79 results on '"Denis, I"'
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2. Tris(trifluoromethyl)germyl biphenyl conjugated molecular system with ferrocenyl substituent: Confirmation of photoinduced intramolecular charge transfer to the germanium center
- Author
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Nikolai L. Ermolaev, Georgy K. Fukin, Andrei S. Shavyrin, Mikhail A. Lopatin, Olga V. Kuznetsova, Denis I. Kryzhkov, Stanislav K. Ignatov, Evgeniy P. Chuhmanov, Nadezhda T. Berberova, and Konstantin P. Pashchenko
- Subjects
Inorganic Chemistry ,Organic Chemistry ,Materials Chemistry ,Physical and Theoretical Chemistry ,Biochemistry - Published
- 2023
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3. Risk factors for death, stroke, and bleeding in 28,628 patients from the GARFIELD-AF registry: Rationale for comprehensive management of atrial fibrillation
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Ibrahim, M., Erga, K., Hole, T., Gjertsen, E., Kirchner-Volker, K., Hubert, K., Helgert, K., Hahn, M., Grytzmann, A., Geyer, J., Gehre, J., Frommhold, R., Fritz, C., Floegel, H., Flint, K., Fleck, A., Diez, S., Dichristin, U., Busch, F., Buckert, D., Bonin, K., Boehme, S., Bergner, K., Babjakova, Z., Mitrovic, V, Mueller, H., Mueller, T., Erdle, W., Schoen, S., Roehnisch, J-U, Salbach, P., Haverkamp, W., Sievers, B., Karolyi, L., Bernhardt, P., Schellong, S., Schwencke, C., Ebert, H-H, Baumbach, S., Abdel-Qader, M., Mueller, K., Kamin, S., Brauer, G., Buchner, T., Lauer, H., Schubert, C., Kolitsch, K., Lilienweiss, V, Leuchtgens, H., Hey, H., Eissing, V, Horstmeier, U., Mayer, P., Vormann, R., Rapp, K-A, Michel, H., Dshabrailov, J., Dorsch, W., Hauk, J., Reimer, D., Hergdt, G., Bindig, H-W, Lehmann, G., Hartmann, H-J, Laessig, T., Omankowsky, S., Caspar, A., Kahl, F., Kropp, M., Zimny, H-H, Stuchlik, G., Babyesiza, A., Schwarz, T., Axthelm, C., Wildenauer, W., Wiswedel, H., Ludwig, N., Sandow, P., Pustelnik, A., Menke, H., Guenoun, M., Boveda, S., Cebron, J-P, Delarche, N., Piot, O., Destrac, S., Marquand, A., Koujan, M. B., Muller, J-J, Loiselet, P., Paganelli, F., Gottwalles, Y., Galinier, M., Le Heuzey, J-Y, Vasankari, T., Rasanen, V, Peltomaki, K., Nappila, H., Koistinen, J., Arola, O., Airaksinen, J., Raatikainen, P., Vesterager, K., Tilma, J., Therkelsen, A., Schou, M., Park, J., Nygaard, A., Leth, M., Jensen, M., Jensen, L., Eriksen, E., Ellervik, C., Bang-Hansen, T., Raymond, I, Ibsen, H., Egstrup, K., Skagen, K., Dominguez, H., Mertz, J., Bruun, M., Loekkegaard, T., Simonsen, P., Solgaard, J., Boerger, J., Markenvard, J., Bremmelgaard, A., Rasmussen, S., Hintze, U., Husted, S., Nielsen, H., Nielsen, J., Zika, J., Zidek, M., Valtova, M., Sveceny, J., Sulc, A., Prochazkova, E., Potuznik, P., Michalik, D., Majernikova, M., Mahdalikova, L., Ludkova, A., Lubanda, H., Lipoldova, J., Lindourkova, A., Labrova, R., Krcova, E., Kratochvilova, R., Kopeckova, I, Janska, L., Hubacova, V, Horejsi, M., Honek, J., Drasnar, T., Dastychova, L., Chlumsky, J., Bultas, J., Novikova, E., Nagibovich, G., Motylev, I, Monako, G., Medvedeva, T., Machilskaya, O., Lileeva, E., Lebedeva, O., Kolesova, T., Ivanova, Y., Gurmach, M., Gubanov, A., Gorshkova, T., Gorbunova, E., Erofeeva, S., Dumikyan, A., Chugunnaya, S., Bitakova, F., Belenkova, Y., Batalov, R., Agakhanyan, A., Edin, A., Nagibovich, O., Shapovalova, Y., Zubeeva, G., Rossovskaya, M., Sobolev, K., Polkanova, E., Moiseeva, Y., Kostenko, V, Novikova, T., Zrazhevskiy, K., Mazur, E., Shutemova, E., Sergeev, M., Chizhov, P., Aleksandrova, E., Miller, O., Barbarash, O., Vishnevsky, A., Drapkina, O., Zateyshchikov, D., Poltavskaya, M., Yakupov, E., Khokhlov, A., Egorova, L., Nikolaev, K., Kolesnikova, A., Kropacheva, E., Zateyshchikova, A., Belenky, D., Kamalov, G., Popov, S., Tereshchenko, S., Libis, R., Eltishcheva, V, Panchenko, E., Zyczynska-Szmon, M., Zakutynska-Kowalczyk, K., Wrobel, M., Wojnowski, L., Wojewoda, P., Wilgat-Szecowka, M., Wilczewski, P., Wierzbicka, A., Wieczorek, W., Wesolowska, K., Wegrzynowska, M., Walasik, P., Tybura, S., Trzcinski, G., Troszczynska, M., Traczyk, T., Szwoch, M., Szumczyk-Muszytowska, G., Szulowska, A., Szuchnik, E., Szkrobka, W., Szczepanska, A., Szalecki, P., Szafranski, J., Sukiennik-Kujawa, M., Stopyra-Poczatek, M., Starak-Marciniak, J., Staniszewska, E., Staneta, P., Splawski, M., Smichura, M., Skalska, J., Sidor, A., Rzyczkowska, B., Rychta, J., Rozewska-Furmanek, D., Roszczyk, N., Rostoff, P., Romaszkiewicz, R., Romanek, J., Rogowski, W., Raczynska, A., Ptaszynski, P., Piotrowicz, R., Pawlik-Rak, E., Pawelska-Buczen, A., Ozgowicz, M., Opielowska-Nowak, B., Nowak, S., Nowak, A., Niemirycz-Makurat, A., Niedek, J., Neubauer-Geryk, J., Mielcarek, M., Miedlar, E., Metzgier-Gumiela, A., Mazur, M., Markiewicz, A., Mariankowski, R., Majewska, K., Machnikowska, M., Lysek-Jozefowicz, A., Luka, J., Loboz-Rudnicka, M., Lip, K., Lichota, E., Lewicka, E., Leszczynski, J., Lesniewska-Krynska, D., Kustrzycka-Kratochwil, D., Kurdzielewicz, W., Krzyzanowski, M., Poli, D., Cappelli, R., Tessitori, M., Martini, G., Caimi, T. M., Moia, M., Di Minno, G., Testa, S., Santoro, R., Tiraferri, E., Ambrosio, G., Agnelli, G., Vandrus, B., Sztanyik, F., Szilagyi, A., Bockova, L., Antonova, P., Durdil, V, Lastuvka, J., Novak, M., Vitovec, J., Spinar, J., Podrazil, P., Honkova, M., Dedek, V, Petrova, I, Pisova, J., Jerabek, O., Burianova, H., Monhart, Z., Kotik, I, Hubac, J., Ferkl, R., Racz, B., Plocova, K., Kotik, L., Olsr, J., Ludka, O., Zidkova, E., Machova, V, Spacek, R., Reichert, P., Jansky, P., Weyn, T., Vydt, T., Verloove, H., Vergauwen, L., Vantomme, C., Vanhauwaert, B., Vanhalst, E., Vandorpe, A., Vandenbroeck, D., Vandekerckhove, Y., Vandekerckhove, H., Van Lier, D., Van Durme, F., Tincani, G., Thyssen, V, Tahon, S., Stockman, I, Smolders, W., Smessaert, C., Simons, N., Semeraro, O., Scheurwegs, C., Salembier, J., Rombouts, H., Richa, J., Raymenants, E., Raepers, M., Postolache, A., Pollet, P., Piamonte, V, Nimmegeers, J., Mestdagh, I, Lips, S., Jacobs, C., Helvasto, L., Hellemans, S., Gits, F., Ghekiere, M., Feys, E., Eykerman, T., Everaert, M., Drieghe, S., Dormal, F., Deweerd, E., Derycker, K., Denie, D., Delvigne, M., Delforge, M., Leyva Rendon, A., Matadamas Hernandez, N., Cardona Munoz, E., Pozas, G., Llamas Esperon, G., Lopez Rosas, E., Villarreal Umana, S., Espinola Zavaleta, N., Cabrera Jardines, R., Ramos Zavala, M. G., Leal Cantu, R., Illescas Diaz, J., Sanchez Diaz, C. J., Villan, C., Vergara, M., Olguin, V, Munoz Oyarzon, J., Molina, E., Lara, C., Campisto, Y., Aguilar, J., Astudillo, C., Rey, C., Charme Vilches, G., Larico Gomez, M., Lanas, F., Forero, A., Montecinos, H., Marin Cuevas, P., Houzvic, C., Conejeros, C., Stockins Fernandez, B. A. J., Potthoff Cardenas, S., Arriagada, G., Bugueno Gutierrez, C., Eggers, G., Corbalan, R., Villaca Guimaraes Filho, F., Vila Boas, L., Vieira Torres, L. G., Vieira Homem, R., Vidal Armaganijan, L., Vicente, C., Viana, T., Vargas, T., Valois, M. V., Unterkircher, B., Trama, L., Toazza Duda, N., Stoll, C., Spolaor, L., Soares, L., Silva, S., Seroqui, M., Santos, M., Santos, I, Santos, D., Ruaro Reichert, T., Roesch, H., Rodrigues, A., Ribeiro, S., Rech, R. L., Ramos Pereira, N., Queirantes, C., Quaia Fortunato, S. C., Poletti, S., Perreira, R., Pereira, V. L., Pereira, L., Pavani, R., Palmegiani, E., Oss Emmer, S., Ormundo, C., Nanzer Vital, C., Mouco, O. M. C. C., Mortari, L., Melo, G., Mazzoni, M., Kuvanova, M., Kurylo, B., Kupriyanova, T., Kungurtseva, O., Kuchuk, P., Kropova, O., Korneeva, O., Konyushenko, D., Heinz, G-U, Zutz, S., Glatzel, D., Rehling, G., Eder, W., Eissfeller, E., Hohensee, H., Riegel, P., Zauzig, H., Schaefer, T., Kopf, A., Kellner, B-T, Gerbaulet, U., Purr, J., Koeniger, G., Darius, H., Suissa, A., Sanchez, D., Rosolin, N., Robin, F., Lemaire, N., Ledure, S., Kemmel, A., Giry, X., Ducasse, E., Dubois, B., Decarsin, N., Corrihons, E., Beltra, C., Barreau, A., Poulard, J-E, Perron, J-M, Falvo, N., Chemin, F., Berneau, J-B, Casassus, F., Fedorowsky, A., Brugnaux, J. P., Nazeyrollas, P., Bearez, E., Mouallem, J., Crousillat, B., Obadia, D., Martelet, M., Doucet, B., Boyes, J-P, Monniot, G., Sellem, F., Navarre, V, Churet, J-B, Bonnefoy, M., Mielot, A., Mahagne, M. H., Neau, J-P, Sibon, I, Vandamme, X., Milandre, L., Rodier, G., Lemaire, M., Huberman, J-P, Fournier, P-Y, Kadouch, J., Ellie, E., Amarenco, P., Zuber, M., Assouline, S., Ohayon, J., Galley, D., Guedj-Meynier, D., Marinho, M. C., Macagnan, A. P., Lustosa, E., Lourenco da Silva Junior, O., Lopes, D., Lino, E. G., Komar, D., Junior, G., Jannuzzi, F., Igansi, F., Hettwer Magedanz, E., Guizzardi, S., Guanaes, D., Gottardo, P., Freire, F., Franchin Ferraz, R., Frack Costantini, C. R., Fonseca, C., Fernandes, E., Felix Lorenzato Fonseca, T., Fabri, P., Esteves, D. C., Ely Pizzato, P., Drummond Wainstein, A. P., Dias, M. A., Dias, C., Del Monaco, M., de Araujo, G. R., Daros, E., da Silveira, J. A., da Silva Paulitsch, F., da Silva, L. S., Costantini Ortiz, C., Costa, M., Correa, C., Codonho Goes, N., Clemente Mingireanov, R., Chokr, M. O., Chieza, F., Cardoso Boscato, S., Caporale, M., Camazzola, F. E., Borges Queiroz, L., Biazus, G., Benez Teixeira Lemos, M. A., Bellotti Lopes, H., Belisario Falchetto, E., Barroso, S., Barbosa, T., Arruda Nakazone, M., Araujo, V, Alves de Oliveira Gomes, J., Agliardi, P., Gomes Ferreira, L. G., do Carmo Borges, N. C., Simoes de Almeida, R., Nigro Maia, L., Tumelero, R. T., de Moura Xavier Moraes Junior, J. B., Aranha Rosito, G. B., Alban, F., Broilo Franca, C. C., Pereira Martins, M., Chemello, D., Pisani, C., Finimundi, H. C., Abdalla Saad, J., Costantini Frack, C. R., Munhoz da Fontoura Tavares, C., Vieira Botelho, R., Lanna Figueiredo, E., Ramos Filho, R. A., Reis, G., Roquette, F., Bertolim Precoma, D., Moncada, C., Alves da Costa, F. A., Da Rocha Rodrigues, T., Del Carlo, C. H., Westerlund Montera, M., Bodanese, L. C., Menezes Lorga Filho, A., Moura Jorge, J. C., Moreira, D., Pires, L., Ferreira Rossi, P. R., Silveira Teixeira, M., Ribeiro, J. M., de Souza Neto, J. D., Kunz Sebba Barroso de Souza, W., Steffens, A., Faria Neto, J., Armaganijan, D., Jaber, J., Sobral Filho, D. C., Barretto, A. C. P., Zurbrigk, F. J., Zillo, M., Yunis, M. E., Vallejo, M., Tufare, A. L., Tonelli, L., Tinto, J. F., Sossich, A., Schygiel, P. O., Sanziani, L. S., Salinger, M., Said Palladino, M. E., Rolandi, F., Rodriguez, M. A., Ricotti, C., Potito, R. N., Pontoriero, J., Perez Prados, G., Novas, V, Navarro, A., Munguia, R., Meirino, A., Mautner, B., Matkovich, J., Martinelli, C., Martinelli, A., Maffei, L., Maehara, G., Lopez, A., Ingratta, M., Hrabar, A. D., Hansen, V, Had, M. de L. M., Gurfinkel, E. P., Gimenez, C. H., Giacomi, M. P., Funosas, C., Foa Torres, M., Fernandez Voena, F., Fanuele, M., Eden, M. F., Diez, F., De Urquiza, I. N., Damonte, A. A., Costamagna, O. J. A., Costabel, J. P., Colombo Berra, F., Carrizo, R., Cappi, A. L., Campisi, V, Cabrini, R., Buzzetti, C., Borchowiec, S., Berli, M., Berli, F., Bergesio, L., Belardi, J. A., Arias, L., de Weerdt, N., de Vos, M., De Coninck, M., De Cleen, D., Conde Y Bolado, A., Casier, T., Capiau, H., Brike, C., Bouvy, C., Blockmans, M., Billiaux, A. C., Barbuto, A-M, Banaeian, F., Ascoop, A-K, Alzand, B., Hermans, K., Thoeng, J., Striekwold, H., Xhaet, O., Verstraete, S., Marechal, P., Beutels, M., Balthazar, Y., Faes, D., Blankoff, I, Purnode, P., Vercammen, J., Ann, W., Hollanders, G., Heyse, A., Voet, J., De Wolf, A., Godart, P., Boussy, T., Mairesse, G., Desfontaines, P., Wollaert, B., Vervoort, G., Capiau, L., Parque, J-L, Vandergoten, P., Paparella, G., Cools, F., Zanolin, D., Woehrer, C., Vonbank, A., Vogel, B., Stoeckloecker, C., Said, A., Mirtl, A., Mark, T., Lischka-Lindner, A., Freihoff, F., Eischer, L., Ebner, K-M, Breier, R., Strohmer, B., Schaflinger, E., Pichler, M., Rasch, H., Sykora, J., Kaserer, P., Eichinger-Hasenauer, S., Lang, W., Gegenhuber, A., Schneeweiss, B., Winkler, M., Huber, K., Podczeck-Schweighofer, A., Hagn, C., Foechterle, J., Drexel, H., Lenz, K., Brodmann, M., Trujillo Cortes, R., Tovar Castaneda, A. C., Sida Perez, P., Santana, G., Salinas, A., Ruiz Cornejo, M., Romero Cardona, G., Roa Castro, V, Rivera Ramos, C., Ramos Gonzalez, M., Pina Toledano, S., Perez Sanchez, J. A., Perez, F., Padilla Macias, P., Ortiz, A., Ochoa Aybar, S., Nikitina, N., Morales, J., Mendoza, N., Martinez Vasquez, D., Mancilla Ortiz, M. C., Izquierdo, T., Hernandez Gonzalez, S., Guajardo, P., Gonzalez Salas, L. G., Gonzalez Garcia, C. L., Gonzalez Felix, E. J., Godoy, K., Garcia Nava, R. H., Flores Silva, F., Espinosa, I, Chavarria, M., Avena, R., Altamirano Bellorin, S., Alfaro, T. A. A., Fajardo Campos, P., Fierro Fierro, O., Morales Cerda, J. D., Arriaga Nava, R., Benavides Gonzalez, M., Nandayapa Flores, O., Bazzoni Ruiz, A., Reyes-Sanchez, R., Chuquiure Valenzuela, E., Cantu Brito, C., Diaz de la Vega, C., Olvera Ruiz, R., Alvarez Lopez, H., Leiva Pons, J. L., Rodriguez Briones, I, Yong, R., Velasco Barcena, J., Flores Martinez, D., Villeda Espinosa, E., Gaona Rodriguez, R., Lopez Prieto, J. J., Hernandez Herrera, C., Lopez Villezca, D., Virgen Carrillo, L., de los Rios Ibarra, M., Garcia Hernandez, N., Arabetti, C., Alvarez D'Amelio, A., Alaguibe, E. D., Ferroni, F., Gomez Vilamajo, O. A., Berli, M. A., Cartasegna, L. R., Sinisi, V. A., Sassone, S., Fosco, M. J., Fernandez, A. A., Egido, J., Dran, R. D., Ramos, J. L., Di Paola, L. A., Zapata, G., Conde, D., Ahuad Guerrero, R. A., Giacomi, G., Centurion, N., Kleiban, A. J., Dragotto, P., Berman, S. G., Fernandez Caputi, V, Sambadaro, G. A., Ingaramo, A. C., Vensentini, N., Luciardi, H. L., Yuksekdag, V, Yilmaz, F., Yildirim, R., Yildirim, E., Alkan, D. Uzun, Seker, T., Sayin, B. Y., Sahiner, L., Sag, H., Quisi, A., Ozcelik, E., Okutucu, S., Karatas, S. Kilic, Karaayvaz, E. B., Ikitimur, B., Genc, D., Felekoglu, M. A., Esen, M., Oto, A., Caliskan, S., Buyukpapuc, M., Budeyri, S., Bireciklioglu, M. F., Aras, F., Alpay, D., Aktas, O., Abdelrahman, H., Aras, D., Okuyan, E., Ersanli, M., Yorgun, H., Demir, M., Sayin, T., Sucu, M., Ozdemir, M., Pekdemir, H., Cayli, M., Ongen, Z., Yeter, E., Aydinlar, A., Yilmaz, O., Ozdemir, K., Ozdogru, I, Altun, A., Yawila, S., Wutthimanop, A., Wongtheptien, W., Wisaratapong, T., Park, B. R., Park, A. R., Noh, I. K., Lee, W. Y., Lee, S., Lee, S. H., Lee, S. E., Lee, R. W., Lee, M-Y, Lee, M. S., Lee, K. R., Lee, K. H., Lee, H-Y, Lee, H. Y., Lee, G. H., Lee, E. H., Lee, C. S., Kim, Y, Kim, S. H. (Sang Hyun), Kim, S. H. (Sang Hee), Kim, M. S., Kim, K. T., Kim, J. A., Kim, J. S. (Jung Sook), Kim, J. S. (Ji Seon), Kim, H. J. (Hyun Ju), Kim, H. J. (Hyeon Jeong), Jung, I-A, Jeong, H. K., Jeon, Y. R., Jeon, S. R., Jeon, H-G, Jang, S., Jang, H-S, Jang, E. M., Hwang, S. W., Her, K. O., Heo, E. S., Han, S., Choi, H. S., Choi, H. K., Choi, E. H., Choi, E. A., Chi, W. J., Baek, A. L., Bae, H., An, H. J., Ahn, J. J., Kim, D. B., Kim, C-J, Hwang, G-S, Jung, B. C., Kim, K-S, Kim, N-H, Yoon, J. H., Park, S. H., Hong, T. J., Cha, T-J, Kwak, J. J., Lim, H. E., On, Y. K., Nam, G-B, Cho, J-G, Sung, J. H., Han, S-J, Park, H. K., Park, J. S., Shin, D-G, Jeon, H-K, Kim, S-H, Cho, M-C, Oh, Y. S., Choi, D. J., Kim, D-K, Park, S. W., Ryu, D. R., Kim, D. H., Jang, S-W, Souto, L., Negri, A., Ferreira Braga, J. C., Kerr Saraiva, J. F., Fernandes Manenti, E. R., Araujo, G. R., Lopes, R., Lopes, A., Kim, J. H., Kim, J-B, Pak, H. N., Oh, S., Yeo, C., Yap, S. Y., Thng, S., Lim, W. T., Lim, G., Lee, Y. M., Jaufeerally, F. R., Chen, D. D., Chow, J. H., Foo, C. G., Ching, C. K., Lim, T. W., Yoshida, K., Yokoyama, Y., Yasui, K., Yamazoe, M., Yamaura, M., Yamamoto, T., Yamamoto, K. (Kunihiko), Yamamoto, K. (Kentaro), Yamamoto, K. (Kenichi), Yamaguchi, H., Yamagishi, T., Yamada, T., Watanabe, M., Washizuka, T., Wakiyama, T., Wakaki, N., Ueyama, Y., Ueda, T., Ueda, O., Uchiyama, H., Tsuzaki, K., Tsuji, T., Tsuchiya, Y., Toru, S., Tohyo, S., Teragawa, H., Taya, K., Tanabe, G., Tana, T., Takenaka, K., Takei, K., Takeda, H., Take, S., Takanaka, C., Takai, H., Takahashi, S., Takahashi, K., Takagi, Y., Takagi, T., Taguchi, A., Tada, M., Suzuki, Y., Suzuki, S. (Susumu), Suzuki, S. (Shunji), Suzuki, S. (Shu), Suzuki, K. (Keita), Suzuki, K. (Kazuo), Sugimoto, C., Suga, T., Shozawa, Y., Shiraiwa, T., Shirai, T., Shinozuka, T., Shinohe, R., Shinohara, H., Shindo, T., Shimoyama, Y., Shimono, H., Shiina, Y., Shibata, N., Ota, A., Oriso, S., Pearce, Y. Onuki, Ono, T., Ono, H., Okuyama, M., Okita, H., Okamoto, K., Okada, M., Ohara, N., Ogawa, T., Nozoe, M., Nomura, S., Nomura, K., Niwa, I., Nishizawa, K., Nishioka, H., Nishino, K., Nishihata, Y., Nishida, Y., Niinuma, H., Niijima, Y., Nariyama, J., Nanke, T., Nakazato, R., Nakayama, T., Nakanishi, N., Nakamura, R., Nakamura, M., Nakahara, S., Nakagomi, A., Nagata, H., Nagata, E., Nagai, S. (Shunichi), Nagai, S. (Sho), Murai, O., Morishita, K., Moriai, O., Mori, T., Mizuno, A., Mizuguchi, I., Miyata, S., Miyashita, A., Miyamoto, H., Miyajima, S., Miyaguchi, S., Miura, N., Mitsuhashi, H., Mineoi, K., Matsuura, Y., Matsushita, K., Matsui, S., Maruyama, Y., Maeda, K., Maeda, I., Kumazaki, T., Kumai, Y., Kozuka, T., Kotani, T., Koshibu, Y., Komatsu, I., Komatsu, H., Kojima, J., Koeda, T., Kobayashi, T., Kito, T., Kitazumi, H., Kitazawa, H., Kira, T., Kim, J., Kawano, S., Kawamoto, T., Kawakami, S., Kawakami, K., Kawai, K., Kawada, Y., Kato, Y., Kato, T., Vorasettakarnkij, Y., Tiyanon, W., Thangpet, O., Tangsirira, A., Suttana, T., Sukklad, P., Suebjaksing, W., Sriwichian, A., Sirichai, R., Silaruks, B., Sawanyawisuth, K., Sanit, K., Ratchasikaew, S., Pumprueg, S., Pornnimitthum, N., Poomiphol, S., Pongmorakot, K., Phunpinyosak, P., Phrommintikul, A., Phangyota, J., Ninwaranon, S., Naratreekoon, B., Kongsin, C., Kitmapawanont, U., Khunkong, K., Khattaroek, R., Inphontan, R., Hongsuppinyo, S., Gunaparn, S., Bamungpong, P., Kaewsuwanna, P., Jai-Aue, S., Bunyapipat, T., Khunrong, P., Hutayanon, P., Santanakorn, Y., Chattranukulchai, P., Chatlaong, B., Cholsaringkarl, D., Boonyapisit, W., Katekangplu, P., Likittanasombat, K., Siriwattana, K., Wongcharoen, W., Silaruks, S., Rungaramsin, S., Chantrarat, T., Pattanaprichakul, S., Laksomya, T., Cheewatanakornkul, S., Kanokphatcharakun, K., Mongkolwongroj, P., Chawanadelert, S., Angchaisuksiri, P., Yun, S. 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Webster, J, Hodgins, I, Vercoe, S, Roome, P, Pinnock, H, Patel, J, Ali, A, Hart, N, Davies, R, Stuart, E, Neden, C, Danielsen, M, Heath, R, Sharma, P, Galloway, S, Hawkins, C, Oliver, R, Aylward, M, Mannion, S, Braddick, M, Edwards, D, Rothwell, A, Sabir, A, Choudhary, F, Khalaque, S, Wilson, A, Peters, S, Coulson, W, Roberts, N, Heer, A, Coates, S, Ward, B, Jackson, D, Walton, S, Shepherd, D, Sterry, M, Wong, T, Boon, M, Bunney, R, Haria-Shah, R, Baron, R, Davies, S, Schatzberger, T, Hargreaves, N, Stephenson, T, Batson, R, Lucraft, L, Myhill, T, Estifano, S, Geatch, D, Wilkinson, J, Veale, R, Forshaw, K, Davies, T, Zaman, K, Vinson, P, Liley, C, Bandrapalli, M, Mcginty, P, Wastling, R, Mceleny, P, Beattie, A, Cooke, P, Wong, M, Gunasegaram, J, Pugsley, M, Ahmad, S, A'Court, C, Ayers, J, Bennett, J, Cartwright, S, Dobson, S, Dooldeniya, C, Flynn, A, Fox, R, Goram, J, Halpin, A, Hay, A, Jacobs, P, Jeffers, L, Lomax, L, Munro, I, Muvva, R, Nadaph, M, Powell, K, Randfield, S, Redpath, D, Reed, R, Rickenbach, M, Rogers, G, Seamark, C, Shewring, J, Simmons, P, Simper, H, Stoddart, H, Sword, A, Thomas, N, Thomson, A, Blenkhorn, A, Singh, B, Van Gaal, W, Abhayaratna, W, Lehman, R, Roberts-Thomson, P, Kilian, J, Coulshed, D, Catanchin, A, Colquhoun, D, Kiat, H, Eccleston, D, French, J, Zimmett, L, Ayres, B, Phan, T, Blombery, P, Crimmins, D, O'Donnell, D, Choi, A, Astridge, P, Arstall, M, Jepson, N, Binnekamp, M, Lee, A, Rogers, J, Starmer, G, Carroll, P, Faunt, J, Aggarwala, A, Barry, L, Batta, C, Beveridge, R, Black, A, Bonner, M, Boys, J, Buckley, E, Campo, M, Carlton, L, Connelly, A, Conway, B, Cresp, D, Dimitri, H, Dixon, S, Dolman, M, Duroux, M, Eskandari, M, Eslick, R, Ferreira-Jardim, A, Fetahovic, T, Fitzpatrick, D, Geraghty, R, Gibbs, J, Grabek, T, Modi, M, Hayes, K, Hegde, M, Hesketh, L, Hoffmann, B, Johnson, K, Juergens, C, Kassam, I, Lawlor, V, Lehman, M, Lehman, S, Leung, D, Mackay, S, Mackenzie, M, Mccarthy, C, Mcintosh, C, Mckeon, L, Morrison, H, Mussap, C, Myers, J, Nagalingam, V, Oldfield, G, O'May, V, Palmer, J, Parsons, L, Patching, K, Patching, T, Paul, V, Plotz, M, Preston, S, Rashad, H, Ratcliffe, M, Raynes, S, Rose, J, Sanders, L, Seremetkoska, M, Setio, H, Shone, S, Shrestha, P, Singh, C, Singleton, C, Stoyanov, N, Sutcliffe, S, Swaraj, K, Tarrant, J, Thompson, S, Tsay, I, Vorster, M, Waldman, A, Wallis, L, Wilford, E, Wong, K, Luton, R, Gupta, M, Pandey, A, Cheung, S, Leader, R, Beaudry, P, Ayala-Paredes, F, Berlingieri, J, Heath, J, Poirier, G, Du Preez, M, Nadeau, R, Dresser, G, Dhillon, R, Hruczkowski, T, Schweitzer, B, Coutu, B, Angaran, P, Macdonald, P, Vizel, S, Fikry, S, Parkash, R, Lavoie, A, Cha, J, Ramjattan, B, Bonet, J, Ahmad, K, Aro, L, Aves, T, Beaudry, K, Bergeron, C, Bigcanoe, J, Bignell, N, Breakwell, L, Burke, E, Carroll, L, Clarke, B, Cleveland, T, Daheb, S, Dehghani, P, Denis, I, Djaidani, Z, Dorian, P, Douglass, S, Dunnigan, J, Ewert, A, Farquhar, D, Fearon, A, Ferleyko, L, Fournier, D, Fox, B, Grenier, M, Gulliver, W, Haveman, K, Hines, C, Hines, K, Jackson, A, Jean, C, Jethoo, G, Kahlon, R, Kelly, S, Kim, R, Korley, V, Kornder, J, Kwan, L, Largy, J, Lewis, C, Lewis, S, Mangat, I, Moor, R, Navratil, J, Neas, I, Otis, J, Otis, R, Pandey, M, Petrie, F, Pinter, A, Raines, M, Roberts, P, Robinson, M, Sas, G, Schulman, S, Snell, L, Spearson, S, Stevenson, J, Trahey, T, Wright, D, El-Aziz, A, Seif, S, El Din, M, El Etriby, S, Elbahry, A, El-Etreby, A, Elkhadem, M, Katta, A, Khairy, T, Mowafy, A, Nawar, M, Ohanissian, A, Reda, A, Reda, M, Salem, H, Sami, N, Samir, S, Setiha, M, Sobhy, M, Soliman, A, Taha, N, Tawfik, M, Zaatout, E, Kettles, D, Bayat, J, Siebert, H, Horak, A, Kelfkens, Y, Garda, R, Pillay, T, Guerra, M, van Zyl, L, Theron, H, Murray, A, Louw, R, Greyling, D, Mntla, P, Ueckermann, V, Loghdey, R, Ismail, S, Ahmed, F, Engelbrecht, J, Ramdass, A, Maharajh, S, Oosthuysen, W, Angel, G, Bester, C, Booysen, M, Boshoff, C, Cannon, C, Cassimjee, S, Chami, C, Conway, G, Davids, A, de Meyer, L, Du Plessis, G, Ellis, T, Henley, L, Karsten, M, Loyd, E, Marks, J, Mavhusa, L, Mostert, M, Page, A, Rikhotso, L, Salie, M, Sasto, J, Shaik, F, Skein, A, Smith, L, Tarr, G, Tau, T, van Zyl, F, Yousef, G, Agrawal, A, Nathani, M, Ibrahim, M, Esheiba, E, Singh, R, Naguib, A, Abu-Mahfouz, M, Al Omairi, M, Al Naeemi, A, Maruthanayagam, R, Bazargani, N, Wassef, A, Gupta, R, Khan, M, Subbaraman, B, Abdul, A, Al Mulla, A, El Bardisy, S, Haridas, P, Jadhav, S, Magdaluyo, K, Makdad, M, Maqsood, I, Mohamed, R, Sharma, N, Sharma, R, Thanzeel, M, Canosa, R, Rama, P, Blumberg, E, Garcia, J, Mullen, P, Wilson, V, Quick, A, Ferrick, K, Kutayli, W, Cox, M, Franco, M, Falkowski, S, Mendelson, R, Williams, M, Miller, S, Beach, S, Alfieri, A, Gutowski, T, Haque, I, Reddy, R, Ahmed, W, Delafontaine, P, Diercks, D, Theodoro, D, Remmel, K, Alberts, M, Ison, R, Noveck, H, Duffy, P, Pitta, S, Nishijima, D, Treasure, C, Asafu-Adjaye, N, Ball, K, Bartlett, M, Bentley, M, Bowers, S, Brown, A, Browne, A, Cameron-Watts, J, Canova, M, Cassidy, D, Cervellione, K, Congal, S, Depauw, J, Dickerson, A, Eley, M, Evans, L, Felpel, S, Ferdinand, K, Fielder, D, Gentry, P, Haideri, A, Hakimi, F, Harbour, T, Hartranft, E, Hawkins, B, Headlee, M, Henson, L, Herrick, C, Hicks, T, Jasinski, S, Jones, A, Jones, L, Jones, P, Karl, S, Keeling, M, Kerr, J, Knowles, P, Langdon, J, Lay, M, Lee, J, Lincoln, T, Malone, E, Merliss, A, Merritt, D, Minardo, J, Mooso, B, Orosco, C, Palumbo, V, Parker, M, Parrott, T, Paserchia, S, Pearl, G, Peterson, J, Pickelsimer, N, Purcell, T, Raynor, J, Raziano, S, Richard, C, Richardson, T, Robertson, C, Sage, A, Sanghera, T, Shaw, P, Shoemaker, J, Smith, K, Stephanie, B, Thatcher, A, Theobald, H, Thompson, N, Treasure, L, Tripti, T, Verdi, C, and Worthy, V
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Registrie ,Male ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,lcsh:Medicine ,Management of atrial fibrillation ,Comorbidity ,030204 cardiovascular system & hematology ,Pathology and Laboratory Medicine ,ACE inhibitor therapy ,Vascular Medicine ,Biochemistry ,Cohort Studies ,0302 clinical medicine ,Risk Factors ,Atrial Fibrillation ,Chronic Kidney Disease ,Medicine and Health Sciences ,030212 general & internal medicine ,Prospective Studies ,Registries ,Lipid Hormones ,lcsh:Science ,Prospective cohort study ,Diuretics ,Stroke ,Aldosterone ,Aged, 80 and over ,Multidisciplinary ,Fibrinolytic Agent ,Pharmaceutics ,Drugs ,Atrial fibrillation ,Cardiovascular therapy ,Death ,Treatment Outcome ,Nephrology ,Cohort ,Female ,Drug therapy ,Arrhythmia ,Cohort study ,Human ,Research Article ,medicine.medical_specialty ,Cardiology ,Hemorrhage ,Risk Assessment ,03 medical and health sciences ,Signs and Symptoms ,Fibrinolytic Agents ,Diagnostic Medicine ,Internal medicine ,Journal Article ,medicine ,Humans ,Vascular Diseases ,Renal Insufficiency, Chronic ,medicine (all) ,Aged ,Heart Failure ,Pharmacology ,business.industry ,Risk Factor ,lcsh:R ,Anticoagulant ,Statins ,Anticoagulants ,Biology and Life Sciences ,medicine.disease ,Hormones ,Prospective Studie ,lcsh:Q ,Cohort Studie ,business ,RC ,Kidney disease - Abstract
Contains fulltext : 190537.pdf (Publisher’s version ) (Open Access) BACKGROUND: The factors influencing three major outcomes-death, stroke/systemic embolism (SE), and major bleeding-have not been investigated in a large international cohort of unselected patients with newly diagnosed atrial fibrillation (AF). METHODS AND RESULTS: In 28,628 patients prospectively enrolled in the GARFIELD-AF registry with 2-year follow-up, we aimed at analysing: (1) the variables influencing outcomes; (2) the extent of implementation of guideline-recommended therapies in comorbidities that strongly affect outcomes. Median (IQR) age was 71.0 (63.0 to 78.0) years, 44.4% of patients were female, median (IQR) CHA2DS2-VASc score was 3.0 (2.0 to 4.0); 63.3% of patients were on anticoagulants (ACs) with or without antiplatelet (AP) therapy, 24.5% AP monotherapy, and 12.2% no antithrombotic therapy. At 2 years, rates (95% CI) of death, stroke/SE, and major bleeding were 3.84 (3.68; 4.02), 1.27 (1.18; 1.38), and 0.71 (0.64; 0.79) per 100 person-years. Age, history of stroke/SE, vascular disease (VascD), and chronic kidney disease (CKD) were associated with the risks of all three outcomes. Congestive heart failure (CHF) was associated with the risks of death and stroke/SE. Smoking, non-paroxysmal forms of AF, and history of bleeding were associated with the risk of death, female sex and heavy drinking with the risk of stroke/SE. Asian race was associated with lower risks of death and major bleeding versus other races. AC treatment was associated with 30% and 28% lower risks of death and stroke/SE, respectively, compared with no AC treatment. Rates of prescription of guideline-recommended drugs were suboptimal in patients with CHF, VascD, or CKD. CONCLUSIONS: Our data show that several variables are associated with the risk of one or more outcomes, in terms of death, stroke/SE, and major bleeding. Comprehensive management of AF should encompass, besides anticoagulation, improved implementation of guideline-recommended therapies for comorbidities strongly associated with outcomes, namely CHF, VascD, and CKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT01090362.
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- 2018
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4. Peroxisomal protein PEX13 functions in selective autophagy
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Prashant Mishra, Shyam Sirasanagandla, Rhea Sumpter, Yongjie Wei, Beth Levine, Denis I. Crane, Ming Y Lee, Zhongju Zou, and Hendrik Rosewich
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0301 basic medicine ,autophagy ,Ubiquitin-Protein Ligases ,Scientific Report ,Peroxin ,Mice, Transgenic ,PEX13 ,Mitochondrion ,Biology ,Biochemistry ,Cell Line ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Mitophagy ,Genetics ,medicine ,Zellweger syndrome ,Peroxisomes ,Animals ,Humans ,Membrane & Intracellular Transport ,RNA, Small Interfering ,Molecular Biology ,Peroxisomal matrix ,Autophagy ,Scientific Reports ,virophagy ,Membrane Proteins ,Peroxisome ,medicine.disease ,Microbiology, Virology & Host Pathogen Interaction ,3. Good health ,Cell biology ,Mitochondria ,Protein Transport ,030104 developmental biology ,Gene Knockdown Techniques ,Autophagy & Cell Death ,Sindbis Virus ,030217 neurology & neurosurgery ,Biogenesis ,Protein Binding - Abstract
PEX13 is an integral membrane protein on the peroxisome that regulates peroxisomal matrix protein import during peroxisome biogenesis. Mutations in PEX13 and other peroxin proteins are associated with Zellweger syndrome spectrum (ZSS) disorders, a subtype of peroxisome biogenesis disorder characterized by prominent neurological, hepatic, and renal abnormalities leading to neonatal death. The lack of functional peroxisomes in ZSS patients is widely accepted as the underlying cause of disease; however, our understanding of disease pathogenesis is still incomplete. Here, we demonstrate that PEX13 is required for selective autophagy of Sindbis virus (virophagy) and of damaged mitochondria (mitophagy) and that disease‐associated PEX13 mutants I326T and W313G are defective in mitophagy. The mitophagy function of PEX13 is shared with another peroxin family member PEX3, but not with two other peroxins, PEX14 and PEX19, which are required for general autophagy. Together, our results demonstrate that PEX13 is required for selective autophagy, and suggest that dysregulation of PEX13‐mediated mitophagy may contribute to ZSS pathogenesis.
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- 2016
5. Mitochondrial changes and oxidative stress in a mouse model of Zellweger syndrome neuropathogenesis
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Mo Chen, Adrian Cuda Banda Meedeniya, Denis I. Crane, C. Cathrin Nourse, and Rani Sadia Rahim
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0301 basic medicine ,Blotting, Western ,Population ,Fluorescent Antibody Technique ,Neuropathology ,Tryptophan Hydroxylase ,Mitochondrion ,Biology ,medicine.disease_cause ,Superoxide dismutase ,03 medical and health sciences ,Glial Fibrillary Acidic Protein ,medicine ,Animals ,Zellweger Syndrome ,education ,Cells, Cultured ,Mice, Knockout ,education.field_of_study ,Zellweger syndrome ,Glial fibrillary acidic protein ,Superoxide Dismutase ,General Neuroscience ,Brain ,Membrane Proteins ,Fibroblasts ,Peroxisome ,medicine.disease ,Mitochondria ,Cell biology ,Mice, Inbred C57BL ,Disease Models, Animal ,Oxidative Stress ,030104 developmental biology ,Microscopy, Fluorescence ,Biochemistry ,biology.protein ,Neuroglia ,Oxidative stress - Abstract
Zellweger syndrome (ZS) is a peroxisome biogenesis disorder that involves significant neuropathology, the molecular basis of which is still poorly understood. Using a mouse model of ZS with brain-restricted deficiency of the peroxisome biogenesis protein PEX13, we demonstrated an expanded and morphologically modified brain mitochondrial population. Cultured fibroblasts from PEX13-deficient mouse embryo displayed similar changes, as well as increased levels of mitochondrial superoxide and membrane depolarization; this phenotype was rescued by antioxidant treatment. Significant oxidative damage to neurons in brain was indicated by products of lipid and DNA oxidation. Similar overall changes were observed for glial cells. In toto, these findings suggest that mitochondrial oxidative stress and aberrant mitochondrial dynamics are associated with the neuropathology arising from PEX13 deficiency.
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- 2016
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6. Protonation and transformations of α-diazo-β-dicarbonyl compounds in superacids: generation of the strongest carbon-centered cationic electrophiles at the protonation of diazomalonates in Friedel–Crafts reactions
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Aleksander V. Vasilyev, Maria A. Sandzhieva, Eugeniy T. Satumov, Irina A. Boyarskaya, Jury J. Medvedev, Valerij A. Nikolaev, and Denis I. Nilov
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010405 organic chemistry ,Organic Chemistry ,Cationic polymerization ,Protonation ,Carbon-13 NMR ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Medicinal chemistry ,Toluene ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,Electrophile ,Organic chemistry ,Diazo ,Benzene ,Friedel–Crafts reaction - Abstract
Protonation of diazodiketones N2C(COR)2 in Bronsted superacids (TfOH, FSO3H, TfOH–SbF5) gives rise to stable and non-reactive O,O-diprotonated at carbonyl oxygens species N2C(C( OH+)R)2, which were studied by means of 1H and 13C NMR. Diazomalonates N2C(CO2Alk)2, contrary to diazodiketones, react with TfOH or HF, releasing nitrogen and producing triflates of oxymalonates TfOCH(CO2Alk)2 or fluoromalonates FCH(CO2Alk)2, respectively. Diazoketoesters N2C(COR)(CO2Alk) react in the same way only with TfOH, but not with HF. The reactions of diazomalonates with arenes ArH (benzene, toluene, xylenes) in TfOH solution yield corresponding Friedel–Crafts reaction products ArCH(CO2Alk)2. According to performed DFT calculations, trication +CH(C( OH+)OMe)2, a possible intermediate, which is derived from protonation of dimethyl diazomalonate, should be the strongest cationic carbon-centered electrophile known up to date.
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- 2016
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7. Tris(trifluoromethyl)germylethynyl derivatives of biphenyl and anthracene: Synthesis, structure, and evidence of the intramolecular charge transfer on the germanium center
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Evgeny P. Chuhmanov, Denis I. Kryzhkov, Stanislav K. Ignatov, Mikhail A. Lopatin, Georgii K. Fukin, Konstantin P. Pashchenko, Boris A. Andreev, Ilya V. Lenin, Nikolai L. Ermolaev, Olga V. Kuznetsova, Andrei S. Shavyrin, and Nadezhda T. Berberova
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Biphenyl ,Anthracene ,Trifluoromethyl ,Silicon ,Organic Chemistry ,chemistry.chemical_element ,Germanium ,Photochemistry ,Biochemistry ,Medicinal chemistry ,Inorganic Chemistry ,chemistry.chemical_compound ,chemistry ,Intramolecular force ,Materials Chemistry ,Molecule ,Physical and Theoretical Chemistry ,Absorption (chemistry) - Abstract
Symmetrical and unsymmetrical 4,4′-biphenyl, and 9,10-anthracene derivatives with tris(trifluoromethyl)germylethynyl –C C–Ge(CF3)3 substitutes have been prepared, their properties have been studied and compared with those of dimethyl(phenyl)silylethynyl –C C–Si(Ph)Me2 compounds. UV–visible absorption, steady-state, and time-resolved fluorescence spectra in solution for this germanium and silicon compounds have been investigated. The process of photoinduced electron-transfer from the aromatic group to the germanium center has been found in the unsymmetrical 4-biphenyl –C C–Ge(CF3)3 molecule. Anthracene derivatives with –C C–Ge(CF3)3 substitutes have been characterized crystallographically.
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- 2015
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8. One-pot tandem hydrophenylation and ionic hydrogenation of 3-phenylpropynoic acid derivatives under superelectrophilic activation
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Denis I. Nilov and Aleksander V. Vasilyev
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Tandem ,Cyclohexane ,Organic Chemistry ,Ionic bonding ,Biochemistry ,Medicinal chemistry ,chemistry.chemical_compound ,Acetylene ,chemistry ,Cascade reaction ,Yield (chemistry) ,Drug Discovery ,Organic chemistry ,Lewis acids and bases ,Benzene - Abstract
The reactions of esters and amides of 3-phenylpropynoic acid with strong Lewis acids AlX 3 (X = Cl, Br) or conjugate Bronsted–Lewis superacids HX-AlX 3 (X = Cl, Br) in benzene and cyclohexane at room temperature afforded 3,3-diphenylpropanoic acid derivatives in up to 94% yield. This tandem reaction of the acetylene bond proceeded by hydrophenylation followed by ionic hydrogenation.
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- 2015
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9. Modified Synthesis of 6-carboxyfluorescein (6-FAM): Application to Probe Labeling for Conventional Cytogenetics
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Svetlana Galkina, Elena Gaginskaya, Denis I Bogomaz, Alexander V. Stepakov, and Alsu F. Saifitdinova
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Conventional cytogenetics ,General Medicine ,In situ hybridization ,Oligonucleotide synthesis ,Biology ,Fluorescence ,Molecular biology ,Molecular cytogenetics ,chemistry.chemical_compound ,Biochemistry ,chemistry ,Nucleic acid ,6-Carboxyfluorescein ,Fluorescein - Abstract
Aims: Fluorescent in situ hybridization (FISH), the routine technique of molecular cytogenetics, is widely used to detect and localize the presence of specific nucleic acids sequences in chromosomes, cell nucl eus space, cells and tissue samples through the use of highly complementary probes to targets sequence. Expansion of FISH method application for research purposes and medical diagnostics requires efficient and low - cost production of labeled nucleic acid probes. Methodology and Results: We developed an effective method of fluorescein hydroxyalkyl
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- 2015
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10. Excess iron modulates endoplasmic reticulum stress-associated pathways in a mouse model of alcohol and high-fat diet-induced liver injury
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Terrence C. H. Tan, Kim R. Bridle, Darrell H. G. Crawford, Lesley Jaskowski, Denis I. Crane, Gregory J. Anderson, Linda M. Fletcher, V. Nathan Subramaniam, and Andrew D. Clouston
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Male ,medicine.medical_specialty ,XBP1 ,Alcohol Drinking ,Iron ,Apoptosis ,Biology ,Diet, High-Fat ,Pathology and Forensic Medicine ,Mice ,Random Allocation ,Internal medicine ,Nonalcoholic fatty liver disease ,Autophagy ,medicine ,Animals ,Obesity ,Endoplasmic Reticulum Chaperone BiP ,Molecular Biology ,Hemochromatosis ,Liver injury ,Endoplasmic reticulum ,Toll-Like Receptors ,Fatty liver ,nutritional and metabolic diseases ,Cell Biology ,Endoplasmic Reticulum Stress ,medicine.disease ,Trace Elements ,Mice, Inbred C57BL ,Disease Models, Animal ,Endocrinology ,Biochemistry ,Unfolded protein response ,Steatohepatitis ,Fatty Liver, Alcoholic - Abstract
Endoplasmic reticulum (ER) stress is an important pathogenic mechanism for alcoholic (ALD) and nonalcoholic fatty liver disease (NAFLD). Iron overload is an important cofactor for liver injury in ALD and NAFLD, but its role in ER stress and associated stress signaling pathways is unclear. To investigate this, we developed a murine model of combined liver injury by co-feeding the mildly iron overloaded, the hemochromatosis gene-null (Hfe(-/)) mouse ad libitum with ethanol and a high-fat diet (HFD) for 8 weeks. This co-feeding led to profound steatohepatitis, significant fibrosis, and increased apoptosis in the Hfe(-/-) mice as compared with wild-type (WT) controls. Iron overload also led to induction of unfolded protein response (XBP1 splicing, activation of IRE-1α and PERK, as well as sequestration of GRP78) and ER stress (increased CHOP protein expression) following HFD and ethanol. This is associated with a muted autophagic response including reduced LC3-I expression and impaired conjugation to LC3-II, reduced beclin-1 protein, and failure of induction of autophagy-related proteins (Atg) 3, 5, 7, and 12. As a result of the impaired autophagy, levels of the sequestosome protein p62 were most elevated in the Hfe(-/-) group co-fed ethanol and HFD. Iron overload reduces the activation of adenosine monophosphate protein kinase associated with ethanol and HFD feeding. We conclude that iron toxicity may modulate hepatic stress signaling pathways by impairing adaptive cellular compensatory mechanisms in alcohol- and obesity-induced liver injury.
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- 2013
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11. Lavoisier
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Duveen, Denis I.
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- 1956
12. Mechanism of impaired microtubule-dependent peroxisome trafficking and oxidative stress in SPAST-mutated cells from patients with Hereditary Spastic Paraplegia
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Yongjun Fan, Gautam Wali, Alan Mackay-Sim, Romal Stewart, Johana Tello Velasquez, Denis I. Crane, Ratneswary Sutharsan, and Carolyn M. Sue
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0301 basic medicine ,Adult ,Spastin ,Hereditary spastic paraplegia ,Movement ,Biology ,medicine.disease_cause ,Microtubules ,Time-Lapse Imaging ,Olfactory Receptor Neurons ,Article ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Neural Stem Cells ,medicine ,Peroxisomes ,Humans ,Age of Onset ,Microtubule severing ,Mutation ,Multidisciplinary ,Spastic Paraplegia, Hereditary ,Neurodegeneration ,Hydrogen Peroxide ,Peroxisome ,medicine.disease ,Tubulin Modulators ,3. Good health ,Cell biology ,Oxidative Stress ,030104 developmental biology ,Biochemistry ,Gene Expression Regulation ,Catalase ,Epothilones ,biology.protein ,030217 neurology & neurosurgery ,Oxidative stress ,Signal Transduction - Abstract
Hereditary spastic paraplegia (HSP) is an inherited neurological condition that leads to progressive spasticity and gait abnormalities. Adult-onset HSP is most commonly caused by mutations in SPAST, which encodes spastin a microtubule severing protein. In olfactory stem cell lines derived from patients carrying different SPAST mutations, we investigated microtubule-dependent peroxisome movement with time-lapse imaging and automated image analysis. The average speed of peroxisomes in patient-cells was slower, with fewer fast moving peroxisomes than in cells from healthy controls. This was not because of impairment of peroxisome-microtubule interactions because the time-dependent saltatory dynamics of movement of individual peroxisomes was unaffected in patient-cells. Our observations indicate that average peroxisome speeds are less in patient-cells because of the lower probability of individual peroxisome interactions with the reduced numbers of stable microtubules: peroxisome speeds in patient cells are restored by epothilone D, a tubulin-binding drug that increases the number of stable microtubules to control levels. Patient-cells were under increased oxidative stress and were more sensitive than control-cells to hydrogen peroxide, which is primarily metabolised by peroxisomal catalase. Epothilone D also ameliorated patient-cell sensitivity to hydrogen-peroxide. Our findings suggest a mechanism for neurodegeneration whereby SPAST mutations indirectly lead to impaired peroxisome transport and oxidative stress.
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- 2016
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13. DEVELOPMENT OF MOLECULAR MARKER FOR ASSESSMENT OF INTRASPECIFIC POLYMORPHISM OF RC GENE CONDITIONING RED PERICARP IN RICE ORYZA SATIVA L
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Zhanna Mukhina, Sergey V Tokmakov, Tatyana V Matveeva, and Denis I Bogomaz
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Oryza sativa ,lcsh:QH426-470 ,Ecology ,пцр ,молекулярный маркер ,Red rice ,food and beverages ,ген rс ,Biology ,Biochemistry ,Intraspecific competition ,lcsh:Genetics ,chemistry.chemical_compound ,chemistry ,Polymorphism (computer science) ,Molecular marker ,Botany ,электрофорез ,Genetics ,краснозерный рис ,Weed ,Gene ,Genetics (clinical) ,Ecology, Evolution, Behavior and Systematics - Abstract
Red rice is the worst field weed in all rice-cultivation areas. Early diagnosis of red rice in primary seed breeding program is an overriding task, which solution directly influences the quality of the rice seeds. Red and red-brown colors of pericarp are determined by two loci at least: Rc and Rd, expressing in conjunction with the Rc gene. In this study we have developed an intragenic codominant molecular marker for the Rc gene and tested it with contrasting as to the seed colour rice varieties examined feature. The efficacy of the marker has been shown for 1142 families of rice, each sample containing 120 plants.
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- 2011
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14. Molecular markers for plant species identification and phylogenetics
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Olga A. Pavlova, Andrey E Demkovich, Denis I Bogomaz, Tatyana V Matveeva, and Ludmila A Lutova
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Ecology ,lcsh:QH426-470 ,Plant species identification ,Biology ,Biochemistry ,Chloroplast ,молекулярные маркеры ,chemistry.chemical_compound ,lcsh:Genetics ,chemistry ,Phylogenetics ,Evolutionary biology ,Polymorphism (computer science) ,днк-фингерпринтинг ,Botany ,растения ,днк-штрихкод ,Genetics ,Genetics (clinical) ,Ecology, Evolution, Behavior and Systematics ,DNA - Abstract
In this review we summarized the information on application of molecular markers for plant species identification and phylogenetics: positive sides and limitations of main markers, representing sequencing data of taxonomically important chloroplast and nuclear DNA regions. Markers, based on polymorphism of PCR and restriction products, are also discussed as accessorial markers in phylogenetic studies.
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- 2011
15. Thermally induced structural changes of intrinsically disordered small heat shock protein Hsp22
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Nikolai B. Gusev, Alexey S. Kazakov, Dmitrii I. Levitsky, and Denis I. Markov
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Protein Denaturation ,Protein Folding ,Circular dichroism ,Hot Temperature ,Biophysics ,Protein Serine-Threonine Kinases ,Intrinsically disordered proteins ,Biochemistry ,Protein Structure, Secondary ,Differential scanning calorimetry ,Heat shock protein ,Humans ,Molecule ,alpha-Crystallins ,Fourier transform infrared spectroscopy ,Heat-Shock Proteins ,Calorimetry, Differential Scanning ,Chemistry ,Organic Chemistry ,Atmospheric temperature range ,Actins ,Protein Structure, Tertiary ,Crystallography ,Mutation ,Downhill folding ,Molecular Chaperones ,Protein Binding - Abstract
We applied different methods (differential scanning calorimetry, circular dichroism, Fourier transform infrared spectroscopy, and intrinsic fluorescence) to investigate the thermal-induced changes in the structure of small heat shock protein Hsp22. It has been shown that this protein undergoes thermal-induced unfolding that occurs within a very broad temperature range (from 27 degrees C to 80 degrees C and above), and this is accompanied by complete disappearance of alpha-helices, significant decrease in beta-sheets content, and by pronounced changes in the intrinsic fluorescence. The results confirm predictions that Hsp22 belongs to the family of intrinsically disordered proteins (IDP) with certain parts of its molecule (presumably, in the alpha-crystallin domain) retaining folded structure and undergoing reversible thermal unfolding. The results are also discussed in terms of downhill folding scenario.
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- 2009
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16. Analysis of Microarray Gene Expression Data
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Denis I. Crane, Christine A. Wells, and Tuan D. Pham
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Computational biology ,Biology ,Bioinformatics ,Biochemistry ,Gene expression profiling ,Computational Mathematics ,Microarray gene expression ,Pharmacogenomics ,Research community ,Gene expression ,Genetics ,Microarray databases ,DNA microarray ,Molecular Biology ,Gene - Abstract
Microarrays provide the biological research community with tremendously rich, sensitive and detailed information on gene expression profiles. Gene expression profiling and gene expression patterns have been found useful for solving a wide variety of important biological and biomedical problems, including the study of metabolic pathways, inference of the functions of unknown genes, diagnosis of diseased states, as well as facilitating the development of individualized drug treatments through pharmacogenomics. Given the significant impact of microarray gene expression data in biological and biomedical research, this breakthrough technology urgently needs the assistance of advanced computational methods for interpreting and utilizing the raw information. This paper reviews several main research directions and methods in the analysis of microarray gene expression data.
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- 2006
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17. Synthesis of protected pseudopeptides from dicarboxylic amino acids by Mitsunobu condensation
- Author
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Elena N. Zvonkova, Denis I. Prokhorov, Vitaliy I. Shvets, Yuliya G. Kirillova, and Natalya P. Boyarskaya
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Dicarboxylic Amino Acids ,Chemistry ,Organic Chemistry ,Drug Discovery ,Condensation ,Organic chemistry ,Molecule ,Mitsunobu reaction ,Biochemistry ,Combinatorial chemistry - Abstract
Four protected pseudopeptides from Glu-, Asp- and Gly-derivatives have been prepared via Mitsunobu condensation. It was shown to be a universal and preparative method which allows the formation of different structural molecules containing reduced peptides.
- Published
- 2005
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18. ANALYSIS OF INTERACTION OF PLANT GENOTYPE AND STRAIN AGROBACTERIUM TUMEFACIENS IN BREEDING OF POTATO RESISTANCE TO COLORADO POTATO BEETLE
- Author
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Denis I Bogomaz
- Subjects
Ecology ,Resistance (ecology) ,lcsh:QH426-470 ,Strain (biology) ,Colorado potato beetle ,fungi ,food and beverages ,устойчивость ,Agrobacterium tumefaciens ,агротрансформация ,Biology ,biology.organism_classification ,Biochemistry ,On resistance ,Transformation (genetics) ,lcsh:Genetics ,Botany ,Genotype ,Genetics ,картофель ,Gene ,Genetics (clinical) ,Ecology, Evolution, Behavior and Systematics - Abstract
Efficiency of potato transformation depends on plant genotype and bacterial strain. Genotypes with high regeneration ability have high transformation ability. It is shown, that transgenosis of Bt gene increases potato resistance to collorado potato beetle, transgenosis of ipt gene does not influence on resistance.
- Published
- 2005
19. An efficient synthesis of novel heterocycle-fused derivatives of 1-oxo-1,2,3,4-tetrahydropyrazine using Ugi condensation
- Author
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Sergey E. Tkachenko, Denis I. Kovrigin, Alexandre M. Shkirando, Alexey P. Ilyn, Julia A. Kuzovkova, Victor V. Potapov, and Alexandre V. Ivachtchenko
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chemistry.chemical_compound ,Scope (project management) ,Chemistry ,Organic Chemistry ,Drug Discovery ,Condensation ,General Medicine ,Biochemistry ,Combinatorial chemistry ,Pyrrole - Abstract
We present a convenient synthesis of novel pyrrole- and indole-fused 1-oxo-1,2,3,4-tetrahydropyrazine heterocyclic structures using a novel modification of four-component Ugi condensation. We demonstrate the usefulness and versatility of the developed approach for the synthesis of variously substituted compounds, and discuss the scope and limitations of the chemistry involved.
- Published
- 2005
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20. Does Interaction between the Motor and Regulatory Domains of the Myosin Head Occur during ATPase Cycle? Evidence from Thermal Unfolding Studies on Myosin Subfragment 1
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Nikolaeva Op, Dmitrii I. Levitsky, Nikolai N. Sluchanko, Daria S. Logvinova, Dmitry S. Ushakov, and Denis I. Markov
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Models, Molecular ,Protein Denaturation ,Myosin ATPase ,ATPase ,lcsh:Medicine ,Fluorescence ,Motor protein ,Myosin head ,Myosin ,Molecular motor ,Animals ,Humans ,Denaturation (biochemistry) ,lcsh:Science ,Protein Unfolding ,Adenosine Triphosphatases ,Multidisciplinary ,Calorimetry, Differential Scanning ,biology ,Chemistry ,lcsh:R ,Myosin Subfragments ,Temperature ,Tryptophan ,Protein Structure, Tertiary ,Adenosine Diphosphate ,Biochemistry ,Domain (ring theory) ,Biophysics ,biology.protein ,lcsh:Q ,Rabbits ,Research Article ,Protein Binding - Abstract
Myosin head (myosin subfragment 1, S1) consists of two major structural domains, the motor (or catalytic) domain and the regulatory domain. Functioning of the myosin head as a molecular motor is believed to involve a rotation of the regulatory domain (lever arm) relative to the motor domain during the ATPase cycle. According to predictions, this rotation can be accompanied by an interaction between the motor domain and the C-terminus of the essential light chain (ELC) associated with the regulatory domain. To check this assumption, we applied differential scanning calorimetry (DSC) combined with temperature dependences of fluorescence to study changes in thermal unfolding and the domain structure of S1, which occur upon formation of the ternary complexes S1-ADP-AlF4 - and S1-ADP-BeFx that mimic S1 ATPase intermediate states S1**-ADP-Pi and S1*-ATP, respectively. To identify the thermal transitions on the DSC profiles (i.e. to assign them to the structural domains of S1), we compared the DSC data with temperature-induced changes in fluorescence of either tryptophan residues, located only in the motor domain, or recombinant ELC mutants (light chain 1 isoform), which were first fluorescently labeled at different positions in their C-terminal half and then introduced into the S1 regulatory domain. We show that formation of the ternary complexes S1-ADP-AlF4 - and S1-ADP-BeFx significantly stabilizes not only the motor domain, but also the regulatory domain of the S1 molecule implying interdomain interaction via ELC. This is consistent with the previously proposed concepts and also adds some new interesting details to the molecular mechanism of the myosin ATPase cycle.
- Published
- 2015
21. GABA<scp>a</scp>receptor α-subunit proteins in human chronic alcoholics
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Peter R. Dodd, Flavia Huygens, Joanne Marie Lewohl, and Denis I. Crane
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Gene isoform ,medicine.medical_specialty ,GABAA receptor ,Central nervous system ,Brain damage ,Biochemistry ,Pathogenesis ,Cellular and Molecular Neuroscience ,Endocrinology ,medicine.anatomical_structure ,Cerebral cortex ,Internal medicine ,Toxicity ,medicine ,medicine.symptom ,Psychology ,Motor cortex - Abstract
Antibodies were raised against specific peptides from N-terminal regions of the α1 and α3 isoforms of the GABAA receptor, and used to assess the relative expression of these proteins in the superior frontal and primary motor cortices of 10 control, nine uncomplicated alcoholic and six cirrhotic alcoholic cases were matched for age and post-mortem delay. The regression of expression on post-mortem delay was not statistically significant for either isoform in either region. In both cortical areas, the regression of α1 expression on age differed significantly between alcoholic cases, which showed a decrease, and normal controls, which did not. Age had no effect on α3 expression. The α1 and α3 isoforms were found to be expressed differentially across cortical regions and showed a tendency to be expressed differentially across case groups. In cirrhotic alcoholics, α1 expression was greater in superior frontal than in motor cortex, whereas this regional difference was not significant in controls or uncomplicated alcoholics. In uncomplicated alcoholics, α3 expression was significantly lower in superior frontal than in motor cortex. Expression of α1 was significantly different from that of α3 in the superior frontal cortex of alcoholics, but not in controls. In motor cortex, there were no significant differences in expression between the isoforms in any case group.
- Published
- 2001
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22. Characterisation of a cDNA Encoding Chick Eukaryotic Translation Initiation Factor-2β
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Denis I. Crane, Wayne Murrell, and Kyra J. Sneesby
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DNA, Complementary ,animal structures ,Eukaryotic Initiation Factor-2 ,Molecular Sequence Data ,Chick Embryo ,macromolecular substances ,Biology ,environment and public health ,Biochemistry ,Endocrinology ,Eukaryotic translation ,Eukaryotic initiation factor ,Complementary DNA ,Genetics ,Animals ,Initiation factor ,Amino Acid Sequence ,Molecular Biology ,Peptide sequence ,Base Sequence ,Sequence Homology, Amino Acid ,cDNA library ,Gene Expression Regulation, Developmental ,Heart ,EIF4A1 ,Molecular biology ,Up-Regulation ,EIF4EBP1 - Abstract
A full length cDNA for the beta subunit of chick (Gallus gallus) eukaryotic translation initiation factor-2 is described. This cDNA was isolated by screening a chick cDNA library with a probe derived via differential display of developing chick heart tissue. Up-regulated expression of eIF-2 beta mRNA was confirmed by reverse Northern dot blot analysis. eIF-2 beta, together with eIF-2 alpha and eIF-2 gamma, comprise subunits of a complex that promotes the binding of methionyl-tRNA to ribosomes during the initiation of protein translation. The nucleotide sequence of the chick eIF-2 beta cDNA predicts a protein of 334 amino acids that has 95%, 93%, 56% and 37% sequence identity with rabbit, human, drosophila and yeast eIF-2 beta, respectively. The deduced eIF-2 beta protein contains a number of functional motifs and domains consistent with the putative function of this protein; these include a potential C2-C2 zinc-finger binding domain, three polylysine regions, and three acidic regions.
- Published
- 2001
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23. Localization of a Portion of Extranuclear ATM to Peroxisomes
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Jonas Carl-Otto Bjorkman, Phil Chen, Padmini Kedar, Dianne Watters, Bernadette Garrone, Kevin J. Spring, Priyadashini Srinivasa, Magtouf Gatei, Geoff W. Birrell, Martin F. Lavin, and Denis I. Crane
- Subjects
Male ,Lipid Peroxides ,DNA damage ,Recombinant Fusion Proteins ,Molecular Sequence Data ,Cell Cycle Proteins ,Ataxia Telangiectasia Mutated Proteins ,Protein Serine-Threonine Kinases ,Biochemistry ,Cell Line ,Peroxisomal Disorders ,Ataxia Telangiectasia ,Mice ,Two-Hybrid System Techniques ,Peroxisomes ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Molecular Biology ,Cell Nucleus ,biology ,Tumor Suppressor Proteins ,Vesicle ,Cell Biology ,Fibroblasts ,Peroxisome ,Catalase ,Immunohistochemistry ,Cell biology ,DNA-Binding Proteins ,medicine.anatomical_structure ,Cell culture ,biology.protein ,Homologous recombination ,Sequence Alignment ,Nucleus ,Biogenesis - Abstract
The gene mutated in the human genetic disorder ataxia-telangiectasia codes for a protein, ATM, the known functions of which include response to DNA damage, cell cycle control, and meiotic recombination. Consistent with these functions, ATM is predominantly present in the nucleus of proliferating cells; however, a significant proportion of the protein has also been detected outside the nucleus in cytoplasmic vesicles. To understand the possible role of extra-nuclear ATM, we initially investigated the nature of these vesicles. In this report we demonstrate that a portion of ATM co-localizes with catalase, that ATM is present in purified mouse peroxisomes, and that there are reduced levels of ATM in the post-mitochondrial membrane fraction of cells from a patient with a peroxisome biogenesis disorder. Furthermore the use of the yeast two-hybrid system demonstrated that ATM interacts directly with a protein involved in the import of proteins into the peroxisome matrix. Because peroxisomes are major sites of oxidative metabolism, we investigated catalase activity and lipid hydroperoxide levels in normal and A-T fibroblasts. Significantly decreased catalase activity and increased lipid peroxidation was observed in several A-T cell lines. The localization of ATM to peroxisomes may contribute to the pleiotropic nature of A-T.
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- 1999
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24. A novel glycosphingolipid from Gram-negative aquatic bacteria
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Denis I. Nikitin, Stanislav G. Batrakov, and Vladimir I Sheichenko
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chemistry.chemical_classification ,Ceramide ,Magnetic Resonance Spectroscopy ,Chromatography ,Molecular Structure ,Spectrophotometry, Infrared ,biology ,Fatty acid ,Cell Biology ,Nuclear magnetic resonance spectroscopy ,Glycosphingolipid ,biology.organism_classification ,Mass spectrometry ,Glycosphingolipids ,Mass Spectrometry ,chemistry.chemical_compound ,Glycolipid ,chemistry ,Biochemistry ,Gram-Negative Bacteria ,lipids (amino acids, peptides, and proteins) ,Molecular Biology ,Bacteria ,Gram - Abstract
The chloroform-methanol extractable lipids of the Gram-negative fresh-water bacteria Arcocella aquatica NO-502 and Flectobacillus major FM were found to contain an unusual ninhydrin-positive glycolipid. It was purified by two-stage silica gel-column chromatography. By the use of IR and (1)H-NMR spectroscopy, mass spectrometry and chemical-degradation experiment, the lipid was established to be 1-O-monoglycosyl ceramide, the carbohydrate moiety of which was the alpha-pyranose-ring form of 7-desoxy-7-amino-D-manno-heptulosonic acid, or 1-hydroxycarbonyl-6-deoxy-6-amino-alpha-D-mannopyranose. The ceramide portion consisted mainly (by 95% in the A. aquatica glycolipid and 80% in the F. major glycolipid) of 2-N-(2'-D-hydroxy-13'-methyltetradecanoyl)-15-methyl-4(E)-hexad ecasph ingenine. The minor molecular species differed from the major one only in fatty acid structure. The glycolipid accounted for 8 and 11% of the total lipids extracted from A. aquatica NO-502 and F. major FM cells, respectively.
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- 1999
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25. A glycine-containing phosphorus-free lipoaminoacid from the gram-negative marine bacterium Cyclobacterium marinus WH
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Denis I. Nikitin, S.G. Batrakov, A.E. Mosezhnyi, and A.O. Ruzhitsky
- Subjects
Chromatography ,biology ,Phosphorus ,Organic Chemistry ,chemistry.chemical_element ,Cell Biology ,biology.organism_classification ,Mass spectrometry ,Biochemistry ,chemistry ,Glycine ,Proton NMR ,Cyclobacterium marinus ,lipids (amino acids, peptides, and proteins) ,Molecular Biology ,Bacteria ,Chemical decomposition ,Gram - Abstract
A phosphorus-free acidic lipid was isolated from the low-polarity fraction of extractable lipids of the gram-negative marine bacterium Cyclobacterium marinus WH . Using IR and 1 H NMR spectroscopy, mass spectrometry, chromatographic techniques, and chemical degradation experiment, the lipid was established to be N -[3- d -(13′-methyltetradecanoyloxy)-15-methylhexadecanoyl]glycine. It constituted about 5% of the total lipids. The same or at least closely related lipid was found to occur in gram-negative fresh-water bacteria belonging to the genera Arcocella and Flectobacillus.
- Published
- 1999
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26. [Untitled]
- Author
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Colin Masters and Denis I. Crane
- Subjects
Cellular differentiation ,Clinical Biochemistry ,Cell Biology ,General Medicine ,Peroxisome ,Biology ,medicine.disease_cause ,Cell biology ,Medical benefit ,Biochemistry ,Organelle ,medicine ,Carcinogenesis ,Molecular Biology ,Calcium signaling - Abstract
This article reviews the currently available data on the role of peroxisomal function in relation to the processes of cell differentiation and carcinogenesis. In regard to tumourigenesis, both genotoxic and non-genotoxic processes have been considered, and the peroxisomal relationships with these phenomena and with differentiation are described at the level of organelle characteristics, enzyme contents, and the involvement of retinoids, steroid hormones, oxygen free radicals, growth factors, apoptosis, omega-3 polyunsaturated fatty acids and the cellular signalling networks. Overall these data serve to illustrate the unique and distinctive role of the peroxisome in differentiation and carcinogenesis, and point to the advantages of considering the peroxisomal involvement in the holistic context of the differentiation dedifferentiation continuum rather than the narrower focus of non-genotoxic carcinogenesis. The review also outlines the potential for medical benefit arising from a fuller understanding of these peroxisomal affiliations.
- Published
- 1998
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27. A method for the quantitation of the α1, α2 and α3 isoforms of the GABAA receptor in human brain using competitive PCR
- Author
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Peter R. Dodd, Joanne Marie Lewohl, and Denis I. Crane
- Subjects
Gene isoform ,Neuroactive steroid ,Transcription, Genetic ,GABAA receptor ,Chemistry ,General Neuroscience ,Receptor expression ,Protein subunit ,Brain ,Receptors, GABA-A ,Polymerase Chain Reaction ,Molecular biology ,GABAA-rho receptor ,Isomerism ,Biochemistry ,medicine ,Humans ,Flunitrazepam ,Receptor ,medicine.drug - Abstract
The GABAA receptor is the site of action of the inhibitory neurotransmitter GABA, as well as a number of pharmacologically important drugs such as benzodiazepines, barbiturates, and ethanol. The GABAA receptor is a pentameric complex composed of distinct polypeptides, which have been divided into five subunit classes on the basis of sequence homology. To date, 17 isoforms of the receptor have been identified and cloned in mammalian brain, and designated alpha 1-6, beta 1-4, gamma 1-4, delta and rho 1-2. In addition, several isoforms exist in alternatively spliced forms (for review see ref.). Studies on recombinant receptors have revealed that receptors constituted from different isoforms exhibit distinct pharmacological properties. For example, the alpha subunit class appears to be responsible for GABA enhancement of benzodiazepine binding. GABAA receptor function is modulated by benzodiazepine agonists such as flunitrazepam and diazepam, barbiturates, anaesthetics, neurosteroids, and ethanol. Chronic treatment of animals with many of these compounds can bring about profound changes in receptor expression and pharmacology. The RT/PCR assay described here was developed to quantify the alpha 1, alpha 2 and alpha 3 isoforms in the same assay. The amount of each isoform was quantified on the basis of a standard curve generated under identical PCR conditions to the target sequences. In this way it is possible to quantify multiple samples in each RT/PCR assay, thereby reducing inter-assay variability. The assay can be applied to quantify the expression of these isoforms in response to acute and chronic drug administration, or in particular disease states. Altered expression may reflect a corresponding change in protein synthesis, or an alteration of the subtype composition of GABAA receptor.
- Published
- 1997
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28. Unusual lipid composition of the gram-negative, freshwater, stalked bacterium Caulobacter bacteroides NP-105
- Author
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Stanislav G. Batrakov, Denis I. Nikitin, Alexandr O. Ruzhitsky, and Vladimir I Sheichenko
- Subjects
Magnetic Resonance Spectroscopy ,biology ,Fatty Acids ,Pseudomonas ,technology, industry, and agriculture ,Biophysics ,biology.organism_classification ,Photosynthesis ,Lipids ,Biochemistry ,Caulobacter ,Residue (chemistry) ,chemistry.chemical_compound ,Endocrinology ,Glycolipid ,chemistry ,Caulobacter bacteroides ,Glycerophospholipid ,lipids (amino acids, peptides, and proteins) ,Chromatography, Thin Layer ,Glycolipids ,Bacteria ,Gram - Abstract
The extractable lipids of the gram-negative, stalked, freshwater bacterium Caulobacter bacteroides NP-105 account for about 9.5% by weight of dry cells, polar lipids comprising up to 95% of the total. The polar lipids consist of five glycolipids, namely, 1,2-diacyl-3-alpha-D-glucopyranosyl-sn-glycerol (I) (34% of the total), 1,2-diacyl-3-alpha-D-[6'-(1",2"-diacyl-sn-glycero-3-phospho)]glucopyranosyl-sn-glycerol (II) (7%), 1,2-diacyl-3-a-D-glucuronopyranosyl-sn-glycerol (III) (17%), 1,2-diacyl-3-alpha-D-(6'-sulfo)quinovopyranosyl-sn-glycerol (V) (9%), and 1,2-diacyl-3-alpha-D-[4'-(alpha-D-glucopyranosyl)] glucuronopyranosyl-sn-glycerol (VI) (28%), and one glycerophospholipid, 1,2-diacyl-sn-glycero-3-phosphoglycerol (IV) (5%). The main fatty acyls of the lipids are n-16:0, cis-18:1 omega7, and cis-11,12-methyleneoctadecanoic (lactobacillic) acid residue. Of the 6 lipids listed, only 3 (I, IV, and V) can be treated as widely encountered. However, sulfonic glycolipid V is a characteristic lipid component of photosynthetic organisms rather than non-photosynthetic ones. Phosphatidyl derivatives of glycosyldiacylglycerols of type II normally occur in gram-positive bacteria, among gram-negative bacteria they have been revealed only in two species of the Pseudomonas genus. Glucuronosyl and alpha-glucosyl-a-glucuronosyl diacylglycerols such as III and VI, respectively, are very rare lipids, the latter being found so far only in a Streptomyces strain.
- Published
- 1997
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29. The biogenesis protein PEX14 is an optimal marker for the identification and localization of peroxisomes in different cell types, tissues, and species in morphological studies
- Author
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Klaus Kuchelmeister, Anca Nenicu, Ingra Stelzig, Eveline Baumgart-Vogt, Srikanth Karnati, Barbara Ahlemeyer, Timm Berg, Phillip Grant, and Denis I. Crane
- Subjects
Male ,Cell type ,Histology ,Immunoelectron microscopy ,SOD2 ,Peroxin ,Biology ,Immunofluorescence ,Kidney ,Mice ,Adrenal Glands ,Testis ,medicine ,Peroxisomes ,Animals ,Humans ,Molecular Biology ,Pancreas ,Cells, Cultured ,chemistry.chemical_classification ,Reactive oxygen species ,medicine.diagnostic_test ,Ovary ,Brain ,Membrane Proteins ,Cell Biology ,Peroxisome ,Cell biology ,Rats ,Repressor Proteins ,Medical Laboratory Technology ,Biochemistry ,chemistry ,Cell culture ,Cats ,Female ,Biomarkers ,Papio - Abstract
Catalase and ABCD3 are frequently used as markers for the localization of peroxisomes in morphological experiments. Their abundance, however, is highly dependent on metabolic demands, reducing the validity of analyses of peroxisomal abundance and distribution based solely on these proteins. We therefore attempted to find a protein which can be used as an optimal marker for peroxisomes in a variety of species, tissues, cell types and also experimental designs, independently of peroxisomal metabolism. We found that the biogenesis protein peroxin 14 (PEX14) is present in comparable amounts in the membranes of every peroxisome and is optimally suited for immunoblotting, immunohistochemistry, immunofluorescence, and immunoelectron microscopy. Using antibodies against PEX14, we could visualize peroxisomes with almost undetectable catalase content in various mammalian tissue sections (submandibular and adrenal gland, kidney, testis, ovary, brain, and pancreas from mouse, cat, baboon, and human) and cell cultures (primary cells and cell lines). Peroxisome labeling with catalase often showed a similar tissue distribution to the mitochondrial enzyme mitochondrial superoxide dismutase (both responsible for the degradation of reactive oxygen species), whereas ABCD3 exhibited a distinct labeling only in cells involved in lipid metabolism. We increased the sensitivity of our methods by using QuantumDots™, which have higher emission yields compared to classic fluorochromes and are unsusceptible to photobleaching, thereby allowing more exact quantification without artificial mistakes due to heterogeneity of individual peroxisomes. We conclude that PEX14 is indeed the best marker for labeling of peroxisomes in a variety of tissues and cell types in a consistent fashion for comparative morphometry.
- Published
- 2013
30. Lipid composition of the gram-negative, budding, seawater bacterium Hyphomonas jannaschiana lacking in phospholipids
- Author
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Irina A. Pitryuk, Denis I. Nikitin, and Stanislav G. Batrakov
- Subjects
Taurine ,Biophysics ,Glucuronates ,Biochemistry ,Mass Spectrometry ,Glycerides ,chemistry.chemical_compound ,Endocrinology ,Glycolipid ,Glucosides ,Gram-Negative Bacteria ,Glycerol ,Moiety ,Seawater ,Phospholipids ,Unsaturated fatty acid ,chemistry.chemical_classification ,Budding ,Chromatography ,biology ,Chemistry ,Fatty acid ,Stereoisomerism ,biology.organism_classification ,lipids (amino acids, peptides, and proteins) ,Glycolipids ,Bacteria - Abstract
The extractable polar lipids of the gram-negative, budding, seawater bacterium Hyphomonas jannaschiana VP-2T were shown to consist of five glycolipids, namely, 1,2-α- d -glucopyranosyl-sn-glycerol (I) (25% of the total lipids), 1,2-diacyl-3-α- d -glucuronopyranosyl-sn-glycerol (II) (41 %), taurine-amide of II (III) (32%), acyl- d -glucuronopyranoside (IV) (0.9%), and acyl-3-O-acyl- d -glucuronopyranoside (V) (0.4%); glycolipid (III) was described by the authors previously. In addition, small amounts of poly(β-hydroxybutyrate) and free fatty acids were present in the lipids extracted. Neither phospholipids nor low-polarity lipids, such as fatty acid esters of glycerol or fatty alcohols, were detected. Glycolipids I, II, IV, V were isolated in chromatographically pure state by chromatography on DEAE-cellulose and silica-gel columns. Their structures were established using chromatographic, spectrometric and chemical-degradation methods. In glyceroglycolipids I and II, unsaturated fatty acid residues were located predominantly at the sn - 1 carbon of the glycerol moiety while saturated ones were linked mainly to the sn - 2 carbon.
- Published
- 1996
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31. Lipid composition of the phosphatidylcholine-producing bacterium Hyphomicrobium vulgare NP-160
- Author
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Stanislav G. Batrakov and Denis I. Nikitin
- Subjects
Chromatography, Gas ,Magnetic Resonance Spectroscopy ,Cardiolipins ,Biophysics ,Phospholipid ,medicine.disease_cause ,Biochemistry ,Phospholipases A ,chemistry.chemical_compound ,Endocrinology ,Phosphatidylcholine ,Glycerol ,medicine ,chemistry.chemical_classification ,Wax ,Chromatography ,Bacteria ,Phosphatidylethanolamines ,Hyphomicrobium vulgare ,Fatty acid ,Ornithine ,Lipids ,chemistry ,visual_art ,Phosphatidylcholines ,visual_art.visual_art_medium ,Chromatography, Thin Layer ,Methanol - Abstract
The extractable lipids of the PC-producing, methylotrophic, budding bacterium Hyphomicrobium vulgare NP-160 grown in a mineral-salts medium containing methanol as the carbon source, were studied by chromatographic and spectrometric methods. They were found to be comprised of PC (35% of the total lipids), PDME (33%), PMME (1%), PE (9%), PG (10%), DPG (6%), and a non-phosphorus, ornithine-containing lipoamino acid, OL (6%). No low-polarity lipids, such as fatty acid esters of glycerol or of other alcohols, were detected. The sole fatty-acyl constituents of PDME and PMME were cis-octadec-11-enoic (cis-vaccenic) acid residues, whereas the other phospholipids contained, in addition, 1 to 5 mol % of MOA (lactobacillic acid) residues located predominantly at the sn-1 position of their glycerol residues. OL consisted of two molecular species, 2-N-[3′-(cis- octadec -11″- enoyloxy ) octadecanoyl ]- l - ornithine and 2-N-[3′-(cis-11″,12″- methyleneoctadecanoyloxy ) octadecanoyl ]- l - ornithine in the molar ratio 94:6. when the culture medium was devoid of phosphate, a threefold increase in OL together with a three-fold decrease in PE were observed, no significant changes in proportions of the remaining lipids occurring. The most striking feature of the lipid composition in this case was the presence of considerable amounts of fatty acid methyl esters, mainly methyl cis-vaccenate, along with minute amounts of wax esters.
- Published
- 1996
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32. A novel glycolipid, taurineamide, from the budding seawater bacterium Hyphomonas jannaschiana
- Author
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Irina A. Pitryuk, Denis I. Nikitin, and Stanislav G. Batrakov
- Subjects
Budding ,biology ,Chemistry ,Biophysics ,Alpha (ethology) ,biology.organism_classification ,Biochemistry ,Residue (chemistry) ,chemistry.chemical_compound ,Endocrinology ,Glycolipid ,Taurineamide ,Glycerol ,Organic chemistry ,lipids (amino acids, peptides, and proteins) ,Seawater ,Bacteria - Abstract
A previously unknown glycolipid has been isolated from the budding seawater bacterium Hyphomonas jannaschiana VP-2T devoid of phospholipids. Using a combination of chromatographic, spectrometric, enzymic- and chemical-degradation methods, the structure of the lipid has been determined to be 1,2- diacyl -3-α- d -glucuronopyranosyl -sn- glycerol taurineamide. Its main fatty acyls are n-16:0, cis-16:1ω7, n-18:0, cis-18:1ω7, and n-19:0. The hydroxyl at the sn-1 position of the glycerol residue is acylated predominantly with unsaturated fatty acids, and the secondary hydroxyl at the sn-2 carbon is acylated mainly with saturated ones.
- Published
- 1996
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33. Pex13p is an SH3 protein of the peroxisome membrane and a docking factor for the predominantly cytoplasmic PTs1 receptor
- Author
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Stephen Jay Gould, Denis I. Crane, Jonas Carl-Otto Bjorkman, James C. Morrell, Jennifer E. Kalish, and Aaron J. Urquhart
- Subjects
Cytoplasm ,Peroxisome-Targeting Signal 1 Receptor ,Genes, Fungal ,Molecular Sequence Data ,Receptors, Cytoplasmic and Nuclear ,Peroxin ,Biology ,Microbodies ,Pichia ,Cell Line ,src Homology Domains ,Humans ,Amino Acid Sequence ,Acetyl-CoA C-Acetyltransferase ,Cloning, Molecular ,Peroxisomal targeting signal ,Peroxisomal Targeting Signal 2 Receptor ,Peroxisomal matrix ,Peroxisomal Targeting Signal 1 ,Cell Membrane ,Membrane Proteins ,Biological Transport ,Cell Biology ,Articles ,Intracellular Membranes ,Sequence Analysis, DNA ,Peroxisome ,Fibroblasts ,Catalase ,Cell biology ,Biochemistry ,Membrane protein ,Genes ,Cell Adhesion Molecules - Abstract
Import of newly synthesized PTS1 proteins into the peroxisome requires the PTS1 receptor (Pex5p), a predominantly cytoplasmic protein that cycles between the cytoplasm and peroxisome. We have identified Pex13p, a novel integral peroxisomal membrane from both yeast and humans that binds the PTS1 receptor via a cytoplasmically oriented SH3 domain. Although only a small amount of Pex5p is bound to peroxisomes at steady state (< 5%), loss of Pex13p further reduces the amount of peroxisome-associated Pex5p by approximately 40-fold. Furthermore, loss of Pex13p eliminates import of peroxisomal matrix proteins that contain either the type-1 or type-2 peroxisomal targeting signal but does not affect targeting and insertion of integral peroxisomal membrane proteins. We conclude that Pex13p functions as a docking factor for the predominantly cytoplasmic PTS1 receptor.
- Published
- 1996
34. Oxidation of adenosine and inosine: the chemistry of 8-oxo-7,8-dihydropurines, purine iminoquinones, and purine quinones as observed by ultrafast spectroscopy
- Author
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Alexander N. Tarnovsky, R. Marshall Wilson, Denis I. Nilov, Dmitry Yurievich Komarov, Andrey S. Mereshchenko, Kanykey E. Karabaeva, and Maxim S. Panov
- Subjects
Purine ,Adenosine ,Photoaffinity labeling ,Molecular Structure ,Spectrum Analysis ,Reactive intermediate ,Quinones ,General Chemistry ,Biochemistry ,Combinatorial chemistry ,Catalysis ,Inosine ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,chemistry ,Nucleophile ,Purines ,medicine ,Organic chemistry ,Azide ,Purine metabolism ,Oxidation-Reduction ,medicine.drug - Abstract
Oxidative damage to purine nucleic acid bases proceeds through quinoidal intermediates derived from their corresponding 8-oxo-7,8-dihydropurine bases. Oxidation studies of 8-oxo-7,8-dihyroadenosine and 8-oxo-7,8-dihydroinosine indicate that these quinoidal species can produce stable cross-links with a wide variety of nucleophiles in the 2-positions of the purines. An azide precursor for the adenosine iminoquinone has been synthesized and applied in ultrafast transient absorption spectroscopic studies. Thus, the adenosine iminoquinone can be observed directly, and its susceptibility to nucleophilic attack with various nucleophiles as well as the stability of the resulting cross-linked species have been evaluated. Finally, these observations indicate that this azide might be a very useful photoaffinity labeling agent, because the reactive intermediate, adenosine iminoquinone, is such a good mimic for the universal purine base adenosine.
- Published
- 2013
35. Peroxisomal Membrane Protein PMP68 of Mouse Liver: Cloning of a cDNA Encompassing the Nucleotide Binding Fold and Epitope Mapping of Monoclonal Antibodies to the Expressed Protein
- Author
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M. Land, Nanhua Chen, Zhang Lu, Denis I. Crane, and R. Ayres
- Subjects
Protein Folding ,Vesicle-associated membrane protein 8 ,DNA, Complementary ,Recombinant Fusion Proteins ,Immunoblotting ,Molecular Sequence Data ,Biophysics ,Biology ,Biochemistry ,Epitopes ,Mice ,Protein sequencing ,Complementary DNA ,Protein A/G ,Animals ,Amino Acid Sequence ,Cloning, Molecular ,Molecular Biology ,Integral membrane protein ,Chromatography, High Pressure Liquid ,Binding Sites ,Base Sequence ,Antibodies, Monoclonal ,Membrane Proteins ,Fusion protein ,Molecular biology ,Mice, Mutant Strains ,Peptide Fragments ,Epitope mapping ,Liver ,Chromatography, Gel ,biology.protein ,ATP-Binding Cassette Transporters ,Electrophoresis, Polyacrylamide Gel ,Female ,Protein G - Abstract
We have isolated and sequenced a cDNA which encodes 376 amino acids toward the carboxy-terminus, and encompassing the putative nucleotide binding fold, of PMP68 (mouse liver peroxisomal integral membrane protein of 68 kDa) the major integral membrane protein of mouse liver peroxisomes. The protein sequence predicted from this cDNA shows 97.9% amino acid identity to this same region of rat liver PMP70, a member of the ATP-binding cassette protein superfamily (K. Kamijo, S. Taketani, S. Yokota, T. Osumi, and T. Hashimoto, 1990, J. Biol. Chem. 265, 4534-4540). The section of the cDNA encoding the hydrophilic and putative cytoplasmic domain of PMP68 was expressed as a recombinant fusion protein in bacteria. Two monoclonal antibodies raised against this protein have been epitope-mapped to peptides generated by cyanogen bromide cleavage of the fusion protein. Antibody 1A4 recognizes a peptide whose sequence contains the first motif of the putative nucleotide binding fold of PMP68, and antibody 8F11 recognizes a carboxy-terminal peptide which includes the second motif of this nucleotide binding fold. These antibodies are expected to be useful in the elucidation of the biological function of this putative membrane transporter.
- Published
- 1995
- Full Text
- View/download PDF
36. Kinetics of Thermal Denaturation and Aggregation of Bovine Serum Albumin
- Author
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Boris I. Kurganov, Nikolay B. Poliansky, Kira A. Markossian, Denis I. Markov, Sergey Yu. Kleymenov, Natalia A. Chebotareva, K. O. Muranov, Vera A. Borzova, V. V. Shubin, and Vita Stein-Margolina
- Subjects
0301 basic medicine ,Protein Denaturation ,Hot Temperature ,Luminescence ,Light ,lcsh:Medicine ,02 engineering and technology ,Protein aggregation ,Bioinformatics ,Physical Chemistry ,Biochemistry ,Scattering ,Aromatic Amino Acids ,Materials Physics ,Denaturation (biochemistry) ,Amino Acids ,Bovine serum albumin ,lcsh:Science ,Multidisciplinary ,Calorimetry, Differential Scanning ,biology ,Organic Compounds ,Chemistry ,Physics ,Electromagnetic Radiation ,Tryptophan ,Classical Mechanics ,Serum Albumin, Bovine ,021001 nanoscience & nanotechnology ,Separation Processes ,Molecular Mass ,Area Under Curve ,Physical Sciences ,Chromatography, Gel ,Sedimentation ,0210 nano-technology ,Research Article ,Computer and Information Sciences ,Hydrodynamic radius ,Materials Science ,Kinetics ,Serum albumin ,Fluid Mechanics ,Research and Analysis Methods ,Continuum Mechanics ,Fluorescence ,Computer Software ,03 medical and health sciences ,Differential scanning calorimetry ,Microscopy, Electron, Transmission ,Dynamic light scattering ,Spectrum Analysis ,Organic Chemistry ,lcsh:R ,Light Scattering ,Chemical Compounds ,Biology and Life Sciences ,Proteins ,Fluid Dynamics ,Elution ,030104 developmental biology ,Chemical Properties ,Hydrodynamics ,biology.protein ,Biophysics ,lcsh:Q ,Ultracentrifugation - Abstract
Thermal aggregation of bovine serum albumin (BSA) has been studied using dynamic light scattering, asymmetric flow field-flow fractionation and analytical ultracentrifugation. The studies were carried out at fixed temperatures (60°C, 65°C, 70°C and 80°C) in 0.1 M phosphate buffer, pH 7.0, at BSA concentration of 1 mg/ml. Thermal denaturation of the protein was studied by differential scanning calorimetry. Analysis of the experimental data shows that at 65°C the stage of protein unfolding and individual stages of protein aggregation are markedly separated in time. This circumstance allowed us to propose the following mechanism of thermal aggregation of BSA. Protein unfolding results in the formation of two forms of the non-native protein with different propensity to aggregation. One of the forms (highly reactive unfolded form, Uhr) is characterized by a high rate of aggregation. Aggregation of Uhr leads to the formation of primary aggregates with the hydrodynamic radius (Rh,1) of 10.3 nm. The second form (low reactive unfolded form, Ulr) participates in the aggregation process by its attachment to the primary aggregates produced by the Uhr form and possesses ability for self-aggregation with formation of stable small-sized aggregates (Ast). At complete exhaustion of Ulr, secondary aggregates with the hydrodynamic radius (Rh,2) of 12.8 nm are formed. At 60°C the rates of unfolding and aggregation are commensurate, at 70°C the rates of formation of the primary and secondary aggregates are commensurate, at 80°C the registration of the initial stages of aggregation is complicated by formation of large-sized aggregates.
- Published
- 2016
- Full Text
- View/download PDF
37. The Pichia pastoris PAS4 gene encodes a ubiquitin-conjugating enzyme required for peroxisome assembly
- Author
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Stephen J. Gould, Denis I. Crane, and Jennifer E. Kalish
- Subjects
Enzyme Gene ,biology ,Mutant ,Peroxisome Proliferation ,Cell Biology ,Ubiquitin-conjugating enzyme ,biology.organism_classification ,Biochemistry ,Pichia pastoris ,Ubiquitin ,biology.protein ,PPARGC1B ,Molecular Biology ,Cysteine - Abstract
We report here the cloning and initial characterization of PAS4, a gene required for peroxisome assembly in the yeast Pichia pastoris. The PAS4 gene encodes a 24-kDa protein (Pas4p) that is located on the cytoplasmic surface of peroxisomes and is induced during peroxisome proliferation. Analysis of the Pas4p sequence revealed a high degree of similarity to ubiquitin-conjugating enzymes, particularly in the region surrounding the putative active-site cysteine residue with which ubiquitin forms a thioester bond. As expected for a ubiquitin-conjugating enzyme, substitution of alanine or serine for the conserved active-site cysteine residue abolished PAS4 function. In addition, a small amount of a 32 kDa form of Pas4p (the predicted size of a Pas4p-ubiquitin conjugate) was detected both in vivo and in vitro. This species was eliminated by reducing agents and was not detected in the cysteine to alanine substitution mutant, suggesting that it is a Pas4p-ubiquitin conjugate. Using a yeast strain that overexpresses a Myc-ubiquitin fusion protein, we demonstrate directly that this conjugate contains ubiquitin. We conclude from these observations that PAS4 is a member of the ubiquitin-conjugating enzyme gene family and that one or more ubiquitination reactions are required for peroxisome assembly.
- Published
- 1994
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38. Developmental variations in the interactions of pyruvate kinase and glyceraldehyde-3-phosphate dehydrogenase with subcellular structure in cavian tissues
- Author
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Denis I. Crane, Colin Masters, and Wayne Murrell
- Subjects
chemistry.chemical_classification ,Aging ,biology ,Muscles ,Myocardium ,Guinea Pigs ,Pyruvate Kinase ,Brain ,Glyceraldehyde-3-Phosphate Dehydrogenases ,Dehydrogenase ,Kidney ,Isozyme ,Guinea pig ,Enzyme ,Liver ,chemistry ,Biochemistry ,biology.protein ,Animals ,Glycolysis ,Epigenetics ,Glyceraldehyde 3-phosphate dehydrogenase ,Pyruvate kinase ,Subcellular Fractions ,Developmental Biology - Abstract
The activities and interactions with cellular structure of glyceraldehyde-3-phosphate dehydrogenase and pyruvate kinase have been studied in the major tissues of the guinea pig during development. The extent of activity variation in these tissues is described along with the putative physiological determinants of these alterations in activity. As to binding, overall the present data provide a firm indication that the extent of enzyme-structure interactions is appreciable at all ontogenic stages, and when viewed in conjunction with other parallel studies on other enzymes and other animals, serve to confirm the broad biological significance of enzyme-structure associations in the compartmentation of glycolysis. The existence and significance of genetic and epigenetic modifications of these enzymes during development is also discussed.
- Published
- 1994
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- View/download PDF
39. Mitochondria, reactive oxygen species and cadmium toxicity in the kidney
- Author
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Glenda C. Gobe and Denis I. Crane
- Subjects
Programmed cell death ,Src Homology 2 Domain-Containing, Transforming Protein 1 ,Apoptosis ,Mitochondrion ,Biology ,Toxicology ,medicine.disease_cause ,Endoplasmic Reticulum ,Kidney ,Antioxidants ,medicine ,Humans ,Cell damage ,chemistry.chemical_classification ,Reactive oxygen species ,Autophagy ,Kidney metabolism ,General Medicine ,Environmental exposure ,Environmental Exposure ,medicine.disease ,Cell biology ,Mitochondria ,Oxidative Stress ,chemistry ,Biochemistry ,Shc Signaling Adaptor Proteins ,Environmental Pollutants ,Kidney Diseases ,Reactive Oxygen Species ,Oxidative stress ,Cadmium - Abstract
The heavy metal cadmium accumulates in kidney cells, particularly those of the proximal tubular epithelium, and the damage this causes is associated with development of chronic kidney disease. One of the causative mechanisms of chronic kidney disease is thought to be oxidative stress. Cadmium induces oxidative stress, but the molecular mechanisms involved in the cell damage from oxidative stress in cadmium-induced chronic kidney disease are not well understood. Mitochondrial damage is likely, given that dysfunctional mitochondria are central to the formation of excess reactive oxygen species (ROS), and are known key intracellular targets for cadmium. Normally, ROS are balanced by natural anti-oxidant enzymes. When mitochondria become dysfunctional, for example, through long term exposure to environmental toxicants like cadmium, they produce less cell energy and more ROS. The imbalance between these ROS and the natural anti-oxidants creates the condition of oxidative stress. The outcomes of mitochondrial injury are manyfold: injured mitochondria perpetuate oxidative stress; the loss of mitochondrial membrane potential causes release of cytochrome-c and activation of caspase pathways that lead to apoptotic deletion of renal cells; and attempts by cells to remove dysfunctional mitochondria through autophagy lead to "autophagic cell death" or apoptosis. Three pathways of mitochondrial regulation (upstream signalling pathways, direct mitochondrial targeting, and downstream cell death effector pathways) are therefore all promising targets for effective anti-oxidant treatment of cadmium toxicity in the kidney.
- Published
- 2010
40. Alpha-Synuclein Abnormalities in Mouse Models of Peroxisome Biogenesis Disorders
- Author
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Myriam Baes, Ann B. Moser, Phyllis L. Faust, Ann Saada, Virginie Loeb, Eugenia Yakunin, Ronit Sharon, and Denis I. Crane
- Subjects
Parkinson's disease ,Cell Survival ,Biology ,medicine.disease_cause ,behavioral disciplines and activities ,Article ,Pathogenesis ,Peroxisomal Disorders ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Mice ,medicine ,Peroxisomes ,Animals ,Phosphorylation ,Alpha-synuclein ,Synucleinopathies ,Adenosine Triphosphatases ,Mice, Knockout ,Zellweger syndrome ,Electron Transport Complex I ,Organelle Biogenesis ,Fatty Acids ,Brain ,Lipid metabolism ,Peroxisome ,medicine.disease ,Cell biology ,Mitochondria ,Disease Models, Animal ,Oxidative Stress ,chemistry ,Biochemistry ,alpha-Synuclein ,ATPases Associated with Diverse Cellular Activities ,Lewy Bodies ,Oxidative stress - Abstract
alpha-Synuclein (alphaS) is a presynaptic protein implicated in Parkinson's disease (PD). Growing evidence implicates mitochondrial dysfunction, oxidative stress, and alphaS-lipid interactions in the gradual accumulation of alphaS in pathogenic forms and its deposition in Lewy bodies, the pathological hallmark of PD and related synucleinopathies. The peroxisomal biogenesis disorders (PBD), with Zellweger syndrome serving as the prototype of this group, are characterized by malformed and functionally impaired peroxisomes. Here we utilized the PBD mouse models Pex2-/-, Pex5-/-, and Pex13-/- to study the potential effects of peroxisomal dysfunction on alphaS-related pathogenesis. We found increased alphaS oligomerization and phosphorylation and its increased deposition in cytoplasmic inclusions in these PBD mouse models. Furthermore, we show that alphaS abnormalities correlate with the altered lipid metabolism and, specifically, with accumulation of long chain, n-6 polyunsaturated fatty acids that occurs in the PBD models.
- Published
- 2010
41. Effects of myosin 'essential' light chain a1 on the aggregation properties of the myosin head
- Author
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Dmitrii I. Levitsky, Denis I. Markov, and Nikolaeva Op
- Subjects
Gene isoform ,“ESSENTIAL” LIGHT CHAINS ,Chemistry ,Intermolecular force ,Immunoglobulin light chain ,Biochemistry ,Myosin head ,Differential scanning calorimetry ,Ionic strength ,Myosin ,Biophysics ,Molecular Medicine ,Molecule ,Molecular Biology ,Biotechnology - Abstract
We compared the thermal aggregation properties of two isoforms of the isolated myosin head (myosin subfragment 1, S1) containing different "essential" (or "alkali") light chains, A1 or A2. Temperature dependencies for the aggregation of these two S1 isoforms, as measured by the increase in turbidity, were compared with the temperature dependencies of their thermal denaturation obtained from differential scanning calorimetry (DSC) experiments. At relatively high ionic strength (in the presence of 100 mM KCl) close to its physiological values in muscle fibers, we have found no appreciable difference between the two S1 isoforms in their thermally induced aggregation. Under these conditions, the aggregation of both S1 isoforms was independent of the protein concentration and resulted from their irreversible denaturation, which led to the cohesion of denatured S1 molecules. In contrast, a significant difference between these S1 isoforms was revealed in their aggregation measured at low ionic strength. Under these conditions, the aggregation of S1 containing a light chain A1 (but not A2) was strongly dependent on protein concentration, the increase of which (from 0.125 to 2.0 mg/ml) shifted the aggregation curve by ~10 degrees towards the lower temperatures. It has been concluded that the aggregation properties of this S1 isoform at low ionic strength is basically determined by intermolecular interactions of the N-terminal extension of the A1 light chain (which is absent in the A2 light chain) with other S1 molecules. These interactions seem to be independent of the S1 thermal denaturation, and they may take place even at low temperature.
- Published
- 2010
42. Ontogenic characteristics of cavian aldolase
- Author
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Colin Masters, Denis I. Crane, and Wayne Murrell
- Subjects
Aging ,Ontogeny ,Guinea Pigs ,Growth ,Biology ,Kidney ,Muscle Development ,Isozyme ,Guinea pig ,Fetus ,Fructose-Bisphosphate Aldolase ,Animals ,Tissue Distribution ,Degree of association ,chemistry.chemical_classification ,Muscles ,Myocardium ,Aldolase A ,Brain ,Heart ,Phenotype ,Isoenzymes ,Enzyme ,Order (biology) ,Liver ,Solubility ,Biochemistry ,chemistry ,biology.protein ,Developmental Biology - Abstract
In order to extend the available information on the ontogenic significance of the interactions between aldolase and cellular structure, the nature and extent of these associations have been studied in the tissues of the guinea pig during development, along with analyses of the isozyme status in the bound and soluble compartments. In all tissues investigated, a significant degree of binding was evident, along with a considerable variation in the degree of association of aldolase with structure during development. Binding was particularly extensive in the early foetal stages and, in general, binding preference was directed towards A-type activity over the B- and C-type of enzyme. The significance of these ontogenic phenomena have been discussed in relation to the variations in phenotype of individual tissues during maturation and the metabolic correlations of this biphasic micro-organization.
- Published
- 1992
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- View/download PDF
43. Identification of a catalase-negative sub-population of peroxisomes induced in mouse liver by clofibrate
- Author
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Alf Poulos, Elmar Klucis, Denis I. Crane, Colin Masters, and Jennifer Hughes
- Subjects
Urate Oxidase ,Immunoelectron microscopy ,Population ,Biophysics ,Peroxisome Proliferation ,Biology ,Microbodies ,Biochemistry ,Mice ,medicine ,Animals ,Clofibrate ,Acetyl-CoA C-Acetyltransferase ,Microscopy, Immunoelectron ,education ,Molecular Biology ,education.field_of_study ,Oxidase test ,Thiolase ,Urate oxidase ,Hydrogen-Ion Concentration ,Peroxisome ,Catalase ,Liver ,Female ,Acyl-CoA Oxidase ,Oxidoreductases ,Subcellular Fractions ,medicine.drug - Abstract
The peroxisomal compartment in mouse liver was investigated using rate sedimentation of liver subfractions on sucrose density gradients. Treatment of mice with clofibrate, a hypolipidemic agent and peroxisome proliferator, resulted in the formation of small particles which were devoid of catalase and urate oxidase, but which were identified as peroxisomal on the basis of content of the clofibrate-induced peroxisomal β-oxidation enzymes (fatty acyl-CoA oxidase, hydratase/dehydrogenase bifunctional protein, and thiolase) and the 68 kDa peroxisomal integral membrane protein. Immunoelectron microscopy confirmed the membrane-bound organellar nature and enzyme composition of these particles. These particles were absent in normal mice, and were increased to a maximal level within 2 days of clofibrate treatment. These data have been taken as indicative of a role of these particles in the mechanism of drug-induced peroxisome proliferation.
- Published
- 1991
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- View/download PDF
44. Small heat shock protein Hsp27 protects myosin S1 from heat-induced aggregation, but not from thermal denaturation and ATPase inactivation
- Author
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Anastasia V. Pivovarova, Ivan S. Chernik, Denis I. Markov, Nikolai B. Gusev, and Dmitrii I. Levitsky
- Subjects
endocrine system ,Protein Denaturation ,Protein Folding ,animal structures ,Hot Temperature ,Light ,ATPase ,Biophysics ,HSP27 Heat-Shock Proteins ,Protein aggregation ,Small heat shock proteins ,urologic and male genital diseases ,Biochemistry ,Thermal denaturation ,Myosin head ,Differential scanning calorimetry ,Dynamic light scattering ,Hsp27 ,Structural Biology ,Heat shock protein ,Myosin ,Genetics ,Animals ,Humans ,Scattering, Radiation ,Phosphorylation ,Myosin subfragment 1 ,Molecular Biology ,Heat-Shock Proteins ,Adenosine Triphosphatases ,biology ,Calorimetry, Differential Scanning ,Chemistry ,Myosin Subfragments ,Cell Biology ,Neoplasm Proteins ,Rats ,embryonic structures ,Mutation ,biology.protein ,Molecular Chaperones - Abstract
We applied different methods, such as turbidity measurements, dynamic light scattering, differential scanning calorimetry and co-sedimentation assay, to analyze the interaction of small heat shock protein Hsp27 with isolated myosin head (myosin subfragment 1, S1) under heat-stress conditions. Upon heating at 43°C, Hsp27 effectively suppresses S1 aggregation, and this effect is enhanced by mutations mimicking Hsp27 phosphorylation. However, Hsp27 was unable to prevent thermal unfolding of myosin heads and to maintain their ATPase activity under heat-shock conditions.Structured summaryMINT-6490863, MINT-6490872:LC1 (S1) (uniprotkb:P02602), Myosin subfragment 1 (S1) (uniprotkb:P02562) and Hsp27 (uniprotkb:P04792) physically interact (MI:0218) by dynamic light scattering (MI:0038)MINT-6490833:LC1 (S1) (uniprotkb:P02602), Myosin subfragment 1 (S1) (uniprotkb:P02562) and Hsp27 (uniprotkb:P04792) physically interact (MI:0218) by cosedimentation (MI:0027)MINT-6490770, MINT-6490782:LC1 (S1) (uniprotkb:P02602), Myosin subfragment 1 (S1) (uniprotkb:P02562) and Hsp27 (uniprotkb:P04792) physically interact (MI:0218) by light scattering (MI:0067)
- Published
- 2007
45. Extraction of fluorescent cell puncta by adaptive fuzzy segmentation
- Author
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Denis I. Crane, Tam H. Nguyen, Tuan H. Tran, and Tuan D. Pham
- Subjects
Statistics and Probability ,Computer science ,Population ,Image processing ,Biochemistry ,Fuzzy logic ,Sensitivity and Specificity ,Cell Line ,Pattern Recognition, Automated ,Fuzzy Logic ,Artificial Intelligence ,Organelle ,Image Interpretation, Computer-Assisted ,Peroxisomes ,Quadtree ,Cluster Analysis ,Humans ,Segmentation ,Computer vision ,education ,Molecular Biology ,education.field_of_study ,business.industry ,Vesicle ,Reproducibility of Results ,Peroxisome ,Fibroblasts ,Partition (database) ,Computer Science Applications ,Computational Mathematics ,Computational Theory and Mathematics ,Microscopy, Fluorescence ,Cytoplasm ,Pattern recognition (psychology) ,Artificial intelligence ,business ,Biogenesis ,Algorithms - Abstract
Motivation: The discrimination and measurement of fluorescent-labeled vesicles using microscopic analysis of fixed cells presents a challenge for biologists interested in quantifying the abundance, size and distribution of such vesicles in normal and abnormal cellular situations. In the specific application reported here, we were interested in quantifying changes to the population of a major organelle, the peroxisome, in cells from normal control patients and from patients with a defect in peroxisome biogenesis. In the latter, peroxisomes are present as larger vesicular structures with a more restricted cytoplasmic distribution. Existing image processing methods for extracting fluorescent cell puncta do not provide useful results and therefore, there is a need to develop some new approaches for dealing with such a task effectively. Results: We present an effective implementation of the fuzzy c-means algorithm for extracting puncta (spots), representing fluorescent-labeled peroxisomes, which are subject to low contrast. We make use of the quadtree partition to enhance the fuzzy c-means based segmentation and to disregard regions which contain no target objects (peroxisomes) in order to minimize considerable time taken by the iterative process of the fuzzy c-means algorithm. We finally isolate touching peroxisomes by an aspect-ratio criterion. The proposed approach has been applied to extract peroxisomes contained in several sets of color images and the results are superior to those obtained from a number of standard techniques for spot extraction. Availability: Image data and computer codes written in Matlab are available upon request from the first author.
- Published
- 2004
46. Isolation and characterisation of a chick cDNA encoding the RNA polymerase common subunit RPB6
- Author
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Mari Kaarbø, Denis I. Crane, and Wayne Murrell
- Subjects
DNA, Complementary ,Molecular Sequence Data ,RNA-dependent RNA polymerase ,Chick Embryo ,Biochemistry ,Ribosome ,Endocrinology ,Rapid amplification of cDNA ends ,Complementary DNA ,Cricetinae ,Genetics ,RNA polymerase I ,Animals ,Humans ,Amino Acid Sequence ,Molecular Biology ,Polymerase ,Conserved Sequence ,biology ,Base Sequence ,Sequence Homology, Amino Acid ,cDNA library ,RNA ,DNA-Directed RNA Polymerases ,Molecular biology ,Rats ,biology.protein - Abstract
The RPB6 cDNA of chicken, encoding one of the small subunits common to all three nuclear DNA-depend-ent RNA polymerases, has been isolated from an expression cDNA library by screening with a differential display derived probe, representing a gene shown to be highly up-regulated in early heart development. The nucleotide sequence of the cDNA isolated predicts a protein sequence of 127 amino acids. This sequence shares 124 amino acids (98 % homology) with the human RNA polymerase II subunit 14.4 kDa (RPB6) and hamster hRPB6 and 123 amino acids (97% homology) with Rattus norvegicus RNA polymerase II subunit RPB6. Other conserved motifs in this protein and potential functions of RPB6 are discussed.
- Published
- 2000
47. Interaction of Pex5p, the type 1 peroxisome targeting signal receptor, with the peroxisomal membrane proteins Pex14p and Pex13p
- Author
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Aaron J. Urquhart, Stephen Jay Gould, Denis I. Crane, and Derek Kennedy
- Subjects
Models, Molecular ,Saccharomyces cerevisiae Proteins ,Peroxisome-Targeting Signal 1 Receptor ,Recombinant Fusion Proteins ,Molecular Sequence Data ,Receptors, Cytoplasmic and Nuclear ,Peptide ,Target peptide ,Biology ,Protein Sorting Signals ,Biochemistry ,SH3 domain ,Pichia ,Fungal Proteins ,Peroxins ,src Homology Domains ,Peroxisomes ,Amino Acid Sequence ,Binding site ,Molecular Biology ,Peroxisomal targeting signal ,chemistry.chemical_classification ,Binding Sites ,Peroxisomal matrix ,Membrane Proteins ,Membrane Transport Proteins ,Cell Biology ,Peroxisome ,Cell biology ,Repressor Proteins ,chemistry ,Mutation ,Carrier Proteins ,Binding domain ,Protein Binding - Abstract
Pex5p, a receptor for peroxisomal matrix proteins with a type 1 peroxisome targeting signal (PTS1), has been proposed to cycle from the cytoplasm to the peroxisomal membrane where it docks with Pex14p and Pex13p, the latter an SH3 domain-containing protein. Using in vitro binding assays we have demonstrated that binding of Pex5p to Pex14p is enhanced when Pex5p is loaded with a PTS1-containing peptide. In contrast, Pex5p binding to Pex13p, which involves only the SH3 domain, occurs at 20-40-fold lower levels and is reduced when Pex5p is preloaded with a PTS1 peptide. Pex14p was also shown to bind weakly to the Pex13p SH3 domain. Site-directed mutagenesis of the Pex13p SH3 domain attenuated binding to Pex5p and Pex14p, consistent with both of these proteins being binding partners for this domain. The SH3 binding site in Pex5p was determined to lie within a 114-residue peptide (Trp(100)-Glu(213)) in the amino-terminal region of the protein. The interaction between this peptide and the SH3 domain was competitively inhibited by Pex14p. We interpret these data as suggesting that docking of the Pex5p-PTS1 protein complex at the peroxisome membrane occurs at Pex14p and that the Pex13p SH3 domain functions as an associated component possibly involved in sequestering Pex5p after relinquishment of the PTS1 protein cargo to components of the translocation machinery.
- Published
- 2000
48. A novel sulfonic-acid analogue of ceramide is the major extractable lipid of the gram-negative marine bacterium Cyclobacterium marinus WH
- Author
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Alexandr O. Ruzhitsky, Denis I. Nikitin, Vladimir I Sheichenko, and Stanislav G. Batrakov
- Subjects
Ceramide ,Magnetic Resonance Spectroscopy ,Biophysics ,Molecular Conformation ,Sulfonic acid ,Ceramides ,Biochemistry ,Mass Spectrometry ,Serine ,chemistry.chemical_compound ,Endocrinology ,Phosphatidylcholine ,Gram-Negative Bacteria ,Glycerol ,Phospholipids ,chemistry.chemical_classification ,Phosphatidylethanolamine ,Molecular Structure ,Phosphatidylethanolamines ,Fatty Acids ,Absolute configuration ,Fatty acid ,Lipids ,chemistry ,Phosphatidylcholines ,Sulfonic Acids ,Peptides - Abstract
The extractable lipids of the gram-negative, sea-water bacterium Cyclobacterium marinus strain WH contain about 94% of polar components which consist of two phospholipids, phosphatidylethanolamine (29% of the total lipids) and phosphatidylcholine (7%), and two phosphorus-free lipids. One of the latter has been shown to be a novel sulfonic-acid analogue of ceramide, 2- d -(2′- d -hydroxy-13′-methyltetradecanoyl) amino-3- d -hydroxy-15-methylhexadec-4 (E)-en-1-sulfonic acid (48%), and other is a lipodipeptide, N-[3- d -(13′-methyltetradecanoyloxy)-15-methylhexadecanoyl] glycyl- l -serine (11%), which has so far been found only in a Flavobacterium sp. strain. The dominant fatty acid residues of the phospholipids are iso-15:0, n-16:0, 16:1 and 18:1, the acyl residues linked to the sn-1 carbon of the glycerol moiety being somewhat more saturated as compared with those located at the sn-2 position. A new procedure for determination of the absolute configuration of 2- and 3-hydroxy fatty acids is briefly described.
- Published
- 1998
49. Kinetics of Thermal Denaturation and Aggregation of Bovine Serum Albumin.
- Author
-
Borzova, Vera A., Markossian, Kira A., Chebotareva, Natalia A., Kleymenov, Sergey Yu., Poliansky, Nikolay B., Muranov, Konstantin O., Stein-Margolina, Vita A., Shubin, Vladimir V., Markov, Denis I., and Kurganov, Boris I.
- Subjects
SERUM albumin ,DENATURATION of proteins ,CLUSTERING of particles ,CHEMICAL kinetics ,ULTRACENTRIFUGATION ,LIGHT scattering - Abstract
Thermal aggregation of bovine serum albumin (BSA) has been studied using dynamic light scattering, asymmetric flow field-flow fractionation and analytical ultracentrifugation. The studies were carried out at fixed temperatures (60°C, 65°C, 70°C and 80°C) in 0.1 M phosphate buffer, pH 7.0, at BSA concentration of 1 mg/ml. Thermal denaturation of the protein was studied by differential scanning calorimetry. Analysis of the experimental data shows that at 65°C the stage of protein unfolding and individual stages of protein aggregation are markedly separated in time. This circumstance allowed us to propose the following mechanism of thermal aggregation of BSA. Protein unfolding results in the formation of two forms of the non-native protein with different propensity to aggregation. One of the forms (highly reactive unfolded form, U
hr ) is characterized by a high rate of aggregation. Aggregation of Uhr leads to the formation of primary aggregates with the hydrodynamic radius (Rh,1 ) of 10.3 nm. The second form (low reactive unfolded form, Ulr ) participates in the aggregation process by its attachment to the primary aggregates produced by the Uhr form and possesses ability for self-aggregation with formation of stable small-sized aggregates (Ast ). At complete exhaustion of Ulr , secondary aggregates with the hydrodynamic radius (Rh,2 ) of 12.8 nm are formed. At 60°C the rates of unfolding and aggregation are commensurate, at 70°C the rates of formation of the primary and secondary aggregates are commensurate, at 80°C the registration of the initial stages of aggregation is complicated by formation of large-sized aggregates. [ABSTRACT FROM AUTHOR]- Published
- 2016
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- View/download PDF
50. The neurochemical pathology of thiamine deficiency: GABAA and glutamateNMDA receptor binding sites in a goat model
- Author
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I. D. Smith, Gregory J. Thomas, Denis I. Crane, Peter R. Dodd, and Andrew McCloskey
- Subjects
Male ,medicine.medical_specialty ,Synaptic Membranes ,Amprolium ,Flunitrazepam ,Biology ,Neurotransmission ,In Vitro Techniques ,Biochemistry ,Receptors, N-Methyl-D-Aspartate ,gamma-Aminobutyric acid ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Internal medicine ,medicine ,Animals ,GABA Modulators ,GABA Agonists ,gamma-Aminobutyric Acid ,Brain Chemistry ,Diazepam binding ,Diazepam ,GABAA receptor ,Muscimol ,Goats ,Glutamate receptor ,Thiamine Deficiency ,Receptors, GABA-A ,Alcoholism ,Disease Models, Animal ,Endocrinology ,chemistry ,NMDA receptor ,Thiamine ,Female ,Neurology (clinical) ,Dizocilpine Maleate ,Excitatory Amino Acid Antagonists ,medicine.drug ,Synaptosomes - Abstract
Synaptic plasma membranes were prepared from four cerebrocortical areas from six male Angora goats made chronically thiamine deficient (TD) by the administration of AmproliumTM (600-900 mg/kg daily for 38-44 d). Four male controls were matched for age (27-30 mo). Four different radioligands were used to characterise GABAA and Glu-RNMDA receptor binding sites. There were marked, localised and contrasting changes in motor cortex, with an increase in GABAA and a decrease in Glu-RNMDA binding site densities. Less clearcut changes of a similar nature were seen in visual cortex. There was no variation in the parameters of GABA-activated [3H]diazepam binding between cortical areas in control goats, but there was a reduction in the maximal response to GABA in all areas in TD goats. There were regional variations in glutamate-activated [3H]MK-801 binding in control goat brain, and a non-selectively reduced maximal response in TD. Alterations in these indices of GABA- and glutamate-mediated neurotransmission may underlie the neurological signs of acute thiamine deficiency in these animals.
- Published
- 1996
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