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2. KDM6A/UTX promotes spermatogenic gene expression across generations and is not required for male fertility

Author

Walters, BW, Rainsford, SR, Heuer, RA, Dias, N, Huang, XF, de Rooij, D, Lesch, BJ, Walters, BW, Rainsford, SR, Heuer, RA, Dias, N, Huang, XF, de Rooij, D, and Lesch, BJ

Abstract

Paternal chromatin undergoes extensive structural and epigenetic changes during mammalian spermatogenesis, producing sperm with an epigenome optimized for the transition to embryogenesis. Lysine demethylase 6a (KDM6A, also called UTX) promotes gene activation in part via demethylation of H3K27me3, a developmentally important repressive modification abundant throughout the epigenome of spermatogenic cells and sperm. We previously demonstrated increased cancer risk in genetically wild-type mice derived from a paternal germ line lacking Kdm6a (Kdm6a cKO), indicating a role for KDM6A in regulating heritable epigenetic states. However, the regulatory function of KDM6A during spermatogenesis is not known. Here, we show that Kdm6a is transiently expressed in spermatogenesis, with RNA and protein expression largely limited to late spermatogonia and early meiotic prophase. Kdm6a cKO males do not have defects in fertility or the overall progression of spermatogenesis. However, hundreds of genes are deregulated upon loss of Kdm6a in spermatogenic cells, with a strong bias toward downregulation coinciding with the time when Kdm6a is expressed. Misregulated genes encode factors involved in chromatin organization and regulation of repetitive elements, and a subset of these genes was persistently deregulated in the male germ line across two generations of offspring of Kdm6a cKO males. Genome-wide epigenetic profiling revealed broadening of H3K27me3 peaks in differentiating spermatogonia of Kdm6a cKO mice, suggesting that KDM6A demarcates H3K27me3 domains in the male germ line. Our findings highlight KDM6A as a transcriptional activator in the mammalian male germ line that is dispensable for spermatogenesis but important for safeguarding gene regulatory state intergenerationally.

Published
2024

3. Adaptive organizational network response in a crisis: The case of five European airports during the COVID-19 pandemic

Author

de Rooij, D., Timen, A., Raab, J., de Rooij, D., Timen, A., and Raab, J.

Abstract

The COVID-19 pandemic posed unprecedented challenges to the joint organizational response of private and public and here especially public health organizations. This is particularly true for airports as central connectors of global travel and trade. For five European airports, we analyzed the interorganizational response based on input from 66 of the 87 different airport partners, using two fictitious scenarios derived from public health practice. We applied organizational design theory and quantitative (network) analysis to show how the four fundamental problems of organizing have been tackled at airports, i.e., task distribution, task allocation, rewards, and information provision. This article shows how the response to COVID-19 in the airport setting needs to be solved within broad and flexible public administrative networks. The thorough understanding of organizational network responses in emergency management following from this article supports future preparedness efforts to deal with complex known and unknown public health threats.

Published
2024

23. The effectiveness and medication costs of three anti-tumour necrosis factor [alpha] agents in the treatment of rheumatoid arthritis from prospective clinical practice data

Author

Kievit, W., Adang, E.M., Fransen, J., Kuper, H.H., van de Laar, M.A.F.J., Jansen, T.L., De Gendt, C.M.A., De Rooij, D.-J.R.A.M., Brus, H.L.M., Van Oijen, P.C.M., and Van Riel, P.C.L.M.

Subjects
Rheumatoid arthritis -- Drug therapy, Rheumatoid arthritis -- Economic aspects, Rheumatoid arthritis -- Patient outcomes, Rheumatoid arthritis -- Research, Medical care, Cost of -- Research, Antirheumatic agents -- Dosage and administration, Antirheumatic agents -- Research, Tumor necrosis factor -- Physiological aspects, Health
Published
2008

32. Spermatoproteasome-deficient mice are proficient in meiotic DNA repair but defective in meiotic exit

Author

Laura Gómez-H, Natalia Felipe-Medina, Rodrigo Garcia-Valiente, de Rooij D, Ignasi Roig, Yazmine B Condezo, Elena Llano, Isabel Ramos, Manuel Sánchez-Martín, and Alberto M. Pendás

Subjects
biology, Spermatid, urogenital system, DNA repair, Histone displacement, Cell biology, Synaptonemal complex, Histone, medicine.anatomical_structure, Meiosis, biology.protein, Homologous chromosome, medicine, Homologous recombination
Abstract

Meiotic recombination generates crossovers which are essential to ensure genome haploidization. The ubiquitin proteasome system regulates meiotic recombination through its association to the synaptonemal complex, a ‘zipper’-like structure that holds homologs and provides the structural framework for meiotic recombination. Here we show that the testis-specific α4s subunit (PSMA8) of the spermatoproteasome is located at the synaptonemal complex and is essential for the assembly of its activator PA200. Accordingly, synapsis-deficient mice show delocalization of PSMA8 from the synaptonemal complex. Genetic analysis of Psma8-deficient mice shows normal meiotic DNA repair, crossing over formation and an increase of spermatocytes at metaphase I and metaphase II which either enter into apoptosis or slip to give rise to an early spermatid arrest and infertility. Thus, spermatoproteasome-dependent histone degradation is dispensable for meiotic recombination. We show that PSMA8 deficiency alters the proteostasis of several key meiotic players such as acetylated histones, SYCP3, SYCP1, CDK1 and TRIP13 which in turn leads to an aberrant meiotic exit and early spermatid arrest prior to the histone displacement process that take place subsequently.

Published
2018
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34. Targeted inactivation of nuclear interaction partner of ALK disrupts meiotic prophase

Author

Illert, A, L, Kawaguchi, H, Antinozzi, C, Bassermann, F, Quintanilla Martinez, L, von Klitzing, C, Hiwatari, M, Peschel, C, De Rooij, D, Morris, S, Barchi, M, Duyster, J, Other Research, and Center for Reproductive Medicine

Subjects
Male, NIPA (ZC3HC1), Immunoblotting, CCNB1, Biology, Mice, Knockout mouse, Prophase, Meiosis, Spermatocytes, Animals, Immunoprecipitation, DNA Breaks, Double-Stranded, Cyclin B1, RNA, Small Interfering, Kinase activity, Nuclear protein, Molecular Biology, Mitosis, Research Articles, Mice, Knockout, Settore BIO/16, Checkpoint, Cell Cycle, Synapsis, Nuclear Proteins, Cell cycle, Flow Cytometry, Immunohistochemistry, Molecular biology, Mice, Mutant Strains, Cell cycle, Knockout mouse, Meiosis, NIPA (ZC3HC1), CCNB1, Checkpoint, Developmental Biology
Abstract

NIPA (nuclear interaction partner of ALK) is an F-box-like protein that monitors the timing of mitotic entry. Constitutively active NIPA delays mitotic entry by preventing accumulation of nuclear cyclin B1. Here, we have investigated the consequences of Nipa inactivation by using a conditional knockout strategy. Nipa-deficient animals are viable but show a lower birth rate and reduced body weight. Furthermore, Nipa-deficient males are sterile owing to a block of spermatogenesis during meiotic prophase. Whereas Nipa−/− mouse embryonic fibroblasts show no severe phenotype, Nipa−/− spermatocytes arrest during stage IV of the epithelial cycle with subsequent TUNEL-positive apoptosis resulting from improper synapsis, defects in the repair of DNA double-stranded breaks and synaptonemal complex formation. Moreover, we show nuclear accumulation of cyclin B1 with a subsequent premature increase in G2/M kinase activity in Nipa−/− spermatocytes. Together, these results reveal a novel role for NIPA in meiosis.

Published
2012
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39. Eular workshop on Rheumatology Research: Noordwijkerhout February 1982

Author

Bjelle, A., Cedergren, B., Wählby, L., Boerbooms, A. P. Th., Geerdink, P. J., van de Putte, L. B. A., Ouweland, F. A. M., Buchanan, R. R. C., Morgan, A., Staines, N. A., Venables, P. J. W., Maini, R. N., Bucknall, R. C., Bacon, P. A., Jones, J. Verrier, Leirisalo, M., Laitinen, O., Bühring, M., Rosak, C., Stöckle, W., Magnet, W., Catogio, L. J., Bernstein, R. M., Black, C. M., Hughes, G. R. V., Maddison, P. J., Charles P. J., Venables P. J. W., Tung Yi., Buchanan R. C., Maini R. N., Deicher, H., Weißbarth, E., Zeller, J., Baruth, B., Delbarre, F., de Gery, A., Kahan, A., de Vries, E., van der Veen, C. J. P., van der Weij, J. P., Klein, F., de Bruijn, A. M., Cats, A., Dreher, R., Coworkers, Duclos, M., Peter, H., Zeidler, H., Rieber, P., Pichler, J., Limany, W., Dunn, N., Hurst, N. P., Denholm, E., Nuki, G., Ebringer, A., Hayes, J., Cowling, P., Ebringer, R., Egeland, T., Forre, Ø., Festen, J. J. M., Kuipers, F. H., Schaars, A. H., Førre, Ø., Waalen, K., Mellbye, O. J., Froebel, K., Lewis, D., Sturrock, R. D., Goldschmeding, R., Limburg, P. C., Pastoor, G. W., Houtman, P. M., Kallenberg, C. G. M., Halberg, P., Lorenzen, I., Bennedsen, J., Rhodes, J. M., Hall, N. D., Eales, L. -J., Blake, D. R., Hunneyball, I. M., Helmke, K., Boeder, T., Teuber, J., Hermanns, P., Veys, E. M., Verbruggen, G., Horsfall, A. C., Mumford, P. A., Schrieber, L., Huber, O., Kluin-Nelemans, H., Vernooy, J., Meyling, F. Gmelig, Derksen, R., Kater, L., Hurst N. P., Nuki G., Husby, G., Gran, J. T., Thorsby, E., Johnson, G. D., Bainbridge, D. R., Holborow, E. J., Bubel, M., Goddard, D. H., Jonsson, J., Norberg, R., Schilling, W., Kalden, R., Leitner, O., Manger, B., Beck, A., Koch, B., de Jong, M. C. J. M., Walstra, T., van der Meulen, J., Kávai, M., Bányai, A., Zsindely, A., Sonkoly, I., Szegedi, Gy., Klareskog, L., Forsum, U., Scheynius, A., Kabelitz, D., Wigzell, H., Koivuranta, P., Repo, H., Kiistala, U., Österman, P., Konttinen, Y., Friman, C., Tolvanen, E., Johansson, E., Konttinen, Y. T., Reitamo, S., Seppä, A., Malmström, M., Lindström, F., Hellquist, H., Olofsson, J., Maddison, PJ., Black, CM., Jayson, MIV, Batchelor, J. R., Walsh, Kl., Bernstein, RM, Catoggio, LJ., Holland, CD., Hughes, GRV, Mbuyi, J. M., Dequeker, J., Förre Ö, Johnsen, W., Meijer, C. J. L. M., de Graaf-Reitsma, C., Lafeber, G. J. M., Meyer, O., Borda-Oriarte, O., Haïm, T., Ryckewaert, A., Mielants, H., Van Steenkiste, M., De Langhe, J., Buchanan, R. C., Moutsopoulos, M., Hooks, J., Mumford, P., Patel, V., Panayi, G. S., Piatier-Tonneau, D., Mach, P. S., Plater-Zyberk, C., Clarke, M., Raeman, F., De Cock, W., Leempoels, J., De Cree, J., Verhaegen, H., Ranki, A., Paavonen, T., Kankaanpää, U., Nilsson, E., Biberfeld, G., Room, G., Saal, J. G., Frank, F., Rauteenstrauch, H., Hadam, M., Fritz, P., Laschner, W., Scheper, R. J., von Blomberg-van der Flier, B. M. E., Boerrigter, G. H., van Bruynzeel, D., van Dinther-Janssen, A. C. H. M., Simon, K. H., Schmidt, R. E., Erhardt, C. C., Melsom, R. D., McCarthy, J., Smeenk, R., Van der Lelij, G., Aarden, L., Staite, N. D., Stierle, H. E., Brown, K. A., Perry, J. D., Swaak, A. J. G., Groenwold, J., Smeenk, R. J. T., Toenes, G. H., Edel, H. H., Eggert, K., Held, E., Hübner, F. K., Schattenkirchner, M., Wegelius, O., Tron, F., Jacob, L., Bach, J. F., Lens, J. W., van den Berg, W. B., van Rijswijk, M. H., van Leeuwen, M. A., van der Giessen, M., The, T. H., van Venrooij, W. J., van Eekelen, C. A. G., Habets, W. J. A., Salden, M. H. L., de Rooij, D. J., Van Wanghe, P., Hermanns, Ph., Van Bruwaene, Ph., De Brabanter, G., De Landsheere, D., Immesoete, C., Walravens, M. J. F., Stevens, E., Warnatz, H., Lemm, G., Wiik, A., Petersen, J., Permin, H., Wollheim, F. A., Carlsson, J., Forsgren, A., Pettersson, H., Youinou, P., Miossec, P., and Le Goff, P.

Published
1982
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41. IX Eular Workshop for Rheumatology Research: Molecular biology of autoantigens, autoantibodies and immunopeptides. Vienna, Austria, March 9–12, 1989

Author

Fournier, C., Texier, B., Chiocchia, G., Boissier, M. C., Herbage, D., Brown, C. M. S., Zyberk, C. Plater, Maini, R. N., Palacios, A., Sieper, J., Heinegard, D., Panayi, G. S., Gentric, A., Mackenzie, L., Lydyard, P. M., Youinou, P., Menzel, E. J., Kaik, B., Sykulev, Yu. K., Guschin, A. Je., Vasiljev, V. I., Ostreiko, K. K., Yeronina, T. V., Tumanova, I. A., Moynier, M., Abderrazik, M., Combe, B., Rucheton, M., Brochier, J., Tuomi, T., Palosuo, T., Heliövaara, M., Aho, K., McHugh, N. J., James, I. E., Kallenberg, C. G. M., Tervaert, J. W. Cohen, Goldschmeding, R., Von Dem Borne, A. E. G. K. R., Bouanani, M., Piechaczyk, M., Pau, B., Bastide, M., Le Page, S., Williams, W., Parkhouse, D., Cambridge, G., Isenberg, D. A., Nimmegeers, J., De Keyser, F., Verbruggen, G., Veys, E. M., Walravens M. J. F., Verdeyen I., Vandepol B., Cortens W., Schatteman, L., Goethals, K., Wu, D. -H., Tavoni, A., Neri, R., Garzelli, C., Vitali, C., Bombardieri, S., Logar, D., Kveder, T., Dobovisek, J., Rozman, B., Menard, H. A., Boire, G., Lopez-Longo, F. J., Masson, Ch., Lapointe, S., Clair, E. W. St., Zerva, L., Moutsopoulos, H. M., Keene, J. D., Pisetsky, D. S., Van Dam, A. P., Cuypers, H. T. M., Winkel, I., Smeenk, R. J. T., Taylor, D., Valente, E., Foster, J. P., Williams, D. G., Stocks, M. R., Caporali, R., De Gennaro, F., Cerino, A., Cobianchi, F., Astaldi-Ricotti, G. C. B., Montecucco, C., Habets, W., Sillekens, P. T. G., Hoet, M. H., McAllister, G., Lerner, M. R., Van Venrooij, W. J., Habets, W. J., Van Der Kemp, A., De Jong, B., Scarpa, R., Pucino, A., Di Girolamo, C., della Valle, G., Larizza, G., Casiere, D., Oriente, P., Paimela, L., Palvimo, J., Kurki, P., Hassfeld, W., Steiner, G., Graninger, W., Smolen, J. S., Lopez-Longo, E. J., Larose, A., Hoet, R., Zewald, R., Smeenk, R., Brinkman, K., Van Den Brink, H., Westgeest, A., Huss, R., Krapf, E. F., Herrmann, M., Leitmann, W., Kalden, J. R., Merétey, K., Cebecauer, L., Böhm, U., Kozakova, D., Brózik, M., Temesvári, P., Nagy, L., Bozic, B., Stegnar, M., Vene, N., Peternel, P., Giuggioli, C., Monti, P., Rossi, G., Ferri, C., Chiellini, S., Baboonian, C., Venables, P. J. W., Roffe, L., Booth, J., Krapf, F., Abuljadayel, I., Ebringer, A., Cox, N. L., Brand, S. R., McIntosh, D. P., Bernstein, R. M., Van Den Broek, M. F., Van Bruggen, M. C. J., Smetsers, T., Kuyer, P., Van De Putte, L., Van Den Berg, W. B., Toivanen, A., Jalkanen, S., Lahesmaa-Rantala, R., Isomäki, O., Pekkola-Heino, K., Merilahti-Palo Saario, R., Von Essen, R., Isomäki, H., Granfors, K., Gaston, J. S. H., Life, P. F., Bailey, L., Bacon, P. A., Khalafpour, S., Wilson, C., Awad, J., Toivanen, P., Saario, R., Skurnik, M., Van Der Straeten, C., Mielants, H., Gazic, M., Hartung, K., Riedel, T., Stannat, S., Specker, Ch., Röther, E., Pirner, K., Schendel, D., Baur, M., Corvetta, A., Peter, H. H., Lakomek, H. J., Deicher, H., Andonopoulos, A. P., Papasteriades, C. A., Drosos, A. A., Dimou, G. S., Shattles, W., Venables, P., Charles, P. J., Markwick, J. R., Venables, P. J., Galeazzi, M., Lulli, P., Tuzi, T., Cappellacci, S., Morellini, M., Trabace, S., Cutrupi, F., Sorrentino, R., Botti, S., Iannicola, C., Costanzi, S., Tosi, R., Gospodinoff, A., Eliaou, J. F., Humbert, H., Balaguer, P., Nicolas, J. C., Sany, J., Clot, J., Sakkas, L. I., Bird, H., Welsh, K. I., Pitzalis, C., Kingsley, G., Haskard, D., Vischer, T. L., Bas, S., Werner-Favre, C., Wohlwend, D., Zubler, R. H., Afeltra, A., De Pita, O., Basso, P., Pietrucci, A., Ferri, G. M., Bonomo, L., Gerli, R., Cernetti, C., Bertotto, A., Agea, E., Arcangeli, C., Lanfrancone, L., Rambotti, P., Crupi, S., Baglioni, A., Spinozzi, F., Papazoglou, S., Skoumi, D., Athanasiou, P., Iliopoulos, A., Stavropoulou, A., Kontomerkos, T., Hendrich, G., Kuipers, J. G., Hammer, M., Schmidt, R. E., Manoussakis, M. N., Germandis, G., Zerva, L. V., Siouna-Fatourou, H. J., Katsikis, P. D., Mavridis, A., Toubert, A., Sadouk, M., de la Tour, B., Vaquero, C., Amor, B., Miossec, P., Naviliat, M., Cretien, I., Banchereau, J., Graninger, P., Aschauer, B., Sinski, A., Smolen, J., Krutmann, J., Kirnbauer, R., Köck, A., Schwarz, T., May, L. T., Sehgal, P. B., Luger, T. A., Field, M., Chu, C. Q., Feldmann, M., Wilbrink, B., Nietfeld, J. J., Helle, M., Boeije, L. C. M., Van Roy, J. L. A. M., Den Otter, W., Aarden, L. A., Huber-Bruning, O., Malejczyk, J., Urbanski, A., Malejczyk, M., Karbowski, A., Völker, W., Feige, U., Otter, W. Den, Malfait, A. M., Wieme, N., Gyselbrecht, L., Van de Loo, A. A. J., Van Lent, P. L. E. M., Haskard, D. O., Wellicome, S., Lanchbury, J., Thornhill, M., Krutmann, K., Gschnait, F., Yaron, M., Yaron, I., Dayer, J. -M., Bleiberg, I., Meyer, F. -A., Maury, C. P. J., Teppo, A. -M., Salo, E., Pelkonen, P., Malfait, A., Cochez, Ph., Gruschwitz, M., Müller, P. U., Wick, G., Madhok, R., Wilson, R., Frame, M., Thompson, J., Sturrock, R. D., Partsch, G., Matucci-Cerinic, M., Marabini, S., Jantsch, S., Neumüller, J., Eberl, R., van Beuningen, H. M., Arntz, O. J., Zlabinger, G. J., Steffen, C., Brand, H. S., Van Kampen, G. P. J., De Koning, M. H. M. T., Kiljan, E., Van Der Korst, J. K., Gemmell, C. G., Swaak, A. J. G., Van Rooyen, A., Hall, N. D., Woolf, A. D., Kantharia, B., Maymo, J., Blake, D. R., Goulding, N. J., Maddison, P. J., Munthe, E., Berntzen, H. B., Fagerhol, M., Mathieu, A., Pala, R., Contu, L., Cirillo, R., Garau, P., Nurchis, P., Viberti, G. C., Meyer, O., Zenklusen, C., Le Thi Huong Du, Z., Gaudouen, C., Mery, J. Ph., Ronco, P., Kahn, M. F., Rasmussen, N., Szpirt, W., Thomsen, B., Humbel, R. L., Ter Borg, E. J., Horst, G., Hummel, E., Limburg, P. C., Aeschilmann, A., Bourgeois, P., De Rooij, D. J., Van de Putte, L. B. A., Verbeek, L., Farinaro, C., Infranzi, E., Couret, M., Ackerman, C., De Vlam, K., Carapic, V., Carapic, D., Annefeld, M., Erne, B., Rosenwasser, L. J., Pazoles, C. J., Otterness, I. G., Hanson, D. C., McDonald, B., Loose, L. D., Dougados, M., Machold, K. P., Wiesenberg-Böttcher, I., Wanner, K., Pignat, W., Altmann, H., Tuschl, H., Bröll, H., Balestrieri, G., Tincani, A., Cattaneo, R., Bertoli, M. T., Martinelli, M., Allegro, F., Meroni, P. L., Balesini, G., Aichinger, G., Schlögl, E., Huber, Ch., Shoenfeld, Y., Fleishmaker, E., Mendlovic, S., Mozes, E., Blank, M., Talal, N., Hogervorst, E. J. M., Van Eden, W., Van Der Zee, R., Psychos, D., Dimou, G., Stefanaki-Nikou, S., Papadimitriou, C. S., Settas, L., Alexiou, P., Dimitriadis, G., Mataftsi, E., Soliou, E., Tourkantonis, A., Babic, M., Jeurissen, M. E. C., and Boerbooms, A. MTh

Published
1989
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48. Meer waarden met dieren : businessplan

Author

Janssens, E., de Rooij, D., Nolles, J., Waggelink, W., and Hopster, H.

Subjects
animal husbandry, agrarisch onderwijs, dierhouderij, animal production, dierlijke productie, agricultural education, Dierenwelzijn en gezondheid, publiek-private samenwerking, Diermanagement (VHL), Nederland, Animal Health & Welfare, public-private cooperation, planning, Netherlands
Abstract

Het Centre of Expertise (CoE) Agrodier richt zich op intensieve publiek-private samenwerking binnen de dierlijke productie-sector met daaraan gekoppeld een hoogwaardig en praktijkgericht onderwijsaanbod met toegepast onderzoek als middel om de kwaliteit te versterken. In het businessplan wordt eerst de positie van Agrodier in de sector toegelicht. Vervolgens wordt de betekenis en meerwaarde van het CoE Agrodier besproken. Het groeimodel en de benodigde aanpak om te komen tot een volwaardige publiek-private samenwerking wordt in het laatste deel uiteengezet.

Published
2013

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