[{"publisher":"Elsevier","quality_controlled":"1","oa":1,"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.","date_published":"2024-04-01T00:00:00Z","doi":"10.1016/j.medengphy.2024.104143","date_created":"2024-03-24T23:00:58Z","has_accepted_license":"1","year":"2024","day":"01","publication":"Medical Engineering and Physics","article_number":"104143","author":[{"full_name":"Silva-Henao, Juan D.","last_name":"Silva-Henao","first_name":"Juan D."},{"first_name":"Sophie","id":"80b0a0ef-4b9f-11ec-b119-8d9d94c4a1d8","last_name":"Schober","full_name":"Schober, Sophie"},{"first_name":"Dieter H.","full_name":"Pahr, Dieter H.","last_name":"Pahr"},{"full_name":"Reisinger, Andreas G.","last_name":"Reisinger","first_name":"Andreas G."}],"article_processing_charge":"Yes (in subscription journal)","title":"Critical loss of primary implant stability in osteosynthesis locking screws under cyclic overloading","citation":{"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.” Medical Engineering and Physics. Elsevier, 2024. https://doi.org/10.1016/j.medengphy.2024.104143.","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.","mla":"Silva-Henao, Juan D., et al. “Critical Loss of Primary Implant Stability in Osteosynthesis Locking Screws under Cyclic Overloading.” Medical Engineering and Physics, vol. 126, 104143, Elsevier, 2024, doi:10.1016/j.medengphy.2024.104143.","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,” Medical Engineering and Physics, vol. 126. Elsevier, 2024.","ama":"Silva-Henao JD, Schober S, Pahr DH, Reisinger AG. Critical loss of primary implant stability in osteosynthesis locking screws under cyclic overloading. Medical Engineering and Physics. 2024;126. doi:10.1016/j.medengphy.2024.104143","apa":"Silva-Henao, J. D., Schober, S., Pahr, D. H., & Reisinger, A. G. (2024). Critical loss of primary implant stability in osteosynthesis locking screws under cyclic overloading. Medical Engineering and Physics. Elsevier. https://doi.org/10.1016/j.medengphy.2024.104143"},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","scopus_import":"1","month":"04","intvolume":" 126","abstract":[{"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.","lang":"eng"}],"oa_version":"Published Version","volume":126,"license":"https://creativecommons.org/licenses/by/4.0/","publication_identifier":{"eissn":["1873-4030"],"issn":["1350-4533"]},"publication_status":"published","file":[{"checksum":"974acbf2731e7382dcf5920ac762e551","file_id":"15177","success":1,"access_level":"open_access","relation":"main_file","content_type":"application/pdf","date_created":"2024-03-25T08:29:52Z","file_name":"2024_MedEngineeringPhysics_SilvaHenao.pdf","creator":"dernst","date_updated":"2024-03-25T08:29:52Z","file_size":10039402}],"language":[{"iso":"eng"}],"type":"journal_article","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","_id":"15164","file_date_updated":"2024-03-25T08:29:52Z","department":[{"_id":"PreCl"}],"date_updated":"2024-03-25T08:31:01Z","ddc":["610"]},{"date_updated":"2023-08-04T09:25:59Z","ddc":["570"],"department":[{"_id":"PreCl"}],"file_date_updated":"2023-01-27T08:23:46Z","_id":"12224","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","type":"journal_article","keyword":["General Agricultural and Biological Sciences","General Biochemistry","Genetics and Molecular Biology","Medicine (miscellaneous)"],"status":"public","publication_status":"published","publication_identifier":{"issn":["2399-3642"]},"language":[{"iso":"eng"}],"file":[{"success":1,"file_id":"12417","checksum":"bd95be1e77090208b79bc45ea8785d0b","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"2022_CommBiology_Muhia.pdf","date_created":"2023-01-27T08:23:46Z","creator":"dernst","file_size":3968356,"date_updated":"2023-01-27T08:23:46Z"}],"volume":5,"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 Mkln1 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 Mkln1 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 Mkln1 ablation.","lang":"eng"}],"oa_version":"Published Version","scopus_import":"1","intvolume":" 5","month":"06","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.","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.” Communications Biology. Springer Nature, 2022. https://doi.org/10.1038/s42003-022-03446-1.","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. Communications Biology. Springer Nature. https://doi.org/10.1038/s42003-022-03446-1","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. Communications Biology. 2022;5. doi:10.1038/s42003-022-03446-1","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).","ieee":"M. W. Muhia et al., “Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes,” Communications Biology, vol. 5. Springer Nature, 2022.","mla":"Muhia, Mary W., et al. “Muskelin Regulates Actin-Dependent Synaptic Changes and Intrinsic Brain Activity Relevant to Behavioral and Cognitive Processes.” Communications Biology, vol. 5, 589, Springer Nature, 2022, doi:10.1038/s42003-022-03446-1."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","external_id":{"isi":["000811777900003"]},"author":[{"last_name":"Muhia","full_name":"Muhia, Mary W","id":"ab7ed20f-09f7-11eb-909c-d5d0b443ee9d","first_name":"Mary W"},{"first_name":"PingAn","full_name":"YuanXiang, PingAn","last_name":"YuanXiang"},{"first_name":"Jan","full_name":"Sedlacik, Jan","last_name":"Sedlacik"},{"last_name":"Schwarz","full_name":"Schwarz, Jürgen R.","first_name":"Jürgen R."},{"first_name":"Frank F.","full_name":"Heisler, Frank F.","last_name":"Heisler"},{"first_name":"Kira V.","last_name":"Gromova","full_name":"Gromova, Kira V."},{"first_name":"Edda","last_name":"Thies","full_name":"Thies, Edda"},{"last_name":"Breiden","full_name":"Breiden, Petra","first_name":"Petra"},{"first_name":"Yvonne","last_name":"Pechmann","full_name":"Pechmann, Yvonne"},{"full_name":"Kreutz, Michael R.","last_name":"Kreutz","first_name":"Michael R."},{"last_name":"Kneussel","full_name":"Kneussel, Matthias","first_name":"Matthias"}],"title":"Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes","article_number":"589","year":"2022","isi":1,"has_accepted_license":"1","publication":"Communications Biology","day":"15","date_created":"2023-01-16T09:48:19Z","doi":"10.1038/s42003-022-03446-1","date_published":"2022-06-15T00:00:00Z","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.","oa":1,"publisher":"Springer Nature","quality_controlled":"1"},{"publication_identifier":{"eissn":["2050084X"]},"publication_status":"published","file":[{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"885b746051a7a6b6e24e3d2781a48fde","file_id":"9609","success":1,"date_updated":"2021-06-28T11:35:30Z","file_size":2500720,"creator":"asandaue","date_created":"2021-06-28T11:35:30Z","file_name":"2021_ELife_Bespalov.pdf"}],"language":[{"iso":"eng"}],"volume":10,"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."}],"oa_version":"Published Version","pmid":1,"scopus_import":"1","month":"05","intvolume":" 10","date_updated":"2023-08-10T13:36:50Z","ddc":["570"],"file_date_updated":"2021-06-28T11:35:30Z","department":[{"_id":"PreCl"}],"_id":"9607","article_type":"original","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","isi":1,"has_accepted_license":"1","year":"2021","day":"24","publication":"eLife","doi":"10.7554/eLife.63294","date_published":"2021-05-24T00:00:00Z","date_created":"2021-06-27T22:01:49Z","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).","quality_controlled":"1","publisher":"eLife Sciences Publications","oa":1,"citation":{"mla":"Bespalov, Anton, et al. “Introduction to the EQIPD Quality System.” ELife, vol. 10, eLife Sciences Publications, 2021, doi:10.7554/eLife.63294.","ama":"Bespalov A, Bernard R, Gilis A, et al. Introduction to the EQIPD quality system. eLife. 2021;10. doi:10.7554/eLife.63294","apa":"Bespalov, A., Bernard, R., Gilis, A., Gerlach, B., Guillén, J., Castagné, V., … Steckler, T. (2021). Introduction to the EQIPD quality system. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.63294","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).","ieee":"A. Bespalov et al., “Introduction to the EQIPD quality system,” eLife, vol. 10. eLife Sciences Publications, 2021.","chicago":"Bespalov, Anton, René Bernard, Anja Gilis, Björn Gerlach, Javier Guillén, Vincent Castagné, Isabel A. Lefevre, et al. “Introduction to the EQIPD Quality System.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/eLife.63294.","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."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"full_name":"Bespalov, Anton","last_name":"Bespalov","first_name":"Anton"},{"last_name":"Bernard","full_name":"Bernard, René","first_name":"René"},{"first_name":"Anja","full_name":"Gilis, Anja","last_name":"Gilis"},{"first_name":"Björn","last_name":"Gerlach","full_name":"Gerlach, Björn"},{"full_name":"Guillén, Javier","last_name":"Guillén","first_name":"Javier"},{"full_name":"Castagné, Vincent","last_name":"Castagné","first_name":"Vincent"},{"full_name":"Lefevre, Isabel A.","last_name":"Lefevre","first_name":"Isabel A."},{"first_name":"Fiona","last_name":"Ducrey","full_name":"Ducrey, Fiona"},{"first_name":"Lee","full_name":"Monk, Lee","last_name":"Monk"},{"full_name":"Bongiovanni, Sandrine","last_name":"Bongiovanni","first_name":"Sandrine"},{"first_name":"Bruce","full_name":"Altevogt, Bruce","last_name":"Altevogt"},{"last_name":"Arroyo-Araujo","full_name":"Arroyo-Araujo, María","first_name":"María"},{"full_name":"Bikovski, Lior","last_name":"Bikovski","first_name":"Lior"},{"first_name":"Natasja","full_name":"De Bruin, Natasja","last_name":"De Bruin"},{"first_name":"Esmeralda","full_name":"Castaños-Vélez, Esmeralda","last_name":"Castaños-Vélez"},{"first_name":"Alexander","full_name":"Dityatev, Alexander","last_name":"Dityatev"},{"last_name":"Emmerich","full_name":"Emmerich, Christoph H.","first_name":"Christoph H."},{"full_name":"Fares, Raafat","last_name":"Fares","first_name":"Raafat"},{"first_name":"Chantelle","last_name":"Ferland-Beckham","full_name":"Ferland-Beckham, Chantelle"},{"last_name":"Froger-Colléaux","full_name":"Froger-Colléaux, Christelle","first_name":"Christelle"},{"last_name":"Gailus-Durner","full_name":"Gailus-Durner, Valerie","first_name":"Valerie"},{"first_name":"Sabine M.","last_name":"Hölter","full_name":"Hölter, Sabine M."},{"first_name":"Martine Cj","last_name":"Hofmann","full_name":"Hofmann, Martine Cj"},{"full_name":"Kabitzke, Patricia","last_name":"Kabitzke","first_name":"Patricia"},{"last_name":"Kas","full_name":"Kas, Martien Jh","first_name":"Martien Jh"},{"last_name":"Kurreck","full_name":"Kurreck, Claudia","first_name":"Claudia"},{"first_name":"Paul","full_name":"Moser, Paul","last_name":"Moser"},{"full_name":"Pietraszek, Malgorzata","last_name":"Pietraszek","first_name":"Malgorzata"},{"last_name":"Popik","full_name":"Popik, Piotr","first_name":"Piotr"},{"first_name":"Heidrun","full_name":"Potschka, Heidrun","last_name":"Potschka"},{"first_name":"Ernesto","last_name":"Prado Montes De Oca","full_name":"Prado Montes De Oca, Ernesto"},{"first_name":"Leonardo","last_name":"Restivo","full_name":"Restivo, Leonardo"},{"first_name":"Gernot","last_name":"Riedel","full_name":"Riedel, Gernot"},{"full_name":"Ritskes-Hoitinga, Merel","last_name":"Ritskes-Hoitinga","first_name":"Merel"},{"first_name":"Janko","full_name":"Samardzic, Janko","last_name":"Samardzic"},{"orcid":"0000-0003-4326-5300","full_name":"Schunn, Michael","last_name":"Schunn","first_name":"Michael","id":"4272DB4A-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Claudia","full_name":"Stöger, Claudia","last_name":"Stöger"},{"last_name":"Voikar","full_name":"Voikar, Vootele","first_name":"Vootele"},{"full_name":"Vollert, Jan","last_name":"Vollert","first_name":"Jan"},{"last_name":"Wever","full_name":"Wever, Kimberley E.","first_name":"Kimberley E."},{"last_name":"Wuyts","full_name":"Wuyts, Kathleen","first_name":"Kathleen"},{"first_name":"Malcolm R.","last_name":"Macleod","full_name":"Macleod, Malcolm R."},{"last_name":"Dirnagl","full_name":"Dirnagl, Ulrich","first_name":"Ulrich"},{"full_name":"Steckler, Thomas","last_name":"Steckler","first_name":"Thomas"}],"external_id":{"pmid":["34028353"],"isi":["000661272000001"]},"article_processing_charge":"No","title":"Introduction to the EQIPD quality system"},{"doi":"10.1016/j.celrep.2021.109274","date_published":"2021-06-22T00:00:00Z","date_created":"2021-06-27T22:01:48Z","day":"22","publication":"Cell Reports","has_accepted_license":"1","isi":1,"year":"2021","quality_controlled":"1","publisher":"Cell Press","oa":1,"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.","title":"A genome-wide library of MADM mice for single-cell genetic mosaic analysis","author":[{"first_name":"Ximena","id":"475990FE-F248-11E8-B48F-1D18A9856A87","full_name":"Contreras, Ximena","last_name":"Contreras"},{"full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207","last_name":"Amberg","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","first_name":"Nicole"},{"first_name":"Amarbayasgalan","id":"70ADC922-B424-11E9-99E3-BA18E6697425","full_name":"Davaatseren, Amarbayasgalan","last_name":"Davaatseren"},{"id":"38853E16-F248-11E8-B48F-1D18A9856A87","first_name":"Andi H","full_name":"Hansen, Andi H","last_name":"Hansen"},{"full_name":"Sonntag, Johanna","last_name":"Sonntag","id":"32FE7D7C-F248-11E8-B48F-1D18A9856A87","first_name":"Johanna"},{"full_name":"Andersen, Lill","last_name":"Andersen","first_name":"Lill"},{"first_name":"Tina","last_name":"Bernthaler","full_name":"Bernthaler, Tina"},{"last_name":"Streicher","full_name":"Streicher, Carmen","first_name":"Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Heger","full_name":"Heger, Anna-Magdalena","id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87","first_name":"Anna-Magdalena"},{"last_name":"Johnson","full_name":"Johnson, Randy L.","first_name":"Randy L."},{"first_name":"Lindsay A.","full_name":"Schwarz, Lindsay A.","last_name":"Schwarz"},{"first_name":"Liqun","full_name":"Luo, Liqun","last_name":"Luo"},{"first_name":"Thomas","full_name":"Rülicke, Thomas","last_name":"Rülicke"},{"full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon"}],"article_processing_charge":"No","external_id":{"isi":["000664463600016"]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"mla":"Contreras, Ximena, et al. “A Genome-Wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis.” Cell Reports, vol. 35, no. 12, 109274, Cell Press, 2021, doi:10.1016/j.celrep.2021.109274.","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).","ieee":"X. Contreras et al., “A genome-wide library of MADM mice for single-cell genetic mosaic analysis,” Cell Reports, vol. 35, no. 12. Cell Press, 2021.","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. Cell Reports. Cell Press. https://doi.org/10.1016/j.celrep.2021.109274","ama":"Contreras X, Amberg N, Davaatseren A, et al. A genome-wide library of MADM mice for single-cell genetic mosaic analysis. Cell Reports. 2021;35(12). doi:10.1016/j.celrep.2021.109274","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.” Cell Reports. Cell Press, 2021. https://doi.org/10.1016/j.celrep.2021.109274.","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."},"project":[{"_id":"2625A13E-B435-11E9-9278-68D0E5697425","grant_number":"24812","name":"Molecular Mechanisms of Radial Neuronal Migration"},{"name":"Molecular Mechanisms of Cerebral Cortex Development","grant_number":"618444","call_identifier":"FP7","_id":"25D61E48-B435-11E9-9278-68D0E5697425"},{"grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425"}],"article_number":"109274","issue":"12","volume":35,"related_material":{"link":[{"description":"News on IST Homepage","url":"https://ist.ac.at/en/news/boost-for-mouse-genetic-analysis/","relation":"press_release"}]},"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","ec_funded":1,"file":[{"date_created":"2021-06-28T14:06:24Z","file_name":"2021_CellReports_Contreras.pdf","creator":"asandaue","date_updated":"2021-06-28T14:06:24Z","file_size":7653149,"file_id":"9613","checksum":"d49520fdcbbb5c2f883bddb67cee5d77","success":1,"access_level":"open_access","relation":"main_file","content_type":"application/pdf"}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["22111247"]},"publication_status":"published","month":"06","intvolume":" 35","scopus_import":"1","oa_version":"Published Version","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."}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"department":[{"_id":"SiHi"},{"_id":"LoSw"},{"_id":"PreCl"}],"file_date_updated":"2021-06-28T14:06:24Z","ddc":["570"],"date_updated":"2023-08-10T13:55:00Z","status":"public","type":"journal_article","article_type":"original","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"_id":"9603"},{"file_date_updated":"2022-05-16T07:07:41Z","department":[{"_id":"PreCl"}],"ddc":["570"],"date_updated":"2023-08-14T11:47:35Z","status":"public","type":"journal_article","article_type":"original","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"_id":"10283","volume":22,"file":[{"file_name":"2021_EmboReports_Restivo.pdf","date_created":"2022-05-16T07:07:41Z","file_size":488583,"date_updated":"2022-05-16T07:07:41Z","creator":"dernst","success":1,"file_id":"11381","checksum":"74743baa6ef431ef60c3de3bc4da045a","content_type":"application/pdf","relation":"main_file","access_level":"open_access"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["1469-221X"],"eissn":["1469-3178"]},"publication_status":"published","month":"11","intvolume":" 22","scopus_import":"1","oa_version":"Published Version","abstract":[{"lang":"eng","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."}],"title":"Towards best practices in research: Role of academic core facilities","author":[{"first_name":"Leonardo","last_name":"Restivo","full_name":"Restivo, Leonardo"},{"first_name":"Björn","last_name":"Gerlach","full_name":"Gerlach, Björn"},{"full_name":"Tsoory, Michael","last_name":"Tsoory","first_name":"Michael"},{"full_name":"Bikovski, Lior","last_name":"Bikovski","first_name":"Lior"},{"last_name":"Badurek","full_name":"Badurek, Sylvia","first_name":"Sylvia"},{"first_name":"Claudia","full_name":"Pitzer, Claudia","last_name":"Pitzer"},{"first_name":"Isabelle C.","full_name":"Kos-Braun, Isabelle C.","last_name":"Kos-Braun"},{"first_name":"Anne Laure Mj","full_name":"Mausset-Bonnefont, Anne Laure Mj","last_name":"Mausset-Bonnefont"},{"full_name":"Ward, Jonathan","last_name":"Ward","first_name":"Jonathan"},{"first_name":"Michael","id":"4272DB4A-F248-11E8-B48F-1D18A9856A87","last_name":"Schunn","full_name":"Schunn, Michael","orcid":"0000-0003-4326-5300"},{"full_name":"Noldus, Lucas P.J.J.","last_name":"Noldus","first_name":"Lucas P.J.J."},{"full_name":"Bespalov, Anton","last_name":"Bespalov","first_name":"Anton"},{"first_name":"Vootele","full_name":"Voikar, Vootele","last_name":"Voikar"}],"external_id":{"isi":["000714350000001"]},"article_processing_charge":"Yes (in subscription journal)","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"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.” EMBO Reports. EMBO Press, 2021. https://doi.org/10.15252/embr.202153824.","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.” EMBO Reports, vol. 22, e53824, EMBO Press, 2021, doi:10.15252/embr.202153824.","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).","ieee":"L. Restivo et al., “Towards best practices in research: Role of academic core facilities,” EMBO Reports, vol. 22. EMBO Press, 2021.","ama":"Restivo L, Gerlach B, Tsoory M, et al. Towards best practices in research: Role of academic core facilities. EMBO Reports. 2021;22. doi:10.15252/embr.202153824","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. EMBO Reports. EMBO Press. https://doi.org/10.15252/embr.202153824"},"article_number":"e53824","date_published":"2021-11-04T00:00:00Z","doi":"10.15252/embr.202153824","date_created":"2021-11-14T23:01:24Z","day":"04","publication":"EMBO Reports","has_accepted_license":"1","isi":1,"year":"2021","publisher":"EMBO Press","quality_controlled":"1","oa":1,"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."},{"oa":1,"quality_controlled":"1","publisher":"Nature Publishing Group","date_created":"2019-07-07T21:59:19Z","date_published":"2019-06-24T00:00:00Z","doi":"10.1038/s41598-019-45579-0","publication":"Scientific Reports","day":"24","year":"2019","isi":1,"has_accepted_license":"1","article_number":"9139","title":"SOCS2 is part of a highly prognostic 4-gene signature in AML and promotes disease aggressiveness","article_processing_charge":"No","external_id":{"isi":["000472597400042"]},"author":[{"full_name":"Nguyen, Chi Huu","last_name":"Nguyen","first_name":"Chi Huu"},{"first_name":"Tobias","full_name":"Glüxam, Tobias","last_name":"Glüxam"},{"first_name":"Angela","full_name":"Schlerka, Angela","last_name":"Schlerka"},{"first_name":"Katharina","id":"2ED6B14C-F248-11E8-B48F-1D18A9856A87","full_name":"Bauer, Katharina","last_name":"Bauer"},{"first_name":"Alexander M.","full_name":"Grandits, Alexander M.","last_name":"Grandits"},{"last_name":"Hackl","full_name":"Hackl, Hubert","first_name":"Hubert"},{"first_name":"Oliver","last_name":"Dovey","full_name":"Dovey, Oliver"},{"last_name":"Zöchbauer-Müller","full_name":"Zöchbauer-Müller, Sabine","first_name":"Sabine"},{"last_name":"Cooper","full_name":"Cooper, Jonathan L.","first_name":"Jonathan L."},{"first_name":"George S.","last_name":"Vassiliou","full_name":"Vassiliou, George S."},{"first_name":"Dagmar","last_name":"Stoiber","full_name":"Stoiber, Dagmar"},{"first_name":"Rotraud","last_name":"Wieser","full_name":"Wieser, Rotraud"},{"full_name":"Heller, Gerwin","last_name":"Heller","first_name":"Gerwin"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"mla":"Nguyen, Chi Huu, et al. “SOCS2 Is Part of a Highly Prognostic 4-Gene Signature in AML and Promotes Disease Aggressiveness.” Scientific Reports, vol. 9, no. 1, 9139, Nature Publishing Group, 2019, doi:10.1038/s41598-019-45579-0.","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).","ieee":"C. H. Nguyen et al., “SOCS2 is part of a highly prognostic 4-gene signature in AML and promotes disease aggressiveness,” Scientific Reports, vol. 9, no. 1. Nature Publishing Group, 2019.","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. Scientific Reports. Nature Publishing Group. https://doi.org/10.1038/s41598-019-45579-0","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. Scientific Reports. 2019;9(1). doi:10.1038/s41598-019-45579-0","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.” Scientific Reports. Nature Publishing Group, 2019. https://doi.org/10.1038/s41598-019-45579-0.","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."},"intvolume":" 9","month":"06","scopus_import":"1","oa_version":"Published Version","abstract":[{"lang":"eng","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."}],"volume":9,"issue":"1","language":[{"iso":"eng"}],"file":[{"date_created":"2019-07-08T15:15:28Z","file_name":"nature_2019_Nguyen.pdf","date_updated":"2020-07-14T12:47:34Z","file_size":2017352,"creator":"kschuh","checksum":"3283522fffadf4b5fc8c7adfe3ba4564","file_id":"6623","content_type":"application/pdf","access_level":"open_access","relation":"main_file"}],"publication_status":"published","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","_id":"6607","file_date_updated":"2020-07-14T12:47:34Z","department":[{"_id":"PreCl"}],"ddc":["576"],"date_updated":"2023-08-28T12:26:51Z"}]