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1. Challenges in QCD matter physics --The scientific programme of the Compressed Baryonic Matter experiment at FAIR

Author

Ablyazimov, T., Abuhoza, A., Adak, R. P., Adamczyk, M., Agarwal, K., Aggarwal, M. M., Ahammed, Z., Ahmad, F., Ahmad, N., Ahmad, S., Akindinov, A., Akishin, P., Akishina, E., Akishina, T., Akishina, V., Akram, A., Al-Turany, M., Alekseev, I., Alexandrov, E., Alexandrov, I., Amar-Youcef, S., Anđelić, M., Andreeva, O., Andrei, C., Andronic, A., Anisimov, Yu., Appelshäuser, H., Argintaru, D., Atkin, E., Avdeev, S., Averbeck, R., Azmi, M. D., Baban, V., Bach, M., Badura, E., Bähr, S., Balog, T., Balzer, M., Bao, E., Baranova, N., Barczyk, T., Bartoş, D., Bashir, S., Baszczyk, M., Batenkov, O., Baublis, V., Baznat, M., Becker, J., Becker, K. -H., Belogurov, S., Belyakov, D., Bendarouach, J., Berceanu, I., Bercuci, A., Berdnikov, A., Berdnikov, Y., Berendes, R., Berezin, G., Bergmann, C., Bertini, D., Bertini, O., Beşliu, C., Bezshyyko, O., Bhaduri, P. P., Bhasin, A., Bhati, A. K., Bhattacharjee, B., Bhattacharyya, A., Bhattacharyya, T. K., Biswas, S., Blank, T., Blau, D., Blinov, V., Blume, C., Bocharov, Yu., Book, J., Breitner, T., Brüning, U., Brzychczyk, J., Bubak, A., Büsching, H., Bus, T., Butuzov, V., Bychkov, A., Byszuk, A., Cai, Xu, Cãlin, M., Cao, Ping, Caragheorgheopol, G., Carević, I., Cătănescu, V., Chakrabarti, A., Chattopadhyay, S., Chaus, A., Chen, Hongfang, Chen, LuYao, Cheng, Jianping, Chepurnov, V., Cherif, H., Chernogorov, A., Ciobanu, M. I., Claus, G., Constantin, F., Csanád, M., D’Ascenzo, N., Das, Supriya, Das, Susovan, de Cuveland, J., Debnath, B., Dementiev, D., Deng, Wendi, Deng, Zhi, Deppe, H., Deppner, I., Derenovskaya, O., Deveaux, C. A., Deveaux, M., Dey, K., Dey, M., Dillenseger, P., Dobyrn, V., Doering, D., Dong, Sheng, Dorokhov, A., Dreschmann, M., Drozd, A., Dubey, A. K., Dubnichka, S., Dubnichkova, Z., Dürr, M., Dutka, L., Dželalija, M., Elsha, V. V., Emschermann, D., Engel, H., Eremin, V., Eşanu, T., Eschke, J., Eschweiler, D., Fan, Huanhuan, Fan, Xingming, Farooq, M., Fateev, O., Feng, Shengqin, Figuli, S. P. D., Filozova, I., Finogeev, D., Fischer, P., Flemming, H., Förtsch, J., Frankenfeld, U., Friese, V., Friske, E., Fröhlich, I., Frühauf, J., Gajda, J., Galatyuk, T., Gangopadhyay, G., García Chávez, C., Gebelein, J., Ghosh, P., Ghosh, S. K., Gläßel, S., Goffe, M., Golinka-Bezshyyko, L., Golovatyuk, V., Golovnya, S., Golovtsov, V., Golubeva, M., Golubkov, D., Gómez Ramírez, A., Gorbunov, S., Gorokhov, S., Gottschalk, D., Gryboś, P., Grzeszczuk, A., Guber, F., Gudima, K., Gumiński, M., Gupta, A., Gusakov, Yu., Han, Dong, Hartmann, H., He, Shue, Hehner, J., Heine, N., Herghelegiu, A., Herrmann, N., Heß, B., Heuser, J. M., Himmi, A., Höhne, C., Holzmann, R., Hu, Dongdong, Huang, Guangming, Huang, Xinjie, Hutter, D., Ierusalimov, A., Ilgenfritz, E. -M., Irfan, M., Ivanischev, D., Ivanov, M., Ivanov, P., Ivanov, Valery, Ivanov, Victor, Ivanov, Vladimir, Ivashkin, A., Jaaskelainen, K., Jahan, H., Jain, V., Jakovlev, V., Janson, T., Jiang, Di, Jipa, A., Kadenko, I., Kähler, P., Kämpfer, B., Kalinin, V., Kallunkathariyil, J., Kampert, K. -H., Kaptur, E., Karabowicz, R., Karavichev, O., Karavicheva, T., Karmanov, D., Karnaukhov, V., Karpechev, E., Kasiński, K., Kasprowicz, G., Kaur, M., Kazantsev, A., Kebschull, U., Kekelidze, G., Khan, M. M., Khan, S. A., Khanzadeev, A., Khasanov, F., Khvorostukhin, A., Kirakosyan, V., Kirejczyk, M., Kiryakov, A., Kiš, M., Kisel, I., Kisel, P., Kiselev, S., Kiss, T., Klaus, P., Kłeczek, R., Klein-Bösing, Ch., Kleipa, V., Klochkov, V., Kmon, P., Koch, K., Kochenda, L., Koczoń, P., Koenig, W., Kohn, M., Kolb, B. W., Kolosova, A., Komkov, B., Korolev, M., Korolko, I., Kotte, R., Kovalchuk, A., Kowalski, S., Koziel, M., Kozlov, G., Kozlov, V., Kramarenko, V., Kravtsov, P., Krebs, E., Kreidl, C., Kres, I., Kresan, D., Kretschmar, G., Krieger, M., Kryanev, A. V., Kryshen, E., Kuc, M., Kucewicz, W., Kucher, V., Kudin, L., Kugler, A., Kumar, Ajit, Kumar, Ashwini, Kumar, L., Kunkel, J., Kurepin, A., Kurepin, N., Kurilkin, A., Kurilkin, P., Kushpil, V., Kuznetsov, S., Kyva, V., Ladygin, V., Lara, C., Larionov, P., Laso García, A., Lavrik, E., Lazanu, I., Lebedev, A., Lebedev, S., Lebedeva, E., Lehnert, J., Lehrbach, J., Leifels, Y., Lemke, F., Li, Cheng, Li, Qiyan, Li, Xin, Li, Yuanjing, Lindenstruth, V., Linnik, B., Liu, Feng, Lobanov, I., Lobanova, E., Löchner, S., Loizeau, P. -A., Lone, S. A., Lucio Martínez, J. A., Luo, Xiaofeng, Lymanets, A., Lyu, Pengfei, Maevskaya, A., Mahajan, S., Mahapatra, D. P., Mahmoud, T., Maj, P., Majka, Z., Malakhov, A., Malankin, E., Malkevich, D., Malyatina, O., Malygina, H., Mandal, M. M., Mandal, S., Manko, V., Manz, S., Marin Garcia, A. M., Markert, J., Masciocchi, S., Matulewicz, T., Meder, L., Merkin, M., Mialkovski, V., Michel, J., Miftakhov, N., Mik, L., Mikhailov, K., Mikhaylov, V., Milanović, B., Militsija, V., Miskowiec, D., Momot, I., Morhardt, T., Morozov, S., Müller, W. F. J., Müntz, C., Mukherjee, S., Muñoz Castillo, C. E., Murin, Yu., Najman, R., Nandi, C., Nandy, E., Naumann, L., Nayak, T., Nedosekin, A., Negi, V. S., Niebur, W., Nikulin, V., Normanov, D., Oancea, A., Oh, Kunsu, Onishchuk, Yu., Ososkov, G., Otfinowski, P., Ovcharenko, E., Pal, S., Panasenko, I., Panda, N. R., Parzhitskiy, S., Patel, V., Pauly, C., Penschuck, M., Peshekhonov, D., Peshekhonov, V., Petráček, V., Petri, M., Petriş, M., Petrovici, A., Petrovici, M., Petrovskiy, A., Petukhov, O., Pfeifer, D., Piasecki, K., Pieper, J., Pietraszko, J., Płaneta, R., Plotnikov, V., Plujko, V., Pluta, J., Pop, A., Pospisil, V., Poźniak, K., Prakash, A., Prasad, S. K., Prokudin, M., Pshenichnov, I., Pugach, M., Pugatch, V., Querchfeld, S., Rabtsun, S., Radulescu, L., Raha, S., Rami, F., Raniwala, R., Raniwala, S., Raportirenko, A., Rautenberg, J., Rauza, J., Ray, R., Razin, S., Reichelt, P., Reinecke, S., Reinefeld, A., Reshetin, A., Ristea, C., Ristea, O., Rodriguez Rodriguez, A., Roether, F., Romaniuk, R., Rost, A., Rostchin, E., Rostovtseva, I., Roy, Amitava, Roy, Ankhi, Rożynek, J., Ryabov, Yu., Sadovsky, A., Sahoo, R., Sahu, P. K., Sahu, S. K., Saini, J., Samanta, S., Sambyal, S. S., Samsonov, V., Sánchez Rosado, J., Sander, O., Sarangi, S., Satława, T., Sau, S., Saveliev, V., Schatral, S., Schiaua, C., Schintke, F., Schmidt, C. J., Schmidt, H. R., Schmidt, K., Scholten, J., Schweda, K., Seck, F., Seddiki, S., Selyuzhenkov, I., Semennikov, A., Senger, A., Senger, P., Shabanov, A., Shabunov, A., Shao, Ming, Sheremetiev, A. D., Shi, Shusu, Shumeiko, N., Shumikhin, V., Sibiryak, I., Sikora, B., Simakov, A., Simon, C., Simons, C., Singaraju, R. N., Singh, A. K., Singh, B. K., Singh, C. P., Singhal, V., Singla, M., Sitzmann, P., Siwek-Wilczyńska, K., Škoda, L., Skwira-Chalot, I., Som, I., Song, Guofeng, Song, Jihye, Sosin, Z., Soyk, D., Staszel, P., Strikhanov, M., Strohauer, S., Stroth, J., Sturm, C., Sultanov, R., Sun, Yongjie, Svirida, D., Svoboda, O., Szabó, A., Szczygieł, R., Talukdar, R., Tang, Zebo, Tanha, M., Tarasiuk, J., Tarassenkova, O., Târzilă, M. -G., Teklishyn, M., Tischler, T., Tlustý, P., Tölyhi, T., Toia, A., Topil’skaya, N., Träger, M., Tripathy, S., Tsakov, I., Tsyupa, Yu., Turowiecki, A., Tuturas, N. G., Uhlig, F., Usenko, E., Valin, I., Varga, D., Vassiliev, I., Vasylyev, O., Verbitskaya, E., Verhoeven, W., Veshikov, A., Visinka, R., Viyogi, Y. P., Volkov, S., Volochniuk, A., Vorobiev, A., Voronin, Aleksey, Voronin, Alexander, Vovchenko, V., Vznuzdaev, M., Wang, Dong, Wang, Xi-Wei, Wang, Yaping, Wang, Yi, Weber, M., Wendisch, C., Wessels, J. P., Wiebusch, M., Wiechula, J., Wielanek, D., Wieloch, A., Wilms, A., Winckler, N., Winter, M., Wiśniewski, K., Wolf, Gy., Won, Sanguk, Wu, Ke-Jun, Wüstenfeld, J., Xiang, Changzhou, Xu, Nu, Yang, Junfeng, Yang, Rongxing, Yin, Zhongbao, Yoo, In-Kwon, Yuldashev, B., Yushmanov, I., Zabołotny, W., Zaitsev, Yu., Zamiatin, N. I., Zanevsky, Yu., Zhalov, M., Zhang, Yifei, Zhang, Yu, Zhao, Lei, Zheng, Jiajun, Zheng, Sheng, Zhou, Daicui, Zhou, Jing, Zhu, Xianglei, Zinchenko, A., Zipper, W., Żoładź, M., Zrelov, P., Zryuev, V., Zumbruch, P., and Zyzak, M.

Published
2017
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3. CBM Collaboration

Author

Ablyazimov, T., Abuhoza, A., Adak, R., Adamczewski-Musch, J., Adamczyk, M., Aggarwal, M.M., Ahammed, Z., Ahmad, F., Ahmad, N., Ahmad, S., Akindinov, A., Akishin, P., Akishina, E., Akishina, T., Akishina, V., Al-Turany, M., Alexandrov, E., Alexandrov, I., Amar-Youcef, S., Anđelić, M., Andreeva, O., Andrei, C., Andronic, A., Anisimov, Yu., Appelshäuser, H., Arend, A., Argintaru, D., Atkin, E., Avdeev, S., Averbeck, R., Azmi, M.D., Baban, V., Bach, M., Badura, E., Baginyan, S., Balle, T., Balog, T., Bandyopadhyay, S., Banerjee, P., Baranova, N., Barczyk, T., Bartoş, D., Bashir, S., Basrak, Z., Baszczyk, M., Batenkov, O., Baublis, V., Baumann, C., Baznat, M., Becker, K.-H., Bel, T., Belogurov, S., Bendarouach, J., Berceanu, I., Bercuci, A., Berdermann, E., Berdnikov, A., Berdnikov, Y., Berendes, R., Bergmann, C., Bertini, D., Bertini, O., Beşliu, C., Bezshyyko, O., Bhaduri, P.P., Bhasin, A., Bhati, A.K., Bhattacharjee, B., Bhattacharyya, A., Bhattacharyya, T.K., Biswas, S., Blau, D., Blume, C., Bocharov, Yu., Böttger, S., Borysova, M., Breitner, T., Brüning, U., Brzychczyk, J., Bubak, A., Büsching, H., Bychkov, A., Byszuk, A., Cai, Xu, Cãlin, M., Cao, Ping, Čaplar, R., Caragheorgheopol, G., Carević, I., Cătănescu, V., Chakrabarti, A., Chatterji, S., Chattopadhyay, Sanatan, Chattopadhyay, Subhasis, Chen, Hongfang, Cheng, Jianping, Chepurnov, V., Chernenko, S., Chernogorov, A., Choi, Kyung-Eon, Ciobanu, M.I., Claus, G., Constantin, F., Covlea, V., Csanád, M., D'Ascenzo, N., Das, S., Davkov, K., Davkov, V., de Cuveland, J., Debnath, B., Dementiev, D., Deng, Zhi, Deppe, H., Deppner, I., Derenovskaya, O., Deveaux, C.A., Deveaux, M., Dey, K., Dey, M., Dillenseger, P., Dobyrn, V., Doering, D., Dorokhov, A., Drozd, A., Dubey, A.K., Dubnichka, S., Dubnichkova, A., Dürr, M., Dulinski, W., Dutka, L., Dželalija, M., Emschermann, D., Engel, H., Eremin, V., Eşanu, T., Eschke, J., Eschweiler, D., Eum, Jongsik, Fan, Huanhuan, Fateev, O., Filozova, I., Finogeev, D., Fischer, P., Flemming, H., Frankenfeld, U., Friese, V., Friske, E., Fröhlich, I., Frühauf, J., Fülöp, Á., Gajda, J., Galatyuk, T., Galkin, A., Galkin, V., Gangopadhyay, G., García Chávez, C., Gašparić, I., Gebelein, J., Ghosh, P., Ghosh, S.K., Goffe, M., Golinka-Bezshyyko, L., Golovatyuk, V., Golovnya, S., Golovtsov, V., Golubeva, M., Golubkov, D., Gómez Ramírez, A., Gorbunov, S., Gorokhov, S., Gottschalk, D., Gryboś, P., Grzeszczuk, A., Guber, F., Gudima, K., Gupta, A., Gusakov, Yu., Haldar, A., Haldar, S., Hartmann, H., Hehner, J., Heidel, K., Heine, N., Hellbär, E., Herghelegiu, A., Herrmann, N., Heß, B., Heuser, J.M., Himmi, A., Höhne, C., Holzmann, R., Huang, Guangming, Huang, Xinjie, Hutsch, J., Hutter, D., Iakovleva, E., Ierusalimov, A., Ilgenfritz, E.-M., Irfan, M., Ivanov, M., Ivanov, Valery, Ivanov, Victor, Ivanov, Vladimir, Ivashkin, A., Jaaskelainen, K., Jahan, H., Jain, V., Jakovlev, V., Janson, T., Jipa, A., Kadenko, I., Kämpfer, B., Kalcher, S., Kalinin, V., Kampert, K.-H., Kang, Tae Im, Kaptur, E., Karabowicz, R., Karavichev, O., Karavicheva, T., Karmanov, D., Karnaukhov, V., Karpechev, E., Kasiński, K., Kasprowicz, G., Kaur, M., Kazantsev, A., Kebschull, U., Kekelidze, G., Khan, M.M., Khan, S.A., Khanzadeev, A., Khasanov, F., Khvorostukhin, A., Kirakosyan, V., Kirejczyk, M., Kiryakov, A., Kiš, M., Kisel, I., Kisel, P., Kiselev, S., Kiss, A., Kiss, T., Klaus, P., Kłeczek, R., Klein-Bösing, Ch., Kleipa, V., Kmon, P., Koch, K., Kochenda, L., Koczoń, P., König, W., Kohn, M., Kolb, B.W., Kolosova, A., Komkov, B., Kopfer, J.M., Korolev, M., Korolko, I., Kotte, R., Kotynia, A., Kovalchuk, A., Kowalski, S., Koziel, M., Kozlov, G., Kravtsov, P., Krebs, E., Kreidl, C., Kresan, D., Kretschmar, G., Kretz, M., Krieger, M., Kryshen, E., Kucewicz, W., Kudin, L., Kugler, A., Kulakov, I., Kunkel, J., Kurepin, A., Kurilkin, P., Kushpil, V., Kyva, V., Ladygin, V., Lara, C., Larionov, P., Laso Garcia, A., Lavrik, E., Lazanu, I., Lebedev, A., Lebedev, S., Lebedeva, E., Lehnert, J., Lehrbach, J., Lemke, F., Li, Cheng, Li, Jin, Li, Qiyan, Li, Yuanjing, Li, Yulan, Lindenstruth, V., Linev, S., Linnik, B., Litvinenko, E., Liu, Feng, Lobanov, I., Lobanova, E., Löchner, S., Loizeau, P.-A., Lucio Martínez, J.A., Lymanets, A., Maevskaya, A., Mahajan, S., Mahapatra, D.P., Mahmoud, T., Maj, P., Majka, Z., Malakhov, A., Malankin, E., Malkevich, D., Malyatina, O., Malygina, H., Mandal, S., Manko, V., Manz, S., Marin, V., Marin Garcia, A.M., Markert, J., Masciocchi, S., Matulewicz, T., Merkin, M., Mialkovski, V., Michel, J., Miftakhov, N., Mikhailov, K., Mikhaylov, V., Milanović, B., Militsija, V., Mir, M.F., Miskowiec, D., Morhardt, T., Müller, W.F.J., Müntz, C., Murin, Yu., Najman, R., Naumann, L., Nayak, T., Nedosekin, A., Neumann, B., Niebur, W., Nikulin, V., Normanov, D., Nüssle, M., Oancea, A., Oh, Kunsu, Onishchuk, Y., Osipov, D., Ososkov, G., Ossetski, D., Otfinowski, P., Ovcharenko, E., Pal, S., Panasenko, I., Panda, N.R., Parzhitskiy, S., Pauly, C., Peng, Haiping, Peric, I., Peshekhonov, D., Peshekhonov, V., Petráček, V., Petriş, M., Petrovici, A., Petrovici, M., Petrovskiy, A., Petukhov, O., Piasecki, K., Pieper, J., Pietraszko, J., Płaneta, R., Plekhanov, E., Plotnikov, V., Plujko, V., Pluta, J., Poliakov, V., Polozov, P., Pop, A., Popov, V., Pospisil, V., Potukuchi, B.V.K.S., Pouryamout, J., Poźniak, K., Prakash, A., Prokudin, M., Pshenichnov, I., Pugach, M., Pugatch, V., Querchfeld, S., Radulescu, L., Raha, S., Raja, W., Rami, F., Raniwala, R., Raniwala, S., Raportirenko, A., Rautenberg, J., Rauza, J., Ray, R., Razin, S., Reichelt, P., Reinecke, S., Reshetin, A., Ristea, C., Ristea, O., Roether, F., Romaniuk, R., Rost, A., Rostchin, E., Rostovtseva, I., Roy, A., Rożynek, J., Ryabov, Yu., Rykalin, V., Sadovsky, A., Sadovsky, S., Sahoo, R., Sahu, P.K., Saini, J., Samanta, S., Sambyal, S.S., Samsonov, V., Sánchez Rosado, J., Sau, S., Saveliev, V., Schatral, S., Schiaua, C., Schmidt, C.J., Schmidt, H.R., Schmidt, K., Schweda, K., Scurtu, A., Seck, F., Seddiki, S., Selyuzhenkov, I., Semennikov, A., Senger, A., Senger, P., Shabunov, A., Shao, Ming, Sharma, M.K., Shumeiko, N., Shumikhin, V., Sikora, B., Simakov, A., Simon, C., Simons, C., Singaraju, R.N., Singh, A.K., Singh, B.K., Singh, C.P., Singhal, V., Siwek-Wilczyńska, K., Škoda, L., Skwira-Chalot, I., Som, I., Song, Jihye, Sorokin, I., Sosin, Z., Soyk, D., Staszel, P., Stavinskiy, A., Stephan, E., Storozhyk, D., Strikhanov, M., Strohauer, S., Stroth, J., Sturm, C., Sultanov, R., Sun, Yongjie, Svoboda, O., Szczygieł, R., Talukdar, R., Tang, Zebo, Tanha, M., Tarasiuk, J., Tarassenkova, O., Târzilă, M.-G., Tiflov, V., Tischler, T., Tlustý, P., Toia, A., Tolyhi, T., Topil'skaya, N., Trageser, C., Trivedy, P., Tsakov, I., Tsyupa, Yu., Turowiecki, A., Uhlig, F., Usenko, E., Valin, I., Vasiliev, T., Vassiliev, I., Verbitskaya, E., Verhoeven, W., Veshikov, A., Visinka, R., Viyogi, Y.P., Volkov, S., Volkov, Yu., Vorobiev, A., Voronin, A., Vovchenko, V., Vznuzdaev, E., Vznuzdaev, M., Wang, Dong, Wang, Yaping, Yi, Wang, Wendisch, C., Wessels, J.P., Wiebusch, M., Wiechula, J., Wiedemann, B., Wielanek, D., Wieloch, A., Winckler, N., Winter, M., Wiśniewski, K., Wohlfeld, D., Wolf, Gy., Sanguk, Won, Wüstenfeld, J., Xiang, Changzhou, Nu, Xu, Yi, Jun-Gyu, Yin, Zhongbao, Yoo, In-Kwon, Yue, Qian, Yuldashev, B., Yushmanov, I., Zabołotny, W., Zaitsev, Yu., Zanevsky, Yu., Zhalov, M., Zhang, Ya Peng, Zhang, Yifei, Zhou, Daicui, Zhu, Xianglei, Zinchenko, A., Zipper, W., Żoładź, M., Zrelov, P., Zryuev, V., Zumbruch, P., and Zyzak, M.

Published
2014
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4. The CBM Collaboration

Author

Abuhoza, A., Adamczewski-Musch, J., Aggarwal, M.M., Ahammed, Z., Ahmad, F., Ahmad, N., Ahmad, S., Akindinov, A., Akishin, P., Akishina, E., Akishina, T., Akishina, V., Al-Turany, M., Amar-Youcef, S., Anđelić, M., Andrei, C., Andronic, A., Anisimov, Yu., Appelshäuser, H., Arend, A., Argintaru, D., Armbruster, T., Atkin, E., Avdeyev, S., Azmi, M.D., Baban, V., Bach, M., Badura, E., Baginyan, S., Balog, T., Bandyopadhyay, S., Banerjee, P., Baranova, N., Bartoş, D., Bashir, S., Basrak, Z., Baszczyk, M., Batenkov, O., Baublis, V., Baumann, C., Becker, K.-H., Bel, T., Belogurov, S., Berceanu, I., Berdermann, E., Berdnikov, A., Berdnikov, Y., Berendes, R., Bergmann, C., Bertini, D., Beşliu, C., Bezshyyko, O., Bhaduri, P.P., Bhasin, A., Bhati, A.K., Bhattacharjee, B., Bhattacharyya, A., Bhattacharyya, T.K., Biswas, S., Blau, D., Blume, C., Bocharov, Yu., Böttger, S., Borysova, M., Bozsogi, B., Breitner, T., Brüning, U., Brzychczyk, J., Bubak, A., Bychkov, A., Cai, Xu, Cãlin, M., Čaplar, R., Caragheorgheopol, G., Carević, I., Cătănescu, V., Chakrabarti, A., Chatterji, S., Chattopadhyay, Sanatan, Chattopadhyay, Subhasis, Chen, Hongfang, Cheng, Jianping, Chepurnov, V., Chernenko, S., Chernogorov, A., Ciobanu, M.I., Claus, G., Constantin, F., Covlea, V., Csanád, M., DʼAscenzo, N., Das, S., Davkov, K., Davkov, V., de Cuveland, J., Debnath, B., Deng, Zhi, Deppe, H., Deppner, I., Derenovskaya, O., Deveaux, M., Dey, K., Dey, M., Dillenseger, P., Dobyrn, V., Doering, D., Domachowski, M., Dorokhov, A., Dritsa, C.A., Dubey, A.K., Dubnichka, S., Dubnichkova, A., Dulinski, W., Dželalija, M., Emschermann, D., Engel, H., Eremin, V., Eşanu, T., Eschke, J., Fateev, O., Fischer, P., Flemming, H., Frankenfeld, U., Friese, V., Fröhlich, I., Frühauf, J., Fülöp, Á., Gajda, J., Galatyuk, T., Galkin, A., Galkin, V., Gangopadhyay, G., Ganti, M.S., García Chávez, C., Gašparić, I., Gebelein, J., Ghosh, P., Ghosh, S.K., Goffe, M., Golovatyuk, V., Golovnya, S., Golovtsov, V., Golubeva, M., Golubkov, D., Gorbunov, S., Gottschalk, D., Gryboś, P., Grzeszczuk, A., Guber, F., Gupta, A., Gusakov, Yu., Haldar, A., Haldar, S., Hartig, M., Hehner, J., Heidel, K., Heine, N., Herghelegiu, A., Herrmann, N., Heß, B., Heuser, J.M., Himmi, A., Höhne, C., Holzmann, R., Huang, Guangming, Hutsch, J., Hutter, D., Ierusalimov, A., Ilgenfritz, E.-M., Irfan, M., Ivanov, Valery, Ivanov, Victor, Ivanov, Vladimir, Ivashkin, A., Jaaskelainen, K., Jakovlev, V., Janson, T., Jipa, A., Kadenko, I., Kämpfer, B., Kalcher, S., Kalinin, V., Kampert, K.-H., Kang, Tae Im, Kaptur, E., Karabowicz, R., Karavichev, O., Karavicheva, T., Karmanov, D., Karnaukhov, V., Karpechev, E., Kasiński, K., Kaur, M., Kazantsev, A., Kebschull, U., Kekelidze, G., Khan, M.M., Khan, S.A., Khanzadeev, A., Khasanov, F., Kirakosyan, V., Kirejczyk, M., Kiš, M., Kisel, I., Kisel, P., Kiselev, S., Kiss, A., Kiss, T., Kłeczek, R., Klein-Bösing, Ch., Kleipa, V., Koch, K., Kochenda, L., Koczoń, P., Kolb, B., Komkov, B., Kopfer, J.M., Korolev, M., Korolko, I., Kotte, R., Kotynia, A., Kovalchuk, A., Kowalski, S., Koziel, M., Kozlov, G., Kravtsov, P., Kreidl, C., Kresan, D., Kretz, M., Krieger, M., Kryshen, E., Kucewicz, W., Kudin, L., Kugler, A., Kulakov, I., Kunkel, J., Kurepin, A., Kyva, V., Ladygin, V., Lara, C., Larionov, P., Laso Garcia, A., Lavrik, E., Lazanu, I., Lebedev, A., Lebedev, S., Lebedeva, E., Lehrbach, J., Lemke, F., Li, Cheng, Li, Jin, Qyian, Li, Li, Yuanjing, Li, Yulan, Lindenstruth, V., Linev, S., Litvinenko, E., Liu, Feng, Lobanov, I., Lobanova, E., Löchner, S., Loizeau, P.-A., Lymanets, A., Maevskaya, A., Mahajan, S., Mahapatra, D.P., Mahmoud, T., Maj, P., Majka, Z., Malakhov, A., Malyatina, O., Malygina, H., Manjavidze, J., Manko, V., Manz, S., Marin, V., Matulewicz, T., Merkin, M., Mialkovski, V., Miftakhov, N., Mikhailov, K., Milanovic, B., Militsija, V., Mir, F., Müller, W.F.J., Müntz, C., Murin, Yu., Naumann, L., Nayak, T., Neumann, B., Niebur, W., Nikulin, V., Nüssle, M., Oancea, A., Kunsu, Oh, Onishchuk, Y., Ososkov, G., Ossetski, D., Otfinowski, P., Ovcharenko, E., Susanta, Pal, Panasenko, I., Parzhitskiy, S., Pauly, C., Peng, Haiping, Peric, I., Peshekhonov, D., Peshekhonov, V., Petráček, V., Petriş, M., Petrovici, A., Petrovici, M., Petrovskiy, A., Petukhov, O., Piasecki, K., Pietraszko, J., Plekhanov, E., Plujko, V., Poliakov, V., Polozov, P., Pop, A., Popov, V., Pospisil, V., Potukuchi, B.V.K.S., Pouryamout, J., Prakash, A., Prokudin, M., Pshenichnov, I., Pugatch, V., Querchfeld, S., Raha, S., Raja, W., Rami, F., Raniwala, R., Raniwala, S., Raportirenko, A., Rautenberg, J., Ray, R., Razin, S., Reichelt, P., Reinecke, S., Reshetin, A., Ristea, C., Ristea, O., Rostchin, E., Rostovtseva, I., Roy, A., Rożynek, J., Ryabov, Yu., Rykalin, V., Sadovsky, A., Sadovsky, S., Sahu, P.K., Saini, J., Sambyal, S.S., Samsonov, V., Sanchez Rosado, J., Saveliev, V., Schatral, S., Schiaua, C., Schmidt, C.J., Schmidt, H.R., Schrader, C., Schweda, K., Scurtu, A., Seddiki, S., Semennikov, A., Senger, A., Senger, P., Shabunov, A., Shao, Ming, Sharma, M.K., Shumikhin, V., Sikora, B., Simakov, A., Simon, C., Simons, C., Singaraju, R.N., Singh, A.K., Singh, B.K., Singh, C.P., Singhal, V., Singla, M., Siwek-Wilczynska, K., Škoda, L., Jihye, Song, Sorokin, I., Soyk, D., Staszel, P., Stavinskiy, A., Stephan, E., Storozhyk, D., Strikhanov, M., Stroth, J., Sturm, C., Sun, Yongjie, Svoboda, O., Szczygieł, R., Talukdar, R., Tang, Zebo, Tarassenkova, O., Târzilă, M., Tiflov, V., Tischler, T., Tlustý, P., Tolyhi, T., Topilʼskaya, N., Trageser, C., Trivedy, P., Tsakov, I., Tsyupa, Yu., Uhlig, F., Usenko, E., Valin, I., Vasiliev, T., Vassiliev, I., Verbitskaya, E., Verhoeven, W., Veshikov, A., Viyogi, Y., Volkov, S., Volkov, Yu., Vorobiev, A., Voronin, A., Vznuzdaev, E., Vznuzdaev, M., Wang, Dong, Wang, Yaping, Wang, Yi, Wendisch, C., Wessels, J.P., Wiechula, J., Wiedemann, B., Winter, M., Wisniewski, K., Wohlfeld, D., Wolf, Gy., Wüstenfeld, J., Xiang, Changzhou, Nu, Xu, Yi, Jun-Gyu, Zhongbao, Yin, Yoo, In-Kwon, Yue, Qian, Yushmanov, I., Zaitsev, Yu., Zanevsky, Yu., Zhalov, M., Zhang, Ya Peng, Zhang, Yifei, Daicui, Zhou, Zhu, Xianglei, Zinchenko, A., Zipper, W., Żoładź, M., Zrelov, P., Zryuev, V., Zumbruch, P., and Zyzak, M.

Published
2013
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5. The CBM Collaboration

Author

Abel, N., Adamczewski, J., Adamova, D., Aggarwal, M.M., Ahmad, N., Ahmad, Z., Akindinov, A., Akishin, P., Akishina, E., Akishina, T., Al-Turany, M., Alyushin, M., Amar-Youcef, S., Ammosov, V., Anđelić, M., Andrei, C., Andronic, A., Anisimov, Yu., Antipin, K., Appelshäuser, H., Arefiev, A., Armbruster, T., Artamonov, A., Atkin, E., Azmi, M.D., Baba, P.V.K.S., Badura, E., Baginyan, S., Bandyopadhyay, S., Baranova, N., Bashindzhagyan, G., Basrak, Z., Baublis, V., Belogurov, S., Berceanu, I., Berdermann, E., Berdnikov, A., Berdnikov, Y., Berendes, R., Bergmann, C., Bertini, D., Besliu, C., Bezshyyko, O., Bhaduri, P., Bhasin, A., Bhati, A.K., Bhattacharjee, B., Bhattacharya, A., Bocharov, Y., Bogolyubsky, M., Boldizsar, L., Bondar, N., Borysova, M., Böttger, S., Braun-Munzinger, P., Brüning, U., Brzychczyk, J., Bubak, A., Čaplar, R., Cai, Xu, Calin, M., Caragheorgheopol, G., Carević, I., Cătănescu, V., Chakraborti, A., Chatterji, S., Chattopadhyay, Subhasis, Chattopadhyay, Sukalyan, Chattopadhyay, Sanatan, Chaus, A., Chen, Hongfang, Cheng, Jianping, Chepurnov, V., Chernenko, S., Chernogorov, A., Chubarov, M., Ciobanu, M., Claus, G., Covlea, V., Cozma, D., Csanád, M., D'Ascenzo, N., Das, D., Das, I., Davkov, V., Davkov, K., De, M., De, R., Debnath, B., Denes, E., Deng, Zhi, Denisova, O., Deppe, H., Deppner, I., Dermenev, A., Deveaux, M., Dey, M., Dorokhov, A., Dritsa, C., Dubey, A., Dulinski, W., Dutt-Mazumdar, A.K., Dutta, T., Dutta, D., DuttaMajumdar, M.R., Dyatchenko, V., Dželalija, M., Engel, H., Esanu, T., Eschke, J., Essel, H., Fateev, O., Ferreira Marques, R., Fischer, P., Flemming, H., Fodor, Z., Fonte, P., Fröhlich, I., Fröning, H., Friese, V., Futo, E., Gašparić, I., Gajda, J., Galatyuk, T., Galkin, V., Galkin, A., Gangopadhyay, G., Gao, Wenxue, Garabatos, C., Gasik, P., Gebelein, J., Ghosh, P., Gilitsky, Yu., Golovatyuk, V., Golovnya, S., Golovtsov, V., Golubeva, M., Golubkov, D., Golutvin, A., González-Díaz, D., Gorbunov, S., Gorokhov, S., Gottschalk, D., Gousakov, Ju., Grosse, E., Gryboś, P., Grzeszczuk, A., Guber, F., Gumenuik, A., Gupta, A., Hartig, M., Heidel, K., Heine, N., Herghelegiu, A., Herrmann, N., Heuser, J., Himmi, A., Höhne, C., Holzmann, R., Hong, Byungsik, Hutsch, J., Ierusalimov, A., Igolkin, S., Ilyushenko, I., Im Kang, Tae, Irfan, M., Ivanov, Valery, Ivanov, V., Ivanov, Victor, Ivashkin, A., Jaaskelainen, K., Jakovlev, V., Jinaru, A., Jipa, A., Kachel, M., Kadenko, I., Kalita, H., Kämpfer, B., Karasev, V., Karavichev, O., Karavicheva, T., Karmanov, D., Karpechev, E., Kashif, E.M., Kasinski, K., Kaur, Manjit, Kazantsev, A., Kebschull, U., Kecskemeti, J., Kekelidze, G., Khan, M.M., Khan, S.A., Khanzadeev, A., Kharlov, Yu., Khasanov, F., Kiš, M., Kim, Junghan, Kirejczyk, M., Kisel, I., Kiselev, S., Kiseleva, A., Kiss, T., Kiss, A., Klein-Bøsing, Ch., Klein-Bøsing, M., Kleipa, V., Kluev, A., Koch, K., Koczoń, P., Kolb, B., Komkov, B., Konstantinov, D., Korobchuk, P., Korolev, M., Korolko, I., Korotkova, N., Kotte, R., Kotynia, A., Kovalchuk, A., Kowalski, S., Koziel, M., Krauze, M., Kreidel, C., Kresan, D., Kryshen, E., Kudin, L., Kudryashov, I., Kugel, A., Kugler, A., Kurepin, A., Løchner, S., Ladygin, V., Lara, C., Lashaev, S., Laszlo, A., Lazanu, I., Lebedev, A., Lebedev, S., Lee, Hayoung, Lemke, F., Li, Cheng, Li, Yuanjing, Li, Yulan, Li, Jin, Lindenstruth, V., Linev, S., Litvinenko, E., Lobanov, I., Lobanova, E., Loizeau, P., Lucenko, V., Lymanets, A., Maevskaya, A., Mahapatra, D.P., Maiatski, V., Maj, P., Majka, Z., Malakhov, A., Malyatina, O., Mangiarotti, A., Manjavidze, J., Manko, V., Männer, R., Manz, S., Matulewicz, T., Matyushevskiy, E., Melnik, A., Merkin, M., Mialkovski, V., Mikhailov, K., Militsija, V., Mir, M.F., Mohanty, B., Müller, W.F.J., Müller-Klieser, S., Müntz, C., Murin, Y., Murthy, G.S.N., Nadtochii, A., Naumann, L., Nayak, T., Niebur, W., Nikulin, V., Nüssle, M., Onishchuk, Y., Ososkov, G., Ossetski, D., Pal, L., Pal, S., Panasenko, Ya., Peric, I., Peshekhonov, D., Peshekhonov, V., Peshenichnov, I., Petráček, V., Petriş, M., Petrovici, M., Petrovici, A., Petrovskiy, A., Piasecki, K., Plekhanov, E., Plujko, V., Poliakov, A., Polozov, P., Pop, A., Popov, V., Pospisil, V., Pozdniakov, V., Prakash, A., Prokudin, M., Pugatch, V., Røhrich, D., Rami, F., Raniwala, R., Raniwala, S., Raportirenko, A., Rasin, V., Reshetin, A., Riabov, Y., Rogachevsky, O., Rostchin, E., Rostovtseva, I., Roy, A., Roy, P., Rożynek, J., Ryazantsev, A., Rykalin, V., Ryzhinskiy, M., Sadovsky, A., Sadovsky, S., Sahu, P.K., Saini, Y., Sambyal, S.S., Samsonov, V., Sang Ryu, Min, Saveliev, V., Schiaua, C., Schmidt, C.J., Schrader, C., Schweda, K., Scurtu, A., Seddiki, S., Seliverstov, D., Semak, A., Semennikov, A., Senger, P., Shao, Ming, Sharkov, G., Shevchenko, V., Sikora, B., Silaev, A., Sim, Kwang-Souk, Simakov, A., Singaraju, R.N., Singh, V., Singh, C.P., Singh, B.K., Singh, A.K., Singhal, V., Sinha, T., Siwek-Wilczynska, K., Skoda, L., Soldatov, A., Solin, L., Soltveit, H.K., Soos, Cs., Sorokin, Y., Staszel, P., Stavinskiy, A., Steinle, C., Stephan, E., Stolpovsky, P., Storozhyk, D., Ströbele, H., Strikhanov, M., Stroth, J., Sun, Yongjie, Sviridov, Y., Szczygieł, R., Tang, Zebo, Tarassenkova, O., Tiflov, V., Tlusty, P., Tolyhi, T., Topil'skaya, N., Torheim, O., Trivedy, P., Tsyupa, Yu., Uhlig, F., Ukhanov, M., Ullaland, K., Vakil, G.B., Valin, I., Vassiliev, I., Velica, S., Vesztergombi, G., Victorov, V., Viyogi, Y.P., Volkov, Y., Volkov, S., Vorobiev, A., Voronin, A., Vznuzdaev, E., Wang, Yaping, Wang, Xiaolian, Wang, Yi, Wendisch, C., Wessels, J., Wilk, A., Winter, M., Wisniewski, K., Wurz, A., Wüstenfeld, J., Xu, Chuncheng, Yi, Jun-Gyu, Yin, Zhongbao, Yoo, In-Kwon, Yue, Qian, Yushmanov, I., Zaets, V., Zaitsev, Y., Zanevsky, Yu., Zelnicek, P., Zhalov, M., Zhang, Ziping, Zhang, Yapeng, Zhou, Daicui, Zhu, Xianglei, Zinchenko, A., Zipper, W., Żoła̧dź, M., Zrelov, P., and Zrjuev, V.

Published
2009
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6. Gut microbiota dysbiosis is associated with altered tryptophan metabolism and dysregulated inflammatory response in COVID-19.

Author

Essex M, Millet Pascual-Leone B, Löber U, Kuhring M, Zhang B, Brüning U, Fritsche-Guenther R, Krzanowski M, Fiocca Vernengo F, Brumhard S, Röwekamp I, Anna Bielecka A, Lesker TR, Wyler E, Landthaler M, Mantei A, Meisel C, Caesar S, Thibeault C, Corman VM, Marko L, Suttorp N, Strowig T, Kurth F, Sander LE, Li Y, Kirwan JA, Forslund SK, and Opitz B

Subjects
Humans, Male, Female, Middle Aged, Metabolome, Inflammation, Kynurenine metabolism, Kynurenine blood, Aged, Adult, COVID-19 microbiology, COVID-19 immunology, Tryptophan metabolism, Gastrointestinal Microbiome, Dysbiosis, SARS-CoV-2, Cytokines blood, Cytokines metabolism
Abstract

The clinical course of COVID-19 is variable and often unpredictable. To test the hypothesis that disease progression and inflammatory responses associate with alterations in the microbiome and metabolome, we analyzed metagenome, metabolome, cytokine, and transcriptome profiles of repeated samples from hospitalized COVID-19 patients and uninfected controls, and leveraged clinical information and post-hoc confounder analysis. Severe COVID-19 was associated with a depletion of beneficial intestinal microbes, whereas oropharyngeal microbiota disturbance was mainly linked to antibiotic use. COVID-19 severity was also associated with enhanced plasma concentrations of kynurenine and reduced levels of several other tryptophan metabolites, lysophosphatidylcholines, and secondary bile acids. Moreover, reduced concentrations of various tryptophan metabolites were associated with depletion of Faecalibacterium, and tryptophan decrease and kynurenine increase were linked to enhanced production of inflammatory cytokines. Collectively, our study identifies correlated microbiome and metabolome alterations as a potential contributor to inflammatory dysregulation in severe COVID-19., (© 2024. The Author(s).)

Published
2024
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7. ISG15 blocks cardiac glycolysis and ensures sufficient mitochondrial energy production during Coxsackievirus B3 infection.

Author

Bredow C, Thery F, Wirth EK, Ochs S, Kespohl M, Kleinau G, Kelm N, Gimber N, Schmoranzer J, Voss M, Klingel K, Spranger J, Renko K, Ralser M, Mülleder M, Heuser A, Knobeloch KP, Scheerer P, Kirwan J, Brüning U, Berndt N, Impens F, and Beling A

Subjects
Animals, Humans, Male, Disease Models, Animal, Enterovirus B, Human pathogenicity, Enterovirus B, Human metabolism, Host-Pathogen Interactions, Mice, Inbred C57BL, Mice, Knockout, Protein Processing, Post-Translational, Signal Transduction, Coxsackievirus Infections metabolism, Coxsackievirus Infections virology, Coxsackievirus Infections genetics, Cytokines genetics, Cytokines metabolism, Energy Metabolism, Glycolysis, Mitochondria, Heart metabolism, Mitochondria, Heart pathology, Myocytes, Cardiac metabolism, Myocytes, Cardiac virology, Myocytes, Cardiac pathology, Ubiquitins metabolism, Ubiquitins genetics
Abstract

Aims: Virus infection triggers inflammation and, may impose nutrient shortage to the heart. Supported by type I interferon (IFN) signalling, cardiomyocytes counteract infection by various effector processes, with the IFN-stimulated gene of 15 kDa (ISG15) system being intensively regulated and protein modification with ISG15 protecting mice Coxsackievirus B3 (CVB3) infection. The underlying molecular aspects how the ISG15 system affects the functional properties of respective protein substrates in the heart are unknown., Methods and Results: Based on the protective properties due to protein ISGylation, we set out a study investigating CVB3-infected mice in depth and found cardiac atrophy with lower cardiac output in ISG15-/- mice. By mass spectrometry, we identified the protein targets of the ISG15 conjugation machinery in heart tissue and explored how ISGylation affects their function. The cardiac ISGylome showed a strong enrichment of ISGylation substrates within glycolytic metabolic processes. Two control enzymes of the glycolytic pathway, hexokinase 2 (HK2) and phosphofructokinase muscle form (PFK1), were identified as bona fide ISGylation targets during infection. In an integrative approach complemented with enzymatic functional testing and structural modelling, we demonstrate that protein ISGylation obstructs the activity of HK2 and PFK1. Seahorse-based investigation of glycolysis in cardiomyocytes revealed that, by conjugating proteins, the ISG15 system prevents the infection-/IFN-induced up-regulation of glycolysis. We complemented our analysis with proteomics-based advanced computational modelling of cardiac energy metabolism. Our calculations revealed an ISG15-dependent preservation of the metabolic capacity in cardiac tissue during CVB3 infection. Functional profiling of mitochondrial respiration in cardiomyocytes and mouse heart tissue by Seahorse technology showed an enhanced oxidative activity in cells with a competent ISG15 system., Conclusion: Our study demonstrates that ISG15 controls critical nodes in cardiac metabolism. ISG15 reduces the glucose demand, supports higher ATP production capacity in the heart, despite nutrient shortage in infection, and counteracts cardiac atrophy and dysfunction., Competing Interests: Conflict of interest: JK conducts paid consultancy for Centogene GmbH. All other authors declare no conflict of interest. The patent application EP21174633 with the title “Computer assisted method for the evaluation of cardiac metabolism” was filed by Charité – Universitätsmedizin Berlin as the employer of NB and Titus Kuehne, with both holding inventorship for this patent application., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Published
2024
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8. Clinically used broad-spectrum antibiotics compromise inflammatory monocyte-dependent antibacterial defense in the lung.

Author

Dörner PJ, Anandakumar H, Röwekamp I, Fiocca Vernengo F, Millet Pascual-Leone B, Krzanowski M, Sellmaier J, Brüning U, Fritsche-Guenther R, Pfannkuch L, Kurth F, Milek M, Igbokwe V, Löber U, Gutbier B, Holstein M, Heinz GA, Mashreghi MF, Schulte LN, Klatt AB, Caesar S, Wienhold SM, Offermanns S, Mack M, Witzenrath M, Jordan S, Beule D, Kirwan JA, Forslund SK, Wilck N, Bartolomaeus H, Heimesaat MM, and Opitz B

Subjects
Humans, Mice, Animals, Monocytes, Klebsiella pneumoniae, Lung, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Anti-Infective Agents pharmacology
Abstract

Hospital-acquired pneumonia (HAP) is associated with high mortality and costs, and frequently caused by multidrug-resistant (MDR) bacteria. Although prior antimicrobial therapy is a major risk factor for HAP, the underlying mechanism remains incompletely understood. Here, we demonstrate that antibiotic therapy in hospitalized patients is associated with decreased diversity of the gut microbiome and depletion of short-chain fatty acid (SCFA) producers. Infection experiments with mice transplanted with patient fecal material reveal that these antibiotic-induced microbiota perturbations impair pulmonary defense against MDR Klebsiella pneumoniae. This is dependent on inflammatory monocytes (IMs), whose fatty acid receptor (FFAR)2/3-controlled and phagolysosome-dependent antibacterial activity is compromized in mice transplanted with antibiotic-associated patient microbiota. Collectively, we characterize how clinically relevant antibiotics affect antimicrobial defense in the context of human microbiota, and reveal a critical impairment of IM´s antimicrobial activity. Our study provides additional arguments for the rational use of antibiotics and offers mechanistic insights for the development of novel prophylactic strategies to protect high-risk patients from HAP., (© 2024. The Author(s).)

Published
2024
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9. Inflammation in Children with CKD Linked to Gut Dysbiosis and Metabolite Imbalance.

Author

Holle J, Bartolomaeus H, Löber U, Behrens F, Bartolomaeus TUP, Anandakumar H, Wimmer MI, Vu DL, Kuhring M, Brüning U, Maifeld A, Geisberger S, Kempa S, Schumacher F, Kleuser B, Bufler P, Querfeld U, Kitschke S, Engler D, Kuhrt LD, Drechsel O, Eckardt KU, Forslund SK, Thürmer A, McParland V, Kirwan JA, Wilck N, and Müller D

Subjects
Humans, Dysbiosis microbiology, Inflammation, Tumor Necrosis Factor-alpha, Child, Adolescent, Cardiovascular Diseases, Gastrointestinal Microbiome physiology, Renal Insufficiency, Chronic complications, Renal Insufficiency, Chronic therapy, Renal Insufficiency, Chronic metabolism
Abstract

Background: CKD is characterized by a sustained proinflammatory response of the immune system, promoting hypertension and cardiovascular disease. The underlying mechanisms are incompletely understood but may be linked to gut dysbiosis. Dysbiosis has been described in adults with CKD; however, comorbidities limit CKD-specific conclusions., Methods: We analyzed the fecal microbiome, metabolites, and immune phenotypes in 48 children (with normal kidney function, CKD stage G3-G4, G5 treated by hemodialysis [HD], or kidney transplantation) with a mean±SD age of 10.6±3.8 years., Results: Serum TNF- α and sCD14 were stage-dependently elevated, indicating inflammation, gut barrier dysfunction, and endotoxemia. We observed compositional and functional alterations of the microbiome, including diminished production of short-chain fatty acids. Plasma metabolite analysis revealed a stage-dependent increase of tryptophan metabolites of bacterial origin. Serum from patients on HD activated the aryl hydrocarbon receptor and stimulated TNF- α production in monocytes, corresponding to a proinflammatory shift from classic to nonclassic and intermediate monocytes. Unsupervised analysis of T cells revealed a loss of mucosa-associated invariant T (MAIT) cells and regulatory T cell subtypes in patients on HD., Conclusions: Gut barrier dysfunction and microbial metabolite imbalance apparently mediate the proinflammatory immune phenotype, thereby driving the susceptibility to cardiovascular disease. The data highlight the importance of the microbiota-immune axis in CKD, irrespective of confounding comorbidities., (Copyright © 2022 by the American Society of Nephrology.)

Published
2022
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10. Identification and validation of small molecule analytes in mouse plasma by liquid chromatography-tandem mass spectrometry: A case study of misidentification of a short-chain fatty acid with a ketone body.

Author

García-Rivera MA, Fernández-Ochoa Á, Brüning U, Fritsche-Guenther R, and Kirwan JA

Subjects
Animals, Chromatography, Liquid methods, Ketone Bodies, Mice, Plasma, Fatty Acids, Volatile metabolism, Tandem Mass Spectrometry methods
Abstract

Recently, there has been growing interest in short-chain fatty acids (SCFA) and ketone bodies (KB) due to their potential use as biomarkers of health and disease. For instance, these diet-related metabolites can be used to monitor and reduce the risk of immune response, diabetes, or cardiovascular diseases. Given the interest in these metabolites, different targeted metabolomic methods based on UPLC-MS/MS have been developed in recent years to detect and quantify SCFA and KB. In this case study, we discovered that applying an existing validated, targeted UPLC-MS/MS method to mouse plasma, resulted in a fragment ion (194 m/z) being originally misidentified as acetic acid (a SCFA), when its original source was 3-hydroxybutyric acid (a KB). Therefore, we report a modified, optimized LC method that can separate both signals. In addition, the metabolite coverage was expanded in this method to detect up to eight SCFA: acetic, propanoic, butyric, isobutyric, 2-methylbutyric, valeric, isovaleric, and hexanoic acids, two KB: 3-hydroxybutyric, and acetoacetic acids, and one related metabolite: 3-hydroxy-3-methylbutyric acid. The optimization of this method increased the selectivity of the UPLC-MS/MS method towards the misidentified compound. These findings encourage the scientific community to increase efforts in validating the original precursor of small molecule fragments in targeted methods., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2022
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11. Quiescent Endothelial Cells Upregulate Fatty Acid β-Oxidation for Vasculoprotection via Redox Homeostasis.

Author

Kalucka J, Bierhansl L, Conchinha NV, Missiaen R, Elia I, Brüning U, Scheinok S, Treps L, Cantelmo AR, Dubois C, de Zeeuw P, Goveia J, Zecchin A, Taverna F, Morales-Rodriguez F, Brajic A, Conradi LC, Schoors S, Harjes U, Vriens K, Pilz GA, Chen R, Cubbon R, Thienpont B, Cruys B, Wong BW, Ghesquière B, Dewerchin M, De Bock K, Sagaert X, Jessberger S, Jones EAV, Gallez B, Lambrechts D, Mazzone M, Eelen G, Li X, Fendt SM, and Carmeliet P

Subjects
Animals, Cell Proliferation, HEK293 Cells, Homeostasis, Humans, Mice, Mice, Inbred C57BL, Oxidation-Reduction, Oxidative Stress, Carnitine O-Palmitoyltransferase metabolism, Energy Metabolism, Fatty Acids metabolism, Human Umbilical Vein Endothelial Cells metabolism, NADP metabolism, Receptor, Notch1 metabolism
Abstract

Little is known about the metabolism of quiescent endothelial cells (QECs). Nonetheless, when dysfunctional, QECs contribute to multiple diseases. Previously, we demonstrated that proliferating endothelial cells (PECs) use fatty acid β-oxidation (FAO) for de novo dNTP synthesis. We report now that QECs are not hypometabolic, but upregulate FAO >3-fold higher than PECs, not to support biomass or energy production but to sustain the tricarboxylic acid cycle for redox homeostasis through NADPH regeneration. Hence, endothelial loss of FAO-controlling CPT1A in CPT1A ΔEC mice promotes EC dysfunction (leukocyte infiltration, barrier disruption) by increasing endothelial oxidative stress, rendering CPT1A ΔEC mice more susceptible to LPS and inflammatory bowel disease. Mechanistically, Notch1 orchestrates the use of FAO for redox balance in QECs. Supplementation of acetate (metabolized to acetyl-coenzyme A) restores endothelial quiescence and counters oxidative stress-mediated EC dysfunction in CPT1A ΔEC mice, offering therapeutic opportunities. Thus, QECs use FAO for vasculoprotection against oxidative stress-prone exposure., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Published
2018
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12. Role of glutamine synthetase in angiogenesis beyond glutamine synthesis.

Author

Eelen G, Dubois C, Cantelmo AR, Goveia J, Brüning U, DeRan M, Jarugumilli G, van Rijssel J, Saladino G, Comitani F, Zecchin A, Rocha S, Chen R, Huang H, Vandekeere S, Kalucka J, Lange C, Morales-Rodriguez F, Cruys B, Treps L, Ramer L, Vinckier S, Brepoels K, Wyns S, Souffreau J, Schoonjans L, Lamers WH, Wu Y, Haustraete J, Hofkens J, Liekens S, Cubbon R, Ghesquière B, Dewerchin M, Gervasio FL, Li X, van Buul JD, Wu X, and Carmeliet P

Subjects
Actins metabolism, Animals, Cell Movement, Endothelial Cells metabolism, Female, Glutamate-Ammonia Ligase deficiency, Glutamate-Ammonia Ligase genetics, Glutamate-Ammonia Ligase physiology, HEK293 Cells, Human Umbilical Vein Endothelial Cells cytology, Human Umbilical Vein Endothelial Cells enzymology, Human Umbilical Vein Endothelial Cells metabolism, Humans, Lipoylation, Mice, Palmitic Acid metabolism, Protein Processing, Post-Translational, Stress Fibers metabolism, rho GTP-Binding Proteins chemistry, rho GTP-Binding Proteins metabolism, rho-Associated Kinases metabolism, Endothelial Cells enzymology, Endothelial Cells pathology, Glutamate-Ammonia Ligase metabolism, Glutamine biosynthesis, Neovascularization, Pathologic
Abstract

Glutamine synthetase, encoded by the gene GLUL, is an enzyme that converts glutamate and ammonia to glutamine. It is expressed by endothelial cells, but surprisingly shows negligible glutamine-synthesizing activity in these cells at physiological glutamine levels. Here we show in mice that genetic deletion of Glul in endothelial cells impairs vessel sprouting during vascular development, whereas pharmacological blockade of glutamine synthetase suppresses angiogenesis in ocular and inflammatory skin disease while only minimally affecting healthy adult quiescent endothelial cells. This relies on the inhibition of endothelial cell migration but not proliferation. Mechanistically we show that in human umbilical vein endothelial cells GLUL knockdown reduces membrane localization and activation of the GTPase RHOJ while activating other Rho GTPases and Rho kinase, thereby inducing actin stress fibres and impeding endothelial cell motility. Inhibition of Rho kinase rescues the defect in endothelial cell migration that is induced by GLUL knockdown. Notably, glutamine synthetase palmitoylates itself and interacts with RHOJ to sustain RHOJ palmitoylation, membrane localization and activation. These findings reveal that, in addition to the known formation of glutamine, the enzyme glutamine synthetase shows unknown activity in endothelial cell migration during pathological angiogenesis through RHOJ palmitoylation.

Published
2018
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13. Tumor vessel disintegration by maximum tolerable PFKFB3 blockade.

Author

Conradi LC, Brajic A, Cantelmo AR, Bouché A, Kalucka J, Pircher A, Brüning U, Teuwen LA, Vinckier S, Ghesquière B, Dewerchin M, and Carmeliet P

Subjects
Animals, Cell Line, Tumor, Cell Proliferation drug effects, Endothelial Cells drug effects, Endothelial Cells metabolism, Human Umbilical Vein Endothelial Cells drug effects, Human Umbilical Vein Endothelial Cells metabolism, Humans, Melanoma, Experimental blood supply, Melanoma, Experimental pathology, Melanoma, Experimental ultrastructure, Mice, Inbred C57BL, Neoplasm Metastasis, Neoplasms pathology, Neovascularization, Pathologic pathology, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms pathology, Phosphofructokinase-2 metabolism, Pyridines pharmacology, Neoplasms blood supply, Neoplasms drug therapy, Neovascularization, Pathologic drug therapy, Phosphofructokinase-2 antagonists & inhibitors
Abstract

Blockade of the glycolytic activator PFKFB3 in cancer cells (using a maximum tolerable dose of 70 mg/kg of the PFKFB3 blocker 3PO) inhibits tumor growth in preclinical models and is currently being tested as a novel anticancer treatment in phase I clinical trials. However, a detailed preclinical analysis of the effects of such maximum tolerable dose of a PFKFB3 blocker on the tumor vasculature is lacking, even though tumor endothelial cells are hyper-glycolytic. We report here that a high dose of 3PO (70 mg/kg), which inhibits cancer cell proliferation and reduces primary tumor growth, causes tumor vessel disintegration, suppresses endothelial cell growth for protracted periods, (model-dependently) aggravates tumor hypoxia, and compromises vascular barrier integrity, thereby rendering tumor vessels more leaky and facilitating cancer cell intravasation and dissemination. These findings contrast to the effects of a low dose of 3PO (25 mg/kg), which induces tumor vessel normalization, characterized by vascular barrier tightening and maturation, but reduces cancer cell intravasation and metastasis. Our findings highlight the importance of adequately dosing a glycolytic inhibitor for anticancer treatment.

Published
2017
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14. Role of glutamine and interlinked asparagine metabolism in vessel formation.

Author

Huang H, Vandekeere S, Kalucka J, Bierhansl L, Zecchin A, Brüning U, Visnagri A, Yuldasheva N, Goveia J, Cruys B, Brepoels K, Wyns S, Rayport S, Ghesquière B, Vinckier S, Schoonjans L, Cubbon R, Dewerchin M, Eelen G, and Carmeliet P

Subjects
Culture Media chemistry, Endothelial Cells metabolism, Glutaminase metabolism, Human Umbilical Vein Endothelial Cells, Humans, Metabolic Networks and Pathways, Neovascularization, Pathologic, Asparagine metabolism, Cell Movement drug effects, Cell Proliferation drug effects, Endothelial Cells drug effects, Endothelial Cells physiology, Glutamine metabolism, Neovascularization, Physiologic drug effects
Abstract

Endothelial cell (EC) metabolism is emerging as a regulator of angiogenesis, but the precise role of glutamine metabolism in ECs is unknown. Here, we show that depriving ECs of glutamine or inhibiting glutaminase 1 (GLS1) caused vessel sprouting defects due to impaired proliferation and migration, and reduced pathological ocular angiogenesis. Inhibition of glutamine metabolism in ECs did not cause energy distress, but impaired tricarboxylic acid (TCA) cycle anaplerosis, macromolecule production, and redox homeostasis. Only the combination of TCA cycle replenishment plus asparagine supplementation restored the metabolic aberrations and proliferation defect caused by glutamine deprivation. Mechanistically, glutamine provided nitrogen for asparagine synthesis to sustain cellular homeostasis. While ECs can take up asparagine, silencing asparagine synthetase (ASNS, which converts glutamine-derived nitrogen and aspartate to asparagine) impaired EC sprouting even in the presence of glutamine and asparagine. Asparagine further proved crucial in glutamine-deprived ECs to restore protein synthesis, suppress ER stress, and reactivate mTOR signaling. These findings reveal a novel link between endothelial glutamine and asparagine metabolism in vessel sprouting., (© 2017 The Authors.)

Published
2017
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15. The role of fatty acid β-oxidation in lymphangiogenesis.

Author

Wong BW, Wang X, Zecchin A, Thienpont B, Cornelissen I, Kalucka J, García-Caballero M, Missiaen R, Huang H, Brüning U, Blacher S, Vinckier S, Goveia J, Knobloch M, Zhao H, Dierkes C, Shi C, Hägerling R, Moral-Dardé V, Wyns S, Lippens M, Jessberger S, Fendt SM, Luttun A, Noel A, Kiefer F, Ghesquière B, Moons L, Schoonjans L, Dewerchin M, Eelen G, Lambrechts D, and Carmeliet P

Subjects
Acetates pharmacology, Acetyl Coenzyme A metabolism, Acetylation drug effects, Animals, Carnitine O-Palmitoyltransferase antagonists & inhibitors, Carnitine O-Palmitoyltransferase genetics, Carnitine O-Palmitoyltransferase metabolism, Cell Differentiation drug effects, Cell Differentiation genetics, Endothelial Cells cytology, Endothelial Cells drug effects, Endothelial Cells metabolism, Epigenesis, Genetic, Female, Histones metabolism, Homeodomain Proteins metabolism, Human Umbilical Vein Endothelial Cells, Humans, Lymphatic Vessels drug effects, Mice, Mice, Inbred C57BL, Oxidation-Reduction drug effects, Protein Biosynthesis, Transcription, Genetic, Tumor Suppressor Proteins metabolism, Umbilical Arteries cytology, Up-Regulation, Fatty Acids chemistry, Fatty Acids metabolism, Lymphangiogenesis drug effects, Lymphangiogenesis genetics, Lymphatic Vessels cytology, Lymphatic Vessels metabolism
Abstract

Lymphatic vessels are lined by lymphatic endothelial cells (LECs), and are critical for health. However, the role of metabolism in lymphatic development has not yet been elucidated. Here we report that in transgenic mouse models, LEC-specific loss of CPT1A, a rate-controlling enzyme in fatty acid β-oxidation, impairs lymphatic development. LECs use fatty acid β-oxidation to proliferate and for epigenetic regulation of lymphatic marker expression during LEC differentiation. Mechanistically, the transcription factor PROX1 upregulates CPT1A expression, which increases acetyl coenzyme A production dependent on fatty acid β-oxidation. Acetyl coenzyme A is used by the histone acetyltransferase p300 to acetylate histones at lymphangiogenic genes. PROX1-p300 interaction facilitates preferential histone acetylation at PROX1-target genes. Through this metabolism-dependent mechanism, PROX1 mediates epigenetic changes that promote lymphangiogenesis. Notably, blockade of CPT1 enzymes inhibits injury-induced lymphangiogenesis, and replenishing acetyl coenzyme A by supplementing acetate rescues this process in vivo.

Published
2017
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