[{"abstract":[{"lang":"eng","text":"Evolutionary studies are often limited by missing data that are critical to understanding the history of selection. Selection experiments, which reproduce rapid evolution under controlled conditions, are excellent tools to study how genomes evolve under selection. Here we present a genomic dissection of the Longshanks selection experiment, in which mice were selectively bred over 20 generations for longer tibiae relative to body mass, resulting in 13% longer tibiae in two replicates. We synthesized evolutionary theory, genome sequences and molecular genetics to understand the selection response and found that it involved both polygenic adaptation and discrete loci of major effect, with the strongest loci tending to be selected in parallel between replicates. We show that selection may favor de-repression of bone growth through inactivating two limb enhancers of an inhibitor, Nkx3-2. Our integrative genomic analyses thus show that it is possible to connect individual base-pair changes to the overall selection response."}],"type":"journal_article","oa_version":"Published Version","file":[{"creator":"apreinsp","content_type":"application/pdf","file_size":6748249,"access_level":"open_access","file_name":"2019_eLife_Castro.pdf","checksum":"fa0936fe58f0d9e3f8e75038570e5a17","date_created":"2019-07-29T07:41:18Z","date_updated":"2020-07-14T12:47:38Z","file_id":"6721","relation":"main_file"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"6713","intvolume":" 8","ddc":["576"],"status":"public","title":"An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice","has_accepted_license":"1","article_processing_charge":"No","day":"06","scopus_import":"1","date_published":"2019-06-06T00:00:00Z","citation":{"chicago":"Castro, João Pl, Michelle N. Yancoskie, Marta Marchini, Stefanie Belohlavy, Layla Hiramatsu, Marek Kučka, William H. Beluch, et al. “An Integrative Genomic Analysis of the Longshanks Selection Experiment for Longer Limbs in Mice.” ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/eLife.42014.","short":"J.P. Castro, M.N. Yancoskie, M. Marchini, S. Belohlavy, L. Hiramatsu, M. Kučka, W.H. Beluch, R. Naumann, I. Skuplik, J. Cobb, N.H. Barton, C. Rolian, Y.F. Chan, ELife 8 (2019).","mla":"Castro, João Pl, et al. “An Integrative Genomic Analysis of the Longshanks Selection Experiment for Longer Limbs in Mice.” ELife, vol. 8, e42014, eLife Sciences Publications, 2019, doi:10.7554/eLife.42014.","apa":"Castro, J. P., Yancoskie, M. N., Marchini, M., Belohlavy, S., Hiramatsu, L., Kučka, M., … Chan, Y. F. (2019). An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.42014","ieee":"J. P. Castro et al., “An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice,” eLife, vol. 8. eLife Sciences Publications, 2019.","ista":"Castro JP, Yancoskie MN, Marchini M, Belohlavy S, Hiramatsu L, Kučka M, Beluch WH, Naumann R, Skuplik I, Cobb J, Barton NH, Rolian C, Chan YF. 2019. An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice. eLife. 8, e42014.","ama":"Castro JP, Yancoskie MN, Marchini M, et al. An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice. eLife. 2019;8. doi:10.7554/eLife.42014"},"publication":"eLife","file_date_updated":"2020-07-14T12:47:38Z","license":"https://creativecommons.org/licenses/by/4.0/","article_number":"e42014","related_material":{"record":[{"id":"9804","relation":"research_data","status":"public"},{"status":"public","relation":"dissertation_contains","id":"11388"}]},"author":[{"first_name":"João Pl","last_name":"Castro","full_name":"Castro, João Pl"},{"full_name":"Yancoskie, Michelle N.","first_name":"Michelle N.","last_name":"Yancoskie"},{"full_name":"Marchini, Marta","first_name":"Marta","last_name":"Marchini"},{"last_name":"Belohlavy","first_name":"Stefanie","orcid":"0000-0002-9849-498X","id":"43FE426A-F248-11E8-B48F-1D18A9856A87","full_name":"Belohlavy, Stefanie"},{"full_name":"Hiramatsu, Layla","first_name":"Layla","last_name":"Hiramatsu"},{"full_name":"Kučka, Marek","first_name":"Marek","last_name":"Kučka"},{"full_name":"Beluch, William H.","last_name":"Beluch","first_name":"William H."},{"last_name":"Naumann","first_name":"Ronald","full_name":"Naumann, Ronald"},{"first_name":"Isabella","last_name":"Skuplik","full_name":"Skuplik, Isabella"},{"first_name":"John","last_name":"Cobb","full_name":"Cobb, John"},{"last_name":"Barton","first_name":"Nicholas H","orcid":"0000-0002-8548-5240","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","full_name":"Barton, Nicholas H"},{"full_name":"Rolian, Campbell","first_name":"Campbell","last_name":"Rolian"},{"full_name":"Chan, Yingguang Frank","last_name":"Chan","first_name":"Yingguang Frank"}],"volume":8,"date_updated":"2024-03-28T23:30:23Z","date_created":"2019-07-28T21:59:17Z","pmid":1,"year":"2019","department":[{"_id":"NiBa"}],"publisher":"eLife Sciences Publications","publication_status":"published","month":"06","doi":"10.7554/eLife.42014","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"isi":["000473588700001"],"pmid":["31169497"]},"isi":1,"quality_controlled":"1"},{"ec_funded":1,"abstract":[{"text":"We study double quantum dots in a Ge/SiGe heterostructure and test their maturity towards singlet-triplet ($S-T_0$) qubits. We demonstrate a large range of tunability, from two single quantum dots to a double quantum dot. We measure Pauli spin blockade and study the anisotropy of the $g$-factor. We use an adjacent quantum dot for sensing charge transitions in the double quantum dot at interest. In conclusion, Ge/SiGe possesses all ingredients necessary for building a singlet-triplet qubit.","lang":"eng"}],"type":"preprint","article_number":"1910.05841","related_material":{"record":[{"id":"10058","status":"public","relation":"dissertation_contains"}]},"author":[{"id":"340F461A-F248-11E8-B48F-1D18A9856A87","last_name":"Hofmann","first_name":"Andrea C","full_name":"Hofmann, Andrea C"},{"full_name":"Jirovec, Daniel","orcid":"0000-0002-7197-4801","id":"4C473F58-F248-11E8-B48F-1D18A9856A87","last_name":"Jirovec","first_name":"Daniel"},{"first_name":"Maxim","last_name":"Borovkov","full_name":"Borovkov, Maxim"},{"full_name":"Prieto Gonzalez, Ivan","first_name":"Ivan","last_name":"Prieto Gonzalez","id":"2A307FE2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7370-5357"},{"first_name":"Andrea","last_name":"Ballabio","full_name":"Ballabio, Andrea"},{"full_name":"Frigerio, Jacopo","first_name":"Jacopo","last_name":"Frigerio"},{"full_name":"Chrastina, Daniel","last_name":"Chrastina","first_name":"Daniel"},{"full_name":"Isella, Giovanni","last_name":"Isella","first_name":"Giovanni"},{"full_name":"Katsaros, Georgios","orcid":"0000-0001-8342-202X","id":"38DB5788-F248-11E8-B48F-1D18A9856A87","last_name":"Katsaros","first_name":"Georgios"}],"oa_version":"Preprint","date_updated":"2024-03-28T23:30:27Z","date_created":"2021-10-01T12:14:51Z","_id":"10065","acknowledgement":"We thank Matthias Brauns for helpful discussions and careful proofreading of the manuscript. This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 844511 and from the FWF project P30207. The research was supported by the Scientific Service Units of IST Austria through resources provided by the MIBA machine shop and the nanofabrication\r\nfacility.","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2019","department":[{"_id":"GeKa"}],"title":"Assessing the potential of Ge/SiGe quantum dots as hosts for singlet-triplet qubits","status":"public","publication_status":"submitted","article_processing_charge":"No","day":"13","month":"10","date_published":"2019-10-13T00:00:00Z","doi":"10.48550/arXiv.1910.05841","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"NanoFab"}],"citation":{"ama":"Hofmann AC, Jirovec D, Borovkov M, et al. Assessing the potential of Ge/SiGe quantum dots as hosts for singlet-triplet qubits. arXiv. doi:10.48550/arXiv.1910.05841","apa":"Hofmann, A. C., Jirovec, D., Borovkov, M., Prieto Gonzalez, I., Ballabio, A., Frigerio, J., … Katsaros, G. (n.d.). Assessing the potential of Ge/SiGe quantum dots as hosts for singlet-triplet qubits. arXiv. https://doi.org/10.48550/arXiv.1910.05841","ieee":"A. C. Hofmann et al., “Assessing the potential of Ge/SiGe quantum dots as hosts for singlet-triplet qubits,” arXiv. .","ista":"Hofmann AC, Jirovec D, Borovkov M, Prieto Gonzalez I, Ballabio A, Frigerio J, Chrastina D, Isella G, Katsaros G. Assessing the potential of Ge/SiGe quantum dots as hosts for singlet-triplet qubits. arXiv, 1910.05841.","short":"A.C. Hofmann, D. Jirovec, M. Borovkov, I. Prieto Gonzalez, A. Ballabio, J. Frigerio, D. Chrastina, G. Isella, G. Katsaros, ArXiv (n.d.).","mla":"Hofmann, Andrea C., et al. “Assessing the Potential of Ge/SiGe Quantum Dots as Hosts for Singlet-Triplet Qubits.” ArXiv, 1910.05841, doi:10.48550/arXiv.1910.05841.","chicago":"Hofmann, Andrea C, Daniel Jirovec, Maxim Borovkov, Ivan Prieto Gonzalez, Andrea Ballabio, Jacopo Frigerio, Daniel Chrastina, Giovanni Isella, and Georgios Katsaros. “Assessing the Potential of Ge/SiGe Quantum Dots as Hosts for Singlet-Triplet Qubits.” ArXiv, n.d. https://doi.org/10.48550/arXiv.1910.05841."},"main_file_link":[{"url":"https://arxiv.org/abs/1910.05841","open_access":"1"}],"external_id":{"arxiv":["1910.05841"]},"oa":1,"publication":"arXiv","project":[{"_id":"26A151DA-B435-11E9-9278-68D0E5697425","grant_number":"844511","name":"Majorana bound states in Ge/SiGe heterostructures","call_identifier":"H2020"},{"_id":"2641CE5E-B435-11E9-9278-68D0E5697425","grant_number":"P30207","call_identifier":"FWF","name":"Hole spin orbit qubits in Ge quantum wells"}]},{"ec_funded":1,"file_date_updated":"2020-07-14T12:47:23Z","article_number":"e41801","volume":8,"date_updated":"2024-03-28T23:30:30Z","date_created":"2019-03-28T13:37:45Z","related_material":{"link":[{"relation":"press_release","description":"News on IST Homepage","url":"https://ist.ac.at/en/news/new-gene-potentially-involved-in-metastasis-identified/"}],"record":[{"relation":"dissertation_contains","id":"6530"},{"id":"8983","relation":"dissertation_contains","status":"public"},{"status":"public","relation":"dissertation_contains","id":"6546"}]},"author":[{"last_name":"Valosková","first_name":"Katarina","id":"46F146FC-F248-11E8-B48F-1D18A9856A87","full_name":"Valosková, Katarina"},{"full_name":"Biebl, Julia","id":"3CCBB46E-F248-11E8-B48F-1D18A9856A87","last_name":"Biebl","first_name":"Julia"},{"full_name":"Roblek, Marko","id":"3047D808-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9588-1389","first_name":"Marko","last_name":"Roblek"},{"last_name":"Emtenani","first_name":"Shamsi","orcid":"0000-0001-6981-6938","id":"49D32318-F248-11E8-B48F-1D18A9856A87","full_name":"Emtenani, Shamsi"},{"full_name":"György, Attila","first_name":"Attila","last_name":"György","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1819-198X"},{"full_name":"Misova, Michaela","id":"495A3C32-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2427-6856","first_name":"Michaela","last_name":"Misova"},{"last_name":"Ratheesh","first_name":"Aparna","orcid":"0000-0001-7190-0776","id":"2F064CFE-F248-11E8-B48F-1D18A9856A87","full_name":"Ratheesh, Aparna"},{"first_name":"Patricia","last_name":"Rodrigues","id":"2CE4065A-F248-11E8-B48F-1D18A9856A87","full_name":"Rodrigues, Patricia"},{"last_name":"Shkarina","first_name":"Katerina","full_name":"Shkarina, Katerina"},{"last_name":"Larsen","first_name":"Ida Signe Bohse","full_name":"Larsen, Ida Signe Bohse"},{"last_name":"Vakhrushev","first_name":"Sergey Y","full_name":"Vakhrushev, Sergey Y"},{"first_name":"Henrik","last_name":"Clausen","full_name":"Clausen, Henrik"},{"orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","last_name":"Siekhaus","first_name":"Daria E","full_name":"Siekhaus, Daria E"}],"publisher":"eLife Sciences Publications","department":[{"_id":"DaSi"}],"publication_status":"published","year":"2019","publication_identifier":{"issn":["2050-084X"]},"month":"03","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"LifeSc"}],"doi":"10.7554/elife.41801","project":[{"grant_number":"24283","_id":"253CDE40-B435-11E9-9278-68D0E5697425","name":"Examination of the role of a MFS transporter in the migration of Drosophila immune cells"},{"_id":"253B6E48-B435-11E9-9278-68D0E5697425","grant_number":"P29638","call_identifier":"FWF","name":"The role of Drosophila TNF alpha in immune cell invasion"},{"grant_number":"334077","_id":"2536F660-B435-11E9-9278-68D0E5697425","name":"Investigating the role of transporters in invasive migration through junctions","call_identifier":"FP7"},{"_id":"25388084-B435-11E9-9278-68D0E5697425","grant_number":"329540","name":"Breaking barriers: Investigating the junctional and mechanobiological changes underlying the ability of Drosophila immune cells to invade an epithelium","call_identifier":"FP7"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","name":"International IST Doctoral Program","call_identifier":"H2020"}],"quality_controlled":"1","isi":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000462530200001"]},"oa":1,"abstract":[{"lang":"eng","text":"Aberrant display of the truncated core1 O-glycan T-antigen is a common feature of human cancer cells that correlates with metastasis. Here we show that T-antigen in Drosophila melanogaster macrophages is involved in their developmentally programmed tissue invasion. Higher macrophage T-antigen levels require an atypical major facilitator superfamily (MFS) member that we named Minerva which enables macrophage dissemination and invasion. We characterize for the first time the T and Tn glycoform O-glycoproteome of the Drosophila melanogaster embryo, and determine that Minerva increases the presence of T-antigen on proteins in pathways previously linked to cancer, most strongly on the sulfhydryl oxidase Qsox1 which we show is required for macrophage tissue entry. Minerva’s vertebrate ortholog, MFSD1, rescues the minerva mutant’s migration and T-antigen glycosylation defects. We thus identify a key conserved regulator that orchestrates O-glycosylation on a protein subset to activate a program governing migration steps important for both development and cancer metastasis."}],"type":"journal_article","file":[{"relation":"main_file","file_id":"6188","date_created":"2019-03-28T14:00:41Z","date_updated":"2020-07-14T12:47:23Z","checksum":"cc0d1a512559d52e7e7cb0e9b9854b40","file_name":"2019_eLife_Valoskova.pdf","access_level":"open_access","content_type":"application/pdf","file_size":4496017,"creator":"dernst"}],"oa_version":"Published Version","intvolume":" 8","ddc":["570"],"status":"public","title":"A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion","_id":"6187","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","has_accepted_license":"1","day":"26","scopus_import":"1","date_published":"2019-03-26T00:00:00Z","citation":{"short":"K. Valosková, J. Bicher, M. Roblek, S. Emtenani, A. György, M. Misova, A. Ratheesh, P. Rodrigues, K. Shkarina, I.S.B. Larsen, S.Y. Vakhrushev, H. Clausen, D.E. Siekhaus, ELife 8 (2019).","mla":"Valosková, Katarina, et al. “A Conserved Major Facilitator Superfamily Member Orchestrates a Subset of O-Glycosylation to Aid Macrophage Tissue Invasion.” ELife, vol. 8, e41801, eLife Sciences Publications, 2019, doi:10.7554/elife.41801.","chicago":"Valosková, Katarina, Julia Bicher, Marko Roblek, Shamsi Emtenani, Attila György, Michaela Misova, Aparna Ratheesh, et al. “A Conserved Major Facilitator Superfamily Member Orchestrates a Subset of O-Glycosylation to Aid Macrophage Tissue Invasion.” ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/elife.41801.","ama":"Valosková K, Bicher J, Roblek M, et al. A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion. eLife. 2019;8. doi:10.7554/elife.41801","ieee":"K. Valosková et al., “A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion,” eLife, vol. 8. eLife Sciences Publications, 2019.","apa":"Valosková, K., Bicher, J., Roblek, M., Emtenani, S., György, A., Misova, M., … Siekhaus, D. E. (2019). A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.41801","ista":"Valosková K, Bicher J, Roblek M, Emtenani S, György A, Misova M, Ratheesh A, Rodrigues P, Shkarina K, Larsen ISB, Vakhrushev SY, Clausen H, Siekhaus DE. 2019. A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion. eLife. 8, e41801."},"publication":"eLife"},{"publication_identifier":{"issn":["2663-337X"]},"month":"06","doi":"10.15479/AT:ISTA:6546","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"Bio"}],"degree_awarded":"PhD","supervisor":[{"full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","last_name":"Siekhaus","first_name":"Daria E"}],"oa":1,"project":[{"name":"Examination of the role of a MFS transporter in the migration of Drosophila immune cells","_id":"253CDE40-B435-11E9-9278-68D0E5697425","grant_number":"24283"}],"file_date_updated":"2021-02-11T11:17:14Z","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"6187"},{"id":"544","relation":"part_of_dissertation","status":"public"}]},"author":[{"id":"46F146FC-F248-11E8-B48F-1D18A9856A87","last_name":"Valosková","first_name":"Katarina","full_name":"Valosková, Katarina"}],"date_created":"2019-06-07T12:49:19Z","date_updated":"2023-09-19T10:15:54Z","year":"2019","department":[{"_id":"DaSi"}],"publisher":"Institute of Science and Technology Austria","publication_status":"published","has_accepted_license":"1","article_processing_charge":"No","day":"07","date_published":"2019-06-07T00:00:00Z","citation":{"ama":"Valosková K. The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration. 2019. doi:10.15479/AT:ISTA:6546","apa":"Valosková, K. (2019). The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6546","ieee":"K. Valosková, “The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration,” Institute of Science and Technology Austria, 2019.","ista":"Valosková K. 2019. The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration. Institute of Science and Technology Austria.","short":"K. Valosková, The Role of a Highly Conserved Major Facilitator Superfamily Member in Drosophila Embryonic Macrophage Migration, Institute of Science and Technology Austria, 2019.","mla":"Valosková, Katarina. The Role of a Highly Conserved Major Facilitator Superfamily Member in Drosophila Embryonic Macrophage Migration. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6546.","chicago":"Valosková, Katarina. “The Role of a Highly Conserved Major Facilitator Superfamily Member in Drosophila Embryonic Macrophage Migration.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6546."},"page":"141","abstract":[{"lang":"eng","text":"Invasive migration plays a crucial role not only during development and homeostasis but also in pathological states, such as tumor metastasis. Drosophila macrophage migration into the extended germband is an interesting system to study invasive migration. It carries similarities to immune cell transmigration and cancer cell invasion, therefore studying this process could also bring new understanding of invasion in higher organisms. In our work, we uncover a highly conserved member of the major facilitator family that plays a role in tissue invasion through regulation of glycosylation on a subgroup of proteins and/or by aiding the precise timing of DN-Cadherin downregulation. \r\n\r\nAberrant display of the truncated core1 O-glycan T-antigen is a common feature of human cancer cells that correlates with metastasis. Here we show that T-antigen in Drosophila melanogaster macrophages is involved in their developmentally programmed tissue invasion. Higher macrophage T-antigen levels require an atypical major facilitator superfamily (MFS) member that we named Minerva which enables macrophage dissemination and invasion. We characterize for the first time the T and Tn glycoform O-glycoproteome of the Drosophila melanogaster embryo, and determine that Minerva increases the presence of T-antigen on proteins in pathways previously linked to cancer, most strongly on the sulfhydryl oxidase Qsox1 which we show is required for macrophage tissue entry. Minerva’s vertebrate ortholog, MFSD1, rescues the minerva mutant’s migration and T-antigen glycosylation defects. We thus identify \r\na key conserved regulator that orchestrates O-glycosylation on a protein subset to activate \r\na program governing migration steps important for both development and cancer metastasis. \r\n"}],"type":"dissertation","alternative_title":["ISTA Thesis"],"oa_version":"Published Version","file":[{"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":14110626,"creator":"khribikova","access_level":"closed","embargo_to":"open_access","file_name":"Katarina Valoskova_PhD thesis_final version.docx","checksum":"68949c2d96210b45b981a23e9c9cd93c","date_updated":"2020-07-14T12:47:33Z","date_created":"2019-06-07T13:00:04Z","relation":"source_file","file_id":"6549"},{"relation":"main_file","file_id":"6550","embargo":"2020-06-07","checksum":"555329cd76e196c96f5278c480ee2e6e","date_created":"2019-06-07T13:00:08Z","date_updated":"2021-02-11T11:17:14Z","access_level":"open_access","file_name":"Katarina Valoskova_PhD thesis_final version.pdf","content_type":"application/pdf","file_size":10054156,"creator":"khribikova"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"6546","title":"The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration","status":"public","ddc":["570"]},{"citation":{"short":"C. Espinoza Martinez, Parvalbumin+ Interneurons Enable Efficient Pattern Separation in Hippocampal Microcircuits, Institute of Science and Technology Austria, 2019.","mla":"Espinoza Martinez, Claudia. Parvalbumin+ Interneurons Enable Efficient Pattern Separation in Hippocampal Microcircuits. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6363.","chicago":"Espinoza Martinez, Claudia . “Parvalbumin+ Interneurons Enable Efficient Pattern Separation in Hippocampal Microcircuits.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6363.","ama":"Espinoza Martinez C. Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits. 2019. doi:10.15479/AT:ISTA:6363","apa":"Espinoza Martinez, C. (2019). Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6363","ieee":"C. Espinoza Martinez, “Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits,” Institute of Science and Technology Austria, 2019.","ista":"Espinoza Martinez C. 2019. Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits. Institute of Science and Technology Austria."},"page":"140","date_published":"2019-04-30T00:00:00Z","day":"30","has_accepted_license":"1","article_processing_charge":"No","_id":"6363","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","title":"Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits","status":"public","ddc":["570"],"file":[{"relation":"main_file","file_id":"6389","embargo":"2020-05-09","date_updated":"2021-02-11T11:17:15Z","date_created":"2019-05-07T16:00:39Z","checksum":"77c6c05cfe8b58c8abcf1b854375d084","file_name":"Espinozathesis_all2.pdf","access_level":"open_access","file_size":13966891,"content_type":"application/pdf","creator":"cespinoza"},{"relation":"source_file","file_id":"6390","checksum":"f6aa819f127691a2b0fc21c76eb09746","date_updated":"2020-07-14T12:47:28Z","date_created":"2019-05-07T16:00:48Z","access_level":"closed","embargo_to":"open_access","file_name":"Espinoza_Thesis.docx","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":11159900,"creator":"cespinoza"}],"oa_version":"Published Version","type":"dissertation","alternative_title":["ISTA Thesis"],"abstract":[{"text":"Distinguishing between similar experiences is achieved by the brain in a process called pattern separation. In the hippocampus, pattern separation reduces the interference of memories and increases the storage capacity by decorrelating similar inputs patterns of neuronal activity into non-overlapping output firing patterns. Winners-take-all (WTA) mechanism is a theoretical model for pattern separation in which a \"winner\" cell suppresses the activity of the neighboring neurons through feedback inhibition. However, if the network properties of the dentate gyrus support WTA as a biologically conceivable model remains unknown. Here, we showed that the connectivity rules of PV+interneurons and their synaptic properties are optimizedfor efficient pattern separation. We found using multiple whole-cell in vitrorecordings that PV+interneurons mainly connect to granule cells (GC) through lateral inhibition, a form of feedback inhibition in which a GC inhibits other GCs but not itself through the activation of PV+interneurons. Thus, lateral inhibition between GC–PV+interneurons was ~10 times more abundant than recurrent connections. Furthermore, the GC–PV+interneuron connectivity was more spatially confined but less abundant than PV+interneurons–GC connectivity, leading to an asymmetrical distribution of excitatory and inhibitory connectivity. Our network model of the dentate gyrus with incorporated real connectivity rules efficiently decorrelates neuronal activity patterns using WTA as the primary mechanism. This process relied on lateral inhibition, fast-signaling properties of PV+interneurons and the asymmetrical distribution of excitatory and inhibitory connectivity. Finally, we found that silencing the activity of PV+interneurons in vivoleads to acute deficits in discrimination between similar environments, suggesting that PV+interneuron networks are necessary for behavioral relevant computations. Our results demonstrate that PV+interneurons possess unique connectivity and fast signaling properties that confer to the dentate gyrus network properties that allow the emergence of pattern separation. Thus, our results contribute to the knowledge of how specific forms of network organization underlie sophisticated types of information processing. \r\n","lang":"eng"}],"oa":1,"doi":"10.15479/AT:ISTA:6363","supervisor":[{"last_name":"Jonas","first_name":"Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M"}],"degree_awarded":"PhD","language":[{"iso":"eng"}],"month":"04","publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-000-8"]},"year":"2019","publication_status":"published","department":[{"_id":"PeJo"}],"publisher":"Institute of Science and Technology Austria","author":[{"orcid":"0000-0003-4710-2082","id":"31FFEE2E-F248-11E8-B48F-1D18A9856A87","last_name":"Espinoza Martinez","first_name":"Claudia ","full_name":"Espinoza Martinez, Claudia "}],"related_material":{"record":[{"id":"21","status":"public","relation":"part_of_dissertation"}]},"date_created":"2019-04-30T11:56:10Z","date_updated":"2023-09-15T12:03:48Z","file_date_updated":"2021-02-11T11:17:15Z"}]