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6. Inquiry based writing workshop

Author

Spence, Luck K.

Subjects
School librarians -- Practice -- Methods, Teaching teams -- Methods, Workshops (Educational programs) -- Management -- Methods, Education, Library and information science, Company business management, Practice, Management, Methods
Abstract

Second-grade teacher, Nancy, was interested in providing her students with rich engagements with non-fiction texts and for help she came to me, the teacher-librarian in her K-5 school with weekly [...]

Published
2009

8. Burmester theory for four-bar-band mechanisms

Author

Luck, K. and Modler, K.-H.

Subjects
Kinematic geometry -- Research, Machinery, Kinematics of -- Research, Mechanical movements -- Research, Engineering and manufacturing industries, Science and technology
Abstract

A band mechanism includes inter alia a flexible band and a disk profile. Such a mechanism can be used for path generation better than a four-bar linkage. Also several plane positions can be realized. This paper investigates the synthesis of four-bar-band mechanisms by using complex vector algebra. Several technical tasks demonstrate the flexible application of such mechanisms. These tasks are formulated according to the well-known Burmester Theory, but with higher claims and a solution achieved by analytical methods. Furthermore, this paper demonstrates that a four-bar linkage is a special case of a four-bar-band mechanism.

Published
1995

14. CYP79D enzymes contribute to jasmonic acid-induced formation of aldoximes and other nitrogenous volatiles in two Erythroxylum species

Author

Luck, K., Jirschitzka, J., Irmisch, S., Huber, M., Gershenzon, J., Köllner, T.G., and Publica

Subjects
Volatiles, Coca, Volatile Organic Compounds, Cytochrome P450 monooxygenase, Plant Science, Cyclopentanes, Real-Time Polymerase Chain Reaction, Erythroxylum, Cytochrome P-450 Enzyme System, Species Specificity, CYP79, Oximes, Amino Acid Sequence, Oxylipins, Nitrogen Compounds, Sequence Alignment, Phylogeny, Research Article, Aldoxime, Plant Proteins
Abstract

Background Amino acid-derived aldoximes and nitriles play important roles in plant defence. They are well-known as precursors for constitutive defence compounds such as cyanogenic glucosides and glucosinolates, but are also released as volatiles after insect feeding. Cytochrome P450 monooxygenases (CYP) of the CYP79 family catalyze the formation of aldoximes from the corresponding amino acids. However, the majority of CYP79s characterized so far are involved in cyanogenic glucoside or glucosinolate biosynthesis and only a few have been reported to be responsible for nitrogenous volatile production. Results In this study we analysed and compared the jasmonic acid-induced volatile blends of two Erythroxylum species, the cultivated South American crop species E. coca and the African wild species E. fischeri. Both species produced different nitrogenous compounds including aliphatic aldoximes and an aromatic nitrile. Four isolated CYP79 genes (two from each species) were heterologously expressed in yeast and biochemically characterized. CYP79D62 from E. coca and CYP79D61 and CYP79D60 from E. fischeri showed broad substrate specificity in vitro and converted L-phenylalanine, L-isoleucine, L-leucine, L-tryptophan, and L-tyrosine into the respective aldoximes. In contrast, recombinant CYP79D63 from E. coca exclusively accepted L-tryptophan as substrate. Quantitative real-time PCR revealed that CYP79D60, CYP79D61, and CYP79D62 were significantly upregulated in jasmonic acid-treated Erythroxylum leaves. Conclusions The kinetic parameters of the enzymes expressed in vitro coupled with the expression patterns of the corresponding genes and the accumulation and emission of (E/Z)-phenylacetaldoxime, (E/Z)-indole-3-acetaldoxime, (E/Z)-3-methylbutyraldoxime, and (E/Z)-2-methylbutyraldoxime in jasmonic acid-treated leaves suggest that CYP79D60, CYP79D61, and CYP79D62 accept L-phenylalanine, L-leucine, L-isoleucine, and L-tryptophan as substrates in vivo and contribute to the production of volatile and semi-volatile nitrogenous defence compounds in E. coca and E. fischeri. Electronic supplementary material The online version of this article (doi:10.1186/s12870-016-0910-5) contains supplementary material, which is available to authorized users.

Published
2016

15. ELM—the database of eukaryotic linear motifs

Author

Dinkel, H., Michael, S., Weatheritt, R. J., Davey, N. E., Van Roey, K., Altenberg, B., Toedt, G., Uyar, B., Seiler, M., Budd, A., Jodicke, L., Dammert, M. A., Schroeter, C., Hammer, M., Schmidt, T., Jehl, P., McGuigan, C., Dymecka, M., Chica, C., Luck, K., Via, A., Chatr-aryamontri, A., Haslam, N., Grebnev, G., Edwards, R. J., Steinmetz, M. O., Meiselbach, H., Diella, F., and Gibson, T. J.

Published
2012
Full Text
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16. Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction

Author

Bonaca, MP, Bhatt, DL, Cohen, M, Steg, PG, Storey, RF, Jensen, EC, Magnani, G, Bansilal, S, Fish, MP, Im, K, Bengtsson, O, Ophuis, TO, Budaj, A, Theroux, P, Ruda, M, Hamm, C, Goto, S, Spinar, J, Nicolau, JC, Kiss, RG, Murphy, SA, Wiviott, SD, Held, P, Braunwald, E, Sabatine, MS, Morin, S, Dantzer, E, Acquilano, D, McGuire, RL, Gannon, JB, Gershman, E, Ahlbom, AM, Boberg, B, Abola, MT, Ardissino, D, Aylward, P, Corbalan, R, Dalby, A, Diaz, R, Hu, DY, Isaza, D, Kamensky, G, Kiss, R, Kontny, F, Lopez-Sendon, J, Medina, F, Montalescot, G, Nicolau, J, Paolasso, E, Parkhomenko, A, Van De Werf, F, Anderson, JL, White, HD, Verheugt, FWA, Pedersen, TR, DeMets, DL, Lowe, C, Arevalo, C, Awtry, E, Berger, C, Croce, K, Desai, A, Gelfand, E, Ho, C, Leeman, D, Link, M, Norden, A, Pande, A, Rost, N, Ruberg, F, Silverman, S, Singhal, A, Vita, J, Alvarisqueta, A, De Gennaro, N, Berli, M, Roude, AE, Di Gennaro, JA, Albisu, JF, Caccavo, A, Torres, M, Cuadrado, J, Bordoni, P, Cuello, J, Aviles, A, Glenny, A, Recoaro, R, Fernandez, R, Strada, BN, Fuentealba, V, Gallo, C, Duran, RG, Garcia, C, Hominal, M, Castoldi, M, Jure, H, Pacora, FF, Lorenzatti, A, Martinez, JM, Macin, S, Cocco, N, MacKinnon, I, Bagnato, MB, Marino, J, Cusimano, S, Arias, V, Focaccia, M, Muntaner, J, Mansilla, V, Poy, C, Prado, A, Paterlini, G, Montana, O, Camino, A, Sala, J, Luciani, C, Vico, M, Morell, Y, Dumont, C, Vottero, E, Zangroniz, P, Lescano, A, Morara, P, Marquez, LL, Patron, FR, Labarta, GB, Sivila, CD, Quiroga, AR, Maffei, L, Sassone, S, Rolandi, F, Vesentini, N, Carnero, G, Del Verme, S, Hershson, A, Figal, JC, Viso, ME, Hii, C, Smith, K, Singh, B, Acampo, M, Rogers, J, ODonoghue, M, Amerena, J, Long, A, Dart, A, Kay, S, Worthley, M, Nimmo, J, Lehman, R, Morrison, H, Dick, R, Savage, C, van Gaal, W, Park, M, Blombery, P, McCarthy, C, Oqueli, E, Hill, D, Sader, M, Vrachas, D, Purnell, P, Vibert, J, Collins, N, Gordon, A, Arstall, M, Rose, J, Aroney, C, Cleave, P, Fitzpatrick, M, Mackenzie, M, Garrahy, P, Hall, C, Nelson, G, Reid, E, Lee, A, Gibbs, J, Thompson, P, Crittenden, J, Hammett, C, Hindom, L, Antonis, P, Manzoney, A, Cross, D, Pollard, C, Brieger, D, Wu, J, Whelan, A, Tulloch, G, Taylor, A, Smith, B, Horowitz, J, Black, M, Boland, J, Malmendier, D, Celen, H, Wendelen, E, Claeys, M, Pieter, M, Cools, F, Simons, N, De Maeseneire, S, De Wolf, L, Brike, C, Dubois, P, Bolado, ACY, Foading-Deffo, B, Tahon, S, Friart, A, Arend, C, Gevaert, S, Verdegem, P, Marechal, P, Gits, F, Pierard, L, Celentano, C, Pirenne, B, Bouvy, C, Renkin, J, Huyberechts, D, Sinnaeve, P, De Velder, L, Stammen, F, Casier, T, Striekwold, H, Van den Broeck, D, Thoeng, J, Goris, R, Timmermans, P, Collard, SJ, Van De Borne, P, De Clippel, M, Wollaert, B, Jacobs, C, Vankelecom, B, Daelemans, Y, Vervoort, G, Drieghe, S, Vranckx, P, Janssen, A, Vrolix, M, Simenon, I, Wijns, W, Delacroix, H, Denie, D, Schoors, D, Lemoine, I, Cornelis, K, Willems, AM, Schroder, E, Domange, J, Greque, G, Machado, H, Armaganijan, D, Del Monaco, MI, da Silva, D, Nakazone, R, Dutra, O, Vaz, R, Daher, R, Rodrigues, D, Guimaraes, A, Teixeira, A, Saraiva, J, Leaes, P, Blacher, M, Maia, L, Nakazone, MA, Manenti, E, Ruschel, K, Marin-Neto, J, Pavao, R, Preto, R, Junior, AA, Oliveira, G, Rassi, S, Sampaio, D, Rossi, PR, dos Santos, L, de Souza, J, Lino, E, Filho, PP, Zucchetti, C, Gomes, M, de Paiva, A, Sousa, AC, Almeida, A, Botelho, R, da Silva, R, Giraldez, R, Franken, M, Faludi, A, Bertolami, M, Hernandes, M, Lucas, N, Carvalho, A, Bertolami, A, Precoma, D, Geralde, L, Pereira, A, Cesar, L, Mioto, B, Marino, R, Rabelo, W, dos Santos, F, Vidotti, M, Mangione, J, Mauro, M, Kormann, A, Ultramari, F, Zimmermann, S, Michalaros, Y, Fonseca, M, Sampaio, C, Eliaschewitz, F, Barbosa, E, Drews, C, de Lorenzo, A, Barros, C, Cancado, G, Neuesnchwander, F, Zimmermann, E, Chompalova, B, Denchev, S, Gocheva, N, Mihov, A, Mincheva, V, Gelev, V, Tisheva, S, Todorov, G, Goudev, A, Parvanova, Z, Todorova, M, Mitkova, M, Smilov, L, Yakovova, S, Milanova, K, Aleksov, N, Mollov, M, Shishmanova, D, Hristova, K, Uzunangelov, Y, Peltegov, V, Karamitev, G, Benov, H, Vasileva, D, Parishev, G, Milcheva, N, Avramov, D, Miteva, B, Stoyanovski, V, Pencheva, G, Nikolova, L, Stancheva, N, Nyagina, M, Markov, D, Spirova, D, Peneva, Y, Peshkov, O, Mitkova, L, Mandzhukova, S, Rangelova, V, Ivanov, K, Krusheva, B, Raycheva, V, Gergova, V, Goranov, K, Stoykov, A, Staleva, M, Rashkova, V, Postadzhian, A, Krancheva, V, Lulova, E, Delchev, G, Cantor, W, Constance, C, Gosselin, G, Marr, D, Pandey, A, Pesant, Y, Pouliot, J, Gladstone, P, McPherson, T, Rupka, D, Saw, J, St-Amour, E, Syan, G, Syan, R, Rosenbloom, A, Vizel, S, Della Siega, A, Halperin, F, Nigro, F, Chehayeb, R, Fell, D, Labonte, R, Nawaz, S, Gupta, M, Ma, P, Glanz, A, Kouz, S, Bhargava, R, Dion, D, Dupuis, R, Grondin, F, Wong, B, Sabbah, E, Hui, W, Belisle, P, Tymchak, W, Montigny, M, Lonn, E, Bose, S, Kincade, D, Gallo, R, Lamy, A, Bell, A, Lemay, M, Bata, I, Kostuk, W, Cheung, S, Petrella, R, Lubelsky, B, Berlingieri, J, Fortin, C, DeYoung, J, Babapulle, M, Landry, D, Gupta, A, Bertrand, O, Jadin, M, Robbins, K, Gauthier, MF, Masson, C, Reyes, V, O'Blenis, G, Clarus, S, Sardin, V, Marquette, S, Bozek, B, Spurrell, D, Thiessen, S, Fox, R, Tremblay, I, Singh, J, Samms, S, Ross, B, Solomon, P, Nelson, S, Roberts, P, Forsyth, C, Lepage, C, McPherson, C, Dewar, C, Dela Cruz, C, Louch, D, Vilag, C, Roy, M, Stata, C, Morissette, A, Ouimet, F, Bilodeau, N, Chausse, I, Kvill, L, Chartrand, MJ, Harris, L, Bolduc, H, Magi, A, Jule, P, Valley, S, Morrissette, J, Power, P, Kailey, P, Thomas, A, Wright, D, Carr, S, Cleveland, T, Dihel, C, Coldwell, J, Schellenberg, S, Viau, C, Watt, M, Corke, R, Shea-Landry, G, Gandhi, A, Tishler, S, Prieto, JC, Noriega, V, Cobos, L, Obreque, C, Potthof, S, Zapata, J, Lucero, F, Luque, M, Pincetti, C, Torres, G, Yanez, M, Vasquez, C, Manriquez, L, Espinoza, MJ, Yovaniniz, P, Grandon, M, Castro, P, Llevaneras, S, Lanas, F, Hidalgo, J, Arriagada, G, Villan, C, Florenzano, F, Chacon, MV, Rodriguez, M, Barreda, B, Raffo, C, Reyes, T, Hu, D, Liu, W, Tan, N, Feng, Y, Dong, Y, Yang, D, Liao, Y, Wei, F, Wei, M, Yan, M, Yan, X, Wang, S, Li, Y, Yuan, Z, Xiong, Y, Zhu, J, Li, S, Ma, G, Chen, L, Li, Z, Liu, Y, Xiong, W, Pang, W, Chen, Y, Lu, G, Chen, Z, Zhao, S, Zhou, H, Huang, J, Gang, Y, Chai, Y, Yang, X, Zhang, Z, Mu, Z, Hernandez, E, Mora, C, Maria, E, Catalan, Y, Reynales, H, Huertas, D, Molina, D, Rendon, N, Sanchez, G, Tellez, R, Botero, R, Salazar, P, Vesga, B, Delgado, P, Herrera, M, Perez, D, Jaramillo, N, Toloza, R, Orozco, A, Bustamante, Y, Jaramillo, C, Garces, G, Saaibi, J, Castillo, J, Arana, C, Gonzalez, M, Urina, M, Ramirez, N, Manzur, F, Rosales, D, Quintero, A, Gonzalez, E, Accini, J, Reyes, M, Elbl, L, Malecha, J, Stanek, L, Jerabek, O, Lubanda, H, Kos, P, Zidkova, E, Vlckova, D, Naplava, R, Ludka, O, Ludkova, A, Soucek, M, Kuchar, J, Poloczek, M, Wasserburger, B, Panovsky, R, Linhart, A, Rihacek, I, Macha, J, Grunfeldova, H, Spinarova, L, Zanova, M, Bren, J, Zarembova, J, Cermak, O, Sembera, Z, Svobodova, I, Monhart, Z, Pleva, L, Sipula, J, Polasek, R, Kolmas, P, Dedek, V, Janota, T, Stipal, R, Kucera, D, Bednarova, J, Broulova, P, Lukac, M, Hanak, P, Reichert, P, Bouchal, P, Turkova, N, Krocova, E, Petrova, I, Matyasek, I, Brychta, T, Machova, V, Marusincova, I, Sperlingova, B, Macquin-Mavier, T, Khalife, K, Galley, D, Elhadad, S, Decoulx, E, Cottin, Y, Coisne, D, Bonnet, JL, Ferrari, E, Range, G, Cayla, G, Goralski, M, Furber, A, Elbaz, M, Aboyans, V, Poulard, JE, Zemour, G, Labeque, JN, Hirsch, JL, Vaquette, B, Livarek, B, Igigabel, P, Lafitte, S, Oudghiri, M, Bertin, B, Beitar, T, Merkling, D, Beltra, C, Maubert, A, El Jarroudi, M, Bichat, F, Berger, N, Fiacchetti, C, Douillet, M, Laure, C, Leperchois-Jacquey, C, Miran, S, Cornet, C, Rosolin, N, Pradel, V, Leparree, S, Doux, N, Mais, C, Sevilla, J, Laurencon, V, Georges, J, Gilard, V, Duprat, C, Giannitsis, E, Schenkenberger, I, Appel, KF, Toursarkissian, N, Bott, J, Nischik, R, Schmidt, E, Jung, T, Steiner, S, Khariouzov, A, Heuer, H, Kadel, C, Hanefeld, M, Weil, J, Koenig, W, Horacek, T, Muenzel, T, Brachmann, J, Weber, D, Wittlich, N, Stellbrink, C, Dungen, HD, Leschke, M, Zeymer, U, Dorsel, T, Voehringer, HF, Dissmann, M, Vom Dahl, J, Derwahl, KM, Trenk, D, Frey, N, Schroeder, T, Foerster, A, Bartels, R, Kisselbach, C, Deigentasch, H, Dreykluft, K, Becker, P, Scheuren, A, Erdas, M, Wipper, J, Schmidt, A, Henzler, A, Winter, K, Fischer, S, Kopf, S, Laschewski, B, Rahn, G, Schrapel, C, Miodek, M, Hildenbrand, S, Fink, P, Gebel, G, Goebel, U, Siepmann, C, Drexler, A, Maiwald, A, Blaich, B, Baumann, S, Iselt, M, Gebhardt, S, Kazcmarek, N, Krug-Hoeren, B, Traubler, B, Nicula, D, Reichenbach, D, Langer, C, Kiroglu, K, Riedel, S, Schulte, M, Borst, M, Katona, A, Vertes, A, Merkely, B, Ungi, I, Kiraly, C, Zolyomi, S, Horvath, I, Lupkovics, G, Edes, I, Simon, E, Czuriga, I, Laszlo, Z, Kancz, S, Takacs, J, Papp, A, Czigany, A, Muller, G, Tas, AS, Polgar, P, Jilling, MJ, Bartal, G, Kerkovits, A, Bodi, M, Benczur, B, Valco, J, Erdei, F, Sebo, J, Korda, A, Turi, T, Becker, D, Kalapos, A, Bosko, M, Pap, G, Magyari, B, Basa, A, Jenei, C, Bakai, J, Unterberger, K, Vas, K, Fulop, G, Nagy, M, Takacs, A, Mate, Z, Szilagyi, A, Nagy, K, Svab, M, Kis, E, Horthy, R, Kantor, F, Sperr, E, Bajcsi, E, Bujdoso, A, Martina, P, Fiscella, A, Marenzi, G, Tamburino, C, Terrosu, P, Presbitero, P, Cuccia, C, Bovenzi, F, Berti, S, Colivicchi, F, Paloscia, L, Scherillo, M, Tartaglione, S, Della Rovere, F, De Cesare, N, Manari, A, Astarita, C, Oltrona, L, Marzilli, M, Caldarola, P, Merlini, P, Celentano, A, Di Sciascio, G, Pajes, G, Silvestri, O, Delfino, R, Bassani, F, Cavallini, C, Fattore, L, Di Lorenzo, L, Notarangelo, F, Stefanin, C, Giacoppo, M, Rubino, M, Dammino, L, Chessa, P, Di Pizzo, A, Musmeci, G, Mazzoni, A, Tyack, K, Aiello, A, Mascellanti, M, Formigli, D, Guglielmino, G, Bernabo, P, Bocciarelli, M, De Iaco, G, Russo, G, Rizzotti, D, Orsini, E, Saponetti, LS, Babbolin, M, De Divitiis, M, Patti, G, Monti, F, Silvestri, N, Valbusa, A, Lazzarotti, M, Puccetti, L, Grikstaite, E, Patrizi, G, Bosco, B, Marchegiano, R, Takenaka, T, Ono, M, Suzuki, M, Hasegawa, K, Domae, H, Fukui, K, Iseki, H, Aoyama, T, Suzuki, C, Sakai, R, Hashimoto, T, Inoko, M, Sasaki, T, Kataoka, T, Okutsu, M, Yasaka, Y, Miyamoto, T, Tomobuchi, Y, Tamura, R, Hosokawa, S, Komura, Y, Takahashi, N, Mima, T, Sadamatsu, K, Fujimoto, K, Matsumura, T, Koide, S, Himi, T, Hashimoto, Y, Yamasaki, M, Okubo, M, Takase, H, Morii, I, Utsu, N, Higashino, Y, Shigematsu, S, Nakagawa, T, Ota, T, Takahashi, W, Kakishita, M, Hayashi, Y, Momiyama, Y, Baden, M, Saeki, T, Hiroi, S, Wada, A, Nakata, A, Nishi, Y, Hirasawa, S, Shibata, Y, Fukuzawa, S, Machida, M, Takama, N, Teranishi, J, Sakuma, K, Abe, Y, Suzuki, A, Yamazaki, A, Nakachi, T, Nagayama, H, Fujino, S, Tsurukai, A, Nojima, S, Ishiguchi, Y, Hada, K, Nakatani, K, Yamamoto, K, Matsuo, A, Yamaguchi, E, Ito, S, Matsuda, M, Onishi, M, Kawanishi, Y, Ohashi, Y, Ochi, K, Miyamoto, S, Ichishita, Y, Iwamoto, H, Sagara, Y, Komori, M, Matsumura, A, Nakashima, R, Kondo, M, Suzuki, K, Kodama, S, Kotajima, H, Fujimoto, N, Honda, K, Iwamoto, M, Okada, S, Ichinose, K, Takinami, N, Takagi, E, Nakano, A, Tomari, H, Yokoyama, T, Matsui, Y, Nishimura, N, Asano, T, Mochiduki, A, Yamashita, S, Okino, S, Hirabayashi, K, Funada, R, Wardeh, AJ, Dille, C, De Melker, EC, van der Spoel, A, Willems, FF, Maassen, E, Westendorp, ICD, Zweers, D, Dunselman, PHJM, Blom, L, Ronner, E, Wissenburg, A, van der Sluis, A, Badings, EA, den Hartog, FR, Singerling, M, Aksoy, I, Heil, A, Tjeerdsma, G, van Daalen, C, Lenderink, T, Lardenois, R, Prins, FJ, Rutten, R, Plomp, J, Veldmeijer, S, De Vries, RJM, Krikken, J, Ophuis, TAJMO, Buvelot, S, Bos, RJ, Tan-Urgert, B, Werner, HA, Wittekoek, M, van Daele, MERM, Bouwens, M, Oomen, A, Meijlis, P, Verheul, JA, Uiterwaal, H, Knufman, N, de Lange, H, Bartels, GL, Hendriks-Van Woerden, M, van Bemmel, B, Beyering, M, Zwart, PAG, Teng, Y, van der Zwaan, C, Havenaar, J, Hermans, WRM, de Graauw, J, Hamraoui, K, Dabrowska, K, de Nooijer, C, Groenenberg, I, Kietselae, BLJH, Muis, L, Hamer, BJB, Hobe, C, van Eck, JWM, Elzebroek, N, Tans, JGM, Stapel, AGT, Nierop, PR, Dirks, M, Kuijper, AFM, Schiks, M, de Groot, MR, Post, G, ten Berg, JM, Bras, R, Koolen, JJ, van Leur, L, Herrman, JPR, Roelse, A, Ebink, C, Jones, B, Lipsic, E, Couperus, M, Bogaard, K, Dijk, A, Pettersen, KI, Fortun, M, Gullestad, L, Stueflotten, W, Popovic, I, Sobye, ET, Hogalmen, G, German, M, Hysing, J, Flagstad, E, Slettom, G, Nordrehaug, JE, Isaksen, A, Graven, T, Haug, H, Sandvik, J, Thunhaug, H, Ronning, PB, Gravrok, B, Lappegard, KT, Enebakk, T, Ronnevik, P, Ronnevik, T, Hurtig, U, Skanke, E, Omland, T, Tobiassen, GM, Berrospi, P, Ragas, Y, Bustamante, G, Marruffo, Y, Chavez, E, Chaname, A, Heredia, J, Gamero, K, Lema, J, Carrion, AM, Rodriguez, V, Cabanillas, N, Rodriguez, A, Zena, N, Segura, L, Rojas, C, Toce, L, Carrera, J, Orihuela, B, Del Portal, M, Roldan, Y, Roldan, G, Rodriguez, J, Chavez, C, Luna, G, Parra, J, Ramos, J, Mogrovejo, W, Godoy, J, Talledo, MZ, Diestra, J, Godoy, A, Matta, M, Pino, C, Vergara, R, Chois, A, Guillen, AM, Medina, J, Chirinos, J, Paredes, A, Quiroz, M, Camacho, L, Gil, M, Cerbito, S, Beltran, J, Tanglao, M, Uy, N, Busa, J, Rogelio, G, Arbis, MG, Prado, JP, Miranda, M, Sulit, DJ, Dioquino, R, Sevilla, R, Soriano, RA, Rosita, RR, Amazona, A, Atilano, A, Lim, E, Ebo, G, Maglasang, P, Palmes, P, Loreno, CA, Tirador, L, Alagban, C, Roxas, DJ, Roxas, JF, Cheng, F, De Guzman, S, Morales, D, Mararac, T, Barbas, B, Barbas, K, Ferrolino, A, Baysac, C, Llarena, AC, Julianes, C, Torun, A, Dalkowski, M, Widejko, K, Derlaga, B, Laskowska, E, Dudek, D, Dziewierz, A, Jozwa, R, Busz-Papiez, B, Pawlowicz, L, Kaczmarczyk, M, Jaworska, K, Skonieczny, G, Kopaczewski, J, Wujkowski, M, Krasowski, W, Krzyzanek, P, Kubica, J, Kozinski, M, Miekus, P, Glaza, M, Podolec, P, Wilkolek, P, Piepiorka, M, Piepiorka-Broniecka, M, Pluta, W, Ploch, M, Rynkiewicz, A, Mosakowska, K, Szpajer, M, Lesinski, D, Szwed, H, Jasek, S, Sciborski, R, Piotrowicz, R, Musial, W, Lisowska, A, Rekosz, J, Kasznicka, M, Korzeniak, R, Staneta, P, Konczakowski, P, Waluszek-Konczakowska, I, Cymerman, K, Lubinski, A, Grycewicz, T, Hiczkiewicz, J, Plucinski, M, Korol, M, Szczech, J, Hawro, M, Skorski, M, Cichon, K, Jankowski, M, Cygler, J, Ottomanska-Cygler, M, Korecki, J, Gulaj, E, Zechowicz, T, Zechowicz, M, Goch, A, Topolinski, B, Ogorek, M, Szczepanska, A, Wojewoda, P, Jagoda, E, Krzyzanowski, W, Muzyk-Osikowicz, M, Jaszczurowski, W, Stasiewski, A, Wietrzynska, J, Miklaszewicz, B, Beme, A, Sudnik, W, Matys, U, Ponikowski, P, Powierza, S, Kim, YH, Choi, DJ, Seung, KB, Lim, DS, Lee, SH, Kim, HS, Bae, JH, Hong, TJ, Hong, MK, Tahk, SJ, Kim, YJ, Yoon, J, Jeong, MH, Chae, JK, Cho, MC, Hong, SK, Hur, SH, Jeong, JO, Her, SH, Lee, JM, Chang, KC, Yoon, CH, Chang, K, Park, J, Choi, S, Park, K, Bae, Y, Lee, H, Kim, BK, Yoon, MH, Park, JS, Jang, H, Kim, C, Cho, EJ, Bae, J, Lee, D, Lee, J, Choi, YY, Dimulescu, D, Vintila, M, Fruntelata, A, Pirvu, O, Stanciulescu, G, Giuca, A, Militaru, C, Radoi, M, Bobescu, E, Crisu, D, Creteanu, M, Minescu, B, Bolohan, F, Manitiu, I, Bengus, C, Iosipescu, L, Ciobotaru, V, Basarab, G, Benedek, I, Constantinescu, M, Cristea, M, Capalneanu, R, Tatu-Chitoiu, G, Huidu, S, Protopopescu, L, Greavu, M, Diaconu, M, Blajan, D, Istratoaie, O, Lican, G, Bisoc, A, Doka, B, Jemna, D, Parasteac, M, Serban, L, Mihai, M, Cioca, G, Ochean, V, Costache, L, Andor, M, Stoica, D, Benedek, T, Sava, N, Anciu, M, Mot, S, Cornaciu, S, Boldueva, S, Golitsyn, S, Karpov, Y, Kobalava, Z, Konstantinov, V, Kuimov, A, Ezhov, M, Panov, A, Novikova, T, Simanenkov, V, Smolenskaya, O, Tsyba, L, Vishnevsky, A, Yakhontova, P, Kislyak, O, Demchenko, E, Yakovlev, A, Ermoshkina, L, Arkhipov, M, Galyavich, A, Strongin, L, Kosmacheva, E, Goloshchekin, B, Sidorenko, B, Izmozherova, N, Shustov, S, Orlikova, O, Lukyanov, Y, Koziolova, N, Nedogoda, S, Statsenko, M, Kotelnikov, M, Osipenko, M, Oshchepkova, E, Bolieva, L, Ryamzina, I, Pavlysh, E, Samokhvalova, M, Mironova, N, Buza, V, Shavarov, A, Serebrenitskaya, M, Khomyakova, L, Safarova, M, Lohovinina, N, Staroverov, I, Bitakova, F, Zakharova, N, Khurs, E, Belenky, D, Kositsyn, D, Rovnykh, Y, Kasatova, T, Lubinskaya, E, Omelchenko, M, Slukhaenko, I, Kozulin, A, Baleeva, L, Pochinka, I, Kizhvatova, N, Laptev, I, Bugrimova, M, Popov, A, Kovalevskaya, E, Orlikov, E, Paltsman, Z, Lamden, D, Surovtseva, M, Tsoma, V, Derevjanchenko, M, Streltsov, S, Bikbulatova, E, Dmitriev, V, Byazrova, S, Khovaeva, Y, Komandenko, O, Dlesk, A, Urban, M, Vinanska, D, Dzupina, A, Hranai, M, Cisar, P, Toth, P, Paulov, S, Sivak, V, Bolvanska, N, Pella, D, Palka, J, Nedelova, I, Benacka, J, Gergel, V, Hatalova, K, Kohut, P, Kovar, F, Knazeje, M, Macek, V, Sinska, R, Bugan, V, Badenhorst, JCW, Erasmus, L, Burgess, LJ, de Necker, I, Corbett, CH, Fouche, L, Dawood, SY, Conradie, C, Delport, EF, Kruger, M, Ebrahim, I, Bobak, C, Nethononda, MR, Nunkoo, T, van Rensburg, FPJ, Middle, R, Horak, AR, Henley, L, Mabin, TA, King, A, Ranjith, N, Ramdas, S, Roodt, A, Coetsee, E, Theron, H, Karsten, M, Van Zyl, LJ, Roscher, M, Venter, TP, de Kock, L, Becker, AC, Swanepoel, J, Ismail, SM, Dalby, AJ, Allman, J, Roux, JP, Christie, H, Naidoo, DP, Vawda, GHM, Manga, P, Olckers, W, Mpe, MT, Farrell, BM, Areses, ELD, Lopez, SV, Fernandez, JMC, Roldan, JG, Pavia, PG, Segovia, AG, Puig, JG, Garcia, VC, Aguilera, RM, Munoa, MD, Cortada, JB, Cereto, PC, Perez, IP, Cid, LP, Basilio, EG, Guerra, PC, Ortiz, AF, Balcones, LDV, Vera, TR, Martinez, JMG, Galvan, ED, Caballero, AH, Blanco, VMR, Lopez, JMR, Franco, MRP, Soriano, FR, Porcar, LC, Fillat, ARC, Moreno, SG, Montejano, MG, Guerrero, JMD, Coronado, JLB, Eizagaechevarria, NM, Araucua, GN, Rubio, AM, Roca, MC, Marimon, XGM, Perales, MV, Gonzalez, AB, Sastre, MP, Juanatey, JRG, Acuna, JMG, Al-Khalili, F, Lof, P, Bandh, S, Myllyla, L, Christensen, K, Johansson, K, Dellborg, M, Hultsberg-Olsson, G, Alstrom, P, Damm, TL, Erlinge, D, Brolin, G, Ravn-Fischer, PA, Johansson, P, Andreen, S, Linderfalk, C, Ram, B, Lindholm, CJ, Assarsson, E, Mooe, T, Lindberg, A, Paren, P, Moodh, J, Svensson, P, Andersson, I, Wodlin, P, Raschperger, A, Skogvard, P, Koch, A, Lind, N, Osberg, L, Nilsson, C, Svensson, K, Bengtsson, M, Samad, B, Nilsson, M, Berglund, E, Lundgren, C, Lindmark, K, Sundholm, C, Aladellie, L, Welin-Berger, B, Guneri, S, Dogan, NB, Ersanli, M, Coskun, U, Cayli, M, Seker, T, Camsari, A, Ozcan, T, Ongen, Z, Karadag, B, Boyaci, B, Sezenoz, B, Pekdemir, H, Hidayet, S, Erol, M, Yalcin, A, Sezer, M, Emet, S, Bozkurt, E, Ozen, MB, Lutay, Y, Dyadyk, O, Kholopov, L, Rudyk, I, Shaposhnikova, Y, Chopey, I, Ternuschak, T, Reshotko, D, Popova, G, Batushkin, V, Gema, A, Vizir, V, Berezyn, O, Lutai, M, Tovstukha, V, Shumakov, V, Pogurelska, O, Sirenko, Y, Rekovets, O, Kraiz, I, Kamenska, E, Tseluyko, V, Yakovleva, L, Yena, L, Artemenko, V, Koval, O, Kaplan, P, Karpenko, O, Nevolina, I, Bazilevych, A, Harbar, M, Rudenko, L, Beregova, O, Mostovyi, Y, Rasputina, L, Vatutin, M, Shevelok, A, Kovalenko, V, Polenova, N, Amosova, K, Tkachenko, L, Volkov, V, Zaprovalna, O, Storey, R, Thomas, M, Pell, A, Moriarty, A, Kinnin, M, Ahsan, A, Burton, J, ORourke, B, Young, J, Lang, C, Forbes, J, Rowlands, D, Hamill, S, Sprigings, D, Cadd, A, de Belder, M, Atkinson, B, Ramsey, M, Fagan, JC, Pye, M, Wright, L, Keeling, P, Hughes, D, Fraser, D, Phillips, H, Muthusamy, R, Lawan, M, Levy, T, Kennard, S, Bodalia, B, Mottram, J, Calvert, J, Brodie, K, Gunstone, A, Douglas, C, Trouton, T, Hunter, B, Gerber, R, Pepper, H, Mathur, A, Andiapen, M, Baumbach, A, Bowles, R, Hildick-Smith, D, McGregor, A, Loh, I, Plocky, J, Adams, K, Clemmer, K, Aggarwal, K, Burkhardt, V, Costa, M, Lemmertz, K, Anderson, J, York, T, Angiolillo, D, Green, E, Sperling, M, Vasquez, E, Aycock, G, Tatum, D, Amin, J, Davidson, A, Hendrix, E, Shepard, L, Strain, J, Michel, K, Talano, J, Szalanski, N, Berk, M, Ibarra, M, Bhagwat, R, Winterrowd, D, Bilazarian, S, Marsters, M, Blonder, R, Graf, L, Brilakis, E, Roesle, M, Byrd, L, Sullivan, A, Longo, J, Pennella, A, Westerhausen, D, Weil, R, Carr, K, Piazza, J, Carr, KW, Castello, R, Hawks, M, Chandna, H, Holly, D, Chandrashekhar, YS, Molinaro, N, Carter, M, Antonino, M, Kosmicki, D, Kelley, M, Richwine, R, Pazier, P, Glasgow, B, Bresee, S, Alexander, J, Concha, M, Martinez, E, Connelly, T, Schenks, R, Cooper, M, Garman, V, Condit, J, White, A, Fialkow, J, Mckercher, M, Luna, M, Soto, G, Prodafikas, J, Rambaud, B, Donovan, J, Mudd, D, Doty, W, Parsons, T, D'Urso, M, Bies, J, Han, J, Treadwell, M, Erickson, B, Dahl, P, Fattal, P, Braem, J, Felten, W, Prior, J, French, W, Barillas, O, Berger, R, Genova, E, Gelernt, M, Cockrell, D, Miller, G, Dumka, K, Gill, S, Elliot, S, Goldberg, R, Barrett, M, Gordon, P, Stern, L, Ayres, T, Rhule, V, Gupta, D, Holton, T, Haddad, T, Jain, J, Hakas, J, McSorley, J, Hamroff, G, Hollenweger, L, Wainwright, W, Jones, S, Casagrande, M, Casagrande, MG, Effat, M, Mardis, R, Henderson, D, Millard, D, Hermany, P, Meissner-Dengler, S, Hinchman, D, Luck, K, Hodson, R, Severson, L, Horwitz, P, Miller, K, Isserman, S, Moore, C, Jan, M, Bilyk, O, Kersh, R, DaCosta, A, Kim, E, Gonzales, C, Kmetzo, J, Taylor, D, Knutson, T, Belanger, B, Hage-Korban, E, Harrington, A, Murdock, D, Heiman, M, Dandekar, U, Khan, M, Khan, G, Lui, H, Holman, L, MacDonald, L, Derbyshire, S, Watkins, K, Mayer, N, Mitchell, B, McCullum, K, Delio-Cox, B, Mckay, R, Cloutier, J, McKenzie, M, Rodkey, K, McLaurin, B, Lack, A, Minisi, A, Jeter, D, Mitchell, R, Keane-Richmond, P, Stine, R, Bullivant, M, Morford, R, White, J, Oberoi, M, Geraldo-Abache, A, O'Dea, D, Mehta, R, Tang, N, Ong, S, Edwards, M, Osborne, J, Alonzo, C, Lev, V, Monroe, J, Popeil, L, Sorrentino, N, Portelli, J, Landi, T, Potu, R, Smith, N, Prashad, R, McDonough, C, Qureshi, M, Howe, A, Raikhel, M, Arsate, M, Rogers, W, Saag, L, Sangrigoli, R, Schwarz, L, Abu-Fadel, M, Hagee, A, Kinnaman, S, McDaniel, V, Wilson, V, Purcell, T, Roberts, J, Riofrio, K, Shah, U, Narang, S, Gredler, F, Knap, P, Shanes, J, Hansen, C, Sharma, M, Gibson, T, Sheldon, W, Bohn, A, Siegel, C, Tibbits, L, Singh, V, Nelson, M, Singh, N, Logwood, D, Randhawa, P, Vargas, B, Stegemoller, R, Cole, B, Aggarwal, R, Johnson, M, Steinhoff, J, Dunaway, B, Patel, K, Boomer, L, Taheri, H, Morgan, K, Tahirkheli, N, Santos, A, Thadani, U, Alexander, D, Bennett, W, Kelley, E, Thomas, J, Macnicholas, D, Varma, S, Evans, S, Vlastaris, A, Bittel, B, Voyce, S, Mack, B, Weiss, R, Fournier, T, Whitney, R, Orosco, C, Willis, J, VonGerichten, S, Wiseman, A, Sharrow, A, Wohns, D, Schuitema, J, Amin, M, Ramus, A, Wilson, W, Moeller, C, Newell, M, Tindell, L, Rivera, W, Kwierant, J, Bretton, E, Corbin, B, Labroo, A, Lopez, C, Brown, C, Craig, M, Lucca, M, Keinanen, T, Eisenberg, S, Fielding, M, Doorey, A, Squire, A, Suresh, D, Frost, J, Teklinski, A, Stone, B, Waksman, R, Griffin, S, Wharton, W, Blakely, J, Fishbein, G, Weller, C, Camp, A, Fisher, S, Meholick, A, Hejna, E, Anderson, R, Long, S, Parikh, S, Norton, N, Vijay, N, Washam, M, Smith, S, and Stepanov, N

Abstract

BACKGROUND The potential benefit of dual antiplatelet therapy beyond 1 year after a myocardial infarction has not been established. We investigated the efficacy and safety of ticagrelor, a P2Y(12) receptor antagonist with established efficacy after an acute coronary syndrome, in this context. METHODS We randomly assigned, in a double-blind 1: 1: 1 fashion, 21,162 patients who had had a myocardial infarction 1 to 3 years earlier to ticagrelor at a dose of 90 mg twice daily, ticagrelor at a dose of 60 mg twice daily, or placebo. All the patients were to receive low-dose aspirin and were followed for a median of 33 months. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The primary safety end point was Thrombolysis in Myocardial Infarction (TIMI) major bleeding. RESULTS The two ticagrelor doses each reduced, as compared with placebo, the rate of the primary efficacy end point, with Kaplan-Meier rates at 3 years of 7.85% in the group that received 90 mg of ticagrelor twice daily, 7.77% in the group that received 60 mg of ticagrelor twice daily, and 9.04% in the placebo group (hazard ratio for 90 mg of ticagrelor vs. placebo, 0.85; 95% confidence interval [CI], 0.75 to 0.96; P = 0.008; hazard ratio for 60 mg of ticagrelor vs. placebo, 0.84; 95% CI, 0.74 to 0.95; P = 0.004). Rates of TIMI major bleeding were higher with ticagrelor (2.60% with 90 mg and 2.30% with 60 mg) than with placebo (1.06%) (P < 0.001 for each dose vs. placebo); the rates of intracranial hemorrhage or fatal bleeding in the three groups were 0.63%, 0.71%, and 0.60%, respectively. CONCLUSIONS In patients with a myocardial infarction more than 1 year previously, treatment with ticagrelor significantly reduced the risk of cardiovascular death, myocardial infarction, or stroke and increased the risk of major bleeding. (Funded by AstraZeneca; PEGASUS-TIMI 54 ClinicalTrials.gov number, NCT01225562.)

Published
2015

17. Asymmetry in inward- and outward-affinity constant of transport explain unidirectional lysine flux in Saccharomyces cerevisiae.

Author

Bianchi, F., Klooster, J.S., Ruiz, S.J., Luck, K., Pols, T., Urbatsch, I.L., Poolman, B., Bianchi, F., Klooster, J.S., Ruiz, S.J., Luck, K., Pols, T., Urbatsch, I.L., and Poolman, B.

Abstract

Contains fulltext : 171926.pdf (publisher's version ) (Open Access), The import of basic amino acids in Saccharomyces cerevisiae has been reported to be unidirectional, which is not typical of how secondary transporters work. Since studies of energy coupling and transport kinetics are complicated in vivo, we purified the major lysine transporter (Lyp1) of yeast and reconstituted the protein into lipid vesicles. We show that the Michaelis constant (KM) of transport from out-to-in is well in the millimolar range and at least 3 to 4-orders of magnitude higher than that of transport in the opposite direction, disfavoring the efflux of solute via Lyp1. We also find that at low values of the proton motive force, the transport by Lyp1 is comparatively slow. We benchmarked the properties of eukaryotic Lyp1 to that of the prokaryotic homologue LysP and find that LysP has a similar KM for transport from in-to-out and out-to-in, consistent with rapid influx and efflux. We thus explain the previously described unidirectional nature of lysine transport in S. cerevisiae by the extraordinary kinetics of Lyp1 and provide a mechanism and rationale for previous observations. The high asymmetry in transport together with secondary storage in the vacuole allow the cell to accumulate basic amino acids to very high levels.

Published
2016

22. Quality improvement in discharge planning through action research

Author

Chenoweth, L and Luck, K

Subjects
Outcome and Process Assessment, Health Care, Quality Assurance, Health Care, Humans, Health Services Research, Planning Techniques, New South Wales, Outcome and Process Assessment (Health Care), Patient Discharge, Decision Making, Organizational, Organizational Innovation
Abstract

Action research can be employed effectively when embarking on quality improvement in healthcare. This article has two aims. The first is to describe and analyze the processes taking place during an action research project that focused on evaluating and improving discharge planning at a large metropolitan teaching hospital in Sydney, Australia. The second is to discuss the factors required to improve health services through action research and the benefits of this as opposed to the traditional quality management approach (EQuIP) employed by Australian health services.

Published
2003

23. ELM--the database of eukaryotic linear motifs

Author

Dinkel, H., primary, Michael, S., additional, Weatheritt, R. J., additional, Davey, N. E., additional, Van Roey, K., additional, Altenberg, B., additional, Toedt, G., additional, Uyar, B., additional, Seiler, M., additional, Budd, A., additional, Jodicke, L., additional, Dammert, M. A., additional, Schroeter, C., additional, Hammer, M., additional, Schmidt, T., additional, Jehl, P., additional, McGuigan, C., additional, Dymecka, M., additional, Chica, C., additional, Luck, K., additional, Via, A., additional, Chatr-aryamontri, A., additional, Haslam, N., additional, Grebnev, G., additional, Edwards, R. J., additional, Steinmetz, M. O., additional, Meiselbach, H., additional, Diella, F., additional, and Gibson, T. J., additional

Published
2011
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25. MAGI-1 PDZ1 / E6CT

Author

Charbonnier, S., primary, Nomine, Y., additional, Ramirez, J., additional, Luck, K., additional, Stote, R.H., additional, Trave, G., additional, Kieffer, B., additional, and Atkinson, R.A., additional

Published
2010
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26. MAGI-1 PDZ1

Author

Charbonnier, S., primary, Nomine, Y., additional, Ramirez, J., additional, Luck, K., additional, Stote, R.H., additional, Trave, G., additional, Kieffer, B., additional, and Atkinson, R.A., additional

Published
2010
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27. Quality improvement in discharge planning through action research.

Author

Chenoweth L and Luck K

Abstract

Action research can be employed effectively when embarking on quality improvement in healthcare. This article has two aims. The first is to describe and analyze the processes taking place during an action research project that focused on evaluating and improving discharge planning at a large metropolitan teaching hospital in Sydney, Australia. The second is to discuss the factors required to improve health services through action research and the benefits of this as opposed to the traditional quality management approach (EQuIP) employed by Australian health services. [ABSTRACT FROM AUTHOR]

Published
2003

29. Latent space policy search for robotics

Author

Luck, K. S., Neumann, G., Berger, E., Peters, J., Amor, H. B., Luck, K. S., Neumann, G., Berger, E., Peters, J., and Amor, H. B.

Abstract

Learning motor skills for robots is a hard task. In particular, a high number of degrees-of-freedom in the robot can pose serious challenges to existing reinforcement learning methods, since it leads to a highdimensional search space. However, complex robots are often intrinsically redundant systems and, therefore, can be controlled using a latent manifold of much smaller dimensionality. In this paper, we present a novel policy search method that performs efficient reinforcement learning by uncovering the low-dimensional latent space of actuator redundancies. In contrast to previous attempts at combining reinforcement learning and dimensionality reduction, our approach does not perform dimensionality reduction as a preprocessing step but naturally combines it with policy search. Our evaluations show that the new approach outperforms existing algorithms for learning motor skills with high-dimensional robots.

36. Histone variant macroH2A1 regulates synchronous firing of replication origins in the inactive X chromosome.

Author

Arroyo M, Casas-Delucchi CS, Pabba MK, Prorok P, Pradhan SK, Rausch C, Lehmkuhl A, Maiser A, Buschbeck M, Pasque V, Bernstein E, Luck K, and Cardoso MC

Abstract

MacroH2A has been linked to transcriptional silencing, cell identity, and is a hallmark of the inactive X chromosome (Xi). However, it remains unclear whether macroH2A plays a role in DNA replication. Using knockdown/knockout cells for each macroH2A isoform, we show that macroH2A-containing nucleosomes slow down replication progression rate in the Xi reflecting the higher nucleosome stability. Moreover, macroH2A1, but not macroH2A2, regulates the number of nano replication foci in the Xi, and macroH2A1 downregulation increases DNA loop sizes corresponding to replicons. This relates to macroH2A1 regulating replicative helicase loading during G1 by interacting with it. We mapped this interaction to a phenylalanine in macroH2A1 that is not conserved in macroH2A2 and the C-terminus of Mcm3 helicase subunit. We propose that macroH2A1 enhances the licensing of pre-replication complexes via DNA helicase interaction and loading onto the Xi., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Published
2024
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37. Generation of a high confidence set of domain-domain interface types to guide protein complex structure predictions by AlphaFold.

Author

Geist JL, Lee CY, Strom JM, de Jesús Naveja J, and Luck K

Subjects
Protein Domains, Models, Molecular, Databases, Protein, Software, Computational Biology methods, Protein Conformation, Proteins chemistry, Proteins metabolism
Abstract

Motivation: While the release of AlphaFold (AF) represented a breakthrough for the prediction of protein complex structures, its sensitivity, especially when using full length protein sequences, still remains limited. Modeling success rates might increase if AF predictions were guided by likely interacting protein fragments. This approach requires available sets of highly confident protein-protein interface types. Computational resources, such as 3did, infer interacting globular domain types from observed contacts in protein structures. Assessing the accuracy of these predicted interface types is difficult because we lack hand-curated reference sets of verified domain-domain interface (DDI) types., Results: To improve protein complex modeling of DDIs by AF, we manually inspected 80 randomly selected DDI types from the 3did resource to generate a first reference set of DDI types. Identified cases of DDI type nonapproval (40%) primarily resulted from inaccurate Pfam domain matches, crystal contacts, and synthetic protein constructs. Using logistic regression, we predicted a subset of 2411 out of 5724 considered DDI types in 3did to be of high confidence, which we subsequently applied to 53 000 human-protein interactions to predict DDIs followed by AF modeling. We obtained highly confident AF models for 604 out of 1129 predicted DDIs. Of note, for 47% of them no confident AF structural model could be obtained using full length protein sequences., Availability and Implementation: Code is available at https://github.com/KatjaLuckLab/DDI&#95;manuscript., (© The Author(s) 2024. Published by Oxford University Press.)

Published
2024
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38. Streamlined screening platforms lead to the discovery of pachysiphine synthase from Tabernanthe iboga.

Author

Kamileen MO, Nakamura Y, Luck K, Heinicke S, Hong B, Colinas M, Lichman BR, and O'Connor SE

Subjects
Plant Proteins metabolism, Plant Proteins genetics, Indole Alkaloids metabolism, Quinolines, Cytochrome P-450 Enzyme System metabolism, Cytochrome P-450 Enzyme System genetics, Nicotiana genetics, Nicotiana enzymology
Abstract

Plant-specialized metabolism is largely driven by the oxidative tailoring of key chemical scaffolds catalyzed by cytochrome P450 (CYP450s) enzymes. Monoterpene indole alkaloids (MIAs) tabersonine and pseudo-tabersonine, found in the medicinal plant Tabernanthe iboga (commonly known as iboga), are tailored with oxidations, and the enzymes involved remain unknown. Here, we developed a streamlined screening strategy to test the activity of T. iboga CYP450s in Nicotiana benthamiana. Using multigene constructs encoding the biosynthesis of tabersonine and pseudo-tabersonine scaffolds, we aimed to uncover the CYP450s responsible for oxidative transformations in these scaffolds. Our approach identified two T. iboga cytochrome P450 enzymes: pachysiphine synthase (PS) and 16-hydroxy-tabersonine synthase (T16H). These enzymes catalyze an epoxidation and site-specific hydroxylation of tabersonine to produce pachysiphine and 16-OH-tabersonine, respectively. This work provides new insights into the biosynthetic pathways of MIAs and underscores the utility of N. benthamiana and Catharanthus roseus as platforms for the functional characterization of plant enzymes., (© 2024 The Author(s). New Phytologist © 2024 New Phytologist Foundation.)

Published
2024
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39. Phenylphenalenones and Linear Diarylheptanoid Derivatives Are Biosynthesized via Parallel Routes in Musella lasiocarpa , the Chinese Dwarf Banana.

Author

Lyu H, Ernst L, Nakamura Y, Okamura Y, Köllner TG, Luck K, Liu B, Chen Y, Beerhues L, Gershenzon J, and Paetz C

Subjects
Molecular Structure, Seeds chemistry, Substrate Specificity, Diarylheptanoids chemistry, Musa chemistry, Phenalenes chemistry
Abstract

Here, we use transcriptomic data from seeds of Musella lasiocarpa to identify five enzymes involved in the formation of dihydrocurcuminoids. Characterization of the substrate specificities of the enzymes reveals two distinct dihydrocurcuminoid pathways leading to phenylphenalenones and linear diarylheptanoid derivatives, the major seed metabolites. Furthermore, we demonstrate the stepwise conversion of dihydrobisdemethoxycurcumin to the phenylphenalenone 4'-hydroxylachnanthocarpone by feeding intermediates to M. lasiocarpa root protein extract.

Published
2024
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40. Systematic discovery of protein interaction interfaces using AlphaFold and experimental validation.

Author

Lee CY, Hubrich D, Varga JK, Schäfer C, Welzel M, Schumbera E, Djokic M, Strom JM, Schönfeld J, Geist JL, Polat F, Gibson TJ, Keller Valsecchi CI, Kumar M, Schueler-Furman O, and Luck K

Subjects
Humans, Membrane Proteins metabolism, Proteins metabolism, Carrier Proteins
Abstract

Structural resolution of protein interactions enables mechanistic and functional studies as well as interpretation of disease variants. However, structural data is still missing for most protein interactions because we lack computational and experimental tools at scale. This is particularly true for interactions mediated by short linear motifs occurring in disordered regions of proteins. We find that AlphaFold-Multimer predicts with high sensitivity but limited specificity structures of domain-motif interactions when using small protein fragments as input. Sensitivity decreased substantially when using long protein fragments or full length proteins. We delineated a protein fragmentation strategy particularly suited for the prediction of domain-motif interfaces and applied it to interactions between human proteins associated with neurodevelopmental disorders. This enabled the prediction of highly confident and likely disease-related novel interfaces, which we further experimentally corroborated for FBXO23-STX1B, STX1B-VAMP2, ESRRG-PSMC5, PEX3-PEX19, PEX3-PEX16, and SNRPB-GIGYF1 providing novel molecular insights for diverse biological processes. Our work highlights exciting perspectives, but also reveals clear limitations and the need for future developments to maximize the power of Alphafold-Multimer for interface predictions., (© 2024. The Author(s).)

Published
2024
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41. Biosynthesis, herbivore induction, and defensive role of phenylacetaldoxime glucoside.

Author

Müller AT, Nakamura Y, Reichelt M, Luck K, Cosio E, Lackus ND, Gershenzon J, Mithöfer A, and Köllner TG

Subjects
Nitriles metabolism, Cytochrome P-450 Enzyme System genetics, Cytochrome P-450 Enzyme System metabolism, Oximes metabolism, Plant Leaves metabolism, Glucosides metabolism, Herbivory
Abstract

Aldoximes are well-known metabolic precursors for plant defense compounds such as cyanogenic glycosides, glucosinolates, and volatile nitriles. They are also defenses themselves produced in response to herbivory; however, it is unclear whether aldoximes can be stored over a longer term as defense compounds and how plants protect themselves against the potential autotoxic effects of aldoximes. Here, we show that the Neotropical myrmecophyte tococa (Tococa quadrialata, recently renamed Miconia microphysca) accumulates phenylacetaldoxime glucoside (PAOx-Glc) in response to leaf herbivory. Sequence comparison, transcriptomic analysis, and heterologous expression revealed that 2 cytochrome P450 enzymes, CYP79A206 and CYP79A207, and the UDP-glucosyltransferase UGT85A123 are involved in the formation of PAOx-Glc in tococa. Another P450, CYP71E76, was shown to convert PAOx to the volatile defense compound benzyl cyanide. The formation of PAOx-Glc and PAOx in leaves is a very local response to herbivory but does not appear to be regulated by jasmonic acid signaling. In contrast to PAOx, which was only detectable during herbivory, PAOx-Glc levels remained high for at least 3 d after insect feeding. This, together with the fact that gut protein extracts of 3 insect herbivore species exhibited hydrolytic activity toward PAOx-Glc, suggests that the glucoside is a stable storage form of a defense compound that may provide rapid protection against future herbivory. Moreover, the finding that herbivory or pathogen elicitor treatment also led to the accumulation of PAOx-Glc in 3 other phylogenetically distant plant species suggests that the formation and storage of aldoxime glucosides may represent a widespread plant defense response., Competing Interests: Conflict of interest statement. All authors declare that they have no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Published
2023
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42. An extended Tudor domain within Vreteno interconnects Gtsf1L and Ago3 for piRNA biogenesis in Bombyx mori.

Author

Bronkhorst AW, Lee CY, Möckel MM, Ruegenberg S, de Jesus Domingues AM, Sadouki S, Piccinno R, Sumiyoshi T, Siomi MC, Stelzl L, Luck K, and Ketting RF

Subjects
Animals, Argonaute Proteins genetics, Argonaute Proteins metabolism, Piwi-Interacting RNA, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, Tudor Domain, Bombyx genetics, Bombyx metabolism
Abstract

Piwi-interacting RNAs (piRNAs) direct PIWI proteins to transposons to silence them, thereby preserving genome integrity and fertility. The piRNA population can be expanded in the ping-pong amplification loop. Within this process, piRNA-associated PIWI proteins (piRISC) enter a membraneless organelle called nuage to cleave their target RNA, which is stimulated by Gtsf proteins. The resulting cleavage product gets loaded into an empty PIWI protein to form a new piRISC complex. However, for piRNA amplification to occur, the new RNA substrates, Gtsf-piRISC, and empty PIWI proteins have to be in physical proximity. In this study, we show that in silkworm cells, the Gtsf1 homolog BmGtsf1L binds to piRNA-loaded BmAgo3 and localizes to granules positive for BmAgo3 and BmVreteno. Biochemical assays further revealed that conserved residues within the unstructured tail of BmGtsf1L directly interact with BmVreteno. Using a combination of AlphaFold modeling, atomistic molecular dynamics simulations, and in vitro assays, we identified a novel binding interface on the BmVreteno-eTudor domain, which is required for BmGtsf1L binding. Our study reveals that a single eTudor domain within BmVreteno provides two binding interfaces and thereby interconnects piRNA-loaded BmAgo3 and BmGtsf1L., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)

Published
2023
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43. Reinventing metabolic pathways: Independent evolution of benzoxazinoids in flowering plants.

Author

Florean M, Luck K, Hong B, Nakamura Y, O'Connor SE, and Köllner TG

Subjects
Benzoxazines metabolism, Poaceae metabolism, Metabolic Networks and Pathways genetics, Plants metabolism, Cytochrome P-450 Enzyme System genetics, Cytochrome P-450 Enzyme System metabolism, Magnoliopsida metabolism
Abstract

Benzoxazinoids (BXDs) form a class of indole-derived specialized plant metabolites with broad antimicrobial and antifeedant properties. Unlike most specialized metabolites, which are typically lineage-specific, BXDs occur sporadically in a number of distantly related plant orders. This observation suggests that BXD biosynthesis arose independently numerous times in the plant kingdom. However, although decades of research in the grasses have led to the elucidation of the BXD pathway in the monocots, the biosynthesis of BXDs in eudicots is unknown. Here, we used a metabolomic and transcriptomic-guided approach, in combination with pathway reconstitution in Nicotiana benthamiana, to identify and characterize the BXD biosynthetic pathways from both Aphelandra squarrosa and Lamium galeobdolon , two phylogenetically distant eudicot species. We show that BXD biosynthesis in A. squarrosa and L. galeobdolon utilize a dual-function flavin-containing monooxygenase in place of two distinct cytochrome P450s, as is the case in the grasses. In addition, we identified evolutionarily unrelated cytochrome P450s, a 2-oxoglutarate-dependent dioxygenase, a UDP-glucosyltransferase, and a methyltransferase that were also recruited into these BXD biosynthetic pathways. Our findings constitute the discovery of BXD pathways in eudicots. Moreover, the biosynthetic enzymes of these pathways clearly demonstrate that BXDs independently arose in the plant kingdom at least three times. The heterogeneous pool of identified BXD enzymes represents a remarkable example of metabolic plasticity, in which BXDs are synthesized according to a similar chemical logic, but with an entirely different set of metabolic enzymes.

Published
2023
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44. Metabolism of plant-derived toxins from its insect host increases the success of the entomopathogenic fungus Beauveria bassiana.

Author

Sun R, Hong B, Reichelt M, Luck K, Mai DT, Jiang X, Gershenzon J, and Vassão DG

Subjects
Animals, Glucosinolates, Insecta, Isothiocyanates, Beauveria, Insecticides, Aphids
Abstract

Beauveria bassiana is a soil fungus that parasitizes a large number of arthropod species, including numerous crop pests, causing white muscardine disease and is therefore used as a biological insecticide. However, some insects, such as the cabbage aphid (Brevicoryne brassicae), defend themselves chemically by sequestering dietary pro-toxins (glucosinolates) from their Brassicales host plants. Glucosinolates are accumulated by cabbage aphids and activated to form toxic isothiocyanates when under attack. While isothiocyanate formation protects aphids against most attackers, B. bassiana is still able to infect the cabbage aphid under natural conditions. We therefore investigated how this fungus is able to circumvent the chemical defense system of the cabbage aphid. Here, we describe how B. bassiana infection activates the cabbage aphid defense system, but the resulting toxins are metabolized by B. bassiana via the mercapturic acid pathway, of which the first step is catalyzed by glutathione-S-transferases of low substrate specificity. This detoxification pathway enhances B. bassiana growth when isothiocyanates are present in natural concentrations, and so appears to be an important factor in fungal parasitization of these chemically defended aphids., (© 2023. The Author(s).)

Published
2023
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45. FUBP1 is a general splicing factor facilitating 3' splice site recognition and splicing of long introns.

Author

Ebersberger S, Hipp C, Mulorz MM, Buchbender A, Hubrich D, Kang HS, Martínez-Lumbreras S, Kristofori P, Sutandy FXR, Llacsahuanga Allcca L, Schönfeld J, Bakisoglu C, Busch A, Hänel H, Tretow K, Welzel M, Di Liddo A, Möckel MM, Zarnack K, Ebersberger I, Legewie S, Luck K, Sattler M, and König J

Subjects
Humans, Introns genetics, RNA Splicing Factors genetics, RNA Splicing Factors metabolism, RNA-Binding Proteins genetics, RNA-Binding Proteins metabolism, RNA Precursors genetics, RNA Precursors metabolism, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, RNA Splice Sites genetics, RNA Splicing
Abstract

Splicing of pre-mRNAs critically contributes to gene regulation and proteome expansion in eukaryotes, but our understanding of the recognition and pairing of splice sites during spliceosome assembly lacks detail. Here, we identify the multidomain RNA-binding protein FUBP1 as a key splicing factor that binds to a hitherto unknown cis-regulatory motif. By collecting NMR, structural, and in vivo interaction data, we demonstrate that FUBP1 stabilizes U2AF2 and SF1, key components at the 3' splice site, through multivalent binding interfaces located within its disordered regions. Transcriptional profiling and kinetic modeling reveal that FUBP1 is required for efficient splicing of long introns, which is impaired in cancer patients harboring FUBP1 mutations. Notably, FUBP1 interacts with numerous U1 snRNP-associated proteins, suggesting a unique role for FUBP1 in splice site bridging for long introns. We propose a compelling model for 3' splice site recognition of long introns, which represent 80% of all human introns., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2023
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46. RNA-dependent interactome allows network-based assignment of RNA-binding protein function.

Author

Fradera-Sola A, Nischwitz E, Bayer ME, Luck K, and Butter F

Subjects
Proteomics, RNA, Messenger genetics, RNA, Messenger metabolism, Protein Interaction Mapping, Saccharomyces cerevisiae Proteins chemistry, Saccharomyces cerevisiae Proteins metabolism, RNA genetics, RNA-Binding Proteins chemistry, RNA-Binding Proteins metabolism, Saccharomyces cerevisiae chemistry, Saccharomyces cerevisiae metabolism
Abstract

RNA-binding proteins (RBPs) form highly diverse and dynamic ribonucleoprotein complexes, whose functions determine the molecular fate of the bound RNA. In the model organism Sacchromyces cerevisiae, the number of proteins identified as RBPs has greatly increased over the last decade. However, the cellular function of most of these novel RBPs remains largely unexplored. We used mass spectrometry-based quantitative proteomics to systematically identify protein-protein interactions (PPIs) and RNA-dependent interactions (RDIs) to create a novel dataset for 40 RBPs that are associated with the mRNA life cycle. Domain, functional and pathway enrichment analyses revealed an over-representation of RNA functionalities among the enriched interactors. Using our extensive PPI and RDI networks, we revealed putative new members of RNA-associated pathways, and highlighted potential new roles for several RBPs. Our RBP interactome resource is available through an online interactive platform as a community tool to guide further in-depth functional studies and RBP network analysis (https://www.butterlab.org/RINE)., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Published
2023
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47. Next-generation large-scale binary protein interaction network for Drosophila melanogaster.

Author

Tang HW, Spirohn K, Hu Y, Hao T, Kovács IA, Gao Y, Binari R, Yang-Zhou D, Wan KH, Bader JS, Balcha D, Bian W, Booth BW, Coté AG, de Rouck S, Desbuleux A, Goh KY, Kim DK, Knapp JJ, Lee WX, Lemmens I, Li C, Li M, Li R, Lim HJ, Liu Y, Luck K, Markey D, Pollis C, Rangarajan S, Rodiger J, Schlabach S, Shen Y, Sheykhkarimli D, TeeKing B, Roth FP, Tavernier J, Calderwood MA, Hill DE, Celniker SE, Vidal M, Perrimon N, and Mohr SE

Subjects
Animals, Drosophila melanogaster genetics, Drosophila melanogaster metabolism, Drosophila genetics, Saccharomyces cerevisiae metabolism, Protein Interaction Mapping methods, Two-Hybrid System Techniques, Protein Interaction Maps genetics, Drosophila Proteins genetics, Drosophila Proteins metabolism
Abstract

Generating reference maps of interactome networks illuminates genetic studies by providing a protein-centric approach to finding new components of existing pathways, complexes, and processes. We apply state-of-the-art methods to identify binary protein-protein interactions (PPIs) for Drosophila melanogaster. Four all-by-all yeast two-hybrid (Y2H) screens of > 10,000 Drosophila proteins result in the 'FlyBi' dataset of 8723 PPIs among 2939 proteins. Testing subsets of data from FlyBi and previous PPI studies using an orthogonal assay allows for normalization of data quality; subsequent integration of FlyBi and previous data results in an expanded binary Drosophila reference interaction network, DroRI, comprising 17,232 interactions among 6511 proteins. We use FlyBi data to generate an autophagy network, then validate in vivo using autophagy-related assays. The deformed wings (dwg) gene encodes a protein that is both a regulator and a target of autophagy. Altogether, these resources provide a foundation for building new hypotheses regarding protein networks and function., (© 2023. The Author(s).)

Published
2023
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48. Ancient origin and conserved gene function in terpene pheromone and defense evolution of stink bugs and hemipteran insects.

Author

Rebholz Z, Lancaster J, Larose H, Khrimian A, Luck K, Sparks ME, Gendreau KL, Shewade L, Köllner TG, Weber DC, Gundersen-Rindal DE, O'Maille P, Morozov AV, and Tholl D

Subjects
Animals, Terpenes metabolism, Pheromones, Phylogeny, Plants genetics, Plants metabolism, Sesquiterpenes metabolism, Heteroptera
Abstract

Insects use diverse arrays of small molecules such as metabolites of the large class of terpenes for intra- and inter-specific communication and defense. These molecules are synthesized by specialized metabolic pathways; however, the origin of enzymes involved in terpene biosynthesis and their evolution in insect genomes is still poorly understood. We addressed this question by investigating the evolution of isoprenyl diphosphate synthase (IDS)-like genes with terpene synthase (TPS) function in the family of stink bugs (Pentatomidae) within the large order of piercing-sucking Hemipteran insects. Stink bugs include species of global pest status, many of which emit structurally related 15-carbon sesquiterpenes as sex or aggregation pheromones. We provide evidence for the emergence of IDS-type TPS enzymes at the onset of pentatomid evolution over 100 million years ago, coinciding with the evolution of flowering plants. Stink bugs of different geographical origin maintain small IDS-type families with genes of conserved TPS function, which stands in contrast to the diversification of TPS genes in plants. Expanded gene mining and phylogenetic analysis in other hemipteran insects further provides evidence for an ancient emergence of IDS-like genes under presumed selection for terpene-mediated chemical interactions, and this process occurred independently from a similar evolution of IDS-type TPS genes in beetles. Our findings further suggest differences in TPS diversification in insects and plants in conjunction with different modes of gene functionalization in chemical interactions., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2023
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49. PARP1 proximity proteomics reveals interaction partners at stressed replication forks.

Author

Mosler T, Baymaz HI, Gräf JF, Mikicic I, Blattner G, Bartlett E, Ostermaier M, Piccinno R, Yang J, Voigt A, Gatti M, Pellegrino S, Altmeyer M, Luck K, Ahel I, Roukos V, and Beli P

Subjects
DNA Breaks, Double-Stranded, DNA Repair, Poly(ADP-ribose) Polymerase Inhibitors pharmacology, DNA Replication, Poly (ADP-Ribose) Polymerase-1 genetics, Proteomics
Abstract

PARP1 mediates poly-ADP-ribosylation of proteins on chromatin in response to different types of DNA lesions. PARP inhibitors are used for the treatment of BRCA1/2-deficient breast, ovarian, and prostate cancer. Loss of DNA replication fork protection is proposed as one mechanism that contributes to the vulnerability of BRCA1/2-deficient cells to PARP inhibitors. However, the mechanisms that regulate PARP1 activity at stressed replication forks remain poorly understood. Here, we performed proximity proteomics of PARP1 and isolation of proteins on stressed replication forks to map putative PARP1 regulators. We identified TPX2 as a direct PARP1-binding protein that regulates the auto-ADP-ribosylation activity of PARP1. TPX2 interacts with DNA damage response proteins and promotes homology-directed repair of DNA double-strand breaks. Moreover, TPX2 mRNA levels are increased in BRCA1/2-mutated breast and prostate cancers, and high TPX2 expression levels correlate with the sensitivity of cancer cells to PARP-trapping inhibitors. We propose that TPX2 confers a mitosis-independent function in the cellular response to replication stress by interacting with PARP1., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Published
2022
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50. Proteome effects of genome-wide single gene perturbations.

Author

Öztürk M, Freiwald A, Cartano J, Schmitt R, Dejung M, Luck K, Al-Sady B, Braun S, Levin M, and Butter F

Subjects
Humans, Proteome genetics, Proteome metabolism, Proteomics methods, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae metabolism, Schizosaccharomyces genetics, Schizosaccharomyces metabolism, Schizosaccharomyces pombe Proteins genetics, Schizosaccharomyces pombe Proteins metabolism
Abstract

Protein abundance is controlled at the transcriptional, translational and post-translational levels, and its regulatory principles are starting to emerge. Investigating these principles requires large-scale proteomics data and cannot just be done with transcriptional outcomes that are commonly used as a proxy for protein abundance. Here, we determine proteome changes resulting from the individual knockout of 3308 nonessential genes in the yeast Schizosaccharomyces pombe. We use similarity clustering of global proteome changes to infer gene functionality that can be extended to other species, such as humans or baker's yeast. Furthermore, we analyze a selected set of deletion mutants by paired transcriptome and proteome measurements and show that upregulation of proteins under stable transcript expression utilizes optimal codons., (© 2022. The Author(s).)

Published
2022
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