Barth, R. and Bureau voor Archeologie
Subjects: Archaeology
Published: 2022
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19. Book Review

Author: Barth, R.
Published: 2024
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20. Bureau voor Archeologie Rapport 931. Weijpoort en Weijland, Nieuwerbrug aan den Rijn, gemeente Bodegraven-Reeuwijk: een bureauonderzoek

Author: Barth, A., Barth, R., and R. Barth (Bureau voor Archeologie)
Subjects: Archaeology
Published: 2022
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21. Prostate cancer and solid organ transplantation: patient management and outcomes.

Author: Lazarovich A, Kristof TW, Steadman S, Dahmen AS, Josephson MA, Barth R, Morgan TM, Timsit MO, and Eggener S
Abstract: Objective: To analyse the management and outcomes of individuals diagnosed with prostate cancer either before or after organ transplantation, as the impact of organ transplantation and associated immunosuppression on the incidence, progression, and mortality of prostate cancer remains an area of substantial clinical interest and uncertainty., Patients and Methods: We conducted a retrospective analysis of patients from two tertiary care centres who had solid organ transplantation and were diagnosed with prostate cancer before or after organ transplantation. Data collected included demographics and clinical information., Results: The cohort consisted of 110 patients with a median (interquartile range [IQR]) age at prostate cancer diagnosis of 62 (56.6-67.2) years and a median (IQR) age at transplantation of 58.6 (52.7-65.3) years. Renal transplantation was the most common (54%). The median (IQR) prostate-specific antigen concentration at prostate cancer diagnosis was 6.2 (4.5-10) ng/mL, and the distribution of American Urological Association risk groups was: low risk, 36%; intermediate risk, 50%; and high risk, 14%. In all, 45 (41%) patients were diagnosed with prostate cancer prior to transplantation. Management included radical prostatectomy (RP; 62%), prostate radiotherapy (RT; 13%), and active surveillance (AS; 18%). During a median (IQR) follow-up of 5.8 (2.5-10) years from prostate cancer diagnosis, one (2%) patient developed metastatic disease. In all, 65 (59%) patients were diagnosed with prostate cancer subsequent to organ transplantation. Management included AS (29%), RT (45%), and RP (15%). During a median (IQR) follow-up of 5.3 (1-8.4) years, three patients (5%) developed metastatic disease. There were no deaths from prostate cancer., Conclusion: A diagnosis of localised prostate cancer should not preclude solid organ transplantation, and the presence of a transplant does not appear to substantially impact risk of prostate cancer progression., (© 2024 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)
Published: 2024
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22. Evaluation of a Ureteral Stent Removal Protocol in Adult Kidney Transplant Recipients.

Author: Krzos PM, Nguyen CT, Kane B, Krishnamoorthy S, Kristof TW, Reynolds LF, Pisano J, Josephson MA, Barth R, and Owen D
Abstract: Existing literature on best practices to reduce the risk of infectious complications associated with ureteral stent removal in kidney transplant recipients is limited. Prior to 2021, a formal process surrounding stent removal was not in place at our institution. In June 2021, a stent removal protocol was established. This protocol included the following: obtaining a preprocedure urine culture, prescribing universal culture-directed antimicrobial prophylaxis, earlier stent removal posttransplant, and patient education. We performed a retrospective quasi-experimental study of kidney transplant recipients who had their stents removed between July 2020 and June 2022. The primary outcome was the incidence of infectious complications within 30 days. Infectious complications were defined as urinary tract infection and bacteremia due to urinary source, as well as hospitalization, emergency department visit, or outpatient encounter for possible urinary tract infection. Secondary objectives included infectious and immunologic complications within 30 days to 1 year from transplant. During this study period, 239 adult kidney transplant recipients were included: 88 in the preprotocol group and 151 in the protocol group. The median time to stent removal was shorter in the protocol group (25 vs 36 days, P < .001). More patients in the protocol group received preprocedure antibiotics (99% vs 36%, P < .001). Infectious complications were higher in the preprotocol group (9% vs 3%, P = .035). Overall, the stent removal protocol was associated with fewer infectious complications (odds ratio, 0.18; 95% CI, 0.05-0.73). Further investigation is necessary to determine which individual interventions, if any, drive this benefit., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
Published: 2024
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23. Diagnostic yield of molecular diagnostics for the atypical pathogens: diagnostic stewardship is warranted.

Author: Rigter M, van Roeden SE, Barth R, and Wegdam-Blans M
Subjects: Humans, Molecular Diagnostic Techniques methods, Molecular Diagnostic Techniques standards
Published: 2024
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24. Genome-wide analysis of the biophysical properties of chromatin and nuclear proteins in living cells with Hi-D.

Author: Valades-Cruz CA, Barth R, Abdellah M, and Shaban HA
Abstract: To understand the dynamic nature of the genome, the localization and rearrangement of DNA and DNA-binding proteins must be analyzed across the entire nucleus of single living cells. Recently, we developed a computational light microscopy technique, called high-resolution diffusion (Hi-D) mapping, which can accurately detect, classify and map diffusion dynamics and biophysical parameters such as the diffusion constant, the anomalous exponent, drift velocity and model physical diffusion from the data at a high spatial resolution across the genome in living cells. Hi-D combines dense optical flow to detect and track local chromatin and nuclear protein motion genome-wide and Bayesian inference to characterize this local movement at nanoscale resolution. Here we present the Python implementation of Hi-D, with an option for parallelizing the calculations to run on multicore central processing units (CPUs). The functionality of Hi-D is presented to the users via user-friendly documented Python notebooks. Hi-D reduces the analysis time to less than 1 h using a multicore CPU with a single compute node. We also present different applications of Hi-D for live-imaging of DNA, histone H2B and RNA polymerase II sequences acquired with spinning disk confocal and super-resolution structured illumination microscopy., (© 2024. Springer Nature Limited.)
Published: 2024
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25. Single-molecule visualization of twin-supercoiled domains generated during transcription.

Author: Janissen R, Barth R, Polinder M, van der Torre J, and Dekker C
Subjects: DNA genetics, DNA-Directed RNA Polymerases genetics, DNA-Directed RNA Polymerases metabolism, RNA, DNA, Bacterial metabolism, DNA, Superhelical genetics, Transcription, Genetic
Abstract: Transcription-coupled supercoiling of DNA is a key factor in chromosome compaction and the regulation of genetic processes in all domains of life. It has become common knowledge that, during transcription, the DNA-dependent RNA polymerase (RNAP) induces positive supercoiling ahead of it (downstream) and negative supercoils in its wake (upstream), as rotation of RNAP around the DNA axis upon tracking its helical groove gets constrained due to drag on its RNA transcript. Here, we experimentally validate this so-called twin-supercoiled-domain model with in vitro real-time visualization at the single-molecule scale. Upon binding to the promoter site on a supercoiled DNA molecule, RNAP merges all DNA supercoils into one large pinned plectoneme with RNAP residing at its apex. Transcription by RNAP in real time demonstrates that up- and downstream supercoils are generated simultaneously and in equal portions, in agreement with the twin-supercoiled-domain model. Experiments carried out in the presence of RNases A and H, revealed that an additional viscous drag of the RNA transcript is not necessary for the RNAP to induce supercoils. The latter results contrast the current consensus and simulations on the origin of the twin-supercoiled domains, pointing at an additional mechanistic cause underlying supercoil generation by RNAP in transcription., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Published: 2024
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26. Dynamin A as a one-component division machinery for synthetic cells.

Author: De Franceschi N, Barth R, Meindlhumer S, Fragasso A, and Dekker C
Subjects: Liposomes, Dynamins metabolism, Endocytosis, Cell Division, Bacteria metabolism, Artificial Cells
Abstract: Membrane abscission, the final cut of the last connection between emerging daughter cells, is an indispensable event in the last stage of cell division and in other cellular processes such as endocytosis, virus release or bacterial sporulation. However, its mechanism remains poorly understood, impeding its application as a cell-division machinery for synthetic cells. Here we use fluorescence microscopy and fluorescence recovery after photobleaching measurements to study the in vitro reconstitution of the bacterial protein dynamin A inside liposomes. Upon external reshaping of the liposomes into dumbbells, dynamin A self-assembles at the membrane neck, resulting in membrane hemi-scission and even full scission. Dynamin A proteins constitute a simple one-component division machinery capable of splitting dumbbell-shaped liposomes, marking an important step towards building a synthetic cell., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Published: 2024
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27. Clinical Evaluation of a Quantitative Imaging Biomarker Supporting Radiological Assessment of Hippocampal Sclerosis.

Author: Rebsamen M, Jin BZ, Klail T, De Beukelaer S, Barth R, Rezny-Kasprzak B, Ahmadli U, Vulliemoz S, Seeck M, Schindler K, Wiest R, Radojewski P, and Rummel C
Subjects: Humans, Hippocampus diagnostic imaging, Hippocampus pathology, Sclerosis diagnostic imaging, Sclerosis pathology, Magnetic Resonance Imaging methods, Biomarkers, Epilepsy, Temporal Lobe diagnostic imaging, Epilepsy, Temporal Lobe pathology, Hippocampal Sclerosis, Epilepsy pathology
Abstract: Objective: To evaluate the influence of quantitative reports (QReports) on the radiological assessment of hippocampal sclerosis (HS) from MRI of patients with epilepsy in a setting mimicking clinical reality., Methods: The study included 40 patients with epilepsy, among them 20 with structural abnormalities in the mesial temporal lobe (13 with HS). Six raters blinded to the diagnosis assessed the 3T MRI in two rounds, first using MRI only and later with both MRI and the QReport. Results were evaluated using inter-rater agreement (Fleiss' kappa [Formula: see text]) and comparison with a consensus of two radiological experts derived from clinical and imaging data, including 7T MRI., Results: For the primary outcome, diagnosis of HS, the mean accuracy of the raters improved from 77.5% with MRI only to 86.3% with the additional QReport (effect size [Formula: see text]). Inter-rater agreement increased from [Formula: see text] to [Formula: see text]. Five of the six raters reached higher accuracies, and all reported higher confidence when using the QReports., Conclusion: In this pre-use clinical evaluation study, we demonstrated clinical feasibility and usefulness as well as the potential impact of a previously suggested imaging biomarker for radiological assessment of HS., (© 2023. The Author(s).)
Published: 2023
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28. Dynamic ParB-DNA interactions initiate and maintain a partition condensate for bacterial chromosome segregation.

Author: Tišma M, Janissen R, Antar H, Martin-Gonzalez A, Barth R, Beekman T, van der Torre J, Michieletto D, Gruber S, and Dekker C
Subjects: Bacteria genetics, Bacterial Proteins metabolism, Chromosome Segregation, DNA, Bacterial metabolism, Chromosomes, Bacterial metabolism
Abstract: In most bacteria, chromosome segregation is driven by the ParABS system where the CTPase protein ParB loads at the parS site to trigger the formation of a large partition complex. Here, we present in vitro studies of the partition complex for Bacillus subtilis ParB, using single-molecule fluorescence microscopy and AFM imaging to show that transient ParB-ParB bridges are essential for forming DNA condensates. Molecular Dynamics simulations confirm that condensation occurs abruptly at a critical concentration of ParB and show that multimerization is a prerequisite for forming the partition complex. Magnetic tweezer force spectroscopy on mutant ParB proteins demonstrates that CTP hydrolysis at the N-terminal domain is essential for DNA condensation. Finally, we show that transcribing RNA polymerases can steadily traverse the ParB-DNA partition complex. These findings uncover how ParB forms a stable yet dynamic partition complex for chromosome segregation that induces DNA condensation and segregation while enabling replication and transcription., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Published: 2023
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29. Normothermic Machine Perfusion of Donor Livers for Transplantation in the United States: A Randomized Controlled Trial.

Author: Chapman WC, Barbas AS, D'Alessandro AM, Vianna R, Kubal CA, Abt P, Sonnenday C, Barth R, Alvarez-Casas J, Yersiz H, Eckhoff D, Cannon R, Genyk Y, Sher L, Singer A, Feng S, Roll G, Cohen A, Doyle MB, Sudan DL, Al-Adra D, Khan A, Subramanian V, Abraham N, Olthoff K, Tekin A, Berg L, Coussios C, Morris C, Randle L, Friend P, and Knechtle SJ
Abstract: Objective: To compare conventional low-temperature storage of transplant donor livers [static cold storage (SCS)] with storage of the organs at physiological body temperature [normothermic machine perfusion (NMP)]., Background: The high success rate of liver transplantation is constrained by the shortage of transplantable organs (eg, waiting list mortality >20% in many centers). NMP maintains the liver in a functioning state to improve preservation quality and enable testing of the organ before transplantation. This is of greatest potential value with organs from brain-dead donor organs (DBD) with risk factors (age and comorbidities), and those from donors declared dead by cardiovascular criteria (donation after circulatory death)., Methods: Three hundred eighty-three donor organs were randomized by 15 US liver transplant centers to undergo NMP (n = 192) or SCS (n = 191). Two hundred sixty-six donor livers proceeded to transplantation (NMP: n = 136; SCS: n = 130). The primary endpoint of the study was "early allograft dysfunction" (EAD), a marker of early posttransplant liver injury and function., Results: The difference in the incidence of EAD did not achieve significance, with 20.6% (NMP) versus 23.7% (SCS). Using exploratory, "as-treated" rather than "intent-to-treat," subgroup analyses, there was a greater effect size in donation after circulatory death donor livers (22.8% NMP vs 44.6% SCS) and in organs in the highest risk quartile by donor risk (19.2% NMP vs 33.3% SCS). The incidence of acute cardiovascular decompensation at organ reperfusion, "postreperfusion syndrome," as a secondary outcome was reduced in the NMP arm (5.9% vs 14.6%)., Conclusions: NMP did not lower EAD, perhaps related to the inclusion of lower-risk liver donors, as higher-risk donor livers seemed to benefit more. The technology is safe in standard organ recovery and seems to have the greatest benefit for marginal donors., Competing Interests: C.C., C.M., L.R., and P.F.: are employed by Organox. The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
Published: 2023
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30. Prenatal Diagnosis and Postnatal Management of a Fetal Pericardial Mass.

Author: Weigel N, Hintz S, Kaplinski M, Barth R, Balakrishnan K, Panelli D, Ma M, and Chitkara R
Subjects: Pregnancy, Female, Humans, Prenatal Care, Prenatal Diagnosis, Hydrops Fetalis diagnosis
Published: 2023
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31. Author Correction: Testing pseudotopological and nontopological models for SMC-driven DNA loop extrusion against roadblock-traversal experiments.

Author: Barth R, Pradhan B, Kim E, Davidson IF, van der Torre J, Peters JM, and Dekker C
Published: 2023
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32. Looping the Genome with SMC Complexes.

Author: Kim E, Barth R, and Dekker C
Subjects: Chromosomes genetics, Chromosomes metabolism, DNA metabolism, Cell Cycle Proteins genetics, Cell Cycle Proteins metabolism, Chromosomal Proteins, Non-Histone genetics, Chromosomal Proteins, Non-Histone metabolism, Multiprotein Complexes chemistry
Abstract: SMC (structural maintenance of chromosomes) protein complexes are an evolutionarily conserved family of motor proteins that hold sister chromatids together and fold genomes throughout the cell cycle by DNA loop extrusion. These complexes play a key role in a variety of functions in the packaging and regulation of chromosomes, and they have been intensely studied in recent years. Despite their importance, the detailed molecular mechanism for DNA loop extrusion by SMC complexes remains unresolved. Here, we describe the roles of SMCs in chromosome biology and particularly review in vitro single-molecule studies that have recently advanced our understanding of SMC proteins. We describe the mechanistic biophysical aspects of loop extrusion that govern genome organization and its consequences.
Published: 2023
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33. Testing pseudotopological and nontopological models for SMC-driven DNA loop extrusion against roadblock-traversal experiments.

Author: Barth R, Pradhan B, Kim E, Davidson IF, van der Torre J, Peters JM, and Dekker C
Subjects: Chromosomal Proteins, Non-Histone metabolism, DNA-Binding Proteins genetics, Bacterial Proteins metabolism, Cell Cycle Proteins metabolism, Chromosomes metabolism, DNA metabolism
Abstract: DNA loop extrusion by structural-maintenance-of-chromosome (SMC) complexes has emerged as a primary organizing principle for chromosomes. The mechanism by which SMC motor proteins extrude DNA loops is still unresolved and much debated. The ring-like structure of SMC complexes prompted multiple models where the extruded DNA is topologically or pseudotopologically entrapped within the ring during loop extrusion. However, recent experiments showed the passage of roadblocks much bigger than the SMC ring size, suggesting a nontopological mechanism. Recently, attempts were made to reconcile the observed passage of large roadblocks with a pseudotopological mechanism. Here we examine the predictions of these pseudotopological models and find that they are not consistent with new experimental data on SMC roadblock encounters. Particularly, these models predict the formation of two loops and that roadblocks will reside near the stem of the loop upon encounter-both in contrast to experimental observations. Overall, the experimental data reinforce the notion of a nontopological mechanism for extrusion of DNA., (© 2023. The Author(s).)
Published: 2023
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34. [Functional Neurological Disorders - A Common but Often Unrecognized Diagnosis].

Author: Barth R and Gegusch M
Subjects: Humans, Conversion Disorder diagnosis, Conversion Disorder psychology, Conversion Disorder therapy, Nervous System Diseases
Abstract: Functional Neurological Disorders - A Common but Often Unrecognized Diagnosis Abstract: Functional neurological disorders are frequent and diverse in the clinical presentation. Psychological factors are part of the development and perpetuation of symptoms; psychiatric comorbidities may be present, but are not an obligatory diagnostic criterion. The diagnosis is primarily made on the basis of anamnesis and positive clinical signs. The commonness and reversibility of the symptoms should be emphasised in the clinical consultation, and the positive clinical signs should be demonstrated. Science-based explanations as well as the bio-psycho-social model can help patients to understand their diagnosis, which is relevant for a successful therapeutic outcome. It is recommended to use the neutral and descriptive term "functional neurological disorder". Treatment of the potentially reversible disease will be interdisciplinary and multimodal.
Published: 2023
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35. CTCF is a DNA-tension-dependent barrier to cohesin-mediated loop extrusion.

Author: Davidson IF, Barth R, Zaczek M, van der Torre J, Tang W, Nagasaka K, Janissen R, Kerssemakers J, Wutz G, Dekker C, and Peters JM
Subjects: Chromatin chemistry, Chromatin genetics, Chromatin metabolism, In Vitro Techniques, Cohesins, CCCTC-Binding Factor metabolism, Cell Cycle Proteins metabolism, Chromosomal Proteins, Non-Histone metabolism, DNA chemistry, DNA metabolism
Abstract: In eukaryotes, genomic DNA is extruded into loops by cohesin 1 . By restraining this process, the DNA-binding protein CCCTC-binding factor (CTCF) generates topologically associating domains (TADs) 2,3 that have important roles in gene regulation and recombination during development and disease 1,4-7 . How CTCF establishes TAD boundaries and to what extent these are permeable to cohesin is unclear 8 . Here, to address these questions, we visualize interactions of single CTCF and cohesin molecules on DNA in vitro. We show that CTCF is sufficient to block diffusing cohesin, possibly reflecting how cohesive cohesin accumulates at TAD boundaries, and is also sufficient to block loop-extruding cohesin, reflecting how CTCF establishes TAD boundaries. CTCF functions asymmetrically, as predicted; however, CTCF is dependent on DNA tension. Moreover, CTCF regulates cohesin's loop-extrusion activity by changing its direction and by inducing loop shrinkage. Our data indicate that CTCF is not, as previously assumed, simply a barrier to cohesin-mediated loop extrusion but is an active regulator of this process, whereby the permeability of TAD boundaries can be modulated by DNA tension. These results reveal mechanistic principles of how CTCF controls loop extrusion and genome architecture., (© 2023. The Author(s).)
Published: 2023
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36. Review Paper on Penetrating Brain Injury: Ethical Quandaries in the Trauma Bay and Beyond.

Author: Zakrison TL, Essig R, Polcari A, McKinley W, Arnold D, Beyene R, Wilson K, Rogers S Jr, Matthews JB, Millis JM, Angelos P, O'Connor M, Mansour A, Goldenberg F, Spiegel T, Horowitz P, Das P, Slidell M, Chokshi N, Okeke I, Barth R, Wilkins HE 3rd, Kass-Hout T, and Lazaridis C
Subjects: Humans, Child, Resuscitation methods, Neurosurgical Procedures, Head Injuries, Penetrating, Brain Injuries, Traumatic, Tissue and Organ Procurement
Abstract: Objective: The aim of this review was to review the ethical and multidisciplinary clinical challenges facing trauma surgeons when resuscitating patients presenting with penetrating brain injury (PBI) and multicavitary trauma., Background: While there is a significant gap in the literature on managing PBI in patients presenting with multisystem trauma, recent data demonstrate that resuscitation and prognostic features for such patients remains poorly described, with trauma guidelines out of date in this field., Methods: We reviewed a combination of recent multidisciplinary evidence-informed guidelines for PBI and coupled this with expert opinion from trauma, neurosurgery, neurocritical care, pediatric and transplant surgery, surgical ethics and importantly our community partners., Results: Traditional prognostic signs utilized in traumatic brain injury may not be applicable to PBI with a multidisciplinary team approach suggested on a case-by-case basis. Even with no role for neurosurgical intervention, neurocritical care, and neurointerventional support may be warranted, in parallel to multicavitary operative intervention. Special considerations should be afforded for pediatric PBI. Ethical considerations center on providing the patient with the best chance of survival. Consideration of organ donation should be considered as part of the continuum of patient, proxy and family-centric support and care. Community input is crucial in guiding decision making or protocol establishment on an institutional level., Conclusions: Support of the patient after multicavitary PBI can be complex and is best addressed in a multidisciplinary fashion with extensive community involvement., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)
Published: 2023
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37. Persistence of long-term insulin independence after islet transplantation and two subsequent pregnancies.

Author: Gondek S, Ogledzinski M, Lin W, Milejczyk K, Juengel B, Potter L, Bachul PJ, Basto L, Perea L, Wang LJ, Tibudan M, Witkowska Z, Barth R, Fung J, and Witkowski P
Abstract: Pregnancy increases metabolic demand for insulin and may lead to the exhaustion of intraportally transplanted islets and post-gestational hyperglycemia. To prevent these complications, we implemented preemptive insulin supplementation during two subsequent pregnancies in an insulin-independent islet transplant recipient. This strategy resulted in optimal blood glucose control during the pregnancies, the preservation of the optimal islet graft function and the postpartum maintenance of long-term insulin independence., Competing Interests: Conflicts of Interest PW served as a consultant to the Dompe Farmaceutici regarding a liver transplantation study and received a grant/ funding to conduct two studies about islet transplantation. The remaining authors declare no conflict of interest.
Published: 2023
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38. Spatially coherent diffusion of human RNA Pol II depends on transcriptional state rather than chromatin motion.

Author: Barth R and Shaban HA
Subjects: Cell Nucleus metabolism, DNA, Humans, Transcription, Genetic, Chromatin, RNA Polymerase II genetics
Abstract: Gene transcription by RNA polymerase II (RNAPol II) is a tightly regulated process in the genomic, temporal, and spatial context. Recently, we have shown that chromatin exhibits spatially coherently moving regions over the entire nucleus, which is enhanced by transcription. Yet, it remains unclear how the mobility of RNA Pol II molecules is affected by transcription regulation and whether this response depends on the coordinated chromatin movement. We applied our Dense Flow reConstruction and Correlation method to analyze nucleus-wide coherent movements of RNA Pol II in living human cancer cells. We observe a spatially coherent movement of RNA Pol II molecules over ≈ 1 μm, which depends on transcriptional activity. Inducing transcription in quiescent cells decreased the coherent motion of RNA Pol II. We then quantify the spatial correlation length of RNA Pol II in the context of DNA motion. RNA Pol II and chromatin spatially coherent motions respond oppositely to transcriptional activities. Our study holds the potential of studying the chromatin environment in different nuclear processes.
Published: 2022
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39. Impact of Steroid Only Induction on Rejection in Simultaneous Liver-Kidney Transplantation.

Author: Ruiz I, Sparkes T, Masters B, Barth R, Maluf D, and Freedman S
Subjects: Adult, Humans, Basiliximab, Immunosuppressive Agents therapeutic use, Graft Rejection prevention & control, Retrospective Studies, Cohort Studies, Antibodies, Monoclonal therapeutic use, Mycophenolic Acid therapeutic use, Tacrolimus therapeutic use, Steroids, Adrenal Cortex Hormones, Kidney, Liver, Kidney Transplantation
Abstract: Introduction: The occurrence of simultaneous liver kidney transplantation has greatly increased; however, the ideal induction and maintenance immunosuppression remains unknown. Question: This evaluation aimed to determine if corticosteroid only induction in simultaneous liver kidney transplant recipients provided adequate prophylaxis against rejection when compared to basiliximab. Design: This was a single center, retrospective, cohort study of adult simultaneous liver kidney transplant recipients from June 2010 to June 2019 receiving corticosteroid only (N = 41) or basiliximab (N = 42) induction. Results: Liver or kidney biopsy proven acute rejection at 3 months was comparable between the corticosteroid only and basiliximab groups (10% vs 7%, P = .67), which persisted through 12 months posttransplant (15% vs 21%, P = .42). The occurrence of any infection at 3 months was increased in the corticosteroid only group relative to the basiliximab group (41% vs 21%, P = .049). Graft and patient survival at 12 months were similar between groups. Maintenance immunosuppression was overall minimized with a tacrolimus goal of 6-8 ng/mL, mycophenolate mofetil dose reduction to 1000 mg/day by 3 months, and early steroid withdrawal in both groups. Conclusion: Our findings suggested that corticosteroid only induction was an effective strategy for preventing rejection in simultaneous liver kidney transplant recipients, even in combination with reduced maintenance immunosuppression.
Published: 2022
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40. SMC complexes can traverse physical roadblocks bigger than their ring size.

Author: Pradhan B, Barth R, Kim E, Davidson IF, Bauer B, van Laar T, Yang W, Ryu JK, van der Torre J, Peters JM, and Dekker C
Subjects: Cell Cycle Proteins, Chromatin, Saccharomyces cerevisiae, Nucleosomes, Nanoparticles
Abstract: Ring-shaped structural maintenance of chromosomes (SMC) complexes like condensin and cohesin extrude loops of DNA. It remains, however, unclear how they can extrude DNA loops in chromatin that is bound with proteins. Here, we use in vitro single-molecule visualization to show that nucleosomes, RNA polymerase, and dCas9 pose virtually no barrier to loop extrusion by yeast condensin. We find that even DNA-bound nanoparticles as large as 200 nm, much bigger than the SMC ring size, also translocate into DNA loops during extrusion by condensin and cohesin. This even occurs for a single-chain version of cohesin in which the ring-forming subunits are covalently linked and cannot open to entrap DNA. The data show that SMC-driven loop extrusion has surprisingly little difficulty in accommodating large roadblocks into the loop. The findings also show that the extruded DNA does not pass through the SMC ring (pseudo)topologically, hence pointing to a nontopological mechanism for DNA loop extrusion., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Published: 2022
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41. Therapeutic Value of Sentinel Lymph Node Biopsy in Patients With Melanoma: A Randomized Clinical Trial.

Author: Crystal JS, Thompson JF, Hyngstrom J, Caracò C, Zager JS, Jahkola T, Bowles TL, Pennacchioli E, Beitsch PD, Hoekstra HJ, Moncrieff M, Ingvar C, van Akkooi A, Sabel MS, Levine EA, Agnese D, Henderson M, Dummer R, Neves RI, Rossi CR, Kane JM 3rd, Trocha S, Wright F, Byrd DR, Matter M, Hsueh EC, MacKenzie-Ross A, Kelley M, Terheyden P, Huston TL, Wayne JD, Neuman H, Smithers BM, Ariyan CE, Desai D, Gershenwald JE, Schneebaum S, Gesierich A, Jacobs LK, Lewis JM, McMasters KM, O'Donoghue C, van der Westhuizen A, Sardi A, Barth R, Barone R, McKinnon JG, Slingluff CL, Farma JM, Schultz E, Scheri RP, Vidal-Sicart S, Molina M, Testori AAE, Foshag LJ, Van Kreuningen L, Wang HJ, Sim MS, Scolyer RA, Elashoff DE, Cochran AJ, and Faries MB
Subjects: Female, Humans, Lymph Node Excision, Lymphatic Metastasis, Male, Prognosis, Sentinel Lymph Node Biopsy methods, Melanoma pathology, Skin Neoplasms pathology, Skin Neoplasms surgery
Abstract: Importance: Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery., Objective: To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases., Design, Setting, and Participants: The second Multicenter Selective Lymphadenectomy Trial (MSLT-II), a prospective multicenter randomized clinical trial, randomized participants with SLN metastases to either CLND or nodal observation. The current analysis examines observation patients with regard to regional nodal recurrence. Trial patients were aged 18 to 75 years with melanoma metastatic to SLN(s). Data were collected from December 2004 to April 2019, and data were analyzed from July 2020 to January 2022., Interventions: Nodal observation with ultrasonography rather than CLND., Main Outcomes and Measures: In-basin nodal recurrence., Results: Of 823 included patients, 479 (58.2%) were male, and the mean (SD) age was 52.8 (13.8) years. Among 855 observed basins, at 10 years, 80.2% (actuarial; 95% CI, 77-83) of basins were free of nodal recurrence. By univariable analysis, freedom from regional nodal recurrence was associated with age younger than 50 years (hazard ratio [HR], 0.49; 95% CI, 0.34-0.70; P < .001), nonulcerated melanoma (HR, 0.36; 95% CI, 0.36-0.49; P < .001), thinner primary melanoma (less than 1.5 mm; HR, 0.46; 95% CI, 0.27-0.78; P = .004), axillary basin (HR, 0.61; 95% CI, 0.44-0.86; P = .005), fewer positive SLNs (1 vs 3 or more; HR, 0.32; 95% CI, 0.14-0.75; P = .008), and SLN tumor burden (measured by diameter less than 1 mm [HR, 0.39; 95% CI, 0.26-0.60; P = .001] or less than 5% area [HR, 0.36; 95% CI, 0.24-0.54; P < .001]). By multivariable analysis, younger age (HR, 0.57; 95% CI, 0.39-0.84; P = .004), thinner primary melanoma (HR, 0.40; 95% CI, 0.22-0.70; P = .002), axillary basin (HR, 0.55; 95% CI, 0.31-0.96; P = .03), SLN metastasis diameter less than 1 mm (HR, 0.52; 95% CI, 0.33-0.81; P = .007), and area less than 5% (HR, 0.58; 95% CI, 0.38-0.88; P = .01) were associated with basin control. When looking at the identified risk factors of age (50 years or older), ulceration, Breslow thickness greater than 3.5 mm, nonaxillary basin, and tumor burden of maximum diameter of 1 mm or greater and/or metastasis area of 5% or greater and excluding missing value cases, basin disease-free rates at 5 years were 96% (95% CI, 88-100) for patients with 0 risk factors, 89% (95% CI, 82-96) for 1 risk factor, 86% (95% CI, 80-93) for 2 risk factors, 80% (95% CI, 71-89) for 3 risk factors, 61% (95% CI, 48-74) for 4 risk factors, and 54% (95% CI, 36-72) for 5 or 6 risk factors., Conclusions and Relevance: This randomized clinical trial was the largest prospective evaluation of long-term regional basin control in patients with melanoma who had nodal observation after removal of a positive SLN. SLN biopsy without CLND cleared disease in the affected nodal basin in most patients, even those with multiple risk factors for in-basin recurrence. In addition to its well-validated value in staging, SLN biopsy may also be regarded as therapeutic in some patients., Trial Registration: ClinicalTrials.gov Identifier: NCT00297895.
Published: 2022
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42. ParB proteins can bypass DNA-bound roadblocks via dimer-dimer recruitment.

Author: Tišma M, Panoukidou M, Antar H, Soh YM, Barth R, Pradhan B, Barth A, van der Torre J, Michieletto D, Gruber S, and Dekker C
Subjects: Chromosome Segregation, DNA metabolism, DNA, Bacterial genetics, DNA, Bacterial metabolism, Protein Binding, Bacillus subtilis genetics, Bacterial Proteins genetics, Bacterial Proteins metabolism
Abstract: The ParAB S system is essential for prokaryotic chromosome segregation. After loading at parS on the genome, ParB (partition protein B) proteins rapidly redistribute to distances of ~15 kilobases from the loading site. It has remained puzzling how this large-distance spreading can occur along DNA loaded with hundreds of proteins. Using in vitro single-molecule fluorescence imaging, we show that ParB from Bacillus subtilis can load onto DNA distantly of parS , as loaded ParB molecules themselves are found to be able to recruit additional ParB proteins from bulk. Notably, this recruitment can occur in cis but also in trans, where, at low tensions within the DNA, newly recruited ParB can bypass roadblocks as it gets loaded to spatially proximal but genomically distant DNA regions. The data are supported by molecular dynamics simulations, which show that cooperative ParB-ParB recruitment can enhance spreading. ParS -independent recruitment explains how ParB can cover substantial genomic distance during chromosome segregation, which is vital for the bacterial cell cycle.
Published: 2022
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43. Pep19 Has a Positive Effect on Insulin Sensitivity and Ameliorates Both Hepatic and Adipose Tissue Phenotype of Diet-Induced Obese Mice.

Author: Silvério R, Barth R, Heimann AS, Reckziegel P, Dos Santos GJ, Romero-Zerbo SY, Bermúdez-Silva FJ, Rafacho A, and Ferro ES
Subjects: Adipose Tissue metabolism, Adipose Tissue, Brown metabolism, Adipose Tissue, White metabolism, Animals, Diet, High-Fat adverse effects, Liver metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Obese, Nerve Tissue Proteins, Obesity drug therapy, Obesity etiology, Obesity metabolism, Phenotype, Insulin Resistance
Abstract: Peptide DIIADDEPLT (Pep19) has been previously suggested to improve metabolic parameters, without adverse central nervous system effects, in a murine model of diet-induced obesity. Here, we aimed to further evaluate whether Pep19 oral administration has anti-obesogenic effects, in a well-established high-fat diet-induced obesity model. Male Swiss mice, fed either a standard diet (SD) or high-fat diet (HFD), were orally administrated for 30 consecutive days, once a day, with saline vehicle or Pep19 (1 mg/kg). Next, several metabolic, morphological, and behavioral parameters were evaluated. Oral administration of Pep19 attenuated HFD body-weight gain, reduced in approximately 40% the absolute mass of the endocrine pancreas, and improved the relationship between circulating insulin and peripheral insulin sensitivity. Pep19 treatment of HFD-fed mice attenuated liver inflammation, hepatic fat distribution and accumulation, and lowered plasma alanine aminotransferase activity. The inguinal fat depot from the SD group treated with Pep19 showed multilocular brown-fat-like cells and increased mRNA expression of uncoupling protein 1 (UCP1), suggesting browning on inguinal white adipose cells. Morphological analysis of brown adipose tissue (BAT) from HFD mice showed the presence of larger white-like unilocular cells, compared to BAT from SD, Pep19-treated SD or HFD mice. Pep19 treatment produced no alterations in mice behavior. Oral administration of Pep19 ameliorates some metabolic traits altered by diet-induced obesity in a Swiss mice model.
Published: 2022
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44. Hepatocyte Nuclear Factor 4-α (HNF4α) controls the insulin resistance-induced pancreatic β-cell mass expansion.

Author: Barth R, Ruoso C, Ferreira SM, de Ramos FC, Lima FB, Boschero AC, and Santos GJD
Subjects: Animals, Basic Helix-Loop-Helix Transcription Factors biosynthesis, Basic Helix-Loop-Helix Transcription Factors genetics, Cell Proliferation genetics, Gene Expression Regulation drug effects, Hepatocyte Nuclear Factor 4 genetics, Homeodomain Proteins biosynthesis, Homeodomain Proteins genetics, Insulin Secretion genetics, Mice, Mice, Knockout, Nerve Tissue Proteins biosynthesis, Nerve Tissue Proteins genetics, Paired Box Transcription Factors biosynthesis, Paired Box Transcription Factors genetics, Trans-Activators biosynthesis, Trans-Activators genetics, Cell Proliferation drug effects, Dexamethasone pharmacology, Hepatocyte Nuclear Factor 4 metabolism, Insulin Resistance, Insulin Secretion drug effects, Insulin-Secreting Cells metabolism
Abstract: Background: Regardless of the etiology, any type of DM presents a reduction of insulin-secreting cell mass, so it is important to investigate pathways that induce the increase of this cell mass., Aim: Based on the fact that (1) HNF4α is crucial for β-cell proliferation, (2) DEX-induced IR promotes β-cell mass expansion, and (3) the stimulation of β-cell mass expansion may be an important target for DM therapies, we aimed to investigate whether DEX-induced proliferation of β pancreatic cells is dependent on HNF4α., Methods: We used WildType (WT) and Knockout (KO) mice for HNF4-α, treated or not with 100 mg/Kg/day of DEX, for 5 consecutive days. One day after the last injection of DEX the IR was confirmed by ipITT and the mice were euthanized for pancreas removal., Results: In comparison to WT, KO mice presented increased glucose tolerance, lower fasting glucose and increased glucose-stimulates insulin secretion (GSIS). DEX induced IR in both KO and WT mice. In addition, DEX-induced β-cell mass expansion and an increase in the Ki67 immunostaining were observed only in WT mice, evidencing that IR-induced β-cell mass expansion is dependent on HNF4α. Also, we observed that DEX-treatment, in an HNF4α-dependent way, promoted an increase in PDX1, PAX4 and NGN3 gene expression., Conclusions: Our results strongly suggest that DEX-induced IR promotes β-cell mass expansion through processes of proliferation and neogenesis that depend on the HNF4α activity, pointing to HNF4α as a possible therapeutic target in DM treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)
Published: 2022
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