[{"OA_type":"hybrid","page":"432-437","publisher":"Springer Nature","day":"01","_id":"18449","article_type":"original","license":"https://creativecommons.org/licenses/by/4.0/","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"has_accepted_license":"1","citation":{"ieee":"S. Schober, S. Klee, and F. Trautinger, “The role of institutional ethics committees in Austria: Report of the Commission on Ethics and Scientific Integrity of the Karl Landsteiner University of Health Sciences 2018–2023,” <i>Wiener Klinische Wochenschrift</i>, vol. 137. Springer Nature, pp. 432–437, 2025.","chicago":"Schober, Sophie, Sascha Klee, and Franz Trautinger. “The Role of Institutional Ethics Committees in Austria: Report of the Commission on Ethics and Scientific Integrity of the Karl Landsteiner University of Health Sciences 2018–2023.” <i>Wiener Klinische Wochenschrift</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1007/s00508-024-02462-x\">https://doi.org/10.1007/s00508-024-02462-x</a>.","apa":"Schober, S., Klee, S., &#38; Trautinger, F. (2025). The role of institutional ethics committees in Austria: Report of the Commission on Ethics and Scientific Integrity of the Karl Landsteiner University of Health Sciences 2018–2023. <i>Wiener Klinische Wochenschrift</i>. Springer Nature. <a href=\"https://doi.org/10.1007/s00508-024-02462-x\">https://doi.org/10.1007/s00508-024-02462-x</a>","ista":"Schober S, Klee S, Trautinger F. 2025. The role of institutional ethics committees in Austria: Report of the Commission on Ethics and Scientific Integrity of the Karl Landsteiner University of Health Sciences 2018–2023. Wiener Klinische Wochenschrift. 137, 432–437.","mla":"Schober, Sophie, et al. “The Role of Institutional Ethics Committees in Austria: Report of the Commission on Ethics and Scientific Integrity of the Karl Landsteiner University of Health Sciences 2018–2023.” <i>Wiener Klinische Wochenschrift</i>, vol. 137, Springer Nature, 2025, pp. 432–37, doi:<a href=\"https://doi.org/10.1007/s00508-024-02462-x\">10.1007/s00508-024-02462-x</a>.","ama":"Schober S, Klee S, Trautinger F. The role of institutional ethics committees in Austria: Report of the Commission on Ethics and Scientific Integrity of the Karl Landsteiner University of Health Sciences 2018–2023. <i>Wiener Klinische Wochenschrift</i>. 2025;137:432-437. doi:<a href=\"https://doi.org/10.1007/s00508-024-02462-x\">10.1007/s00508-024-02462-x</a>","short":"S. Schober, S. Klee, F. Trautinger, Wiener Klinische Wochenschrift 137 (2025) 432–437."},"language":[{"iso":"eng"}],"abstract":[{"text":"Research involving human subjects or identifiable human material and data must be assessed by an ethics committee. The Karl Landsteiner University of Health Sciences has established a Commission on Ethics and Scientific Integrity to evaluate medical research conducted by its faculty and students and at its affiliated hospitals.\r\nAll projects submitted to the Commission on Ethics and Scientific Integrity between 2018 and 2023 were analyzed regarding their major characteristics, the duration of the evaluation process, and votes issued.\r\nA total of 520 applications were electronically submitted during the observation period. Most of the studies were retrospective data analyses in the field of oncology, psychology and surgery. Most studies included less than 100 volunteers. Of the applications 50% received a final vote within 5 months, during which several revision rounds took place. Overall, about 77% of votes issued during the observation period were positive and 2% were rejections. In 11% files were closed due to withdrawal. In 11% final votes were pending at the end of the observation period due to requests for revisions.\r\nOur results emphasize the importance of institutional ethics committees using the example of the Commission on Ethics and Scientific Integrity at the Karl Landsteiner University. Such committees fill a gap in evaluating research not covered by Austrian legal regulations. Continuous development of standards, operating procedures, and national and international collaborations are required to assess and minimize risks to trial subjects and to provide a safe and productive environment for research in human medicine and related fields.","lang":"eng"}],"PlanS_conform":"1","date_updated":"2025-12-30T06:55:59Z","type":"journal_article","volume":137,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa":1,"date_published":"2025-07-01T00:00:00Z","corr_author":"1","department":[{"_id":"PreCl"}],"publication_status":"published","intvolume":"       137","publication_identifier":{"issn":["0043-5325"],"eissn":["1613-7671"]},"author":[{"id":"80b0a0ef-4b9f-11ec-b119-8d9d94c4a1d8","full_name":"Schober, Sophie","first_name":"Sophie","last_name":"Schober"},{"first_name":"Sascha","last_name":"Klee","full_name":"Klee, Sascha"},{"first_name":"Franz","last_name":"Trautinger","full_name":"Trautinger, Franz"}],"date_created":"2024-10-20T22:02:07Z","isi":1,"month":"07","status":"public","year":"2025","quality_controlled":"1","title":"The role of institutional ethics committees in Austria: Report of the Commission on Ethics and Scientific Integrity of the Karl Landsteiner University of Health Sciences 2018–2023","scopus_import":"1","ddc":["570"],"external_id":{"isi":["001329812000001"]},"oa_version":"Published Version","doi":"10.1007/s00508-024-02462-x","file_date_updated":"2025-12-30T06:54:03Z","file":[{"relation":"main_file","date_updated":"2025-12-30T06:54:03Z","date_created":"2025-12-30T06:54:03Z","file_name":"2025_WrKlinischeWochenschrift_Schober.pdf","access_level":"open_access","file_size":580791,"checksum":"321be8a584117feaea9f3feaa28caabd","success":1,"creator":"dernst","content_type":"application/pdf","file_id":"20880"}],"OA_place":"publisher","publication":"Wiener Klinische Wochenschrift","acknowledgement":"Open access funding provided by Karl Landsteiner University.","article_processing_charge":"Yes (via OA deal)"},{"corr_author":"1","ec_funded":1,"date_published":"2025-03-01T00:00:00Z","main_file_link":[{"url":"https://doi.org/10.1038/s41593-025-01874-w","open_access":"1"}],"publication_status":"published","department":[{"_id":"MaJö"},{"_id":"PreCl"}],"date_created":"2025-02-23T23:01:58Z","isi":1,"author":[{"id":"2E7C4E78-F248-11E8-B48F-1D18A9856A87","full_name":"Vega Zuniga, Tomas A","first_name":"Tomas A","last_name":"Vega Zuniga"},{"last_name":"Sumser","first_name":"Anton L","id":"3320A096-F248-11E8-B48F-1D18A9856A87","full_name":"Sumser, Anton L","orcid":"0000-0002-4792-1881"},{"orcid":"0000-0003-2012-9947","full_name":"Symonova, Olga","id":"3C0C7BC6-F248-11E8-B48F-1D18A9856A87","first_name":"Olga","last_name":"Symonova"},{"first_name":"Peter","last_name":"Koppensteiner","orcid":"0000-0002-3509-1948","full_name":"Koppensteiner, Peter","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Schmidt, Florian","id":"A2EF226A-AF19-11E9-924C-0525E6697425","first_name":"Florian","last_name":"Schmidt"},{"last_name":"Jösch","first_name":"Maximilian A","full_name":"Jösch, Maximilian A","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3937-1330"}],"intvolume":"        28","publication_identifier":{"issn":["1097-6256"],"eissn":["1546-1726"]},"year":"2025","status":"public","month":"03","scopus_import":"1","title":"A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics","quality_controlled":"1","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"Bio"}],"OA_place":"publisher","doi":"10.1038/s41593-025-01874-w","oa_version":"Published Version","external_id":{"isi":["001416866800001"],"pmid":["39930095"]},"acknowledgement":"We thank Y. Ben-Simon for generously making viral vectors for retrograde tracing available, as well as J. Watson and F. Marr for reagents. We also thank R. Shigemoto, W. Młynarski and members of the Neuroethology group for their comments on the manuscript and L. Burnett for her schematic drawings. This research was supported by the Scientific Service Units of ISTA through resources provided by Scientific Computing, the Preclinical Facility, the Lab Support Facility and the Imaging and Optics Facility, in particular F. Lange, M. Schunn and T. Asenov. This work was supported by European Research Council Starting Grant no. 756502 (M.J.) and European Research Council Consolidator Grant no. 101086580 (M.J.); and EMBO ALTF grant no. 1098-2017 (A.S.) and Human Frontiers Science Program grant no. LT000256/2018-L (A.S.). Open access funding provided by Institute of Science and Technology (IST Austria).","pmid":1,"publication":"Nature Neuroscience","article_processing_charge":"Yes (via OA deal)","OA_type":"hybrid","publisher":"Springer Nature","day":"01","related_material":{"link":[{"relation":"press_release","url":"https://ista.ac.at/en/news/high-tech-video-optimization-in-our-brain/","description":"News on ISTA Website"}],"record":[{"id":"18579","status":"public","relation":"research_data"}]},"_id":"19076","article_type":"original","article_number":"7278","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"has_accepted_license":"1","citation":{"ama":"Vega Zuniga TA, Sumser AL, Symonova O, Koppensteiner P, Schmidt F, Jösch MA. A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics. <i>Nature Neuroscience</i>. 2025;28. doi:<a href=\"https://doi.org/10.1038/s41593-025-01874-w\">10.1038/s41593-025-01874-w</a>","short":"T.A. Vega Zuniga, A.L. Sumser, O. Symonova, P. Koppensteiner, F. Schmidt, M.A. Jösch, Nature Neuroscience 28 (2025).","mla":"Vega Zuniga, Tomas A., et al. “A Thalamic Hub-and-Spoke Network Enables Visual Perception during Action by Coordinating Visuomotor Dynamics.” <i>Nature Neuroscience</i>, vol. 28, 7278, Springer Nature, 2025, doi:<a href=\"https://doi.org/10.1038/s41593-025-01874-w\">10.1038/s41593-025-01874-w</a>.","ista":"Vega Zuniga TA, Sumser AL, Symonova O, Koppensteiner P, Schmidt F, Jösch MA. 2025. A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics. Nature Neuroscience. 28, 7278.","ieee":"T. A. Vega Zuniga, A. L. Sumser, O. Symonova, P. Koppensteiner, F. Schmidt, and M. A. Jösch, “A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics,” <i>Nature Neuroscience</i>, vol. 28. Springer Nature, 2025.","chicago":"Vega Zuniga, Tomas A, Anton L Sumser, Olga Symonova, Peter Koppensteiner, Florian Schmidt, and Maximilian A Jösch. “A Thalamic Hub-and-Spoke Network Enables Visual Perception during Action by Coordinating Visuomotor Dynamics.” <i>Nature Neuroscience</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1038/s41593-025-01874-w\">https://doi.org/10.1038/s41593-025-01874-w</a>.","apa":"Vega Zuniga, T. A., Sumser, A. L., Symonova, O., Koppensteiner, P., Schmidt, F., &#38; Jösch, M. A. (2025). A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics. <i>Nature Neuroscience</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41593-025-01874-w\">https://doi.org/10.1038/s41593-025-01874-w</a>"},"date_updated":"2025-09-30T10:40:49Z","abstract":[{"lang":"eng","text":"For accurate perception and motor control, an animal must distinguish between sensory experiences elicited by external stimuli and those elicited by its own actions. The diversity of behaviors and their complex influences on the senses make this distinction challenging. Here, we uncover an action–cue hub that coordinates motor commands with visual processing in the brain’s first visual relay. We show that the ventral lateral geniculate nucleus (vLGN) acts as a corollary discharge center, integrating visual translational optic flow signals with motor copies from saccades, locomotion and pupil dynamics. The vLGN relays these signals to correct action-specific visual distortions and to refine perception, as shown for the superior colliculus and in a depth-estimation task. Simultaneously, brain-wide vLGN projections drive corrective actions necessary for accurate visuomotor control. Our results reveal an extended corollary discharge architecture that refines early visual transformations and coordinates actions via a distributed hub-and-spoke network to enable visual perception during action."}],"language":[{"iso":"eng"}],"oa":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","project":[{"grant_number":"756502","_id":"2634E9D2-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Circuits of Visual Attention"},{"name":"Action Selection in the Midbrain: Neuromodulation of Visuomotor Senses","grant_number":"101086580","_id":"bdaf81a8-d553-11ed-ba76-c95961984540"},{"name":"Connecting sensory with motor processing in the superior colliculus","_id":"264FEA02-B435-11E9-9278-68D0E5697425","grant_number":"ALTF 1098-2017"},{"_id":"266D407A-B435-11E9-9278-68D0E5697425","grant_number":"LT000256","name":"Neuronal networks of salience and spatial detection in the murine superior colliculus"}],"volume":28,"type":"journal_article"},{"citation":{"ista":"Rica R, Klein K, Johnson L, Carta G, Sarcevic M, Langer F, Rademacher C, Wawrzinek R, Quattrone F, Sparber F. Langerhans cell-targeted protein delivery enhances antigen-specific cellular immune response. Molecular Therapy.","chicago":"Rica, Ramona, Klara Klein, Litty Johnson, Gabriele Carta, Mirza Sarcevic, Freyja Langer, Christoph Rademacher, Robert Wawrzinek, Federica Quattrone, and Florian Sparber. “Langerhans Cell-Targeted Protein Delivery Enhances Antigen-Specific Cellular Immune Response.” <i>Molecular Therapy</i>. Elsevier, n.d. <a href=\"https://doi.org/10.1016/j.ymthe.2025.10.008\">https://doi.org/10.1016/j.ymthe.2025.10.008</a>.","ieee":"R. Rica <i>et al.</i>, “Langerhans cell-targeted protein delivery enhances antigen-specific cellular immune response,” <i>Molecular Therapy</i>. Elsevier.","apa":"Rica, R., Klein, K., Johnson, L., Carta, G., Sarcevic, M., Langer, F., … Sparber, F. (n.d.). Langerhans cell-targeted protein delivery enhances antigen-specific cellular immune response. <i>Molecular Therapy</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.ymthe.2025.10.008\">https://doi.org/10.1016/j.ymthe.2025.10.008</a>","ama":"Rica R, Klein K, Johnson L, et al. Langerhans cell-targeted protein delivery enhances antigen-specific cellular immune response. <i>Molecular Therapy</i>. doi:<a href=\"https://doi.org/10.1016/j.ymthe.2025.10.008\">10.1016/j.ymthe.2025.10.008</a>","short":"R. Rica, K. Klein, L. Johnson, G. Carta, M. Sarcevic, F. Langer, C. Rademacher, R. Wawrzinek, F. Quattrone, F. Sparber, Molecular Therapy (n.d.).","mla":"Rica, Ramona, et al. “Langerhans Cell-Targeted Protein Delivery Enhances Antigen-Specific Cellular Immune Response.” <i>Molecular Therapy</i>, Elsevier, doi:<a href=\"https://doi.org/10.1016/j.ymthe.2025.10.008\">10.1016/j.ymthe.2025.10.008</a>."},"type":"journal_article","oa":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"lang":"eng","text":"Targeted antigen delivery to immune cells, particularly dendritic cells, has emerged as a promising strategy to enhance therapeutic efficacy of vaccines, while minimizing adverse effects associated with conventional immunization. In this study, we use our previously described small glycomimetic molecule that is selectively recognized by the Langerhans cell (LC)-specific surface receptor Langerin and demonstrate specific delivery of protein antigens to these specialized dendritic cells. Our results show that Langerin-mediated antigen delivery significantly enhances the immune response in vivo, resulting in increased expansion and activation of antigen-specific T cells, compared to immunization with unmodified antigen. We demonstrate the feasibility of our LC-targeted platform for immune cell-specific immunization with protein antigen and underscore the potential of LCs as an access point for next-generation vaccines and immunotherapies."}],"language":[{"iso":"eng"}],"date_updated":"2025-12-29T09:55:05Z","OA_type":"green","_id":"20858","article_type":"original","publisher":"Elsevier","day":"04","doi":"10.1016/j.ymthe.2025.10.008","oa_version":"Preprint","OA_place":"repository","title":"Langerhans cell-targeted protein delivery enhances antigen-specific cellular immune response","quality_controlled":"1","scopus_import":"1","article_processing_charge":"No","publication":"Molecular Therapy","acknowledgement":"This project was generously supported by Seedfinancing (grant no. P2282679) of the Austrian Bundesministerium für Digitalisierung und Wirtschaftsstandort and the Bundesministerium für Klimaschutz, Umwelt, Energie, Mobilität, Innovation, und Technologie, handled by the Austrian Wirtschaftsservice (aws), as well as by Life Science Call 2022 (grant no. FO999896442) of the Austrian Research Promotion Agency (FFG). We thank Mag. Michael Schunn from the PCF of the Institute of Science and Technology Austria for his continuous technical support.","department":[{"_id":"PreCl"}],"publication_status":"inpress","date_published":"2025-10-04T00:00:00Z","main_file_link":[{"url":"https://doi.org/10.1101/2025.05.05.652195","open_access":"1"}],"status":"public","month":"10","year":"2025","author":[{"last_name":"Rica","first_name":"Ramona","full_name":"Rica, Ramona"},{"last_name":"Klein","first_name":"Klara","full_name":"Klein, Klara"},{"first_name":"Litty","last_name":"Johnson","full_name":"Johnson, Litty"},{"full_name":"Carta, Gabriele","last_name":"Carta","first_name":"Gabriele"},{"first_name":"Mirza","last_name":"Sarcevic","full_name":"Sarcevic, Mirza"},{"first_name":"Freyja","last_name":"Langer","full_name":"Langer, Freyja","id":"3C1BE782-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Christoph","last_name":"Rademacher","full_name":"Rademacher, Christoph"},{"full_name":"Wawrzinek, Robert","first_name":"Robert","last_name":"Wawrzinek"},{"full_name":"Quattrone, Federica","first_name":"Federica","last_name":"Quattrone"},{"full_name":"Sparber, Florian","first_name":"Florian","last_name":"Sparber"}],"publication_identifier":{"eissn":["1525-0024"],"issn":["1525-0016"]},"date_created":"2025-12-28T23:01:26Z"},{"date_created":"2024-10-13T22:01:51Z","isi":1,"author":[{"first_name":"Maria","last_name":"Kitsara","full_name":"Kitsara, Maria"},{"full_name":"Smajlhodžić-Deljo, Merima","first_name":"Merima","last_name":"Smajlhodžić-Deljo"},{"first_name":"Lejla","last_name":"Gurbeta Pokvic","full_name":"Gurbeta Pokvic, Lejla"},{"first_name":"Bettina","last_name":"Bert","full_name":"Bert, Bettina"},{"full_name":"Bubalo, Nataliia","last_name":"Bubalo","first_name":"Nataliia"},{"full_name":"Erden, Sevilay","last_name":"Erden","first_name":"Sevilay"},{"full_name":"Franco, Nuno Henrique","first_name":"Nuno Henrique","last_name":"Franco"},{"first_name":"Giuseppe","last_name":"Chirico","full_name":"Chirico, Giuseppe"},{"full_name":"Gómez Raja, Jonathan","last_name":"Gómez Raja","first_name":"Jonathan"},{"full_name":"Gonzalez-Uarquin, Fernando","last_name":"Gonzalez-Uarquin","first_name":"Fernando"},{"full_name":"Lang, Annemarie","first_name":"Annemarie","last_name":"Lang"},{"full_name":"Linklater, Nicole","first_name":"Nicole","last_name":"Linklater"},{"full_name":"Mojsova, Sandra","last_name":"Mojsova","first_name":"Sandra"},{"full_name":"Olsson, I. Anna S.","first_name":"I. Anna S.","last_name":"Olsson"},{"full_name":"Sandvig, Ioanna","last_name":"Sandvig","first_name":"Ioanna"},{"full_name":"Schaffert, Alexandra","last_name":"Schaffert","first_name":"Alexandra"},{"full_name":"Schmit, Marthe","first_name":"Marthe","last_name":"Schmit"},{"last_name":"Schober","first_name":"Sophie","id":"80b0a0ef-4b9f-11ec-b119-8d9d94c4a1d8","full_name":"Schober, Sophie"},{"full_name":"Sevastre, Bogdan","last_name":"Sevastre","first_name":"Bogdan"},{"full_name":"Wilflingseder, Doris","last_name":"Wilflingseder","first_name":"Doris"},{"full_name":"Ahluwalia, Arti","first_name":"Arti","last_name":"Ahluwalia"},{"last_name":"Neuhaus","first_name":"Winfried","full_name":"Neuhaus, Winfried"}],"intvolume":"        52","publication_identifier":{"eissn":["2632-3559"],"issn":["0261-1929"]},"year":"2024","status":"public","month":"11","date_published":"2024-11-01T00:00:00Z","publication_status":"published","department":[{"_id":"PreCl"}],"publication":"Alternatives to Laboratory Animals","pmid":1,"article_processing_charge":"No","scopus_import":"1","title":"Introducing the COST action ‘Improving the Quality of Biomedical Science with 3Rs Concepts’ (IMPROVE)","quality_controlled":"1","external_id":{"isi":["001348633700007"],"pmid":["39333027"]},"doi":"10.1177/02611929241286024","oa_version":"None","publisher":"SAGE Publications","day":"01","_id":"18310","article_type":"original","OA_type":"closed access","page":"326-333","date_updated":"2025-09-08T09:56:39Z","language":[{"iso":"eng"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","type":"journal_article","volume":52,"issue":"6","citation":{"ama":"Kitsara M, Smajlhodžić-Deljo M, Gurbeta Pokvic L, et al. Introducing the COST action ‘Improving the Quality of Biomedical Science with 3Rs Concepts’ (IMPROVE). <i>Alternatives to Laboratory Animals</i>. 2024;52(6):326-333. doi:<a href=\"https://doi.org/10.1177/02611929241286024\">10.1177/02611929241286024</a>","short":"M. Kitsara, M. Smajlhodžić-Deljo, L. Gurbeta Pokvic, B. Bert, N. Bubalo, S. Erden, N.H. Franco, G. Chirico, J. Gómez Raja, F. Gonzalez-Uarquin, A. Lang, N. Linklater, S. Mojsova, I.A.S. Olsson, I. Sandvig, A. Schaffert, M. Schmit, S. Schober, B. Sevastre, D. Wilflingseder, A. Ahluwalia, W. Neuhaus, Alternatives to Laboratory Animals 52 (2024) 326–333.","mla":"Kitsara, Maria, et al. “Introducing the COST Action ‘Improving the Quality of Biomedical Science with 3Rs Concepts’ (IMPROVE).” <i>Alternatives to Laboratory Animals</i>, vol. 52, no. 6, SAGE Publications, 2024, pp. 326–33, doi:<a href=\"https://doi.org/10.1177/02611929241286024\">10.1177/02611929241286024</a>.","ista":"Kitsara M, Smajlhodžić-Deljo M, Gurbeta Pokvic L, Bert B, Bubalo N, Erden S, Franco NH, Chirico G, Gómez Raja J, Gonzalez-Uarquin F, Lang A, Linklater N, Mojsova S, Olsson IAS, Sandvig I, Schaffert A, Schmit M, Schober S, Sevastre B, Wilflingseder D, Ahluwalia A, Neuhaus W. 2024. Introducing the COST action ‘Improving the Quality of Biomedical Science with 3Rs Concepts’ (IMPROVE). Alternatives to Laboratory Animals. 52(6), 326–333.","chicago":"Kitsara, Maria, Merima Smajlhodžić-Deljo, Lejla Gurbeta Pokvic, Bettina Bert, Nataliia Bubalo, Sevilay Erden, Nuno Henrique Franco, et al. “Introducing the COST Action ‘Improving the Quality of Biomedical Science with 3Rs Concepts’ (IMPROVE).” <i>Alternatives to Laboratory Animals</i>. SAGE Publications, 2024. <a href=\"https://doi.org/10.1177/02611929241286024\">https://doi.org/10.1177/02611929241286024</a>.","ieee":"M. Kitsara <i>et al.</i>, “Introducing the COST action ‘Improving the Quality of Biomedical Science with 3Rs Concepts’ (IMPROVE),” <i>Alternatives to Laboratory Animals</i>, vol. 52, no. 6. SAGE Publications, pp. 326–333, 2024.","apa":"Kitsara, M., Smajlhodžić-Deljo, M., Gurbeta Pokvic, L., Bert, B., Bubalo, N., Erden, S., … Neuhaus, W. (2024). Introducing the COST action ‘Improving the Quality of Biomedical Science with 3Rs Concepts’ (IMPROVE). <i>Alternatives to Laboratory Animals</i>. SAGE Publications. <a href=\"https://doi.org/10.1177/02611929241286024\">https://doi.org/10.1177/02611929241286024</a>"}},{"OA_type":"hybrid","page":"347-350","day":"01","publisher":"Springer Nature","article_type":"letter_note","_id":"18587","has_accepted_license":"1","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"citation":{"mla":"Lauwereyns, Jan, et al. “Toward a Common Interpretation of the 3Rs Principles in Animal Research.” <i>Lab Animal</i>, vol. 53, Springer Nature, 2024, pp. 347–50, doi:<a href=\"https://doi.org/10.1038/s41684-024-01476-2\">10.1038/s41684-024-01476-2</a>.","short":"J. Lauwereyns, J. Bajramovic, B. Bert, S. Camenzind, J. De Kock, A. Elezović, S. Erden, F. Gonzalez-Uarquin, Y.I. Ulman, O.I. Hoffmann, M. Kitsara, N. Kostomitsopoulos, W. Neuhaus, B. Petit-Demouliere, S. Pollo, B. Riso, S. Schober, A. Sotiropoulos, A. Thomas, A. Vitale, D. Wilflingseder, A. Ahluwalia, Lab Animal 53 (2024) 347–350.","ama":"Lauwereyns J, Bajramovic J, Bert B, et al. Toward a common interpretation of the 3Rs principles in animal research. <i>Lab Animal</i>. 2024;53:347-350. doi:<a href=\"https://doi.org/10.1038/s41684-024-01476-2\">10.1038/s41684-024-01476-2</a>","apa":"Lauwereyns, J., Bajramovic, J., Bert, B., Camenzind, S., De Kock, J., Elezović, A., … Ahluwalia, A. (2024). Toward a common interpretation of the 3Rs principles in animal research. <i>Lab Animal</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41684-024-01476-2\">https://doi.org/10.1038/s41684-024-01476-2</a>","chicago":"Lauwereyns, Jan, Jeffrey Bajramovic, Bettina Bert, Samuel Camenzind, Joery De Kock, Alisa Elezović, Sevilay Erden, et al. “Toward a Common Interpretation of the 3Rs Principles in Animal Research.” <i>Lab Animal</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41684-024-01476-2\">https://doi.org/10.1038/s41684-024-01476-2</a>.","ieee":"J. Lauwereyns <i>et al.</i>, “Toward a common interpretation of the 3Rs principles in animal research,” <i>Lab Animal</i>, vol. 53. Springer Nature, pp. 347–350, 2024.","ista":"Lauwereyns J, Bajramovic J, Bert B, Camenzind S, De Kock J, Elezović A, Erden S, Gonzalez-Uarquin F, Ulman YI, Hoffmann OI, Kitsara M, Kostomitsopoulos N, Neuhaus W, Petit-Demouliere B, Pollo S, Riso B, Schober S, Sotiropoulos A, Thomas A, Vitale A, Wilflingseder D, Ahluwalia A. 2024. Toward a common interpretation of the 3Rs principles in animal research. Lab Animal. 53, 347–350."},"language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"Many scientific breakthroughs have depended on animal research, yet the ethical concerns surrounding the use of animals in experimentation have long prompted discussions about humane treatment and responsible scientific practice. First articulated by Russell and Burch, the 3Rs Principles of Replacement, Reduction, and Refinement have gained widespread recognition as basic guidelines for animal research. Over time, the 3Rs have transcended the research community, influencing policy decisions, animal welfare advocacy and public perception of animal experimentation. Despite their broad acceptance, interpretations of the 3Rs vary substantially, shaping statutory frameworks at various levels, with both technical and practical impacts."}],"date_updated":"2025-09-08T14:50:31Z","type":"journal_article","volume":53,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","oa":1,"date_published":"2024-12-01T00:00:00Z","department":[{"_id":"PreCl"}],"publication_status":"published","intvolume":"        53","publication_identifier":{"issn":["0093-7355"],"eissn":["1548-4475"]},"author":[{"full_name":"Lauwereyns, Jan","first_name":"Jan","last_name":"Lauwereyns"},{"last_name":"Bajramovic","first_name":"Jeffrey","full_name":"Bajramovic, Jeffrey"},{"first_name":"Bettina","last_name":"Bert","full_name":"Bert, Bettina"},{"full_name":"Camenzind, Samuel","last_name":"Camenzind","first_name":"Samuel"},{"full_name":"De Kock, Joery","last_name":"De Kock","first_name":"Joery"},{"last_name":"Elezović","first_name":"Alisa","full_name":"Elezović, Alisa"},{"last_name":"Erden","first_name":"Sevilay","full_name":"Erden, Sevilay"},{"first_name":"Fernando","last_name":"Gonzalez-Uarquin","full_name":"Gonzalez-Uarquin, Fernando"},{"full_name":"Ulman, Yesim Isil","first_name":"Yesim Isil","last_name":"Ulman"},{"last_name":"Hoffmann","first_name":"Orsolya Ivett","full_name":"Hoffmann, Orsolya Ivett"},{"first_name":"Maria","last_name":"Kitsara","full_name":"Kitsara, Maria"},{"full_name":"Kostomitsopoulos, Nikolaos","first_name":"Nikolaos","last_name":"Kostomitsopoulos"},{"full_name":"Neuhaus, Winfried","first_name":"Winfried","last_name":"Neuhaus"},{"full_name":"Petit-Demouliere, Benoit","last_name":"Petit-Demouliere","first_name":"Benoit"},{"full_name":"Pollo, Simone","first_name":"Simone","last_name":"Pollo"},{"full_name":"Riso, Brígida","last_name":"Riso","first_name":"Brígida"},{"first_name":"Sophie","last_name":"Schober","full_name":"Schober, Sophie","id":"80b0a0ef-4b9f-11ec-b119-8d9d94c4a1d8"},{"last_name":"Sotiropoulos","first_name":"Athanassia","full_name":"Sotiropoulos, Athanassia"},{"full_name":"Thomas, Aurélie","first_name":"Aurélie","last_name":"Thomas"},{"full_name":"Vitale, Augusto","first_name":"Augusto","last_name":"Vitale"},{"full_name":"Wilflingseder, Doris","last_name":"Wilflingseder","first_name":"Doris"},{"full_name":"Ahluwalia, Arti","first_name":"Arti","last_name":"Ahluwalia"}],"date_created":"2024-11-24T23:01:49Z","isi":1,"month":"12","status":"public","year":"2024","quality_controlled":"1","title":"Toward a common interpretation of the 3Rs principles in animal research","scopus_import":"1","ddc":["570"],"file_date_updated":"2024-12-03T14:07:04Z","external_id":{"isi":["001355264100001"],"pmid":["39548348"]},"doi":"10.1038/s41684-024-01476-2","oa_version":"Published Version","OA_place":"publisher","file":[{"date_updated":"2024-12-03T14:07:04Z","date_created":"2024-12-03T14:07:04Z","access_level":"open_access","file_name":"2024_LabAnimal_Lauwereyns.pdf","checksum":"67fc140f761581a291591f075e49b88d","success":1,"file_size":967252,"content_type":"application/pdf","creator":"dernst","file_id":"18614","relation":"main_file"}],"publication":"Lab Animal","pmid":1,"acknowledgement":"This publication is based upon work from the Ethics Crossover Group within the COST Action IMPROVE (“3Rs concepts to improve the quality of biomedical science”), CA21139, supported by COST (European Cooperation in Science and Technology). We acknowledge the input and advice from Dr. Susanna Louhimies.","article_processing_charge":"No"},{"ddc":["610"],"oa_version":"Published Version","external_id":{"pmid":["38621845"],"isi":["001219145400001"]},"doi":"10.1016/j.medengphy.2024.104143","file_date_updated":"2024-03-25T08:29:52Z","file":[{"relation":"main_file","file_name":"2024_MedEngineeringPhysics_SilvaHenao.pdf","access_level":"open_access","date_created":"2024-03-25T08:29:52Z","date_updated":"2024-03-25T08:29:52Z","creator":"dernst","file_id":"15177","content_type":"application/pdf","file_size":10039402,"checksum":"974acbf2731e7382dcf5920ac762e551","success":1}],"quality_controlled":"1","title":"Critical loss of primary implant stability in osteosynthesis locking screws under cyclic overloading","scopus_import":"1","article_processing_charge":"Yes (in subscription journal)","pmid":1,"publication":"Medical Engineering and Physics","acknowledgement":"The authors declare no conflict of interest related to this study. This project was funded by the Gesellschaft fuer Forschungsfoerderung Niederoesterreich m.b.H. Life Science Call 2017 Grant No. LS17004 and Science call 2019 Dissertationen Grant No. SC19014. No ethical approval was required for this study.","department":[{"_id":"PreCl"}],"publication_status":"published","date_published":"2024-04-01T00:00:00Z","month":"04","status":"public","year":"2024","publication_identifier":{"issn":["1350-4533"],"eissn":["1873-4030"]},"intvolume":"       126","author":[{"last_name":"Silva-Henao","first_name":"Juan D.","full_name":"Silva-Henao, Juan D."},{"last_name":"Schober","first_name":"Sophie","full_name":"Schober, Sophie","id":"80b0a0ef-4b9f-11ec-b119-8d9d94c4a1d8"},{"full_name":"Pahr, Dieter H.","last_name":"Pahr","first_name":"Dieter H."},{"first_name":"Andreas G.","last_name":"Reisinger","full_name":"Reisinger, Andreas G."}],"date_created":"2024-03-24T23:00:58Z","isi":1,"citation":{"mla":"Silva-Henao, Juan D., et al. “Critical Loss of Primary Implant Stability in Osteosynthesis Locking Screws under Cyclic Overloading.” <i>Medical Engineering and Physics</i>, vol. 126, 104143, Elsevier, 2024, doi:<a href=\"https://doi.org/10.1016/j.medengphy.2024.104143\">10.1016/j.medengphy.2024.104143</a>.","ama":"Silva-Henao JD, Schober S, Pahr DH, Reisinger AG. Critical loss of primary implant stability in osteosynthesis locking screws under cyclic overloading. <i>Medical Engineering and Physics</i>. 2024;126. doi:<a href=\"https://doi.org/10.1016/j.medengphy.2024.104143\">10.1016/j.medengphy.2024.104143</a>","short":"J.D. Silva-Henao, S. Schober, D.H. Pahr, A.G. Reisinger, Medical Engineering and Physics 126 (2024).","ieee":"J. D. Silva-Henao, S. Schober, D. H. Pahr, and A. G. Reisinger, “Critical loss of primary implant stability in osteosynthesis locking screws under cyclic overloading,” <i>Medical Engineering and Physics</i>, vol. 126. Elsevier, 2024.","chicago":"Silva-Henao, Juan D., Sophie Schober, Dieter H. Pahr, and Andreas G. Reisinger. “Critical Loss of Primary Implant Stability in Osteosynthesis Locking Screws under Cyclic Overloading.” <i>Medical Engineering and Physics</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.medengphy.2024.104143\">https://doi.org/10.1016/j.medengphy.2024.104143</a>.","apa":"Silva-Henao, J. D., Schober, S., Pahr, D. H., &#38; Reisinger, A. G. (2024). Critical loss of primary implant stability in osteosynthesis locking screws under cyclic overloading. <i>Medical Engineering and Physics</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.medengphy.2024.104143\">https://doi.org/10.1016/j.medengphy.2024.104143</a>","ista":"Silva-Henao JD, Schober S, Pahr DH, Reisinger AG. 2024. Critical loss of primary implant stability in osteosynthesis locking screws under cyclic overloading. Medical Engineering and Physics. 126, 104143."},"has_accepted_license":"1","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"article_number":"104143","volume":126,"type":"journal_article","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","oa":1,"language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"Primary implant stability, which refers to the stability of the implant during the initial healing period is a crucial factor in determining the long-term success of the implant and lays the foundation for secondary implant stability achieved through osseointegration. Factors affecting primary stability include implant design, surgical technique, and patient-specific factors like bone quality and morphology. In vivo, the cyclic nature of anatomical loading puts osteosynthesis locking screws under dynamic loads, which can lead to the formation of micro cracks and defects that slowly degrade the mechanical connection between the bone and screw, thus compromising the initial stability and secondary stability of the implant. Monotonic quasi-static loading used for testing the holding capacity of implanted screws is not well suited to capture this behavior since it cannot capture the progressive deterioration of peri‑implant bone at small displacements. In order to address this issue, this study aims to determine a critical point of loss of primary implant stability in osteosynthesis locking screws under cyclic overloading by investigating the evolution of damage, dissipated energy, and permanent deformation. A custom-made test setup was used to test implanted 2.5 mm locking screws under cyclic overloading test. For each loading cycle, maximum forces and displacement were recorded as well as initial and final cycle displacements and used to calculate damage and energy dissipation evolution. The results of this study demonstrate that for axial, shear, and mixed loading significant damage and energy dissipation can be observed at approximately 20 % of the failure force. Additionally, at this load level, permanent deformations on the screw-bone interface were found to be in the range of 50 to 150 mm which promotes osseointegration and secondary implant stability. This research can assist surgeons in making informed preoperative decisions by providing a better understanding of the critical point of loss of primary implant stability, thus improving the long-term success of the implant and overall patient satisfaction."}],"date_updated":"2025-09-04T13:11:03Z","article_type":"original","_id":"15164","day":"01","publisher":"Elsevier"},{"_id":"15385","related_material":{"record":[{"relation":"used_in_publication","status":"public","id":"17142"}]},"publisher":"Institute of Science and Technology Austria","day":"15","citation":{"ieee":"L. Burnett <i>et al.</i>, “Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice.” Institute of Science and Technology Austria, 2024.","chicago":"Burnett, Laura, Peter Koppensteiner, Olga Symonova, Tomas Masson, Tomas A Vega Zuniga, Ximena Contreras, Thomas Rülicke, Ryuichi Shigemoto, Gaia Novarino, and Maximilian A Jösch. “Shared Behavioural Impairments in Visual Perception and Place Avoidance across Different Autism Models Are Driven by Periaqueductal Grey Hypoexcitability in Setd5 Haploinsufficient Mice.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/AT:ISTA:15385\">https://doi.org/10.15479/AT:ISTA:15385</a>.","apa":"Burnett, L., Koppensteiner, P., Symonova, O., Masson, T., Vega Zuniga, T. A., Contreras, X., … Jösch, M. A. (2024). Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:15385\">https://doi.org/10.15479/AT:ISTA:15385</a>","ista":"Burnett L, Koppensteiner P, Symonova O, Masson T, Vega Zuniga TA, Contreras X, Rülicke T, Shigemoto R, Novarino G, Jösch MA. 2024. Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:15385\">10.15479/AT:ISTA:15385</a>.","mla":"Burnett, Laura, et al. <i>Shared Behavioural Impairments in Visual Perception and Place Avoidance across Different Autism Models Are Driven by Periaqueductal Grey Hypoexcitability in Setd5 Haploinsufficient Mice</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:15385\">10.15479/AT:ISTA:15385</a>.","ama":"Burnett L, Koppensteiner P, Symonova O, et al. Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice. 2024. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:15385\">10.15479/AT:ISTA:15385</a>","short":"L. Burnett, P. Koppensteiner, O. Symonova, T. Masson, T.A. Vega Zuniga, X. Contreras, T. Rülicke, R. Shigemoto, G. Novarino, M.A. Jösch, (2024)."},"tmp":{"image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)"},"license":"https://creativecommons.org/licenses/by-nc/4.0/","has_accepted_license":"1","keyword":["ASD","periaqueductal gray","perception","behavior","potassium channels"],"type":"research_data","oa":1,"user_id":"68b8ca59-c5b3-11ee-8790-cd641c68093d","abstract":[{"text":"Relevant information about the data can be found in the 'Readme_Data.txt' file. \r\nA previous version of the publication can be found on BioRxiv: https://www.biorxiv.org/content/10.1101/2022.10.11.511691v4\r\nand published in Plos Biology (2024)","lang":"eng"}],"date_updated":"2025-09-08T07:57:11Z","department":[{"_id":"MaJö"},{"_id":"PreCl"},{"_id":"SiHi"},{"_id":"RySh"},{"_id":"GaNo"}],"date_published":"2024-05-15T00:00:00Z","corr_author":"1","status":"public","month":"05","year":"2024","author":[{"first_name":"Laura","last_name":"Burnett","orcid":"0000-0002-8937-410X","full_name":"Burnett, Laura","id":"3B717F68-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Koppensteiner, Peter","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3509-1948","last_name":"Koppensteiner","first_name":"Peter"},{"first_name":"Olga","last_name":"Symonova","orcid":"0000-0003-2012-9947","full_name":"Symonova, Olga","id":"3C0C7BC6-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Masson","first_name":"Tomas","id":"93ac43e8-8599-11eb-9b86-f6efb0a4c207","full_name":"Masson, Tomas","orcid":"0000-0002-2634-6283"},{"id":"2E7C4E78-F248-11E8-B48F-1D18A9856A87","full_name":"Vega Zuniga, Tomas A","last_name":"Vega Zuniga","first_name":"Tomas A"},{"full_name":"Contreras, Ximena","id":"475990FE-F248-11E8-B48F-1D18A9856A87","first_name":"Ximena","last_name":"Contreras"},{"full_name":"Rülicke, Thomas","first_name":"Thomas","last_name":"Rülicke"},{"first_name":"Ryuichi","last_name":"Shigemoto","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","last_name":"Novarino","first_name":"Gaia"},{"id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","full_name":"Jösch, Maximilian A","orcid":"0000-0002-3937-1330","last_name":"Jösch","first_name":"Maximilian A"}],"date_created":"2024-05-13T15:04:04Z","file_date_updated":"2024-05-16T09:08:20Z","oa_version":"Published Version","doi":"10.15479/AT:ISTA:15385","ddc":["570"],"file":[{"relation":"main_file","creator":"mjoesch","file_id":"15396","content_type":"application/zip","file_size":"1149617663","success":1,"checksum":"9205eb0876f0f08552dbad80d6884b4b","file_name":"PatchClamp.zip","access_level":"open_access","date_updated":"2024-05-15T06:09:17Z","date_created":"2024-05-15T06:09:17Z"},{"relation":"main_file","creator":"mjoesch","content_type":"application/zip","file_id":"15397","success":1,"file_size":"564903112","access_level":"open_access","file_name":"SiliconProbe.zip","date_created":"2024-05-15T06:09:12Z","date_updated":"2024-05-15T06:09:12Z"},{"date_updated":"2024-05-15T06:09:14Z","date_created":"2024-05-15T06:09:14Z","file_name":"WesternBlot.zip","access_level":"open_access","file_size":"11685703","success":1,"checksum":"49a807bbab06b5fada38f532e2176e2e","content_type":"application/zip","creator":"mjoesch","file_id":"15398","relation":"main_file"},{"relation":"main_file","access_level":"open_access","file_name":"Behaviour.zip","date_updated":"2024-05-15T06:09:38Z","date_created":"2024-05-15T06:09:38Z","creator":"mjoesch","file_id":"15399","content_type":"application/zip","checksum":"beeeeaa43770090f3b291209ed6b0623","success":1,"file_size":"1335626779"},{"access_level":"open_access","file_name":"Readme_Data.txt","date_updated":"2024-05-16T09:08:20Z","date_created":"2024-05-16T09:08:20Z","creator":"mjoesch","file_id":"15400","content_type":"text/plain","checksum":"8862ad7719388304d1d19f8e7db8bb00","success":1,"file_size":18841,"relation":"main_file"}],"title":"Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"M-Shop"},{"_id":"LifeSc"},{"_id":"Bio"}],"article_processing_charge":"No","acknowledgement":"We thank Armel Nicolas, Bella Bruszel and Ewelina Dutkiewicz from the ISTA Mass Spectrometry Service (Lab Services Facilities) for all Proteomics work, including samples preparation, LC/MS data acquisition, searches and data evaluation. We thank Prof. Peter Jonas for his suggestion on the involvement of potassium channels and members of the Neuroethology group for their comments on the manuscript. Katalin Szigeti and Julie Murmann for experimental help. This research was supported by the Scientific Service Units of ISTA through resources provided by the Lab Support Facility, the Imaging and Optics Facility, the Machine Shop Unit and the Preclinical Facility, especially Freyja Langer and Michael Schunn. "},{"acknowledgement":"Ajap1HA/HA and Ajap1W183C/+ mice were generated in collaboration with Pawel Pelczar at the center for transgenic models at the University of Basel, Switzerland. We thank the imaging core facility (IMCF, University of Basel) and in particular A. Ferrand for the technical assistance provided on the OMX 3D-SIM microscope.\r\nThis work was supported by a grant from the Swiss National Science Foundation (SNF) to B.B. (31003A-152970, 310030B-201291), an NIH grant to E.A. and E.H.S. (R01NS058721), DFG grants to B.F. (TRR 152 project ID 239283807, FA 332/15-1, 16-1), and grants to P.S. from AIMS-2-TRIALS, which are supported by the Innovative Medicines Initiatives from the European Commission joint undertaking under grant agreement No 777394.","pmid":1,"publication":"Science Advances","article_processing_charge":"Yes","scopus_import":"1","title":"Monoallelic de novo AJAP1 loss-of- function variants disrupt trans-synaptic control of neurotransmitter release","quality_controlled":"1","OA_place":"publisher","file":[{"relation":"main_file","date_created":"2024-07-22T06:29:27Z","date_updated":"2024-07-22T06:29:27Z","access_level":"open_access","file_name":"2024_ScienceAdv_Früh.pdf","success":1,"checksum":"9cbc4501fcd4ba1c0811fd244031422b","file_size":7241489,"creator":"dernst","file_id":"17287","content_type":"application/pdf"}],"doi":"10.1126/sciadv.adk5462","oa_version":"Published Version","external_id":{"pmid":["38985877"],"isi":["001280159000022"]},"file_date_updated":"2024-07-22T06:29:27Z","ddc":["570"],"date_created":"2024-07-21T22:01:01Z","isi":1,"author":[{"first_name":"Simon","last_name":"Früh","full_name":"Früh, Simon"},{"last_name":"Boudkkazi","first_name":"Sami","full_name":"Boudkkazi, Sami"},{"id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","full_name":"Koppensteiner, Peter","orcid":"0000-0002-3509-1948","last_name":"Koppensteiner","first_name":"Peter"},{"last_name":"Sereikaite","first_name":"Vita","full_name":"Sereikaite, Vita"},{"full_name":"Chen, Li Yuan","first_name":"Li Yuan","last_name":"Chen"},{"full_name":"Fernandez-Fernandez, Diego","first_name":"Diego","last_name":"Fernandez-Fernandez"},{"first_name":"Pascal D.","last_name":"Rem","full_name":"Rem, Pascal D."},{"full_name":"Ulrich, Daniel","first_name":"Daniel","last_name":"Ulrich"},{"full_name":"Schwenk, Jochen","last_name":"Schwenk","first_name":"Jochen"},{"full_name":"Chen, Ziyang","last_name":"Chen","first_name":"Ziyang"},{"full_name":"Monnier, Elodie Le","first_name":"Elodie Le","last_name":"Monnier"},{"full_name":"Fritzius, Thorsten","first_name":"Thorsten","last_name":"Fritzius"},{"full_name":"Innocenti, Sabrina M.","last_name":"Innocenti","first_name":"Sabrina M."},{"last_name":"Besseyrias","first_name":"Valérie","full_name":"Besseyrias, Valérie"},{"last_name":"Trovò","first_name":"Luca","full_name":"Trovò, Luca"},{"full_name":"Stawarski, Michal","first_name":"Michal","last_name":"Stawarski"},{"full_name":"Argilli, Emanuela","first_name":"Emanuela","last_name":"Argilli"},{"last_name":"Sherr","first_name":"Elliott H.","full_name":"Sherr, Elliott H."},{"first_name":"Bregje","last_name":"Van Bon","full_name":"Van Bon, Bregje"},{"full_name":"Kamsteeg, Erik Jan","last_name":"Kamsteeg","first_name":"Erik Jan"},{"full_name":"Iascone, Maria","last_name":"Iascone","first_name":"Maria"},{"full_name":"Pilotta, Alba","last_name":"Pilotta","first_name":"Alba"},{"full_name":"Cutrì, Maria R.","last_name":"Cutrì","first_name":"Maria R."},{"last_name":"Azamian","first_name":"Mahshid S.","full_name":"Azamian, Mahshid S."},{"full_name":"Hernández-García, Andrés","first_name":"Andrés","last_name":"Hernández-García"},{"last_name":"Lalani","first_name":"Seema R.","full_name":"Lalani, Seema R."},{"full_name":"Rosenfeld, Jill A.","first_name":"Jill A.","last_name":"Rosenfeld"},{"first_name":"Xiaonan","last_name":"Zhao","full_name":"Zhao, Xiaonan"},{"first_name":"Tiphanie P.","last_name":"Vogel","full_name":"Vogel, Tiphanie P."},{"last_name":"Ona","first_name":"Herda","full_name":"Ona, Herda"},{"last_name":"Scott","first_name":"Daryl A.","full_name":"Scott, Daryl A."},{"full_name":"Scheiffele, Peter","first_name":"Peter","last_name":"Scheiffele"},{"last_name":"Strømgaard","first_name":"Kristian","full_name":"Strømgaard, Kristian"},{"full_name":"Tafti, Mehdi","last_name":"Tafti","first_name":"Mehdi"},{"full_name":"Gassmann, Martin","last_name":"Gassmann","first_name":"Martin"},{"full_name":"Fakler, Bernd","last_name":"Fakler","first_name":"Bernd"},{"last_name":"Shigemoto","first_name":"Ryuichi","full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444"},{"full_name":"Bettler, Bernhard","first_name":"Bernhard","last_name":"Bettler"}],"intvolume":"        10","publication_identifier":{"eissn":["2375-2548"]},"year":"2024","status":"public","month":"07","date_published":"2024-07-12T00:00:00Z","publication_status":"published","department":[{"_id":"RySh"},{"_id":"PreCl"}],"date_updated":"2025-09-08T08:15:54Z","abstract":[{"lang":"eng","text":"Adherens junction–associated protein 1 (AJAP1) has been implicated in brain diseases; however, a pathogenic mechanism has not been identified. AJAP1 is widely expressed in neurons and binds to γ-aminobutyric acid type B receptors (GBRs), which inhibit neurotransmitter release at most synapses in the brain. Here, we show that AJAP1 is selectively expressed in dendrites and trans-synaptically recruits GBRs to presynaptic sites of neurons expressing AJAP1. We have identified several monoallelic AJAP1 variants in individuals with epilepsy and/or neurodevelopmental disorders. Specifically, we show that the variant p.(W183C) lacks binding to GBRs, resulting in the inability to recruit them. Ultrastructural analysis revealed significantly decreased presynaptic GBR levels in Ajap1−/− and Ajap1W183C/+ mice. Consequently, these mice exhibited reduced GBR-mediated presynaptic inhibition at excitatory and inhibitory synapses, along with impaired synaptic plasticity. Our study reveals that AJAP1 enables the postsynaptic neuron to regulate the level of presynaptic GBR-mediated inhibition, supporting the clinical relevance of loss-of-function AJAP1 variants."}],"language":[{"iso":"eng"}],"oa":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","volume":10,"type":"journal_article","issue":"28","article_number":"adk5462","has_accepted_license":"1","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"citation":{"mla":"Früh, Simon, et al. “Monoallelic de Novo AJAP1 Loss-of- Function Variants Disrupt Trans-Synaptic Control of Neurotransmitter Release.” <i>Science Advances</i>, vol. 10, no. 28, adk5462, American Association for the Advancement of Science, 2024, doi:<a href=\"https://doi.org/10.1126/sciadv.adk5462\">10.1126/sciadv.adk5462</a>.","short":"S. Früh, S. Boudkkazi, P. Koppensteiner, V. Sereikaite, L.Y. Chen, D. Fernandez-Fernandez, P.D. Rem, D. Ulrich, J. Schwenk, Z. Chen, E.L. Monnier, T. Fritzius, S.M. Innocenti, V. Besseyrias, L. Trovò, M. Stawarski, E. Argilli, E.H. Sherr, B. Van Bon, E.J. Kamsteeg, M. Iascone, A. Pilotta, M.R. Cutrì, M.S. Azamian, A. Hernández-García, S.R. Lalani, J.A. Rosenfeld, X. Zhao, T.P. Vogel, H. Ona, D.A. Scott, P. Scheiffele, K. Strømgaard, M. Tafti, M. Gassmann, B. Fakler, R. Shigemoto, B. Bettler, Science Advances 10 (2024).","ama":"Früh S, Boudkkazi S, Koppensteiner P, et al. Monoallelic de novo AJAP1 loss-of- function variants disrupt trans-synaptic control of neurotransmitter release. <i>Science Advances</i>. 2024;10(28). doi:<a href=\"https://doi.org/10.1126/sciadv.adk5462\">10.1126/sciadv.adk5462</a>","apa":"Früh, S., Boudkkazi, S., Koppensteiner, P., Sereikaite, V., Chen, L. Y., Fernandez-Fernandez, D., … Bettler, B. (2024). Monoallelic de novo AJAP1 loss-of- function variants disrupt trans-synaptic control of neurotransmitter release. <i>Science Advances</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/sciadv.adk5462\">https://doi.org/10.1126/sciadv.adk5462</a>","chicago":"Früh, Simon, Sami Boudkkazi, Peter Koppensteiner, Vita Sereikaite, Li Yuan Chen, Diego Fernandez-Fernandez, Pascal D. Rem, et al. “Monoallelic de Novo AJAP1 Loss-of- Function Variants Disrupt Trans-Synaptic Control of Neurotransmitter Release.” <i>Science Advances</i>. American Association for the Advancement of Science, 2024. <a href=\"https://doi.org/10.1126/sciadv.adk5462\">https://doi.org/10.1126/sciadv.adk5462</a>.","ieee":"S. Früh <i>et al.</i>, “Monoallelic de novo AJAP1 loss-of- function variants disrupt trans-synaptic control of neurotransmitter release,” <i>Science Advances</i>, vol. 10, no. 28. American Association for the Advancement of Science, 2024.","ista":"Früh S, Boudkkazi S, Koppensteiner P, Sereikaite V, Chen LY, Fernandez-Fernandez D, Rem PD, Ulrich D, Schwenk J, Chen Z, Monnier EL, Fritzius T, Innocenti SM, Besseyrias V, Trovò L, Stawarski M, Argilli E, Sherr EH, Van Bon B, Kamsteeg EJ, Iascone M, Pilotta A, Cutrì MR, Azamian MS, Hernández-García A, Lalani SR, Rosenfeld JA, Zhao X, Vogel TP, Ona H, Scott DA, Scheiffele P, Strømgaard K, Tafti M, Gassmann M, Fakler B, Shigemoto R, Bettler B. 2024. Monoallelic de novo AJAP1 loss-of- function variants disrupt trans-synaptic control of neurotransmitter release. Science Advances. 10(28), adk5462."},"day":"12","publisher":"American Association for the Advancement of Science","article_type":"original","_id":"17280","OA_type":"gold","DOAJ_listed":"1"},{"citation":{"ista":"Cheung GT, Pauler F, Koppensteiner P, Hippenmeyer S. 2024. Protocol for mapping cell lineage and cell-type identity of clonally-related cells in situ using MADM-CloneSeq. STAR Protocols. 5(3), 103168.","apa":"Cheung, G. T., Pauler, F., Koppensteiner, P., &#38; Hippenmeyer, S. (2024). Protocol for mapping cell lineage and cell-type identity of clonally-related cells in situ using MADM-CloneSeq. <i>STAR Protocols</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xpro.2024.103168\">https://doi.org/10.1016/j.xpro.2024.103168</a>","ieee":"G. T. Cheung, F. Pauler, P. Koppensteiner, and S. Hippenmeyer, “Protocol for mapping cell lineage and cell-type identity of clonally-related cells in situ using MADM-CloneSeq,” <i>STAR Protocols</i>, vol. 5, no. 3. Elsevier, 2024.","chicago":"Cheung, Giselle T, Florian Pauler, Peter Koppensteiner, and Simon Hippenmeyer. “Protocol for Mapping Cell Lineage and Cell-Type Identity of Clonally-Related Cells in Situ Using MADM-CloneSeq.” <i>STAR Protocols</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.xpro.2024.103168\">https://doi.org/10.1016/j.xpro.2024.103168</a>.","short":"G.T. Cheung, F. Pauler, P. Koppensteiner, S. Hippenmeyer, STAR Protocols 5 (2024).","ama":"Cheung GT, Pauler F, Koppensteiner P, Hippenmeyer S. Protocol for mapping cell lineage and cell-type identity of clonally-related cells in situ using MADM-CloneSeq. <i>STAR Protocols</i>. 2024;5(3). doi:<a href=\"https://doi.org/10.1016/j.xpro.2024.103168\">10.1016/j.xpro.2024.103168</a>","mla":"Cheung, Giselle T., et al. “Protocol for Mapping Cell Lineage and Cell-Type Identity of Clonally-Related Cells in Situ Using MADM-CloneSeq.” <i>STAR Protocols</i>, vol. 5, no. 3, 103168, Elsevier, 2024, doi:<a href=\"https://doi.org/10.1016/j.xpro.2024.103168\">10.1016/j.xpro.2024.103168</a>."},"issue":"3","article_number":"103168","has_accepted_license":"1","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","tmp":{"image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"oa":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","project":[{"grant_number":"F7805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression"}],"volume":5,"type":"journal_article","date_updated":"2025-12-30T10:54:12Z","abstract":[{"lang":"eng","text":"The lineage relationship of clonally-related cells offers important insights into the ontogeny and cytoarchitecture of the brain in health and disease. Here, we provide a protocol to concurrently assess cell lineage relationship and cell-type identity among clonally-related cells in situ. We first describe the preparation and screening of acute brain slices containing clonally-related cells labeled using mosaic analysis with double markers (MADM). We then outline steps to collect RNA from individual cells for downstream applications and cell-type identification using RNA sequencing.\r\nFor complete details on the use and execution of this protocol, please refer to Cheung et al.\r\n1"}],"language":[{"iso":"eng"}],"APC_amount":"804 EUR","OA_type":"gold","_id":"17232","article_type":"original","day":"20","publisher":"Elsevier","OA_place":"publisher","file":[{"relation":"main_file","file_name":"2024_STARProtoc_Cheung2.pdf","access_level":"open_access","date_created":"2025-01-09T12:16:53Z","date_updated":"2025-01-09T12:16:53Z","content_type":"application/pdf","creator":"dernst","file_id":"18810","file_size":6445556,"success":1,"checksum":"464f52ecc6ec92f509552823bb82bf79"}],"doi":"10.1016/j.xpro.2024.103168","file_date_updated":"2025-01-09T12:16:53Z","oa_version":"Published Version","external_id":{"pmid":["38968076"]},"ddc":["570"],"scopus_import":"1","title":"Protocol for mapping cell lineage and cell-type identity of clonally-related cells in situ using MADM-CloneSeq","quality_controlled":"1","acknowledged_ssus":[{"_id":"Bio"},{"_id":"M-Shop"},{"_id":"PreCl"}],"article_processing_charge":"Yes","acknowledgement":"We thank R. Beattie and T. Asenov for designing and producing components of the multi-well slice recover chamber. We thank R. Shigemoto for providing equipment access. We thank C. Streicher and A. Heger for mouse breeding support. This work was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging & Optics, Miba Machine Shop, and Preclinical facilities. G.C. received funding from the European Commission (IST plus postdoctoral fellowship) and S.H. was funded by ISTA institutional funds and the Austrian Science Fund Special Research Programmes (FWF SFB-F78 Neuro Stem Modulation).","pmid":1,"publication":"STAR Protocols","publication_status":"published","department":[{"_id":"SiHi"},{"_id":"PreCl"}],"corr_author":"1","date_published":"2024-09-20T00:00:00Z","year":"2024","status":"public","month":"09","date_created":"2024-07-14T22:01:10Z","author":[{"first_name":"Giselle T","last_name":"Cheung","orcid":"0000-0001-8457-2572","id":"471195F6-F248-11E8-B48F-1D18A9856A87","full_name":"Cheung, Giselle T"},{"orcid":"0000-0002-7462-0048","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","full_name":"Pauler, Florian","first_name":"Florian","last_name":"Pauler"},{"orcid":"0000-0002-3509-1948","full_name":"Koppensteiner, Peter","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","first_name":"Peter","last_name":"Koppensteiner"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","first_name":"Simon"}],"publication_identifier":{"eissn":["2666-1667"]},"intvolume":"         5"},{"citation":{"ista":"Muhia MW, YuanXiang P, Sedlacik J, Schwarz JR, Heisler FF, Gromova KV, Thies E, Breiden P, Pechmann Y, Kreutz MR, Kneussel M. 2022. Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes. Communications Biology. 5, 589.","apa":"Muhia, M. W., YuanXiang, P., Sedlacik, J., Schwarz, J. R., Heisler, F. F., Gromova, K. V., … Kneussel, M. (2022). Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes. <i>Communications Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s42003-022-03446-1\">https://doi.org/10.1038/s42003-022-03446-1</a>","ieee":"M. W. Muhia <i>et al.</i>, “Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes,” <i>Communications Biology</i>, vol. 5. Springer Nature, 2022.","chicago":"Muhia, Mary W, PingAn YuanXiang, Jan Sedlacik, Jürgen R. Schwarz, Frank F. Heisler, Kira V. Gromova, Edda Thies, et al. “Muskelin Regulates Actin-Dependent Synaptic Changes and Intrinsic Brain Activity Relevant to Behavioral and Cognitive Processes.” <i>Communications Biology</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s42003-022-03446-1\">https://doi.org/10.1038/s42003-022-03446-1</a>.","short":"M.W. Muhia, P. YuanXiang, J. Sedlacik, J.R. Schwarz, F.F. Heisler, K.V. Gromova, E. Thies, P. Breiden, Y. Pechmann, M.R. Kreutz, M. Kneussel, Communications Biology 5 (2022).","ama":"Muhia MW, YuanXiang P, Sedlacik J, et al. Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes. <i>Communications Biology</i>. 2022;5. doi:<a href=\"https://doi.org/10.1038/s42003-022-03446-1\">10.1038/s42003-022-03446-1</a>","mla":"Muhia, Mary W., et al. “Muskelin Regulates Actin-Dependent Synaptic Changes and Intrinsic Brain Activity Relevant to Behavioral and Cognitive Processes.” <i>Communications Biology</i>, vol. 5, 589, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s42003-022-03446-1\">10.1038/s42003-022-03446-1</a>."},"article_number":"589","has_accepted_license":"1","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa":1,"volume":5,"type":"journal_article","keyword":["General Agricultural and Biological Sciences","General Biochemistry","Genetics and Molecular Biology","Medicine (miscellaneous)"],"date_updated":"2024-10-09T21:03:48Z","language":[{"iso":"eng"}],"abstract":[{"text":"Muskelin (Mkln1) is implicated in neuronal function, regulating plasma membrane receptor trafficking. However, its influence on intrinsic brain activity and corresponding behavioral processes remains unclear. Here we show that murine <jats:italic>Mkln1</jats:italic> knockout causes non-habituating locomotor activity, increased exploratory drive, and decreased locomotor response to amphetamine. Muskelin deficiency impairs social novelty detection while promoting the retention of spatial reference memory and fear extinction recall. This is strongly mirrored in either weaker or stronger resting-state functional connectivity between critical circuits mediating locomotor exploration and cognition. We show that <jats:italic>Mkln1</jats:italic> deletion alters dendrite branching and spine structure, coinciding with enhanced AMPAR-mediated synaptic transmission but selective impairment in synaptic potentiation maintenance. We identify muskelin at excitatory synapses and highlight its role in regulating dendritic spine actin stability. Our findings point to aberrant spine actin modulation and changes in glutamatergic synaptic function as critical mechanisms that contribute to the neurobehavioral phenotype arising from <jats:italic>Mkln1</jats:italic> ablation.","lang":"eng"}],"_id":"12224","article_type":"original","day":"15","publisher":"Springer Nature","file":[{"relation":"main_file","date_created":"2023-01-27T08:23:46Z","date_updated":"2023-01-27T08:23:46Z","file_name":"2022_CommBiology_Muhia.pdf","access_level":"open_access","file_size":3968356,"checksum":"bd95be1e77090208b79bc45ea8785d0b","success":1,"file_id":"12417","content_type":"application/pdf","creator":"dernst"}],"ddc":["570"],"external_id":{"isi":["000811777900003"]},"doi":"10.1038/s42003-022-03446-1","oa_version":"Published Version","file_date_updated":"2023-01-27T08:23:46Z","scopus_import":"1","quality_controlled":"1","title":"Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes","article_processing_charge":"No","acknowledgement":"The authors are grateful to the UKE Animal Facilities (Hamburg) for animal husbandry and Dr. Bastian Tiemann for his veterinary expertise and supervision of animal care. We thank Dr. Franco Lombino for critically reading the manuscript and for helpful discussion. This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG) (FOR2419-KN556/11-1, FOR2419-KN556/11-2, KN556/12-1) and the Landesforschungsförderung Hamburg (LFF-FV76) to M.K.\r\nOpen Access funding enabled and organized by Projekt DEAL.","publication":"Communications Biology","publication_status":"published","department":[{"_id":"PreCl"}],"corr_author":"1","date_published":"2022-06-15T00:00:00Z","year":"2022","month":"06","status":"public","date_created":"2023-01-16T09:48:19Z","isi":1,"intvolume":"         5","publication_identifier":{"issn":["2399-3642"]},"author":[{"id":"ab7ed20f-09f7-11eb-909c-d5d0b443ee9d","full_name":"Muhia, Mary W","first_name":"Mary W","last_name":"Muhia"},{"full_name":"YuanXiang, PingAn","last_name":"YuanXiang","first_name":"PingAn"},{"first_name":"Jan","last_name":"Sedlacik","full_name":"Sedlacik, Jan"},{"full_name":"Schwarz, Jürgen R.","last_name":"Schwarz","first_name":"Jürgen R."},{"full_name":"Heisler, Frank F.","first_name":"Frank F.","last_name":"Heisler"},{"full_name":"Gromova, Kira V.","first_name":"Kira V.","last_name":"Gromova"},{"first_name":"Edda","last_name":"Thies","full_name":"Thies, Edda"},{"full_name":"Breiden, Petra","last_name":"Breiden","first_name":"Petra"},{"first_name":"Yvonne","last_name":"Pechmann","full_name":"Pechmann, Yvonne"},{"last_name":"Kreutz","first_name":"Michael R.","full_name":"Kreutz, Michael R."},{"full_name":"Kneussel, Matthias","last_name":"Kneussel","first_name":"Matthias"}]},{"publication":"EMBO Reports","acknowledgement":"This EQIPD project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement no. 777364. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA. LR was supported by the Faculty of Biology and Medicine, University of Lausanne. VV was supported by Biocenter Finland and the Jane and Aatos Erkko Foundation. CP and IKB received funding from the Federal Ministry of Education and Research (BMBF, grant 01PW18001). SB from the Vienna BioCenter Core Facilities (VBCF) Preclinical Phenotyping Facility acknowledges funding from the Austrian Federal Ministry of Education, Science & Research; and the City of Vienna. MT is an incumbent of the Carolito Stiftung Research Fellow Chair in Neurodegenerative Diseases. We thank Dr. Katja Kivinen (Helsinki Institute of Life Science) for discussions and feedback.","article_processing_charge":"Yes (in subscription journal)","title":"Towards best practices in research: Role of academic core facilities","quality_controlled":"1","scopus_import":"1","oa_version":"Published Version","doi":"10.15252/embr.202153824","file_date_updated":"2022-05-16T07:07:41Z","external_id":{"isi":["000714350000001"]},"ddc":["570"],"file":[{"relation":"main_file","file_size":488583,"checksum":"74743baa6ef431ef60c3de3bc4da045a","success":1,"content_type":"application/pdf","file_id":"11381","creator":"dernst","date_updated":"2022-05-16T07:07:41Z","date_created":"2022-05-16T07:07:41Z","file_name":"2021_EmboReports_Restivo.pdf","access_level":"open_access"}],"author":[{"full_name":"Restivo, Leonardo","first_name":"Leonardo","last_name":"Restivo"},{"last_name":"Gerlach","first_name":"Björn","full_name":"Gerlach, Björn"},{"last_name":"Tsoory","first_name":"Michael","full_name":"Tsoory, Michael"},{"full_name":"Bikovski, Lior","last_name":"Bikovski","first_name":"Lior"},{"first_name":"Sylvia","last_name":"Badurek","full_name":"Badurek, Sylvia"},{"full_name":"Pitzer, Claudia","first_name":"Claudia","last_name":"Pitzer"},{"full_name":"Kos-Braun, Isabelle C.","last_name":"Kos-Braun","first_name":"Isabelle C."},{"last_name":"Mausset-Bonnefont","first_name":"Anne Laure Mj","full_name":"Mausset-Bonnefont, Anne Laure Mj"},{"full_name":"Ward, Jonathan","first_name":"Jonathan","last_name":"Ward"},{"last_name":"Schunn","first_name":"Michael","full_name":"Schunn, Michael","id":"4272DB4A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4326-5300"},{"last_name":"Noldus","first_name":"Lucas P.J.J.","full_name":"Noldus, Lucas P.J.J."},{"full_name":"Bespalov, Anton","first_name":"Anton","last_name":"Bespalov"},{"last_name":"Voikar","first_name":"Vootele","full_name":"Voikar, Vootele"}],"intvolume":"        22","publication_identifier":{"eissn":["1469-3178"],"issn":["1469-221X"]},"isi":1,"date_created":"2021-11-14T23:01:24Z","status":"public","month":"11","year":"2021","date_published":"2021-11-04T00:00:00Z","department":[{"_id":"PreCl"}],"publication_status":"published","abstract":[{"text":"During the past decade, the scientific community and outside observers have noted a concerning lack of rigor and transparency in preclinical research that led to talk of a “reproducibility crisis” in the life sciences (Baker, 2016; Bespalov & Steckler, 2018; Heddleston et al, 2021). Various measures have been proposed to address the problem: from better training of scientists to more oversight to expanded publishing practices such as preregistration of studies. The recently published EQIPD (Enhancing Quality in Preclinical Data) System is, to date, the largest initiative that aims to establish a systematic approach for increasing the robustness and reliability of biomedical research (Bespalov et al, 2021). However, promoting a cultural change in research practices warrants a broad adoption of the Quality System and its underlying philosophy. It is here that academic Core Facilities (CF), research service providers at universities and research institutions, can make a difference. It is fair to assume that a significant fraction of published data originated from experiments that were designed, run, or analyzed in CFs. These academic services play an important role in the research ecosystem by offering access to cutting-edge equipment and by developing and testing novel techniques and methods that impact research in the academic and private sectors alike (Bikovski et al, 2020). Equipment and infrastructure are not the only value: CFs employ competent personnel with profound knowledge and practical experience of the specific field of interest: animal behavior, imaging, crystallography, genomics, and so on. Thus, CFs are optimally positioned to address concerns about the quality and robustness of preclinical research.","lang":"eng"}],"language":[{"iso":"eng"}],"date_updated":"2023-08-14T11:47:35Z","type":"journal_article","volume":22,"oa":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","tmp":{"image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"has_accepted_license":"1","article_number":"e53824","citation":{"apa":"Restivo, L., Gerlach, B., Tsoory, M., Bikovski, L., Badurek, S., Pitzer, C., … Voikar, V. (2021). Towards best practices in research: Role of academic core facilities. <i>EMBO Reports</i>. EMBO Press. <a href=\"https://doi.org/10.15252/embr.202153824\">https://doi.org/10.15252/embr.202153824</a>","chicago":"Restivo, Leonardo, Björn Gerlach, Michael Tsoory, Lior Bikovski, Sylvia Badurek, Claudia Pitzer, Isabelle C. Kos-Braun, et al. “Towards Best Practices in Research: Role of Academic Core Facilities.” <i>EMBO Reports</i>. EMBO Press, 2021. <a href=\"https://doi.org/10.15252/embr.202153824\">https://doi.org/10.15252/embr.202153824</a>.","ieee":"L. Restivo <i>et al.</i>, “Towards best practices in research: Role of academic core facilities,” <i>EMBO Reports</i>, vol. 22. EMBO Press, 2021.","ista":"Restivo L, Gerlach B, Tsoory M, Bikovski L, Badurek S, Pitzer C, Kos-Braun IC, Mausset-Bonnefont ALM, Ward J, Schunn M, Noldus LPJJ, Bespalov A, Voikar V. 2021. Towards best practices in research: Role of academic core facilities. EMBO Reports. 22, e53824.","mla":"Restivo, Leonardo, et al. “Towards Best Practices in Research: Role of Academic Core Facilities.” <i>EMBO Reports</i>, vol. 22, e53824, EMBO Press, 2021, doi:<a href=\"https://doi.org/10.15252/embr.202153824\">10.15252/embr.202153824</a>.","short":"L. Restivo, B. Gerlach, M. Tsoory, L. Bikovski, S. Badurek, C. Pitzer, I.C. Kos-Braun, A.L.M. Mausset-Bonnefont, J. Ward, M. Schunn, L.P.J.J. Noldus, A. Bespalov, V. Voikar, EMBO Reports 22 (2021).","ama":"Restivo L, Gerlach B, Tsoory M, et al. Towards best practices in research: Role of academic core facilities. <i>EMBO Reports</i>. 2021;22. doi:<a href=\"https://doi.org/10.15252/embr.202153824\">10.15252/embr.202153824</a>"},"publisher":"EMBO Press","day":"04","_id":"10283","article_type":"original"},{"file":[{"content_type":"application/pdf","file_id":"9609","creator":"asandaue","file_size":2500720,"success":1,"checksum":"885b746051a7a6b6e24e3d2781a48fde","file_name":"2021_ELife_Bespalov.pdf","access_level":"open_access","date_updated":"2021-06-28T11:35:30Z","date_created":"2021-06-28T11:35:30Z","relation":"main_file"}],"ddc":["570"],"oa_version":"Published Version","doi":"10.7554/eLife.63294","file_date_updated":"2021-06-28T11:35:30Z","external_id":{"pmid":["34028353"],"isi":["000661272000001"]},"scopus_import":"1","quality_controlled":"1","title":"Introduction to the EQIPD quality system","article_processing_charge":"No","acknowledgement":"This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777364. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. The authors are very grateful to Martin Heinrich (Abbvie, Ludwigshafen, Germany) for the exceptional IT support and programming the EQIPD Planning Tool and the Creator Tool and to Dr Shai Silberberg (NINDS, USA), Dr. Renza Roncarati (PAASP Italy) and Dr Judith Homberg (Radboud University, Nijmegen) for highly stimulating contributions to the discussions and comments on earlier versions of this manuscript. We also wish to express our thanks to Dr. Sara Stöber (concentris research management GmbH, Fürstenfeldbruck, Germany) for excellent and continuous support of this project. Creation of the EQIPD Stakeholder group was supported by Noldus Information Technology bv (Wageningen, the Netherlands).","publication":"eLife","pmid":1,"publication_status":"published","department":[{"_id":"PreCl"}],"date_published":"2021-05-24T00:00:00Z","year":"2021","month":"05","status":"public","isi":1,"date_created":"2021-06-27T22:01:49Z","intvolume":"        10","publication_identifier":{"eissn":["2050-084X"]},"author":[{"full_name":"Bespalov, Anton","first_name":"Anton","last_name":"Bespalov"},{"full_name":"Bernard, René","last_name":"Bernard","first_name":"René"},{"first_name":"Anja","last_name":"Gilis","full_name":"Gilis, Anja"},{"first_name":"Björn","last_name":"Gerlach","full_name":"Gerlach, Björn"},{"first_name":"Javier","last_name":"Guillén","full_name":"Guillén, Javier"},{"full_name":"Castagné, Vincent","last_name":"Castagné","first_name":"Vincent"},{"full_name":"Lefevre, Isabel A.","first_name":"Isabel A.","last_name":"Lefevre"},{"first_name":"Fiona","last_name":"Ducrey","full_name":"Ducrey, Fiona"},{"first_name":"Lee","last_name":"Monk","full_name":"Monk, Lee"},{"first_name":"Sandrine","last_name":"Bongiovanni","full_name":"Bongiovanni, Sandrine"},{"full_name":"Altevogt, Bruce","last_name":"Altevogt","first_name":"Bruce"},{"last_name":"Arroyo-Araujo","first_name":"María","full_name":"Arroyo-Araujo, María"},{"first_name":"Lior","last_name":"Bikovski","full_name":"Bikovski, Lior"},{"full_name":"De Bruin, Natasja","last_name":"De Bruin","first_name":"Natasja"},{"first_name":"Esmeralda","last_name":"Castaños-Vélez","full_name":"Castaños-Vélez, Esmeralda"},{"full_name":"Dityatev, Alexander","last_name":"Dityatev","first_name":"Alexander"},{"last_name":"Emmerich","first_name":"Christoph H.","full_name":"Emmerich, Christoph H."},{"last_name":"Fares","first_name":"Raafat","full_name":"Fares, Raafat"},{"full_name":"Ferland-Beckham, Chantelle","last_name":"Ferland-Beckham","first_name":"Chantelle"},{"full_name":"Froger-Colléaux, Christelle","first_name":"Christelle","last_name":"Froger-Colléaux"},{"full_name":"Gailus-Durner, Valerie","first_name":"Valerie","last_name":"Gailus-Durner"},{"last_name":"Hölter","first_name":"Sabine M.","full_name":"Hölter, Sabine M."},{"full_name":"Hofmann, Martine Cj","last_name":"Hofmann","first_name":"Martine Cj"},{"first_name":"Patricia","last_name":"Kabitzke","full_name":"Kabitzke, Patricia"},{"full_name":"Kas, Martien Jh","first_name":"Martien Jh","last_name":"Kas"},{"first_name":"Claudia","last_name":"Kurreck","full_name":"Kurreck, Claudia"},{"full_name":"Moser, Paul","last_name":"Moser","first_name":"Paul"},{"last_name":"Pietraszek","first_name":"Malgorzata","full_name":"Pietraszek, Malgorzata"},{"first_name":"Piotr","last_name":"Popik","full_name":"Popik, Piotr"},{"last_name":"Potschka","first_name":"Heidrun","full_name":"Potschka, Heidrun"},{"full_name":"Prado Montes De Oca, Ernesto","last_name":"Prado Montes De Oca","first_name":"Ernesto"},{"first_name":"Leonardo","last_name":"Restivo","full_name":"Restivo, Leonardo"},{"last_name":"Riedel","first_name":"Gernot","full_name":"Riedel, Gernot"},{"full_name":"Ritskes-Hoitinga, Merel","first_name":"Merel","last_name":"Ritskes-Hoitinga"},{"full_name":"Samardzic, Janko","last_name":"Samardzic","first_name":"Janko"},{"first_name":"Michael","last_name":"Schunn","orcid":"0000-0003-4326-5300","full_name":"Schunn, Michael","id":"4272DB4A-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Claudia","last_name":"Stöger","full_name":"Stöger, Claudia"},{"full_name":"Voikar, Vootele","first_name":"Vootele","last_name":"Voikar"},{"first_name":"Jan","last_name":"Vollert","full_name":"Vollert, Jan"},{"first_name":"Kimberley E.","last_name":"Wever","full_name":"Wever, Kimberley E."},{"first_name":"Kathleen","last_name":"Wuyts","full_name":"Wuyts, Kathleen"},{"full_name":"Macleod, Malcolm R.","last_name":"Macleod","first_name":"Malcolm R."},{"first_name":"Ulrich","last_name":"Dirnagl","full_name":"Dirnagl, Ulrich"},{"last_name":"Steckler","first_name":"Thomas","full_name":"Steckler, Thomas"}],"citation":{"mla":"Bespalov, Anton, et al. “Introduction to the EQIPD Quality System.” <i>ELife</i>, vol. 10, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/eLife.63294\">10.7554/eLife.63294</a>.","short":"A. Bespalov, R. Bernard, A. Gilis, B. Gerlach, J. Guillén, V. Castagné, I.A. Lefevre, F. Ducrey, L. Monk, S. Bongiovanni, B. Altevogt, M. Arroyo-Araujo, L. Bikovski, N. De Bruin, E. Castaños-Vélez, A. Dityatev, C.H. Emmerich, R. Fares, C. Ferland-Beckham, C. Froger-Colléaux, V. Gailus-Durner, S.M. Hölter, M.C. Hofmann, P. Kabitzke, M.J. Kas, C. Kurreck, P. Moser, M. Pietraszek, P. Popik, H. Potschka, E. Prado Montes De Oca, L. Restivo, G. Riedel, M. Ritskes-Hoitinga, J. Samardzic, M. Schunn, C. Stöger, V. Voikar, J. Vollert, K.E. Wever, K. Wuyts, M.R. Macleod, U. Dirnagl, T. Steckler, ELife 10 (2021).","ama":"Bespalov A, Bernard R, Gilis A, et al. Introduction to the EQIPD quality system. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/eLife.63294\">10.7554/eLife.63294</a>","apa":"Bespalov, A., Bernard, R., Gilis, A., Gerlach, B., Guillén, J., Castagné, V., … Steckler, T. (2021). Introduction to the EQIPD quality system. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.63294\">https://doi.org/10.7554/eLife.63294</a>","chicago":"Bespalov, Anton, René Bernard, Anja Gilis, Björn Gerlach, Javier Guillén, Vincent Castagné, Isabel A. Lefevre, et al. “Introduction to the EQIPD Quality System.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/eLife.63294\">https://doi.org/10.7554/eLife.63294</a>.","ieee":"A. Bespalov <i>et al.</i>, “Introduction to the EQIPD quality system,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","ista":"Bespalov A, Bernard R, Gilis A, Gerlach B, Guillén J, Castagné V, Lefevre IA, Ducrey F, Monk L, Bongiovanni S, Altevogt B, Arroyo-Araujo M, Bikovski L, De Bruin N, Castaños-Vélez E, Dityatev A, Emmerich CH, Fares R, Ferland-Beckham C, Froger-Colléaux C, Gailus-Durner V, Hölter SM, Hofmann MC, Kabitzke P, Kas MJ, Kurreck C, Moser P, Pietraszek M, Popik P, Potschka H, Prado Montes De Oca E, Restivo L, Riedel G, Ritskes-Hoitinga M, Samardzic J, Schunn M, Stöger C, Voikar V, Vollert J, Wever KE, Wuyts K, Macleod MR, Dirnagl U, Steckler T. 2021. Introduction to the EQIPD quality system. eLife. 10."},"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"has_accepted_license":"1","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","oa":1,"volume":10,"type":"journal_article","date_updated":"2026-04-02T13:55:57Z","language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"While high risk of failure is an inherent part of developing innovative therapies, it can be reduced by adherence to evidence-based rigorous research practices. Numerous analyses conducted to date have clearly identified measures that need to be taken to improve research rigor. Supported through the European Union's Innovative Medicines Initiative, the EQIPD consortium has developed a novel preclinical research quality system that can be applied in both public and private sectors and is free for anyone to use. The EQIPD Quality System was designed to be suited to boost innovation by ensuring the generation of robust and reliable preclinical data while being lean, effective and not becoming a burden that could negatively impact the freedom to explore scientific questions. EQIPD defines research quality as the extent to which research data are fit for their intended use. Fitness, in this context, is defined by the stakeholders, who are the scientists directly involved in the research, but also their funders, sponsors, publishers, research tool manufacturers and collaboration partners such as peers in a multi-site research project. The essence of the EQIPD Quality System is the set of 18 core requirements that can be addressed flexibly, according to user-specific needs and following a user-defined trajectory. The EQIPD Quality System proposes guidance on expectations for quality-related measures, defines criteria for adequate processes (i.e., performance standards) and provides examples of how such measures can be developed and implemented. However, it does not prescribe any pre-determined solutions. EQIPD has also developed tools (for optional use) to support users in implementing the system and assessment services for those research units that successfully implement the quality system and seek formal accreditation. Building upon the feedback from users and continuous improvement, a sustainable EQIPD Quality System will ultimately serve the entire community of scientists conducting non-regulated preclinical research, by helping them generate reliable data that are fit for their intended use."}],"_id":"9607","article_type":"original","publisher":"eLife Sciences Publications","day":"24"},{"volume":35,"type":"journal_article","project":[{"name":"Molecular mechanisms of radial neuronal migration","grant_number":"24812","_id":"2625A13E-B435-11E9-9278-68D0E5697425"},{"name":"Molecular Mechanisms of Cerebral Cortex Development","call_identifier":"FP7","grant_number":"618444","_id":"25D61E48-B435-11E9-9278-68D0E5697425"},{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","oa":1,"language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"Mosaic analysis with double markers (MADM) offers one approach to visualize and concomitantly manipulate genetically defined cells in mice with single-cell resolution. MADM applications include the analysis of lineage, single-cell morphology and physiology, genomic imprinting phenotypes, and dissection of cell-autonomous gene functions in vivo in health and disease. Yet, MADM can only be applied to <25% of all mouse genes on select chromosomes to date. To overcome this limitation, we generate transgenic mice with knocked-in MADM cassettes near the centromeres of all 19 autosomes and validate their use across organs. With this resource, >96% of the entire mouse genome can now be subjected to single-cell genetic mosaic analysis. Beyond a proof of principle, we apply our MADM library to systematically trace sister chromatid segregation in distinct mitotic cell lineages. We find striking chromosome-specific biases in segregation patterns, reflecting a putative mechanism for the asymmetric segregation of genetic determinants in somatic stem cell division."}],"date_updated":"2026-04-02T14:04:28Z","citation":{"mla":"Contreras, Ximena, et al. “A Genome-Wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis.” <i>Cell Reports</i>, vol. 35, no. 12, 109274, Cell Press, 2021, doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109274\">10.1016/j.celrep.2021.109274</a>.","short":"X. Contreras, N. Amberg, A. Davaatseren, A.H. Hansen, J. Sonntag, L. Andersen, T. Bernthaler, C. Streicher, A.-M. Heger, R.L. Johnson, L.A. Schwarz, L. Luo, T. Rülicke, S. Hippenmeyer, Cell Reports 35 (2021).","ama":"Contreras X, Amberg N, Davaatseren A, et al. A genome-wide library of MADM mice for single-cell genetic mosaic analysis. <i>Cell Reports</i>. 2021;35(12). doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109274\">10.1016/j.celrep.2021.109274</a>","apa":"Contreras, X., Amberg, N., Davaatseren, A., Hansen, A. H., Sonntag, J., Andersen, L., … Hippenmeyer, S. (2021). A genome-wide library of MADM mice for single-cell genetic mosaic analysis. <i>Cell Reports</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.celrep.2021.109274\">https://doi.org/10.1016/j.celrep.2021.109274</a>","chicago":"Contreras, Ximena, Nicole Amberg, Amarbayasgalan Davaatseren, Andi H Hansen, Johanna Sonntag, Lill Andersen, Tina Bernthaler, et al. “A Genome-Wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis.” <i>Cell Reports</i>. Cell Press, 2021. <a href=\"https://doi.org/10.1016/j.celrep.2021.109274\">https://doi.org/10.1016/j.celrep.2021.109274</a>.","ieee":"X. Contreras <i>et al.</i>, “A genome-wide library of MADM mice for single-cell genetic mosaic analysis,” <i>Cell Reports</i>, vol. 35, no. 12. Cell Press, 2021.","ista":"Contreras X, Amberg N, Davaatseren A, Hansen AH, Sonntag J, Andersen L, Bernthaler T, Streicher C, Heger A-M, Johnson RL, Schwarz LA, Luo L, Rülicke T, Hippenmeyer S. 2021. A genome-wide library of MADM mice for single-cell genetic mosaic analysis. Cell Reports. 35(12), 109274."},"tmp":{"image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"has_accepted_license":"1","article_number":"109274","issue":"12","_id":"9603","article_type":"original","related_material":{"link":[{"url":"https://ist.ac.at/en/news/boost-for-mouse-genetic-analysis/","description":"News on IST Homepage","relation":"press_release"}]},"day":"22","publisher":"Cell Press","article_processing_charge":"No","pmid":1,"publication":"Cell Reports","acknowledgement":"We thank the Bioimaging, Life Science, and Pre-Clinical Facilities at IST Austria; M.P. Postiglione, C. Simbriger, K. Valoskova, C. Schwayer, T. Hussain, M. Pieber, and V. Wimmer for initial experiments, technical support, and/or assistance; R. Shigemoto for sharing iv (Dnah11 mutant) mice; and M. Sixt and all members of the Hippenmeyer lab for discussion. This work was supported by National Institutes of Health grants ( R01-NS050580 to L.L. and F32MH096361 to L.A.S.). L.L. is an investigator of HHMI. N.A. received support from FWF Firnberg-Programm ( T 1031 ). A.H.H. is a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences . This work also received support from IST Austria institutional funds , FWF SFB F78 to S.H., the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme ( FP7/2007-2013 ) under REA grant agreement no 618444 to S.H., and the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement no. 725780 LinPro ) to S.H.","ddc":["570"],"external_id":{"pmid":["34161767"],"isi":["000664463600016"]},"doi":"10.1016/j.celrep.2021.109274","file_date_updated":"2021-06-28T14:06:24Z","oa_version":"Published Version","file":[{"relation":"main_file","file_name":"2021_CellReports_Contreras.pdf","access_level":"open_access","date_created":"2021-06-28T14:06:24Z","date_updated":"2021-06-28T14:06:24Z","file_id":"9613","creator":"asandaue","content_type":"application/pdf","file_size":7653149,"checksum":"d49520fdcbbb5c2f883bddb67cee5d77","success":1}],"quality_controlled":"1","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"title":"A genome-wide library of MADM mice for single-cell genetic mosaic analysis","scopus_import":"1","month":"06","status":"public","year":"2021","publication_identifier":{"eissn":["2211-1247"]},"intvolume":"        35","author":[{"last_name":"Contreras","first_name":"Ximena","id":"475990FE-F248-11E8-B48F-1D18A9856A87","full_name":"Contreras, Ximena"},{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207","last_name":"Amberg","first_name":"Nicole"},{"id":"70ADC922-B424-11E9-99E3-BA18E6697425","full_name":"Davaatseren, Amarbayasgalan","first_name":"Amarbayasgalan","last_name":"Davaatseren"},{"full_name":"Hansen, Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87","last_name":"Hansen","first_name":"Andi H"},{"last_name":"Sonntag","first_name":"Johanna","id":"32FE7D7C-F248-11E8-B48F-1D18A9856A87","full_name":"Sonntag, Johanna"},{"last_name":"Andersen","first_name":"Lill","full_name":"Andersen, Lill"},{"full_name":"Bernthaler, Tina","last_name":"Bernthaler","first_name":"Tina"},{"first_name":"Carmen","last_name":"Streicher","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87"},{"id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87","full_name":"Heger, Anna-Magdalena","first_name":"Anna-Magdalena","last_name":"Heger"},{"full_name":"Johnson, Randy L.","last_name":"Johnson","first_name":"Randy L."},{"full_name":"Schwarz, Lindsay A.","last_name":"Schwarz","first_name":"Lindsay A."},{"first_name":"Liqun","last_name":"Luo","full_name":"Luo, Liqun"},{"first_name":"Thomas","last_name":"Rülicke","full_name":"Rülicke, Thomas"},{"last_name":"Hippenmeyer","first_name":"Simon","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061"}],"date_created":"2021-06-27T22:01:48Z","isi":1,"department":[{"_id":"SiHi"},{"_id":"LoSw"},{"_id":"PreCl"}],"publication_status":"published","date_published":"2021-06-22T00:00:00Z","ec_funded":1},{"publisher":"Nature Publishing Group","day":"24","_id":"6607","date_updated":"2023-08-28T12:26:51Z","abstract":[{"text":"Acute myeloid leukemia (AML) is a heterogeneous disease with respect to its genetic and molecular basis and to patients´ outcome. Clinical, cytogenetic, and mutational data are used to classify patients into risk groups with different survival, however, within-group heterogeneity is still an issue. Here, we used a robust likelihood-based survival modeling approach and publicly available gene expression data to identify a minimal number of genes whose combined expression values were prognostic of overall survival. The resulting gene expression signature (4-GES) consisted of 4 genes (SOCS2, IL2RA, NPDC1, PHGDH), predicted patient survival as an independent prognostic parameter in several cohorts of AML patients (total, 1272 patients), and further refined prognostication based on the European Leukemia Net classification. An oncogenic role of the top scoring gene in this signature, SOCS2, was investigated using MLL-AF9 and Flt3-ITD/NPM1c driven mouse models of AML. SOCS2 promoted leukemogenesis as well as the abundance, quiescence, and activity of AML stem cells. Overall, the 4-GES represents a highly discriminating prognostic parameter in AML, whose clinical applicability is greatly enhanced by its small number of genes. The newly established role of SOCS2 in leukemia aggressiveness and stemness raises the possibility that the signature might even be exploitable therapeutically.","lang":"eng"}],"language":[{"iso":"eng"}],"oa":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","volume":9,"type":"journal_article","issue":"1","article_number":"9139","has_accepted_license":"1","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"citation":{"short":"C.H. Nguyen, T. Glüxam, A. Schlerka, K. Bauer, A.M. Grandits, H. Hackl, O. Dovey, S. Zöchbauer-Müller, J.L. Cooper, G.S. Vassiliou, D. Stoiber, R. Wieser, G. Heller, Scientific Reports 9 (2019).","ama":"Nguyen CH, Glüxam T, Schlerka A, et al. SOCS2 is part of a highly prognostic 4-gene signature in AML and promotes disease aggressiveness. <i>Scientific Reports</i>. 2019;9(1). doi:<a href=\"https://doi.org/10.1038/s41598-019-45579-0\">10.1038/s41598-019-45579-0</a>","mla":"Nguyen, Chi Huu, et al. “SOCS2 Is Part of a Highly Prognostic 4-Gene Signature in AML and Promotes Disease Aggressiveness.” <i>Scientific Reports</i>, vol. 9, no. 1, 9139, Nature Publishing Group, 2019, doi:<a href=\"https://doi.org/10.1038/s41598-019-45579-0\">10.1038/s41598-019-45579-0</a>.","ista":"Nguyen CH, Glüxam T, Schlerka A, Bauer K, Grandits AM, Hackl H, Dovey O, Zöchbauer-Müller S, Cooper JL, Vassiliou GS, Stoiber D, Wieser R, Heller G. 2019. SOCS2 is part of a highly prognostic 4-gene signature in AML and promotes disease aggressiveness. Scientific Reports. 9(1), 9139.","apa":"Nguyen, C. H., Glüxam, T., Schlerka, A., Bauer, K., Grandits, A. M., Hackl, H., … Heller, G. (2019). SOCS2 is part of a highly prognostic 4-gene signature in AML and promotes disease aggressiveness. <i>Scientific Reports</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/s41598-019-45579-0\">https://doi.org/10.1038/s41598-019-45579-0</a>","chicago":"Nguyen, Chi Huu, Tobias Glüxam, Angela Schlerka, Katharina Bauer, Alexander M. Grandits, Hubert Hackl, Oliver Dovey, et al. “SOCS2 Is Part of a Highly Prognostic 4-Gene Signature in AML and Promotes Disease Aggressiveness.” <i>Scientific Reports</i>. Nature Publishing Group, 2019. <a href=\"https://doi.org/10.1038/s41598-019-45579-0\">https://doi.org/10.1038/s41598-019-45579-0</a>.","ieee":"C. H. Nguyen <i>et al.</i>, “SOCS2 is part of a highly prognostic 4-gene signature in AML and promotes disease aggressiveness,” <i>Scientific Reports</i>, vol. 9, no. 1. Nature Publishing Group, 2019."},"isi":1,"date_created":"2019-07-07T21:59:19Z","author":[{"first_name":"Chi Huu","last_name":"Nguyen","full_name":"Nguyen, Chi Huu"},{"full_name":"Glüxam, Tobias","first_name":"Tobias","last_name":"Glüxam"},{"full_name":"Schlerka, Angela","last_name":"Schlerka","first_name":"Angela"},{"full_name":"Bauer, Katharina","id":"2ED6B14C-F248-11E8-B48F-1D18A9856A87","first_name":"Katharina","last_name":"Bauer"},{"last_name":"Grandits","first_name":"Alexander M.","full_name":"Grandits, Alexander M."},{"full_name":"Hackl, Hubert","first_name":"Hubert","last_name":"Hackl"},{"last_name":"Dovey","first_name":"Oliver","full_name":"Dovey, Oliver"},{"last_name":"Zöchbauer-Müller","first_name":"Sabine","full_name":"Zöchbauer-Müller, Sabine"},{"first_name":"Jonathan L.","last_name":"Cooper","full_name":"Cooper, Jonathan L."},{"first_name":"George S.","last_name":"Vassiliou","full_name":"Vassiliou, George S."},{"full_name":"Stoiber, Dagmar","last_name":"Stoiber","first_name":"Dagmar"},{"first_name":"Rotraud","last_name":"Wieser","full_name":"Wieser, Rotraud"},{"last_name":"Heller","first_name":"Gerwin","full_name":"Heller, Gerwin"}],"intvolume":"         9","year":"2019","status":"public","month":"06","date_published":"2019-06-24T00:00:00Z","publication_status":"published","department":[{"_id":"PreCl"}],"publication":"Scientific Reports","article_processing_charge":"No","scopus_import":"1","title":"SOCS2 is part of a highly prognostic 4-gene signature in AML and promotes disease aggressiveness","quality_controlled":"1","file":[{"content_type":"application/pdf","file_id":"6623","creator":"kschuh","file_size":2017352,"checksum":"3283522fffadf4b5fc8c7adfe3ba4564","file_name":"nature_2019_Nguyen.pdf","access_level":"open_access","date_updated":"2020-07-14T12:47:34Z","date_created":"2019-07-08T15:15:28Z","relation":"main_file"}],"file_date_updated":"2020-07-14T12:47:34Z","oa_version":"Published Version","doi":"10.1038/s41598-019-45579-0","external_id":{"isi":["000472597400042"]},"ddc":["576"]}]