Search

Your search keyword '"Camenisch, G."' showing total 194 results
Start Over Author "Camenisch, G."
194 results on '"Camenisch, G."'

1. Morphometric analysis of epithelial bladder cancer on tissue and cellular scale

Author

Lampart, F., primary, Vetter, R., additional, Yamauchi, K., additional, Runser, S., additional, Wang, Y., additional, Murelis, A., additional, Meer, F., additional, Stromeier, N., additional, Hussherr, M-D., additional, Camenisch, G., additional, Rentsch, C., additional, Le Magnen, C., additional, Müller, D.J., additional, Bubendorf, L., additional, and Iber, D., additional

Published
2023
Full Text
View/download PDF

2. Microsatellite diversity of the Nordic type of goats in relation to breed conservation: how relevant is pure ancestry?

Author

Lenstra, J.A., Tigchelaar, J., Biebach, I., Hallsson, J.H., Kantanen, J., Nielsen, V.H., Pompanon, F., Naderi, S., Rezaei, H.R., Sæther, N., Ertugrul, O., Grossen, C., Camenisch, G., VosLoohuis, M., van Straten, M., de Poel, E.A., Windig, J., Oldenbroek, K., AboShehada, Mahamoud, Marsan, Paolo Ajmone, Tarrayrah, Jamil Al, Angiolillo, Antonella, Baret, Philip, Baumung, Roswitha, BejaPereira, Albano, Bertaglia, Marco, Bordonaro, Salvatore, Brandt, Horst, Bruford, Mike, Caloz, Régis, Canali, Gabriele, Canon, Javier, Cappuccio, Irene, Carta, Antonello, Cicogna, Mario, Crepaldi, Paola, Dalamitra, Stella, Dobi, Petrit, Dunner, Susana, DʼUrso, Giuseppe, El Barody, M. A. A., England, Phillip, Erhardt, Georg, Ertuğrul, Okan, Glowatzki, MarieLouise, IbeaghaAwemu, Eveline, Strzelec, Ewa, Fadlaoui, Aziz, Fornarelli, Francesca, Garcia, David, Georgoudis, Andreas, Giovenzana, Stefano, Gutscher, Katja, Hewitt, Godfrey, Hoda, Anila, Istvan, Anton, Jones, Sam, Joost, Stéphane, Juma, Gabriela, Karetsou, Katerina, Kliambas, Georgios, Koban, Evren, Krugmann, Daniela, Kutita, Olga, Lazlo, Fesus, Ligda, Christina, Lipsky, Shirin, Luikart, Gordon, Lühken, Gesine, Marilli, Marta, Marletta, Donata, Milanesi, Elisabetta, Negrini, Riccardo, Nijman, Isaäc J., Niznikowski, Roman, ObexerRuff, Gabriela, Papachristoforou, Christos, Pariset, Lorraine, Peter, Marco Pellecchia, Christina, Perez, Trinidad, Pietrolà, Emilio, Pilla, Fabio, Popielarczyk, Dominik, Prinzenberg, MariaEva, Roosen, Jutta, Scarpa, Riccardo, Sechi, Tiziana, Taberlet, Pierre, Taylor, Martin, Togan, Inci, Trommetter, Michel, Valentini, Alessio, Van Cann, Lisette M., Vlaic, Augustin, Wiskin, Louise, and Zundel, Stéphanie

Published
2017
Full Text
View/download PDF

6. Dense sampling of bird diversity increases power of comparative genomics (vol 587, pg 252, 2020)

Author

Feng, S, Stiller, J, Deng, Y, Armstrong, J, Fang, Q, Reeve, AH, Xie, D, Chen, G, Guo, C, Faircloth, BC, Petersen, B, Wang, Z, Zhou, Q, Diekhans, M, Chen, W, Andreu-Sanchez, S, Margaryan, A, Howard, JT, Parent, C, Pacheco, G, Sinding, M-HS, Puetz, L, Cavill, E, Ribeiro, AM, Eckhart, L, Fjeldsa, J, Hosner, PA, Brumfield, RT, Christidis, L, Bertelsen, MF, Sicheritz-Ponten, T, Tietze, DT, Robertson, BC, Song, G, Borgia, G, Claramunt, S, Lovette, IJ, Cowen, SJ, Njoroge, P, Dumbacher, JP, Ryder, OA, Fuchs, J, Bunce, M, Burt, DW, Cracraft, J, Meng, G, Hackett, SJ, Ryan, PG, Jonsson, KA, Jamieson, IG, da Fonseca, RR, Braun, EL, Houde, P, Mirarab, S, Suh, A, Hansson, B, Ponnikas, S, Sigeman, H, Stervander, M, Frandsen, PB, van der Zwan, H, van der Sluis, R, Visser, C, Balakrishnan, CN, Clark, AG, Fitzpatrick, JW, Bowman, R, Chen, N, Cloutier, A, Sackton, TB, Edwards, SV, Foote, DJ, Shakya, SB, Sheldon, FH, Vignal, A, Soares, AER, Shapiro, B, Gonzalez-Solis, J, Ferrer-Obiol, J, Rozas, J, Riutort, M, Tigano, A, Friesen, V, Dalen, L, Urrutia, AO, Szekely, T, Liu, Y, Campana, MG, Corvelo, A, Fleischer, RC, Rutherford, KM, Gemmell, NJ, Dussex, N, Mouritsen, H, Thiele, N, Delmore, K, Liedvogel, M, Franke, A, Hoeppner, MP, Krone, O, Fudickar, AM, Mila, B, Ketterson, ED, Fidler, AE, Friis, G, Parody-Merino, AM, Battley, PF, Cox, MP, Lima, NCB, Prosdocimi, F, Parchman, TL, Schlinger, BA, Loiselle, BA, Blake, JG, Lim, HC, Day, LB, Fuxjager, MJ, Baldwin, MW, Braun, MJ, Wirthlin, M, Dikow, RB, Ryder, TB, Camenisch, G, Keller, LF, DaCosta, JM, Hauber, ME, Louder, MIM, Witt, CC, McGuire, JA, Mudge, J, Megna, LC, Carling, MD, Wang, B, Taylor, SA, Del-Rio, G, Aleixo, A, Vasconcelos, ATR, Mello, CV, Weir, JT, Haussler, D, Li, Q, Yang, H, Wang, J, Lei, F, Rahbek, C, Gilbert, MTP, Graves, GR, Jarvis, ED, Paten, B, Zhang, G, Feng, S, Stiller, J, Deng, Y, Armstrong, J, Fang, Q, Reeve, AH, Xie, D, Chen, G, Guo, C, Faircloth, BC, Petersen, B, Wang, Z, Zhou, Q, Diekhans, M, Chen, W, Andreu-Sanchez, S, Margaryan, A, Howard, JT, Parent, C, Pacheco, G, Sinding, M-HS, Puetz, L, Cavill, E, Ribeiro, AM, Eckhart, L, Fjeldsa, J, Hosner, PA, Brumfield, RT, Christidis, L, Bertelsen, MF, Sicheritz-Ponten, T, Tietze, DT, Robertson, BC, Song, G, Borgia, G, Claramunt, S, Lovette, IJ, Cowen, SJ, Njoroge, P, Dumbacher, JP, Ryder, OA, Fuchs, J, Bunce, M, Burt, DW, Cracraft, J, Meng, G, Hackett, SJ, Ryan, PG, Jonsson, KA, Jamieson, IG, da Fonseca, RR, Braun, EL, Houde, P, Mirarab, S, Suh, A, Hansson, B, Ponnikas, S, Sigeman, H, Stervander, M, Frandsen, PB, van der Zwan, H, van der Sluis, R, Visser, C, Balakrishnan, CN, Clark, AG, Fitzpatrick, JW, Bowman, R, Chen, N, Cloutier, A, Sackton, TB, Edwards, SV, Foote, DJ, Shakya, SB, Sheldon, FH, Vignal, A, Soares, AER, Shapiro, B, Gonzalez-Solis, J, Ferrer-Obiol, J, Rozas, J, Riutort, M, Tigano, A, Friesen, V, Dalen, L, Urrutia, AO, Szekely, T, Liu, Y, Campana, MG, Corvelo, A, Fleischer, RC, Rutherford, KM, Gemmell, NJ, Dussex, N, Mouritsen, H, Thiele, N, Delmore, K, Liedvogel, M, Franke, A, Hoeppner, MP, Krone, O, Fudickar, AM, Mila, B, Ketterson, ED, Fidler, AE, Friis, G, Parody-Merino, AM, Battley, PF, Cox, MP, Lima, NCB, Prosdocimi, F, Parchman, TL, Schlinger, BA, Loiselle, BA, Blake, JG, Lim, HC, Day, LB, Fuxjager, MJ, Baldwin, MW, Braun, MJ, Wirthlin, M, Dikow, RB, Ryder, TB, Camenisch, G, Keller, LF, DaCosta, JM, Hauber, ME, Louder, MIM, Witt, CC, McGuire, JA, Mudge, J, Megna, LC, Carling, MD, Wang, B, Taylor, SA, Del-Rio, G, Aleixo, A, Vasconcelos, ATR, Mello, CV, Weir, JT, Haussler, D, Li, Q, Yang, H, Wang, J, Lei, F, Rahbek, C, Gilbert, MTP, Graves, GR, Jarvis, ED, Paten, B, and Zhang, G

Abstract

A Correction to this paper has been published: https://doi.org/10.1038/s41586-021-03473-8.

Published
2021

8. Dense sampling of bird diversity increases power of comparative genomics

Author

Feng, S, Stiller, J, Deng, Y, Armstrong, J, Fang, Q, Reeve, AH, Xie, D, Chen, G, Guo, C, Faircloth, BC, Petersen, B, Wang, Z, Zhou, Q, Diekhans, M, Chen, W, Andreu-Sanchez, S, Margaryan, A, Howard, JT, Parent, C, Pacheco, G, Sinding, M-HS, Puetz, L, Cavill, E, Ribeiro, AM, Eckhart, L, Fjeldsa, J, Hosner, PA, Brumfield, RT, Christidis, L, Bertelsen, MF, Sicheritz-Ponten, T, Tietze, DT, Robertson, BC, Song, G, Borgia, G, Claramunt, S, Lovette, IJ, Cowen, SJ, Njoroge, P, Dumbacher, JP, Ryder, OA, Fuchs, J, Bunce, M, Burt, DW, Cracraft, J, Meng, G, Hackett, SJ, Ryan, PG, Jonsson, KA, Jamieson, IG, da Fonseca, RR, Braun, EL, Houde, P, Mirarab, S, Suh, A, Hansson, B, Ponnikas, S, Sigeman, H, Stervander, M, Frandsen, PB, van der Zwan, H, van der Sluis, R, Visser, C, Balakrishnan, CN, Clark, AG, Fitzpatrick, JW, Bowman, R, Chen, N, Cloutier, A, Sackton, TB, Edwards, SV, Foote, DJ, Shakya, SB, Sheldon, FH, Vignal, A, Soares, AER, Shapiro, B, Gonzalez-Solis, J, Ferrer-Obiol, J, Rozas, J, Riutort, M, Tigano, A, Friesen, V, Dalen, L, Urrutia, AO, Szekely, T, Liu, Y, Campana, MG, Corvelo, A, Fleischer, RC, Rutherford, KM, Gemmell, NJ, Dussex, N, Mouritsen, H, Thiele, N, Delmore, K, Liedvogel, M, Franke, A, Hoeppner, MP, Krone, O, Fudickar, AM, Mila, B, Ketterson, ED, Fidler, AE, Friis, G, Parody-Merino, AM, Battley, PF, Cox, MP, Lima, NCB, Prosdocimi, F, Parchman, TL, Schlinger, BA, Loiselle, BA, Blake, JG, Lim, HC, Day, LB, Fuxjager, MJ, Baldwin, MW, Braun, MJ, Wirthlin, M, Dikow, RB, Ryder, TB, Camenisch, G, Keller, LF, DaCosta, JM, Hauber, ME, Louder, MIM, Witt, CC, McGuire, JA, Mudge, J, Megna, LC, Carling, MD, Wang, B, Taylor, SA, Del-Rio, G, Aleixo, A, Vasconcelos, ATR, Mello, CV, Weir, JT, Haussler, D, Li, Q, Yang, H, Wang, J, Lei, F, Rahbek, C, Gilbert, MTP, Graves, GR, Jarvis, ED, Paten, B, Zhang, G, Feng, S, Stiller, J, Deng, Y, Armstrong, J, Fang, Q, Reeve, AH, Xie, D, Chen, G, Guo, C, Faircloth, BC, Petersen, B, Wang, Z, Zhou, Q, Diekhans, M, Chen, W, Andreu-Sanchez, S, Margaryan, A, Howard, JT, Parent, C, Pacheco, G, Sinding, M-HS, Puetz, L, Cavill, E, Ribeiro, AM, Eckhart, L, Fjeldsa, J, Hosner, PA, Brumfield, RT, Christidis, L, Bertelsen, MF, Sicheritz-Ponten, T, Tietze, DT, Robertson, BC, Song, G, Borgia, G, Claramunt, S, Lovette, IJ, Cowen, SJ, Njoroge, P, Dumbacher, JP, Ryder, OA, Fuchs, J, Bunce, M, Burt, DW, Cracraft, J, Meng, G, Hackett, SJ, Ryan, PG, Jonsson, KA, Jamieson, IG, da Fonseca, RR, Braun, EL, Houde, P, Mirarab, S, Suh, A, Hansson, B, Ponnikas, S, Sigeman, H, Stervander, M, Frandsen, PB, van der Zwan, H, van der Sluis, R, Visser, C, Balakrishnan, CN, Clark, AG, Fitzpatrick, JW, Bowman, R, Chen, N, Cloutier, A, Sackton, TB, Edwards, SV, Foote, DJ, Shakya, SB, Sheldon, FH, Vignal, A, Soares, AER, Shapiro, B, Gonzalez-Solis, J, Ferrer-Obiol, J, Rozas, J, Riutort, M, Tigano, A, Friesen, V, Dalen, L, Urrutia, AO, Szekely, T, Liu, Y, Campana, MG, Corvelo, A, Fleischer, RC, Rutherford, KM, Gemmell, NJ, Dussex, N, Mouritsen, H, Thiele, N, Delmore, K, Liedvogel, M, Franke, A, Hoeppner, MP, Krone, O, Fudickar, AM, Mila, B, Ketterson, ED, Fidler, AE, Friis, G, Parody-Merino, AM, Battley, PF, Cox, MP, Lima, NCB, Prosdocimi, F, Parchman, TL, Schlinger, BA, Loiselle, BA, Blake, JG, Lim, HC, Day, LB, Fuxjager, MJ, Baldwin, MW, Braun, MJ, Wirthlin, M, Dikow, RB, Ryder, TB, Camenisch, G, Keller, LF, DaCosta, JM, Hauber, ME, Louder, MIM, Witt, CC, McGuire, JA, Mudge, J, Megna, LC, Carling, MD, Wang, B, Taylor, SA, Del-Rio, G, Aleixo, A, Vasconcelos, ATR, Mello, CV, Weir, JT, Haussler, D, Li, Q, Yang, H, Wang, J, Lei, F, Rahbek, C, Gilbert, MTP, Graves, GR, Jarvis, ED, Paten, B, and Zhang, G

Abstract

Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity1-4. Sparse taxon sampling has previously been proposed to confound phylogenetic inference5, and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species.

Published
2020

10. Microsatellite diversity of the Nordic type of goats in relation to breed conservation: How relevant is pure ancestry?

Author

Lenstra, J. A., Biebach, I., Hallsson, J. H., Kantanen, J., Nielsen, V. H., Pompanon, F., Naderi, S., Rezaei, H. R., Sæther, N., Ertugrul, O., Grossen, C., Camenisch, G., Vos-Loohuis, M., van Straten, M., de Poel, E. A., Windig, J., Oldenbroek, K., LS IRAS Tox Algemeen, Biochemisch laboratorium, dIRAS RA-1, and dCSCA AVR

Subjects
Diversity, Goats, Microsatellite, Conservation
Abstract

In the last decades, several endangered breeds of livestock species have been re-established effectively. However, the successful revival of the Dutch and Danish Landrace goats involved crossing with exotic breeds and the ancestry of the current populations is therefore not clear. We have generated genotypes for 27 FAO-recommended microsatellites of these landraces and three phenotypically similar Nordic-type landraces and compared these breeds with central European, Mediterranean and south-west Asian goats. We found decreasing levels of genetic diversity with increasing distance from the south-west Asian domestication site with a south-east-to-north-west cline that is clearly steeper than the Mediterranean east-to-west cline. In terms of genetic diversity, the Dutch Landrace comes next to the isolated Icelandic breed, which has an extremely low diversity. The Norwegian coastal goat and the Finnish and Icelandic landraces are clearly related. It appears that by a combination of mixed origin and a population bottleneck, the Dutch and Danish Land-races are separated from the other breeds. However, the current Dutch and Danish populations with the multicoloured and long-horned appearance effectively substitute for the original breed, illustrating that for conservation of cultural heritage, the phenotype of a breed is more relevant than pure ancestry and the genetic diversity of the original breed. More in general, we propose that for conservation, the retention of genetic diversity of an original breed and of the visual phenotype by which the breed is recognized and defined needs to be considered separately.

Published
2017

11. Resurrecting Darwin's Niata - Anatomical, biomechanical, genetic, and morphometric studies of morphological novelty in cattle

Author

Veitschegger, K, Wilson, LAB, Nussberger, B, Camenisch, G, Keller, LF, Wroe, S, Sánchez-Villagra, MR, Veitschegger, K, Wilson, LAB, Nussberger, B, Camenisch, G, Keller, LF, Wroe, S, and Sánchez-Villagra, MR

Abstract

The Niata was a cattle variety from South America that figured prominently in writings on evolution by Charles Darwin. Its shortened head and other aspects of its unusual morphology have been subject of unsettled discussions since Darwin's time. Here, we examine the anatomy, cranial shape, skull biomechanics, and population genetics of the Niata. Our results show that the Niata was a viable variety of cattle and exhibited anatomical differences to known chondrodysplastic forms. In cranial shape and genetic analysis, the Niata occupies an isolated position clearly separated from other cattle. Computational biomechanical model comparison reveals that the shorter face of the Niata resulted in a restricted distribution and lower magnitude of stress during biting. Morphological and genetic data illustrate the acquisition of novelty in the domestication process and confirm the distinct nature of the Niata cattle, validating Darwin's view that it was a true breed.

Published
2018

12. Microsatellite diversity of the Nordic type of goats in relation to breed conservation: How relevant is pure ancestry?

Author

LS IRAS Tox Algemeen, Biochemisch laboratorium, dIRAS RA-1, dCSCA AVR, Lenstra, J. A., Biebach, I., Hallsson, J. H., Kantanen, J., Nielsen, V. H., Pompanon, F., Naderi, S., Rezaei, H. R., Sæther, N., Ertugrul, O., Grossen, C., Camenisch, G., Vos-Loohuis, M., van Straten, M., de Poel, E. A., Windig, J., Oldenbroek, K., LS IRAS Tox Algemeen, Biochemisch laboratorium, dIRAS RA-1, dCSCA AVR, Lenstra, J. A., Biebach, I., Hallsson, J. H., Kantanen, J., Nielsen, V. H., Pompanon, F., Naderi, S., Rezaei, H. R., Sæther, N., Ertugrul, O., Grossen, C., Camenisch, G., Vos-Loohuis, M., van Straten, M., de Poel, E. A., Windig, J., and Oldenbroek, K.

Published
2017

13. Microsatellite diversity of the Nordic type of goats in relation to breed conservation: how relevant is pure ancestry?

Author

Lenstra, J. A, Tigchelaar, J., Biebach, I., Hallsson, J. H., Kantanen, J., Nielsen, V. H., Pompanon, F., Naderi, S., Rezaei, H. R., Sæther, N., Ertugrul, O., Grossen, C., Camenisch, G., Vos Loohuis, M., van Straten, M., de Poel, E. A., Windig, J., Oldenbroek, K., Abo Shehada, Mahamoud, Ajmone Marsan, Paolo, Tarrayrah, Jamil Al, Angiolillo, Antonella, Baret, Philip, Baumung, Roswitha, Beja Pereira, Albano, Bertaglia, Marco, Bordonaro, Salvatore, Brandt, Horst, Bruford, Mike, Caloz, Régi, Canali, Gabriele, Canon, Javier, Cappuccio, Irene, Carta, Antonello, Cicogna, Mario, Crepaldi, Paola, Dalamitra, Stella, Dobi, Petrit, Dunner, Susana, D'Urso, Giuseppe, El Barody, M. A. A., England, Phillip, Erhardt, Georg, Ertuğrul, Okan, Glowatzki, Marie Louise, Ibeagha Awemu, Eveline, Strzelec, Ewa, Fadlaoui, Aziz, Fornarelli, Francesca, Garcia, David, Georgoudis, Andrea, Giovenzana, Stefano, Gutscher, Katja, Hewitt, Godfrey, Hoda, Anila, Istvan, Anton, Jones, Sam, Joost, Stephane, Juma, Gabriela, Karetsou, Katerina, Kliambas, Georgio, Koban, Evren, Krugmann, Daniela, Kutita, Olga, Lazlo, Fesu, Ligda, Christina, Lipsky, Shirin, Luikart, Gordon, Lühken, Gesine, Marilli, Marta, Marletta, Donata, Milanesi, Elisabetta, Negrini, Riccardo, Nijman, Isaäc J., Niznikowski, Roman, Obexer Ruff, Gabriela, Papachristoforou, Christo, Pariset, Lorraine, Peter, Marco Pellecchia, Christina, Null, Perez, Trinidad, Pietrolà, Emilio, Pilla, Fabio, Popielarczyk, Dominik, Prinzenberg, Maria Eva, Roosen, Jutta, Scarpa, Riccardo, Sechi, Tiziana, Taberlet, Pierre, Taylor, Martin, Togan, Inci, Trommetter, Michel, Valentini, Alessio, Van Cann, Lisette M., Vlaic, Augustin, Wiskin, Louise, Zundel, Stéphanie, Ajmone Marsan, Paolo (ORCID:0000-0003-3165-4579), Canali, Gabriele (ORCID:0000-0001-9244-8184), Negrini, Riccardo (ORCID:0000-0002-8735-0286), Lenstra, J. A, Tigchelaar, J., Biebach, I., Hallsson, J. H., Kantanen, J., Nielsen, V. H., Pompanon, F., Naderi, S., Rezaei, H. R., Sæther, N., Ertugrul, O., Grossen, C., Camenisch, G., Vos Loohuis, M., van Straten, M., de Poel, E. A., Windig, J., Oldenbroek, K., Abo Shehada, Mahamoud, Ajmone Marsan, Paolo, Tarrayrah, Jamil Al, Angiolillo, Antonella, Baret, Philip, Baumung, Roswitha, Beja Pereira, Albano, Bertaglia, Marco, Bordonaro, Salvatore, Brandt, Horst, Bruford, Mike, Caloz, Régi, Canali, Gabriele, Canon, Javier, Cappuccio, Irene, Carta, Antonello, Cicogna, Mario, Crepaldi, Paola, Dalamitra, Stella, Dobi, Petrit, Dunner, Susana, D'Urso, Giuseppe, El Barody, M. A. A., England, Phillip, Erhardt, Georg, Ertuğrul, Okan, Glowatzki, Marie Louise, Ibeagha Awemu, Eveline, Strzelec, Ewa, Fadlaoui, Aziz, Fornarelli, Francesca, Garcia, David, Georgoudis, Andrea, Giovenzana, Stefano, Gutscher, Katja, Hewitt, Godfrey, Hoda, Anila, Istvan, Anton, Jones, Sam, Joost, Stephane, Juma, Gabriela, Karetsou, Katerina, Kliambas, Georgio, Koban, Evren, Krugmann, Daniela, Kutita, Olga, Lazlo, Fesu, Ligda, Christina, Lipsky, Shirin, Luikart, Gordon, Lühken, Gesine, Marilli, Marta, Marletta, Donata, Milanesi, Elisabetta, Negrini, Riccardo, Nijman, Isaäc J., Niznikowski, Roman, Obexer Ruff, Gabriela, Papachristoforou, Christo, Pariset, Lorraine, Peter, Marco Pellecchia, Christina, Null, Perez, Trinidad, Pietrolà, Emilio, Pilla, Fabio, Popielarczyk, Dominik, Prinzenberg, Maria Eva, Roosen, Jutta, Scarpa, Riccardo, Sechi, Tiziana, Taberlet, Pierre, Taylor, Martin, Togan, Inci, Trommetter, Michel, Valentini, Alessio, Van Cann, Lisette M., Vlaic, Augustin, Wiskin, Louise, Zundel, Stéphanie, Ajmone Marsan, Paolo (ORCID:0000-0003-3165-4579), Canali, Gabriele (ORCID:0000-0001-9244-8184), and Negrini, Riccardo (ORCID:0000-0002-8735-0286)

Abstract

In the last decades, several endangered breeds of livestock species have been re-established effectively. However, the successful revival of the Dutch and Danish Landrace goats involved crossing with exotic breeds and the ancestry of the current populations is therefore not clear. We have generated genotypes for 27 FAO-recommended microsatellites of these landraces and three phenotypically similar Nordic-type landraces and compared these breeds with central European, Mediterranean and south-west Asian goats. We found decreasing levels of genetic diversity with increasing distance from the south-west Asian domestication site with a south-east-to-north-west cline that is clearly steeper than the Mediterranean east-to-west cline. In terms of genetic diversity, the Dutch Landrace comes next to the isolated Icelandic breed, which has an extremely low diversity. The Norwegian coastal goat and the Finnish and Icelandic landraces are clearly related. It appears that by a combination of mixed origin and a population bottleneck, the Dutch and Danish Land-races are separated from the other breeds. However, the current Dutch and Danish populations with the multicoloured and long-horned appearance effectively substitute for the original breed, illustrating that for conservation of cultural heritage, the phenotype of a breed is more relevant than pure ancestry and the genetic diversity of the original breed. More in general, we propose that for conservation, the retention of genetic diversity of an original breed and of the visual phenotype by which the breed is recognized and defined needs to be considered separately.

Published
2017

14. HIF Prolyl-4-Hydroxylase PHD2 protein abundance depends on integral membrane-anchoring of FKBP38

Author

Barth, S, Edlich, F, Berchner-Pfannschmidt, U, Gneuss, S, Jahreis, G, Hasgall, P A, Fandrey, J, Wenger, R H, Camenisch, G, University of Zurich, and Camenisch, G

Subjects
1307 Cell Biology, 1303 Biochemistry, 10076 Center for Integrative Human Physiology, 1312 Molecular Biology, 570 Life sciences, biology, 610 Medicine & health, 10052 Institute of Physiology
Published
2009
Full Text
View/download PDF

16. Epolones induce erythropoietin expression via hypoxia-inducible factor-1α activation

Author

Wanner, R. M., Spielmann, P., Deborah Stroka, Camenisch, G., Camenisch, I., Scheid, A., Houck, D. R., Bauer, C., Gassmann, M., and Wenger, R. H.

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Abstract

Induction of erythropoietin (Epo) expression under hypoxic conditions is mediated by the heterodimeric hypoxia-inducible factor (HIF)-1. Following binding to the 3′ hypoxia-response element (HRE) of the Epo gene, HIF-1 markedly enhances Epo transcription. To facilitate the search for HIF-1 (ant)agonists, a hypoxia-reporter cell line (termed HRCHO5) was constructed containing a stably integrated luciferase gene under the control of triplicated heterologous HREs. Among various agents tested, we identified a class of substances called epolones, which induced HRE-dependent reporter gene activity in HRCHO5 cells. Epolones are fungal products known to induce Epo expression in hepatoma cells. We found that epolones (optimal concentration 4-8 μmol/L) potently induce HIF-1α protein accumulation and nuclear translocation as well as HIF-1 DNA binding and reporter gene transactivation. Interestingly, the activity of a compound related to the fungal epolones, ciclopirox olamine (CPX), was blocked after addition of ferrous iron. This suggests that CPX might interfere with the putative heme oxygen sensor, as has been proposed for the iron chelator deferoxamine mesylate (DFX). However, about 10-fold higher concentrations of DFX (50-100 μmol/L) than CPX were required to maximally induce reporter gene activity in HRCHO5 cells. Moreover, structural, functional, and spectrophotometric data imply a chelator:iron stoichiometry of 1:1 for DFX but 3:1 for CPX. Because the iron concentration in the cell culture medium was determined to be 16 μmol/L, DFX but not CPX function can be explained by complete chelation of medium iron. These results suggest that the lipophilic epolones might induce HIF-1α by intracellular iron chelation.

Published
2000
Full Text
View/download PDF

18. The transcription factor encyclopedia

Author

Dimas, Y, Camenisch, G, Wenger, R H, Wasserman, Wyeth, et al, and University of Zurich

Subjects
1307 Cell Biology, 1105 Ecology, Evolution, Behavior and Systematics, 1311 Genetics, 10076 Center for Integrative Human Physiology, 570 Life sciences, biology, 610 Medicine & health, 10052 Institute of Physiology
Published
2012

19. Identifying Y-chromosomal diversity by long-template PCR

Author

Wandeler, P, Camenisch, G, University of Zurich, and Wandeler, P

Subjects
10127 Institute of Evolutionary Biology and Environmental Studies, 1105 Ecology, Evolution, Behavior and Systematics, 1311 Genetics, 1305 Biotechnology, 570 Life sciences, biology, 590 Animals (Zoology)
Published
2011

20. The putative RNA helicase HELZ promotes cell proliferation, translation initiation and ribosomal protein S6 phosphorylation

Author

Hasgall, P A, Hoogewijs, D, Faza, M B, Panse, V G, Wenger, R H, Camenisch, G, and University of Zurich

Subjects
1000 Multidisciplinary, 1300 General Biochemistry, Genetics and Molecular Biology, 10076 Center for Integrative Human Physiology, 570 Life sciences, biology, 610 Medicine & health, 1100 General Agricultural and Biological Sciences, 10052 Institute of Physiology
Published
2011

23. Male germ cell expression of the PAS domain kinase PASKIN and its novel target eukaryotic translation elongation factor eEF1A1

Author

Eckhardt, K, Troger, J, Reissmann, J, Katschinski, D M, Wagner, K F, Stengel, P, Paasch, U, Hunziker, P, Borter, E, Barth, S, Schlafli, P, Spielmann, P, Stiehl, D P, Camenisch, G, Wenger, R H, University of Zurich, and Wenger, R H

Subjects
570 Life sciences, biology, 610 Medicine & health, 10071 Functional Genomics Center Zurich, 1314 Physiology, U7 Systems Biology / Functional Genomics, 10052 Institute of Physiology
Published
2007
Full Text
View/download PDF

27. Dysregulation of Hypoxia-Inducible Factor by Presenilin/ Gamma-Secretase Loss-of-Function Mutations

Author

Kaufmann, M R, Barth, S, Konietzko, U, Wu, Bei, Egger, Sascha, Kunze, Reiner, Marti, Hugo H, Hick, Meike, Müller, Ulrike, Camenisch, G, Wenger, R H, Kaufmann, M R, Barth, S, Konietzko, U, Wu, Bei, Egger, Sascha, Kunze, Reiner, Marti, Hugo H, Hick, Meike, Müller, Ulrike, Camenisch, G, and Wenger, R H

Abstract

Presenilin (PSEN) 1 and 2 are the catalytic components of the Gamma-secretase complex, which cleaves a variety of proteins, including the amyloid precursor protein (APP). Proteolysis of APP leads to the formation of the APP intracellular domain (AICD) and amyloid Beta that is crucially involved in the pathogenesis of Alzheimer’s disease. Prolyl-4-hydroxylase-domain (PHD) proteins regulate the hypoxia inducible factors (HIFs), the master regulators of the hypoxic response.Wepreviously identified the FK506 binding protein 38 (FKBP38)as a negative regulator of PHD2. Genetic ablation of PSEN1/2 has been shown to increase FKBP38 protein levels. Therefore, we investigated the role of PSEN1/2 in the oxygen sensing pathway using a variety of genetically modified cell and mouse lines. Increased FKBP38 protein levels and decreased PHD2 protein levels were found in PSEN1/2-deficient mouse embryonic fibroblasts and in the cortex of forebrain-specific PSEN1/2 conditional double knock-out mice. Hypoxic HIF-1alpha protein accumulation and transcriptional activity were decreased, despite reduced PHD2 protein levels. Proteolytic gamma-secretase function ofPSEN1/2wasneeded for proper HIF activation. Intriguingly, PSEN1/2 mutations identified in Alzheimer patients differentially affected the hypoxicresponse, involving the generation of AICD. Together,our results suggest a direct role for PSEN in the regulation of the oxygen sensing pathway via the APP/AICD cleavage cascade.

Published
2013

29. The Transcription Factor Encyclopedia

Author

Yusuf, D, Butland, SL, Swanson, MI, Bolotin, E, Ticoll, A, Cheung, WA, Zhang, XYC, Dickman, CTD, Fulton, DL, Lim, JS, Schnabl, JM, Ramos, OHP, Vasseur-Cognet, M, de Leeuw, CN, Simpson, EM, Ryffel, GU, Lam, EW-F, Kist, R, Wilson, MSC, Marco-Ferreres, R, Brosens, JJ, Beccari, LL, Bovolenta, P, Benayoun, BA, Monteiro, LJ, Schwenen, HDC, Grontved, L, Wederell, E, Mandrup, S, Veitia, RA, Chakravarthy, H, Hoodless, PA, Mancarelli, MM, Torbett, BE, Banham, AH, Reddy, SP, Cullum, RL, Liedtke, M, Tschan, MP, Vaz, M, Rizzino, A, Zannini, M, Frietze, S, Farnham, PJ, Eijkelenboom, A, Brown, PJ, Laperriere, D, Leprince, D, de Cristofaro, T, Prince, KL, Putker, M, del Peso, L, Camenisch, G, Wenger, RH, Mikula, M, Rozendaal, M, Mader, S, Ostrowski, J, Rhodes, SJ, Van Rechem, C, Boulay, G, Olechnowicz, SWZ, Breslin, MB, Lan, MS, Nanan, KK, Wegner, M, Hou, J, Mullen, RD, Colvin, SC, Noy, PJ, Webb, CF, Witek, ME, Ferrell, S, Daniel, JM, Park, J, Waldman, SA, Peet, DJ, Taggart, M, Jayaraman, P-S, Karrich, JJ, Blom, B, Vesuna, F, O'Geen, H, Sun, Y, Gronostajski, RM, Woodcroft, MW, Hough, MR, Chen, E, Europe-Finner, GN, Karolczak-Bayatti, M, Bailey, J, Hankinson, O, Raman, V, LeBrun, DP, Biswal, S, Harvey, CJ, DeBruyne, JP, Hogenesch, JB, Hevner, RF, Heligon, C, Luo, XM, Blank, MC, Millen, KJ, Sharlin, DS, Forrest, D, Dahlman-Wright, K, Zhao, C, Mishima, Y, Sinha, S, Chakrabarti, R, Portales-Casamar, E, Sladek, FM, Bradley, PH, Wasserman, WW, Yusuf, D, Butland, SL, Swanson, MI, Bolotin, E, Ticoll, A, Cheung, WA, Zhang, XYC, Dickman, CTD, Fulton, DL, Lim, JS, Schnabl, JM, Ramos, OHP, Vasseur-Cognet, M, de Leeuw, CN, Simpson, EM, Ryffel, GU, Lam, EW-F, Kist, R, Wilson, MSC, Marco-Ferreres, R, Brosens, JJ, Beccari, LL, Bovolenta, P, Benayoun, BA, Monteiro, LJ, Schwenen, HDC, Grontved, L, Wederell, E, Mandrup, S, Veitia, RA, Chakravarthy, H, Hoodless, PA, Mancarelli, MM, Torbett, BE, Banham, AH, Reddy, SP, Cullum, RL, Liedtke, M, Tschan, MP, Vaz, M, Rizzino, A, Zannini, M, Frietze, S, Farnham, PJ, Eijkelenboom, A, Brown, PJ, Laperriere, D, Leprince, D, de Cristofaro, T, Prince, KL, Putker, M, del Peso, L, Camenisch, G, Wenger, RH, Mikula, M, Rozendaal, M, Mader, S, Ostrowski, J, Rhodes, SJ, Van Rechem, C, Boulay, G, Olechnowicz, SWZ, Breslin, MB, Lan, MS, Nanan, KK, Wegner, M, Hou, J, Mullen, RD, Colvin, SC, Noy, PJ, Webb, CF, Witek, ME, Ferrell, S, Daniel, JM, Park, J, Waldman, SA, Peet, DJ, Taggart, M, Jayaraman, P-S, Karrich, JJ, Blom, B, Vesuna, F, O'Geen, H, Sun, Y, Gronostajski, RM, Woodcroft, MW, Hough, MR, Chen, E, Europe-Finner, GN, Karolczak-Bayatti, M, Bailey, J, Hankinson, O, Raman, V, LeBrun, DP, Biswal, S, Harvey, CJ, DeBruyne, JP, Hogenesch, JB, Hevner, RF, Heligon, C, Luo, XM, Blank, MC, Millen, KJ, Sharlin, DS, Forrest, D, Dahlman-Wright, K, Zhao, C, Mishima, Y, Sinha, S, Chakrabarti, R, Portales-Casamar, E, Sladek, FM, Bradley, PH, and Wasserman, WW

Abstract

Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe.

Published
2012

33. Oxygen tension modulates beta-globin switching in embryoid bodies

Author

Bichet, S, Wenger, R H, Camenisch, G, Rolfs, A, Ehleben, W, Porwol, T, Acker, H, Fandrey, J, Bauer, C, Gassmann, M, University of Zurich, and Gassmann, M

Subjects
1303 Biochemistry, 1311 Genetics, 1305 Biotechnology, 1312 Molecular Biology, 570 Life sciences, biology, 10052 Institute of Physiology
Published
1999
Full Text
View/download PDF

34. Monitoring of wild birds for Newcastle disease virus in Switzerland using real time RT-PCR

Author

Camenisch, G, Bandli, R, Hoop, R, Camenisch, G, Bandli, R, and Hoop, R

Abstract

Wild birds are considered to be the natural reservoir of the Newcastle disease virus (NDV; avian paramyxovirus-1) causing New-castle disease, and are often suspected to be involved in outbreaks in domesticated birds. To assess the epidemiologic status of wild birds living, or overwintering, in Switzerland, 3,049 cloacal swabs covering the period 2003–2006 were screened for NDV, using real time RT-PCR. All samples were negative. This result seems in contrast with previously performed serologic screenings of wild birds.

Published
2008

36. Oxygen-dependent ATF-4 stability is mediated by the PHD3 oxygen sensor

Author

Köditz, J, Nesper, J, Wottawa, M, Stiehl, D P, Camenisch, G, Franke, C, Myllyharju, J, Wenger, R H, Katschinski, D M, Köditz, J, Nesper, J, Wottawa, M, Stiehl, D P, Camenisch, G, Franke, C, Myllyharju, J, Wenger, R H, and Katschinski, D M

Abstract

The activating transcription factor-4 (ATF-4) is translationally induced under anoxic conditions, mediates part of the unfolded protein response following endoplasmic reticulum (ER) stress, and is a critical regulator of cell fate. Here, we identified the zipper II domain of ATF-4 to interact with the oxygen sensor prolyl-4-hydroxylase domain 3 (PHD3). The PHD inhibitors dimethyloxalylglycine (DMOG) and hypoxia, or proteasomal inhibition, all induced ATF-4 protein levels. Hypoxic induction of ATF-4 was due to increased protein stability, but was independent of the ubiquitin ligase von Hippel-Lindau protein (pVHL). A novel oxygen-dependent degradation (ODD) domain was identified adjacent to the zipper II domain. Mutations of 5 prolyl residues within this ODD domain or siRNA-mediated down-regulation of PHD3, but not of PHD2, was sufficient to stabilize ATF-4 under normoxic conditions. These data demonstrate that PHD-dependent oxygen-sensing recruits both the hypoxia-inducible factor (HIF) and ATF-4 systems, and hence not only confers adaptive responses but also cell fate decisions.

Published
2007

37. Glucose-stimulated insulin production in mice deficient for the PAS kinase PASKIN.

Author

Borter, E, Niessen, M, Zuellig, R, Spinas, G A, Spielmann, P, Camenisch, G, Wenger, R H, Borter, E, Niessen, M, Zuellig, R, Spinas, G A, Spielmann, P, Camenisch, G, and Wenger, R H

Abstract

The Per-ARNT-Sim (PAS) domain serine/threonine kinase PASKIN, or PAS kinase, links energy flux and protein synthesis in yeast and regulates glycogen synthase in mammals. A recent report suggested that PASKIN mRNA, protein, and kinase activity are increased in pancreatic islet beta-cells under hyperglycemic conditions and that PASKIN is necessary for insulin gene expression. We previously generated Paskin knockout mice by targeted replacement of the kinase domain with the beta-geo fusion gene encoding beta-galactosidase reporter activity. Here we show that no 5-bromo-4-chloro-3-indolyl-ss-d-galactopyranoside (X-gal) staining was observed in islet beta-cells derived from Paskin knockout mice, irrespective of the ambient glucose concentration, whereas adenoviral expression of the lacZ gene in beta-cells showed strong X-gal staining. No induction of PASKIN mRNA could be detected in insulinoma cell lines or in islet beta-cells. Increasing glucose concentrations resulted in PASKIN-independent induction of insulin mRNA levels and insulin release. PASKIN mRNA levels were high in testes but undetectable in pancreas and in islet beta-cells. Finally, blood glucose levels and glucose tolerance after intraperitoneal glucose injection were indistinguishable between Paskin wild-type and knockout mice. These results suggest that Paskin gene expression is not induced by glucose in pancreatic beta-cells and that glucose-stimulated insulin production is independent of PASKIN.

Published
2007

39. Copper-dependent activation of hypoxia-inducible factor (HIF)-1: implications for ceruloplasmin regulation

Author

Martin, F, Linden, T, Katschinski, D M, Oehme, F, Flamme, I, Mukhopadhyay, C K, Eckhardt, K, Tröger, J, Barth, S, Camenisch, G, Wenger, R H, Martin, F, Linden, T, Katschinski, D M, Oehme, F, Flamme, I, Mukhopadhyay, C K, Eckhardt, K, Tröger, J, Barth, S, Camenisch, G, and Wenger, R H

Abstract

Cellular oxygen partial pressure is sensed by a family of prolyl-4-hydroxylase domain (PHD) enzymes that modify hypoxia-inducible factor (HIF)alpha subunits. Upon hydroxylation under normoxic conditions, HIFalpha is bound by the von Hippel-Lindau tumor suppressor protein and targeted for proteasomal destruction. Since PHD activity is dependent on oxygen and ferrous iron, HIF-1 mediates not only oxygen- but also iron-regulated transcriptional gene expression. Here we show that copper (CuCl(2)) stabilizes nuclear HIF-1alpha under normoxic conditions, resulting in hypoxia-response element (HRE)-dependent reporter gene expression. In in vitro hydroxylation assays CuCl(2) inhibited prolyl-4-hydroxylation independently of the iron concentration. Ceruloplasmin, the main copper transport protein in the plasma and a known HIF-1 target in vitro, was also induced in vivo in the liver of hypoxic mice. Both hypoxia and CuCl(2) increased ceruloplasmin (as well as vascular endothelial growth factor [VEGF] and glucose transporter 1 [Glut-1]) mRNA levels in hepatoma cells, which was due to transcriptional induction of the ceruloplasmin gene (CP) promoter. In conclusion, our data suggest that PHD/HIF/HRE-dependent gene regulation can serve as a sensory system not only for oxygen and iron but also for copper metabolism, regulating the oxygen-, iron- and copper-binding transport proteins hemoglobin, transferrin, and ceruloplasmin, respectively.

Published
2005

43. Induction and nuclear translocation of hypoxia-inducible factor-1 (HIF-1): heterodimerization with ARNT is not necessary for nuclear accumulation of HIF-1alpha

Author

Chilov, D, Camenisch, G, Kvietikova, I, Ziegler, U, Gassmann, M, Wenger, R H, Chilov, D, Camenisch, G, Kvietikova, I, Ziegler, U, Gassmann, M, and Wenger, R H

Abstract

Hypoxia-inducible factor-1 (HIF-1) is a master regulator of mammalian oxygen homeostasis. HIF-1 consists of two subunits, HIF-1alpha and the aryl hydrocarbon receptor nuclear translocator (ARNT). Whereas hypoxia prevents proteasomal degradation of HIF-1alpha, ARNT expression is thought to be oxygen-independent. We and others previously showed that ARNT is indispensable for HIF-1 DNA-binding and transactivation function. Here, we have used ARNT-mutant mouse hepatoma and embryonic stem cells to examine the requirement of ARNT for accumulation and nuclear translocation of HIF-1alpha in hypoxia. As shown by immunofluorescence, HIF-1alpha accumulation in the nucleus of hypoxic cells was independent of the presence of ARNT, suggesting that nuclear translocation is intrinsic to HIF-1alpha. Co-immunoprecipitation of HIF-1alpha together with ARNT could be performed in nuclear extracts but not in cytosolic fractions, implying that formation of the HIF-1 complex occurs in the nucleus. A proteasome inhibitor and a thiol-reducing agent could mimic hypoxia by inducing HIF-1alpha in the nucleus, indicating that escape from proteolytic degradation is sufficient for accumulation and nuclear translocation of HIF-1alpha. During biochemical separation, both HIF-1alpha and ARNT tend to leak from the nuclei in the absence of either subunit, suggesting that heterodimerization is required for stable association within the nuclear compartment. Nuclear stabilization of the heterodimer might also explain the hypoxically increased total cellular ARNT levels observed in some of the cell lines examined.

Published
1999

44. A polyoma-based episomal vector efficiently expresses exogenous genes in mouse embryonic stem cells.

Author

Camenisch, G, Gruber, M, Donoho, G, Van Sloun, P, Wenger, R H, Gassmann, M, Camenisch, G, Gruber, M, Donoho, G, Van Sloun, P, Wenger, R H, and Gassmann, M

Abstract

We describe the ability of novel episomally maintained vectors to efficiently promote gene expression in embryonic stem (ES) cells as well as in established mouse cell lines. Extrachromosomal maintenance of our vectors is based on the presence of polyoma virus DNA sequences, including the origin of replication harboring a mutant enhancer (PyF101), and a modified version of the polyoma early region (LT20) encoding the large T antigen only. Reporter gene expression from such extrachromosomally replicating vectors was approximately 10-fold higher than expression from replication-incompetent control plasmids. After transfection of different ES cell lines, the polyoma virus-derived plasmid variant pMGD20neo (7.2 kb) was maintained episomally in 16% of the G418-resistant clones. No chromosomal integration of pMGD20neo vector DNA was detected in ES cells that contained episomal vector DNA even after long term passage. The vector's replication ability was not altered after insertion of up to 10 kb hprt gene fragments. Besides undifferentiated ES cells, the polyoma-based vectors were also maintained extrachromosomally in differentiating ES cells and embryoid bodies as well as in established mouse cell lines.

Published
1996

47. Pharmacokinetics of the oral direct renin inhibitor aliskiren in combination with digoxin, atorvastatin, and ketoconazole in healthy subjects: the role of p-glycoprotein in the disposition of aliskiren.

Author

Vaidyanathan S, Camenisch G, Schuetz H, Reynolds C, Yeh C, Bizot M, Dieterich HA, Howard D, and Dole WP

Abstract

This study investigated the potential pharmacokinetic interaction between the direct renin inhibitor aliskiren and modulators of P-glycoprotein and cytochrome P450 3A4 (CYP3A4). Aliskiren stimulated in vitro P-glycoprotein ATPase activity in recombinant baculovirus-infected Sf9 cells with high affinity (K(m) 2.1 mumol/L) and was transported by organic anion-transporting peptide OATP2B1-expressing HEK293 cells with moderate affinity (K(m) 72 mumol/L). Three open-label, multiple-dose studies in healthy subjects investigated the pharmacokinetic interactions between aliskiren 300 mg and digoxin 0.25 mg (n = 22), atorvastatin 80 mg (n = 21), or ketoconazole 200 mg bid (n = 21). Coadministration with aliskiren resulted in changes of <30% in AUC(tau) and C(max,ss) of digoxin, atorvastatin, o-hydroxy-atorvastatin, and rho-hydroxy-atorvastatin, indicating no clinically significant interaction with P-glycoprotein or CYP3A4 substrates. Aliskiren AUC(tau) was significantly increased by coadministration with atorvastatin (by 47%, P < .001) or ketoconazole (by 76%, P < .001) through mechanisms most likely involving transporters such as P-glycoprotein and organic anion-transporting peptide and possibly through metabolic pathways such as CYP3A4 in the gut wall. These results indicate that aliskiren is a substrate for but not an inhibitor of P-glycoprotein. On the basis of the small changes in exposure to digoxin and atorvastatin and the <2-fold increase in exposure to aliskiren during coadministration with atorvastatin and ketoconazole, the authors conclude that the potential for clinically relevant drug interactions between aliskiren and these substrates and/or inhibitors of P-glycoprotein/CPY3A4/OATP is low. [ABSTRACT FROM AUTHOR]

Published
2008
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results